On the Determinism of Multi-core Processors

Hard real time systems are evolving in order to respond to the increasing demand in complex functionalities while taking advantage of newer hardware. Software development for safety critical systems has to comply with strict requirements that will facilitate the certification process. During this process, each part of the system is evaluated, requiring a certain level of assurance in order to provide confidence in the product. In particular there must be a level of confidence that the system behaves deterministically that may be based on functionality, resources and time. The success of system verification depends greatly on the capacity to determine its exact behavior. Nonetheless, hardware evolved in order to maximize the average computation power throughput with little to no regard to the deterministic aspect. Therefore modern architectural features of processors, like pipelines, cache memories and co-processors, make it hard to verify that all the needed properties are respected. The multi-core is furthermore difficult to analyze as the architecture employs mechanisms that compromise strong spatial and temporal partitioning when using shared resources without rigorous access control like shared caches or shared input/outputs. In this paper we identify and analyze the main sources of nondeterminism of the multi-cores with regard to the timing estimation. Precise determination of the worst case execution time is a challenging task even in single-core architectures. The problems are accentuated in the multi-core context mainly due to the resource sharing that can lead to highly complex interactions or to nondeterminism. Most of the units that generate behaviors that are hard to take into account can be deactivated, but it is not always easy to predict the impact on the performance. Nevertheless some of the features cannot be disabled (such as the out of order execution or some nondeterministic crossbar access policies) which leads to the invalidation of the respective platform for applications with high criticality level. We will address the problematic units, propose configuration or architecture guidelines and estimate their impact on the performance and determinism of the system

Left Ventricular Trabeculations Decrease the Wall Shear Stress and Increase the Intra-Ventricular Pressure Drop in CFD Simulations

The aim of the present study is to characterize the hemodynamics of left ventricular (LV) geometries to examine the impact of trabeculae and papillary muscles (PMs) on blood flow using high performance computing (HPC). Five pairs of detailed and smoothed LV endocardium models were reconstructed from high-resolution magnetic resonance images (MRI) of ex-vivo human hearts. The detailed model of one LV pair is characterized only by the PMs and few big trabeculae, to represent state of art level of endocardial detail. The other four detailed models obtained include instead endocardial structures measuring ≥1 mm2 in cross-sectional area. The geometrical characterizations were done using computational fluid dynamics (CFD) simulations with rigid walls and both constant and transient flow inputs on the detailed and smoothed models for comparison. These simulations do not represent a clinical or physiological scenario, but a characterization of the interaction of endocardial structures with blood flow. Steady flow simulations were employed to quantify the pressure drop between the inlet and the outlet of the LVs and the wall shear stress (WSS). Coherent structures were analyzed using the Q-criterion for both constant and transient flow inputs. Our results show that trabeculae and PMs increase the intra-ventricular pressure drop, reduce the WSS and disrupt the dominant single vortex, usually present in the smoothed-endocardium models, generating secondary small vortices. Given that obtaining high resolution anatomical detail is challenging in-vivo, we propose that the effect of trabeculations can be incorporated into smoothed ventricular geometries by adding a porous layer along the LV endocardial wall. Results show that a porous layer of a thickness of 1.2·10−2 m with a porosity of 20 kg/m2 on the smoothed-endocardium ventricle models approximates the pressure drops, vorticities and WSS observed in the detailed models.This paper has been partially funded by CompBioMed project, under H2020-EU.1.4.1.3 European Union’s Horizon 2020 research and innovation programme, grant agreement n◦ 675451. FS is supported by a grant from Severo Ochoa (n◦ SEV-2015-0493-16-4), Spain. CB is supported by a grant from the Fundació LaMarató de TV3 (n◦ 20154031), Spain. TI and PI are supported by the Institute of Engineering in Medicine, USA, and the Lillehei Heart Institute, USA.Peer ReviewedPostprint (published version

Effects of detailed ventricular anatomy on the blood flow

The presented study is a preliminary test and analysis of the role of trabeculae and papillary muscles in the hemodynamics of the left ventricle (LV)

Radiomics and Machine Learning for Skeletal Muscle Injury Recovery Prediction

Injuries; Muscles; RadiomicsLesions; Músculs; RadiòmicaLesiones; Músculos; RadiómicaRadiomics as a novel quantitative approach to medical imaging is an emerging area in the field of radiology. Artificial intelligence offers promising tools for exploiting and analyzing radiomics. The objective of the present study is to propose a methodology for the design, development, and evaluation of machine learning (ML) models for the prediction of the recovery progress of skeletal muscle injury over time in rats using radiomics. Radiomics were extracted from contrast enhanced computed tomography (CT) data and ML algorithms were trained and compared for their predictive value based on different CT imaging parameters. Ten different ML regression algorithms were tested and the optimal combination of radiomics for each algorithm and CT imaging parameter settings combination was studied. The best ensemble learning model, trained on the 70 kVp, 100 mA imaging parameter dataset, achieved a mean absolute error score of 1.22. The results suggest that radiomics extracted from CT images can be used as input in ML regression algorithms to predict the volume of a skeletal muscle injury in rats. Moreover, the results show that CT imaging settings impact the predictive performance of the ML regression models, indicating that lower values of tube current and peak kilovoltage contribute to more accurate predictions.10.13039/100010671-European Union’s Horizon Research and Innovation Program (Grant Number: 761031

Evaluating the roles of detailed endocardial structures on right ventricular haemodynamics by means of CFD simulations

Computational modelling plays an important role in right ventricular (RV) haemodynamic analysis. However, current approaches use smoothed ventricular anatomies. The aim of this study is to characterise RV haemodynamics including detailed endocardial structures like trabeculae, moderator band, and papillary muscles. Four paired detailed and smoothed RV endocardium models (2 male and 2 female) were reconstructed from ex vivo human hearts high‐resolution magnetic resonance images. Detailed models include structures with ≥1 mm2 cross‐sectional area. Haemodynamic characterisation was done by computational fluid dynamics simulations with steady and transient inflows, using high‐performance computing. The differences between the flows in smoothed and detailed models were assessed using Q‐criterion for vorticity quantification, the pressure drop between inlet and outlet, and the wall shear stress. Results demonstrated that detailed endocardial structures increase the degree of intra‐ventricular pressure drop, decrease the wall shear stress, and disrupt the dominant vortex creating secondary small vortices. Increasingly turbulent blood flow was observed in the detailed RVs. Female RVs were less trabeculated and presented lower pressure drops than the males. In conclusion, neglecting endocardial structures in RV haemodynamic models may lead to inaccurate conclusions about the pressures, stresses, and blood flow behaviour in the cavity.The DICOMdatasetswere provided by the Visible Heart R Laboratory, obtained byMRI scanning of perfusion fixed hearts that were graciously donated by the organ donors and their families through LifeSource. Part of the simulation hours were provided by the CompBioMed project in the Archer supercomputer, EPCC, UK.Peer ReviewedPostprint (author's final draft

Phenotyping Type 2 Diabetes in Terms of Myocardial Insulin Resistance and Its Potential Cardiovascular Consequences: A New Strategy Based on 18F-FDG PET/CT

Cardiovascular risk; Myocardial insulin resistance; Type 2 diabetesRisc cardiovascular; Resistència miocàrdica a la insulina; Diabetis tipus 2Riesgo cardiovascular; Resistencia miocárdica a la insulina; Diabetes tipo 2Background: Systemic insulin resistance is generally postulated as an independent risk factor of cardiovascular events in type 2 diabetes (T2D). However, the role of myocardial insulin resistance (mIR) remains to be clarified. Methods: Two 18F-FDG PET/CT scans were performed on forty-three T2D patients at baseline and after hyperinsulinemic–euglycemic clamp (HEC). Myocardial insulin sensitivity (mIS) was determined by measuring the increment in myocardial 18F-FDG uptake after HEC. Coronary artery calcium scoring (CACs) and myocardial radiodensity (mRD) were assessed by CT. Results: After HEC, seventeen patients exhibited a strikingly enhancement of myocardial 18F-FDG uptake and twenty-six a marginal increase, thus revealing mIS and mIR, respectively. Patients with mIR showed higher mRD (HU: 38.95 [33.81–44.06] vs. 30.82 [21.48–38.02]; p = 0.03) and CACs > 400 (AU: 52% vs. 29%; p = 0.002) than patients with mIS. In addition, HOMA-IR and mIS only showed a correlation in those patients with mIR. Conclusions: 18F-FDG PET combined with HEC is a reliable method for identifying patients with mIR. This subgroup of patients was found to be specifically at high risk of developing cardiovascular events and showed myocardial structural changes. Moreover, the gold-standard HOMA-IR index was only associated with mIR in this subgroup of patients. Our results open up a new avenue for stratifying patients with cardiovascular risk in T2D.This research was funded by the Carlos III Health Institute and the European Regional Development Fund (PI16/02064 and PI20/01588) and AGAUR (2017SGR1303 and 2017SGR1144)

Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026

Background The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95$7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95$43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and$37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained

Image based analysis and modeling of the detailed cardiac ventricular anatomy

The role of trabeculations and their normal morphological expression in the human heart is still unclear. Clinical studies have shown that excessive trabeculation can cause heart failure due to diastolic and systolic dysfunction, thromboembolism and arrhythmias. Quantifying and modeling those structures could provide us insights into their function, their influence on cardiac performance and also their connection with cardiomyopathies. The contributions of this thesis can be summarized as follows: 1) a simplified model of the trabeculated left ventricle (LV) to study the impact of trabeculations on stroke volume, strain and pump capacity of the LVs of different geometries, 2) a simple as well as a more elaborate method for geometry independent parametrization of the detailed cardiac left and right ventricular anatomy, 3) a framework for visualization and statistical analysis of the trabeculations, and 4) a longitudinal analysis of the cardiac trabeculations in a mouse embryo at different gestational stages.El papel de las trabéculas cardíacas y su morfología normal en el corazón humano todavía es desconocido. Estudios clínicos han demostrado que la trabeculacíon excesiva puede causar insuficiencia cardíaca debido a disfunción diastólica y sistólica, tromboembolismo y arritmias. El modelado y cuantificación de estas nos puede dar una idea de su función, su influencia en el rendimiento cardíaco y también su conexión con cardiomiopatías. Las contribuciones de la presente tesis son los siguientes: 1) un modelo simplificado del ventrículo izquierdo trabeculado para estudiar el impacto de las trabéculas sobre el volumen, la deformación y el gasto cardíaco de los ventrículos con diferentes geometrías, 2) un método simplificado, así como un método más complejo para la parametrización independiente de la geometría cardíaca detallada de los ventrículos izquierdo y derecho, 3) un framework para la visualización y el análisis estadístico de las trabeculaciones, y 4) un análisis longitudinal de las trabéculas cardíacas en un embrión de ratón en diferentes etapas gestacionales

Relationship between the left ventricular size and the amount of trabeculations

Contemporary imaging modalities offer non-invasive quantification of myocardial deformation; however, they make gross assumptions about internal structure of the cardiac walls. Our aim is to study the possible impact of the trabeculations on the stroke volume, strain and capacity of differently sized ventricles. The cardiac left ventricle is represented by an ellipsoid and the trabeculations by a tissue occupying a fixed volume. The ventricular contraction is modelled by scaling the ellipsoid whereupon the measurements of longitudinal strain, end-diastolic, end-systolic and stroke volume are derived and compared. When the trabeculated and non-trabeculated ventricles, having the same geometry and deformation pattern, contain the same amount of blood and contract with the same strain, we observed an increased stroke volume in our model of the trabeculated ventricle. When these ventricles contain and eject the same amount of blood, we observed a reduced strain in the trabeculated case. We identified that a trade-off between the strain and the amount of trabeculations could be reached with a 0.35-0.41 cm dense trabeculated layer, without blood filled recesses (for a ventricle with end-diastolic volume of about 150 ml). A trabeculated ventricle can work at lower strains compared to a non-trabeculated ventricle to produce the same stroke volume, which could be a possible explanation why athletes and pregnant women develop reversible signs of left ventricular non-compaction, since the trabeculations could help generating extra cardiac output. This knowledge might help to assess heart failure patients with dilated cardiomyopathies who often show signs of non-compaction.The research leading to these results has received funding by EU FP7 for research, technological development and demonstration under grant agreement VP2HF (no. 611823), Spanish Ministry of Economy and Competitiveness (grant TIN2011-28067, TIN2014-52923-R, the Maria de Maeztu Units of Excellence Programme MDM-2015-0502) and FEDER. B. Paun is supported by the grant FI-DGR 2014 (2014 FI B01238) from the Generalitat de Catalunya. C. Butakoff is supported by a grant from the Fundació La Marató de TV3 (nº 20154031), Spain