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- Shrine, N, et al.
(author)
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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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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Journal article (peer-reviewed)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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- Albrecht, Eva, et al.
(author)
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Telomere length in circulating leukocytes is associated with lung function and disease
- 2014
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 43:4, s. 983-992
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Journal article (peer-reviewed)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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- Eleftheriadis, Georgios K., et al.
(author)
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Automated digital design for 3D-printed individualized therapies
- 2021
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 599
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Journal article (peer-reviewed)abstract
- Customization of pharmaceutical products is a central requirement for personalized medicines. However, the existing processing and supply chain solutions do not support such manufacturing-on-demand approaches. In order to solve this challenge, three-dimensional (3D) printing has been applied for customization of not only the dose and release characteristics, but also appearance of the product (e.g., size and shape). A solution for customization can be realized via non-expert-guided processing of digital designs and drug dose. This study presents a proof-of-concept computational algorithm which calculates the optimal dimensions of grid-like orodispersible films (ODFs), considering the recommended dose. Further, the algorithm exports a digital design file which contains the required ODF configuration. Cannabidiol (CBD) was incorporated in the ODFs, considering the simple correspondence between the recommended dose and the patient's weight. The ODFs were 3D-printed and characterized for their physicochemical, mechanical, disintegration and drug release properties. The algorithm was evaluated for its accuracy on dose estimation, highlighting the reproducibility of individualized ODFs. The in vitro performance was principally affected by the thickness and volume of the grid-like structures. The concept provides an alternative approach that promotes automation in the manufacturing of personalized medications in distributed points of care, such as hospitals and local pharmacies.
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- Kaprio, J, et al.
(author)
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The Older Finnish Twin Cohort - 45 Years of Follow-up
- 2019
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In: 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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Journal article (peer-reviewed)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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- Calcatelli, A., et al.
(author)
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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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In: Metrologia. - 0026-1394 .- 1681-7575. ; 42:SUPPL.
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Journal article (peer-reviewed)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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