Three-dimensional flow characteristics in ventricular assist devices: Impact of valve design and operating conditions

ObjectiveThe use of paracorporeal ventricular assist devices has become a well-established procedure for patients with cardiogenic shock. However, implantation of ventricular assist devices is often associated with severe complications, such as thrombosis inside the ventricular assist device and subsequent embolic events. It was the purpose of this study to use flow-sensitive 4-dimensional magnetic resonance imaging for a detailed analysis of the 3-dimensional (3D) flow dynamics inside a clinical routine ventricular assist device and to study the effect of different system adjustments and a new valve design on flow patterns.MethodsA routinely used clinical paracorporeal ventricular assist device was integrated into a magnetic resonance-compatible mock loop. Flow-sensitive 3D magnetic resonance imaging was performed to measure time-resolved 3-directional flow velocities (spatial resolution ∼ 1.2 mm, temporal resolution = 42.4 ms) in the entire device under ideal conditions (full fill, full empty, ejection fraction = 88%), insufficient filling (ejection fraction = 81%), and insufficient emptying (ejection fraction = 67%) of the pump chamber. In addition, a new valve design was evaluated. Flexible control and monitoring of pressures at inlet and outlet were used to generate realistic boundary conditions.ResultsFlow pattern changes for different operating conditions were clearly identified and included reduced velocities during systolic outflow for impaired filling (78% reduction in pump flow compared with optimal operating conditions) and impaired clearing of the pump chamber for insufficient emptying (52% reduction). For all operating conditions, 3D visualization revealed vortex flow inside the ventricular assist device at typical locations of thrombus formation near the valve systems. Most noticeably, the new valve design provided similar global ventricular assist device function (pump flow 3.6 L/min), but vortex formation was eliminated.ConclusionsThe results of this study provide insight into the mechanisms underlying possible thrombus formation inside a ventricular assist device and the effect of different system adjustments. The presented methods may permit the optimization of future ventricular assist device systems with respect to optimal flow conditions

Real-time grammar processing by native and non-native speakers : constructions unique to the second language

We investigated second language (L2) comprehension of grammatical structures that are unique to the L2, and which are known to cause persistent difficulties in production. A visual-world eye-tracking experiment focused on online comprehension of English articles by speakers of the article-lacking Mandarin, and a control group of English native speakers. The results show that non-native speakers from article-lacking backgrounds can incrementally utilise the information signalled by L2 articles in real time to constrain referential domains and resolve reference more efficiently. The findings support the hypothesis that L2 processing does not always over-rely on pragmatic affordances, and that some morphosyntactic structures unique to the target language can be processed in a targetlike manner in comprehension – despite persistent difficulties with their production. A novel proposal, based on multiple meaning-to-form, but consistent form-to-meaning mappings, is developed to account for such comprehension–production asymmetries

Hemodynamic forces in the left and right ventricles of the human heart using 4D flow magnetic resonance imaging: Phantom validation, reproducibility, sensitivity to respiratory gating and free analysis software

8siPurpose To investigate the accuracy, reproducibility and sensitivity to respiratory gating, field strength and ventricle segmentation of hemodynamic force quantification in the left and right ventricles of the heart (LV and RV) using 4D-flow magnetic resonance imaging (MRI), and to provide free hemodynamic force analysis software. Materials and methods A pulsatile flow phantom was imaged using 4D flow MRI and laser-based particle image velocimetry (PIV). Cardiac 4D flow MRI was performed in healthy volunteers at 1.5T (n = 23). Reproducibility was investigated using MR scanners from two different vendors on the same day (n = 8). Subsets of volunteers were also imaged without respiratory gating (n = 17), at 3T on the same day (n = 6), and 1–12 days later on the same scanner (n = 9, median 6 days). Agreement was measured using the intraclass correlation coefficient (ICC). Results Phantom validation showed good accuracy for both scanners (Scanner 1: bias -14±9%, y = 0.82x+0.08, R2 = 0.96, Scanner 2: bias -12±8%, y = 0.99x-0.08, R2 = 1.00). Force reproducibility was strong in the LV (0.09±0.07 vs 0.09±0.07 N, bias 0.00±0.04 N, ICC = 0.87) and RV (0.09±0.06 vs 0.09±0.05 N, bias 0.00±0.03, ICC = 0.83). Strong to very strong agreement was found for scans with and without respiratory gating (LV/RV: ICC = 0.94/0.95), scans on different days (ICC = 0.92/0.87), and 1.5T and 3T scans (ICC = 0.93/0.94). Conclusion Software for quantification of hemodynamic forces in 4D-flow MRI was developed, and results show high accuracy and strong to very strong reproducibility for both the LV and RV, supporting its use for research and clinical investigations. The software including source code is released freely for research.openopenTöger, Johannes; Arvidsson, Per M.; Bock, Jelena; Kanski, Mikael; Pedrizzetti, Gianni; Carlsson, Marcus; Arheden, Håkan; Heiberg, EinarTöger, Johannes; Arvidsson, Per M.; Bock, Jelena; Kanski, Mikael; Pedrizzetti, Gianni; Carlsson, Marcus; Arheden, Håkan; Heiberg, Eina

Complex Patterns of Chromosome 11 Aberrations in Myeloid Malignancies Target CBL, MLL, DDB1 and LMO2

Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs). Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%). Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR) on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013). One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements