TBD

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ZOOM ID: 997 8258 4700 (Biomedical Mathematics Online Colloquium), (pw: 1234) + Google Map

I will report on some recent results on modelling the heart, the external circulation, and their application to problems of clinical relevance. I will show that a proper integration between PDE-based and machine-learning algorithms can improve the computational efficiency and enhance the generality of our iHEART simulator.

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ZOOM ID: 997 8258 4700 (Biomedical Mathematics Online Colloquium), (pw: 1234) + Google Map

TBD

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ZOOM ID: 997 8258 4700 (Biomedical Mathematics Online Colloquium), (pw: 1234) + Google Map

Interpreting data using mechanistic mathematical models provides a foundation for discovery and decision-making in all areas of science and engineering. Key steps in using mechanistic mathematical models to interpret data include: (i) identifiability analysis; (ii) parameter estimation; and (iii) model prediction. Here we present a systematic, computationally efficient likelihood-based workflow that addresses all three steps in a unified way. Recently developed methods for constructing profile-wise prediction intervals enable this workflow and provide the central linkage between different workflow components. These methods propagate profile-likelihood-based confidence sets for model parameters to predictions in a way that isolates how different parameter combinations affect model predictions. We show how to extend these profile-wise prediction intervals to two-dimensional interest parameters, and then combine profile-wise prediction confidence sets to give an overall prediction confidence set that approximates the full likelihood-based prediction confidence set well. We apply our methods to a range of synthetic data and real-world ecological data describing re-growth of coral reefs on the Great Barrier Reef after some external disturbance, such as a tropical cyclone or coral bleaching event.

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ZOOM ID: 997 8258 4700 (Biomedical Mathematics Online Colloquium), (pw: 1234) + Google Map

The Hypothalamic-Pituitary-Adrenal (HPA) axis is the key regulatory pathway responsible for maintaining homeostasis under conditions of real or perceived stress. Endocrine responses to stressors are mediated by adrenocorticotrophic hormone (ACTH) and corticosteroid (CORT) hormones. In healthy, non-stressed conditions, ACTH and CORT exhibit highly correlated ultradian pulsatility with an amplitude modulated by circadian processes. Disruption of these hormonal rhythms can occur as a result of stressors or in the very early stages of disease. Despite the fact that misaligned endocrine rhythms are associated with increased morbidity, a quantitative understanding of their mechanistic origin and pathogenicity is missing. Mathematically, the HPA axis can be understood as a dynamical system that is optimised to respond and adapt to perturbations. Normally, the body copes well with minor disruptions, but finds it difficult to withstand severe, repeated or long-lasting perturbations. Whilst a healthy HPA axis maintains a certain degree of robustness to stressors, its fragility in diseased states is largely unknown, and this understanding constitutes a critical step toward the development of digital tools to support clinical decision-making. This talk will explore how these challenges are being addressed by combining high-resolution biosampling techniques with mathematical and computational analysis methods. This interdisciplinary approach is helping us quantify the inter-individual variability of daily hormone profiles and develop novel “dynamic biomarkers” that serve as a normative reference and to signal endocrine dysfunction. By shifting from a qualitative to a quantitative description of the HPA axis, these insights bring us a step closer to personalised clinical interventions for which timing is key.

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ZOOM ID: 997 8258 4700 (Biomedical Mathematics Online Colloquium), (pw: 1234) + Google Map