Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of approximately 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

Associations between perception of wellness and health-related quality of life, comorbidities, modifiable lifestyle factors and demographics in older Australians

Aim: The associations between perceived wellness and health-related quality of life, comorbidities and modifiable lifestyle factors in older adults were explored. Methods: Self-administered questionnaires including the Perceived Wellness Survey and the 36-Item Short Form of the Medical Outcomes Study version two were distributed to 328 community-living adults aged 65 years and over. Results: Results showed positive associations between perception of wellness and health-related quality of life. General health (r(249) = 0.66, P < 0.01), vitality (r(249) = 0.59, P < 0.01) and mental health (r(249) = 0.52, P < 0.01) had the strongest association; and social functioning (r(249) = 0.3, P < 0.01) and pain (r(249) = 0.36, P < 0.01) the lowest. Perceived wellness was influenced by hearing, mobility, memory, chronic disease, exercise, gambling and single status. Conclusion: The study identified that perceived wellness in older adults is a multidimensional construct.

Unincorporated associations as entities : a matter of balance between regulation and facilitation?

Small non-profit organisations play a vital role in the creation of social capital and resilience of civil society in Australia. A number of government inquiries have recently been commissioned to propose reform to non-profit enterprise and it is timely to examine the suitability of legal structures available for small non-profit organisations. This article reviews the characteristics of small Australian non-profit organisations and the legal treatment of similar associations in New Zealand, the United Kingdom, Europe, Canada and United States to inform possible reform strategies. Reforms are then proposed for small Australian unincorporated organisations which allow them access to the benefits of separate legal entity status, but with regulation proportionate to the risks posed to the broader community.

The 2006 CSRC guidelines for articles of Association of Chinese listed companies : critiquing from an Australian perspective

Compares the Chinese Securities and Regulatory Commission's guidelines for articles of association of listed companies issued in 2006 with 'replaceable' rules in the Australian Corporations Act 2001. Discusses the provisions of the Chinese guidelines and the Australian rules on corporate constitution, interpretation, a company's representative, object clauses, shareholders' powers and meetings and directors. Questions whether the Chinese guidelines facilitate effective corporate governance.

Knowledge and attitudes about Vitamin D and impact on sun protection practices among urban office workers in Brisbane, Australia

Background: Sun exposure is the main source of vitamin D. Increasing scientific and media attention to the potential health benefits of sun exposure may lead to changes in sun exposure behaviors. Methods: To provide data that might help frame public health messages, we conducted an online survey among office workers in Brisbane, Australia, to determine knowledge and attitudes about vitamin D and associations of these with sun protection practices. Of the 4,709 people invited to participate, 2,867 (61%) completed the questionnaire. This analysis included 1,971 (69%) participants who indicated that they had heard about vitamin D. Results: Lack of knowledge about vitamin D was apparent. Eighteen percent of people were unaware of the bone benefits of vitamin D but 40% listed currently unconfirmed benefits. Over half of the participants indicated that more than 10 minutes in the sun was needed to attain enough vitamin D in summer, and 28% indicated more than 20 minutes in winter. This was significantly associated with increased time outdoors and decreased sunscreen use. People believing sun protection might cause vitamin D deficiency (11%) were less likely to be frequent sunscreen users (summer odds ratio, 0.63; 95% confidence interval, 0.52-0.75). Conclusions: Our findings suggest that there is some confusion about sun exposure and vitamin D, and that this may result in reduced sun-protective behavior. Impact: More information is needed about vitamin D production in the skin. In the interim, education campaigns need to specifically address the vitamin D issue to ensure that skin cancer incidence does not increase.

Analysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia

Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated.

Securities market regulators’ use of the ‘please explain’ queries sanction and its power of compliance

The aim of this study is to investigate the compliance impact of price queries issued by a securities market operator to its participating firms. Market operators in Australia and New Zealand, such as the Australian Securities Exchange and the New Zealand Securities Exchange, have the regulatory power in their rules to issue queries to its market participants to explain unusual fluctuations in trading price or volume in the market. The operator will issue a price query where it believes that the market has not been fully informed as to price relevant information. Responsive regulation has informed much of the regulatory debate in securities laws in our region. We posit that price queries are one strategy that a market operator can use in communicating its enforcement expectations to its stakeholder. However, whilst responsive regulation informs regulatory choices, an alternate view seeks to explain why participants respond to these regulatory strategies, and we use disclosure behaviour after price queries to test compliance behaviour

Structured feature extraction using association rules

As of today, opinion mining has been widely used to iden- tify the strength and weakness of products (e.g., cameras) or services (e.g., services in medical clinics or hospitals) based upon people's feed- back such as user reviews. Feature extraction is a crucial step for opinion mining which has been used to collect useful information from user reviews. Most existing approaches only find individual features of a product without the structural relationships between the features which usually exists. In this paper, we propose an approach to extract features and feature relationship, represented as tree structure called a feature hi- erarchy, based on frequent patterns and associations between patterns derived from user reviews. The generated feature hierarchy profiles the product at multiple levels and provides more detailed information about the product. Our experiment results based on some popularly used review datasets show that the proposed feature extraction approach can identify more correct features than the baseline model. Even though the datasets used in the experiment are about cameras, our work can be ap- plied to generate features about a service such as the services in hospitals or clinics.

Standardising corneal nerve fibre length for nerve tortuosity increases its association with measures of diabetic neuropathy

AIMS: Recent studies on corneal markers have advocated corneal nerve fibre length as the most important measure of diabetic peripheral neuropathy. The aim of this study was to determine if standardizing corneal nerve fibre length for tortuosity increases its association with other measures of diabetic peripheral neuropathy. METHODS: Two hundred and thirty-one individuals with diabetes with either predominantly mild or absent neuropathic changes and 61 control subjects underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10-g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length and corneal nerve fibre tortuosity were measured using corneal confocal microscopy. A tortuosity-standardised corneal nerve fibre length variable was generated by dividing corneal nerve fibre length by corneal nerve fibre tortuosity. Differences in corneal nerve morphology between individuals with and without diabetic peripheral neuropathy and control subjects were determined and associations were estimated between corneal morphology and established tests of, and risk factors for, diabetic peripheral neuropathy. RESULTS: The tortuosity-standardised corneal nerve fibre length variable was better than corneal nerve fibre length in demonstrating differences between individuals with diabetes, with and without neuropathy (tortuosity-standardised corneal nerve fibre length variable: 70.5 ± 27.3 vs. 84.9 ± 28.7, P < 0.001, receiver operating characteristic area under the curve = 0.67; corneal nerve fibre length: 15.9 ± 6.9 vs. 18.4 ± 6.2 mm/mm(2) , P = 0.004, receiver operating characteristic area under the curve = 0.64). Furthermore, the tortuosity-standardised corneal nerve fibre length variable demonstrated a significant difference between the control subjects and individuals with diabetes, without neuropathy, while corneal nerve fibre length did not (tortuosity-standardised corneal nerve fibre length variable: 94.3 ± 27.1 vs. 84.9 ± 28.7, P = 0.028; corneal nerve fibre length: 20.1 ± 6.3 vs. 18.4 ± 6.2 mm/mm(2) , P = 0.084). Correlations between corneal nerve fibre length and established measures of neuropathy and risk factors for neuropathy were higher when a correction was made for the nerve tortuosity. CONCLUSIONS: Standardizing corneal nerve fibre length for tortuosity enhances the ability to differentiate individuals with diabetes, with and without neuropathy.

The Australian Nonprofit Sector Legal and Accounting Almanac 2013

INTRODUCTION CASES For a number of years, Professor Myles McGregor-Lowndes, Frances Hannah and Anne Overell have compiled one to two page summaries of cases involving nonprofit organisations and published them on The Australian Centre for Philanthropy and Nonprofit Studies, Developing Your Organisation (DYO) website.1 You can be alerted of new case summaries as they are posted to the DYO website by subscribing to the ACPNS RSS feed or the ACPNS twitter service.2 There were some very significant cases during 2013, such as Commissioner of Taxation v Cancer & Bowel Research Association (see case notes 2.8.2 and 2.8.11), The Hunger Project case which is under appeal, but could change the face of PBI jurisprudence (see case note 2.8.7) while Home Health Pty Ltd retained the PBI status quo but might have been different if appealed (see case note 2.8.8). For sheer interest there is nothing better in my 30 odd years of reading tax and charity judgements than case involving The Study and Prevention of Psychological Diseases Foundation Incorporated (see case note 2.1.1). It even rivals some of the more bizarre cases from the US jurisdiction of which St Joseph Abbey v Castille (case note 2.10.9) is certainly ‘dead centre’. A set of cases which stand out for attention are those involving New Zealand’s Christchurch Cathedral which anyone with responsibility for heritage-listed buildings should study carefully, for implications in relation to their own circumstances. A number of cases summarised in this Almanac are working their way through the appeals process and care should be taken with their application. In addition, some of the cases are from jurisdictions outside Australia, and readers should exercise caution when considering the implications of these cases for Australian law. LEGISLATION The Almanac includes a review of major statutory amendments during 2013, which are relevant to the nonprofit sector in all Australian jurisdictions. Special thanks must go to Nathan MacDonald and the JusticeConnect team for providing legislative updates for Victoria. SPECIAL ISSUES DURING 2013 A number of legal practitioners have contributed articles on significant legal issues facing nonprofit organisations: charitable trusts giving to government entities (Alice Macdougall); workplace bullying (Tim Longwill); and privacy (James Tan and Nina Brewer). WORLD ROUND-UP Major developments from the UK and Ireland (Kerry O’Halloran), Canada (Peter Broder), New Zealand (Michael Gousmett and Susan Barker) and Jamaica (Frances Hannah) are all summarised in a review of a significant part of the common law charity jurisdictions. WHAT DOES 2014 HOLD The final section moves from looking in the rear view mirror to peering out the front windscreen to discern the reform agenda. The view from the windscreen in 2013 was of considerable reform traffic at the Commonwealth level jostling for a place in the parliamentary agenda. This year is quite different with a smaller number of vehicles ahead, but the potential for significant impact.

Incorporated associations

Non-profit community groups such as sporting clubs, charities, interest groups and community associations can be formally incorporated and recognised by the law. More than 21,000 associations are already incorporated in Queensland. The governing legislation is the Associations Incorporate Act 1981 (Qld) (the Act) and the Associations Incorporate regulation 1999 (Qld) (The Regulation). The Queensland Department of Justice and Attorney General is responsible for administering this Act and incorporating associations and does so through the Office of Fair Trading. This chapter covers some of the basic concepts and procedures for incorporating an association under the Act. The Act and the Regulation are usually amended at least once a year, and current materials are available on the Queensland Government legislation website.

Transcriptional pathway signatures predict MEK addiction and response to selumetinib (AZD6244)

Selumetinib (AZD6244, ARRY-142886) is a selective, non-ATP-competitive inhibitor of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-1/2. The range of antitumor activity seen preclinically and in patients highlights the importance of identifying determinants of response to this drug. In large tumor cell panels of diverse lineage, we show that MEK inhibitor response does not have an absolute correlation with mutational or phospho-protein markers of BRAF/MEK, RAS, or phosphoinositide 3-kinase (PI3K) activity. We aimed to enhance predictivity by measuring pathway output through coregulated gene networks displaying differential mRNA expression exclusive to resistant cell subsets and correlated to mutational or dynamic pathway activity. We discovered an 18-gene signature enabling measurement of MEK functional output independent of tumor genotype. Where the MEK pathway is activated but the cells remain resistant to selumetinib, we identified a 13-gene signature that implicates the existence of compensatory signaling from RAS effectors other than PI3K. The ability of these signatures to stratify samples according to functional activation of MEK and/or selumetinib sensitivity was shown in multiple independent melanoma, colon, breast, and lung tumor cell lines and in xenograft models. Furthermore, we were able to measure these signatures in fixed archival melanoma tumor samples using a single RT-qPCR-based test and found intergene correlations and associations with genetic markers of pathway activity to be preserved. These signatures offer useful tools for the study of MEK biology and clinical application of MEK inhibitors, and the novel approaches taken may benefit other targeted therapies.

Cartels – What are they and how to avoid being part of one : the implications of University fee deregulation

Universities supply a range of services to students. These include most obviously, tuition services in relation to undergraduate and postgraduate courses; research supervision services in relation to research degrees; as well as consultancy services in relation to Government and industry work. For the purposes of the CCA, universities are trading corporations. They engage in trade or commerce through the provision of a range of services for reward. As such Universities are subject to the same rules and regulations that govern the conduct of other trading corporations, such Coles and Woolworths. As senior officers and managers of a trading corporation you need to acquire some basic understanding of the rules that govern competition in the education sector. In other sectors, companies generally undertake a risk assessment of those areas where they are most at risk of contravening the CCA; to ascertain in advance how problems might arise so that they can put in place strategies to mitigate the risk of inadvertent contraventions.

A call for better care: the impact of postnatal contact services on women’s parenting confidence and experiences of postpartum care in Queensland, Australia

Background Universal postnatal contact services are provided in several Australian states, but their impact on women’s postnatal care experience has not been evaluated. Furthermore, there is lack of evidence or consensus about the optimal type and amount of postpartum care after hospital discharge for maternal outcomes. This study aimed to assess the impact of providing Universal Postnatal Contact Service (UPNCS) funding to public birthing facilities in Queensland, Australia on women’s postnatal care experiences, and associations between amount and type (telephone or home visits) of contact on parenting confidence, and perceived sufficiency and quality of postnatal care. Methods Data collected via retrospective survey of postnatal women (N = 3,724) were used to compare women who birthed in UPNCS-funded and non-UPNCS-funded facilities on parenting confidence, sufficiency of postnatal care, and perceived quality of postnatal care. Associations between receiving telephone and home visits and the same outcomes, regardless of UPNCS funding, were also assessed. Results Women who birthed in an UPNCS-funded facility were more likely to receive postnatal contact, but UPNCS funding was not associated with parenting confidence, or perceived sufficiency or perceived quality of care. Telephone contact was not associated with parenting confidence but had a positive dose–response association with perceived sufficiency and quality. Home visits were negatively associated with parenting confidence when 3 or more were received, had a positive dose–response association with perceived sufficiency and were positively associated with perceived quality when at least 6 were received. Conclusions Funding for UPNCS is unlikely to improve population levels of maternal parenting confidence, perceived sufficiency or quality of postpartum care. Where only minimal contact can be provided, telephone may be more effective than home visits for improving women’s perceived sufficiency and quality of care. Additional service initiatives may be needed to improve women’s parenting confidence.