SofTMech with MIT and POLIMI (SofTMechMP)
Lead Research Organisation:
University of Glasgow
Department Name: School of Mathematics & Statistics
Abstract
Soft tissue related diseases (heart, cancer, eyes) are among the leading causes of death worldwide. Despite extensive
biomedical research, a major challenge is a lack of mathematical models that predict soft tissue mechanics across
subcellular to whole organ scales during disease progression. Given the tremendous scope, the unmet clinical needs, our
limited manpower, and the existence of complementary expertise, we seek to forge NEW collaborations with two world-leading
research centres: MIT and POLIMI, to embark on two challenging themes that will significantly stretch the initial
SofTMech remit: A) Test-based microscale modelling and upscaling, and B) Beyond static hyperelastic material to include
viscoelasticity, nonlinear poroelasticity, tissue damage and healing. Our research will lead to a better understanding of how
our bodies work, and this knowledge will be applied to help medical researchers and clinicians in developing new therapies
to minimise the damage caused by disease progression and implants, and to develop more effective treatments.
The added value will be a major leap forward in the UK research. It will enable us to model soft tissue damage and healing
in many clinical applications, to study the interaction between tissue and implants, and to ensure model reproducibility
through in vitro validations. The two underlying themes will provide the key feedback between tissue and cells and the
response of cells to dynamic local environments. For example, advanced continuum mechanics approaches will shed new
light on the influence of cell adhesion, angiogenesis and stromal cell-tumour interactions in cancer growth and spread, and
on wound healing implant insertion that can be tested with in vitro and in vivo systems. Our theoretical framework will
provide insight for the design of new experiments.
Our proposal is unique, timely and cost-effectively because advances in micro- and nanotechnology from MIT and POLIMI
now enable measurements of sub-cellular, single cell, and cell-ECM dynamics, so that new theories of soft tissue
mechanics at the nano- and micro-scales can be tested using in vitro prototypes purposely built for SofTMech. Bridging
the gaps between models at different scales is beyond the ability of any single centre. SofTMech-MP will cluster the critical
mass to develop novel multiscale models that can be experimentally tested by biological experts within the three world-leading
Centres. SofTMech-MP will endeavour to unlock the chain of events leading from mechanical factors at subcellular
nanoscales to cell and tissue level biological responses in healthy and pathological states by building a new mathematics
capacity.
Our novel multiscale modelling will lead to new mathematics including new numerical methods, that will be informed
and validated by the design and implementation of experiments at the MIT and POLIMI centres. This will be of enormous
benefit in attacking problems involving large deformation poroelasticity, nonlinear viscoelasticity, tissue dissection, stent-related
tissue damage, and wound healing development. We will construct and analyse data-based models of cellular and
sub-cellular mechanics and other responses to dynamic local anisotropic environments, test hypotheses in mechanistic
models, and scale these up to tissue-level models (evolutionary equations) for growth and remodelling that will take into
account the dynamic, inhomogeneous, and anisotropic movement of the tissue. Our models will be simulated in the
various projects by making use of the scientific computing methodologies, including the new computer-intensive methods
for learning the parameters of the differential equations directly from noisy measurements of the system, and new methods
for assessing alternative structures of the differential equations, corresponding to alternative hypotheses about the
underlying biological mechanisms.
biomedical research, a major challenge is a lack of mathematical models that predict soft tissue mechanics across
subcellular to whole organ scales during disease progression. Given the tremendous scope, the unmet clinical needs, our
limited manpower, and the existence of complementary expertise, we seek to forge NEW collaborations with two world-leading
research centres: MIT and POLIMI, to embark on two challenging themes that will significantly stretch the initial
SofTMech remit: A) Test-based microscale modelling and upscaling, and B) Beyond static hyperelastic material to include
viscoelasticity, nonlinear poroelasticity, tissue damage and healing. Our research will lead to a better understanding of how
our bodies work, and this knowledge will be applied to help medical researchers and clinicians in developing new therapies
to minimise the damage caused by disease progression and implants, and to develop more effective treatments.
The added value will be a major leap forward in the UK research. It will enable us to model soft tissue damage and healing
in many clinical applications, to study the interaction between tissue and implants, and to ensure model reproducibility
through in vitro validations. The two underlying themes will provide the key feedback between tissue and cells and the
response of cells to dynamic local environments. For example, advanced continuum mechanics approaches will shed new
light on the influence of cell adhesion, angiogenesis and stromal cell-tumour interactions in cancer growth and spread, and
on wound healing implant insertion that can be tested with in vitro and in vivo systems. Our theoretical framework will
provide insight for the design of new experiments.
Our proposal is unique, timely and cost-effectively because advances in micro- and nanotechnology from MIT and POLIMI
now enable measurements of sub-cellular, single cell, and cell-ECM dynamics, so that new theories of soft tissue
mechanics at the nano- and micro-scales can be tested using in vitro prototypes purposely built for SofTMech. Bridging
the gaps between models at different scales is beyond the ability of any single centre. SofTMech-MP will cluster the critical
mass to develop novel multiscale models that can be experimentally tested by biological experts within the three world-leading
Centres. SofTMech-MP will endeavour to unlock the chain of events leading from mechanical factors at subcellular
nanoscales to cell and tissue level biological responses in healthy and pathological states by building a new mathematics
capacity.
Our novel multiscale modelling will lead to new mathematics including new numerical methods, that will be informed
and validated by the design and implementation of experiments at the MIT and POLIMI centres. This will be of enormous
benefit in attacking problems involving large deformation poroelasticity, nonlinear viscoelasticity, tissue dissection, stent-related
tissue damage, and wound healing development. We will construct and analyse data-based models of cellular and
sub-cellular mechanics and other responses to dynamic local anisotropic environments, test hypotheses in mechanistic
models, and scale these up to tissue-level models (evolutionary equations) for growth and remodelling that will take into
account the dynamic, inhomogeneous, and anisotropic movement of the tissue. Our models will be simulated in the
various projects by making use of the scientific computing methodologies, including the new computer-intensive methods
for learning the parameters of the differential equations directly from noisy measurements of the system, and new methods
for assessing alternative structures of the differential equations, corresponding to alternative hypotheses about the
underlying biological mechanisms.
Planned Impact
Academic beneficiaries:
Multi-scale soft tissue modelling, based on biological processes and specifically designed
experiments, attacks the grand challenge of integrating cellular and sub-cellular mechanics with tissue and organ scale
mechanics that lies at the core of biomechanics research. Thus, the project will contribute to both basic and applied
sciences, as well as the translational (healthcare) domain. Our novel statistical inference methods will provide powerful
tools that will also be of benefit to cognate disciplines, like pathway medicine and systems biology.
The project will train 2 RAs and 11 PhD students, and benefit 50+ PhD students supervised by the applicants. It will aid early career researchers in the team to develop their international leadership, and expand cutting-edge soft tissue mechanics research in the UK. The
computational framework will be licensed for commercial software development to provide easy access for nonmathematicians.
Beneficiaries in EPSRC Healthcare Technologies:
The research will generate new models for studying many different soft
tissue diseases, and form the backbone of generic soft tissue modelling applicable to many additional health challenges. It
will contribute to "Novel treatment and therapeutic technologies" by providing the means to simulate tissue growth, cancer
invasion and cell migration, and inform the design of new experimental methods for cell and tissue growth, and drug
delivery, for heart and cancer applications and beyond. Our models will help to identify new biomarkers in MRI,
contributing to "Enhanced prediction and diagnosis in real time and at the point of care". As the tools can be used for the
development of experimental methods and translation of experimental results into clinical practice, it is also linked to
"Design, Manufacture and Integration of Healthcare Technologies".
Socio-Economic impact:
SofTMech-MP will enhance the quality of life and health in the UK, and beyond, and enhance the
UK's global competitiveness by addressing the most important healthcare problems. Heart disease is the leading killer in
the world, responsible for ~30% of all deaths each year. Cancer is the second deadliest disease, and the World Health
Organization projects that without immediate action, the global number of deaths from cancer will increase by nearly 80%
by 2030. Retinal degenerative diseases will affect 196 million people worldwide in 2020, predicted to rise to 288 million by 2040. Our
research will generate a range of reproducible models for studying these diseases that will facilitate translational medical
research to enhance diagnosis, treatment, and prevention. By developing test- and data-based modelling, we will examine
how cellular changes affect stress and strain distributions within organs, what drives functional responses within cells, and
which parameters are strongly associated with adverse remodelling leading to heart failure, wound healing after implants,
retinal detachment, or cancer metastasis. This fundamental research will significantly advance our understanding of
disease pathogenesis, diagnosis and responses to therapy, and hence move clinical research forward.
SofTMech-MP will raise awareness of our research to new and existing groups by networking activities, increase
knowledge transfers by involving new clinical/industrial partners through networking and Dialogues, and influence the
effectiveness of public services and policy by engagement with the Turing Gateway to Mathematics. Ultimately, our research will improve
the quality of life of all and lead to health economic benefits for the NHS and wider society.
Multi-scale soft tissue modelling, based on biological processes and specifically designed
experiments, attacks the grand challenge of integrating cellular and sub-cellular mechanics with tissue and organ scale
mechanics that lies at the core of biomechanics research. Thus, the project will contribute to both basic and applied
sciences, as well as the translational (healthcare) domain. Our novel statistical inference methods will provide powerful
tools that will also be of benefit to cognate disciplines, like pathway medicine and systems biology.
The project will train 2 RAs and 11 PhD students, and benefit 50+ PhD students supervised by the applicants. It will aid early career researchers in the team to develop their international leadership, and expand cutting-edge soft tissue mechanics research in the UK. The
computational framework will be licensed for commercial software development to provide easy access for nonmathematicians.
Beneficiaries in EPSRC Healthcare Technologies:
The research will generate new models for studying many different soft
tissue diseases, and form the backbone of generic soft tissue modelling applicable to many additional health challenges. It
will contribute to "Novel treatment and therapeutic technologies" by providing the means to simulate tissue growth, cancer
invasion and cell migration, and inform the design of new experimental methods for cell and tissue growth, and drug
delivery, for heart and cancer applications and beyond. Our models will help to identify new biomarkers in MRI,
contributing to "Enhanced prediction and diagnosis in real time and at the point of care". As the tools can be used for the
development of experimental methods and translation of experimental results into clinical practice, it is also linked to
"Design, Manufacture and Integration of Healthcare Technologies".
Socio-Economic impact:
SofTMech-MP will enhance the quality of life and health in the UK, and beyond, and enhance the
UK's global competitiveness by addressing the most important healthcare problems. Heart disease is the leading killer in
the world, responsible for ~30% of all deaths each year. Cancer is the second deadliest disease, and the World Health
Organization projects that without immediate action, the global number of deaths from cancer will increase by nearly 80%
by 2030. Retinal degenerative diseases will affect 196 million people worldwide in 2020, predicted to rise to 288 million by 2040. Our
research will generate a range of reproducible models for studying these diseases that will facilitate translational medical
research to enhance diagnosis, treatment, and prevention. By developing test- and data-based modelling, we will examine
how cellular changes affect stress and strain distributions within organs, what drives functional responses within cells, and
which parameters are strongly associated with adverse remodelling leading to heart failure, wound healing after implants,
retinal detachment, or cancer metastasis. This fundamental research will significantly advance our understanding of
disease pathogenesis, diagnosis and responses to therapy, and hence move clinical research forward.
SofTMech-MP will raise awareness of our research to new and existing groups by networking activities, increase
knowledge transfers by involving new clinical/industrial partners through networking and Dialogues, and influence the
effectiveness of public services and policy by engagement with the Turing Gateway to Mathematics. Ultimately, our research will improve
the quality of life of all and lead to health economic benefits for the NHS and wider society.
Organisations
- University of Glasgow (Lead Research Organisation)
- University College London (Collaboration)
- Dassault Systèmes (United Kingdom) (Project Partner)
- InSilicoTrials Technologies (Project Partner)
- Translumina GmbH (Project Partner)
- GlaxoSmithKline (United Kingdom) (Project Partner)
- Humanitas University (Project Partner)
- Siemens plc (UK) (Project Partner)
- Terumo Vascutek (Project Partner)
- Massachusetts Institute of Technology (Project Partner)
- NHS GREATER GLASGOW AND CLYDE (Project Partner)
- Kirkstall (United Kingdom) (Project Partner)
- NHS Research Scotland (Project Partner)
- Politecnico di Milano (Project Partner)
- Biomer Technology (United Kingdom) (Project Partner)
- InnoScot Health (Project Partner)
- Boston Scientific (United States) (Project Partner)
- Vascular Flow Technologies (Project Partner)
Publications
Zhuan X
(2022)
Volumetric growth of soft tissues evaluated in the current configuration.
in Biomechanics and modeling in mechanobiology
Yang Y
(2022)
Classification of Myocardial Blood Flow based on Dynamic Contrast-Enhanced Magnetic Resonance Imaging using Hierarchical Bayesian Models
in Journal of the Royal Statistical Society Series C: Applied Statistics
Yang Y
(2024)
Automatic detection of myocardial ischaemia using generalisable spatio-temporal hierarchical Bayesian modelling of DCE-MRI.
in Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society
Wang Z
(2022)
Simulation of fluid-structure interaction during the phaco-emulsification stage of cataract surgery
in International Journal of Mechanical Sciences
Wang Y
(2023)
Strain stiffening retards growth instability in residually stressed biological tissues
in Journal of the Mechanics and Physics of Solids
Wang Y
(2021)
A ghost structure finite difference method for a fractional FitzHugh-Nagumo monodomain model on moving irregular domain
in Journal of Computational Physics
Wang D
(2021)
Multiple Steady and Oscillatory Solutions in a Collapsible Channel Flow
in International Journal of Applied Mechanics
Wang D
(2023)
Flow-induced surface instabilities in a flexible-walled channel with a heavy wall
in Journal of Fluid Mechanics
Wang D
(2021)
Energetics of collapsible channel flow with a nonlinear fluid-beam model
in Journal of Fluid Mechanics
Villa C
(2021)
Mechanical Models of Pattern and Form in Biological Tissues: The Role of Stress-Strain Constitutive Equations
in Bulletin of Mathematical Biology
Villa C
(2022)
A novel nonlocal partial differential equation model of endothelial progenitor cell cluster formation during the early stages of vasculogenesis.
in Journal of theoretical biology
Thekkethil N
(2023)
A stabilized linear finite element method for anisotropic poroelastodynamics with application to cardiac perfusion
in Computer Methods in Applied Mechanics and Engineering
Sykes R
(2023)
Invasive coronary microvascular function assessment: pharmacological versus exercise testing.
in Heart (British Cardiac Society)
Spennati G
(2021)
Organotypic platform for studying cancer cell metastasis.
in Experimental cell research
Smilowitz NR
(2023)
Coronary Microvascular Disease in Contemporary Clinical Practice.
in Circulation. Cardiovascular interventions
Singh SP
(2021)
Extracellular Signalling Modulates Scar/WAVE Complex Activity through Abi Phosphorylation.
in Cells
Simitev RD
(2023)
Phenomenological analysis of simple ion channel block in large populations of uncoupled cardiomyocytes.
in Mathematical medicine and biology : a journal of the IMA
Roque-Piedra A
(2023)
Effective Properties of Homogenised Nonlinear Viscoelastic Composites
in Materials
Romaszko L
(2021)
Neural network-based left ventricle geometry prediction from CMR images with application in biomechanics.
in Artificial intelligence in medicine
Richardson SIH
(2021)
A poroelastic immersed finite element framework for modelling cardiac perfusion and fluid-structure interaction.
in International journal for numerical methods in biomedical engineering
RamÃrez-Torres A
(2023)
Effective properties of fractional viscoelastic composites via two-scale asymptotic homogenization
in Mathematical Methods in the Applied Sciences
RamÃrez-Torres A
(2021)
Two-scale, non-local diffusion in homogenised heterogeneous media
in Archive of Applied Mechanics
Qi N
(2022)
Estimations of Critical Clear Corneal Incisions Required for Lens Insertion in Cataract Surgery: A Mathematical Aspect
in Frontiers in Physiology
Paun LM
(2020)
Assessing model mismatch and model selection in a Bayesian uncertainty quantification analysis of a fluid-dynamics model of pulmonary blood circulation.
in Journal of the Royal Society, Interface
Ong P
(2023)
Invasive Assessments For Coronary Vasomotor Disorders: Current State of the Art Methods Collection.
in Journal of visualized experiments : JoVE
Mortensen P
(2021)
Addendum: Action potential propagation and block in a model of atrial tissue with myocyte-fibroblast coupling.
in Mathematical medicine and biology : a journal of the IMA
Morrow AJ
(2020)
Rationale and design of the Medical Research Council's Precision Medicine with Zibotentan in Microvascular Angina (PRIZE) trial.
in American heart journal
Morris PD
(2022)
Coronary physiological assessment in the catheter laboratory: haemodynamics, clinical assessment and future perspectives.
in Heart (British Cardiac Society)
Miller L
(2020)
Effective balance equations for poroelastic composites
in Continuum Mechanics and Thermodynamics
Miller L
(2023)
Effective Governing Equations for Viscoelastic Composites
in Materials
Miller L
(2024)
Effective double-poroelasticity derived via homogenization of two non-interacting solid phases percolated by a viscous fluid
in European Journal of Mechanics - A/Solids
Miller L
(2021)
Double poroelasticity derived from the microstructure
in Acta Mechanica
Miller L
(2023)
Homogenised governing equations for pre-stressed poroelastic composites
in Continuum Mechanics and Thermodynamics
Miller L
(2023)
Investigating the effects of microstructural changes induced by myocardial infarction on the elastic parameters of the heart.
in Biomechanics and modeling in mechanobiology
Miller L
(2021)
Homogenized Balance Equations for Nonlinear Poroelastic Composites
in Applied Sciences
Miller L
(2023)
Micromechanical analysis of the effective stiffness of poroelastic composites
in European Journal of Mechanics - A/Solids
Miller L
(2024)
Homogenization of a coupled electrical and mechanical bidomain model for the myocardium
in Mathematics and Mechanics of Solids
McQueen A
(2021)
Do we really understand how drug eluted from stents modulates arterial healing?
in International journal of pharmaceutics
McQueen A
(2022)
An intricate interplay between stent drug dose and release rate dictates arterial restenosis.
in Journal of controlled release : official journal of the Controlled Release Society
McErlane J
(2023)
Cardiac Biomarkers and Right Ventricular Dysfunction Are Associated Independently With 1-Year Mortality in Patients With COVID-19 Receiving Mechanical Ventilation
in CHEST Critical Care
McErlane J
(2022)
Right ventricular free wall longitudinal strain is independently associated with mortality in mechanically ventilated patients with COVID-19.
in Annals of intensive care
Description | Cell modelling: Using Gaussian process enhanced semi-automatic approximate Bayesian computation, we have performed parameter inference in a stochastic differential equation system for chemotaxis. Our findings show how local deformations of the cell membrane (so-called pseudopods) drive cell movement, how these deformations depend on the diffusion and reactions of certain chemicals (activators and inhibitors) in the cell membrane, how a variation of the chemical reaction and diffusion parameters induces different cell movement modes, and how these parameters can be estimated, along with sound uncertainty quantification, from cell movement data. Dr Jakub Koery (RA1) has constructed an extensive literature review on the structure of the eukaryotic cell cytoskeleton and models for cross-linked polymer networks. He has formulated a new discrete model for a cross-linked cytoskeletal network formed of both actin and vimentin filaments and shown how this model can be upscaled to a continuum description. He has used these models to examine the deformation of the network in response to the prescribed motion of an embedded rigid bead (to mimic optical tweezers experiments for estimating cell rheology conducted by our collaborators at MIT), elucidating the force-displacement curve. Asymptotic reductions of the continuum model facilitate an analytical approximation for the gradient of the force-displacement curve in terms of the cell and bead properties, providing a new way to use the experiments to estimate cell material parameters. He has further been able to extend his continuum description of the cell cytoskeleton to formulate a new strain energy functional which can be implemented directly into computational descriptions of the cell. Dr Namshad Thekkethil (RA2) has performed finite element simulations using this new strain energy functional, incorporating it into a large-scale poroviscoelastic formulation including viscosity of both the cytoskeletal structure and the cytosol. The predictions of this model show good qualitative agreement with the experimental results from the MIT lab, as well as some interesting new insights, this is being written up for publication. Negative chemotaxis, where eukaryotic cells migrate away from repellents, is important throughout biology, for example in nervous system patterning and resolution of inflammation. However, the mechanisms by which molecules repel migrating cells are unknown. Here, we use a combination of modelling and experiments with Dictyostelium cells to show that competition between different ligands that bind to the same receptor leads to effective chemorepulsion. 8-CPT-cAMP, widely described as a simple chemorepellent, is inactive on its own, and only repels cells if it interacts with the attractant cAMP. If cells degrade either competing ligand, the pattern of migration becomes more complex; cells may be repelled in one part of a gradient but attracted elsewhere, leading to populations moving in different directions in the same assay, or converging in an arbitrary place. More counterintuitively still, two chemicals can each attract cells on their own, but repel cells when combined together. We have thus identified a new mechanism that drives reverse chemotaxis, verified by mathematical models and experiments with real cells, and important anywhere several ligands compete for the same receptors. Elasticity and porous media flow: We have modelled cardiac perfusion with improved numerical efficiency, we studied the fibre effects on poroelasticity as well as set up several reproducible numerical examples for future benchmark. We have successfully coupled the coronary vessel network with the poroelastic myocardium model, enabling a two way feedback in cardiac perfusion. This computational framework is published in IJNMBE (Richardson et al. 2022). We also have developed new numerical methods for an immerse interface model for both hyperelastic and poroelastic material, which allows higher resolution and is much faster than the original solver, and the work is published in CMAME (Thekkethil et al. 2023). We revealed the role of microscale solid matrix compressibility (Dehghani, et al. 2020) on the mechanical behaviour of poroelastic materials and derived a new model which describes the macroscale mechanics and effective coefficients of both linear elastic (Miller & Penta, CMT, 2020) hyperleastic poroelastic composites (Miller & Penta, AP, 2021) , and double poroelastic media (Miller & Penta, AM, 2021). We have further shown the applicability of the new model (Miller & Penta, CMT, 2020) by performing numerical simulations which show that our new poroelastic model should normally be used when the porosity exceeds a 5% threshold if the solid matrix is heterogeneous (Miller & Penta, 2023) and the specific microstructural arrangement of the composites subphases that can justify macroscale isotropy (Miller & Penta, AM, 2021). We also investigated the role of inhomogeneous body forces in driving fluid flow in heterogeneous porous media. We derived a new model which can be used to predict the role of magnetic (or electric) fields on ferrofluids (or electrolytes) flowing in porous and their interplay with the heterogeneous porous structure (Penta et al. 2021) Growth and Remodelling: Using a new theory that allows the growth tensor to be defined in the current loaded configuration (Zhuan and Luo, 2022), we are investigating various new growth laws for general soft tissues, and developing a new EPSRC grant proposal based on this work. We developed a novel framework for modelling pathological cardiac growth and remodelling based on constrained mixture theory using updated reference configuration. Different biological constituent's adaptations under pathological conditions were integrated together, including the ground matrix, myofibres and collagen network. Our results have shown that this constrained mixture motivated growth and remodelling model can capture different phenotypes of maladaptive left ventricle growth and remodelling. This work is submitted to a top journal in biomechanics and currently under revision. Moreover, to improve the active contraction model of the myocardium, we have proposed a new hybrid active contraction model for myocardial dynamics abstracted from sarcomere by combining the phenomenologically active-stress based Hill model and the micro-structurally motivated active strain approach. This work is published in Computers in Biology and Medicine (2022). In terms of cancer modelling, we have developed new mathematical models derived by asymptotic homogenisation to address transport of fluid, drug, and heat in vascularised tumours subjected to cancer hyperthermia therapy conducted by both small (extravasating) (Sariri et al,2022), and large (adhering) nanoparticles Sariri et al,2023). In the latter work, we have determined how to achieve safe hyperthermic conditions on parameters such as magnetic field intensity and tumour microvasculature properties, so that experimental setups can be adapted depending on patient-specific pathological conditions. We have also developed a new mathematical model of stress-mediated growth based on the unloaded configuration that considers either the residual stress or the deformation gradient relative to the unloaded configuration as a growth variable. This makes it possible to analyze stress-mediated growth without the need to invoke the existence of a fictitious stress-free grown configuration (Huang, et al. 2021) Viscoelasticity: Dr. Yangkun Du (RA3) used a second-order elasticity theory to capture larger amplitude deformations and material nonlinearity, and provided a general solution for the contact problem for deformations that are second-order in indentation amplitude with arbitrary indenter profiles. Moreover, we derived analytical solutions by using either parabolic or quartic surfaces to mimic a spherical indenter. This has been used as a basis for formulating the finite deformation indentation of a soft half-space with a rigid indenter in order to obtain a finite deformation generalization of the linearly elastic Hertz indentation result. We also developed a new model for hierarchical viscoelastic composites and computed three-scales homogenised properties for wavy layered structures analytically. We also implemented a new semi-analytical scheme (AHMFE, i.e. Asymptotic Homogenisation Method Finite Elements) via which we computed (a) the effective properties of isotropic viscoelastic composites in three dimensions (Cruz-González et al. IJES, 2020), (b) extended the formulation to compute the effective properties for both long and short (i.e. cylindrical inclusions) anisotropic fibres (Cruz-González et al. AES, 2021). We have also recently developed a new theoretical model for three-scales, hierarchical viscoelastic materials and derived the homogenised effective coefficients for non-perfectly periodic laminated composites (Cruz-González et al. MAMS, 2021). and proved its reliability and advantages by numerical validation in (Cruz-González et al. EJMAS, 2022). Heart mechanics modelling: Ventricle-valve Interaction we extended the left ventricle model to include the mitral valve model, and then added the left atrium model, linked with the pulmonary circulation. In collaboration with Mark Danton (consultant cardiac surgeon), we obtained interesting new results about these sub-systems of the heart, compared with clinical observations. The work is published in BMMB and presented at various conferences, workshops. We also improved the modelling of the myocardium by adding details of the cellular level. The heart muscle cells (myocytes) in the myocardium and the scaffold (collagen network) have very delicate structures to maximize the pumping function. Existing studies usually consider main features (i.e. average muscle orientations), but miss features like dispersion. In this new work both the passive and active heart muscle models include the myocyte and collagen dispersions, and the work is published in R Soc Open Science (2020) and JEM (2021). Myofibre dispersions along different directions were further analysed in a human left ventricle model by taking into account both the myofibre dispersion and the sheet fibre dispersion. The descriptive capability of this dispersion model was first studied by fitting it to ex vivo experimental data, and then in a heart model for both passive response and active response. The results are published in Mathematical Biosciences and Engineering (2022, part I and II). Electrophysiology: We investigated the behaviour of electrosensitive multiscale materials and derived a new set of effective balance equations for composites characterised by a discontinuity in both the electric and the mechanical properties (Stefano, et al. ZAMP, 2020). Five further studies of the electrophysiology of cardiomyocytes and hiPSC-cardiomyocytes have been published in this period. In (Mortensen et al., 2021) we developed an analytical theory of action potential block due to non-uniform distributions of fibroblast cells in atrial tissue, namely fibroblast barrier distribution and myocyte strait distribution. In (Costa et al., 2021) we tested the hypothesis that the co-culturing of human-induced pluripotent stem cell-derived cardiomyocytes (hiCMs) with a human embryonic kidney (HEK) cell-line expressing the Kir2.1 channel (HEK-IK1) can generate an electrical syncytium with an adult-like cardiac electrophysiology. The electrical and mechanical activity of co-cultures using different HEK-IK1:hiCM ratios was measured and compared with co-cultures using wildtype (HEK-WT:hiCM) or hiCM alone on days 3-8 after plating and a computational model of the co-culture was developed to explain the observed electrophysiological effects. In (Huethorst et al., 2022) we studied the spatiotemporal features of contraction of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) arranged in monolayers interacting mechanically via cell-cell and cell-substrate adhesion and in the presence of Isoprenaline. To clarify the underlying mechanisms, further gene expression and computational studies were performed. We found that HiPSC-CM monolayers exhibited multiphasic contractile profiles on rigid surfaces in contrast to hydrogels, substrate-free cultures or single cells where only simple twitch-like time-courses were observed and concluded that flexible substrates are necessary for normal twitch-like contractility kinetics and interpretation of inotropic interventions. In (Lachaud et al. 2022) we reported and analysed electrophysiological heterogeneity in large populations of rabbit ventricular cardiomyocytes. APD in ~50 isolated cells from subregions of the LV free wall of 17 rabbit hearts were measured using a voltage-sensitive dye and significant (i) regional differences in action potential (AP) waveform, (ii) AP waveform differences in cells isolated from a single region, (iii) variability of the contribution of individual ion currents in cells with similar AP durations (APDs) were found. Highly variable changes in APD occurred after IK(r) or ICa(L) block that included a sub-population of cells (HR) with an exaggerated (hyper) response to IK(r) inhibition. A set of 4471 AP models matching the experimental APD90 distribution was generated from a larger population of models created by random variation of the maximum conductances (Gmax) of 8 key ion channels/exchangers/pumps. This set reproduced the pattern of cell-specific responses to ICa(L) and IK(r) block, including the HR sub-population. The models exhibited a wide range of Gmax values with constrained relationships linking ICa(L) with IK(r), ICl, INCX, and INaK. In (Simitev et al. 2023), a methodology was developed for quantifying the individual electrophysiological properties of large numbers of uncoupled cardiomyocytes under ion channel block in terms of the parameters values of a conceptual fast-slow model of electrical excitability. The approach was applied to the experimental data of (Lachaud et al., 2022, Cardiovasc. Res.). Drug action was represented by a multiplicative factor to an effective ion conductance, a closed form asymptotic expression for APD was derived and inverted to determine model parameters as functions of APD and ?APD for each myocyte. The explicit APD expression and the resulting set of model parameter values allow (a) direct evaluation of conditions necessary to maintain fixed APD or ?APD, (b) predictions of the proportion of cells remaining excitable after drug application, (c) predictions of stimulus period dependency and (d) predictions of dose-response curves, the latter being in agreement with additional experimental data. In (Aziz and Simitev, 2022) we developed a robust method along with open-source numerical code for estimation of the parameter values of a relatively simple but mathematically accurate archetypal model of single-cell cardiac from measurements of the morphology of single-stimulus action potentials derived from detailed ionic current models and from experimental myocyte measurements. An archetypal model that accurately reproduces a variety of wet-lab and synthetic electrophysiology data offers a number of mathematical and computational advantages. Damage and homogenization: We have been developing a new theoretical multiscale model which couples the mechanical response of a linear elastic composite with the evolution of the damage. Application to aortic dissection: The medical device manufacturer, Terumo-Aortic, has funded a PhD student, Sathish Kumar, to study the design and deployment of fabric-coated stents to treat aortic dissection, with a focus on reducing the likelihood of stent-induced new entry tear (SINE). The deliverables for Terumo-Aortic will include Abaqus computer programs to simulate and test the biomechanical performance, and interaction with the soft tissue of the arterial wall, of new and existing stents. The research project will make use of the new mathematical and computational models of soft tissue damage being developed by SofTMechMP. To date, representative computational models of arteries have been constructed from images and meshed. Algorithms have been developed to estimate residual stress and the unloaded configuration for these models to permit realistic calculations of stress and strain in the arterial wall based on the HGO constitutive law. Computational models of specific stents and their deployment have been constructed and used to identify contact regions of high stress and strain that are likely sites of damage to the wall. Studies of critical pressures for tear propagation in idealised 3D aortic wall models have been undertaken, and current work is focussed on integrating the dissection models with in situ stents. Applications to stent for occluded coronary arteries: We obtained analytical and numerical studies of shape memory polymers stent and found that radial strength of stent is a function of the radius of the stent and periodic numbers of the unit cell in the circumferential direction. We identified influences of vessel curvature and plaque composition on drug transport in the arterial wall following drug-eluting stent implantation. We identified how stent expansion alters drug transport properties of the arterial wall. Arising from this work are a number of publications (Corti et al. 2021). Investigators from UoG and POLIMI reported on a novel 3D model of drug-coated balloon treatment of calcified superficial arteries, uncovering the influence on drug kinetics of the geometrical and compositional features of the vessel, balloon design characteristics and procedural aspects (Escuer et al. 2021).. In collaboration with clinical and experimental collaborators, we re-explored our current understanding of how antiproliferative drugs coated on stents and balloons reduce proliferation of vascular smooth muscle cells (SMCs). Our findings call into question the accuracy of existing mathematical models of cell proliferation subject to drug exposure and current thinking regarding the drugs' mechanism of action, potentially having important implications on the interpretation of current computational models and their future use to optimise and control drug release from stents and drug-coated balloons. We developed a series of multiphysics models to explore the influence of fluid flow on drug release from drug-filled implants, used in cardiovascular ad orthopaedic applications, elucidating the influence of fluid flow and material properties on the drug release profile. We developed a series of multiphysics models to explore the influence of fluid flow on drug release from drug-filled implants, used in cardiovascular ad orthopaedic applications, elucidating the influence of fluid flow and material properties on the drug release profile (King et al. Phar. Res, 2022). Applications to the eye: In collaboration with clinicians, we used a computational model to study routine cataract operations and identified key parameters in affecting tissue damage during these operations and pointed out how to minimise these damages (Qi et al. 2022). Dr Jakub Koery (RA1) has also developed a new mechanical model for the human cornea, describing the tissue as a discrete array of cross-linked collagen lamellae, in collaboration with Prof Anna Pandolfi (POLIMI). This model has been upscaled to form a novel new continuum description of the cornea and will be used to investigate (and optimise) corneal cross-linking therapies for keratoconus. Parameter inference and sensitivity study: Personalized computational cardiac models are considered to be a unique and powerful tool in modern cardiology, integrating the knowledge of physiology, pathology and fundamental laws of mechanics in one framework. They have the potential to improve risk prediction in cardiac patients and assist in the development of new treatments. However, in order to use these models for clinical decision support, it is important that both the impact of model parameter perturbations on the predicted clinical quantities of interest as well as the uncertainty of parameter estimation are properly quantified, where the first task is a priori in nature (meaning independent of any specific clinical data), while the second task is carried out a posteriori (meaning after specific clinical data have been obtained). We have addressed these challenges for a widely used constitutive law of passive myocardium (the Holzapfel-Ogden model), using global sensitivity analysis (SA) to address the first challenge, and inverse uncertainty quantification (UQ) for the second challenge. Our study reveals insights into the relation between SA and UQ, elucidates the dependence of parameter sensitivity and estimation uncertainty on external factors, like left ventricular cavity pressure, and sheds new light on cardio-mechanic model formulation, with particular focus on the Holzapfel-Ogden myocardial model (Lazarus et al., 2022). A challenging problem of in vivo parameter estimation in cardiac mechanics is the substantial computational complexity; this is a result of the fact that we have to repeatedly carry out forward simulations from the mathematical model as part of an iterative optimisation scheme. We have addressed this difficulty by building a black-box emulator, which replaces the original mathematical model by a statistical surrogate model. We have compared (Dalton et al., 2020a) and improved on (Dalton et al., 2020b) state-of-the-art methods. To further expand this work, we have worked on "opening the black box" by applying message passing algorithms from machine learning to the left ventricular mesh as a computationally faster alternative to numerically solving the finite element equations (Dalton et al., 2021). |
Exploitation Route | All the outcomes have been or will be published in international journals as open access. Most data and codes are accessible through GitHub or similar open-source repositories. We also run regular workshops and outreach events to ensure end-users know about our research developments. |
Sectors | Education,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Description | SofTMechMP is an International Centre to Centre Collaboration between the SofTMech Centre for Multiscale Soft Tissue Mechanics (www.softmech.org) and two world-leading research centres at Massachusetts Institute of Technology (MIT) in the USA and Politecnico di Milano (POLIMI) in Italy, funded by the EPSRC. Its exciting programme of research addresses important new mathematical challenges driven by clinical needs, such as tissue damage and healing, by developing multiscale soft tissue models that are reproducible and testable against experiments. Long term impacts are envisioned in areas such as tissue dissection, stent-related tissue damage, and wound healing development. Heart disease has a strong negative impact on society. In the United Kingdom alone, there are ~1.5 million people living with the burden of a heart attack. In developing countries, too, heart disease is becoming an increasing problem. Unfortunately, the exact mechanisms by which heart failure occurs are poorly understood. On a more optimistic note, a revolution is underway in healthcare and medicine - numerical simulations are increasingly being used to help diagnose and treat heart disease and devise patient-specific therapies. The Centre started on 1st January 2020 and some activities have been significantly delayed by the Covid-19 Pandemic, so economic and social impacts are not expected till later in the award. However, SofTMechMP has an impressive range of project partners that it engages with to advance research and ultimately deliver real-world impact. These include Biomer Technology Ltd; Boston Scientific; Dassault Systemes; GlaxoSmithKline plc (GSK); Humanitas University; InSilicoTrials Technologies; Kirkstall Ltd; Massachusetts Institute of Technology; NHS; Polytechnic University of Milan; Scottish Health Innovations Ltd; Siemens; Terumo Aortic; Translumina GmbH; Vascular Flow Technologies. Moreover, the SofTMech Centre has also been successful in the award of EPSRC funding for The SofTMech Statistical Emulation and Translation Hub (EP/T017899/1) whose focus is on Translation and Impact. |
First Year Of Impact | 2021 |
Sector | Education,Healthcare |
Description | A modelling study of right ventricular function in repaired tetralogy of fallot for predicting outcome and impact of pulmonary valve replacement |
Amount | £185,505 (GBP) |
Funding ID | PG/22/10930 |
Organisation | British Heart Foundation (BHF) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2022 |
End | 10/2025 |
Description | IEC\NSFC\191622 - International Exchanges 2019 Cost Share (NSFC) Royal Society-Newton Mobility Grant |
Amount | £12,000 (GBP) |
Funding ID | IEC\NSFC\191622 - International Exchanges 2019 Cost Share (NSFC) |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2020 |
End | 03/2022 |
Description | Leverhulme Research Fellowship (Professor Nick Hill) |
Amount | £55,000 (GBP) |
Organisation | The Leverhulme Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2021 |
End | 04/2022 |
Description | SofTMech with MIT and POLIMI (SofTMechMP) |
Amount | £1,599,530 (GBP) |
Funding ID | EP/S030875/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2020 |
End | 06/2025 |
Description | The SofTMech Statistical Emulation and Translation Hub |
Amount | £1,225,134 (GBP) |
Funding ID | EP/T017899/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2021 |
End | 02/2025 |
Title | Action potential propagation and block in a model of atrial tissue with myocyte-fibroblast coupling |
Description | n/a |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | n/a |
URL | http://researchdata.gla.ac.uk/id/eprint/1104 |
Title | Cardiac Modelling with dispersed myofibre and collagen structures |
Description | It is the accompanying dataset and model the paper "modelling of fibre dispersion and its effects on cardiac mechanics from diastole to systole", accepted in the Journal of Engineering Mathematics. It implements two different fibre dispersion models within two ventricular finite element models: a bi-ventricular rabbit heart and a human left ventricular model. |
Type Of Material | Computer model/algorithm |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | This study highlights the importance of fibre dispersion in cardiac mechanics, and for the first time to investigate how to incorporate a complex fibre dispersion distribution into a cardiac mechanics model. This work has been presented in the Living Heart Project Seminar, and we are working with the Virtual Human Team from Dassault System to implement it in the Living Heart Project. |
URL | https://github.com/HaoGao/DispersedFibresMyocardiumModelling |
Title | Code for Estimation of Parameters for an Archetypal Model of Cardiomyocyte Membrane Potentials |
Description | This is a suite of MATLAB/Octave functions for numerical solution of and for estimation of the parameter values of the cardiomyocyte membrane potential model of Biktashev et al. (Bull Math Biol, 70(2), 2008,doi:10.1007/s11538-007-9267-0) - "the archetypal model". In particular, the code can be used determine parameter values for the archetypal model such that its solutions approximate the action potential traces and the action potential duration restitution curves of (a) other electrophysiologically detailed mathematical models of the transmembrane ionic currents of single cardiac myocytes - "target models", as well as (b) traces and curves measured experimentally - "target data". Data and functions for several detailed ionic models from the CellML physiological model repository (cellml.org) are included as examples of usage. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | N/A |
URL | https://zenodo.org/record/4568662 |
Title | Energetics of a collapsible channel flow with a nonlinear fluid-beam model |
Description | Data for figures in 'Energetics of a collapsible channel flow with a nonlinear fluid-beam model' |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | http://researchdata.gla.ac.uk/id/eprint/1112 |
Title | Fibre Dispersion Myocardial Mechanics |
Description | It contains the computational models for the following two papers 1. Guan, D., Mei, Y., Xu, L., Cai, L., Luo, X., & Gao, H. (2022). Effects of dispersed fibres in myocardial mechanics, Part I: passive response. Mathematical Biosciences and Engineering, 19(4), 3972-3993. 2. Guan, D., Wang, Y., Xu, L., Cai, L., Luo, X., & Gao, H. (2022). Effects of dispersed fibres in myocardial mechanics, Part II: active response. Mathematical Biosciences and Engineering, 19(4), 4101-4119. Published Year: 2022 |
Type Of Material | Computer model/algorithm |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | This work has attracted interest from the Virtual Human Team from Dassault System. It will further improve the cardiac modelling by including detailed fibre dispersion, in particular in fibrosis modelling. |
URL | https://github.com/HaoGao/FibreDispersionMyocardialMechanics |
Title | Flow-induced surface instabilities in a flexible-walled channel with a heavy wall |
Description | Supporting data for 'Flow-induced surface instabilities in a flexiblewalled channel with a heavy wall' |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | http://researchdata.gla.ac.uk/id/eprint/1232 |
Title | GlasgowHeart: A Magnetic Resonance Imaging-derived 'virtual twin' cardiac mechanics platform |
Description | A personalized biomechanical cardiac modelling framework, aimed at the mechanistic understanding of individual patients' cardiac remodelling in the longer-term and risk-stratification. Our long-term aim is to be able to revolutionise clinical practice through accurate risk-stratification and virtual testing. Four modules are currently available in GlasgowHeart: 1) image processing, 2) biomechanics modelling, 3) personalization, inference and machine learning of left ventricular (LV) mechanics and 4) statistical emulation as shown in Figure 1. Modules 1, 2 and 3 have been developed in MATLAB by the co-authors, and module 4 is programmed in Python using Tensor Flow, Scikit-learn, XGBoost to use advanced machine-learning methods. For computational modelling in module 2, we further use LibMesh, IBAMR, Fenics for solving nonlinear systems, Visit and Paraview for 3D visualization. Module 2 can also work with other commercial packages for biomechanics simulations (ABAQUS, FEAP). |
Type Of Material | Computer model/algorithm |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | This framework has been developed over the last ten years and contributed to various projects and funding applications. Recently it was presented in SCMR 2021 conference in the open-source software demo session. |
URL | https://github.com/HaoGao/GlasgowHeart |
Title | Global stability analysis of flexible channel flow with a hyperelastic wall |
Description | Data for figures in 'Global stability analysis of flexible channel flow with a hyperelastic wall' |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | http://researchdata.gla.ac.uk/id/eprint/1113 |
Title | Multiple Steady and Oscillatory Solutions in a Collapsible Channel Flow |
Description | |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | http://researchdata.gla.ac.uk/id/eprint/1165 |
Title | Sensitivity Analysis and Inverse Uncertainty Quantification for the Left Ventricular Passive Mechanic |
Description | It contains the codes and data for the paper 'Sensitivity Analysis and Inverse Uncertainty Quantification for the Left Ventricular Passive Mechanics'. This work performs structural identifiability and practical identifiability analysis for a widely used constitutive law of passive myocardium (the Holzapfel-Ogden model), using global sensitivity analysis to assess structural identifiability, and inverse-uncertainty quantification to assess practical identifiability. |
Type Of Material | Computer model/algorithm |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | It elucidates the dependence of parameter identifiability on external factors for the first time in a nonlinear cardiomechanic model, with a particular focus on the H-O myocardial model. |
URL | https://github.com/HaoGao/ho-uncertainty-quantification |
Description | New academic collabration |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Collaboration with Dr. Jack Lee on heart perfusion modelling enables us to make use of their detailed coronary circulation model and expertise. |
Collaborator Contribution | Expertise and data |
Impact | Collaboration is still ongoing. No output yet. |
Start Year | 2021 |
Title | Code for Estimation of Parameters for an Archetypal Model of Cardiomyocyte Membrane Potentials |
Description | This is a suite of MATLAB/Octave functions for numerical solution of and for estimation of the parameter values of the cardiomyocyte membrane potential model of Biktashev et al. (Bull Math Biol, 70(2), 2008,doi:10.1007/s11538-007-9267-0) - "the archetypal model". In particular, the code can be used determine parameter values for the archetypal model such that its solutions approximate the action potential traces and the action potential duration restitution curves of (a) other electrophysiologically detailed mathematical models of the transmembrane ionic currents of single cardiac myocytes - "target models", as well as (b) traces and curves measured experimentally - "target data". Data and functions for several detailed ionic models from the CellML physiological model repository (cellml.org) are included as examples of usage. |
Type Of Technology | Software |
Year Produced | 2021 |
Open Source License? | Yes |
Impact | NA |
URL | https://zenodo.org/record/4568662 |
Title | GlasgowHeart |
Description | GlasgowHeart platform for personalized modelling of the human heart. It is organized into 4 modules, and each can be run separately. Currently, MatLab is the main programming language and using scripts for run, this will require certain knowledge of Matlab. In the future, we will develop a GUI package for easy use. The four modules are image processing, biomechanics modelling, personalization, and parameter inference of left ventricular (LV) mechanics and statistical emulation. |
Type Of Technology | Software |
Year Produced | 2021 |
Open Source License? | Yes |
Impact | The package is actively being used by the researchers from the SofTMech Centre and supports a few cardiac research projects. |
Description | BAMC minisymposium on Soft Tissue Growth and Remodelling |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | I organized a BAMC mini-symposium on Soft Tissue Growth and Remodelling with colleagues, which has attracted more than 50 audience |
Year(s) Of Engagement Activity | 2022 |
Description | CardiARC Zone |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | At the end of May 2022, We organized the CardiARC Zone at the ARCADIA festival, including a hands-on table with heart competitions and a VR suite in which a virtual heart was rotated moved and sliced as it popped up within the virtual laboratory. The CardiaARC Zone has attracted 100+ participants from school kids to the general public, to professionals and to the patient group. It has sparked many questions and discussions afterwards. |
Year(s) Of Engagement Activity | 2022 |
URL | http://www.softmech.org/newsround/headline_872341_en.html |
Description | Cardiac Digital Twin Workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | It is a one-day workshop to provide a forum on cardiac digital twins with presentations from clinicians, industry representatives, and academic researchers. Challenges and opportunities have been discussed extensively in the workshop. |
Year(s) Of Engagement Activity | 2023 |
Description | Computationally efficient parameter estimation and uncertainty quantification in complex physiological systems |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited keynote lecture given at the 2nd International Conference on Statistics: Theory and Applications (ICSTA'20), held as a virtual conference via Zoom, 19-21 August 2020. |
Year(s) Of Engagement Activity | 2021 |
URL | https://2020.icsta.net/program/ |
Description | IAA impact festival 2022 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | We have shown the research carried out in the SofTMech centre on mathematical modelling of the heart, in particular the projects funded by IAA, including the recent one on the investigation of cardiac injury in relation to COVID-19, to target mechanism understanding of both the short and long term effects of COVID-19. We have met researchers from different fields and industry representatives which have sparked some very interesting questions, in particular the potential commercialization of mathematical models developed in SofTMech. |
Year(s) Of Engagement Activity | 2022 |
URL | https://impactfestival.hw.ac.uk/ |
Description | Interview for BBC Scotland News, 12th November 2020: Colin Berry |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Colin Berry discussing the effects of long COVID on BBC News on the 12th November, 2020. The purpose was to make the general public aware that some people who become infected with COVID suffer long lasting effects. |
Year(s) Of Engagement Activity | 2020 |
URL | https://twitter.com/UofGMVLS/status/1326844312525606914 |
Description | Joint CDT conference (Team member Prof. Matthew Dalby, Director of Glasgow lifETIME CDT) - a meeting between CDTs based in Glasgow, Birmingham, Leeds, Manchester, Liverpool, Aston, Sheffield, Keele, Nottingham and Loughborough |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | The following EPSRC Centres for Doctoral Training across the UK regenerative medicine field and the UK society for biomaterials came together online on 24th and 25th June 2020: EPSRC-SFI Joint CDT in Engineered Tissues for Discovery, Industry and Medicine (LifETIME) EPSRC/MRC CDT in Regenerative Medicine EPSRC/MRC CDT in Regenerative Medicine EPSRC Advanced Biomedical Materials CDT (ABM) EPSRC CDT in Tissue Engineering and Regenerative Medicine (TERM) Doctoral Network for Technologies in Healthy Ageing (Ageing) The CDTs showcased their research to professionals and other PhD students within the field via Zoom. The conference will began with keynote speaker Prof Liam Grover, Director of the Healthcare Technologies Institute (HTI) at the University of Birmingham. The conference then broke out into six themes across two days. During each session there were presentations from later year CDT students within the field and poster and flash talks from early year students. Time was also allowed to view posters on the UKSB website in advance of the poster discussion session. |
Year(s) Of Engagement Activity | 2020 |
URL | https://lifetime-cdt.org/agenda-of-cdt-events/ |
Description | LifETIME Centre for Doctoral Training stakeholder day (Team Member Prof. Matthew Dalby, Director of the LifETIME CDT) - a meeting between industry, academics, charities and funders to enhance student training. Jan 2021. |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | LifeTIME Centre for Doctoral Training (LifeTIME CDT) stakeholder day. Professor Matthew Dalby is the Director of the lifETIME CDT; the meeting was held to discuss ideas on enhancing student training. The partners were from industry, academia, charities and funders. The stakeholder day will bring together LifETIME students, academics, industry partners, iClub members and steering group. The purpose of the stakeholder day was to capture our stakeholder views from which the management will use to refine the CDTs impact strategy. In the morning a facilitator captured CDT subjects, highlighted and raised by stakeholders. These subjects then formed the basis for the discussion points in the afternoon. The afternoon consisted of six co-current discussions over three different sessions. Each session 30 minutes long and stakeholders had the chance to attend the discussion most important and relevant to them. The discussion sessions used open space principles and responses and suggestions will be collected. There was als an opportunity for all attendees to network. |
Year(s) Of Engagement Activity | 2021 |
URL | https://lifetime-cdt.org/agenda-of-cdt-events/ |
Description | LifeTIME Centre for Doctoral Training student day (Team Member Prof. Matthew Dalby, Director of the lifETIME CDT) - a meeting between industry, academics, charities and funders to develop student networking abilities and allow them to show their work to different sectors. Sept 2020. |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | the first LifETIME Student Day took place on Thursday 10th September 2020 via Zoom. The student day will brought together lifETIME academics, partners, iClub, steering board and students. During the event the 2019 cohortl showcased their research projects and th industrial partners will presented a 5-minute pitch about their company and technologies. This was followed by talks from the funders. |
Year(s) Of Engagement Activity | 2020 |
URL | https://lifetime-cdt.org/agenda-of-cdt-events/ |
Description | Plenary talk at the International Forum on coompuational heart modelling |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Up to 100 people attended this event, organized by the North-West Polytechnic University |
Year(s) Of Engagement Activity | 2021 |
URL | http://xygg.nwpu.edu.cn |
Description | Presentation of GlasgowHeart Platform in SCMR 2021 meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | This is the first time to present the Glasgow heart modelling framework to clinicians in one of the largest meetings in the cardiac magnetic resonance imaging community, SCMR 2021. The audiences consist of clinicians, imaging experts, industry partners, etc. The presentation was given in the first software demo session of the SCMR meeting, which brings the mechanic model one step closer to clinicians. The meeting committee believes that biomechanical biomarkers shall be included in the diagnosis guideline, and encourage more open-source software within the society of cardiac magnetic resonance. |
Year(s) Of Engagement Activity | 2021 |
URL | https://scmr2021.process.y-congress.com/scientificProcess/Schedule/?setLng=en |
Description | Presentation: Emulation and Uncertainty Quantification in Cardiac Modelling |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | This was an academic engagement event organised by the Cambridge Mathematics of Information in Healthcare Hub. Around 50 researchers attended this event, and I have given a talk on emulation and uncertainty quantification in cardiac modelling. Questions, discussion afterwards and potential collaborations were sparked. |
Year(s) Of Engagement Activity | 2022 |
URL | https://gateway.newton.ac.uk/event/tgm126 |
Description | Research visits and seminars at the University of Auckland, Auckland Bioengineering Institute, and Department of Maths, University of Canterbury, Christchurch |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Both students and researchers, including other international visitors, attended the talks during the visits, which sparkled questions and discussion afterwards, and laid the foundation for future collaborations. |
Year(s) Of Engagement Activity | 2020 |
Description | SofTMech Soft Tissue workshop 2021 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | The 5th Soft Tissue workshop took place from 1st-3rd June 2021. The workshop focused on the most recent advances in the field of soft tissue mechanics, with a clear vision of the landscape of multiscale soft tissue modelling and both fundamental and translational research. |
Year(s) Of Engagement Activity | 2021 |
Description | SofTMech Training Day 8th January 2021 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | On Friday 8th January 2021 an on-line training day organised by the SofTMech Training Committee led by Professor Dirk Husmeier and Dr Peter Stewart was held. The workshop was mainly aimed at PhD students and postdocs, but also welcomed staff members who were interested in closer future collaborations. 51 people registered for the workshop with 48 attending. Postgraduate and Staff from the University of Glasgow, University of Plymouth, Terumo Aortic, Politecnio Milano (POLIMI) (Italy), MIT (US), EPFL and North Carolina State University attended. The aims of the day were : To give the mathematical modellers a brief overview of state-of-the-art statistical inference in complex systems. To give statisticians an opportunity to learn about the basic mathematical modelling principles relevant to our projects. To allow participants to talk together in small groups of 4/5, repeated a few times via Zoom breakout rooms (Speed dating); meeting people from other institutions with the view to future collaboration. The day also included a presentation by David Hand on "Dark Data" This recent training day allowed the University of Glasgow staff and postgraduate students to meet staff and students from their partner Institutions in POLIMI, MIT and working on similar areas and this has the potential to lead to future collaborative projects. |
Year(s) Of Engagement Activity | 2021 |
URL | http://www.softmech.org/events/headline_763982_en.html |
Description | SofTMech Training Programme event (14th-28th November): PhD Course: An Introduction to Nonlinear Solid Mechanics led by Anna Pandolfi from the Politecnico di Milano |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Rigorous introduction to nonlinear solid mechanics, especially addressing finite kinematics, material frame indifference, constitutive models within a thermodynamic framework. Analysis of nonlinear material behaviors. Specific topics: 1. Mathematical preliminaries. Dual basis. Tensors. 2. Kinematics of deformations. Motions, kinematics of local deformation. Polar decomposition. 3. Conservation laws (mass, linear & angular momentum, energy). Thermodynamics. Virtual work principle. 4. Constitutive theories. Coleman-Noll's theory. Material frame indifference. Thermodynamic potentials. Kinetic relations. Material classification. 5. Hyperelasticity. Elasticity symmetry. Internal constraints. Elastic materials: isotropic, transversally isotropic, anisotropic materials. 6. Finite Plasticity. Multiplicative decomposition of the deformation gradient. Exponential and logarithmic mapping. J2 plasticity. Pressure dependent plasticity. 7. Special materials: fiber reinforced tissues, liquid crystals |
Year(s) Of Engagement Activity | 2022 |
URL | http://www.softmech.org/media/Media_894442_smxx.pdf |
Description | SofTMech Training Programme event (24.3.22): Attending an Academic Conference & Networking |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | This half day informal training event was aimed at Early Career Researchers; its aim was to prepare them for attending an in person academic conference. Having been unable to attend in person due to COVID this was especially valuable. The following topics were covered: what actually happens at an academic conference? what can I hope to get out it? how do I network effectively? The event also included a practical exercise on preparing an elevator pitch for networking with senior academics. Several of the students have gone on to attend in person workshops and conferences. |
Year(s) Of Engagement Activity | 2022 |
URL | http://www.softmech.org/trainingtheleadersoftomorrow/#d.en.835979 |
Description | SofTMech Training Programme event (31.5.22): PhD Poster Competition |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | The event was an in-person Poster competition open to PhD students from SofTMech and CMALS. Prior to the event two videos on Effective Poster Presentations were posted on the SofTMech website for any potential competitors to study. 28 people registered for the event; 17 presented posters. After two years of the pandemic this event gave a valuable opportunity to at last ask questions in person, for discussion and perhaps just as importantly to meet some colleagues for the first time. Students participated in the event from the University of Glasgow Schools of Mathematics and Statistics, Biomedical Engineering, Ultrasonic Engineering and Computational Mechanics. Students came from the University of Strathclyde departments of Mathematics & Statistics and Biomedical Engineering. Prior to the event the students arrived early to set up their posters. The event was opened by Dr Sean McGinty, Director of CMAL (Centre of Mathematics & Life Sciences at University of Glasgow)) A series of 1 min flash presentations, where each student had to give an overview of their poster by displaying a maximum of 2 PowerPoint slides, set the scene for the poster viewing. One of the students even gave directions to where his poster was; it worked as he finished 2nd ! The posters were judged by a combination of a panel of members of staff and also by the students themselves, who were each allowed one vote for their favourite poster. The standard of posters was high across the board. Certificates and vouchers were awarded to the best three posters. We hope the experience of this event will help all the students as they progress in their careers. |
Year(s) Of Engagement Activity | 2022 |
URL | http://www.softmech.org/trainingtheleadersoftomorrow/#d.en.848318 |
Description | SofTMech Training Programme: Figure Making Workshop 09.03.23 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | This was an interactive presentation on how to produce figures. The topics covered included: Thinking about your audience, tools for making figures, colour use, captions, display, file format. The students were able to give their answers on each section of the presentation and these were displayed and discussed before going on to the next section. 8 students attended. Their feedback from the workshop was also captured and was very positive. |
Year(s) Of Engagement Activity | 2023 |
URL | http://www.softmech.org/trainingtheleadersoftomorrow/#d.en.910377 |
Description | SofTMech Training Workshop Scientific Computation 2022 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Training day for PhD students on Scientific Computation, held on 28th January 2022. The event attracted more than 40 participants from Maths-in-Healthcare centres from around the UK. Sparked questions and discussion afterwards. |
Year(s) Of Engagement Activity | 2022 |
Description | Special Interest Group on the Fluid Mechanics of the Eye |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Since the COVID lockdown, Peter Stewart has organised virtual study groups on the fluid mechanics of the eye. The first event took place on 30th November 2020 and there have been 6 subsequent meetings across 2021 and 2022. These events have gathered clinicians and modellers (including some PhD students) to derive mathematical models pertinent to the eye. In particular, we have modelled: (1) uveoscleral flow as a drug delivery platform to the macula (2) formation of macular holes in aging eyes. Several publications are in preparation. We are hosting a follow up conference in Bath in June 2022, funded by the Macular Society. |
Year(s) Of Engagement Activity | 2020,2021,2022 |
URL | https://eyefluidssig.wordpress.com/history/ |
Description | Statistical inference in cardiac mechanics |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Talk given to the Royal Statistical Society local Glasgow group on 12th March 2020, which sparked questions and discussions afterwards, both over coffee and via follow-up emails. |
Year(s) Of Engagement Activity | 2020 |
URL | https://sites.google.com/site/rssglasgow/events |
Description | Statistical inference in cardiovascular modelling |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Three of Dirk Husmeier's PhD students and postdocs gave talks at an event organised by the Royal Statistical Society Glasgow local group on 9 February 2021, with the following titles: Mihaela Paun The importance of allowing for model mismatch in cardiovascular modelling Alan Lazarus Improving cardio-mechanic parameter estimation by including prior knowledge derived from ex-vivo data Agnieszka Borowska Bayesian optimisation for improving accuracy and efficiency of cardio-mechanic parameter estimation The event was delivered via ZOOM, and lead to a stimulating discussion between speakers and participants (also via Zoom). |
Year(s) Of Engagement Activity | 2021 |
URL | https://rss.org.uk/training-events/events/statistical-inference-in-cardiovascular-modelling/#eventov... |
Description | Talk at 9th International Biofluid Mechanics And Vascular Mechanobiology Symposium |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Maintain the tradition of excellence and the spirit of the International Bio-fluid Mechanics and Vascular Mechano-Biology Symposia that have evolved to be a unique opportunity for reviewing recent major milestones and achievements in all areas of biofluid mechanics, experimental and computational, from molecule and cell to organ levels and corresponding mechano-biological processes, therapeutics, and cardiovascular devices. The event gathered scientists, clinicians, and practitioners from around the world to explore and assess the latest frontiers of Bio-Fluid Mechanics and Vascular Mechano-Biology, and set important directions for further research and development, and education. The symposium provided an opportunity for investigators to interact with peers, young and seniors, for development of new collaborations, as well as enhancement of existing ones. |
Year(s) Of Engagement Activity | 2020 |
URL | https://9thbiofluids.com/ |
Description | Talk on "Forward and Inverse Uncertainty Quantification in Cardiac Mechanics" at ICSTA 2022 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Talk at ICSTA 2022 (International Conference on Statistics: Theory and Applications) on "Forward and Inverse Uncertainty Quantification in Cardiac Mechanics" |
Year(s) Of Engagement Activity | 2022 |
URL | https://2022.icsta.net/ |
Description | The lifETIME (Engineered Tissues for Discovery, Industry and Medicine) CDT; Director: Matthew Dalby: Stakeholder Day 21.01.21 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | The stakeholder day brought together LifETIME students, academics, industry partners, iClub members and the steering group. The purpose of the stakeholder day was to capture our stakeholder views from which the management will use to refine the CDTs impact strategy. In the morning a facilitator captured CDT subjects, highlighted and raised by stakeholders. These subjects then formed the basis for the discussion points in the afternoon. The afternoon consisted of six co-current discussions over three different sessions. Each session waa 30 minutes long and stakeholders attended the discussion most important and relevant to them. |
Year(s) Of Engagement Activity | 2021 |
URL | https://lifetime-cdt.org/agenda-of-cdt-events/previous-events/ |
Description | The lifETIME (Engineered Tissues for Discovery, Industry and Medicine) CDT; Director: Matthew Dalby: Student Day 7.11.21 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | The student day brought together lifETIME academics, partners, iClub, steering board and students. During this event to showcase their research the 2019 students presented posters and the 2020 students presented quickfire presentations. Industrial partners and academics also presented short talks. The questions and discussions helped shape future research. |
Year(s) Of Engagement Activity | 2021 |
URL | https://lifetime-cdt.org/agenda-of-cdt-events/previous-events/ |
Description | The lifETIME (Engineered Tissues for Discovery, Industry and Medicine) CDT; Director: Matthew Dalby: Twitter Conference 10th & 11th June 2021 |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | The LifETIME Twitter Conference was an online event held entirely over Twitter using the hashtag #futureleadersinregenmed to bring together the LifETIME CDT cohort and the wider scientific community to share research, engage in scientific discussions and network. The 2019 LifETIME students each presented 3 tweets during the two day event. The discussion could be joined by searching for the hashtag #futureleadersinregenmed allowing people to see all posts that are related to the conference. |
Year(s) Of Engagement Activity | 2021 |
URL | https://lifetime-cdt.org/agenda-of-cdt-events/previous-events/ |
Description | Towards a virtual eye |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Workshop to begin working toward a virtual eye, following our earlier work as part of the Special Interest Group for the fluid mechanics of the eye. Event held at University of Bath, June 2022. Organised by SofTMech CI Prof Peter Stewart. Funded by the Macular Society. Outcome in the form of a white paper: Roadmap to the virtual eye, to be published by the Macular Society Discussions have stimulated a number of applications for further funding. |
Year(s) Of Engagement Activity | 2022 |
Description | Twitter Account |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | SofTMech Twitter Account which covers a number of SofTMech and SofTMech related grants. Main purpose to give information on research activities, events including social, advertise job opportunities to a wide audience, and announce graduations, prizes and achievements of the group. In addition to use the Re-tweet feature of Twitter to advertise information from partner groups or followers. The account has 201 followers and follows 171 other Twitter accounts. Impacts arising from the Account are quick dissemination of material. |
Year(s) Of Engagement Activity | 2020,2021,2022 |
URL | https://twitter.com/home |