• This is a pre-copyedited, author-produced PDF of an article accepted for publication in Mathematical Medicine and Biology following peer review.The January 18, 2013Abstract A simple mathematical model framework is developed to describe the hormonal interactions of the human menstrual cycle along the hypothalamus-pituitary-ovaries axis. The framework is designed so that it can be readily extended to model processes that disrupt the normal functioning cycle. The model in its most basic formulation exhibits multiple periodic solutions, one of which shows the key characteristics of a menstrual cycle, whilst the others indicate possible abnormalities sometimes observed in women of reproductive age. The basic model is extended to encompass receptor down-regulation as a mechanism to describe the desensitisation of the pituitary to continuous stimulation of hypothalamic hormone, a hormonal therapy that is commonly prescribed prior to the surgical procedure for the removal of uterine myomas. Though the mechanisms for desensitisation are likely to be more complex, the model results are in good qualitative agreement with physiological observations.

A system of partial differential equations is developed to describe the formation and clearance of amyloid β (Aβ) and the subsequent buildup of Aβ plaques in the brain, which are associated with Alzheimer's disease. The Aβ related proteins are divided into five distinct categories depending on their size. In addition to enzymatic degradation, the clearance via diffusion and the outflow of interstitial fluid (ISF) into the surrounding cerebral spinal fluid (CSF) are considered. Treating the brain tissue as a porous medium, a simplified two-dimensional circular geometry is assumed for the transverse section of the brain leading to a nonlinear, coupled system of PDEs. Asymptotic analysis is carried out for the steady states of the spatially homogeneous system in the vanishingly small limit of Aβ clearance rate. The PDE model is studied numerically for two cases, a spherically symmetric case and a more realistic 2D asymmetric case, allowing for nonuniform boundary conditions. Our investigations demonstrate that ISF advection is a key component in reproducing the clinically observed accumulation of plaques on the outer boundaries. Furthermore, ISF circulation serves to enhance Aβ clearance over diffusion alone and that non-uniformities in ISF drainage into the CSF can lead to local clustering of plaques. Analysis of the model also demonstrates that plaque formation does not directly correspond to the high presence of toxic oligomers.

Uterine myomas or fibroids are common, benign smooth-muscle tumours that can grow to 10 cm or more in diameter and are routinely removed surgically. They are typically slow growing, well-vascularised, spherical tumours that, on a macro-scale, are a structurally uniform, hard elastic material. We present a multi-phase mathematical model of a fully vascularised myoma growing within a surrounding elastic tissue. Adopting a continuum approach, the model assumes the conservation of mass and momentum of four phases, namely cells/collagen, extracellular fluid, arterial and venous phases. The cell/collagen phase is treated as a poro-elastic material, based on a linear stress-strain relationship, and Darcy's law is applied to describe flow in the extracellular fluid and the two vascular phases. The supply of extracellular fluid is dependent on the capillary flow rate and mean capillary pressure expressed in terms of the arterial and venous pressures. Cell growth and division is limited to the myoma domain and dependent on the local stress in the material. The resulting model consists of a system of non-linear partial differential equations with two moving boundaries.Numerical solutions of the model successfully reproduce qualitatively the clinically observed three-phase "fast-slow-fast" growth profile that is typical for myomas. The results suggest that this growth profile requires stress-induced resistance to growth by the surrounding tissue and a switch like cell growth response to stress. Analysis of large-time solutions reveal that whilst there is a functioning vasculature throughout the myoma exponential growth results, otherwise power-law growth is predicted. An extensive survey of the effect of parameters on model solutions is also presented and, in particular, the enhanced growth caused by factors such as oestrogen is predicted by the model.

In-host mutation of a cross-species infectious disease to a form that is transmissible between humans has resulted with devastating global pandemics in the past. We use simple mathematical models to describe this process with the aim to better understand the emergence of an epidemic resulting from such a mutation and the extent of measures that are needed to control it. The feared outbreak of a human-human transmissible form of avian influenza leading to a global epidemic is the paradigm for this study. We extend the SIR approach to derive a deterministic and a stochastic formulation to describe the evolution of two classes of susceptible and infected states and a removed state, leading to a system of ordinary differential equations and a stochastic equivalent based on a Markov process. For the deterministic model, the contrasting timescale of the mutation process and disease infectiousness is exploited in two limits using asymptotic analysis in order to determine, in terms of the model parameters, necessary conditions for an epidemic to take place and timescales for the onset of the epidemic, the size and duration of the epidemic and the maximum level of the infected individuals at one time. Furthermore, the basic reproduction number R is determined from asymptotic analysis of a distinguished limit. Comparisons between the deterministic and stochastic model demonstrate that stochasticity has little effect on most aspects of an epidemic, but does have significant impact on its onset particularly for smaller populations and lower mutation rates for representatively large populations. The deterministic model is extended to investigate a range of quarantine and vaccination programmes, whereby in the two asymptotic limits analysed, quantitative estimates on the outcomes and effectiveness of these control measures are established.

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