Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia

Genome-wide association studies followed by replication provide a powerful approach to map genetic risk factors for asthma. We sought to search for new variants associated with asthma and attempt to replicate the association with four loci reported previously (ORMDL3, PDE4D, DENND1B and IL1RL1). Genome-wide association analyses of individual single nucleotide polymorphisms (SNPs), rare copy number variants (CNVs) and overall CNV burden were carried out in 986 asthma cases and 1846 asthma-free controls from Australia. The most-associated locus in the SNP analysis was ORMDL3 (rs6503525, P = 4.8 x 10(-)(7)). Five other loci were associated with P < 10(-)(5), most notably the chemokine CXC motif ligand 14 (CXCL14) gene (rs31263, P = 7.8 x 10(-)(6)). We found no evidence for association with the specific risk variants reported recently for PDE4D, DENND1B and ILR1L1. However, a variant in IL1RL1 that is in low linkage disequilibrium with that reported previously was associated with asthma risk after accounting for all variants tested (rs10197862, gene wide P = 0.01). This association replicated convincingly in an independent cohort (P = 2.4 x 10(-)(4)). A 300-kb deletion on chromosome 17q21 was associated with asthma risk, but this did not reach experiment-wide significance. Asthma cases and controls had comparable CNV rates, length and number of genes affected by deletions or duplications. In conclusion, we confirm the association between asthma risk and variants in ORMDL3 and identify a novel risk variant in IL1RL1. Follow-up of the 17q21 deletion in larger cohorts is warranted.

Hendra Virus and Horse Owners – Risk Perception and Management

Hendra virus is a highly pathogenic novel paramyxovirus causing sporadic fatal infection in horses and humans in Australia. Species of fruit-bats (genus Pteropus), commonly known as flying-foxes, are the natural host of the virus. We undertook a survey of horse owners in the states of Queensland and New South Wales, Australia to assess the level of adoption of recommended risk management strategies and to identify impediments to adoption. Survey questionnaires were completed by 1431 respondents from the target states, and from a spectrum of industry sectors. Hendra virus knowledge varied with sector, but was generally limited, with only 13% of respondents rating their level of knowledge as high or very high. The majority of respondents (63%) had seen their state’s Hendra virus information for horse owners, and a similar proportion found the information useful. Fifty-six percent of respondents thought it moderately, very or extremely likely that a Hendra virus case could occur in their area, yet only 37% said they would consider Hendra virus if their horse was sick. Only 13% of respondents stabled their horses overnight, although another 24% said it would be easy or very easy to do so, but hadn’t done so. Only 13% and 15% of respondents respectively had horse feed bins and water points under solid cover. Responses varied significantly with state, likely reflecting different Hendra virus history. The survey identified inconsistent awareness and/or adoption of available knowledge, confusion in relation to Hendra virus risk perception, with both over-and under-estimation of true risk, and lag in the uptake of recommended risk minimisation strategies, even when these were readily implementable. However, we also identified frustration and potential alienation by horse owners who found the recommended strategies impractical, onerous and prohibitively expensive. The insights gained from this survey have broader application to other complex risk-management scenarios.

Identifying risk-efficient strategies using stochastic frontier analysis and simulation: An application to irrigated cropping in Australia

In irrigated cropping, as with any other industry, profit and risk are inter-dependent. An increase in profit would normally coincide with an increase in risk, and this means that risk can be traded for profit. It is desirable to manage a farm so that it achieves the maximum possible profit for the desired level of risk. This paper identifies risk-efficient cropping strategies that allocate land and water between crop enterprises for a case study of an irrigated farm in Southern Queensland, Australia. This is achieved by applying stochastic frontier analysis to the output of a simulation experiment. The simulation experiment involved changes to the levels of business risk by systematically varying the crop sowing rules in a bioeconomic model of the case study farm. This model utilises the multi-field capability of the process based Agricultural Production System Simulator (APSIM) and is parameterised using data collected from interviews with a collaborating farmer. We found sowing rules that increased the farm area sown to cotton caused the greatest increase in risk-efficiency. Increasing maize area also improved risk-efficiency but to a lesser extent than cotton. Sowing rules that increased the areas sown to wheat reduced the risk-efficiency of the farm business. Sowing rules were identified that had the potential to improve the expected farm profit by ca. $50,000 Annually, without significantly increasing risk. The concept of the shadow price of risk is discussed and an expression is derived from the estimated frontier equation that quantifies the trade-off between profit and risk.

Developing enterprise curriculum: Building on rock, not sand

Entrepreneurial education is the process of providing individuals with the ability to recognise commercial opportunities and the insight, self-esteem, knowledge and skills to act on them. It includes instruction in opportunity recognition, commercialising a concept, marshalling resources in the face of risk, and initiating a business venture. It also includes instruction in traditional business disciplines such as management, marketing, information systems and finance. The purpose of this paper is to describe the design and introduction of a new program in Entrepreneurship at the University of Tasmania. Rather than adopt a traditional business school (passive learning) approach, within this program the method and responsibility of learning has largely been reversed through the process of student centred learning. This method of learning represents a challenging departure from the traditional mainstream teaching practices. In considering the benefits achievable from this teaching method, this paper also considers the difficulties in transferring increased responsibility to students to manage their futures.

Flying-Fox Roost Disturbance and Hendra Virus Spillover Risk

Bats of the genus Pteropus (flying-foxes) are the natural host of Hendra virus (HeV) which periodically causes fatal disease in horses and humans in Australia. The increased urban presence of flying-foxes often provokes negative community sentiments because of reduced social amenity and concerns of HeV exposure risk, and has resulted in calls for the dispersal of urban flying-fox roosts. However, it has been hypothesised that disturbance of urban roosts may result in a stress-mediated increase in HeV infection in flying-foxes, and an increased spillover risk. We sought to examine the impact of roost modification and dispersal on HeV infection dynamics and cortisol concentration dynamics in flying-foxes. The data were analysed in generalised linear mixed models using restricted maximum likelihood (REML). The difference in mean HeV prevalence in samples collected before (4.9%), during (4.7%) and after (3.4%) roost disturbance was small and non-significant (P = 0.440). Similarly, the difference in mean urine specific gravity-corrected urinary cortisol concentrations was small and non-significant (before = 22.71 ng/mL, during = 27.17, after = 18.39) (P= 0.550). We did find an underlying association between cortisol concentration and season, and cortisol concentration and region, suggesting that other (plausibly biological or environmental) variables play a role in cortisol concentration dynamics. The effect of roost disturbance on cortisol concentration approached statistical significance for region, suggesting that the relationship is not fixed, and plausibly reflecting the nature and timing of disturbance. We also found a small positive statistical association between HeV excretion status and urinary cortisol concentration. Finally, we found that the level of flying-fox distress associated with roost disturbance reflected the nature and timing of the activity, highlighting the need for a ‘best practice’ approach to dispersal or roost modification activities. The findings usefully inform public discussion and policy development in relation to Hendra virus and flying-fox management.

Destinations, disasters and public relations: Stakeholder engagement in multi-phase disaster management

Research about disasters in tourism has emerged in earnest since the 1990s covering insights for preparedness and response. However, recently, authors have called for more systematic and holistic approaches to tourism disaster management research. To address this gap, this study adopted a public relations perspective to refocus attention to relationships and stakeholder expectations of destination communities across multiple phases of disaster management. The authors used a mixed method approach and developed a battery of disaster management attributes by conducting interviews and analyzing industry documents and the extant literature. These attributes formed part of a survey of tourism businesses. Exploratory factor analysis resulted in a two factor solution: - i) business disaster preparedness, and; - ii) destination disaster response and recovery. Findings also show that participants reported a gap between the importance and destination performance of these attributes. In particular, tourism businesses perceived destinations did not adequately engage in disaster preparedness activities, which had implications for disaster response and recovery.

Serum bilirubin concentration is modified by UGT1A1 Haplotypes and influences risk of type-2 diabetes in the Norfolk Island Genetic Isolate

Background Located in the Pacific Ocean between Australia and New Zealand, the unique population isolate of Norfolk Island has been shown to exhibit increased prevalence of metabolic disorders (type-2 diabetes, cardiovascular disease) compared to mainland Australia. We investigated this well-established genetic isolate, utilising its unique genomic structure to increase the ability to detect related genetic markers. A pedigree-based genome-wide association study of 16 routinely collected blood-based clinical traits in 382 Norfolk Island individuals was performed. Results A striking association peak was located at chromosome 2q37.1 for both total bilirubin and direct bilirubin, with 29 SNPs reaching statistical significance (P < 1.84 × 10−7). Strong linkage disequilibrium was observed across a 200 kb region spanning the UDP-glucuronosyltransferase family, including UGT1A1, an enzyme known to metabolise bilirubin. Given the epidemiological literature suggesting negative association between CVD-risk and serum bilirubin we further explored potential associations using stepwise multivariate regression, revealing significant association between direct bilirubin concentration and type-2 diabetes risk. In the Norfolk Island cohort increased direct bilirubin was associated with a 28 % reduction in type-2 diabetes risk (OR: 0.72, 95 % CI: 0.57-0.91, P = 0.005). When adjusted for genotypic effects the overall model was validated, with the adjusted model predicting a 30 % reduction in type-2 diabetes risk with increasing direct bilirubin concentrations (OR: 0.70, 95 % CI: 0.53-0.89, P = 0.0001). Conclusions In summary, a pedigree-based GWAS of blood-based clinical traits in the Norfolk Island population has identified variants within the UDPGT family directly associated with serum bilirubin levels, which is in turn implicated with reduced risk of developing type-2 diabetes within this population.

Effects of Metabolic Risk Factors and Type 1 Diabetes on Brain Glucose and Brain Metabolites

The metabolic syndrome and type 1 diabetes are associated with brain alterations such as cognitive decline brain infarctions, atrophy, and white matter lesions. Despite the importance of these alterations, their pathomechanism is still poorly understood. This study was conducted to investigate brain glucose and metabolites in healthy individuals with an increased cardiovascular risk and in patients with type 1 diabetes in order to discover more information on the nature of the known brain alterations. We studied 43 20- to 45-year-old men. Study I compared two groups of non-diabetic men, one with an accumulation of cardiovascular risk factors and another without. Studies II to IV compared men with type 1 diabetes (duration of diabetes 6.7 ± 5.2 years, no microvascular complications) with non-diabetic men. Brain glucose, N-acetylaspartate (NAA), total creatine (tCr), choline, and myo-inositol (mI) were quantified with proton magnetic resonance spectroscopy in three cerebral regions: frontal cortex, frontal white matter, thalamus, and in cerebellar white matter. Data collection was performed for all participants during fasting glycemia and in a subgroup (Studies III and IV), also during a hyperglycemic clamp that increased plasma glucose concentration by 12 mmol/l. In non-diabetic men, the brain glucose concentration correlated linearly with plasma glucose concentration. The cardiovascular risk group (Study I) had a 13% higher plasma glucose concentration than the control group, but no difference in thalamic glucose content. The risk group thus had lower thalamic glucose content than expected. They also had 17% increased tCr (marker of oxidative metabolism). In the control group, tCr correlated with thalamic glucose content, but in the risk group, tCr correlated instead with fasting plasma glucose and 2-h plasma glucose concentration in the oral glucose tolerance test. Risk factors of the metabolic syndrome, most importantly insulin resistance, may thus influence brain metabolism. During fasting glycemia (Study II), regional variation in the cerebral glucose levels appeared in the non-diabetic subjects but not in those with diabetes. In diabetic patients, excess glucose had accumulated predominantly in the white matter where the metabolite alterations were also the most pronounced. Compared to the controls values, the white matter NAA (marker of neuronal metabolism) was 6% lower and mI (glia cell marker) 20% higher. Hyperglycemia is therefore a potent risk factor for diabetic brain disease and the metabolic brain alterations may appear even before any peripheral microvascular complications are detectable. During acute hyperglycemia (Study III), the increase in cerebral glucose content in the patients with type 1 diabetes was, dependent on brain region, between 1.1 and 2.0 mmol/l. An every-day hyperglycemic episode in a diabetic patient may therefore as much as double brain glucose concentration. While chronic hyperglycemia had led to accumulation of glucose in the white matter, acute hyperglycemia burdened predominantly the gray matter. Acute hyperglycemia also revealed that chronic fluctuation in blood glucose may be associated with alterations in glucose uptake or in metabolism in the thalamus. The cerebellar white matter appeared very differently from the cerebral (Study IV). In the non-diabetic men it contained twice as much glucose as the cerebrum. Diabetes had altered neither its glucose content nor the brain metabolites. The cerebellum seems therefore more resistant to the effects of hyperglycemia than is the cerebrum.

Governance of enterprise Information and Technology: A new core competency for boards of directors

With the level of digital disruption that is affecting businesses around the globe, you might expect high levels of Governance of Enterprise Information and Technology (GEIT) capability within boards. Boards and their senior executives know technology is important. More than 90% of boards and senior executives currently identify technology as essential to their current businesses, and to their organization’s future. But as few as 16% have sufficient GEIT capability. Global Centre for Digital Business Transformation’s recent research contains strong indicators of the need for change. Despite board awareness of both the likelihood and impact of digital disruption, things digital are still not viewed as a board-level matter in 45% of companies. And, it’s not just the board. The lack of board attention to technology can be mirrored at senior executive level as well. When asked about their organization’s attitude towards digital disruption, 43% of executives said their business either did not recognise it as a priority or was not responding appropriately. A further 32% were taking a “follower” approach, a potentially risky move as we will explain. Given all the evidence that boards know information and technology (I&T***) is vital, that they understand the inevitably, impact and speed of digital change and disruption, why are so many boards dragging their heels? Ignoring I&T disruption and refusing to build capability at board level is nothing short of negligence. Too many boards risk flying blind without GEIT capability [2]. To help build decision quality and I&T governance capability, this research: • Confirms a pressing need to build individual competency and cumulative, across-board capability in governing I&T • Identifies six factors that have rapidly increased the need, risk and urgency • Finds that boards may risk not meeting their duty of care responsibilities when it comes to I&T oversight • Highlights barriers to building capability details three GEIT competencies that boards and executives can use for evaluation, selection, recruitment and professional development.

Corporate philanthropy, reputation risk management and shareholder value: A study of Australian corporate giving

This study examines the role of corporate philanthropy in the management of reputation risk and shareholder value of the top 100 ASX listed Australian firms for the three years 2011-2013. The results of this study demonstrate the business case for corporate philanthropy and hence encourage corporate philanthropy by showing increasing firms’ investment in corporate giving as a percentage of profit before tax, increases the likelihood of an increase in shareholder value. However, the proviso is that firms must also manage their reputation risk at the same time. There is a negative association between corporate giving and shareholder value (Tobin’s Q) which is mitigated by firms’ management of reputation. The economic significance of this result is that for every cent in the dollar the firm spends on corporate giving, Tobin’s Q will decrease by 0.413%. In contrast, if the firm increase their reputation by 1 point then Tobin’s Q will increase by 0.267%. Consequently, the interaction of corporate giving and reputation risk management is positively associated with shareholder value. These results are robust while controlling for potential endogeneity and reverse causality. This paper assists both academics and practitioners by demonstrating that the benefits of corporate philanthropy extend beyond a gesture to improve reputation or an attempt to increase financial performance, to a direct collaboration between all the factors where the benefits far outweigh the costs.

Global and EU governance for sustainable forest management with special reference to capacity building in Ethiopia and Southern Sudan

The purpose of this study was to produce information on and practical recommendations for informed decision-making on and capacity building for sustainable forest management (SFM) and good forest governance. This was done within the overall global framework for sustainable development with special emphasis on the EU and African frameworks and on Southern Sudan and Ethiopia in particular. The case studies on Southern Sudan and Ethiopia focused on local, national and regional issues. Moreover, this study attempted to provide both theoretical and practical new insight. The aim was to build an overall theoretical framework and to study its key contents and main implications for SFM and good forest governance at all administration levels, for providing new tools for capacity building in natural resources management. The theoretical framework and research approach were based on the original research problem and the general and specific aims of the study. The key elements of the framework encompass sustainable development, global and EU governance, sustainable forest management (SFM), good forest governance, as well as international and EU law. The selected research approach comprised matrix-based assessment of international, regional (EU and Africa) and national (Southern Sudan and Ethiopia) policy and legal documents. The specific case study on Southern Sudan also involved interviews and group discussions with local community members and government officials. As a whole, this study attempted to link the global, regional, national and local levels in forest-sector development and especially to analyse how the international policy development in environmental and forestry issues is reflected in field-level progress towards SFM and good forest governance, for the specific cases of Southern Sudan and Ethiopia. The results on Southern Sudan focused on the existing situation and perceived needs in capacity building for SFM and good forest governance at all administration levels. Specifically, the results of the case study on Southern Sudan presented the current situation in selected villages in the northern parts of Renk County in Upper Nile State, and the implications of Multilateral Environmental Agreements (MEAs) and of the new forest policy framework for capacity building actions. The results on Ethiopia focused on training, extension, research, education and new curriculum development within higher education institutions and particularly at the Wondo Genet College of Forestry and Natural Resources (WGCF-NR), which administratively lies under Hawassa University. The results suggest that, for both cases studies, informed decision-making on and capacity building for SFM and good forest governance require comprehensive, long-term, cross-sectoral, coherent and consistent approaches within the dynamic and evolving overall global framework, including its multiple inter-linked levels. The specific priority development and focus areas comprised the establishment of SFM and good forest governance in accordance with the overall sustainable development priorities and with more focus on the international trade in forest products that are derived from sustainable and legal sources with an emphasis on effective forest law enforcement and governance at all levels. In Upper Nile State in Southern Sudan there were positive development signals such as the will of the local people to plant more multipurpose trees on farmlands and range lands as well as the recognition of the importance of forests and trees for sustainable rural development where food security is a key element. In addition, it was evident that the local communities studied in Southern Sudan also wanted to establish good governance systems through partnerships with all actors and through increased local responsibilities. The results also suggest that the implementation of MEAs at the local level in Southern Sudan requires mutually supportive and coherent approaches within the agreements as well as significantly more resources and financial and technical assistance for capacity building, training and extension. Finally, the findings confirm the importance of full utilization of the existing local governance and management systems and their traditional and customary knowledge and practices, and of new development partnerships with full participation of all stakeholders. The planned new forest law for Southern Sudan, based on an already existing new forest policy, is expected to recognize the roles of local-level actors, and it would thus obviously facilitate the achieving of sustainable forest management.

Essays on Stock Option Compensation and the Role of Incentives and Risk (summary section only)

Managerial pay-for-performance sensitivity has increased rapidly around the world. Early empirical research showed that pay-for-performance sensitivity resulting from stock ownership and stock options appeared to be quite low during the 1970s and early 1980s in the U.S. However, recent empirical research from the U.S. shows an enormous increase in pay-for-performance sensitivity. The global trend has also reached Finland, where stock options have become a major ingredient of executive compensation. The fact that stock options seem to be an appealing form of remuneration from a theoretical point of view combined with the observation that the use of this compensation form has increased significantly during the recent years, implies that research on the dynamics of stock option compensation is highly relevant for the academic community, as well as for practitioners and regulators. The research questions of the thesis are analyzed in four separate essays. The first essay examines whether stock option compensation practices of Finnish firms are consistent with predictions from principal-agent theory. The second essay explores one of the major puzzles in the compensation literature by studying determinants of stock option contract design. In theory, optimal contract design should vary according to firm characteristics. However, in the U.S., variation in contract design seems to be surprisingly low, a phenomenon generally attributed to tax and accounting considerations. In Finland, however, firms are not subject to stringent contracting restrictions, and the variation in contract design tends, in fact, to be quite substantial. The third essay studies the impact of price- and risk incentives arising from stock option compensation on firm investment. In addition, the essay explores one of the most debated questions in the literature, in particular, the relation between incentives and firm performance. Finally, several strands of literature in both economics and corporate finance hypothesize that economic uncertainty is related to corporate decision-making. Previous research has shown that risk tends to slow down firm investment. In the fourth essay, it is hypothesized that firm risk slows down growth from a more universal perspective. Consistent with this view, it is shown that risk not only tends to slow down firm investment, but also employment growth. Moreover, the essay explores whether the nature of firms’ compensation policies, in particular, whether firms make use of stock option compensation, affects the relation between risk and firm growth. In summary, the four essays contribute to the current understanding of stock options as a form of equity incentives, and how incentives and risk affect corporate decision-making. By this, the thesis promotes the knowledge related to the modern theory of the firm.

Political Risk in Credit Evaluation: Empirical Studies and Survey Results

Financing trade between economic agents located in different countries is affected by many types of risks, resulting from incomplete information about the debtor, the problems of enforcing international contracts, or the prevalence of political and financial crises. Trade is important for economic development and the availability of trade finance is essential, especially for developing countries. Relatively few studies treat the topic of political risk, particularly in the context of international lending. This thesis explores new ground to identify links between political risk and international debt defaults. The core hypothesis of the study is that the default probability of debt increases with increasing political risk in the country of the borrower. The thesis consists of three essays that support the hypothesis from different angles of the credit evaluation process. The first essay takes the point of view of an international lender assessing the credit risk of a public borrower. The second investigates creditworthiness assessment of companies. The obtained results are substantiated in the third essay that deals with an extensive political risk survey among finance professionals in developing countries. The financial instruments of core interest are export credit guaranteed debt initiated between the Export Credit Agency of Finland and buyers in 145 countries between 1975 and 2006. Default events of the foreign credit counterparts are conditioned on country-specific macroeconomic variables, corporate-specific accounting information as well as political risk indicators from various international sources. Essay 1 examines debt issued to government controlled institutions and conditions public default events on traditional macroeconomic fundamentals, in addition to selected political and institutional risk factors. Confirming previous research, the study finds country indebtedness and the GDP growth rate to be significant indicators of public default. Further, it is shown that public defaults respond to various political risk factors. However, the impact of the risk varies between countries at different stages of economic development. Essay 2 proceeds by investigating political risk factors as conveivable drivers of corporate default and uses traditional accounting variables together with new political risk indicators in the credit evaluation of private debtors. The study finds links between corporate default and leverage, as well as between corporate default and the general investment climate and measeures of conflict in the debtor country. Essay 3 concludes the thesis by offering survey evidence on the impact of political risk on debt default, as perceived and experienced by 103 finance professionals in 38 developing countries. Taken together, the results of the thesis suggest that various forms of political risk are associated with international debt defaults and continue to pose great concerns for both international creditors and borrowers in developing countries. The study provides new insights on the importance of variable selection in country risk analysis, and shows how political risk is actually perceived and experienced in the riskier, often lower income countries of the global economy.

Building and Using Existing Hunspell Dictionaries and TEX Hyphenators as Finite-State Automata

There are numerous formats for writing spellcheckers for open-source systems and there are many descriptions for languages written in these formats. Similarly, for word hyphenation by computer there are TEX rules for many languages. In this paper we demonstrate a method for converting these spell-checking lexicons and hyphenation rule sets into finite-state automata, and present a new finite-state based system for writer’s tools used in current open-source software such as Firefox, OpenOffice.org and enchant via the spell-checking library voikko.