Genome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.
In the North Sea, carcass failures have over the last years been the largest failure category for flexible pipes, causing multiple riser replacements [1]. The carcass failures could be split into two groups: axial tear-off and collapse. In order to determine the resistance to collapse, a 3D analysis model has been built using the explicit finite element (FE) program LS-Dyna. In addition, the LS-Dyna results were compared with a simplified 2D FE approach, using the non-linear implicit solver MARC. The 3D model allows for more complex sensitivities, such as curved pipe and carcass tension. The FE analyses were based upon measured carcass profile geometries and material data from hardness measurements at several positions along the carcass profile, including effects of strain hardening during manufacturing. Three different carcass profiles of three different risers were analysed. The study includes sensitivities on straight and curved pipe sections, axial preloaded carcass, carcass ovality, radial gap between carcass and pressure sheets and pressure increase velocity. Collapse resistance of axial strained carcass and bent pipe is not well documented and this paper will highlight some of the observed effects. The results from the FE analyses showed good correlation between the vendor data [2] both in shape of the buckling mode and capacity.
This paper presents results from a case study performed to evaluate the residual capacity of a 6″ flexible pipe when exposed to corrosion damages in the tensile armour. A three-dimensional nonlinear finite element model was developed using the computer code MARC to evaluate the increase in mean and dynamic stresses for a given number of damaged inner tensile armor wires. The study also includes the effect of these damages with respect to the associated stresses in the pressure spiral. Furthermore, the implications of a sequence of wire failures with respect to the accumulated time until cross-section failure in a probabilistic sense are addressed.
A digital twin is proposed to quantify the loads and mitigate the risk of rupture during the recovery operation of a flexible riser with severe structural weakness (30% of broken wires in the outer tensile armor layer). The allowable axial tension is compared with the loads expected during operation to establish safe operating limits. The digital twin is divided into a local model and a global model. The local analysis uses a finite element model to investigate how stresses on tensile armor wires change when the number of broken wires increases. It considers all pipe layers and two configurations, 1) straight and 2) with a curvature expected during the recovery operation. The FPSO motion performance is calibrated by offshore field measurements and improved RAOs for the global analysis are provided based on the measured motions. Finally, the allowable axial load from the local analysis is compared with the expected loads from the global analysis. The local model is simulated stepwise with 0 - 28 broken wires and indicated a reduction of 83% in allowable axial load with 25 broken wires. The results were combined with global simulations considering different sea states to provide insights about how close the loads might be to the allowable limit during operation and what loads the riser was subjected to since the last broken wires were detected. This analysis allowed the identification of the most critical steps in operation and helped to design the procedure to achieve ALARP risks. Finally, operating limits were discussed to keep the estimated load inside the established limits.
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