Predicting the outcomes of HIV treatment interruptions using computational modelling

In the past 30 years, HIV infection made a transition from fatal to chronic disease due to the emergence of potent treatment largely suppressing viral replication. However, this medication must be administered life-long on a regular basis to maintain viral suppression and is not always well tolerated. Any interruption of treatment causes residual virus to be reactivated and infection to progress, where the underlying processes occurring and consequences for the immune system are still poorly understood. Nonetheless, treatment interruptions are common due to adherence issues or limited access to antiretroviral drugs. Early clinical studies, aiming at application of treatment interruptions in a structured way, gave contradictory results concerning patient safety, discouraging further trials. In-silico models potentially add to knowledge but a review of the Literature indicates most current models used for studying treatment interruptions (equation-based), neglect recent clinical findings of collagen formation in lymphatic tissue due to HIV and its crucial role in immune system stability and efficacy. The aim of this research is the construction and application of so-called ‘Bottom-Up’ models to allow improved assessment of these processes in relation to HIV treatment interruptions. In this regard, a novel computational model based on 2D Cellular Automata for lymphatic tissue depletion and associated damage to the immune system was developed. Hence, (i) using this model, the influence of spatial distribution of collagen formation on HIV infection progression speed was evaluated while discussing aspects of computational performance. Further, (ii) direct Monte Carlo simulations were employed to explore the accumulation of tissue impairment due to repeated treatment interruptions and consequences for long-term prognosis. Finally, (iii) an inverse Monte Carlo approach was used to reconstruct yet unknown characteristics of patient groups. This is based on sparse data from past clinical studies on treatment interruptions with the aim of explaining their contradictory results

Non-determinism in the narrative structure of video games

PhD ThesisAt the present time, computer games represent a finite interactive system. Even in their more experimental forms, the number of possible interactions between player and NPCs (non-player characters) and among NPCs and the game world has a finite number and is led by a deterministic system in which events can therefore be predicted. This implies that the story itself, seen as the series of events that will unfold during gameplay, is a closed system that can be predicted a priori. This study looks beyond this limitation, and identifies the elements needed for the emergence of a non-finite, emergent narrative structure. Two major contributions are offered through this research. The first contribution comes in the form of a clear categorization of the narrative structures embracing all video game production since the inception of the medium. In order to look for ways to generate a non-deterministic narrative in games, it is necessary to first gain a clear understanding of the current narrative structures implemented and how their impact on users’ experiencing of the story. While many studies have observed the storytelling aspect, no attempt has been made to systematically distinguish among the different ways designers decide how stories are told in games. The second contribution is guided by the following research question: Is it possible to incorporate non-determinism into the narrative structure of computer games? The hypothesis offered is that non-determinism can be incorporated by means of nonlinear dynamical systems in general and Cellular Automata in particular

CA and Monte Carlo models of HIV infection

The models presented are discrete Monte Carlo(MC) and Cellular Automata(CA) representations of the interaction of HIV with the immune system. HIV is characterised by the depletion of Helper T cells in the body. Helper T cells are essential to the correct regulation of the immune system. Their degradation leaves the body incapable of defending itself, even against what is usually an unharmful infection. The models consider just four cell types the Macrophage, M, the helper T cell, H , the cytotoxic Killer cell, C and the virus, V. Each cell type can either be in high concentration (1) or low concentration (0). An up d a te of a site consists of nearest-neighbour interaction followed by intra-site interactions. The nearest-neighbour interaction represents the influence of a site’s surroundings on it. The intra-site interactions are Boolean equations which represent a succinct interpretation of HIV infection and its effect on the host immune system. Mutation is considered via a probabilistic parameter P m u t - Each cell type has inherent mobility due to the nearest-neighbour interactions, explicit mobility is explored by a probabilistic parameter Pmob• The MC and CA .simulations differ in their updating, with CA updating is synchronous and with MC it is asynchronous. MC is explored as an alternative to the CA model form. Due to th e Boolean concentrations of the cell types, synchronous (CA) updating leads to overshooting, there is either complete viral dominance or immune dominance and no intermediate state. Asynchronous (MC) updating smoothes these extremes; intermediate states between immuno-dominance and immuno-deficiency exist. These intermediate states offer new insight into the dynamics of HIV and the immune system. Asynchronous updating gives clearly defined growth patterns and this enables th e exploration of critical points. One such critical point is the value of Pmut for which the cross-over between immune dominance and deficiency occurs. Also characteristics of the disease progression such as latency can be investigated

Automatic detection and classification of leukaemia cells

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Today, there is a substantial number of software and research groups that focus on the development of image processing software to extract useful information from medical images, in order to assist and improve patient diagnosis. The work presented in this thesis is centred on processing of images of blood and bone marrow smears of patients suffering from leukaemia, a common type of cancer. In general, cancer is due to aberrant gene expression, which is caused by either mutations or epigenetic changes in DNA. Poor diet and unhealthy lifestyle may trigger or contribute to these changes, although the underlying mechanism is often unknown. Importantly, many cancer types including leukaemia are curable and patient survival and treatment can be improved, subject to prompt diagnosis. In particular, this study focuses on Acute Myeloid Leukaemia (AML), which can be of eight distinct types (M0 to M7), with the main objective to develop a methodology to automatically detect and classify leukaemia cells into one of the above types. The data was collected from the Department of Haematology, Universiti Sains Malaysia, in Malaysia. Three main methods, namely Cellular Automata, Heuristic Search and classification using Neural Networks are facilitated. In the case of Cellular Automata, an improved method based on the 8-neighbourhood and rules were developed to remove noise from images and estimate the radius of the potential blast cells contained in them. The proposed methodology selects the starting points, corresponding to potential blast cells, for the subsequent seeded heuristic search. The Seeded Heuristic employs a new fitness function for blast cell detection. Furthermore, the WEKA software is utilised for classification of blast cells and hence images, into AML subtypes. As a result accuracy of 97.22% was achieved in the classification of blasts into M3 and other AML subtypes. Finally, these algorithms are integrated into an automated system for image processing. In brief, the research presented in this thesis involves the use of advanced computational techniques for processing and classification of medical images, that is, images of blood samples from patients suffering from leukaemia.The Institute of Higher Education of Malaysia and the Universiti Sains Islam Malaysia (USIM)

Cellular Automata

Modelling and simulation are disciplines of major importance for science and engineering. There is no science without models, and simulation has nowadays become a very useful tool, sometimes unavoidable, for development of both science and engineering. The main attractive feature of cellular automata is that, in spite of their conceptual simplicity which allows an easiness of implementation for computer simulation, as a detailed and complete mathematical analysis in principle, they are able to exhibit a wide variety of amazingly complex behaviour. This feature of cellular automata has attracted the researchers' attention from a wide variety of divergent fields of the exact disciplines of science and engineering, but also of the social sciences, and sometimes beyond. The collective complex behaviour of numerous systems, which emerge from the interaction of a multitude of simple individuals, is being conveniently modelled and simulated with cellular automata for very different purposes. In this book, a number of innovative applications of cellular automata models in the fields of Quantum Computing, Materials Science, Cryptography and Coding, and Robotics and Image Processing are presented