Patterns and rules for sensitivity and elasticity in population projection matrices

Sensitivity and elasticity analysis of population projection matrices (PPMs) are established tools in the analysis of structured populations, allowing comparison of the contributions made by different demographic rates to population growth. In some commonly used structures of PPM, however, there are mathematically inevitable patterns in the relative sensitivity and elasticity of certain demographic rates. We take a simulation approach to investigate these mathematical constraints for a range of PPM models. Our results challenge some previously proposed constraints on sensitivity and elasticity. We also identify constraints beyond those which have already been proven mathematically, and promote them as candidates for future mathematical proof. A general theme among these rules is that changes to the demographic rates of older or larger individuals have less impact on population growth than do equivalent changes among younger or smaller individuals. However, the validity of these rules in each case depends on the choice between sensitivity and elasticity, the growth rate of the population and the PPM structure used. If the structured population conforms perfectly to the assumptions of the PPM used to model it, the rules we describe represent biological reality, allowing us to prioritise management strategies in the absence of detailed demographic data. Conversely, if the model is a poor fit to the population (specifically; if demographic rates within stages are heterogeneous) such analyses could lead to inappropriate management prescriptions. Our results emphasise the importance of choosing a structured population model which fits the demographics of the population

Treatment of Abscessed Primary Molars Utilizing Lesion Sterilization and Tissue Repair: Literature Review and Report of Three Cases

Purpose: The purpose of this report was to review an emerging alternative treatment to pulpectomies and extractions for nonvital primary teeth called lesion sterilization and tissue repair (LSTR) and provide the results of three clinical case applications. LSTR is a noninstrumentation endodontic treatment that involves a triantibiotic mixture in a propylene glycol vehicle, which is used to disinfect root canal systems. This concept was developed by the cariology research unit of the School of Dentistry, Niigata University, Niigata, Niigata Prefecture, Japan. This article reviews the development of the technique, clinical procedures required for the technique, three clinical applications and radiographic documentation and follow-up, and a short literature review of the current evidence supporting its application in clinical practice

Using systems biology to investigate how age-related changes in TGFβ signalling alter pro-inflammatory stimuli

PhD ThesisOsteoarthritis (OA) is a degenerative condition caused by dysregulation of multiple molecular signalling pathways. This dysregulation results in damage to cartilage, a smooth and protective tissue that enables low friction articulation of synovial joints. Matrix metalloproteinases (MMPs), especially MMP13, are key enzymes in the cleavage of type II collagen which is a vital component for cartilage integrity. Various stimuli have been identified as inducers of MMP expression such as excessive load, injury and inflammation. Although previously considered a non-inflammatory arthritis, recent research has shown that inflammation may play an important role in OA development. A novel meta-analysis of microarray data from OA patients was used to create a cytoscape network representative of human OA. This enabled the identification of key processes in OA development, of which inflammation was prominent. Examining various different signalling pathways highlighted a role for transforming growth factor beta (TGFβ) in protecting against pro-inflammatory cytokine-mediated MMP expression. Indeed, TGFβ plays key roles in all facets of cartilage biology including development and maintenance of cartilage integrity. With age there is a change in the ratio of two TGFβ type I receptors (ALK1/ALK5), a shift that results in TGFβ losing its protective role in cartilage homeostasis. Instead, TGFβ promotes cartilage degradation and this correlates with the spontaneous development of OA in murine models. However, the mechanism by which TGFβ protects against pro-inflammatory responses and how this changes with age has not been extensively studied. Mathematical modelling has previously revealed how stochastic changes in TGFβ signalling during ageing led to the upregulation of MMPs. I have expanded the TGFβ section of this model to incorporate the pro-inflammatory stimulus interleukin-1 (IL-1) + oncostatin M (OSM) in order to investigate how TGFβ mediates MMP repression, specifically MMP-13. TGFβ signalling appears to interact with the activator protein 1 (AP-1) complex, which has an important role in MMP upregulation. However, the model indicates this interaction alone is insufficient to mediate the full effect of TGFβ, predicting it may also reduce MMP-13 mRNA stability. Furthermore, the model enabled me to predict how age alters these interactions; it suggested TGFβ would provide limited repression with a prolonged inflammatory response. Combining the modelled genes with the microarray network provided a global overview of how alterations in one pathway can affect others and lead to OA development. This study therefore demonstrates the power of combining computational biology with experimentally-derived data to provide insight into the importance of TGFβ signalling, and how age-related changes can lead to cartilage damage and OA development.Centre of Integrated Research into Musculoskeletal Ageing (CIMA), Arthritis research UK and the Medical Research Counci

Raising the higher school leaving age in Western Australia: A governmental analysis of power and practice

This thesis reports on a study into the Western Australian state government policy to raise the compulsory school leaving age (RSLA). In 2006, the compulsory school leaving age in Western Australia was increased from age 15 to 16 years, and again in 2008 from age 16 to 17 years, where it has remained since. This thesis is informed by Michel Foucault’s theory of governmentality and has adapted the governmentality literature into framework that supports a research methodology. Within this orientation, the research is guided by the question: What are the discourses, rationalities, technologies and ethics of the Raised School Leaving Age policy in Western Australia? Fourteen semi-structured interviews were conducted with authorities charged with managing and coordinating young people’s participation. As well, 184 policy documents and other ‘grey materials’ were analysed. Two key conclusions are drawn. First, RSLA entails a narrow and reductionist ontology, and, consequently, its theory and practice of the problem of attrition and early school leaving is diminished. Second, it is rooted in a deficit view of young people producing contradictory practices that expect young people to be self-reliant, entrepreneurial and independent, even though they are construed as being at-risk, inept and damaged. The result is a policy myopia that sidelines critical debate about the context of schools themselves as being complicit in the problem of early school leaving and student disengagement. It also turns youth unemployment and underemployment into a problem of the individual who is seen to have failed to manage their participation, and thus RSLA ignores the role of wider economic forces in producing a difficult labour market experience for many young people. This thesis provides an account of the thinking and practices of RSLA insofar as it is conceptualised as an expression of modern governing over young people’s lives

An economic analysis of trading on private information by external administrators: international comparisons

This paper examines the regulation of trades in listed securities by external administrators (EAs), such as trustees in bankruptcy, liquidators, receivers, and administrators on the basis of private information. We consider the economic policy issues associated with such trades. The principal considerations counsel in favour of taking a permissive approach. These are: the difficulties of associating trades with insider information, given the EA's necessarily short expected holding period, the asymmetric application of the insider trading prohibition to sales (rather than decisions not to sell), the market incentives not to misuse private information that apply to EAs, and the unlikelihood that the EA has monopolistic access to the information in question. We consider these considerations by reference to a number of hypothetical scenarios. The paper argues that the law should regulate the subject by coupling a broad exemption for EAs with a "goiod faith" proviso, a continuous disclosure obligation, and a requirement to sell "all or nothing" of a holding of listed securities

Epithelial organization and cyst lumen expansion require efficient Sec13-Sec31-driven secretion

Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13–Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture