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- Mishra, A., et al.
(author)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Journal article (peer-reviewed)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 9. |
- Damineli, Bruno L., et al.
(author)
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Effects of filler mineralogy on the compressive strength of cementitious mortars
- 2021
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In: Construction and Building Materials. - : Elsevier BV. - 0950-0618 .- 1879-0526. ; 299
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Journal article (peer-reviewed)abstract
- Substituting cement with fillers is crucial to formulate cost-effective cementitious materials with low CO2 emissions. However, despite limestone, there is a lack of knowledge of fillers from other mineralogical sources for use in cementitious pastes. This study investigates the effects of characteristics of fillers from 6 mineralogical sources on the reactivity and compressive strength of the cementitious pastes, which could allow increasing industrial possibilities. The filler density and the paste total bound water content allowed to determine the paste porosity, which has a much better fit with the compressive strength than the water-binder ratio.
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| 10. |
- Damineli, B. L., et al.
(author)
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Viscosity prediction of cement-filler suspensions using interference model : A route for binder efficiency enhancement
- 2016
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In: Cement and Concrete Research. - : Elsevier. - 0008-8846 .- 1873-3948. ; 84, s. 8-19
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Journal article (peer-reviewed)abstract
- Producing cementitious materials with low CO2 emissions is a key challenge for sustainability, considering the increasing demand for cement and the inefficacy of current industrial solutions. Improving the efficiency of binder use is mandatory, so that binder replacement by inert fillers with lower environmental loads is an alternative, which demands careful control of the rheological behaviour to decrease the water demand of pastes. Dispersion and packing models are well known, but other less explored parameters of raw materials (surface area, density, roughness) and paste (water content, distance between particles) determine the interaction among particles, affecting the paste's rheological behaviour. The aim of this paper is to assess the influence of inert fillers on the rheological behaviour of cementitious pastes. A range of 12 inert fillers with varied aspects was evaluated. The results indicated a good agreement between the Casson viscosity and the interference parameter calculated using the interference model.
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| 11. |
- Heijstek, M W, et al.
(author)
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EULAR recommendations for vaccination in paediatric patients with rheumatic diseases.
- 2011
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:10, s. 1704-12
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Journal article (peer-reviewed)abstract
- Evidence-based recommendations for vaccination of paediatric patients with rheumatic diseases (PaedRD) were developed by following the EULAR standardised procedures for guideline development. The EULAR task force consisted of (paediatric) rheumatologists/immunologists, one expert in vaccine evaluation, one expert in public health and infectious disease control, and one epidemiologist. A systematic literature review was conducted in MEDLINE, EMBASE, and abstracts of the EULAR and American College of Rheumatology meetings of 2008/9. The level of evidence and strength of recommendation were based on customary scoring systems. Delphi voting was applied to assess the level of agreement between task force members. 107 papers and eight abstracts were used. The majority of papers considered seasonal influenza (41) or pneumococcal (23) vaccination. 26 studies were performed specifically in paediatric patients, and the majority in adult rheumatoid arthritis and systemic lupus erythematosus patients. Fifteen recommendations were developed with an overall agreement of 91.7%. More research is needed on the safety and immunogenicity of (live-attenuated) vaccination in PaedRD, particularly in those using biologicals, and the effect of vaccination on prevention of infections.
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| 12. |
- Heijstek, M W, et al.
(author)
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Vaccination in paediatric patients with auto-immune rheumatic diseases: A systemic literature review for the European League against Rheumatism evidence-based recommendations.
- 2011
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In: Autoimmunity reviews. - : Elsevier BV. - 1873-0183 .- 1568-9972. ; 11:2, s. 112-122
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To analyze available evidence on vaccinations in paediatric patients with rheumatic and autoinflammatory diseases. This evidence formed the basis of the recently constructed European League against Rheumatism (EULAR) recommendations for vaccination of these patients. METHODS: A systematic literature review in the MEDLINE and EMBASE databases was conducted using various terms for vaccinations, paediatric rheumatic and autoinflammatory diseases and immunosuppressive drugs. Only papers on paediatric patients (<18years of age) were selected. A panel of 13 experts in the field graded methodological quality and extracted data using predefined criteria. RESULTS: 27 papers were available. No studies were found on autoinflammatory diseases. 14 studies considered live-attenuated vaccines. Evidence so far supports the safety and immunogenicity of non-live composite vaccines, although studies were underpowered to accurately assess safety. Live-attenuated vaccines did not cause disease flares or severe adverse events, not even in patients on methotrexate and low dose glucocorticosteroids. Seven patients on anti-TNFalpha therapy were described receiving the live-attenuated measles, mumps, rubella (n=5) or varicella (n=2) booster without severe adverse events. CONCLUSIONS: Data on safety and efficacy of vaccinations in paediatric patients with rheumatic diseases is reassuring, but too limited to draw definite conclusions. More research is needed on the safety and efficacy of especially live-attenuated vaccines in patients with rheumatic and autoinflammatory diseases using high dose immunosuppressive drugs.
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