Value added products from modified kaolins : new chemical routes to new markets

Chemical treatments of kaolins to produce nanocrystalline or "X-ray amorphous", stable aluminosilicates with variable - but reproducible - types of micro- and meso-porosity have been developed. These materials show cation exchange capacities and surface area values significantly higher (ranging from 10x to 100x) than kaolin and show good acid resistance to pH~3.0. The combination of these properties offers strong potential for many new applications of kaolin-derived materials in large worldwide markets such as environmental remediation and catalysis. Kaolin amorphous derivative (KAD) is well-suited to removal of many toxic metals down to ppb range from acid mine drainage. Engineering development trials of the KAD manufacturing process and the utilisation of KAD in polluted waters such as acid mine drainage indicates that scale-up from bench-scale is not a barrier to market entry.

Inter-cycle variability of in-cylinder pressure parameters in an ethanol fumigated common rail diesel engine

The effects of ethanol fumigation on the inter-cycle variability of key in-cylinder pressure parameters in a modern common rail diesel engine have been investigated. Specifically, maximum rate of pressure rise, peak pressure, peak pressure timing and ignition delay were investigated. A new methodology for investigating the start of combustion was also proposed and demonstrated—which is particularly useful with noisy in-cylinder pressure data as it can have a significant effect on the calculation of an accurate net rate of heat release indicator diagram. Inter-cycle variability has been traditionally investigated using the coefficient of variation. However, deeper insight into engine operation is given by presenting the results as kernel density estimates; hence, allowing investigation of otherwise unnoticed phenomena, including: multi-modal and skewed behaviour. This study has found that operation of a common rail diesel engine with high ethanol substitutions (>20% at full load, >30% at three quarter load) results in a significant reduction in ignition delay. Further, this study also concluded that if the engine is operated with absolute air to fuel ratios (mole basis) less than 80, the inter-cycle variability is substantially increased compared to normal operation.

Mobius markets : professional families in rural educational markets

Australia has many isolated communities that require human services provided by qualified professionals. Maintaining a viable and equitable spread of such educational capital across space as a public good is a challenge. Reports investigating this problem repeatedly point to ‘family issues’ such as limited options for children’s education, and limited access to ongoing professional development, as deterrents for rural/remote employment despite lucrative incentive schemes. This paper draws on semi-structured interviews with 30 parents of school-aged children, who work as doctors, nurses, teachers and police in six rural/remote towns in Queensland. We asked them how their family units reconcile career opportunities with educational strategy for family members over time and space. This paper considers these issues as a sociology of education problem in a context of educational marketisation and spiralling credentialism. This paper offers the concept of ‘mobius markets’ to capture the cyclical and intergenerational process underway in middle class professional families of investing in educational capitals, maintaining or maximising their value and profiting from them. A mobius strip is the topological anomaly of a single loop with one twist in it, whereby the loop becomes one continuous surface, not the double-sided shape it appears to be. This project is interested in how the middle class professional family is similarly on a constant circuit, investing in educational capitals, upgrading their currency/value, and profiting from them. This elaborated sense of educational markets extends the more usual sociological focus on school choice.

Meta-regulation approach of law : a potential legal strategy to develop socially responsible business self-regulation in least developed common law countries

In the corporate regulation landscape, 'meta-regulation' is a comparatively new legal approach. The sketchy role of state promulgated authoritative laws in pluralized society and scepticism in corporate self-regulation's role have resulted in the development of this legal approach. It has opened up possibilities to synthesize corporate governance to add social values in corporate self-regulation. The core of this approach is the fusion of responsive and reflexive legal strategies to combine regulators and regulatees for reaching a particular goal. This paper argues that it is a potential strategy that can be successfully deployed to develop a socially responsible corporate culture for the business enterprises, so that they will be able to acquire social, environmental and ethical values in their self-regulation sustainably. Taking Bangladeshi corporate laws as an instance, this paper also evaluates the scope of incorporating this approach in laws of the least developed common law countries in general.

Destination brand equity for Australia : testing a model of CBBE in short haul and long haul markets

The study of destination brand performance measurement has only emerged in earnest as a field in the tourism literature since 2007. The concept of consumer-based brand equity (CBBE) is gaining favour from services marketing researchers as an alternative to the traditional ‘net-present-value of future earnings’ method of measuring brand equity. The perceptions-based CBBE model also appears suitable for examining destination brand performance, where a financial brand equity valuation on a destination marketing organisation’s (DMO) balance sheet is largely irrelevant. This is the first study to test and compare the model in both short and long haul markets. The paper reports the results of tests of a CBBE model for Australia in a traditional short haul market (New Zealand) and an emerging long haul market (Chile). The data from both samples indicated destination brand salience, brand image, and brand value are positively related to purchase intent for Australia in these two disparate markets.

Construction Prices : the Market Effect

Teachers of construction economics and estimating have for a long time recognised that there is more to construction pricing than detailed calculation of costs (to the contractor). We always get to the point where we have to say "of course, experience or familiarity of the market is very important and this needs judgement, intuition, etc". Quite how important is the matter in construction pricing is not known and we tend to trivialise its effect. If judgement of the market has a minimal effect, little harm would be done, but if it is really important then some quite serious consequences arise which go well beyond the teaching environment. Major areas of concern for the quantity surveyor are in cost modelling and cost planning - neither of which pay any significant attention to the market effect. There are currently two schools of thought about the market effect issue. The first school is prepared to ignore possible effects until more is known. This may be called the pragmatic school. The second school exists solely to criticise the first school. We will call this the antagonistic school. Neither the pragmatic nor the antagonistic schools seem to be particularly keen to resolve the issue one way or the other. The founder and leader of the antagonistic school is Brian Fine whose paper in 1974 is still the basic text on the subject, and in which he coined the term 'socially acceptable' price to describe what we now recognise as the market effect. Mr Fine's argument was then, and is since, that the uncertainty surrounding the contractors' costing and cost estimating process is such that the uncertainty surrounding the contractors' cost that it logically leads to a market-orientated pricing approach. Very little factual evidence, however, seems to be available to support these arguments in any conclusive manner. A further, and more important point for the pragmatic school, is that, even if the market effect is as important as Mr Fine believes, there are no indications of how it can be measured, evaluated or predicted. Since 1974 evidence has been accumulating which tends to reinforce the antagonists' view. A review of the literature covering both contractors' and designers' estimates found many references to the use of value judgements in construction pricing (Ashworth & Skitmore, 1985), which supports the antagonistic view in implying the existence of uncertainty overload. The most convincing evidence emerged quite by accident in some research we recently completed with practicing quantity surveyors in estimating accuracy (Skitmore, 1985). In addition to demonstrating that individual quantity surveyors and certain types of buildings had significant effect on estimating accuracy, one surprise result was that only a very small amount of information was used by the most expert surveyors for relatively very accurate estimates. Only the type and size of building, it seemed, was really relevant in determining accuracy. More detailed information about the buildings' specification, and even a sight to the drawings, did not significantly improve their accuracy level. This seemed to offer clear evidence that the constructional aspects of the project were largely irrelevant and that the expert surveyors were somehow tuning in to the market price of the building. The obvious next step is to feed our expert surveyors with more relevant 'market' information in order to assess its effect. The problem with this is that our experts do not seem able to verbalise their requirements in this respect - a common occurrence in research of this nature. The lack of research into the nature of market effects on prices also means the literature provides little of benefit. Hence the need for this study. It was felt that a clearer picture of the nature of construction markets would be obtained in an environment where free enterprise was a truly ideological force. For this reason, the United States of America was chosen for the next stage of our investigations. Several people were interviewed in an informal and unstructured manner to elicit their views on the action of market forces on construction prices. Although a small number of people were involved, they were thought to be reasonably representative of knowledge in construction pricing. They were also very well able to articulate their views. Our initial reaction to the interviews was that our USA subjects held very close views to those held in the UK. However, detailed analysis revealed the existence of remarkably clear and consistent insights that would not have been obtained in the UK. Further evidence was also obtained from literature relating to the subject and some of the interviewees very kindly expanded on their views in later postal correspondence. We have now analysed all the evidence received and, although a great deal is of an anecdotal nature, we feel that our findings enable at least the basic nature of the subject to be understood and that the factors and their interrelationships can now be examined more formally in relation to construction price levels. I must express my gratitude to the Royal Institution of Chartered Surveyors' Educational Trust and the University of Salford's Department of Civil Engineering for collectively funding this study. My sincere thanks also go to our American participants who freely gave their time and valuable knowledge to us in our enquiries. Finally, I must record my thanks to Tim and Anne for their remarkable ability to produce an intelligible typescript from my unintelligible writing.

Ignition delay in an ethanol fumigated common rail diesel engine

A novel method for determining ignition delay is presented. This method utilises combustion resonance as a means of determining the onset of ignition. Results are shown from an ethanol fumigation study comprising of substitutions up to 50% at full, three-quarter and half load. It has been demonstrated that at full load there is a decrease in ignition delay with increasing ethanol substitutions, whereas at half load there is an increase in ignition delay with increasing ethanol substitutions. It is suggested that this conflicting result is a consequence of the auto ignition of ethanol.

Essays on volatility and liquidity in financial markets

The price formation of financial assets is a complex process. It extends beyond the standard economic paradigm of supply and demand to the understanding of the dynamic behavior of price variability, the price impact of information, and the implications of trading behavior of market participants on prices. In this thesis, I study aggregate market and individual assets volatility, liquidity dimensions, and causes of mispricing for US equities over a recent sample period. How volatility forecasts are modeled, what determines intradaily jumps and causes changes in intradaily volatility and what drives the premium of traded equity indexes? Are they induced, for example, by the information content of lagged volatility and return parameters or by macroeconomic news, changes in liquidity and volatility? Besides satisfying our intellectual curiosity, answers to these questions are of direct importance to investors developing trading strategies, policy makers evaluating macroeconomic policies and to arbitrageurs exploiting mispricing in exchange-traded funds. Results show that the leverage effect and lagged absolute returns improve forecasts of continuous components of daily realized volatility as well as jumps. Implied volatility does not subsume the information content of lagged returns in forecasting realized volatility and its components. The reported results are linked to the heterogeneous market hypothesis and demonstrate the validity of extending the hypothesis to returns. Depth shocks, signed order flow, the number of trades, and resiliency are the most important determinants of intradaily volatility. In contrast, spread shock and resiliency are predictive of signed intradaily jumps. There are fewer macroeconomic news announcement surprises that cause extreme price movements or jumps than those that elevate intradaily volatility. Finally, the premium of exchange-traded funds is significantly associated with momentum in net asset value and a number of liquidity parameters including the spread, traded volume, and illiquidity. The mispricing of industry exchange traded funds suggest that limits to arbitrage are driven by potential illiquidity.

China’s new creative strategy : the utilization of cultural soft power and new markets

This book examines different aspects of Asian popular culture, including films, TV, music, comedy, folklore, cultural icons, the Internet and theme parks. It raises important questions such as – What are the implications of popularity of Asian popular culture for globalization? Do regional forces impede the globalizing of cultures? Or does the Asian popular culture flow act as a catalyst or conveying channel for cultural globalization? Does the globalization of culture pose a threat to local culture? It addresses two seemingly contradictory and yet parallel processes in the circulation of Asian popular culture: the interconnectedness between Asian popular culture and western culture in an era of cultural globalization that turns subjects such as Pokémon, Hip Hop or Cosmopolitan into truly global phenomena, and the local derivatives and versions of global culture that are necessarily disconnected from their origins in order to cater for the local market. It thereby presents a collective argument that, whilst local social formations, and patterns of consumption and participation in Asia are still very much dependent on global cultural developments and the phenomena of modernity, yet such dependence is often concretized, reshaped and distorted by the local media to cater for the local market. Contents: Introduction: Asian Popular Culture: The Global (Dis)continuity Anthony Y.H. Fung Part 1: The Dominance of Global Continuity: Cultural Localization and Adaptation 1. One Region, Two Modernities: Disneyland in Tokyo and Hong Kong Micky Lee and Anthony Y.H. Fung 2. Comic Travels: Disney Publishing in the People’s Republic of China Jennifer Altehenger 3. When Chinese Youth Meet Harry Potter: Translating Consumption and Middle Class Identification John Nguyet Erni 4.New Forms of Transborder Visuality in Urban China: Saving Face for Magazine Covers Eric Kit-Wai Ma 5. Cultural Consumption and Masculinity: A Case Study of GQ Magazine Covers in Taiwan Hong-Chi Shiau Part 2: Global Discontinuity: The Local Absorption of Global Culture 6. An Unlocalized and Unglobalized Subculture: English Language Independent Music in Singapore Kai Khiun Liew and Shzr Ee Tan 7. The Localized Production of Jamaican Music in Thailand Viriya Sawangchot 8. Consuming Online Games in Taiwan: Global Games and Local Market Lai-Chi Chen 9. The Rise of the Korean Cinema in Inbound and Outbound Globalization Shin Dong Kim Part 3: Cultural Domestication: A New Form of Global Continuity 10. Pocket Capitalism and Virtual Intimacy: Pokémon as a Symptom of Post-Industrial Youth Culture Anne Allison 11. Playing the Global Game: Japan Brand and Globalization Kukhee Choo Part 4: China as a Rising Market: Cultural Antagonism and Globalization 12. China’s New Creative Strategy: The Utilization of Cultural Soft Power and New Markets Michael Keane and Bonnie Liu 13. Renationalizing Hong Kong Cinema: The Gathering Force of the Mainland Market Michael Curtin

Factors associated with common mental disorders during the transition to adulthood : do emerging adults and ‘early starters’ differ? Findings from an Australian birth cohort study

Background: Despite increasing diversity in pathways to adulthood, choices available to young people are influenced by environmental, familial and individual factors, namely access to socioeconomic resources, family support and mental and physical health status. Young people from families with higher socioeconomic position (SEP) are more likely to pursue tertiary education and delay entry to adulthood, whereas those from low socioeconomic backgrounds are less likely to attain higher education or training, and more likely to partner and become parents early. The first group are commonly termed ‘emerging adults’ and the latter group ‘early starters’. Mental health disorders during this transition can seriously disrupt psychological, social and academic development as well as employment prospects. Depression, anxiety and most substance use disorders have early onset during adolescence and early adulthood with approximately three quarters of lifetime psychiatric disorders having emerged by 24 years of age. Aims: This thesis aimed to explore the relationships between mental health, sociodemographic factors and family functioning during the transition to adulthood. Four areas were investigated: 1) The key differences between emerging adults and ‘early starters’, were examined and focused on a series of social, economic, and demographic factors as well as DSM-IV diagnoses; 2) Methodological issues associated with the measurement of depression and anxiety in young adults were explored by comparing a quantitative measure of symptoms of anxiety and depression (Achenbach’s YSR and YASR internalising scales) with DSM-IV diagnosed depression and anxiety. 3) The association between family SEP and DSM-IV depression and anxiety was examined in relation to the different pathways to adulthood. 4) Finally, the association between pregnancy loss, abortion and miscarriage, and DSM-IV diagnoses of common psychiatric disorders was assessed in young women who reported early parenting, experiencing a pregnancy loss, or who had never been pregnant. Methods: Data were taken from the Mater University Study of Pregnancy (MUSP), a large birth cohort started in 1981 in Brisbane, Australia. 7223 mothers and their children were assessed five times, at 6 months, 5, 14 and 21 years after birth. Over 3700 young adults, aged 18 to 23 years, were interviewed at the 21-year phase. Respondents completed an extensive series of self-reported questionnaires and a computerised structured psychiatric interview. Three outcomes were assessed at the 21-year phase. Mental health disorders diagnosed by a computerised structured psychiatric interview (CIDI-Auto), the prevalence of DSM-IV depression, anxiety and substance use disorders within the previous 12-month, during the transition (between ages of 18 and 23 years) or lifetime were examined. The primary outcome “current stage in the transition to adulthood” was developed using a measure conceptually constructed from the literature. The measure was based on important demographic markers, and these defined four independent groups: emerging adults (single with no children and living with parents), and three categories of ‘early starter’, singles (with no children or partner, living independently), those with a partner (married or cohabitating but without children) and parents. Early pregnancy loss was assessed using a measure that also defined four independent groups and was based on pregnancy outcomes in the young women This categorised the young women into those who were never pregnant, women who gave birth to a live child, and women who reported some form of pregnancy loss, either an abortion or a spontaneous miscarriage. A series of analyses were undertaken to test the study aims. Potential confounding and mediating factors were prospectively measured between the child’s birth and the 21-year phase. Binomial and multinomial logistic regression was used to estimate the risk of relevant outcomes, and the associations were reported as odds ratios (OR) and 95% confidence intervals (95%CI). Key findings: The thesis makes a number of important contributions to our understanding of the transition to adulthood, particularly in relation to the mental health consequences associated with different pathways. Firstly, findings from the thesis clearly showed that young people who parented or partnered early fared worse across most of the economic and social factors as well as the common mental disorders when compared to emerging adults. That is, young people who became early parents were also more likely to experience recent anxiety (OR=2.0, 95%CI 1.5-2.8) and depression (OR=1.7, 95%CI 1.1-2.7) than were emerging adults after taking into account a range of confounding factors. Singles and those partnering early also had higher rates of lifetime anxiety and depression than emerging adults. Young people who partnered early, but were without children, had decreased odds of recent depression; this may be due to the protective effect of early marriage against depression. It was also found that young people who form families early had an increased risk of cigarette smoking (parents OR=3.7, 95%CI 2.9-4.8) compared to emerging adults, but not heavy alcohol (parents OR=0.4, 95%CI 0.3-0.6) or recent illicit drug use. The high rates of cigarette smoking and tobacco use disorders in ‘early starters’ were explained by common risk factors related to early adversity and lower SEP. Having a child and early marriage may well function as a ‘turning point’ for some young people, it is not clear whether this is due to a conscious decision to disengage from a previous ‘substance using’ lifestyle or simply that they no longer have the time to devote to such activities because of child caring. In relation to the methodological issues associated with assessing common mental disorders in young adults, it was found that although the Achenbach empirical internalising scales successfully predicted both later DSM-IV depression (YSR OR=2.3, 95%CI 1.7-3.1) and concurrently diagnosed depression (YASR OR=6.9, 95%CI 5.0- 9.5) and anxiety (YASR OR=5.1, 95%CI 3.8- 6.7), the scales discriminated poorly between young people with or without DSM-IV diagnosed mood disorder. Sensitivity values (the proportion of true positives) for the internalising scales were surprisingly low. Only a third of young people with current DSM-IV depression (range for each of the scales was between 34% to 42%) were correctly identified as cases by the YASR internalising scales, and only a quarter with current anxiety disorder (range of 23% to 31%) were correctly identified. Also, use of the DSM-oriented scales increased sensitivity only marginally (for depression between 2-8%, and anxiety between 2-6%) above the standard Achenbach scales. This is despite the fact that the DSM-oriented scales were originally developed to overcome the poor prediction of DSM-IV diagnoses by the Achenbach scales. The internalising scales, both standard and DSM-oriented, were much more effective at identifying young people with comorbid depression and anxiety, with OR’s 10.1 to 21.7 depending on the internalising scale used. SEP is an important predictor of both an early transition to adulthood and the experience of anxiety during that time Family income during adolescence was a strong predictor of early parenting and partnering before age 24 but not early independent living. Compared to families in the upper quintile, young people from families with low income were nearly twice as likely to live with a partner and four times more likely to become parents (OR ranged from 2.6 to 4.0). This association remained after adjusting for current employment and education level. Children raised in low income families were 30% more likely to have an anxiety disorder (OR=1.3, 95%CI 0.9-1.9), but not depression, as young adults when compared to children from wealthier families. Emerging adults and ‘early starters’ from low income families did not differ in their likelihood of having a later anxiety disorder. Young women reporting a pregnancy loss had nearly three times the odds of experiencing a lifetime illicit drug disorder (excluding cannabis) [abortion OR=3.6, 95%CI 2.0-6.7 and miscarriage OR=2.6, 95%CI 1.2-5.4]. Abortion was associated with alcohol use disorder (OR=2.1, 95%CI 1.3- 3.5) and 12-month depression (OR=1.9, 95%CI 1.1- 3.1). These finding suggest that the association identified by Fergusson et al between abortion and later psychiatric disorders in young women may be due to pregnancy loss and not to abortion, per se. Conclusion: Findings from this thesis support the view that young people who parent or partner early have a greater burden of depression and anxiety when compared to emerging adults. As well, young women experiencing pregnancy loss, from either abortion or miscarriage, are more likely to experience depression and anxiety than are those who give birth to a live infant or who have never been pregnant. Depression, anxiety and substance use disorders often go unrecognised and untreated in young people; this is especially true in young people from lower SEP. Early identification of these common mental health disorders is important, as depression and anxiety experienced during the transition to adulthood have been found to seriously disrupt an individual’s social, educational and economic prospects in later life.

Analysis of 3 common polymorphisms in the KCNK18 gene in an Australian migraine case-control cohort

Migraine is a common neurological disorder characterised by temporary disabling attacks of severe head pain and associated disturbances. There is significant evidence to suggest a genetic aetiology to the disease however few causal mutations have been conclusively linked to the migraine subtypes Migraine with (MA) or without Aura (MO). The Potassium Channel, Subfamily K, member 18 (KCNK18) gene, coding the potassium channel TRESK, is the first gene in which a rare mutation resulting in a non-functional truncated protein has been identified and causally linked to MA in a multigenerational family. In this study, three common polymorphisms in the KCNK18 gene were analysed for genetic variation in an Australian case-control migraine population consisting of 340 migraine cases and 345 controls. No association was observed for the polymorphisms examined with the migraine phenotype or with any haplotypes across the gene. Therefore even though the KCNK18 gene is the only gene to be causally linked to MA our studies indicate that common genetic variation in the gene is not a contributor to MA.

Understanding worker perceptions of common incidents at roadworks in Queensland

The process of building safer roads and roadsides needs to be managed to minimise risks to both the road using public and roadworkers. However, detailed and accurate data on fatalities and injuries at roadworks across Australia are not available. The lack of reliable safety records and consequent poor understanding of the hazards at roadworks motivated this research to examine the common trends in incidents and to understand workers' perceptions of the causes of incidents at roadworks. To achieve these aims, 66 roadworks personnel were interviewed in Queensland including road construction workers, traffic controllers, engineers, and managers. Qualitative analyses identified several major issues and themes. Vehicles driving into work areas, traffic controllers hit by vehicles, rear end crashes at roadwork approaches, and reversing incidents involving work vehicles and machinery were the most common types of incidents. Roadworkers perceived driver errors, such as violation of speed limits, distracted driving, and ignoring signage and traffic controllers' instructions as the main causes of the incidents.

Genome-wide association study reveals three susceptibility loci for common migraine in the general population

Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10(-6)) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 × 10(-9); rs10166942, OR = 0.85, P = 5.5 × 10(-12); and rs11172113, OR = 0.90, P = 4.3 × 10(-9)). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology.

Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non-Hodgkin's lymphoma

Recent developments in genomic technologies have resulted in increased understanding of pathogenic mechanisms and emphasized the importance of central survival pathways. Here, we use a novel bioinformatic based integrative genomic profiling approach to elucidate conserved mechanisms of lymphomagenesis in the three commonest non-Hodgkin's lymphoma (NHL) entities: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia. By integrating genome-wide DNA copy number analysis and transcriptome profiling of tumor cohorts, we identified genetic lesions present in each entity and highlighted their likely target genes. This revealed a significant enrichment of components of both the apoptosis pathway and the mitogen activated protein kinase pathway, including amplification of the MAP3K12 locus in all three entities, within the set of genes targeted by genetic alterations in these diseases. Furthermore, amplification of 12p13.33 was identified in all three entities and found to target the FOXM1 oncogene. Amplification of FOXM1 was subsequently found to be associated with an increased MYC oncogenic signaling signature, and siRNA-mediated knock-down of FOXM1 resulted in decreased MYC expression and induced G2 arrest. Together, these findings underscore genetic alteration of the MAPK and apoptosis pathways, and genetic amplification of FOXM1 as conserved mechanisms of lymphomagenesis in common NHL entities. Integrative genomic profiling identifies common central survival mechanisms and highlights them as attractive targets for directed therapy.

Investigation of Association between PFO complicated by cryptogenic stroke and a common variant of the cardiac transcription factor GATA4

Patent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke.