Insights into a multidrug resistant Escherichia coli pathogen of the globally disseminated ST131 lineage : genome analysis and virulence mechanisms

Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI.

Conjugation of carcinogens by 6 class glutathione S-transferases : mechanisms and relevance to variations in human risk

Conjugation of chemicals with glutathione (GSH) can lead to decreased or increased toxicity. A genetic deficiency in the GSH S-transferase μ class gene M1 has been hypothesized to lead to greater risk of lung cancer in smokers. Recently a gene deletion polymorphism involving the human θ enzyme T1 has been described; the enzyme is present in erythrocytes and can be readily assayed. A rat θ class enzyme, 5-5, has structural and catalytic similarity and the protein was expressed in the Salmonella typhimurium tester strain TA1535. Expression of the cDNA vector increased the mutagenicity of ethylene dibromide and several methylene dihalides. Mutations resulting from the known GSH S-transferase substrate 1,2-epoxy-3-(4′nitrophenoxy)propane were decreased in the presence of the transferase. Expression of transferase 5-5 increased mutations when 1,2,3,4-diepoxybutane (butadiene diepoxide), 4-bromo-1,2-epoxybutane, or 1,3-dichloracetone were added. The latter compound is a model for the putative 1,2-dibromo-3-chloropropane oxidation product 1-bromo-3-chloroacetone. These genotoxicity and genotyping assays may be of use in further studies of the roles of GSH S-transferase θ enzymes in bioactivation and detoxication and any changes in risk due to polymorphism.

Convergence in the ownership and governance of East Asian firms

In the past decade, policymakers in over 70 markets have introduced corporate governance codes or best practice guidelines. In East Asia, they have been introduced in Hong Kong in 1999 and 2006, Indonesia in 2000 and 2007, Malaysia in 2000 and 2007, the Philippines in 2002, Singapore iu 2001 and 2005, South Korea in 2003, Taiwan iu 2002 and Thailand iu 2006. The common focus of these codes is to encourage but not force companies to improve their corporate governance practices to a specified target level, e.g., board independence of 30%. Another commonality is that the guidelines apply to all listed companies regardless of their ownership structure or other characteristics.

Exploring the usefulness of structural–functional approaches to analyse governance of planning systems

Existing planning theories tend to be limited in their analytical scope and often fail to account for the impact of many interactions between the multitudes of stakeholders involved in strategic planning processes. Although many theorists rejected structural–functional approaches from the 1970s, this article argues that many of structural–functional concepts remain relevant and useful to planning practitioners. In fact, structural–functional approaches are highly useful and practical when used as a foundation for systemic analysis of real-world, multi-layered, complex planning systems to support evidence-based governance reform. Such approaches provide a logical and systematic approach to the analysis of the wider governance of strategic planning systems that is grounded in systems theory and complementary to existing theories of complexity and planning. While we do not propose its use as a grand theory of planning, this article discusses how structural–functional concepts and approaches might be applied to underpin a practical analysis of the complex decision-making arrangements that drive planning practice, and to provide the evidence needed to target reform of poorly performing arrangements.

Institutional investors, political connections and analyst following in Malaysia

We examine the association between institutional ownership, political connections, and analyst following in Malaysia from 1999 to 2009. Based on 940 firm-year observations, we document a positive relation between institutional ownership, particularly by Employees Provident Fund (EPF), and analyst following, thus supporting the governance role that institutional investors play in promoting corporate transparency. However, there is no evidence that political connections matter to analyst following. The monitoring role of institutional investors, including EPF, does not appear to be any different between politically connected and non-connected firms.

On the efficacy of key corporate governance recommendations in mid-tier companies : window-dressing or value-adding?

This paper examins the relationship between firm performance and key board and audit committee variables in a sample of mid-tier listed Australian firms. Unlike the UK where the corporate governance Code specifically outlines special arrangements for companies outside the FTSE 350 index, the ASX Corporate Governance recommendations make no special provisions for mid-tier companies. Consequently, mid-tier Australian companies may be expending scarce resources in conforming with recommendations that are not value-creating.

Institutional investors, risk/return and corporate governance : practical lessons from the Global Financial Crisis

The global grown in institutional investors means that firms can no longer ignore their influence in capital markets. However, not all institutional investors have the same motives to influence the firms they invest in. Institution investors' ability to influence management depends on the size of their investment and whether they have any business relations with the firm. Using a sample of Australian firms from 2006 to 2008, our empirical results show that the proportion of a company's shares held by institutional investors is positively associated with firm governance ratings, risk and profitability. This study shows that a positive association between risk and return is associated with large active institutional ownership, which we interpret as shareholders with sufficient power to pressure management to increase short-term profits.

Convergence in European corporate governance : the audit committee concept

This paper analyses recent corporate governance codes issued by 20 countries for evidence of convergence in corporate governance systems in Europe. The analysis shows that there has been a degree of convergence towards an Anglo-Saxon model of corporate governance as the audit committee concept is widely accepted in countries with both unitary and two-tier governance systems. Further, the latest audit committee recommendations in countries that have issued several governance codes show a strengthening of the recommendations for an audit committee over time in line with the Anglo-Saxon audit committee concept and convergence with the debate in the US and UK on issues such as the independence and financial expertise of members. However, consistent with the literature on the convergence of European corporate governance systems, at an operational level there is limited consistency in the recommended structure and role of audit committees.

Volunteering and recent governance reforms

The regulatory reforms touching volunteer governs over the last 25 years are identified and analysed. BOth direct reforms such as the Australian Charities and Not-for-profits Commission's (ACNC) governance standards and society--wide indirect reforms to workplace health and safety, civil liability and deemed liability provisions are discussed in this chapter.

The ACNC's new governance rules

Australian charities have a new regulator in the form of the Australian Charities and Not-for-profits Commission (ACNC) which began operations in December 2012; and new governance rules which applied from 1 July 2013. While there is some uncertainty over the ACNC's future, the new legislative framework currently applies to approximately 58,000 charities which seek federal tax concessions and other benefits, and includes governance standards that apply across charitable organisational forms (company, trust and association) with some exceptions. The governance standards are a minimum benchmark that many charities will already meet, if they are companies or incorporated associations.

Fred’s Flow (Canada) and Murphy Well (Australia) : thick komatiitic lava flows with contrasting compositions, emplacement mechanisms and water contents

Two Archaean komatiitic flows, Fred’s Flow in Canada and the Murphy Well Flow in Australia, have similar thicknesses (120 and 160 m) but very different compositions and internal structures. Their contrasting differentiation profiles are keys to determine the cooling and crystallization mechanisms that operated during the eruption of Archaean ultramafic lavas. Fred’s Flow is the type example of a thick komatiitic basalt flow. It is strongly differentiated and consists of a succession of layers with contrasting textures and compositions. The layering is readily explained by the accumulation of olivine and pyroxene in a lower cumulate layer and by evolution of the liquid composition during downward growth of spinifex-textured rocks within the upper crust. The magmas that erupted to form Fred’s Flow had variable compositions, ranging from 12 to 20 wt% MgO, and phenocryst contents from 0 to 20 vol%. The flow was emplaced by two pulses. A first ~20-m-thick pulse was followed by another more voluminous but less magnesian pulse that inflated the flow to its present 120 m thickness. Following the second pulse, the flow crystallized in a closed system and differentiated into cumulates containing 30–38 wt% MgO and a residual gabbroic layer with only 6 wt% MgO. The Murphy Well Flow, in contrast, has a remarkably uniform composition throughout. It comprises a 20-m-thick upper layer of fine-grained dendritic olivine and 2–5 vol% amygdales, a 110–120 m intermediate layer of olivine porphyry and a 20–30 m basal layer of olivine orthocumulate. Throughout the flow, MgO contents vary little, from only 30 to 33 wt%, except for the slightly more magnesian basal layer (38–40 wt%). The uniform composition of the flow and dendritic olivine habits in the upper 20 m point to rapid cooling of a highly magnesian liquid with a composition like that of the bulk of the flow. Under equilibrium conditions, this liquid should have crystallized olivine with the composition Fo94.9, but the most magnesian composition measured by electron microprobe in samples from the flow is Fo92.9. To explain these features, we propose that the parental liquid contained around 32 wt% MgO and 3 wt% H2O. This liquid degassed during the eruption, creating a supercooled liquid that solidified quickly and crystallized olivine with non-equilibrium textures and compositions.

Corporate governance and bankruptcy risk

We examine how firm characteristics, particularly the degree of firm complexity and the firm’s need for specialty knowledge, affect the relationship between corporate governance and the risk of bankruptcy. We find that having larger boards reduces the risk of bankruptcy only for complex firms. Our results also suggest that the proportion of inside directors on the board is inversely associated with the risk of bankruptcy in firms that require more specialist knowledge, and that the reverse is true in technically unsophisticated firms. The results further reveal that the additional explanatory power from corporate governance variables becomes stronger as the time to bankruptcy is increased, implying that although corporate governance variables are important predictors, governance changes are likely to be too late to save a firm on the verge of bankruptcy.

Numerical investigation of deformation and failure mechanisms of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays

This thesis is a comprehensive study of deformation and failure mechanisms in bone at nano- and micro-scale levels. It explores the mechanical behaviour of osteopontin-hydroxyapatite interfaces and mineralized collagen fibril arrays, through atomistic molecular dynamics and finite element simulations. This thesis shows some main factors contributing to the excellent material properties of bone and provides some guidelines for development of new artificial biological materials and medical implants.

Corporate governance quality, audit fees and non-audit services fees

This paper extends prior research on the relationship between governance quality and auditor remuneration.We examine the influence of audit committee effectiveness (ACE), a proxy for governance quality, on audit fees (AF) and non-audit services fees (NASF) using a new composite measure comprising audit committee independence, expertise, diligence and size. We find that after controlling for board of director characteristics, there is a significant positive association between ACE and AF only for larger clients. Our results indicate that effective audit committees undertake more monitoring which results in wider audit scope and higher audit fees. Contrary to our expectations, we find the association between ACE and NASF to be positive and significant, especially for larger clients. This suggests that larger clients are more likely to purchase non-audit services (NAS) even in the presence of effective audit committees probably due to the complexity of their activities. Overall, our findings support regulatory initiatives aimed at improving corporate governance quality.