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- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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- Sakornsakolpat, Phuwanat, et al.
(författare)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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- Ehsanimehr, S., et al.
(författare)
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Sustainable Flame-Retardant Flax Fabrics by Engineered Layer-by-Layer Surface Functionalization with Phytic Acid and Polyethylenimine
- 2023
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Ingår i: Fire technology. - : Springer Science and Business Media LLC. - 0015-2684 .- 1572-8099.
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Tidskriftsartikel (refereegranskat)abstract
- New generation of mission-oriented fabrics meets advanced requirements; such as electrical conductivity, flame retardancy, and anti-bacterial properties. However, sustainability concerns still are on-demand in fabrication of multi-functional fabrics. In this work, we used a bio-based phosphorus molecule (phytic acid, PA) to reinforce flax fabrics against flame via layer-by-layer consecutive surface modification. First, the flax fabric was treated with PA. Then, polyethylenimine (PEI) was localized above it to create negative charges, and finally PA was deposited as top-layer. Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDX), and inductively-coupled plasma atomic emission spectrometry (ICP-AES) proved successful chemical treatment. Pyrolysis-combustion flow calorimetry (PCFC) showed significant drop by about 77% in the peak of heat release rate (pHRR) from 215 W/g for untreated to 50 W/g for treated flax fabric. Likewise, the total heat release (THR) decreased by more than three times from 11 to 3.2 kJ/g. Mechanical behavior of the treated flax fabric was completely different from untreated flax fabrics, changing from almost highly-strengthened behavior with short elongation at break to a rubber-like behavior with significantly higher elongation at break. Surface friction resistance was also improved, such that the abrasion resistance of the modified fabrics increased up to 30,000 rub cycles without rupture.
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- Wilkinson, Tom M. A., et al.
(författare)
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Non-typeable Haemophilus influenzae protein vaccine in adults with COPD : A phase 2 clinical trial
- 2019
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 37:41, s. 6102-6111
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Tidskriftsartikel (refereegranskat)abstract
- Loss of airway microbial diversity is associated with non-typeable Haemophilus influenzae (NTHi) infection and increased risk of exacerbation in chronic obstructive pulmonary disease (COPD). We assessed the safety and immunogenicity of an investigational vaccine containing NTHi antigens, recombinant protein D (PD) and combined protein E and Pilin A (PE-PilA), and AS01 adjuvant in adults with moderate/-severe COPD and prior exacerbations. In this phase 2, observer-blind, controlled trial (NCT02075541), 145 COPD patients aged 40-80 years randomly (1:1) received two doses of NTHi vaccine or placebo 60 days apart, on top of standard care. Reactogenicity in the 7-day post-vaccination period was higher following NTHi vaccine than placebo. Most solicited adverse events (AEs) were mild/moderate. At least one unsolicited AE was reported during the 30-day post-vaccination period by 54.8% of NTHi vaccine and 51.4% of placebo recipients. One serious AE (placebo group) was assessed by the investigator as vaccine-related. Anti-PD, anti-PE and anti-PiIA geometric mean antibody concentrations increased up to 30 days after each NTHi vaccine dose, waned thereafter, but remained higher than baseline (non-overlapping confidence intervals) up to 13 months post-dose 2. The frequency of specific CD4(+) T cells increased following two doses of NTHi vaccine and remained higher than baseline. Exploratory analysis showed a statistically non-significant lower yearly rate of moderate/severe exacerbations in the NTHi vaccine group than following placebo (1.49 versus 1.73) in the one-year period post-dose 2, with estimated vaccine efficacy of 13.3% (95% confidence interval -24.2 to 39.5; p = 0.44). The NTHi vaccine had an acceptable safety and reactogenicity profile and good immunogenicity in adults with COPD.
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