On the analysis of mixed-index time fractional differential equation systems

In this paper we study the class of mixed-index time fractional differential equations in which different components of the problem have different time fractional derivatives on the left hand side. We prove a theorem on the solution of the linear system of equations, which collapses to the well-known Mittag-Leffler solution in the case the indices are the same, and also generalises the solution of the so-called linear sequential class of time fractional problems. We also investigate the asymptotic stability properties of this class of problems using Laplace transforms and show how Laplace transforms can be used to write solutions as linear combinations of generalised Mittag-Leffler functions in some cases. Finally we illustrate our results with some numerical simulations.Comment: 21 pages, 6 figures (some are made up of sub-figures - there are 15 figures or sub-figures

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Low rank Runge-Kutta methods, symplecticity and stochastic Hamiltonian problems with additive noise

Full-text article is free to read on the publisher website. In this paper we extend the ideas of Brugnano, Iavernaro and Trigiante in their development of HBVM($s,r$) methods to construct symplectic Runge-Kutta methods for all values of $s$ and $r$ with $s\geq r$. However, these methods do not see the dramatic performance improvement that HBVMs can attain. Nevertheless, in the case of additive stochastic Hamiltonian problems an extension of these ideas, which requires the simulation of an independent Wiener process at each stage of a Runge-Kutta method, leads to methods that have very favourable properties. These ideas are illustrated by some simple numerical tests for the modified midpoint rule

Effective numerical methods for simulating diffusion on a spherical surface in three dimensions

In order to construct an algorithm for homogeneous diffusive motion that lives on a sphere, we consider the equivalent process of a randomly rotating spin vector of constant length. By introducing appropriate sets of random variables based on cross products, we construct families of methods with increasing efficacy that exactly preserve the spin modulus for every realisation. This is done by exponentiating an antisymmetric matrix whose entries are these random variables that are Gaussian in the simplest case.</p

Stability Switching in Lotka-Volterra and Ricker-Type Predator-Prey Systems with Arbitrary Step Size

Dynamical properties of numerically approximated discrete systems may become inconsistent with those of the corresponding continuous-time system. We present a qualitative analysis of the dynamical properties of two-species Lotka-Volterra and Ricker-type predator-prey systems under discrete and continuous settings. By creating an arbitrary time discretisation, we obtain stability conditions that preserve the characteristics of continuous-time models and their numerically approximated systems. Here, we show that even small changes to some of the model parameters may alter the system dynamics unless an appropriate time discretisation is chosen to return similar dynamical behaviour to what is observed in the corresponding continuous-time system. We also found similar dynamical properties of the Ricker-type predator-prey systems under certain conditions. Our results demonstrate the need for preliminary analysis to identify which dynamical properties of approximated discretised systems agree or disagree with the corresponding continuous-time systems.</p

Mathematical Models of Cancer Cell Plasticity

Quantitative modelling is increasingly important in cancer research, helping to integrate myriad diverse experimental data into coherent pictures of the disease and able to discriminate between competing hypotheses or suggest specific experimental lines of enquiry and new approaches to therapy. Here, we review a diverse set of mathematical models of cancer cell plasticity (a process in which, through genetic and epigenetic changes, cancer cells survive in hostile environments and migrate to more favourable environments, respectively), tumour growth, and invasion. Quantitative models can help to elucidate the complex biological mechanisms of cancer cell plasticity. In this review, we discuss models of plasticity, tumour progression, and metastasis under three broadly conceived mathematical modelling techniques: discrete, continuum, and hybrid, each with advantages and disadvantages. An emerging theme from the predictions of many of these models is that cell escape from the tumour microenvironment (TME) is encouraged by a combination of physiological stress locally (e.g., hypoxia), external stresses (e.g., the presence of immune cells), and interactions with the extracellular matrix. We also discuss the value of mathematical modelling for understanding cancer more generally.</p

Estimates on the coverage of parameter space using populations of models

In this paper we provide estimates for the coverage of parameter space when using Latin Hypercube Sampling, which forms the basis of building so-called populations of models. The estimates are obtained using combinatorial counting arguments to determine how many trials, k, are needed in order to obtain specified parameter space coverage for a given value of the discretisation size n. In the case of two dimensions, we show that if the ratio (Ø) of trials to discretisation size is greater than 1, then as n becomes moderately large the fractional coverage behaves as 1-exp-ø. We compare these estimates with simulation results obtained from an implementation of Latin Hypercube Sampling using MATLAB

Agent-based Modelling to Study Protocognition Abilities of the Tumour Microenvironment (TME)

Cancer occurs when abnormal cells grow in an uncontrolled way. Interaction between tumour cells and the tumour microenvironment (TME) is affects tumour cell progression and metastasis. It represents protocognitive abilities of tumour cells. Understanding this process is a key to blocking or slowing the spread of cancer cells and to developing better treatment strategies. Hence, it is important to investigate intra-tumoural communication to decide new therapies for cancer. In this research work, an agent-based model is developed to study the intra-tumoural communication under cellular stress. This model will provide the basis to investigate protocognition activities of the tumour cells and to develop new treatment strategies for cancer.</p