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- Jones, G., et al.
(author)
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Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n=48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p=4x10(-17)), arthritis (GDF5p=4x10(-13)), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing. Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.
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- Butcher, L, et al.
(author)
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Higher sRAGE Levels Predict Mortality in Frail Older Adults with Cardiovascular Disease
- 2021
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In: Gerontology. - : S. Karger AG. - 1423-0003 .- 0304-324X. ; 67:2, s. 202-210
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Journal article (peer-reviewed)abstract
- <b><i>Introduction:</i></b> The evidence that blood levels of the soluble receptor for advanced glycation end products (sRAGE) predict mortality in people with cardiovascular diseases (CVD) is inconsistent. To clarify this matter, we investigated if frailty status influences this association. <b><i>Methods:</i></b> We analysed data of 1,016 individuals (median age, 75 years) from 3 population-based European cohorts, enrolled in the FRAILOMIC project. Participants were stratified by history of CVD and frailty status. Mortality was recorded during 8 years of follow-up. <b><i>Results:</i></b> In adjusted Cox regression models, baseline serum sRAGE was positively associated with an increased risk of mortality in participants with CVD (HR 1.64, 95% CI 1.09–2.49, <i>p</i> = 0.019) but not in non-CVD. Within the CVD group, the risk of death was markedly enhanced in the frail subgroup (CVD-F, HR 1.97, 95% CI 1.18–3.29, <i>p</i> = 0.009), compared to the non-frail subgroup (CVD-NF, HR 1.50, 95% CI 0.71–3.15, <i>p</i> = 0.287). Kaplan-Meier analysis showed that the median survival time of CVD-F with high sRAGE (>1,554 pg/mL) was 2.9 years shorter than that of CVD-F with low sRAGE, whereas no survival difference was seen for CVD-NF. Area under the ROC curve analysis demonstrated that for CVD-F, addition of sRAGE to the prediction model increased its prognostic value. <b><i>Conclusions:</i></b> Frailty status influences the relationship between sRAGE and mortality in older adults with CVD. sRAGE could be used as a prognostic marker of mortality for these individuals, particularly if they are also frail.
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- García-Mañas, F., et al.
(author)
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Experimental evaluation of feedforward tuning rules
- 2021
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In: Control Engineering Practice. - : Elsevier BV. - 0967-0661. ; 114
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Journal article (peer-reviewed)abstract
- This paper presents a practical comparison for some of the most relevant tuning rules for feedforward compensators that have been published in the recent years. The work is focused on the rejection of disturbances that affect the process output. The different tuning rules are evaluated in simulation and several performance indices are calculated in order to provide a quantitative comparison. All the tuning rules are compared against a standard feedback controller and the classical open-loop design method for feedforward compensators. Furthermore, two of the analysed tuning rules are tested in a real process for the first time. To that end, a traditional greenhouse was selected as a test bed for an experimental evaluation of the feedforward controllers in the context of a challenging control problem with significant disturbances.
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