Pulmonary vein flow split effects in patient-specific simulations of left atrial flow

Disruptions to left atrial (LA) blood flow, such as those caused by atrial fibrillation (AF), can lead to thrombosis in the left atrial appendage (LAA) and an increased risk of systemic embolism. LA hemodynamics are influenced by various factors, including LA anatomy and function, and pulmonary vein (PV) inflow conditions. In particular, the PV flow split can vary significantly among and within patients depending on multiple factors. In this study, we investigated how changes in PV flow split affect LA flow transport, focusing for the first time on blood stasis in the LAA, using a high-fidelity patient-specific computational fluid dynamics (CFD) model. We use an Immersed Boundary Method, simulating the flow in a fixed, uniform Cartesian mesh and imposing the movement of the LA walls with a moving Lagrangian mesh generated from 4D Computerized Tomography images. We analyzed LA anatomies from eight patients with varying atrial function, including three with AF and either a LAA thrombus or a history of Transient Ischemic Attacks (TIAs). Using four different flow splits (60/40% and 55/45% through right and left PVs, even flow rate, and same velocity through each PV), we found that flow patterns are sensitive to PV flow split variations, particularly in planes parallel to the mitral valve. Changes in PV flow split also had a significant impact on blood stasis and could contribute to increased risk for thrombosis inside the LAA, particularly in patients with AF and previous LAA thrombus or a history of TIAs. Our study highlights the importance of considering patient-specific PV flow split variations when assessing LA hemodynamics and identifying patients at increased risk for thrombosis and stroke. This knowledge is relevant to planning clinical procedures such as AF ablation or the implementation of LAA occluders.This work was partially supported by Comunidad de Madrid (Synergy Grant Y2018/BIO-4858 PREFI-CM), Spanish Research Agency (AEI, grant number PID2019-107279RB-I00), Instituto de Salud Carlos III (grant numbers PI15/02211-ISBITAMI and DTS/1900063-ISBIFLOW), and by the EU-European Regional Development Fund. Funding for open access charge: Universidad de Málaga /CBU

Pulmonary vein flow split effects in patient-specific simulations of left atrial flow

Disruptions to left atrial (LA) blood flow, such as those caused by atrial fibrillation (AF), can lead to thrombosis in the left atrial appendage (LAA) and an increased risk of systemic embolism. LA hemodynamics are influenced by various factors, including LA anatomy and function, and pulmonary vein (PV) inflow conditions. In particular, the PV flow split can vary significantly among and within patients depending on multiple factors. In this study, we investigated how changes in PV flow split affect LA flow transport, focusing for the first time on blood stasis in the LAA, using a high-fidelity patient-specific computational fluid dynamics (CFD) model. We use an Immersed Boundary Method, simulating the flow in a fixed, uniform Cartesian mesh and imposing the movement of the LA walls with a moving Lagrangian mesh generated from 4D Computerized Tomography images. We analyzed LA anatomies from eight patients with varying atrial function, including three with AF and either a LAA thrombus or a history of Transient Ischemic Attacks (TIAs). Using four different flow splits (60/40% and 55/45% through right and left PVs, even flow rate, and same velocity through each PV), we found that flow patterns are sensitive to PV flow split variations, particularly in planes parallel to the mitral valve. Changes in PV flow split also had a significant impact on blood stasis and could contribute to increased risk for thrombosis inside the LAA, particularly in patients with AF and previous LAA thrombus or a history of TIAs. Our study highlights the importance of considering patient-specific PV flow split variations when assessing LA hemodynamics and identifying patients at increased risk for thrombosis and stroke. This knowledge is relevant to planning clinical procedures such as AF ablation or the implementation of LAA occluders.This work was partially supported by Comunidad de Madrid (Synergy Grant Y2018/BIO-4858 PREFI-CM), Spanish Research Agency (AEI, grant number PID2019-107279RB-I00), Instituto de Salud Carlos III (grant numbers PI15/02211-ISBITAMI and DTS/1900063-ISBIFLOW), and by the EU-European Regional Development Fund . Funding for open access charge: Universidad de Málaga / CBUA

Demonstration of Patient-Specific Simulations to Assess Left Atrial Appendage Thrombogenesis Risk

Atrial fibrillation (AF) alters left atrial (LA) hemodynamics, which can lead to thrombosis in the left atrial appendage (LAA), systemic embolism and stroke. A personalized risk-stratification of AF patients for stroke would permit improved balancing of preventive anticoagulation therapies against bleeding risk. We investigated how LA anatomy and function impact LA and LAA hemodynamics, and explored whether patient-specific analysis by computational fluid dynamics (CFD) can predict the risk of LAA thrombosis. We analyzed 4D-CT acquisitions of LA wall motion with an in-house immersed-boundary CFD solver. We considered six patients with diverse atrial function, three with either a LAA thrombus (removed digitally before running the simulations) or a history of transient ischemic attacks (LAAT/TIA-pos), and three without a LAA thrombus or TIA (LAAT/TIA-neg). We found that blood inside the left atrial appendage of LAAT/TIA-pos patients had marked alterations in residence time and kinetic energy when compared with LAAT/TIA-neg patients. In addition, we showed how the LA conduit, reservoir and booster functions distinctly affect LA and LAA hemodynamics. Finally, fixed-wall and moving-wall simulations produced different LA hemodynamics and residence time predictions for each patient. Consequently, fixed-wall simulations risk-stratified our small cohort for LAA thrombosis worse than moving-wall simulations, particularly patients with intermediate LAA residence time. Overall, these results suggest that both wall kinetics and LAA morphology contribute to LAA blood stasis and thrombosis.This work was partially supported by the Comunidad de Madrid (Sinergias Y2018/BIO-4858 PREFI-CM), Cátedra Excelencia UC3M-Santander, Ministry of Education of Spain (Salvador de Madariaga program), the US NHLBI (NCAI-UCCAI-2017-06-6), the United States American Heart Association (AHA 20POST35200401), and the 2019 UCSD GEM Program. Computational time provided by XSEDE (Comet) and RES (Altamira) is gratefully acknowledged

Design Concepts of Polycarbonate-Based Intervertebral Lumbar Cages: Finite Element Analysis and Compression Testing

This work explores the viability of 3D printed intervertebral lumbar cages based on biocompatible polycarbonate (PC-ISO® material). Several design concepts are proposed for the generation of patient-specific intervertebral lumbar cages. The 3D printed material achieved compressive yield strength of 55 MPa under a specific combination of manufacturing parameters. The literature recommends a reference load of 4,000 N for design of intervertebral lumbar cages. Under compression testing conditions, the proposed design concepts withstand between 7,500 and 10,000 N of load before showing yielding. Although some stress concentration regions were found during analysis, the overall viability of the proposed design concepts was validated

Stress-Softening and Residual Strain Effects in Suture Materials

This work focuses on the experimental characterization of suture material samples of MonoPlus, Monosyn, polyglycolic acid, polydioxanone 2–0, polydioxanone 4–0, poly(glycolide-co-epsilon-caprolactone), nylon, and polypropylene when subjected to cyclic loading and unloading conditions. It is found that all tested suture materials exhibit stress-softening and residual strain effects related to the microstructural material damage upon deformation from the natural, undistorted state of the virgin suture material. To predict experimental observations, a new constitutive material model that takes into account stress-softening and residual strain effects is developed. The basis of this model is the inclusion of a phenomenological nonmonotonous softening function that depends on the strain intensity between loading and unloading cycles. The theory is illustrated by modifying the non-Gaussian average-stretch, full-network model to capture stress-softening and residual strains by using pseudoelasticity concepts. It is shown that results obtained from theoretical simulations compare well with suture material experimental data

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass