An exploration of the positive and negative relationships associated with the development of asthma and atopic disorders in primary school children in Cork

Childhood asthma, allergic rhinitis and eczema are complex heterogenic chronic inflammatory allergic disorders which constitute a major burden to children, their families. The prevalence of childhood allergic disorders is increasing worldwide and merely rudimentary understanding exists regarding causality, or the influence of the environment on disease expression. Phase Three of the International Study of Asthma and Allergy in Childhood (ISAAC) reported that Irish adolescents had the 4th highest eczema and rhinoconjunctivitis prevalence and 3rd highest asthma prevalence in the world. There are no ISAAC data pertaining to young Irish children. In 2002, Sturley reported a high prevalence of current asthma in Cork primary school children aged 6-9 years. This thesis comprises of three cross-sectional studies which examined the prevalence of and associations with childhood allergy and a quasi-retrospective cohort study which observed the natural history of allergy from 6-9 until 11-13 years. Although not part of ISAAC, data was attained by parentally completed ISAAC-based questionnaires, using the ISAAC protocol. The prevalence, natural history and risk factors of childhood allergy in Ireland, as described in this thesis, echo those in worldwide allergy research. The variations of prevalence in different populations worldwide and the recurring themes of associations between childhood allergy and microbial exposures, from farming environments and/or gastrointestinal infections, as shown in this thesis, strengthen the mounting evidence that microbial exposure on GALT may hold the key to the mechanisms of allergy development. In this regard, probiotics may be an area of particular interest in allergy modification. Although their effects in relation to allergy, have been investigated now for several years, our knowledge of their diversity, complex functions and interactions with gut microflora, remain rudimentary. Birth cohort studies which include genomic and microbiomic research are recommended in order to examine the underlying mechanisms and the natural course of allergic diseases.

Phase transitions and nonlinear phenomena in neuronal network models

Communication and cooperation between billions of neurons underlie the power of the brain. How do complex functions of the brain arise from its cellular constituents? How do groups of neurons self-organize into patterns of activity? These are crucial questions in neuroscience. In order to answer them, it is necessary to have solid theoretical understanding of how single neurons communicate at the microscopic level, and how cooperative activity emerges. In this thesis we aim to understand how complex collective phenomena can arise in a simple model of neuronal networks. We use a model with balanced excitation and inhibition and complex network architecture, and we develop analytical and numerical methods for describing its neuronal dynamics. We study how interaction between neurons generates various collective phenomena, such as spontaneous appearance of network oscillations and seizures, and early warnings of these transitions in neuronal networks. Within our model, we show that phase transitions separate various dynamical regimes, and we investigate the corresponding bifurcations and critical phenomena. It permits us to suggest a qualitative explanation of the Berger effect, and to investigate phenomena such as avalanches, band-pass filter, and stochastic resonance. The role of modular structure in the detection of weak signals is also discussed. Moreover, we find nonlinear excitations that can describe paroxysmal spikes observed in electroencephalograms from epileptic brains. It allows us to propose a method to predict epileptic seizures. Memory and learning are key functions of the brain. There are evidences that these processes result from dynamical changes in the structure of the brain. At the microscopic level, synaptic connections are plastic and are modified according to the dynamics of neurons. Thus, we generalize our cortical model to take into account synaptic plasticity and we show that the repertoire of dynamical regimes becomes richer. In particular, we find mixed-mode oscillations and a chaotic regime in neuronal network dynamics.

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