A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms. �� 2013 Mechelli et al.

Caught in the act of collaboration: Students��� experiences of collective learning within a real-world design studio context

This study is an evaluation of design students��� perceptions of the benefits of collective learning in a real-world collaborative design studio. Third year students worked in inter-disciplinary teams representing architecture, interior design, landscape architecture, and industrial design. Responding to a real-world brief and in consultation with an industry partner client and early childhood education pre-service teachers, the teams were required to collectively propose a design response for a community-based child and family centre, on an iconic koala sanctuary site. Data were collected using several methods including a participatory action research method, through the form of a large analogue, collaborative jigsaw puzzle. Using a grounded theory methodology, qualitative data were thematically analysed to reveal six distinct aspects of collaboration, which positively impacted the students��� learning experience. The results of this study include recommendations for improving real world collaboration in the design studio in preparation for students��� transition into professional practice.

Pharmacology in one semester [Version 3, Semester 1, 2014]

- For use in Introductory Units/Courses to Biomedical/Science Students - For use with Allied Health Students who are taking pharmacology as a Unit/Course or a part Unit/Course

Viewing systematic reviews and meta-analysis in social research through different lenses

Systematic reviews and meta-analyses are used to combine results across studies to determine an overall effect. Meta-analysis is especially useful for combining evidence to inform social policy, but meta-analyses of applied social science research may encounter practical issues arising from the nature of the research domain. The current paper identifies potential resolutions to four issues that may be encountered in systematic reviews and meta-analyses in social research. The four issues are: scoping and targeting research questions appropriate for meta-analysis; selecting eligibility criteria where primary studies vary in research design and choice of outcome measures; dealing with inconsistent reporting in primary studies; and identifying sources of heterogeneity with multiple confounded moderators. The paper presents an overview of each issue with a review of potential resolutions, identified from similar issues encountered in meta-analysis in medical and biological sciences. The discussion aims to share and improve methodology in systematic reviews and meta-analysis by promoting cross-disciplinary communication, that is, to encourage 'viewing through different lenses'.

Targeting EMT in cancer: opportunities for pharmacological intervention

���EMT is important for embryonic development, wound healing, and placentation. ���Some cancers appear to exploit this process for increased metastatic potential. ���Therefore, this pathway is of great therapeutic interest in the treatment of cancer. The spread of cancer cells to distant organs represents a major clinical challenge in the treatment of cancer. Epithelial���mesenchymal transition (EMT) has emerged as a key regulator of metastasis in some cancers by conferring an invasive phenotype. As well as facilitating metastasis, EMT is thought to generate cancer stem cells and contribute to therapy resistance. Therefore, the EMT pathway is of great therapeutic interest in the treatment of cancer and could be targeted either to prevent tumor dissemination in patients at high risk of developing metastatic lesions or to eradicate existing metastatic cancer cells in patients with more advanced disease. In this review, we discuss approaches for the design of EMT-based therapies in cancer, summarize evidence for some of the proposed EMT targets, and review the potential advantages and pitfalls of each approach

Moffatt vortices induced by the motion of a contact line

A recent hydrodynamic theory of liquid slippage on a solid substrate (Kirkinis & Davis, Phys. Rev. Lett., vol. 110, 2013, 234503) gives rise to a sequence of eddies (Moffatt vortices) that co-move with a moving contact line (CL) in a liquid wedge. The presence of these vortices is established through secular equations that depend on the dynamic contact angle �� and capillary number Ca. The limiting case �����O is associated with the appearance of such vortices in a channel. The vortices are generated by the relative motion of the interfaces, which in turn is due to the motion of the CL. This effect has yet to be observed in experiment.

Prevalence and risk factors for oral HPV infection in young Australians

The prevalence of human papillomavirus (HPV)���associated head and neck cancers is increasing, but the prevalence of oral HPV infection in the wider community remains unknown. We sought to determine the prevalence of, and identify risk factors for, oral HPV infection in a sample of young, healthy Australians. For this study, we recruited 307 Australian university students (18���35 years). Participants reported anonymously about basic characteristics, sexual behaviour, and alcohol, tobacco and illicit drugs use. We collected oral rinse samples from all participants for HPV testing and typing. Seven of 307 (2.3%) students tested positive for oral HPV infection (3 HPV-18, one each of HPV-16, -67, -69, -90), and six of them were males (p = 0.008). Compared to HPV negative students, those with oral HPV infection were more likely to have received oral sex from more partners in their lifetime (p = 0.0004) and in the last year (p = 0.008). We found no statistically significant associations with alcohol consumption, smoking or numbers of partners for passionate kissing or sexual intercourse. In conclusion, oral HPV infection was associated with male gender and receiving oral sex in our sample of young Australians.

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children���s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child���s cognitive abilities at age twelve.

Rethinking Culture and Diversity in Early Childhood Preservice Teacher Education: Looking at Teaching and Learning Through an Interdisciplinary Lens

Early Childhood Education (ECE) has a long history of building foundations for children to achieve their full potential, enabling parents to participate in the economy while children are cared for, addressing poverty and disadvantage, and building individual, community and societal resources. In so doing, ECE has developed a set of cultural practices and ways of knowing that shape the field and the people who work within it. ECE, consequently, is frequently described as unique and special (Moss, 2006; Penn, 2011). This works to define and distinguish the field while, simultaneously, insulating it from other contexts, professions, and ideas. Recognising this dualism illuminates some of the risks and challenges of operating in an insular and isolated fashion. In the 21st century, there are new challenges for children, families and societies to which ECE must respond if it is to continue to be relevant. One major issue is how ECE contributes to transition towards more sustainable ways of living. Addressing this contemporary social problem is one from which Early Childhood teacher education has been largely absent (Davis & Elliott, 2014), despite the well recognised but often ignored role of education in contributing to sustainability. Because of its complexity, sustainability is sometimes referred to as a ���wicked problem��� (Rittel & Webber, 1973; Australian Public Service Commission, 2007) requiring alternatives to ���business as usual��� problem solving approaches. In this chapter, we propose that addressing such problems alongside disciplines other than Education enables the Early Childhood profession to have its eyes opened to new ways of thinking about our work, potentially liberating us from the limitations of our ���unique��� and idiosyncratic professional cultures. In our chapter, we focus on understandings of culture and diversity, looking to broaden these by exploring the different ���cultures��� of the specialist fields of ECE and Design (in this project, we worked with students studying Architecture, Industrial Design, Landscape Architecture and Interior Design). We define culture not as it is typically represented, i.e. in relation to ideas and customs of particular ethnic and language groups, but to the ideas and practices of people working in different disciplines and professions. We assert that different specialisms have their own ���cultural��� practices. Further, we propose that this kind of theoretical work helps us to reconsider ways in which ECE might be reframed and broadened to meet new challenges such as sustainability and as yet unknown future challenges and possibilities. We explore these matters by turning to preservice Early Childhood teacher education (in Australia) as a context in which traditional views of culture and diversity might be reconstructed. We are looking to push our specialist knowledge boundaries and to extend both preservice teachers and academics beyond their comfort zones by engaging in innovative interdisciplinary learning and teaching. We describe a case study of preservice Early Childhood teachers and designers working in collaborative teams, intersecting with a ���real-world��� business partner. The joint learning task was the design of an early learning centre based on sustainable design principles and in which early Education for Sustainability (EfS) would be embedded Data were collected via focus group and individual interviews with students in ECE and Design. Our findings suggest that interdisciplinary teaching and learning holds considerable potential in dismantling taken-for-granted cultural practices, such that professional roles and identities might be reimagined and reconfigured. We conclude the chapter with provocations challenging the ways in which culture and diversity in the field of ECE might be reconsidered within teacher education.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis. �� 2011 Macmillan Publishers Limited. All rights reserved.

Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci

To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P 10 800), we found association with SNPs in two gene deserts at 2p15 (rs10865331; combined P = 1.9 �� 10 19) and 21q22 (rs2242944; P = 8.3 �� 10 20), as well as in the genes ANTXR2 (rs4333130; P = 9.3 �� 10 8) and IL1R2 (rs2310173; P = 4.8 �� 10 7). We also replicated previously reported associations at IL23R (rs11209026; P = 9.1 �� 10 14) and ERAP1 (rs27434; P = 5.3 �� 10 12). This study reports four genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility. �� 2010 Nature America, Inc. All rights reserved.

Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990���2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refi nements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2���4 billion and 1���6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537���6 million in 1990 to 764���8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114���87 per 1000 people to 110���31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21��1% in 1990 to 31��2% in 2013. Interpretation Ageing of the world���s population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to nonfatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.

How to choose a healthy, eco-friendly childcare centre

The early years have been recognized as a ���natural starting point��� for education for sustainability. ECEfS is a newly emerging area and Australian educators, teacher educators, and researchers are leaders in this field. Indeed, there is a growing list of exemplary kindergartens, child care centres, preschools, and preps across the country engaged in EfS focusing on a range of topics that include, for example, water education, reducing energy use, recycling, growing gardens, and cleaning up parks and creeks. Some centres focus more on the social dimensions of sustainability ��� strengthening Indigenous communities, working with the elderly, supporting the unemployed, fostering gender equality in their communities, being more socially inclusive. There is mounting evidence that early lessons in sustainability help reshape adult sustainability actions in homes, schools and communities.

Valuing Indigenous heritage through multimodal literacy

The study on which this presentation is based focuses on the particular ways in which students��� counter-narratives about race were embedded in multimodal and digital design in the development of a digital cultural heritage. The multimodal texts were analysed as a site for students��� views of Indigenous oppression in relation to the colonial powers and ownership of the land in Australian history. In this presentation, Kathy will demonstrate how pedagogies that explore counter-narratives of cultural heritage in the official curriculum can encourage students to reframe their own racial identity, while challenging dominant white, historical narratives of colonial conquest, race, and power. In the second part of this session, Indigenous Principal, John Davis and teachers from HymbaYumba Community Hub will provide a school-based, Indigenous panel to inspire educators with authentic ways to embed Indigenous knowledge in the curriculum.

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.