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- Patel, Riyaz S., et al.
(författare)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 2. |
- Patel, Riyaz S., et al.
(författare)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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- Berg, Daniel, 1977
(författare)
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A Comprehensive Approach to Modeling and Control of Thermomechanical Pulping Processes
- 2005
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The central issue of the thesis is modeling and control of the Thermomechanical Pulp (TMP) process in which large refiners are used to produce pulp for newsprint. The TMP process is one of the most complex and versatile, electricity consuming industrial processes today. In this thesis, modeling has been addressed from many different perspectives, timescales and levels of detail, to enable a more thorough understanding of the process. The theories comprise mill-wide energy modeling, dynamic modeling and control of a refiner line and modeling of the refiner zone process. The modeling theories are verified using measurements from a full-scale refiner line and include measurements of temperatures and high-frequency pressure fluctuations inside the refining zones. In this thesis, a complete model describing the TMP process from an energy perspective is presented. As the steam produced in the refiners is used at the paper mill together with additional steam from a power plant, a reduction in energy consumption in the TMP-plant does not necessarily imply lower overall energy usage. With the derived mill-wide energy model, a complete energy optimization can be performed. The refiner line is a complex dynamic system where the internal interconnection, the dynamics of the unit operations, the production rate and possible stiction in control valves determine the major part of the plant's dynamic behavior. To illustrate this, a dynamic model of the refiner line has been included in the thesis and has also been implemented on-line parallel to the true refiner line. Moreover, a theory for control of the refiner has been derived as a 3 x 3 decoupling strategy using load, consistency and temperature at a certain radius in the refining zone as outputs. This relatively complex control structure appears to be a reasonable solution, but sensitive to model uncertainties. It is shown that a more robust choice for control would therefore be a 2 x 2 decoupling control, or exchange an output, preferably the load to another, possibly a soft sensor, output. The physical models of the defibration process presented in this thesis use temperatures and pressure measurements in the refining zone. The consistency estimation routine has proven to be faster than the online measurements and more accurate than a pure energy balance of the refiner. The principal contribution is, however, the increased understanding of the refining process as it gives plausible explanation to the refining mechanism, most notably of the refining work distribution in the refining zone and the transfer of macroscopic motion to inner energy via viscous dissipation. Finally, the measured pressure signals presented are shown to be the generated dynamic pressure as bars pass over the sensor. It is also concluded that the pressure measurements, and thereby the defibration, differ between the two refining zones in the specific refiner studied. The energy content in important frequency peaks are also found to vary with operation point.
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