| 1. |
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- 2019
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Journal article (peer-reviewed)
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| 2. |
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| 3. |
- Lindblad-Toh, Kerstin, et al.
(author)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Journal article (peer-reviewed)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.
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| 4. |
- Abbasi, Rasha, et al.
(author)
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IceCube search for neutrinos from GRB 221009A
- 2023
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In: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
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Conference paper (peer-reviewed)abstract
- GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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| 5. |
- Fresard, Laure, et al.
(author)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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In: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Journal article (peer-reviewed)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 6. |
- Weinstein, John N., et al.
(author)
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The cancer genome atlas pan-cancer analysis project
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Research review (peer-reviewed)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.
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| 7. |
- Wilkinson, Jack, et al.
(author)
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Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions
- 2024
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:3
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Journal article (peer-reviewed)abstract
- Introduction Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions.Methods and analysis The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare.Ethics and dissemination The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.
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| 8. |
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| 9. |
- Johansson, Mattias, et al.
(author)
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The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study
- 2019
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:1
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Journal article (peer-reviewed)abstract
- Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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| 10. |
- Leite, Melina de Souza, et al.
(author)
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Major axes of variation in tree demography across global forests
- 2024
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In: Ecography. - 0906-7590 .- 1600-0587.
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Journal article (peer-reviewed)abstract
- The future trajectory of global forests is closely intertwined with tree demography, and a major fundamental goal in ecology is to understand the key mechanisms governing spatio-temporal patterns in tree population dynamics. While previous research has made substantial progress in identifying the mechanisms individually, their relative importance among forests remains unclear mainly due to practical limitations. One approach to overcome these limitations is to group mechanisms according to their shared effects on the variability of tree vital rates and quantify patterns therein. We developed a conceptual and statistical framework (variance partitioning of Bayesian multilevel models) that attributes the variability in tree growth, mortality, and recruitment to variation in species, space, and time, and their interactions – categories we refer to as organising principles (OPs). We applied the framework to data from 21 forest plots covering more than 2.9 million trees of approximately 6500 species. We found that differences among species, the species OP, proved a major source of variability in tree vital rates, explaining 28–33% of demographic variance alone, and 14–17% in interaction with space, totalling 40–43%. Our results support the hypothesis that the range of vital rates is similar across global forests. However, the average variability among species declined with species richness, indicating that diverse forests featured smaller interspecific differences in vital rates. Moreover, decomposing the variance in vital rates into the proposed OPs showed the importance of unexplained variability, which includes individual variation, in tree demography. A focus on how demographic variance is organized in forests can facilitate the construction of more targeted models with clearer expectations of which covariates might drive a vital rate. This study therefore highlights the most promising avenues for future research, both in terms of understanding the relative contributions of groups of mechanisms to forest demography and diversity, and for improving projections of forest ecosystems.
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| 11. |
- Parker, Louis P., et al.
(author)
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Cannulation configuration and recirculation in venovenous extracorporeal membrane oxygenation
- 2022
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Journal article (peer-reviewed)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.
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| 12. |
- Parker, Louis P., et al.
(author)
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Chapter 15 - Multiphysics flow modeling in the aorta
- 2024
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In: Biomechanics of the Aorta. - : Elsevier BV. ; , s. 321-345
-
Book chapter (other academic/artistic)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.
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| 13. |
- Parker, Louis P., et al.
(author)
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Computational Fluid Dynamics of the Right Atrium : A Comparison of Modeling Approaches in a Range of Flow Conditions
- 2022
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In: Journal of Engineering and Science in Medical Diagnostics and Therapy. - : ASME International. - 2572-7958 .- 2572-7966. ; 5:3
-
Journal article (peer-reviewed)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.
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| 14. |
- Parker, Louis P., et al.
(author)
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Hemodynamic and recirculation performance of dual lumen cannulas for venovenous extracorporeal membrane oxygenation
- 2023
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
-
Journal article (peer-reviewed)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.
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| 15. |
- Parker, Louis P., et al.
(author)
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Impact of altered vena cava flow rates on right atrium flow characteristics
- 2022
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In: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 132:5, s. 1167-1178
-
Journal article (peer-reviewed)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.
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| 16. |
- Parker, Louis P., et al.
(author)
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In silico parametric analysis of femoro-jugular venovenous ECMO and return cannula dynamics : In silico analysis of femoro-jugular VV ECMO
- 2024
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In: Medical Engineering and Physics. - : Elsevier BV. - 1350-4533 .- 1873-4030. ; 125
-
Journal article (peer-reviewed)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.
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| 17. |
- Parker, Louis P., et al.
(author)
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Venovenous extracorporeal membrane oxygenation drainage cannula performance : From generalized to patient-averaged vessel model
- 2024
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In: Physics of fluids. - : AIP Publishing. - 1070-6631 .- 1089-7666. ; 36:6
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Journal article (peer-reviewed)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.
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| 18. |
- Parker, Peter, et al.
(author)
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Design and Democracy
- 2018
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In: Care/create/act. - : Blauwdruk. - 9789492474308 ; , s. 285-291
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Book chapter (other academic/artistic)abstract
- Landscape architects today love run-down areas, the challenge of temporary projects, hands-on activities, working with people, and the aesthetics of the transitory. They often experience themselves as part of a particularly democratic process of space production when given the opportunity to address urban redevelopment through temporary interventions, claiming to make a difference to conventional ways of planning and building. Alternative forms of power, they feel, can be enacted through new forms of professional expertise, with public authorities accepting or fostering these precarious production modes, and with designers in the role of activists. The much lauded emergence of temporary bottom-up projects in urban redevelopment areas also raises the question of their true democratic potential. Often presented as enabling new forms of democracy and participatory planning for imagining and building new urban forms and new professional profiles, they also carry the danger of abusing people’s resources for tacit interests of societally established power groups and of derailing into ‘people-washing’. To distinguish between democratic enhancement and its abuse requires mining the notion of democracy. In this essay we do so in crossing research on the spatial aspects of democracy with theory on radical participation in order to develop a frame for judgment of concrete projects.
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| 19. |
- Parker, Peter, et al.
(author)
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Investigating the democratic potential of temporary uses in urban redevelopment projects
- 2018
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In: Enabling Urban Alternatives: Crises, Contestation, and Cooperation. - Singapore : Palgrave Macmillan. - 9789811315305 - 9789811315312 ; , s. 85-108
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Book chapter (peer-reviewed)abstract
- In this chapter we shed light on enabling urban alternatives that arise through novel ways of governance and collaboration, observed in current urban redevelopment projects in Europe. Often instated on left-over industrial, commercial or infrastructural areas and premises, the projects we are concerned with are driven by municipal authorities, public or private developers who offer parts of the spaces under redevelopment for temporary appropriation by users who conventionally play a secondary if not marginal role in the formation of new urban districts: youngsters, freelancers, small businesses, start-ups, associations, groups representing subcultures. These processes seem to empower novel constellations of actors in urban development. However, there is already a substantial body of research pointing out how temporary uses may provide a means of normalizing precarious forms of rental and are exploited for gentrification and branding purposes. A starting point of the chapter is therefore that these initiatives are ambiguous.We argue that it is important to consider democratic implications of temporary use as this practice becomes increasingly accepted and enabled by public sector actors. The chapter then brings together research on spatial aspects of democracy with theory on radical participation in order to develop a heuristic framework for assessing democratic potentials of temporary use and briefly illustrates this in relation to two examples. We contend that such a framework will enable an informed approach to temporary use by activists, professional designers and authorities. The overarching purpose is to enable this kind of informed approach and thereby make it possible for more people to experience democracy in urban development and create more varied urban alternatives.
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| 20. |
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| 21. |
- Rorro, Federico, 1993-
(author)
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Flow characterisation of drainage cannulae and centrifugal pumps used in extracorporeal membrane oxygenation: an experimental investigation
- 2024
-
Doctoral thesis (other academic/artistic)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.
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| 22. |
- Sandoval-Castellanos, Edson, et al.
(author)
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Ancient mitogenomes from Pre-Pottery Neolithic Central Anatolia and the effects of a Late Neolithic bottleneck in sheep (Ovis aries)
- 2024
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In: SCIENCE ADVANCES. - 2375-2548. ; 10:15
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Journal article (peer-reviewed)abstract
- Occupied between similar to 10,300 and 9300 years ago, the Pre-Pottery Neolithic site of Asikli Hoyuk in Central Anatolia went through early phases of sheep domestication. Analysis of 629 mitochondrial genomes from this and numerous sites in Anatolia, southwest Asia, Europe, and Africa produced a phylogenetic tree with excessive coalescences (nodes) around the Neolithic, a potential signature of a domestication bottleneck. This is consistent with archeological evidence of sheep management at Asikli Hoyuk which transitioned from residential stabling to open pasturing over a millennium of site occupation. However, unexpectedly, we detected high genetic diversity throughout Asikli Hoyuk's occupation rather than a bottleneck. Instead, we detected a tenfold demographic bottleneck later in the Neolithic, which caused the fixation of mitochondrial haplogroup B in southwestern Anatolia. The mitochondrial genetic makeup that emerged was carried from the core region of early Neolithic sheep management into Europe and dominates the matrilineal diversity of both its ancient and the billion-strong modern sheep populations.
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| 23. |
- Scelo, Ghislaine, et al.
(author)
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Genome-wide association study identifies multiple risk loci for renal cell carcinoma.
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10-10), 3p22.1 (rs67311347, P=2.5 × 10-8), 3q26.2 (rs10936602, P=8.8 × 10-9), 8p21.3 (rs2241261, P=5.8 × 10-9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8), 11q22.3 (rs74911261, P=2.1 × 10-10) and 14q24.2 (rs4903064, P=2.2 × 10-24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
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| 24. |
- Sinko, Patrick D., et al.
(author)
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Estimation of the concentration boundary layer adjacent to a flat surface using computational fluid dynamics
- 2024
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 653
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Journal article (peer-reviewed)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.
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| 25. |
- von Seidlein, Lorenz, et al.
(author)
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The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial
- 2019
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In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 16:2
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Journal article (peer-reviewed)abstract
- Background The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao Peoples Democratic Republic, where artemisinin resistance is prevalent. Methods and findings After establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin-and piperaquine- resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention. Conclusions Added to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination.
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| 26. |
- Watson, Hunna J., et al.
(author)
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Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
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In: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
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Journal article (peer-reviewed)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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