Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Shared common variants in prostate cancer and blood lipids

Background Epidemiological and clinical studies suggest comorbidity between prostate cancer (PCA) and cardiovascular disease (CVD) risk factors. However, the relationship between these two phenotypes is still not well understood. Here we sought to identify shared genetic loci between PCA and CVD risk factors. Methods We applied a genetic epidemiology method based on conjunction false discovery rate (FDR) that combines summary statistics from different genome-wide association studies (GWAS), and allows identification of genetic overlap between two phenotypes. We evaluated summary statistics from large, multi-centre GWA studies of PCA (n = 50 000) and CVD risk factors (n = 200 000) [triglycerides (TG), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, systolic blood pressure, body mass index, waist-hip ratio and type 2 diabetes (T2D)]. Enrichment of single nucleotide polymorphisms (SNPs) associated with PCA and CVD risk factors was assessed with conditional quantile-quantile plots and the Anderson-Darling test. Moreover, we pinpointed shared loci using conjunction FDR. Results We found the strongest enrichment of P-values in PCA was conditional on LDL and conditional on TG. In contrast, we found only weak enrichment conditional on HDL or conditional on the other traits investigated. Conjunction FDR identified altogether 17 loci; 10 loci were associated with PCA and LDL, 3 loci were associated with PCA and TG and additionally 4 loci were associated with PCA, LDL and TG jointly (conjunction FDR < 0.01). For T2D, we detected one locus adjacent to HNF1B. Conclusions We found polygenic overlap between PCA predisposition and blood lipids, in particular LDL and TG, and identified 17 pleiotropic gene loci between PCA and LDL, and PCA and TG, respectively. These findings provide novel pathobiological insights and may have implications for trials using targeting lipid-lowering agents in a prevention or cancer setting.

Patient decision aids in routine maternity care: Benefits, barriers, and new opportunities

Background and aim Participation in decision-making, supported by comprehensive and quality information provision, is increasingly emphasised as a priority for women in maternity care. Patient decision aids are tools that can offer women greater access to information and guidance to participate in maternity care decision-making. Relative to their evaluation in controlled settings, the implementation of patient decision aids in routine maternity care has received little attention and our understanding of which approaches may be effective is limited. This paper critically discusses the application of patient decision aids in routine maternity care and explores viable solutions for promoting their successful uptake. Discussion A range of patient decision aids have been developed for use within maternity care, and controlled trials have highlighted their positive impact on the decision-making process for women. Nevertheless, evidence of successful patient decision aid implementation in real world health care settings is lacking due to practical and ideological barriers that exist. Patient-directed social marketing campaigns are a relatively novel approach to patient decision aid delivery that may facilitate their adoption in maternity care, at least in the short-term, by overcoming common implementation barriers. Social marketing may also be particularly well suited to maternity care, given the unique characteristics of this health context. Conclusions The potential of social marketing campaigns to facilitate patient decision aid adoption in maternity care highlights the need for pragmatic trials to evaluate their effectiveness. Identifying which sub-groups of women are more or less likely to respond to these strategies will further direct implementation.

CYP19A1 fine-mapping and Mendelian randomization: Estradiol is causal for endometrial cancer

Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8x10(-11)). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4x10(-8)). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.

Identification of seven loci affecting mean telomere length and their association with disease

Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 x 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

NAPLAN, achievement gaps and embedding Indigenous perspectives in schooling: Disrupting the decolonial option

In 2004, the Queensland State Government rolled out the Embedding Aboriginal and Torres Strait Islander Perspectives in Schooling (EATSIPS) program. The policy was relaunched in 2009. This initiative aimed to improve Indigenous student learning outcomes, improve relationships between schools and Indigenous communities, and to develop a deeper understanding and respect for traditional and contemporary Aboriginal and Torres Strait Islander cultures amongst all students (EATSIPS 2011: 13). We are interested in the social justice possibilities of EATSIPS and its potential contribution to Reconciliation between Indigenous and non-Indigenous Australia. We are also interested in whether schooling practices informed by EAT-SIPS could reflect decolonising opportunities. This point is illustrated by the fact that, from 2009, it was mandatory for all state-school teachers to undergo professional development in EATSIPS, and all state schools underwent an EATSIPS audit of their policy, curriculum and pedagogical practices...

‘Lemon Laws’: an inquiry into consumer protections and remedies for buyers of new motor vehicles

1. Under the Terms of Reference for the Committee’s Inquiry, ‘lemons’ are defined as ‘new motor vehicles with numerous, severe defects that re-occur despite multiple repair attempts or where defects have caused a new motor vehicle to be out of service for a prolonged period of time’. Consumers are currently protected in relation to lemon purchases by the Australian Consumer Law (ACL) located in Schedule 2 of the Competition and Consumer Act 2010 (Cth) (CCA). The ACL applies as a law of Queensland pursuant to the Fair Trading Act 1989 (Qld). The voluntary recall and consumer guarantees law took effect on 1 January 2011. 2. In 2006, the Government of Victoria made a commitment to introduce a lemon law into the provisions of the then Fair Trading Act 1999 (Vic). The public consultation process on the proposal to introduce a lemon law for motor vehicle purchases in Victoria was conducted by Ms Janice Munt MP, with the assistance of Consumer Affairs Victoria (CAV). CAV released an Issues Paper to canvas with industry and the community options for the development and introduction of a motor vehicle lemon law.(Consumer Affairs Victoria, Introducing Victorian motor vehicle lemon laws, Issues Paper, (September, 2007). 3. A CAV report prepared by Janice Munt MP was released in July, 2008 (Consumer Affairs Victoria, Motor Cars: A report on the motor vehicle lemon law consultations (July 2008) (Victorian Lemon Law Report). However, the Victorian proposal was overtaken by events leading to the adoption of a uniform consumer protection law in all Australian jurisdictions, the ACL. 4. The structure of this submission is to consider first the three different bases upon which consumers can obtain relief for economic loss arising from defects in motor vehicles. The second part of the submission considers the difficulties encountered by consumers in litigating motor vehicle disputes in the courts and tribunals. The third part of the submission examines the approach taken in other jurisdictions to resolving motor vehicle disputes. The final part of the submission considers a number of possible reforms that could be made to the existing law and its enforcement to reduce consumer detriment arising from the purchase of ‘lemon’ motor vehicles. 5. There are three principal bases upon which a consumer can obtain redress for defects in new motor vehicles under the ACL. The first is where the manufacturer admits liability and initiates the voluntary recall procedure provided for in s 128 of the ACL. Under this basis the manufacturer generally repairs or replaces the part subject to the recall free of charge. The second basis is where the manufacturer or dealer denies liability and the consumer is initiates proceedings in the court or tribunal seeking a statutory remedy under the ACL, the nature of which will depend on whether the failure to comply with the consumer guarantee was major or not. The third basis upon which a consumer can obtain redress is pursuant to public enforcement by the ACCC. Each basis will be considered in this part. What all three bases have in common is the need to conduct an investigation to identify the nature of the defect and how it arose.

Bringing up Children Gran’s Way: Insights from a research project on Indigenous child and youth mental health

Background In 2000, the Mater Child and Youth Mental Health Service Indigenous consultant saw that Indigenous families were isolated from kinship networks following the assimilation policy and clinicians were largely unaware of these socio-cultural histories. Experiences of marginalisation by mainstream society and services were exacerbated by assumptions clinicians made about this population. To enhance Mater’s care the consultant undertook research with Indigenous Elders. The project, “Bringing up Children Gran’s Way”, on which the presenter is the research advisor, was funded by AIATSIS. Aims Increase service quality Improve staff confidence, skills and satisfaction working with this population Promote the wellbeing of Indigenous families Acknowledge the significance of Elders and extended family networks. Methods Over 2006/07 the team used narrative and Indigenous methodologies, (e.g. yarning circles and the use of Indigenous research staff) to arrange and audio-record structured interviews with 19 Aboriginal Elders, on growing up and parenting. The participants were recruited by the Indigenous consultant and gave written consent, following ethical approval and information giving. The team immersed themselves in the material by repeated reading of the transcripts to note recurring themes in Elders’ narratives. Findings The recurring themes included the importance of cultural protocols and extended family; impacts of being ‘under the Act and stories of surviving change; culture, spiritualty and religion; trans-generational impacts; childrearing and the need to reconcile with Elders. Discussion The narratives show Elders resilience in the face of enduring impact of policies of genocide and assimilation. Clinicians need to approach their work with a deeper understanding of the diversity of clients’ social experience and cultural identity. Clinicians need to examine their own cultural assumptions about this population. Conclusion The dissemination of the knowledge and experience of Elders is a matter of social justice and crucial for the well-being of future generations and for improved service access.

Head motion and Inattention/Hyperactivity share common genetic influences: Implications for fMRI studies of ADHD

Head motion (HM) is a well known confound in analyses of functional MRI (fMRI) data. Neuroimaging researchers therefore typically treat HM as a nuisance covariate in their analyses. Even so, it is possible that HM shares a common genetic influence with the trait of interest. Here we investigate the extent to which this relationship is due to shared genetic factors, using HM extracted from resting-state fMRI and maternal and self report measures of Inattention and Hyperactivity-Impulsivity from the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour (SWAN) scales. Our sample consisted of healthy young adult twins (N = 627 (63% females) including 95 MZ and 144 DZ twin pairs, mean age 22, who had mother-reported SWAN; N = 725 (58% females) including 101 MZ and 156 DZ pairs, mean age 25, with self reported SWAN). This design enabled us to distinguish genetic from environmental factors in the association between head movement and ADHD scales. HM was moderately correlated with maternal reports of Inattention (r = 0.17, p-value = 7.4E-5) and Hyperactivity-Impulsivity (r = 0.16, p-value = 2.9E-4), and these associations were mainly due to pleiotropic genetic factors with genetic correlations [95% CIs] of rg = 0.24 [0.02, 0.43] and rg = 0.23 [0.07, 0.39]. Correlations between self-reports and HM were not significant, due largely to increased measurement error. These results indicate that treating HM as a nuisance covariate in neuroimaging studies of ADHD will likely reduce power to detect between-group effects, as the implicit assumption of independence between HM and Inattention or Hyperactivity-Impulsivity is not warranted. The implications of this finding are problematic for fMRI studies of ADHD, as failing to apply HM correction is known to increase the likelihood of false positives. We discuss two ways to circumvent this problem: censoring the motion contaminated frames of the RS-fMRI scan or explicitly modeling the relationship between HM and Inattention or Hyperactivity-Impulsivity

Consumers' perceptions and attitudes towards firms' green marketing initiatives: How do they influence green consumption?

This thesis examines green marketing and green consumption behaviours addressing limited understandings about how consumers interpret their green consumption behaviour in their everyday lives; what motivates people to purchase green products, and what barriers exist to this behaviour. Findings reveal that enhancing green consumption through green marketing depends on consumers' enthusiasm to engage in green practices and green behavioural influences. The research supports the need for qualitative research to provide rich insights into relationships between consumer behaviour, green marketing and green consumption and builds a stronger knowledge foundation by introducing social practice theory into the marketing discipline.

Literacy leadership and accountability practices: Holding onto ethics in ways that count

Despite the rhetoric of schools serving the needs of specific communities, it is evident that the work of teachers and principals is shaped by government imperatives to demonstrate success according to a set of standard ‘benchmarks’. In this chapter, we draw from our current study of new forms of educational leadership emerging in South Australian public primary schools to explore the ways in which test-based accountability requirements are being mediated by principals in schools that serve high poverty communities. Taking an institutional ethnography approach we focus on the everyday work of a principal and a literacy leader in one suburban primary school to show the complexity of the impact of national testing on practices of literacy leadership. We elaborate on the inescapable textual framings and tasks faced by the principal and literacy leader, and those that they create and modify – such as a common literacy agreement and ‘literacy chats’ between a literacy leader and classroom teacher – in order to ‘hold on to ethics’. We argue that while leaders’ and teachers’ everyday work is regulated by ‘ruling relations’ (Smith, 1999), it is also organic and responsive to the local context. We conclude with a reflection on the important situated work that school leaders do in mediating trans-local policies that might otherwise close down possibilities for engaging ethically with students and their learning in a particular school.

The problem of simplification: Think-tanks, recipes, equity and ‘Turning around low-performing schools’

Non-government actors such as think-tanks are playing an important role in Australian policy work. As governments increasingly outsource policy work previously done by education departments and academics to these new policy actors, more think-tanks have emerged that represent a wide range of political views and ideological positions. This paper looks at the emergence of the Grattan Institute as one significant player in Australian education policy with a particular emphasis on Grattan’s report ‘Turning around low-performing schools’. Grattan exemplifies many of the facets of Barber’s ‘deliverology’, as they produce reports designed to be easily digested, simply actioned and provide reassurance that there is an answer, often through focusing on ‘what works’ recipes. ‘Turning around low-performing schools’ is a perfect example of this deliverology. However, a close analysis of the Report suggests that it contains four major problems which seriously impact its usefulness for schools and policymakers: it ignores data that may be more important in explaining the turn-around of schools, the Report is overly reliant on NAPLAN data, there are reasons to be suspicious about the evidence assembled, and finally the Report falls into a classic trap of logic—the post hoc fallacy.

Besides tracking: Simulation of RFID marketing and beyond

This paper asks a new question: how we can use RFID technology in marketing products in supermarkets and how we can measure its performance or ROI (Return-on-Investment). We try to answer the question by proposing a simulation model whereby customers become aware of other customers' real-time shopping behavior and may hence be influenced by their purchases and the levels of purchases. The proposed model is orthogonal to sales model and can have the similar effects: increase in the overall shopping volume. Managers often struggle with the prediction of ROI on purchasing such a technology, this simulation sets to provide them the answers of questions like the percentage of increase in sales given real-time purchase information to other customers. The simulation is also flexible to incorporate any given model of customers' behavior tailored to particular supermarket, settings, events or promotions. The results, although preliminary, are promising to use RFID technology for marketing products in supermarkets and provide several dimensions to look for influencing customers via feedback, real-time marketing, target advertisement and on-demand promotions. Several other parameters have been discussed including the herd behavior, fake customers, privacy, and optimality of sales-price margin and the ROI of investing in RFID technology for marketing purposes. © 2010 Springer Science+Business Media B.V.

An eroding social justice agenda: The case of physical education and health edu-business in schools

In this paper we draw on current research to explore notions of a socially just Health and Physical Education (HPE), in light of claims that a neoliberal globalisation promotes markets over the states, and a new individualism that privileges self-interest over the collective good. We also invite readers to consider United Nations Educational, Scientific and Cultural Organization’s ambition for PE in light of preliminary findings from an Australian led research project exploring national and international patterns of outsourcing HPE curricula. Data were sourced from this international research project through a mixed method approach. Each external provider engaged in four phases of research activity: (a) Web-audits, (b) Interviews with external providers, (c) Network diagrams, and (d) School partner interviews and observations. Results We use these data to pose what we believe to be three emerging lines of inquiry and challenge for a socially just school HPE within neoliberal times. In particular our data indicates that the marketization of school HPE is strengthening an emphasis on individual responsibility for personal health, elevating expectations that schools and teachers will “fill the welfare gap” and finally, influencing the nature and purchase of educative HPE programs in schools. The apparent proliferation of external providers of health work, HPE resources and services reflects the rise and pervasiveness of neoliberalism in education. We conclude that this global HPE landscape warrants attention to investigate the extent to which external providers’ resources are compatible with schooling’s educative and inclusive mandates.