29,236 research outputs found

    Data-driven modelling of biological multi-scale processes

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    Biological processes involve a variety of spatial and temporal scales. A holistic understanding of many biological processes therefore requires multi-scale models which capture the relevant properties on all these scales. In this manuscript we review mathematical modelling approaches used to describe the individual spatial scales and how they are integrated into holistic models. We discuss the relation between spatial and temporal scales and the implication of that on multi-scale modelling. Based upon this overview over state-of-the-art modelling approaches, we formulate key challenges in mathematical and computational modelling of biological multi-scale and multi-physics processes. In particular, we considered the availability of analysis tools for multi-scale models and model-based multi-scale data integration. We provide a compact review of methods for model-based data integration and model-based hypothesis testing. Furthermore, novel approaches and recent trends are discussed, including computation time reduction using reduced order and surrogate models, which contribute to the solution of inference problems. We conclude the manuscript by providing a few ideas for the development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and Multiscale Dynamics (American Scientific Publishers

    Advances in computational modelling for personalised medicine after myocardial infarction

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    Myocardial infarction (MI) is a leading cause of premature morbidity and mortality worldwide. Determining which patients will experience heart failure and sudden cardiac death after an acute MI is notoriously difficult for clinicians. The extent of heart damage after an acute MI is informed by cardiac imaging, typically using echocardiography or sometimes, cardiac magnetic resonance (CMR). These scans provide complex data sets that are only partially exploited by clinicians in daily practice, implying potential for improved risk assessment. Computational modelling of left ventricular (LV) function can bridge the gap towards personalised medicine using cardiac imaging in patients with post-MI. Several novel biomechanical parameters have theoretical prognostic value and may be useful to reflect the biomechanical effects of novel preventive therapy for adverse remodelling post-MI. These parameters include myocardial contractility (regional and global), stiffness and stress. Further, the parameters can be delineated spatially to correspond with infarct pathology and the remote zone. While these parameters hold promise, there are challenges for translating MI modelling into clinical practice, including model uncertainty, validation and verification, as well as time-efficient processing. More research is needed to (1) simplify imaging with CMR in patients with post-MI, while preserving diagnostic accuracy and patient tolerance (2) to assess and validate novel biomechanical parameters against established prognostic biomarkers, such as LV ejection fraction and infarct size. Accessible software packages with minimal user interaction are also needed. Translating benefits to patients will be achieved through a multidisciplinary approach including clinicians, mathematicians, statisticians and industry partners

    A Process Modelling Framework Based on Point Interval Temporal Logic with an Application to Modelling Patient Flows

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    This thesis considers an application of a temporal theory to describe and model the patient journey in the hospital accident and emergency (A&E) department. The aim is to introduce a generic but dynamic method applied to any setting, including healthcare. Constructing a consistent process model can be instrumental in streamlining healthcare issues. Current process modelling techniques used in healthcare such as flowcharts, unified modelling language activity diagram (UML AD), and business process modelling notation (BPMN) are intuitive and imprecise. They cannot fully capture the complexities of the types of activities and the full extent of temporal constraints to an extent where one could reason about the flows. Formal approaches such as Petri have also been reviewed to investigate their applicability to the healthcare domain to model processes. Additionally, to schedule patient flows, current modelling standards do not offer any formal mechanism, so healthcare relies on critical path method (CPM) and program evaluation review technique (PERT), that also have limitations, i.e. finish-start barrier. It is imperative to specify the temporal constraints between the start and/or end of a process, e.g., the beginning of a process A precedes the start (or end) of a process B. However, these approaches failed to provide us with a mechanism for handling these temporal situations. If provided, a formal representation can assist in effective knowledge representation and quality enhancement concerning a process. Also, it would help in uncovering complexities of a system and assist in modelling it in a consistent way which is not possible with the existing modelling techniques. The above issues are addressed in this thesis by proposing a framework that would provide a knowledge base to model patient flows for accurate representation based on point interval temporal logic (PITL) that treats point and interval as primitives. These objects would constitute the knowledge base for the formal description of a system. With the aid of the inference mechanism of the temporal theory presented here, exhaustive temporal constraints derived from the proposed axiomatic system’ components serves as a knowledge base. The proposed methodological framework would adopt a model-theoretic approach in which a theory is developed and considered as a model while the corresponding instance is considered as its application. Using this approach would assist in identifying core components of the system and their precise operation representing a real-life domain deemed suitable to the process modelling issues specified in this thesis. Thus, I have evaluated the modelling standards for their most-used terminologies and constructs to identify their key components. It will also assist in the generalisation of the critical terms (of process modelling standards) based on their ontology. A set of generalised terms proposed would serve as an enumeration of the theory and subsume the core modelling elements of the process modelling standards. The catalogue presents a knowledge base for the business and healthcare domains, and its components are formally defined (semantics). Furthermore, a resolution theorem-proof is used to show the structural features of the theory (model) to establish it is sound and complete. After establishing that the theory is sound and complete, the next step is to provide the instantiation of the theory. This is achieved by mapping the core components of the theory to their corresponding instances. Additionally, a formal graphical tool termed as point graph (PG) is used to visualise the cases of the proposed axiomatic system. PG facilitates in modelling, and scheduling patient flows and enables analysing existing models for possible inaccuracies and inconsistencies supported by a reasoning mechanism based on PITL. Following that, a transformation is developed to map the core modelling components of the standards into the extended PG (PG*) based on the semantics presented by the axiomatic system. A real-life case (from the King’s College hospital accident and emergency (A&E) department’s trauma patient pathway) is considered to validate the framework. It is divided into three patient flows to depict the journey of a patient with significant trauma, arriving at A&E, undergoing a procedure and subsequently discharged. Their staff relied upon the UML-AD and BPMN to model the patient flows. An evaluation of their representation is presented to show the shortfalls of the modelling standards to model patient flows. The last step is to model these patient flows using the developed approach, which is supported by enhanced reasoning and scheduling

    Genetic and Neuroanatomical Support for Functional Brain Network Dynamics in Epilepsy

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    Focal epilepsy is a devastating neurological disorder that affects an overwhelming number of patients worldwide, many of whom prove resistant to medication. The efficacy of current innovative technologies for the treatment of these patients has been stalled by the lack of accurate and effective methods to fuse multimodal neuroimaging data to map anatomical targets driving seizure dynamics. Here we propose a parsimonious model that explains how large-scale anatomical networks and shared genetic constraints shape inter-regional communication in focal epilepsy. In extensive ECoG recordings acquired from a group of patients with medically refractory focal-onset epilepsy, we find that ictal and preictal functional brain network dynamics can be accurately predicted from features of brain anatomy and geometry, patterns of white matter connectivity, and constraints complicit in patterns of gene coexpression, all of which are conserved across healthy adult populations. Moreover, we uncover evidence that markers of non-conserved architecture, potentially driven by idiosyncratic pathology of single subjects, are most prevalent in high frequency ictal dynamics and low frequency preictal dynamics. Finally, we find that ictal dynamics are better predicted by white matter features and more poorly predicted by geometry and genetic constraints than preictal dynamics, suggesting that the functional brain network dynamics manifest in seizures rely on - and may directly propagate along - underlying white matter structure that is largely conserved across humans. Broadly, our work offers insights into the generic architectural principles of the human brain that impact seizure dynamics, and could be extended to further our understanding, models, and predictions of subject-level pathology and response to intervention

    Seizure-onset mapping based on time-variant multivariate functional connectivity analysis of high-dimensional intracranial EEG : a Kalman filter approach

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    The visual interpretation of intracranial EEG (iEEG) is the standard method used in complex epilepsy surgery cases to map the regions of seizure onset targeted for resection. Still, visual iEEG analysis is labor-intensive and biased due to interpreter dependency. Multivariate parametric functional connectivity measures using adaptive autoregressive (AR) modeling of the iEEG signals based on the Kalman filter algorithm have been used successfully to localize the electrographic seizure onsets. Due to their high computational cost, these methods have been applied to a limited number of iEEG time-series (< 60). The aim of this study was to test two Kalman filter implementations, a well-known multivariate adaptive AR model (Arnold et al. 1998) and a simplified, computationally efficient derivation of it, for their potential application to connectivity analysis of high-dimensional (up to 192 channels) iEEG data. When used on simulated seizures together with a multivariate connectivity estimator, the partial directed coherence, the two AR models were compared for their ability to reconstitute the designed seizure signal connections from noisy data. Next, focal seizures from iEEG recordings (73-113 channels) in three patients rendered seizure-free after surgery were mapped with the outdegree, a graph-theory index of outward directed connectivity. Simulation results indicated high levels of mapping accuracy for the two models in the presence of low-to-moderate noise cross-correlation. Accordingly, both AR models correctly mapped the real seizure onset to the resection volume. This study supports the possibility of conducting fully data-driven multivariate connectivity estimations on high-dimensional iEEG datasets using the Kalman filter approach

    Comparison of panel codes for aerodynamic analysis of airfoils

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    Cieľom tejto práce bolo vytvorenie prehľadu v súčasnosti používaných implementácií panelových metód pre aerodynamické výpočty charakteristík 2D profilov. Základný popis princípu panelovej metódy, porovnanie jednotlivých implementácií a zhodnotenie ich možností (presnosť, aplikovateľnosť) na typické úlohy. V práci boli použité tri rôzne panelové programy: Xfoil, JavaFoil a XFLR5. Práca bola obohatená o meranie v aerodynamickom tuneli.The purpose of this study is to create an overview of currently the most used panel codes for computation of aerodynamic characteristics of 2D airfoils. Description of the basic principles of panel code, comparison of various implementation and evaluation (accuracy, applicability) for typical tasks. In this thesis there were used three different panel codes: Xfoil, JavaFoil and XFLR5. Thesis was enriched by measurement in wind tunnel.
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