| 1. |
- Loth, Daan W, et al.
(författare)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Tidskriftsartikel (refereegranskat)abstract
- Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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| 2. |
- Artigas Soler, María, et al.
(författare)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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| 3. |
- Shrine, N, et al.
(författare)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Tidskriftsartikel (refereegranskat)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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| 4. |
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| 5. |
- Repapi, Emmanouela, et al.
(författare)
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Genome-wide association study identifies five loci associated with lung function.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:1, s. 36-44
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
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| 6. |
- Spets, J.-P, et al.
(författare)
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Starch and cellulose as fuel sources for low temperature direct mode fuel cells
- 2008
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Ingår i: The Open Fuel Cells Journal. - : Bentham Open. - 1875-9327. ; 1, s. 1-3
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Tidskriftsartikel (refereegranskat)abstract
- This paper is a study about a direct mode fuel cell with a near-neutral-state and alkaline electrolytes. The aim of study was to develop a fuel cell, which operates directly by mixing the fuel with the electrolyte. This arrangement helps to avoid inserting membranes and additional bacterial cultures in fuel cell. The target is also to create a fuel cell with a capacity of few mWcm-2 with the starch as a fuel. Also, glucose and sorbitol have been tested as fuel for the fuel cell.
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| 7. |
- Calcatelli, A., et al.
(författare)
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Results of the regional key comparison EUROMET.M.P-K1.a in the pressure range from 0.1 Pa to 1000 Pa
- 2005
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Ingår i: Metrologia. - 0026-1394 .- 1681-7575. ; 42:SUPPL.
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Tidskriftsartikel (refereegranskat)abstract
- Within EUROMET a regional key comparison (EUROMET.M.P-K1.a) was performed in order to compare national vacuum standards in the pressure range from 0.1 Pa to 1000 Pa. The participants were BNM-LNE (France), CEM (Spain), OMH (Hungary), IMGC-CNR (Italy), NPL (United Kingdom), MIKES (Finland), PTB (Germany), NMi (The Netherlands), SP (Sweden) and UME (Turkey). IMGC-CNR acted as pilot laboratory. The measurements were carried out from November 1998 to April 2002. The chosen pressure values (from 0.1 Pa to 1000 Pa) cover the most commonly required range for calibration in low-pressure applications. The transfer standards were commercially available capacitance diaphragm gauges (CDGs): one of them was prepared for the comparison by BNM-LNE (Fr) and two were prepared by IMGC-CNR (It). Two sensors had 133 Pa full scale (one absolute and one relative used as absolute) and one 1333 Pa full scale (absolute). For the two 133 Pa full scale sensors seven pressure steps were generated between 0.1 Pa and 100 Pa; for the 1333 Pa full scale sensor nine pressure steps were generated generally between 0.1 Pa and 1000 Pa. The uncertainty of the generated pressure was reported by each participant in the tables of the results that consisted in the generated pressure value, the uncertainty of the generated pressure, the reading of the gauge and the temperature of the standard at each target pressure. The pilot laboratory has analysed the results, after application of the correction for thermal transpiration, in terms of gauge factors for each gauge, and the combined uncertainty was evaluated by considering, besides the component due to the standards, taking into account the components due to the transfer standards to guarantee a uniform uncertainty analysis for all the participants. At each target pressure a EUROMET reference pressure was calculated; finally the difference between the pressures generated by each laboratory from the reference values was calculated and compared with its expanded uncertainty. The results of most of the laboratories showed a good agreement with the reference values. Only a few values of two laboratories were significantly off the reference values. From the available data a linkage to the CCM.P-K4 key comparison results from 1 Pa to 1000 Pa was possible by means of the results of three laboratories in the (1-30) Pa range and two for the (100-1000) Pa range who took part in both the comparisons. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the Mutual Recognition Arrangement (MRA).
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| 8. |
- Demirkan, Ayse, et al.
(författare)
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Genetic architecture of circulating lipid levels
- 2011
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 19:7, s. 813-819
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Tidskriftsartikel (refereegranskat)abstract
- Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture of circulating lipids involves a number of undiscovered variants with very small effects, and that increasing GWAS sample sizes will enable the identification of novel variants that regulate lipid levels.
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| 9. |
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| 10. |
- Jackson, Victoria E, et al.
(författare)
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Meta-analysis of exome array data identifies six novel genetic loci for lung function.
- 2018
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
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| 11. |
- Kaprio, J, et al.
(författare)
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The Older Finnish Twin Cohort - 45 Years of Follow-up
- 2019
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Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 22:4, s. 240-254
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Tidskriftsartikel (refereegranskat)abstract
- The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945–1957 in 2011–2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938–1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.
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| 12. |
- Obeidat, Ma'en, et al.
(författare)
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A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:5, s. e19382-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). Objectives: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. Methods: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. Results: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3 x 10(-5). The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81 x 10(-5)), CNTN5 (P = 4.37 x 10(-4)), and TRPV4 (P = 1.58 x 10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41 x 10(-5)), followed by PDE4D (P = 1.22 x 10(-4)). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38 x 10(-4)), and ESR1 (P = 5.42 x 10(-4)) among ever-smokers. Conclusions: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population.
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| 13. |
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| 14. |
- Spets, J-P, et al.
(författare)
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Bioorganic materials as a fuel source for low-temperature direct-mode fuel cells
- 2010
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Ingår i: Electrochimica Acta. - : Elsevier BV. - 0013-4686 .- 1873-3859. ; 55:26, s. 7706-7709
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Tidskriftsartikel (refereegranskat)abstract
- In this study a direct-mode fuel cell in which the fuel and electrolyte are mixed with each other is tested. An alkaline electrolyte is used. The aim was to develop a fuel cell which operates directly by mixing the fuel with the electrolyte. The target is to create a fuel cell with a capacity of a few mW cm(-2) with starch as a fuel source. Starch, glucose, and sorbitol were tested as fuels for the fuel cell. With the selected fuel cell type and with glucose as the fuel, a maximum current density of 8 mA cm(-2) with a voltage of 0.5 V was obtained.
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| 15. |
- Spets, J. -P, et al.
(författare)
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Direct glucose fuel cell with the anion exchange membrane in the near-neutral-state electrolyte
- 2012
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Ingår i: International Journal of Electrochemical Science. - 1452-3981. ; 7:12, s. 11696-11705
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Tidskriftsartikel (refereegranskat)abstract
- This paper deals with the direct glucose fuel cell with an electrolyte at near-neutral-state pH value at room temperature by incorporating an anion exchange membrane (AEM) that was directly attached to a cathode. The wetted surface of the cathode was exposed to the AEM without implementing hot-pressing. The current-voltage curves were measured and the specific energy values for glucose were calculated for every test. Different concentrations of glucose were used and the results show that the lower the concentration of glucose, the higher is the specific energy, apparently showing higher utilization of the fuel with high Coulombic efficiency.
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| 16. |
- Spets, J.-P, et al.
(författare)
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Direct-Mode Glucose Fuel Cells with Near-Neutral-State Electrolytes : Anode Electrode Studies with Different Catalysts and Electrolytes
- 2009
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Ingår i: The Open Fuels & Energy Science Journal. - : Bentham Open. - 1876-973X. ; 2, s. 82-86
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, a direct-mode glucose fuel cell with a neutral-state and near-neutral-state aqueous electrolytes is studied. The near-neutral state electrolytes are important for two reasons. Firstly, the pH of the electrolytes would be near the pH of liquid in living cells. Secondly, the neutral electrolyte would enable good corrosion resistance of catalyst materials. Three different catalyst materials, i.e. Pt-Pd, Raney-Ni and Ni-porphyrin complex, are tested in an anode half-cell configuration with one neutral-state (battery water) and with two near-neutral-state aqueous electrolytes, i.e. modified Krebs-Ringer (K-R) and phosphate, both buffered to a pH value of 7.4. Pt-Pd catalyst in the aqueous K-R electrolyte maintains the negative voltage of the anode half cell with higher current densities that the nickel catalysts do. To estimate the operation of the direct-mode glucose fuel cell, the K-R electrolyte from the anode half-cell tests is tested also in the cathode half-cell with combined catalyst of cobalt porphyrin complex and of spinel. The open circuit voltages and polarisation curves are measured. Also, preliminary results and oxidation degrees of glucose in the tests are shown. Based on our half cell measurements, there are high development demands for the electro-catalysts, which could work efficiently in the near-neutral-state electrolytes.
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| 17. |
- Spets, J. -P, et al.
(författare)
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Effect of temperature on a direct glucose anion exchange membrane fuel cell in a near-neutral-state electrolyte
- 2013
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Ingår i: International Journal of Electrochemical Science. - 1452-3981. ; 8:1, s. 1226-1236
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Tidskriftsartikel (refereegranskat)abstract
- A direct glucose anion exchange membrane fuel cell (AEMFC) with a near-neutral-state electrolyte was studied at varying temperatures of 20, 30 and 37 ° C at two different concentrations of glucose of 0.1 and 0.3 M and with three concentrations of electrolyte of 0.1, 0.2 and 0.3 M [PO4]tot. The prime objective was to show how specific energy (W kg-1 glucose) of the direct glucose AEMFC is related to the operation temperature and concentrations of the species. Current and voltage values were measured together with the pHs and conductivities of the electrolytes. No component analysis of the final products after the fuel cell operation were done as the oxidation products of glucose is believed to be mainly gluconic acid and unreacted glucose as shown in the low Coulombic efficiency based on the exchange of 24 e-. Temperature, electrolyte and glucose concentrations have shown to have pronounced effect for the achievement of the highest energy capacity of 5.15 Wh kg-1 glucose.
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| 18. |
- Spets, J. P., et al.
(författare)
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Enhancement of glucose electro-oxidation by an external electromagnetic field in direct-mode fuel cells
- 2010
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Ingår i: Journal of Power Sources. - : Elsevier BV. - 0378-7753 .- 1873-2755. ; 195:2, s. 475-479
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Tidskriftsartikel (refereegranskat)abstract
- In this study a direct-mode fuel cell in which the fuel and electrolyte are mixed with each other is tested. An alkaline electrolyte is used. The direct-mode fuel cell is exposed to an externally generated electromagnetic field between electrodes to cause both the splitting of the fuel molecule into smaller units (i.e. electrochemical reforming) and an increase in the activity of catalyst materials on the fuel before electrochemical oxidation. The target is to create a fuel cell with a capacity range of a few mW cm(-2) with glucose as a fuel. In the selected fuel cell type with glucose as the fuel, a maximum current density of 13 mA cm(-2) was obtained. On the basis of the tests it seems to be possible to use the glucose-fuelled cell in small-scale applications, e. g. in small electronic devices.
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| 19. |
- Spets, J. -P., et al.
(författare)
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Production of glucose by starch and cellulose acid hydrolysis and its use as a fuel in low-temperature direct-mode fuel cells
- 2010
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Ingår i: THERMEC 2009, PTS 1-4. - Berlin. ; , s. 1164-1169
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The use of glucose, which is produced from the acid hydrolysis of starch and cellulose, is studied as a fuel in a low-temperature direct-mode fuel cell (LTDMFC) with an alkaline electrolyte. Glucose is regarded as being as good a fuel as bioethanol, because both the fuels give 2 electrons per molecule in the fuel cell without carbonisation problems. However, glucose can be produced with fewer processing stages from starch and cellulose than can bioethanol. In the LTDMFC the fuel and the electrolyte are mixed with each other and the fuel cell is equipped only with metal catalysts. Cellulose as a fuel is of great importance because the fuel for the energy production is not taken from food production. A description of an acid hydrolysis method for starch and cellulose is presented. Values for glucose concentrations in each hydrolysate are analysed by means of a chromatographic method. Each glucose hydrolysate was made alkaline by adding of potassium hydroxide before feed in the fuel cell. Polarisation curves were measured, and they were found to produce lower current density values when compared to earlier tests with pure glucose. The Coulombic efficiency of pure glucose electrochemical oxidation in LTDMFC, which was calculated from a ratio of detected current capacity (As) to the maximum current capacity with the release of two electrons per molecule, was also found to be very low. Concerning the hydrolysates, the glucose concentrations were found to have values that were too low when compared to the earlier tests with pure glucose in a concentration of 1 M. The further development demands for the system under consideration are indicated. The concentration of glucose in the hydrolysate is essential to achieve high enough current density values in the LTDMFC.
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| 20. |
- Spets, J.-P, et al.
(författare)
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The Progress in the Ongoing Development Work : Enhancement of GlucoseElectro-Oxidation in Direct-Mode Fuel Cells - An Update
- 2009
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Ingår i: The Open Fuel Cells Journal. - : Bentham Open. - 1875-9327. ; 2, s. 11-14
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Tidskriftsartikel (refereegranskat)abstract
- This study deals with the R&D regarding the direct glucose fuel cell with a capacity of increasing the power density with glucose as a fuel. The direct-mode fuel cell in which the fuel and the alkaline electrolyte are mixed with each other is tested at room temperature. The direct-mode fuel cell is exposed to an externally generated electromagnetic field with 4 GHz sine signals between electrodes to cause both the splitting of the fuel molecule and the electrochemical oxidation. As a result from the use of the higher frequency signals, a maximum current density of 15 mAcm-2 has been achieved with the total voltage of 0.5 V.
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| 21. |
- Spets, J. -P, et al.
(författare)
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The Simultaneous Uses of the Direct-Mode Bioorganic Fuel Cell and the Function Generator for the Enhancement of the Glucose Electro-chemical Oxidation
- 2010
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Ingår i: International Journal of Electrochemical Science. - 1452-3981. ; 5:4, s. 547-555
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Tidskriftsartikel (refereegranskat)abstract
- In this study a test of the direct-mode bioorganic fuel cell (DMBFC) in which the fuel and the alkaline electrolyte are mixed with each other at two temperatures of 20 and 35 degrees C are carried out. The direct-mode bioorganic fuel cell is exposed to an externally generated electromagnetic field with simultaneous discharging in order to split the fuel molecule before the electrochemical oxidation at the two operation temperatures. The current-voltage characteristics are measured and analyzed. The liquid phase of the fuel-electrolyte concentration of the glucose was analysed both before and after the electrochemical tests at the operation temperature 20 degrees C. The aim is to continue with the development of the direct-mode glucose fuel cell by increasing the power density range by several mWcm(-2). This type of the fuel cell with glucose as a fuel has increased to the specific capacity levels of 120.8 and 132.7 Ah / kg glucose at the temperatures of 20 degrees C and 35 degrees C, respectively.
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| 22. |
- Albrecht, Eva, et al.
(författare)
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Telomere length in circulating leukocytes is associated with lung function and disease
- 2014
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 43:4, s. 983-992
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Tidskriftsartikel (refereegranskat)abstract
- Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Kauppila, JH, et al.
(författare)
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Cohort profile: gastric cancer in the population-based, Finnish National Esophago-Gastric Cancer Cohort (FINEGO) Study
- 2020
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:10, s. e039574-
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Tidskriftsartikel (refereegranskat)abstract
- The Finnish National Esophago-Gastric Cancer Cohort (FINEGO) was established with the aim of identifying factors that could contribute to improved outcomes in oesophago-gastric cancer. The aim of this study is to describe the patients with gastric cancer included in FINEGO.ParticipantsA total of 10 457 patients with gastric cancer or tumour diagnosis in the Finnish Cancer Registry or the Finnish Patient Registry during 1987–2016 were included in the cohort, with follow-up from Causes of Death Registry until 31 December 2016. All of the participants were at least 18 years of age, and had undergone either resectional or endoscopic mucosal surgery with curative or palliative intent.Findings to dateOf the 10 457 patients, 90.1% were identified to have cancer in both cancer and patient registries. In all, the median age was 70 at the time of surgery, 54.5% of the patients were men and 64.4% had no comorbidities. Education data were available for 31.1% of the patients, of whom the majority had had <12 years of formal education. Of the 7798 with cancer staging data available, 41.1% had a local cancer. Adenocarcinoma was the most common (94.2%) histological type. Almost all patients underwent open gastrectomy and 214% in hospitals with annual volume of more than 30 gastrectomies per year. A total of 8561 deaths occurred during the study period, of which 6474 were due to oesophago-gastric cancers. The 5-year survival was 34.6% and 5-year cancer-specific survival was 39.7%.Future plansThe data in FINEGO can be currently used for registry-based research but is being expanded by data extraction from patient records and scanning of histological samples from the Finnish biobanks. Initially, we are planning on studies on the national trends in treatment and mortality, and studies on the demographic factors and their influence on survival.
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| 28. |
- Kulmala, J., et al.
(författare)
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Association between mid- to late life physical fitness and dementia : evidence from the CAIDE study
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 276:3, s. 296-307
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. This study investigated the association between perceived physical fitness at midlife, changes in perceived fitness during the three decades from mid-to late life and dementia risk. Design. Prospective cohort study. Setting. Cardiovascular risk factors, ageing and incidence of dementia (CAIDE) study. Subjects. Subjects were selected from four independent, random samples of population-based cardiovascular surveys and were first examined in 1972, 1977, 1982 or 1987, when they were on average 50 years old. The CAIDE target population included 3559 individuals. A random sample of 2000 individuals still alive in 1997 was drawn for re-examinations (performed in 1998 and 2005-2008) that consisted of cognitive assessments, with 1511 subjects participating in at least one re-examination. Dementia diagnoses were also confirmed from national registers for the entire target population. Main outcome measure. All-cause dementia. Results. Poor physical fitness at midlife was associated with increased dementia risk in the entire target population [hazard ratio (HR), 1.5; 95% confidence interval (CI), 1.1-2.0]. In participants, odds ratio (OR) was 2.0 (95% CI, 0.9-4.0). This association was significant in apolipoprotein E epsilon 4 allele (APO epsilon 4) noncarriers (OR, 4.3; 95% CI, 1.4-13.3), men (HR, 1.8; 95% CI, 1.1-3.0) and people with chronic conditions (HR, 2.9; 95% CI, 1.3-6.6). A decline in fitness after midlife was also associated with dementia (OR, 3.0; 95% CI, 1.7-5.1), which was significant amongst both men and women and more pronounced in APOE epsilon 4 carriers (OR, 4.4; 95% CI, 2.1-9.1). Conclusions. Perceived poor physical fitness reflects a combination of biological and lifestyle-related factors that can increase dementia risk. A simple question about perceived physical fitness may reveal at-risk individuals who could benefit from preventive interventions.
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- Mikkola, T. M., et al.
(författare)
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Influence of long-term postmenopausal hormone-replacement therapy on estimated structural bone strength: A study in discordant monozygotic twins
- 2011
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431. ; 26:3, s. 546-52
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Tidskriftsartikel (refereegranskat)abstract
- Although postmenopausal hormone-replacement therapy (HRT) is known to prevent fractures, knowledge on the influence of long-term HRT on bone strength and its determinants other than areal bone mineral density is scarce. This study used a genetically controlled design with 24 monozygotic female twin pairs aged 54 to 72 years in which one cotwin was using HRT (mean duration 8 years) and the other had never used HRT. Estimated bone strength, cross-sectional area, volumetric bone mineral density, bone mineral mass, and cross-sectional density and mass distributions were assessed in the tibial shaft, distal tibia, and distal radius with peripheral computed tomography (pQCT). In the tibial shaft, HRT users had 9% [95% confidence interval (CI) 3%-15%] higher estimated bending strength than their nonusing cotwins. Larger cortical area and higher cortical bone mineral density accounted for this difference. The cortex was larger in the HRT users in the endocortical region. In the distal tibia, estimated compressive strength was 24% (95% CI 9%-40%) higher and in the distal radius 26% (95% CI 11%-41%) higher in the HRT users than in their nonusing cotwins owing to higher volumetric bone mineral density. No difference between users and nonusers was observed in total bone cross-sectional area in any measured bone site. The added mineral mass in the HRT users was distributed evenly within and between bone sites. In postmenopausal women, long-term HRT preserves estimated bone strength systemically by preventing bone mineral loss similarly in body weight-loaded and non-weight-loaded bone. (c) 2011 American Society for Bone and Mineral Research.
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- Putaala, J., et al.
(författare)
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Undetermined stroke with an embolic pattern-a common phenotype with high early recurrence risk
- 2015
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 47:5, s. 406-413
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Undetermined strokes with an embolic pattern (USEP) represent a common phenotype. We assessed their frequency and compared USEP with cardioembolic stroke with a known source and non-cardioembolic stroke etiology. Methods. Study patients were 540 consecutive ischemic stroke patients admitted to Helsinki University Hospital with primary end-point of recurrent stroke in a 21-month follow-up. Cox regression adjusting for CHA(2)DS(2)-VASc and anticoagulation estimated the risk of USEP on recurrent stroke. Results. A total of 229 (42.4%) patients had a non-cardioembolic stroke etiology, 184 (34.1%) had a cardioembolic stroke with a known source, and 127 (23.5%) were classified as USEP. USEP patients had less diabetes and prior TIA, with more severe symptoms than the non-cardioembolic stroke cases. They were younger, had fewer comorbidities, and less severe symptoms than the cardioembolic stroke patients. Cumulative risk of recurrent stroke was 10.0% (95% CI 4.1%-15.9%) for USEP, 5.0% (1.1%-8.9%) for cardioembolic strokes, and 5.0% (3.0%-7.0%) for non-cardioembolic strokes (P = 0.089). USEP associated with a higher risk of recurrent stroke compared to non-cardioembolic strokes (hazard ratio 2.36, 95% CI 1.02-5.47; P = 0.046) and cardioembolic stroke with a known source (1.83, 1.07-3.14; P = 0.028). Conclusions. Despite their younger age and more favorable risk factor profile compared with other phenotypes, USEP exhibited a high risk of stroke recurrence.
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- Soderstrom, HK, et al.
(författare)
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Cohort profile: a nationwide population-based retrospective assessment of oesophageal cancer in the Finnish National Esophago-Gastric Cancer Cohort (FINEGO)
- 2020
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:10, s. e039575-
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Tidskriftsartikel (refereegranskat)abstract
- The Finnish National Esophago-Gastric Cancer Cohort (FINEGO) was established to combine the available registry data with detailed patient information to form a comprehensive, retrospective, population-based research platform of surgically treated oesophageal and gastric cancer in Finland. This cohort profile describes the 2045 surgically treated patients with oesophageal cancer included in the FINEGO cohort.ParticipantsRegistry data were collected from the National Cancer, Patient, Education and Death Registries from 1 January 1987 to 31 December 2016. All patients over 18 years of age, who had either curative surgery, palliative surgery or salvage surgery for primary cancer in the oesophagus are included in this study.Findings to date2045 patients had surgery for oesophageal cancer in the selected time period. 67.2% were man, and the majority had only minor comorbidities. The proportions of adenocarcinomas and squamous cell carcinomas were 43.1% and 44.4%, respectively, and 12.5% had other or missing histology. Only about 23% of patients received neoadjuvant therapy. Oesophagectomy was the treatment of choice and most patients were treated at low-volume centres, but median annual hospital volume increased over time. Median overall survival was 23 months, 5-year survival for all patients in the cohort was 32.9% and cancer-specific survival was 36.5%.Future plansEven though Finland only has a population of 5.5 million, surgery for oesophageal carcinoma has not been centralised and therefore previously reported results have mostly been small, single-centre cohorts. Because of FINEGO, we now have a population-based, unselected cohort of surgically treated patients, enabling research on national trends over time regarding oesophageal cancer, including patient characteristics, tumour histology, stage and neoadjuvant treatment, surgical techniques, hospital volumes and patient mortality. Data collection is ongoing, and the cohort will be expanded to include more detailed data from patient records and national biobanks.
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- Surakka, Ida, et al.
(författare)
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A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:10, s. e1002333-
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain similar to 25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79 x 10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
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| 42. |
- Thunberg, S., et al.
(författare)
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Dose reduction in mammography with photon counting imaging
- 2004
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. ; , s. 457-465
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Konferensbidrag (refereegranskat)abstract
- The purpose of this study was to investigate if the glandular dose to the breast in mammography can significantly be reduced without compromising image quality, when using photon counting technology, in a multi-slit scanning photon counting detector, compared to a conventional film mammography system and commercial available digital mammography systems with TFT-array detectors. A CDMAM phantom study, with two different thicknesses of additional PMMA absorber, 4 cm and 7 cm respectively, has shown that multi-slit scanning photon counting detector technology can reduce the dose, without reducing the image quality. This comparison was made to two commercial available digital mammography systems Senographe 2000D (from GEMS) and Selenia (from Lorad). The results show that dose can be reduced with 63% to 77%, depending on object thickness, when using XCT for mammography. This dose reduction has also been verified clinically through a small pilot study with patients and specimen, where the comparison was made between XCT and film.
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| 44. |
- Boetker, Johan P, et al.
(författare)
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Anhydrate to hydrate solid-state transformations of carbamazepine and nitrofurantoin in biorelevant media studied in situ using time-resolved synchrotron X-ray diffraction.
- 2016
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Ingår i: European Journal of Pharmaceutics and Biopharmaceutics. - : Elsevier BV. - 0939-6411. ; 100, s. 119-127
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Tidskriftsartikel (refereegranskat)abstract
- Transformation of the solid-state form of a drug compound in the lumen of the gastrointestinal tract may alter the drug bioavailability and in extreme cases result in patient fatalities. The solution-mediated anhydrate-to-hydrate phase transformation was examined using an in vitro model with different biorelevant media, simulated fasted and fed state intestinal fluids containing bile salt and dioleoylphosphatidylcholine (DOPC) micelles, DOPC/sodium dodecyl sulfate (SDS) mixture, bile salt solution and water. Two anhydrate compounds (carbamazepine, CBZ and nitrofurantoin, NF) with different overall transformation time into hydrate form were used as model compounds. The transformations were monitored using direct structural information from time-resolved synchrotron X-ray diffraction. The kinetics of these transformations were estimated using multivariate data analysis (principal component analysis, PCA) and compared to those for nitrofurantoin (NF). The study showed that the solution-mediated phase transformation of CBZ anhydrate was remarkably faster in the DOPC/SDS medium compared to transformation in all the other aqueous dispersion media. The conversion time for CBZ anhydrate in water was shorter than for DOPC/SDS but still faster than the conversion seen in fed and fasted state micellar media. The conversion of CBZ anhydrate to hydrate was the slowest in the solution containing bile salt alone. In contrast, the solution-mediated phase transformations of NF did only show limited kinetic dependence on the dispersion media used, indicating the complexity of the nucleation process. Furthermore, when the CBZ and NF material was compacted into tablets the transformation times were remarkably slower. Results suggest that variations in the composition of the contents of the stomach/gut may affect the recrystallization kinetics, especially when investigating compounds with relatively fast overall transformation time, such as CBZ.
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| 47. |
- Hagg, S, et al.
(författare)
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Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
- 2017
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:4, s. e1100-
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Tidskriftsartikel (refereegranskat)abstract
- The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (β=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (β=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (β=−0.053; 95% CI: −0.087, −0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (β=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10−5), whereas carriers performed better in STROOP (β=−0.074; 95% CI: −0.140, −0.009; P=0.03). Causal associations were found for STROOP only (β=−0.598 per s.d.-increase of TL; 95% CI: −1.125, −0.072; P=0.026), with a larger effect in ɛ4-carriers (β=−0.699; 95% CI: −1.330, −0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.
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