| 1. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
|
|
| 3. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Lindblad-Toh, Kerstin, et al.
(författare)
-
Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
-
Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
|
|
| 7. |
- Weinstein, John N., et al.
(författare)
-
The cancer genome atlas pan-cancer analysis project
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
-
Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
|
|
| 8. |
- Apergis-Schoute, John, et al.
(författare)
-
Editorial : Neuronal Co-transmission
- 2019
-
Ingår i: Frontiers in Neural Circuits. - : FRONTIERS MEDIA SA. - 1662-5110. ; 13
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 9. |
- Caddy, Harrison T., et al.
(författare)
-
Modelling large scale artery haemodynamics from the heart to the eye in response to simulated microgravity
- 2024
-
Ingår i: npj Microgravity. - : Nature Research. - 2373-8065. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated variations in haemodynamics in response to simulated microgravity across a semi-subject-specific three-dimensional (3D) continuous arterial network connecting the heart to the eye using computational fluid dynamics (CFD) simulations. Using this model we simulated pulsatile blood flow in an upright Earth gravity case and a simulated microgravity case. Under simulated microgravity, regional time-averaged wall shear stress (TAWSS) increased and oscillatory shear index (OSI) decreased in upper body arteries, whilst the opposite was observed in the lower body. Between cases, uniform changes in TAWSS and OSI were found in the retina across diameters. This work demonstrates that 3D CFD simulations can be performed across continuously connected networks of small and large arteries. Simulated results exhibited similarities to low dimensional spaceflight simulations and measured data—specifically that blood flow and shear stress decrease towards the lower limbs and increase towards the cerebrovasculature and eyes in response to simulated microgravity, relative to an upright position in Earth gravity.
|
|
| 10. |
- Frantz, Laurent A. F., et al.
(författare)
-
Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe
- 2019
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:35, s. 17231-17238
-
Tidskriftsartikel (refereegranskat)abstract
- Archaeological evidence indicates that pig domestication had begun by similar to 10,500 y before the present ( BP) in the Near East, and mitochondrial DNA ( mtDNA) suggests that pigs arrived in Europe alongside farmers similar to 8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
|
|
| 11. |
- Munshi, Bijit, et al.
(författare)
-
Surgical Decision Making in Uncomplicated Type B Aortic Dissection : A Survey of Australian/New Zealand and European Surgeons
- 2020
-
Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 60:2, s. 194-200
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: There is controversy about the role of pre-emptive thoracic endovascular aortic repair (TEVAR) in uncomplicated type B aortic dissection (TBAD). The aim was to understand expert opinions and the factors influencing decision making. Methods: In 2018, surgeons from Australia/New Zealand (ANZ) and Europe (EUR) were contacted to participate in an online survey which comprised questions about preferences for pre-emptive TEVAR, followed by five case scenarios, and two ranking questions for anatomical and technical risk factors respectively. Case 1 was designed to favour TEVAR in a hypertensive patient with partial false lumen thrombosis and large diameter (aortic >= 40 mm, false lumen >= 22 mm). Case 2 had no risk factors mandating TEVAR, according to current evidence. Cases 3, 4, and 5 were designed to test one risk factor respectively, large entry tear on the inner aortic curvature (>= 10 mm), partial false lumen thrombosis, and large diameter alone. Results: There were 75 responses, 42 from EUR and 33 from ANZ. Almost half of surgeons (49.3%) endorsed preemptive TEVAR with 82.3% preferring to perform TEVAR in the subacute phase. In Case 1 and 5, 58.3% and 52.8% of surgeons respectively chose TEVAR, the highest rates obtained in the survey. Cases 1 and 5 included large diameters >= 40 mm, which were ranked the highest in importance when surgeons considered anatomical risk factors. Surgeons who recommend pre-emptive TEVAR were more likely to choose TEVAR in both Case 1 (83.3% vs. 33.3%, p < .001, 95% CI 27.6%-65.8%) and Case 5 (69.4% vs. 38.2%, p = .008, 95% CI 8.2%-50.0%). Conclusion: In this survey about uncomplicated TBAD, about half of surgeons recommended pre-emptive TEVAR in selected cases. The surgeon's predisposition towards intervention and large diameters appear to be the most influential factors in decision making. These findings underline the uncertainty in today's practice and emphasise the need for better predictive tools.
|
|
| 12. |
- Parker, Louis P., et al.
(författare)
-
Cannulation configuration and recirculation in venovenous extracorporeal membrane oxygenation
- 2022
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Venovenous extracorporeal membrane oxygenation is a treatment for acute respiratory distress syndrome. Femoro-atrial cannulation means blood is drained from the inferior vena cava and returned to the superior vena cava; the opposite is termed atrio-femoral. Clinical data comparing these two methods is scarce and conflicting. Using computational fluid dynamics, we aim to compare atrio-femoral and femoro-atrial cannulation to assess the impact on recirculation fraction, under ideal conditions and several clinical scenarios. Using a patient-averaged model of the venae cavae and right atrium, commercially-available cannulae were positioned in each configuration. Additionally, occlusion of the femoro-atrial drainage cannula side-holes with/without reduced inferior vena cava inflow (0-75%) and retraction of the atrio-femoral drainage cannula were modelled. Large-eddy simulations were run for 2-6L/min circuit flow, obtaining time-averaged flow data. The model showed good agreement with clinical atrio-femoral recirculation data. Under ideal conditions, atrio-femoral yielded 13.5% higher recirculation than femoro-atrial across all circuit flow rates. Atrio-femoral right atrium flow patterns resembled normal physiology with a single large vortex. Femoro-atrial cannulation resulted in multiple vortices and increased turbulent kinetic energy at > 3L/min circuit flow. Occluding femoro-atrial drainage cannula side-holes and reducing inferior vena cava inflow increased mean recirculation by 11% and 32%, respectively. Retracting the atrio-femoral drainage cannula did not affect recirculation. These results suggest that, depending on drainage issues, either atrio-femoral or femoro-atrial cannulation may be preferrable. Rather than cannula tip proximity, the supply of available venous blood at the drainage site appears to be the strongest factor affecting recirculation.
|
|
| 13. |
- Parker, Louis P., et al.
(författare)
-
Chapter 15 - Multiphysics flow modeling in the aorta
- 2024
-
Ingår i: Biomechanics of the Aorta. - : Elsevier BV. ; , s. 321-345
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Complex physics and biochemistry, the wide range of temporal and spatial scales to be captured, and the significant inter- and intraindividual variations make the description of the blood flow in the human aorta a difficult task. Although computational tools are mature, said aspects challenge aortic biomechanical models, and the approach must always be tailored to the question at hand. Besides being highly pulsatile, the curvature and tortuosity of the aortic geometry strongly impacts the flow dynamics with aortic pathologies may even lead to turbulent flow. In the following chapter, the characteristics of blood and different modeling approaches for rheology, species transport and thrombus/stenosis development will be addressed.
|
|
| 14. |
- Parker, Louis P., et al.
(författare)
-
Computational Fluid Dynamics of the Right Atrium : A Comparison of Modeling Approaches in a Range of Flow Conditions
- 2022
-
Ingår i: Journal of Engineering and Science in Medical Diagnostics and Therapy. - : ASME International. - 2572-7958 .- 2572-7966. ; 5:3
-
Tidskriftsartikel (refereegranskat)abstract
- The right atrium (RA) combines flows from the inferior (IVC) and superior vena cava (SVC). Here RA mixing is simulated using computational fluid dynamics, comparing four modeling approaches. A patient-averaged model (11 M cells) was created from four volunteers. We compared: (1) unsteady k–ω Reynolds-averaged Navier–Stokes (URANS) (2) implicit large eddy simulation with second-order upwind convection scheme (iLES-SOU) (3) iLES with bounded-central difference convection scheme (iLES-BCD) and (4) LES with wall-adapting local eddy-viscosity (LES-WALE). A constant inlet flow rate of 6 L/min was applied with both IVC/SVC contributions ranging from 30–70%. A higher density mesh (37 M cells) was also simulated for models 2 and 4 (equal IVC/SVC flow) to assess the accuracy of models 1–4. Results from the 11 M cell LES-WALE model showed good agreement with the 37 M cell meshes. All four 11 M cell models captured the same large-scale flow structures. There were local differences in velocity, time-averaged wall shear stress, and IVC/SVC mixing when compared to LES-WALE, particularly at high SVC flow. Energy spectra and velocity animations from the LES-WALE model suggest the presence of transitional flow. For the general flow structures, all four methods provide similar results, though local quantities can vary greatly. On coarse meshes, the convection scheme and subgrid-scale (SGS) model have a significant impact on results. For RA flows, URANS should be avoided and iLES models are sensitive to convection scheme unless used on a highly resolved grid.
|
|
| 15. |
- Parker, Louis P., et al.
(författare)
-
Hemodynamic and recirculation performance of dual lumen cannulas for venovenous extracorporeal membrane oxygenation
- 2023
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Venovenous extracorporeal membrane oxygenation (ECMO) can be performed with two single lumen cannulas (SLCs) or one dual-lumen cannula (DLC) where low recirculation fraction (Rf) is a key performance criterion. DLCs are widely believed to have lower Rf , though these have not been directly compared. Similarly, correct positioning is considered critical although its impact is unclear. We aimed to compare two common bi-caval DLC designs and quantify R f in several positions. Two different commercially available DLCs were sectioned, measured, reconstructed, scaled to 27Fr and simulated in our previously published patient-averaged computational model of the right atrium (RA) and venae cavae at 2–6 L/min. One DLC was then used to simulate ± 30° and ± 60° rotation and ± 4 cm insertion depth. Both designs had low Rf (< 7%) and similar SVC/IVC drainage fractions and pressure drops. Both cannula reinfusion ports created a high-velocity jet and high shear stresses in the cannula (> 413 Pa) and RA (> 52 Pa) even at low flow rates. Caval pressures were abnormally high (16.2–23.9 mmHg) at low flow rates. Rotation did not significantly impact Rf . Short insertion depth increased Rf (> 31%) for all flow rates whilst long insertion only increased Rf at 6 L/min (24%). Our results show that DLCs have lower Rf compared to SLCs at moderate-high flow rates (> 4 L/min), but high shear stresses. Obstruction from DLCs increases caval pressures at low flow rates, a potential reason for increased intracranial hemorrhages. Cannula rotation does not impact Rf though correct insertion depth is critical.
|
|
| 16. |
- Parker, Louis P., et al.
(författare)
-
Impact of altered vena cava flow rates on right atrium flow characteristics
- 2022
-
Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 132:5, s. 1167-1178
-
Tidskriftsartikel (refereegranskat)abstract
- The right atrium (RA) combines the superior vena cava (SVC) and inferior vena cava (IVC) flows. Treatments like extracorporeal membrane oxygenation (ECMO) and hemodialysis by catheter alter IVC/SVC flows. Here we assess how altered IVC/SVC flow contributions impact RA flow. Four healthy volunteers were imaged with computerized tomography (CT), reconstructed and combined into a patient-averaged model. Large eddy simulations (LESs) were performed for a range of IVC/SVC flow contributions (30%-70% each, increments of 5%) and common flow metrics were recorded. Model sensitivity to reconstruction domain extent, constant/pulsatile inlets, and hematocrit was also assessed. Consistent with literature, a single vortex occupied the central RA across all flowrates with a smaller counter-rotating vortex, not previously reported, in the auricle. Vena cava flow was highly helical. RA turbulent kinetic energy (TKE; P = 0.027) and time-averaged wall shear stress (WSS; P < 0.001) increased with SVC flow. WSS was lower in the auricle (2 Pa, P < 0.001). WSS in the vena cava was equal at IVC/SVC = 65/35%. The model was highly sensitive to the reconstruction domain with cropped geometries lacking helicity in the venae cavae, altering the RA flow. The RA flow was not significantly affected by constant inlets or hematocrit. The commonly reported vortex in in the central RA is confirmed; however, a new, smaller vortex was also recorded in the auricle. When IVC flow dominates, as is normal, TKE in the RA is reduced and WSS in the venae cavae equalize. Significant helicity exists in the vena cava, as a result of distal geometry and this geometry appears crucial to accurately simulating RA flow. NEW & NOTEWORTHY Right atrium turbulent kinetic energy increases as the proportion of flow entering from the superior vena cava is increased. Although the commonly reported large right atrium vortex was confirmed across all flow scenarios, a new smaller vortex is observed in the right auricle. The caval veins exhibit highly helical flow and this appears to be the result of distal venous morphology.
|
|
| 17. |
- Parker, Louis P., et al.
(författare)
-
In silico parametric analysis of femoro-jugular venovenous ECMO and return cannula dynamics : In silico analysis of femoro-jugular VV ECMO
- 2024
-
Ingår i: Medical Engineering and Physics. - : Elsevier BV. - 1350-4533 .- 1873-4030. ; 125
-
Tidskriftsartikel (refereegranskat)abstract
- Background: : Increasingly, computational fluid dynamics (CFD) is helping explore the impact of variables like: cannula design/size/position/flow rate and patient physiology on venovenous (VV) extracorporeal membrane oxygenation (ECMO). Here we use a CFD model to determine what role cardiac output (CO) plays and to analyse return cannula dynamics. Methods: : Using a patient-averaged model of the right atrium and venae cava, we virtually inserted a 19Fr return cannula and a 25Fr drainage cannula. Running large eddy simulations, we assessed cardiac output at: 3.5–6.5 L/min and ECMO flow rate at: 2–6 L/min. We analysed recirculation fraction (Rf), time-averaged wall shear stress (TAWSS), pressure, velocity, and turbulent kinetic energy (TKE) and extracorporeal flow fraction (EFF = ECMO flow rate/CO). Results: : Increased ECMO flow rate and decreased CO (high EFF) led to increased Rf (R = 0.98, log fit). Negative pressures developed in the venae cavae at low CO and high ECMO flow (high CR). Mean return cannula TAWSS was >10 Pa for all ECMO flow rates, with majority of the flow exiting the tip (94.0–95.8 %). Conclusions: : Our results underpin the strong impact of CO on VV ECMO. A simple metric like EFF, once supported by clinical data, might help predict Rf for a patient at a given ECMO flow rate. The return cannula imparts high shear stresses on the blood, largely a result of the internal diameter.
|
|
| 18. |
- Parker, Louis P., et al.
(författare)
-
Proximal false lumen thrombosis is associated with low false lumen pressure and fewer complications in type B aortic dissection
- 2022
-
Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 75:4, s. 1181-1190.e5
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Improved risk stratification is a key priority for type B aortic dissection (TBAD). Partial false lumen thrombus morphology is an emerging predictor of complications. However, partial thrombosis is poorly defined, and its evaluation in clinical studies has been inconsistent. Thus, we aimed to characterize the hemodynamic pressure in TBAD and determine how the pressure relates to the false lumen thrombus morphology and clinical events. Methods: The retrospective admission computed tomography angiograms of 69 patients with acute TBAD were used to construct three-dimensional computational models for simulation of cyclical blood flow and calculation of pressure. The patients were categorized by the false lumen thrombus morphology as minimal, extensive, proximal or distal thrombosis. Linear regression analysis was used to compare the luminal pressure difference between the true and false lumen for each morphology group. The effect of morphology classification on the incidence of acute complications within 14 days was studied using logistic regression adjusted for clinical parameters. A survival analysis for adverse aortic events at 1 year was also performed using Cox regression. Results: Of the 69 patients, 44 had experienced acute complications and 45 had had an adverse aortic event at 1 year. The mean +/- standard deviation age was 62.6 +/- 12.6 years, and 75.4% were men. Compared with the patients with minimal thrombosis, those with proximal thrombosis had a reduced false lumen pressure by 10.1 mm Hg (95% confidence interval [CI], 4.3-15.9 mm Hg; P = .001). The patients who had not experienced an acute complication had had a reduced relative false lumen pressure (-6.35 mm Hg vs -0.62 mm Hg; P = .03). Proximal thrombosis was associated with fewer acute complications (odds ratio, 0.17; 95% CI, 0.04-0.60; P = .01) and 1-year adverse aortic events (hazard ratio, 0.36; 95% CI, 0.16-0.80; P = .01). Conclusions: We found that proximal false lumen thrombosis was a marker of reduced false lumen pressure. This might explain how proximal false lumen thrombosis appears to be protective of acute complications (eg, refractory hypertension or pain, aortic rupture, visceral or limb malperfusion, acute expansion) and adverse aortic events within the first year.
|
|
| 19. |
- Parker, Louis P., et al.
(författare)
-
Venovenous extracorporeal membrane oxygenation drainage cannula performance : From generalized to patient-averaged vessel model
- 2024
-
Ingår i: Physics of fluids. - : AIP Publishing. - 1070-6631 .- 1089-7666. ; 36:6
-
Tidskriftsartikel (refereegranskat)abstract
- Venovenous extracorporeal membrane oxygenation is used for respiratory support in the most severe cases of acute respiratory distress syndrome. Blood is drained from the large veins, oxygenated in an artificial lung, and returned to the right atrium (RA). In this study, we have used large eddy simulations to simulate a single-stage “lighthouse” drainage cannula in a patient-averaged model of the large veins and RA, including the return cannula. We compared the results with previous experimental and numerical studies of these cannulas in idealized tube geometries. According to the simulations, wall proximity at the drainage holes and the presence of the return cannula greatly increased drainage through the tip (33% at 5 L/min). We then simulated a multi-stage device in the same patient-averaged model, showing similar recirculation performance across the range of extracorporeal membrane oxygenation (ECMO) flow rates compared to the lighthouse cannula. Mean and maximum time-averaged wall shear stress were slightly higher for the lighthouse design. At high ECMO flow rates, the multi-stage device developed a negative caval pressure, which may be a cause of drainage obstruction in a clinical environment. Finally, through calculation of the energy spectra and vorticity field, we observed ring-like vortices inside the cannula originating from the side holes, most prominent in the proximal position. Our work highlights the important differences between a patient-derived and simplified venous model, with the latter tending to underestimate tip drainage. We also draw attention to the different dynamics of single-stage and multistage drainage cannulas, which may guide clinical use.
|
|
| 20. |
|
|
| 21. |
- Rorro, Federico, 1993-
(författare)
-
Flow characterisation of drainage cannulae and centrifugal pumps used in extracorporeal membrane oxygenation: an experimental investigation
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Extracorporeal membrane oxygenation (ECMO) is a life-saving treatment for acute respiratory and/or circulatory failure. Typically driven by a centrifugal pump, blood is drained from the patient via one drainage cannula, oxygenated by a membrane lung and returned to the patient via the return cannula. Although lifesaving, ECMO is associated with thromboembolic and haemolytic complications in part related to the mechanical stresses experienced by blood in the ECMO circuit. This thesis focuses on the fluid dynamics of ECMO pumps and cannulae with the aim to improve the fundamental understanding of flow structures and overall performance of the respective components during different operating conditions. Experimental studies were conducted with particle image velocimetry (cannula flows) and high speed video recordings (pump characterisation, complex geometry). The dynamics of an isolated drainage cannula placed in a glasstube with dimensions similar to the inferior vena cava were studied considering two different cannula tip designs. Seven centrifugal pumps were investigated to evaluate pump mechanical performance and the development, for low flow rates, of backflow at the pump inlet. The dynamics leading to backflow was investigated together with numerical simulations. The results showed higher shear stress levels in a blunt cannula compared to a lighthouse tip cannula. The latter drained the highest volume fraction through the most proximal side-holes and not the tip. Cannula position relative to the wall did not alter these results. In pumps with a shroud over the impeller blades stable recirculation zones were observed on the sides of the pump inlet. These recirculating regions were formed by vortical structures detaching from the peripheral (suction) side of impeller blades and migrating over the shroud towards the pump inlet. This work increases the fluid dynamical understanding of centrifugal pumps and cannulae used for ECMO. In particular, data on detailed design features influencing inherent pump recirculation are revealed which may impact futurepump designs. Such changes have the potential to significantly reduce patient complications.
|
|
| 22. |
- Sinko, Patrick D., et al.
(författare)
-
Estimation of the concentration boundary layer adjacent to a flat surface using computational fluid dynamics
- 2024
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 653
-
Tidskriftsartikel (refereegranskat)abstract
- Dissolution-permeation (D/P) experiments are widely used during preclinical development due to producing results with better predictability than traditional monophasic experiments. However, it is difficult to compare absorption across in vitro setups given the propensity to only report apparent permeability. We therefore developed an approach to predict the concentration boundary layer for any D/P device by using computational fluid dynamics (CFD). The Navier-Stokes and continuity equation in 2D were solved numerically in MATLAB and by finite element methods in COMSOL v6.1 to predict the momentum (ηf′) and concentration ηg boundary layer for a flow over a flat plate, i.e. the classical Blasius boundary layer flow. A MATLAB algorithm was developed to calculate the edge of either boundary layer. The methodology to determine the concentration boundary layer based on Blasius's analysis provided an accurate estimate for both ηf′ and ηg, resulting in, ηf′/ηg, at high Schmidt numbers (Sc ∼ 1000) within 14 % of the Blasius solution and 6.6 % of the accepted Schmidt number correlation (Sc1/3=ηf′/ηg). The methodology based on the Blasius analysis of the concentration boundary layer using velocity and concentration profiles computed using CFD presented herein will enable characterization/analysis of complex D/P apparatuses used in preclinical development, where an analytical solution may not be available.
|
|
