Wound healing angiogenesis : the clinical implications of a simple mathematical model

Nonhealing wounds are a major burden for health care systems worldwide. In addition, a patient who suffers from this type of wound usually has a reduced quality of life. While the wound healing process is undoubtedly complex, in this paper we develop a deterministic mathematical model, formulated as a system of partial differential equations, that focusses on an important aspect of successful healing: oxygen supply to the wound bed by a combination of diffusion from the surrounding unwounded tissue and delivery from newly formed blood vessels. While the model equations can be solved numerically, the emphasis here is on the use of asymptotic methods to establish conditions under which new blood vessel growth can be initiated and wound-bed angiogenesis can progress. These conditions are given in terms of key model parameters including the rate of oxygen supply and its rate of consumption in the wound. We use our model to discuss the clinical use of treatments such as hyperbaric oxygen therapy, wound bed debridement, and revascularisation therapy that have the potential to initiate healing in chronic, stalled wounds.

Mathematical modelling of tumour-induced angiogenesis

The growth of solid tumours beyond a critical size is dependent upon angiogenesis, the formation of new blood vessels from an existing vasculature. Tumours may remain dormant at microscopic sizes for some years before switching to a mode in which growth of a supportive vasculature is initiated. The new blood vessels supply nutrients, oxygen, and access to routes by which tumour cells may travel to other sites within the host (metastasize). In recent decades an abundance of biological research has focused on tumour-induced angiogenesis in the hope that treatments targeted at the vasculature may result in a stabilisation or regression of the disease: a tantalizing prospect. The complex and fascinating process of angiogenesis has also attracted the interest of researchers in the field of mathematical biology, a discipline that is, for mathematics, relatively new. The challenge in mathematical biology is to produce a model that captures the essential elements and critical dependencies of a biological system. Such a model may ultimately be used as a predictive tool. In this thesis we examine a number of aspects of tumour-induced angiogenesis, focusing on growth of the neovasculature external to the tumour. Firstly we present a one-dimensional continuum model of tumour-induced angiogenesis in which elements of the immune system or other tumour-cytotoxins are delivered via the newly formed vessels. This model, based on observations from experiments by Judah Folkman et al., is able to show regression of the tumour for some parameter regimes. The modelling highlights a number of interesting aspects of the process that may be characterised further in the laboratory. The next model we present examines the initiation positions of blood vessel sprouts on an existing vessel, in a two-dimensional domain. This model hypothesises that a simple feedback inhibition mechanism may be used to describe the spacing of these sprouts with the inhibitor being produced by breakdown of the existing vessel's basement membrane. Finally, we have developed a stochastic model of blood vessel growth and anastomosis in three dimensions. The model has been implemented in C++, includes an openGL interface, and uses a novel algorithm for calculating proximity of the line segments representing a growing vessel. This choice of programming language and graphics interface allows for near-simultaneous calculation and visualisation of blood vessel networks using a contemporary personal computer. In addition the visualised results may be transformed interactively, and drop-down menus facilitate changes in the parameter values. Visualisation of results is of vital importance in the communication of mathematical information to a wide audience, and we aim to incorporate this philosophy in the thesis. As biological research further uncovers the intriguing processes involved in tumourinduced angiogenesis, we conclude with a comment from mathematical biologist Jim Murray, Mathematical biology is : : : the most exciting modern application of mathematics.

Mathematical modelling of the drying of sol gel microspheres

This thesis presents a mathematical model of the evaporation of colloidal sol droplets suspended within an atmosphere consisting of water vapour and air. The main purpose of this work is to investigate the causes of the morphologies arising within the powder collected from a spray dryer into which the precursor sol for Synroc™ is sprayed. The morphology is of significant importance for the application to storage of High Level Liquid Nuclear Waste. We begin by developing a model describing the evaporation of pure liquid droplets in order to establish a framework. This model is developed through the use of continuum mechanics and thermodynamic theory, and we focus on the specific case of pure water droplets. We establish a model considering a pure water vapour atmosphere, and then expand this model to account for the presence of an atmospheric gas such as air. We model colloidal particle-particle interactions and interactions between colloid and electrolyte using DLVO Theory and reaction kinetics, then incorporate these interactions into an expression for net interaction energy of a single particle with all other particles within the droplet. We account for the flow of material due to diffusion, advection, and interaction between species, and expand the pure liquid droplet models to account for the presence of these species. In addition, the process of colloidal agglomeration is modelled. To obtain solutions for our models, we develop a numerical algorithm based on the Control Volume method. To promote numerical stability, we formulate a new method of convergence acceleration. The results of a MATLAB™ code developed from this algorithm are compared with experimental data collected for the purposes of validation, and further analysis is done on the sensitivity of the solution to various controlling parameters.

Evaluating the economics of the Australian National Hand Hygiene Initiative

The National Hand Hygiene Initiative, implemented in Australia in 2009, is currently being evaluated for effectiveness and cost-effectiveness by a multidisciplinary team of researchers. Data from a wide range of sources are being harvested to address the research questions. The data are observational and appropriate statistical and economic modelling methods are being used. Decision makers will be provided with new knowledge about how hand hygiene interventions should be organised and what investment decisions are justified. This is novel research and the authors are unaware of any other evaluation of hand hygiene improvement initiatives. This paper describes the evaluation currently underway.

The economics of happiness : a lifetime perspective

The three studies in this thesis focus on happiness and age and seek to contribute to our understanding of happiness change over the lifetime. The first study contributes by offering an explanation for what was evolving to a ‘stylised fact’ in the economics literature, the U-shape of happiness in age. No U-shape is evident if one makes a visual inspection of the age happiness relationship in the German socio-economic panel data, and, it seems counter-intuitive that we just have to wait until we get old to be happy. Eliminating the very young, the very old, and the first timers from the analysis did not explain away regression results supporting the U-shape of happiness in age, but fixed effect analysis did. Analysis revealed found that reverse causality arising from time-invariant individual traits explained the U-shape of happiness in age in the German population, and the results were robust across six econometric methods. Robustness was added to the German fixed effect finding by replicating it with the Australian and the British socio-economic panel data sets. During analysis of the German data an unexpected finding emerged, an exceedingly large negative linear effect of age on happiness in fixed-effect regressions. There is a large self-reported happiness decline by those who remain in the German panel. A similar decline over time was not evident in the Australian or the British data. After testing away age, time and cohort effects, a time-in-panel effect was found. Germans who remain in the panel for longer progressively report lower levels of happiness. Because time-in-panel effects have not been included in happiness regression specifications, our estimates may be biased; perhaps some economics of the happiness studies, that used German panel data, need revisiting. The second study builds upon the fixed-effect finding of the first study and extends our view of lifetime happiness to a cohort little visited by economists, children. Initial analysis extends our view of lifetime happiness beyond adulthood and revealed a happiness decline in adolescent (15 to 23 year-old) Australians that is twice the size of the happiness decline we see in older Australians (75 to 86 yearolds), who we expect to be unhappy due to declining income, failing health and the onset of death. To resolve a difference of opinion in the literature as to whether childhood happiness decreases, increases, or remains flat in age; survey instruments and an Internet-based survey were developed and used to collect data from four hundred 9 to 14 year-old Australian children. Applying the data to a Model of Childhood Happiness revealed that the natural environment life-satisfaction domain factor did not have a significant effect on childhood happiness. However, the children’s school environment and interactions with friends life-satisfaction domain factors explained over half a steep decline in childhood happiness that is three times larger than what we see in older Australians. Adding personality to the model revealed what we expect to see with adults, extraverted children are happier, but unexpectedly, so are conscientious children. With the steep decline in the happiness of young Australians revealed and explanations offered, the third study builds on the time-invariant individual trait finding from the first study by applying the Australian panel data to an Aggregate Model of Average Happiness over the lifetime. The model’s independent variable is the stress that arises from the interaction between personality and the life event shocks that affect individuals and peers throughout their lives. Interestingly, a graphic depiction of the stress in age relationship reveals an inverse U-shape; an inverse U-shape that looks like the opposite of the U-shape of happiness in age we saw in the first study. The stress arising from life event shocks is found to explain much of the change in average happiness over a lifetime. With the policy recommendations of economists potentially invoking unexpected changes in our lives, the ensuing stress and resulting (un)happiness warrant consideration before economists make policy recommendations.

Meeting under the “Omei” Tree in the Torres Strait Islands : networks and funds of knowledge of mathematical ideas

This paper focuses on the turning point experiences that worked to transform the researcher during a preliminary consultation process to seek permission to conduct of a small pilot project on one Torres Strait Island. The project aimed to learn from parents how they support their children in their mathematics learning. Drawing on a community research design, a consultative meeting was held with one Torres Strait Islander community to discuss the possibility of piloting a small project that focused on working with parents and children to learn about early mathematics processes. Preliminary data indicated that parents use networks in their community. It highlighted the funds of knowledge of mathematics that exist in the community and which are used to teach their children. Such knowledges are situated within a community’s unique histories, culture and the voices of the people. “Omei” tree means the Tree of Wisdom in the Island community.

Numerical simulation of a fractional mathematical model for epidermal wound healing

A number of mathematical models investigating certain aspects of the complicated process of wound healing are reported in the literature in recent years. However, effective numerical methods and supporting error analysis for the fractional equations which describe the process of wound healing are still limited. In this paper, we consider numerical simulation of fractional model based on the coupled advection-diffusion equations for cell and chemical concentration in a polar coordinate system. The space fractional derivatives are defined in the Left and Right Riemann-Liouville sense. Fractional orders in advection and diffusion terms belong to the intervals (0; 1) or (1; 2], respectively. Some numerical techniques will be used. Firstly, the coupled advection-diffusion equations are decoupled to a single space fractional advection-diffusion equation in a polar coordinate system. Secondly, we propose a new implicit difference method for simulating this equation by using the equivalent of the Riemann-Liouville and Gr¨unwald-Letnikov fractional derivative definitions. Thirdly, its stability and convergence are discussed, respectively. Finally, some numerical results are given to demonstrate the theoretical analysis.

Visualising mathematical knowledge and understanding

Contemporary mathematics education attempts to instil within learners the conceptualization of mathematics as a highly organized and inter-connected set of ideas. To support this, a means to graphically represent this organization of ideas is presented which reflects the cognitive mechanisms that shape a learner’s understanding. This organisation of information may then be analysed, with the view to informing the design of mathematics instruction in face-to-face and/or computer-mediated learning environments. However, this analysis requires significant work to develop both theory and practice.

Jabberwocky : the complexities of mathematical English

Mathematical English is a unique language based on ordinary English, with the addition of highly stylised formal symbol systems. Some words have a redefined status. Mathematical English has its own lexicon, syntax, semantics and literature. It is more difficult to understand than ordinary English. Ability in basic interpersonal communication does not necessarily result in proficiency in the use of mathematical English. The complex nature of mathematical English may impact upon the ability of students to succeed in mathematical and numeracy assessment. This article presents a review of the literature about the complexities of mathematical English. It includes examples of more than fifty language features that have been shown to add to the challenge of interpreting mathematical texts. Awareness of the complexities of mathematical English is an essential skill needed by mathematics teachers when teaching and when designing assessment tasks.

Real, complex, and binary semantic vectors

This paper presents a combined structure for using real, complex, and binary valued vectors for semantic representation. The theory, implementation, and application of this structure are all significant. For the theory underlying quantum interaction, it is important to develop a core set of mathematical operators that describe systems of information, just as core mathematical operators in quantum mechanics are used to describe the behavior of physical systems. The system described in this paper enables us to compare more traditional quantum mechanical models (which use complex state vectors), alongside more generalized quantum models that use real and binary vectors. The implementation of such a system presents fundamental computational challenges. For large and sometimes sparse datasets, the demands on time and space are different for real, complex, and binary vectors. To accommodate these demands, the Semantic Vectors package has been carefully adapted and can now switch between different number types comparatively seamlessly. This paper describes the key abstract operations in our semantic vector models, and describes the implementations for real, complex, and binary vectors. We also discuss some of the key questions that arise in the field of quantum interaction and informatics, explaining how the wide availability of modelling options for different number fields will help to investigate some of these questions.

Experiences with implementing common mathematical operations using field programmable gate arrays

Many computationally intensive scientific applications involve repetitive floating point operations other than addition and multiplication which may present a significant performance bottleneck due to the relatively large latency or low throughput involved in executing such arithmetic primitives on commod- ity processors. A promising alternative is to execute such primitives on Field Programmable Gate Array (FPGA) hardware acting as an application-specific custom co-processor in a high performance reconfig- urable computing platform. The use of FPGAs can provide advantages such as fine-grain parallelism but issues relating to code development in a hardware description language and efficient data transfer to and from the FPGA chip can present significant application development challenges. In this paper, we discuss our practical experiences in developing a selection of floating point hardware designs to be implemented using FPGAs. Our designs include some basic mathemati cal library functions which can be implemented for user defined precisions suitable for novel applications requiring non-standard floating point represen- tation. We discuss the details of our designs along with results from performance and accuracy analysis tests.

Econometric fellows and Nobel Laureates in economics

An academic award is method by which peers offer recognition of intellectual efforts. In this paper we take a purely descriptive look at the relationship between becoming a Fellow of the Econometric Society and receiving the Nobel Prize in economics. We discover some interesting aspects: of all 69 Nobel Prize Laureates between 1969 and 2011, only 9 of them were not also Fellows. Moreover, the proportion of future novel winners among the Fellows has been quite high throughout time and a large share of researchers who became Fellows between the 1930s and 1950s became Nobel Laureates at a later stage. On average, researchers became Fellows relatively early in their career (14.9 years after their PhD) and those who were subsequently made Nobel Laureates became Fellows earlier than other researchers. Interestingly, Harvard and MIT have been the dominant PhD granting institutions to generate Fellows and Nobel Laureates in the past.

Students’ approaches to learning a new mathematical model

In this article, we report on the findings of an exploratory study into the experience of undergraduate students as they learn new mathematical models. Qualitative and quanti- tative data based around the students’ approaches to learning new mathematical models were collected. The data revealed that students actively adopt three approaches to under- standing a new mathematical model: gathering information for the task of understanding the model, practising with and using the model, and finding interrelationships between elements of the model. We found that the students appreciate mathematical models that have a real world application and that this can be used to engage students in higher level learning approaches.