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Background: The concept of planetary health underscores the intricate relationship between environmental concerns and global health. This interconnection raises an important question related to cross-sectoral policy development: to what extent are environmental issues integrated into global health governance? To address this question, this study examines resolutions adopted by the World Health Assembly (WHA) from 1948 to 2023., Methods: Based on a systematic text search for environmental issues, this study examines the evolution of the occurrence and content of resolutions adopted by the WHA and the structure and pattern of connectivity of the normative network of resolutions regarding environment-related resolutions from 1948 to 2023. Environment-related resolutions were processed in the Python environment using relevant packages, such as Pandas, Numpy, and Matplotlib. Regular expressions were employed to identify citations among resolutions and construct a directed citation network. The network was then examined using NetworkX and Graph-Tool., Findings: Despite important variations in the attention dedicated to environmental issues in resolutions adopted by the WHA, the proportion of environment-related resolutions adopted each year has increased. The number of topics and their diversity have also expanded. Although environment-specific resolutions are well connected to each other, they are more weakly connected to environment-related resolutions, and not well connected to non-environment-related resolutions, suggesting potential silos in policy development. This study shows that several topical entry points exist for a deeper integration of environmental concerns in global health governance., Interpretation: The findings of this study indicate not only the growing reference to environmental concerns in global health governance, but also an evolution of the understanding of the environment as a key driver of the health of the people. However, there remains room for more comprehensive integration across all areas of global health policy. The study emphasises both the need for active participation in global environmental governance processes that affect health and the importance of minimising the health sector's contribution to environmental problems., Funding: None., Competing Interests: Declaration of interests PSJ acknowledges funding from the European Union (ERC, INFLUX, 101039376). NL has a mandate as UN Special Rapporteur on Minority Issues. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

MRI, a widespread non-invasive medical imaging modality, is highly sensitive to patient motion. Despite many attempts over the years, motion correction remains a difficult problem and there is no general method applicable to all situations. We propose a retrospective method for motion estimation and correction to tackle the problem of in-plane rigid-body motion, apt for classical 2D Spin-Echo scans of the brain, which are regularly used in clinical practice. Due to the sequential acquisition of k-space, motion artifacts are well localized. The method leverages the power of deep neural networks to estimate motion parameters in k-space and uses a model-based approach to restore degraded images to avoid "hallucinations". Notable advantages are its ability to estimate motion occurring in high spatial frequencies without the need of a motion-free reference. The proposed method operates on the whole k-space dynamic range and is moderately affected by the lower SNR of higher harmonics. As a proof of concept, we provide models trained using supervised learning on 600k motion simulations based on motion-free scans of 43 different subjects. Generalization performance was tested with simulations as well as in-vivo. Qualitative and quantitative evaluations are presented for motion parameter estimations and image reconstruction. Experimental results show that our approach is able to obtain good generalization performance on simulated data and in-vivo acquisitions. We provide a Python implementation at https://gitlab.unige.ch/Oscar.Dabrowski/sismik_mri/.

Circulatory models can significantly help develop new ways to alleviate the burden of stroke on society. However, it is not always easy to know what hemodynamics conditions to impose on a numerical model or how to simulate porous media, which ineluctably need to be addressed in strokes. We propose a validated open-source, flexible, and publicly available lattice-Boltzmann numerical framework for such problems and present its features in this chapter. Among them, we propose an algorithm for imposing pressure boundary conditions. We show how to use the method developed by Walsh et al. (Comput Geosci 35(6):1186-1193, 2009) to simulate the permeability law of any porous medium. Finally, we illustrate the features of the framework through a thrombolysis model., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

One of the routine clinical treatments to eliminate ischemic stroke thrombi is injecting a biochemical product into the patient's bloodstream, which breaks down the thrombi's fibrin fibers: intravenous or intravascular thrombolysis. However, this procedure is not without risk for the patient; the worst circumstances can cause a brain hemorrhage or embolism that can be fatal. Improvement in patient management drastically reduced these risks, and patients who benefited from thrombolysis soon after the onset of the stroke have a significantly better 3-month prognosis, but treatment success is highly variable. The causes of this variability remain unclear, and it is likely that some fundamental aspects still require thorough investigations. For that reason, we conducted in vitro flow-driven fibrinolysis experiments to study pure fibrin thrombi breakdown in controlled conditions and observed that the lysis front evolved non-linearly in time. To understand these results, we developed an analytical 1D lysis model in which the thrombus is considered a porous medium. The lytic cascade is reduced to a second-order reaction involving fibrin and a surrogate pro-fibrinolytic agent. The model was able to reproduce the observed lysis evolution under the assumptions of constant fluid velocity and lysis occurring only at the front. For adding complexity, such as clot heterogeneity or complex flow conditions, we propose a 3-dimensional mesoscopic numerical model of blood flow and fibrinolysis, which validates the analytical model's results. Such a numerical model could help us better understand the spatial evolution of the thrombi breakdown, extract the most relevant physiological parameters to lysis efficiency, and possibly explain the failure of the clinical treatment. These findings suggest that even though real-world fibrinolysis is a complex biological process, a simplified model can recover the main features of lysis evolution., (© 2023. Springer Nature Limited.)

From a complexity perspective on governance, multilateral diplomacy is based on interactions between people, ideas, norms, policies and institutions. This article uses a computer-assisted methodology to better understand governance systems as a network of norms. All World Health Assembly (WHA) resolutions that were available from 1948 to 2022 were collected from the WHO Institutional Repository for Information Sharing (IRIS) database. Regular expressions were used to identify how resolutions cite other resolutions and the resulting relationships were analysed as a normative network. The findings show that WHA resolutions constitute a complex network of interconnected global health issues. This network is characterised by several community patterns. While chain-like patterns are associated with specific diseases programmes, radial patterns are characteristic of highly important procedural decisions that member states reaffirm in similar situations. Finally, densely connected communities correspond to contested topics and emergencies. While these emergeng patterns suggest the relevance of using network analysis to understand global health norms in international organisations, we reflect on how this computational approach can be extended to provide new understandings of how multilateral governance systems work, and to address some important contemporary questions about the effects of regime complexity on global health diplomacy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The goal of this work is to advance the characteristics of existing lattice Boltzmann Dirichlet velocity boundary schemes in terms of the accuracy, locality, stability, and mass conservation for arbitrarily grid-inclined straight walls, curved surfaces, and narrow fluid gaps, for both creeping and inertial flow regimes. We reach this objective with two infinite-member boundary classes: (1) the single-node "Linear Plus" (LI^{+}) and (2) the two-node "Extended Multireflection" (EMR). The LI^{+} unifies all directional rules relying on the linear combinations of up to three pre- or postcollision populations, including their "ghost-node" interpolations and adjustable nonequilibrium approximations. On this basis, we propose three groups of LI^{+} nonequilibrium local corrections: (1) the LI_{1}^{+} is parametrized, meaning that its steady-state solution is physically consistent: the momentum accuracy is viscosity-independent in Stokes flow, and it is fixed by the Reynolds number (Re) in inertial flow; (2) the LI_{3}^{+} is parametrized, exact for arbitrary grid-rotated Poiseuille force-driven Stokes flow and thus most accurate in porous flow; and (3) the LI_{4}^{+} is parametrized, exact for pressure and inertial term gradients, and hence advantageous in very narrow porous gaps and at higher Reynolds range. The directional, two-relaxation-time collision operator plays a crucial role for all these features, but also for efficiency and robustness of the boundary schemes due to a proposed nonequilibrium linear stability criterion which reliably delineates their suitable coefficients and relaxation space. Our methodology allows one to improve any directional rule for Stokes or Navier-Stokes accuracy, but their parametrization is not guaranteed. In this context, the parametrized two-node EMR class enlarges the single-node schemes to match exactness in a grid-rotated linear Couette flow modeled with an equilibrium distribution designed for the Navier-Stokes equation (NSE). However, exactness of a grid-rotated Poiseuille NSE flow requires us to perform (1) the modification of the standard NSE term for exact bulk solvability and (2) the EMR extension towards the third neighbor node. A unique relaxation and equilibrium exact configuration for grid-rotated Poiseuille NSE flow allows us to classify the Galilean invariance characteristics of the boundary schemes without any bulk interference; in turn, its truncated solution suggests how, when increasing the Reynolds number, to avoid a deterioration of the mass-leakage rate and momentum accuracy due to a specific Reynolds scaling of the kinetic relaxation collision rate. The optimal schemes and strategies for creeping and inertial regimes are then singled out through a series of numerical tests, such as grid-rotated channels and rotated Couette flow with wall-normal injection, cylindrical porous array, and Couette flow between concentric cylinders, also comparing them against circular-shape fitted FEM solutions.

The transport of platelets in blood is commonly assumed to obey an advection-diffusion equation with a diffusion constant given by the so-called Zydney-Colton theory. Here we reconsider this hypothesis based on experimental observations and numerical simulations including a fully resolved suspension of red blood cells and platelets subject to a shear. We observe that the transport of platelets perpendicular to the flow can be characterized by a non-trivial distribution of velocities with and exponential decreasing bulk, followed by a power law tail. We conclude that such distribution of velocities leads to diffusion of platelets about two orders of magnitude higher than predicted by Zydney-Colton theory. We tested this distribution with a minimal stochastic model of platelets deposition to cover space and time scales similar to our experimental results, and confirm that the exponential-powerlaw distribution of velocities results in a coefficient of diffusion significantly larger than predicted by the Zydney-Colton theory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kotsalos, Raynaud, Lätt, Dutta, Dubois, Zouaoui Boudjeltia and Chopard.)

MRI is a non-invasive medical imaging modality that is sensitive to patient motion, which constitutes a major limitation in most clinical applications. Solutions may arise from the reduction of acquisition times or from motion-correction techniques, either prospective or retrospective. Benchmarking the latter methods requires labeled motion-corrupted datasets, which are uncommon. Up to our best knowledge, no protocol for generating labeled datasets of MRI images corrupted by controlled motion has yet been proposed. Hence, we present a methodology allowing the acquisition of reproducible motion-corrupted MRI images as well as validation of the system's performance by motion estimation through rigid-body volume registration of fast 3D echo-planar imaging (EPI) time series. A proof-of-concept is presented, to show how the protocol can be implemented to provide qualitative and quantitative results. An MRI-compatible video system displays a moving target that volunteers equipped with customized plastic glasses must follow to perform predefined head choreographies. Motion estimation using rigid-body EPI time series registration demonstrated that head position can be accurately determined (with an average standard deviation of about 0.39 degrees). A spatio-temporal upsampling and interpolation method to cope with fast motion is also proposed in order to improve motion estimation. The proposed protocol is versatile and straightforward. It is compatible with all MRI systems and may provide insights on the origins of specific motion artifacts. The MRI and artificial intelligence research communities could benefit from this work to build in-vivo labeled datasets of motion-corrupted MRI images suitable for training/testing any retrospective motion correction or machine learning algorithm., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Introduction: The flow diverter stent (FDS) has become a first-line treatment for numerous intra-cranial aneurysms (IAs) by promoting aneurysm thrombosis. However, the biological phenomena underlying its efficacy remain unknown. We proposed a method to collect in situ blood samples to explore the flow diversion effect within the aneurysm sac. In this feasibility study, we assessed the plasma levels of nucleotides within the aneurysm sac before and after flow diversion treatment., Materials and Methods: In total, 14 patients with unruptured IAs who were selected for FDS implantation were prospectively recruited from February 2015 to November 2015. Two catheters dedicated to (1) FDS deployment and (2) the aneurysm sac were used to collect blood samples within the parent artery (P1) and the aneurysm sac before (P2) and after (P3) flow diversion treatment. The plasma levels of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) at each collection point were quantified with liquid chromatography and tandem mass spectrometry., Results: The aneurysms were extradural in nine (64.3%) patients and intra-dural in five (35.7%) patients. They presented an average diameter of 15.5 ± 7.1 mm, height of 15.8 ± 4.6 mm, and volume of 2,549 ± 2,794 ml. In all patients (100%), 16 FDS implantations and 42 in situ blood collections were performed successfully without any complications associated with the procedure. The ATP, ADP, and AMP concentrations within the aneurysm sac were decreased after flow diversion ( p = 0.005, p = 0.03, and p = 0.12, respectively). Only the ATP levels within the aneurysm sac after flow diversion were significantly correlated with aneurysm volume (adjusted R 2 = 0.43; p = 0.01)., Conclusion: In situ blood collection within unruptured IAs during a flow diversion procedure is feasible and safe. Our results suggest that the flow diversion technique is associated with changes in the nucleotide plasma levels within the aneurysm sac., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Eker, Lubicz, Cortese, Delporte, Berhouma, Chopard, Costalat, Bonafé, Alix-Panabières, Van Anwterpen and Zouaoui Boudjeltia.)

Cardio/cerebrovascular diseases (CVD) have become one of the major health issue in our societies. But recent studies show that the present pathology tests to detect CVD are ineffectual as they do not consider different stages of platelet activation or the molecular dynamics involved in platelet interactions and are incapable to consider inter-individual variability. Here we propose a stochastic platelet deposition model and an inferential scheme to estimate the biologically meaningful model parameters using approximate Bayesian computation with a summary statistic that maximally discriminates between different types of patients. Inferred parameters from data collected on healthy volunteers and different patient types help us to identify specific biological parameters and hence biological reasoning behind the dysfunction for each type of patients. This work opens up an unprecedented opportunity of personalized pathology test for CVD detection and medical treatment., Competing Interests: The authors have declared that no competing interests exist.

This perspective paper considers thrombolysis in the context of ischemic strokes, intending to build eventually a numerical model capable of simulating the thrombolytic treatment and predicting patient outcomes. Numerical modeling is a scientific methodology based on an abstraction of a system but requires understanding their spatio-temporal interactions. However, although important, the current knowledge on thrombolysis is fragmented in contributions from which it is difficult to obtain a complete picture of the process, especially in a clinically relevant setup. This paper discusses, from a general point of view, how to develop a numerical model to describe the evolution of a patient clot under the action of a thrombolytic drug. We will present critical, yet fundamental, open questions that have emerged during this elaboration and discuss original experimental observations that challenge some of our current knowledge of thrombolysis., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In cardiovascular disorders, the study of thrombocytes, commonly known as platelets, is highly important since they are involved in blood clotting, essential in hemostasis, and they can in pathological situations affect the blood circulation. In this paper, single deposited platelets are measured using interferometric digital holographic microscopy. We have shown that the average optical height of platelets is significantly lower in healthy volunteers than in dialyzed patients, meaning a better spreading. It demonstrates the great interest for assessing this parameter in any patients, and therefore the high potential of analyzing single spread platelets using digital holographic microscopy in fundamental research as well as a diagnostic tool in routine laboratories, for usual blood tests., Competing Interests: The authors declare no conflict of interest., (© 2021 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

It has been observed in vitro that complete clot lysis is generally preceded by a slow phase of lysis during which the degradation seems to be inefficient. However, this slow regime was merely noticed, but not yet quantitatively discussed. In our experiments, we observed that the lysis ubiquitously occurred in two distinct regimes, a slow and a fast lysis regime. We quantified extensively the duration of these regimes for a wide spectrum of experimental conditions and found that on average, the slow regime lasts longer than the fast one, meaning that during most of the process, the lysis is ineffective. We proposed a computational model in which the properties of the binding of the proteins change during the lysis: first, the biochemical reactions take place at the surface of the fibrin fibers, then in the bulk, resulting in the observed fast lysis regime. This simple hypothesis appeared to be sufficient to reproduce with a great accuracy the lysis profiles obtained experimentally., (Copyright © 2021 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

We propose a procedure to implement Dirichlet velocity boundary conditions for complex shapes that use data from a single node only, in the context of the lattice Boltzmann method. Two ideas are at the base of this approach. The first is to generalize the geometrical description of boundary conditions combining bounce-back rule with interpolations. The second is to enhance them by limiting the interpolation extension to the proximity of the boundary. Despite its local nature, the resulting method exhibits second-order convergence for the velocity field and shows similar or better accuracy than the well-established Bouzidi's scheme for curved walls [M. Bouzidi, M. Firdaouss, and P. Lallemand, Phys. Fluids 13, 3452 (2001)]PHFLE61070-663110.1063/1.1399290. Among the infinite number of possibilities, we identify several meaningful variants of the method, discerned by their approximation of the second-order nonequilibrium terms and their interpolation coefficients. For each one, we provide two parametrized versions that produce viscosity independent accuracy at steady state. The method proves to be suitable to simulate moving rigid objects or surfaces moving following either the rigid body dynamics or a prescribed kinematic. Also, it applies uniformly and without modifications in the whole domain for any shape, including corners, narrow gaps, or any other singular geometry.

•A detailed, practical description of a 2D lattice Boltzmann (LB) free-surface model and its coupling with a 1D LB shallow water model is provided.•A Python code is provided, that implements the Gaussian droplet benchmark of the research article (Thorimbert et al., 2019) corresponding to this method article.•Particular attention is given to the details of the free-surface implementation which, in the literature, vary among authors. These ambiguities must be addressed in order to build a reproducible scheme, as well as the exact implementation and parameters of the coupling model proposed in the associated research article., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

We propose a highly versatile computational framework for the simulation of cellular blood flow focusing on extreme performance without compromising accuracy or complexity. The tool couples the lattice Boltzmann solver Palabos for the simulation of blood plasma, a novel finite-element method (FEM) solver for the resolution of deformable blood cells, and an immersed boundary method for the coupling of the two phases. The design of the tool supports hybrid CPU-GPU executions (fluid, fluid-solid interaction on CPUs, deformable bodies on GPUs), and is non-intrusive, as each of the three components can be replaced in a modular way. The FEM-based kernel for solid dynamics outperforms other FEM solvers and its performance is comparable to state-of-the-art mass-spring systems. We perform an exhaustive performance analysis on Piz Daint at the Swiss National Supercomputing Centre and provide case studies focused on platelet transport, implicitly validating the accuracy of our tool. The tests show that this versatile framework combines unprecedented accuracy with massive performance, rendering it suitable for upcoming exascale architectures., Competing Interests: We declare we have no competing interests., (© 2020 The Authors.)

Red blood cells (RBCs) in pathological situations undergo biochemical and conformational changes, leading to alterations in rheology involved in cardiovascular events. The shape of RBCs in volunteers and stable and exacerbated chronic obstructive pulmonary disease (COPD) patients was analyzed. The effects of RBC spherization on platelet transport (displacement in the flow field caused by their interaction with RBCs) were studied in vitro and by numerical simulations. RBC spherization was observed in COPD patients compared with volunteers. In in vitro experiments at a shear rate of 100 s -1 , treatment of RBCs with neuraminidase induced greater sphericity, which mainly affected platelet aggregates without changing aggregate size. At 400 s -1 , neuraminidase treatment changes both the size of the aggregates and the number of platelet aggregates. Numerical simulations indicated that RBC spherization induces an increase of the platelet mean square displacement, which is traditionally linked to the platelet diffusion coefficient. RBCs of COPD patients are more spherical than healthy volunteers. Experimentally, RBC spherization induces increased platelet transport to the wall. Additional studies are needed to understand the link between the effect of RBCs on platelet transport and the increased cardiovascular events observed in COPD patients., (© 2020 New York Academy of Sciences.)

Many organs are formed through folding of an epithelium. This change in shape is usually attributed to tissue heterogeneities, for example, local apical contraction. In contrast, compressive stresses have been proposed to fold a homogeneous epithelium by buckling. While buckling is an appealing mechanism, demonstrating that it underlies folding requires measurement of the stress field and the material properties of the tissue, which are currently inaccessible in vivo. Here, we show that monolayers of identical cells proliferating on the inner surface of elastic spherical shells can spontaneously fold. By measuring the elastic deformation of the shell, we infer the forces acting within the monolayer and its elastic modulus. Using analytical and numerical theories linking forces to shape, we find that buckling quantitatively accounts for the shape changes of our monolayers. Our study shows that forces arising from epithelial growth in three-dimensional confinement are sufficient to drive folding by buckling., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The fibrin clot is gelatinous matter formed upon injury to stop blood loss and is later destroyed by fibrinolysis, an enzymatic cascade with feedback. Pharmacological fibrinolysis stimulation is also used to destroy pathological, life-threatening clots and thrombi (thrombolysis). The regulation of the nonlinear spatially nonuniform fibrinolytic process in thrombolysis is not currently well understood. We developed a reaction-diffusion-advection model of thrombolysis by tissue plasminogen activator (TPA) in an occluded vessel with a pressure gradient. Sensitivity-analysis-based model reduction was used to reveal the critical processes controlling different steps of thrombolysis. The propagation of thrombolysis in the system without flow was predominantly controlled by TPA diffusion, whereas transport of other active components was rendered nonessential either by their high fibrin-binding parameters and short lifetimes or their initial uniform distribution. The concentration of the main TPA inhibitor plasminogen activator inhibitor 1 (PAI-1) controlled both the extent of lysis propagation and the shape of fibrin spatial distribution during lysis. Interestingly, PAI-1 remained important even when its concentration was an order of magnitude below that of TPA because of its role at the edge of the diffusing TPA front. The system was robust to reaction rate constant perturbations. Using these data, a reduced model of thrombolysis was proposed. In the presence of flow, convection of TPA was the critical controlling process; although the role of PAI-1 concentration was much less in the presence of flow, its influence became greater in the presence of collateral bypassing vessels, which sufficiently reduced TPA flux through the thrombus. Flow bypass through the collateral vessel caused a decrease in TPA flux in the clotted vessel, which increased the PAI-1/TPA ratio, thus making PAI-1-induced inhibition relevant for the regulation of spatial lysis up to its arrest., (Copyright © 2020 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

The lattice Boltzmann method (LBM) is known to suffer from stability issues when the collision model relies on the BGK approximation, especially in the zero viscosity limit and for non-vanishing Mach numbers. To tackle this problem, two kinds of solutions were proposed in the literature. They consist in changing either the numerical discretization (finite-volume, finite-difference, spectral-element, etc.) of the discrete velocity Boltzmann equation (DVBE), or the collision model. In this work, the latter solution is investigated in detail. More precisely, we propose a comprehensive comparison of (static relaxation time based) collision models, in terms of stability, and with preliminary results on their accuracy, for the simulation of isothermal high-Reynolds number flows in the (weakly) compressible regime. It starts by investigating the possible impact of collision models on the macroscopic behaviour of stream-and-collide based D2Q9-LBMs, which clarifies the exact physical properties of collision models on LBMs. It is followed by extensive linear and numerical stability analyses, supplemented with an accuracy study based on the transport of vortical structures over long distances. In order to draw conclusions as generally as possible, the most common moment spaces (raw, central, Hermite, central Hermite and cumulant), as well as regularized approaches, are considered for the comparative studies. LBMs based on dynamic collision mechanisms (entropic collision, subgrid-scale models, explicit filtering, etc.) are also briefly discussed. This article is part of the theme issue 'Fluid dynamics, soft matter and complex systems: recent results and new methods'.

Over the last decades, several types of collision models have been proposed to extend the validity domain of the lattice Boltzmann method (LBM), each of them being introduced in its own formalism. This article proposes a formalism that describes all these methods within a common mathematical framework, and in this way allows us to draw direct links between them. Here, the focus is put on single and multirelaxation time collision models in either their raw moment, central moment, cumulant, or regularized form. In parallel with that, several bases (nonorthogonal, orthogonal, Hermite) are considered for the polynomial expansion of populations. General relationships between moments are first derived to understand how moment spaces are related to each other. In addition, a review of collision models further sheds light on collision models that can be rewritten in a linear matrix form. More quantitative mathematical studies are then carried out by comparing explicit expressions for the post-collision populations. Thanks to this, it is possible to deduce the impact of both the polynomial basis (raw, Hermite, central, central Hermite, cumulant) and the inclusion of regularization steps on isothermal LBMs. Extensive results are provided for the D1Q3, D2Q9, and D3Q27 lattices, the latter being further extended to the D3Q19 velocity discretization. Links with the most common two and multirelaxation time collision models are also provided for the sake of completeness. This work ends by emphasizing the importance of an accurate representation of the equilibrium state, independently of the choice of moment space. As an addition to the theoretical purpose of this article, general instructions are provided to help the reader with the implementation of the most complicated collision models.

In this position paper, we discuss two relevant topics: (i) generic multiscale computing on emerging exascale high-performing computing environments, and (ii) the scaling of such applications towards the exascale. We will introduce the different phases when developing a multiscale model and simulating it on available computing infrastructure, and argue that we could rely on it both on the conceptual modelling level and also when actually executing the multiscale simulation, and maybe should further develop generic frameworks and software tools to facilitate multiscale computing. Next, we focus on simulating multiscale models on high-end computing resources in the face of emerging exascale performance levels. We will argue that although applications could scale to exascale performance relying on weak scaling and maybe even on strong scaling, there are also clear arguments that such scaling may no longer apply for many applications on these emerging exascale machines and that we need to resort to what we would call multi-scaling. This article is part of the theme issue 'Multiscale modelling, simulation and computing: from the desktop to the exascale'.

Cardio/cerebrovascular diseases (CVD) have become one of the major health issue in our societies. Recent studies show the existing clinical tests to detect CVD are ineffectual as they do not consider different stages of platelet activation or the molecular dynamics involved in platelet interactions. Further they are also incapable to consider inter-individual variability. A physical description of platelets deposition was introduced recently in Chopard et al. (2017), by integrating fundamental understandings of how platelets interact in a numerical model, parameterized by five parameters. These parameters specify the deposition process and are relevant for a biomedical understanding of the phenomena. One of the main intuition is that these parameters are precisely the information needed for a pathological test identifying CVD captured and that they capture the inter-individual variability. Following this intuition, here we devise a Bayesian inferential scheme for estimation of these parameters, using experimental observations, at different time intervals, on the average size of the aggregation clusters, their number per mm 2 , the number of platelets, and the ones activated per μℓ still in suspension. As the likelihood function of the numerical model is intractable due to the complex stochastic nature of the model, we use a likelihood-free inference scheme approximate Bayesian computation (ABC) to calibrate the parameters in a data-driven manner. As ABC requires the generation of many pseudo-data by expensive simulation runs, we use a high performance computing (HPC) framework for ABC to make the inference possible for this model. We consider a collective dataset of seven volunteers and use this inference scheme to get an approximate posterior distribution and the Bayes estimate of these five parameters. The mean posterior prediction of platelet deposition pattern matches the experimental dataset closely with a tight posterior prediction error margin, justifying our main intuition and providing a methodology to infer these parameters given patient data. The present approach can be used to build a new generation of personalized platelet functionality tests for CVD detection, using numerical modeling of platelet deposition, Bayesian uncertainty quantification, and High performance computing.

We consider a multi-agent model of a simple economical system and study the impacts of a wave of immigrants on the stability of the system. Our model couples a labor market with a goods market. We first create a stable economy with N agents and study the impact of adding n new workers in the system. The time to reach a new equilibrium market is found to obey a power law in n. The new wages and market prices are observed to decrease as 1/n, whereas the wealth of agents remains unchanged., Competing Interests: The authors have declared that no competing interests exist.

The numerical simulation of flow diverters like stents contributes to the development and improvement of endovascular stenting procedures, leading ultimately to an improved treatment of intracranial aneurysms. Due to the scale difference between the struts of flow diverters and the full artery, it is common to avoid fully resolved simulations at the level of the stent porosity. Instead, the effect of stents on the flow is represented by a heuristic continuum model. However, the commonly used porous media models describe the properties of flow diverters only partially, because they do not explicitly account for the deflection of the flow direction by the stent. We show that this deficiency can be circumvented by adopting the theoretical framework of screen models. The article first reviews existing screen models. It then proposes an explicit formula for the drag and the deflection coefficient, as predicted by each model, for both perpendicular and inclined angles. The results of 2D numerical simulations are used to formulate a generalization of these formulas, to achieve best results in the case of stent modeling. The obtained model is then validated, again through 2D numerical simulation., (Copyright © 2017 John Wiley & Sons, Ltd.)

The early stages of clot formation in blood vessels involve platelet adhesion-aggregation. Although these mechanisms have been extensively studied, gaps in their understanding still persist. We have performed detailed in vitro experiments, using the well-known Impact-R device, and developed a numerical model to better describe and understand this phenomenon. Unlike previous studies, we took into account the differential role of pre-activated and non-activated platelets, as well as the three-dimensional nature of the aggregation process. Our investigation reveals that blood albumin is a major parameter limiting platelet aggregate formation in our experiment. Simulations are in very good agreement with observations and provide quantitative estimates of the adhesion and aggregation rates that are hard to measure experimentally. They also provide a value of the effective diffusion of platelets in blood subject to the shear rate produced by the Impact-R., Competing Interests: We declare we have no competing interests.

Motivation: Bayesian inference is widely used nowadays and relies largely on Markov chain Monte Carlo (MCMC) methods. Evolutionary biology has greatly benefited from the developments of MCMC methods, but the design of more complex and realistic models and the ever growing availability of novel data is pushing the limits of the current use of these methods., Results: We present a parallel Metropolis-Hastings (M-H) framework built with a novel combination of enhancements aimed towards parameter-rich and complex models. We show on a parameter-rich macroevolutionary model increases of the sampling speed up to 35 times with 32 processors when compared to a sequential M-H process. More importantly, our framework achieves up to a twentyfold faster convergence to estimate the posterior probability of phylogenetic trees using 32 processors when compared to the well-known software MrBayes for Bayesian inference of phylogenetic trees., Availability and Implementation: https://bitbucket.org/XavMeyer/hogan., Contact: nicolas.salamin@unil.ch., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author 2016. Published by Oxford University Press.)

This article presents a three-dimensional numerical framework for the simulation of fluid-fluid immiscible compounds in complex geometries, based on the multiple-relaxation-time lattice Boltzmann method to model the fluid dynamics and the color-gradient approach to model multicomponent flow interaction. New lattice weights for the lattices D3Q15, D3Q19, and D3Q27 that improve the Galilean invariance of the color-gradient model as well as for modeling the interfacial tension are derived and provided in the Appendix. The presented method proposes in particular an approach to model the interaction between the fluid compound and the solid, and to maintain a precise contact angle between the two-component interface and the wall. Contrarily to previous approaches proposed in the literature, this method yields accurate solutions even in complex geometries and does not suffer from numerical artifacts like nonphysical mass transfer along the solid wall, which is crucial for modeling imbibition-type problems. The article also proposes an approach to model inflow and outflow boundaries with the color-gradient method by generalizing the regularized boundary conditions. The numerical framework is first validated for three-dimensional (3D) stationary state (Jurin's law) and time-dependent (Washburn's law and capillary waves) problems. Then, the usefulness of the method for practical problems of pore-scale flow imbibition and drainage in porous media is demonstrated. Through the simulation of nonwetting displacement in two-dimensional random porous media networks, we show that the model properly reproduces three main invasion regimes (stable displacement, capillary fingering, and viscous fingering) as well as the saturating zone transition between these regimes. Finally, the ability to simulate immiscible two-component flow imbibition and drainage is validated, with excellent results, by numerical simulations in a Berea sandstone, a frequently used benchmark case used in this field, using a complex geometry that originates from a 3D scan of a porous sandstone. The methods presented in this article were implemented in the open-source PALABOS library, a general C++ matrix-based library well adapted for massive fluid flow parallel computation.

Background: Flow diverter (FD) intervention is an emerging endovascular technique for treating intracranial aneurysms. High flow-diversion efficiency is desired to accelerate thrombotic occlusion inside the aneurysm; however, the risk of post-stenting stenosis in the parent artery is posed when flow-diversion efficiency is pursued by simply decreasing device porosity. For improving the prognosis of FD intervention, we develop an optimization method for the design of patient-specific FD devices that maintain high levels of porosity., Methods: An automated structure optimization method for FDs with helix-like wires was developed by applying a combination of lattice Boltzmann fluid simulation and simulated annealing procedure. Employing intra-aneurysmal average velocity as the objective function, the proposed method tailored the wire structure of an FD to a given vascular geometry by rearranging the starting phase of the helix wires., Results: FD optimization was applied to two idealized (S and C) vascular models and one realistic (R) model. Without altering the original device porosity of 80%, the flow-reduction rates of optimized FDs were improved by 5, 2, and 28% for the S, C, and R models, respectively. Furthermore, the aneurysmal flow patterns after optimization exhibited marked alterations. We confirmed that the disruption of bundle of inflow is of great help in blocking aneurysmal inflow. Axial displacement tests suggested that the optimal FD implanted in the R model possesses good robustness to tolerate uncertain axial positioning errors., Conclusions: The optimization method developed in this study can be used to identify the FD wire structure with the optimal flow-diversion efficiency. For a given vascular geometry, custom-designed FD structure can maximally reduce the aneurysmal inflow with its porosity maintained at a high level, thereby lowering the risk of post-stenting stenosis. This method facilitates the study of patient-specific designs for FD devices.

Most intracranial aneurysms morphologic studies focused on characterization of size, location, aspect ratio, relationship to the surrounding vasculature and hemodynamics. However, the spatial orientation with respect to the gravity direction has not been taken into account although it could trigger various hemodynamic conditions. The present work addresses this possibility. It was divided in two parts: 1) the orientations of 18, 3D time-of-flight MRI (3D TOF MRI), scans of saccular aneurysms were analyzed. This investigation suggested that there was no privileged orientation for cerebral aneurysms. The aneurysms were oriented in the brain as follows: 9 - down, 9 - up; 11 - right, 7 - left; 6 - front, 12 - back. 2) Based on these results, subsidiary in vitro experiments were performed, analyzing the behavior of red blood cells (RBCs) within a silicone model of aneurysm before and after flow diverter stent (FDS) deployment in the parent vessel. These experiments used a test bench that reproduces physiological pulsatile flow conditions for two orientations: an aneurysm sack pointing either up (opposite to gravitational force) and down (along the gravitational force). The results showed that the orientation of an aneurysm significantly affects the intra-aneurysmal RBCs behavior after stenting, and therefore that gravity can affect the intra-aneurysm behavior of RBCs. This suggests that the patient׳s aneurysm orientation could impact the outcome of the FDS treatment. The implementation of this effect in patient-specific numerical and preoperative decision support techniques could contribute to better understand the intrasaccular biological and hemodynamic events induced by FDS., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Particular intra-aneurysmal blood flow conditions, created naturally by the growth of an aneurysm or induced artificially by implantation of a flow diverter stent (FDS), can potentiate intra-aneurysmal thrombosis. The aim of this study was to identify hemodynamic indicators, relevant to this process, which could be used as a prediction of the success of a preventive endovascular treatment., Method: A cross sectional study on 21 patients was carried out to investigate the possible association between intra-aneurysmal spontaneous thrombus volume and the dome to neck aspect ratio (AR) of the aneurysm. The mechanistic link between these two parameters was further investigated through a Fourier analysis of the intra-aneurysmal shear rate (SR) obtained by computational fluid dynamics (CFD). This analysis was first applied to 10 additional patients (4 with and 6 without spontaneous thrombosis) and later to 3 patients whose intracranial aneurysms only thrombosed after FDS implantation., Results: The cross sectional study revealed an association between intra-aneurysmal spontaneous thrombus volume and the AR of the aneurysm (R(2)=0.67, p<0.001). Fourier analysis revealed that in cases where thrombosis occurred, the SR harmonics 0, 1, and 2 were always less than 25/s, 10/s, and 5/s, respectively, and always greater than these values where spontaneous thrombosis was not observed., Conclusions: Our study suggests the existence of an SR threshold below which thrombosis will occur. Therefore, by analyzing the SR on patient specific data with CFD techniques, it may be potentially possible to predict whether or the intra-aneurysmal flow conditions, after FDS implantation, will become prothrombotic., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

In this work we use a computational cell-based model to study the influence of the mechanical properties of cells on the mechanics of epithelial tissues. We analyze the effect of the model parameters on the elasticity and the mechanical response of tissues subjected to stress loading application. We compare our numerical results with experimental measurements of epithelial cell monolayer mechanics. Unlike previous studies, we have been able to estimate in physical units the parameter values that match the experimental results. A key observation is that the model parameters must vary with the tissue strain. In particular, it was found that, while the perimeter contractility and the area elasticity of cells remain constant at lower strains (<20%), they must increase to respond to larger strains (>20%). However, above a threshold of 50% extension, the cells stop counteracting the tissue strain and reduce both their perimeter contractility and area elasticity.

We propose a new numerical model to describe thrombus formation in cerebral aneurysms. This model combines CFD simulations with a set of bio-mechanical processes identified as being the most important to describe the phenomena at a large space and time scales. The hypotheses of the model are based on in vitro experiments and clinical observations. We document that we can reproduce very well the shape and volume of patient specific thrombus segmented in giant aneurysms., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Systems medicine is the application of systems biology concepts, methods, and tools to medical research and practice. It aims to integrate data and knowledge from different disciplines into biomedical models and simulations for the understanding, prevention, cure, and management of complex diseases. Complex diseases arise from the interactions among disease-influencing factors across multiple levels of biological organization from the environment to molecules. To tackle the enormous challenges posed by complex diseases, we need a modeling and simulation framework capable of capturing and integrating information originating from multiple spatiotemporal and organizational scales. Multiscale modeling and simulation in systems medicine is an emerging methodology and discipline that has already demonstrated its potential in becoming this framework. The aim of this chapter is to present some of the main concepts, requirements, and challenges of multiscale modeling and simulation in systems medicine.

Platelet spreading and retraction play a pivotal role in the platelet plugging and the thrombus formation. In routine laboratory, platelet function tests include exhaustive information about the role of the different receptors present at the platelet surface without information on the 3D structure of platelet aggregates. In this work, we develop, a method in Digital Holographic Microscopy (DHM) to characterize the platelet and aggregate 3D shapes using the quantitative phase contrast imaging. This novel method is suited to the study of platelets physiology in clinical practice as well as the development of new drugs.

Background: Mammals exhibit a remarkable variety of phenotypes and comparative studies using novel model species are needed to uncover the evolutionary developmental mechanisms generating this diversity. Here, we undertake a developmental biology and numerical modeling approach to investigate the development of skin appendages in the spiny mouse, Acomys dimidiatus., Results: We demonstrate that Acomys spines, possibly involved in display and protection, are enlarged awl hairs with a concave morphology. The Acomys spines originate from enlarged placodes that are characterized by a rapid downwards growth which results in voluminous follicles. The dermal condensation (dermal papilla) at the core of the follicle is very large and exhibits a curved geometry. Given its off-centered position, the dermal papilla generates two waves of anisotropic proliferation, first of the posterior matrix, then of the anterior inner root sheath (IRS). Higher in the follicle, the posterior and anterior cortex cross-section areas substantially decrease due to cortex cell elongation and accumulation of keratin intermediate filaments. Milder keratinization in the medulla gives rise to a foamy material that eventually collapses under the combined compression of the anterior IRS and elongation of the cortex cells. Simulations, using linear elasticity theory and the finite-element method, indicate that these processes are sufficient to replicate the time evolution of the Acomys spine layers and the final shape of the emerging spine shaft., Conclusions: Our analyses reveal how hair follicle morphogenesis has been altered during the evolution of the Acomys lineage, resulting in a shift from ancestral awl follicles to enlarged asymmetrical spines. This study contributes to a better understanding of the evolutionary developmental mechanisms that generated the great diversity of skin appendage phenotypes observed in mammals.

Multiscale simulations model phenomena across natural scales using monolithic or component-based code, running on local or distributed resources. In this work, we investigate the performance of distributed multiscale computing of component-based models, guided by six multiscale applications with different characteristics and from several disciplines. Three modes of distributed multiscale computing are identified: supplementing local dependencies with large-scale resources, load distribution over multiple resources, and load balancing of small- and large-scale resources. We find that the first mode has the apparent benefit of increasing simulation speed, and the second mode can increase simulation speed if local resources are limited. Depending on resource reservation and model coupling topology, the third mode may result in a reduction of resource consumption.