Evaluation of polymorphisms in predicted target sites for micro RNAs differentially expressed in endometriosis

Previous microarray analyses identified 22 microRNAs (miRNAs) differentially expressed in paired ectopic and eutopic endometrium of women with and without endometriosis. To investigate further the role of these miRNAs in women with endometriosis, we conducted an association study aiming to explore the relationship between endometriosis risk and single-nucleotide polymorphisms (SNPs) in miRNA target sites for these differentially expressed miRNAs. A panel of 102 SNPs in the predicted miRNA binding sites were evaluated for an endometriosis association study and an ingenuity pathway analysis was performed. Fourteen rare variants were identified in this study. We found SNP rs14647 in the Wolf-Hirschhorn syndrome candidate gene1 (WHSC1) 3'UTR (untranslated region) was associated with endometriosis-related infertility presenting an odds ratio of 12.2 (95% confidence interval = 2.4-60.7, P = 9.03 x 10(-5)). SNP haplotype AGG in the solute carrier family 22, member 23 (SLC22A23) 3'UTR was associated with endometriosis-related infertility and more severe disease. With the individual genotyping data, ingenuity pathways analysis identified the tumour necrosis factor and cyclin-dependant kinase inhibitor as major factors in the molecular pathways. Significant associations between WHSC1 alleles and endometriosis-related infertility and SLC22A23 haplotypes and the disease severe stage were identified. These findings may help focus future research on subphenotypes of this disease. Replication studies in independent large sample sets to confirm and characterize the involvement of the gene variation in the pathogenesis of endometriosis are needed.

Social Audit Regulation Within the NGO Sector: Practices of NGOs Operating in Bangladesh and Indonesia

Social audit is one of those important mechanisms for strengthening NGOs’ accountability to poor communities (as NGOs’ key beneficiaries). However, conducting social audits within the NGO sector often rests on the individual interests and priorities of donors or NGOs themselves, effectively resulting in self-selection bias, and limiting the effectiveness and usefulness of social audits as a control and evaluation mechanism. The purpose of this chapter is to identify the prevalence, scale, and scope of social audits within the NGO sector, particularly NGOs engaging in microenterprise development programs. Accordingly, this study examined 20 NGOs operating in two countries - Bangladesh and Indonesia. Data were collected from publicly available sources and in-depth interviews with senior executives of the participating NGOs. Further, 10 interviews were conducted with a small sample of beneficiaries (individuals or groups from four of the participating NGOs) in order to gain an understanding of beneficiaries’ perceptions of the NGOs’ social audit mechanism. The findings reveal a range of approaches to social audit among NGOs, as well as the usefulness and limitations of this mechanism for strengthening NGO accountability, particularly to beneficiaries. Findings highlight that within the NGOs investigated the conduct of social audits remained voluntary and was strongly dependant on donors’ requirements. As social audit regulation within the NGO sector is minimal, the findings provide regulators with valuable guidance for better understanding the value of social audit as a mechanism to strengthen accountability of the NGO sector, particularly accountability to beneficiaries.

Common genetic influences underlie comorbidity of migraine and endometriosis

We examined the co-occurrence of migraine and endometriosis within the largest known collection of families containing multiple women with surgically confirmed endometriosis and in an independent sample of 815 monozygotic and 457 dizygotic female twin pairs. Within the endometriosis families, a significantly increased risk of migrainous headache was observed in women with endometriosis compared to women without endometriosis (odds ratio [OR] 1.57, 95% confidence interval [CI]: 1.12-2.21, P=0.009). Bivariate heritability analyses indicated no evidence for common environmental factors influencing either migraine or endometriosis but significant genetic components for both traits, with heritability estimates of 69 and 49%, respectively. Importantly, a significant additive genetic correlation (r(G) = 0.27, 95% CI: 0.06-0.47) and bivariate heritability (h(2)=0.17, 95% CI: 0.08-0.27) was observed between migraine and endometriosis. Controlling for the personality trait neuroticism made little impact on this association. These results confirm the previously reported comorbidity between migraine and endometriosis and indicate common genetic influences completely explain their co-occurrence within individuals. Given pharmacological treatments for endometriosis typically target hormonal pathways and a number of findings provide support for a relationship between hormonal variations and migraine, hormone-related genes and pathways are highly plausible candidates for both migraine and endometriosis. Therefore, taking into account the status of both migraine and endometriosis may provide a novel opportunity to identify the genes underlying them. Finally, we propose that the analysis of such genetically correlated comorbid traits can increase power to detect genetic risk loci through the use of more specific, homogenous and heritable phenotypes.

Drivers' ability to absorb information from co-located signs along motorways

The paper presents initial findings from an Austroads funded project NT1782 Ability to Absorb Information through Electronic and Static Signs. The paper aims to investigate how easily messages displayed on co-located signs can be absorbed, and if drivers can absorb messages and take appropriate action without any adverse impact on the safety and efficiency of driving. Co-location of three types of signs under motorway conditions was investigated: direction signs (DS), variable message signs (VMS) and variable speed limits/lane control signs (VSL/LCS). The authors reviewed global wide practices and research evidence on different types of sign co-locations. It was found that dual co-location of VSL/LCS, VMS and/or DS is a practical arrangement which has been widely practised overseas and in Australia. Triple co-location of VSL/LCS, VMS and DS is also practised overseas but is still new to the Australian driving community. The NT1782 project also employed an advanced driving simulator (ADS) to further investigate the possible impacts of sign co-location on drivers’ responses in an emergency situation and there were no obviously adverse impacts have been identified from the ADS study. The authors consolidated all findings and concluded that although there is no clear evidence showing that triple co-location gives rise to riskier behaviour, this proposition should be viewed with caution. Further evaluation of triple co-location in a real-life setting is called for.

Corporate Social Responsibility (CSR) in junior and mid-tier Australian resources companies operating in developing nations - beyond the public relations offensive

NIt is now widely accepted that corporations have a responsibility to benefit society, as well as generate profit. This study used institutional theory to explore how the complex and contested notion of corporate social responsibility is understood and practiced by junior and mid-tier Australian resources companies operating in the world's most impoverished countries. The study found that CSR meaning and practice in this large but little researched group of companies was shaped by complex pressures at the global, industry, organisational and individual levels. Importantly, the study also revealed striking contradictions and ambiguities between participants' CSR aspirations and their actions and accountability.

Parents as co-researchers at home: Using an observational method to document young children’s use of technology

This paper discusses the use of observational video recordings to document young children’s use of technology in their homes. Although observational research practices have been used for decades, often with video-based techniques, the participant group in this study (i.e., very young children) and the setting (i.e., private homes), provide a rich space for exploring the benefits and limitations of qualitative observation. The data gathered in this study point to a number of key decisions and issues that researchers must face in designing observational research, particularly where non-researchers (in this case, parents) act as surrogates for the researcher at the data collection stage. The involvement of parents and children as research videographers in the home resulted in very rich and detailed data about children’s use of technology in their daily lives. However, limitations noted in the dataset (e.g., image quality) provide important guidance for researchers developing projects using similar methods in future. The paper provides recommendations for future observational designs in similar settings and/or with similar participant groups.

Creating the reasonable adventurer: The co-evolution of student and learning environment

Purpose: This paper seeks to address the issue of how are graduate skills developed. The focus is not on which skills, but rather what type of learning environments is required within Higher Education to support the development of skills valued and demanded by SMEs within Australia. Approach: This paper takes a step back to consider the underlying issue of how an individual student's habits of thought are altered. In doing so, the past works of Morgan, Dewey, Whitehead, and Tyler are synthesized with the modern work of Baxter Magolda, Heath, and Biggs. Findings: It is argued that that without the development of a student-centred learning environment, most graduates will not develop the types of skills demanded by SMEs in a meaningfully way. That the failure to treat knowledge and skills as equal drivers of curriculum design will result in an imbalance that relegates skill development to a secondary learning outcome. Practical Implications: By removing the distraction of what skills should be developed, a clearer focus is possible regarding how educators should assist students to develop a broad array of generic graduate skills. From this perspective, skills can be viewed as an essential element of the educational process, rather than a new element that must be squeezed in between content. Value of Paper: This paper extends recent discussion of skills development through the use of an evolutionary perspective. Viewed as a process of creating social change, education becomes increasingly connected to a world that lays beyond institutional boundaries, thus promoting the notion of developing graduates for the world that awaits them.

The first cut is the deepest: Repeated interactions of co-authorship and academic productivity in Nobel laureate teams

Despite much in-depth investigation of factors influencing the co-authorship evolution in various scientific fields, our knowledge about how efficiency or creativity is linked to the longevity of collaborative relationships remains very limited. We explore what Nobel laureates’ co-authorship patterns reveal about the nature of scientific collaborations looking at the intensity and success of scientific collaborations across fields and across laureates’ collaborative lifecycles in physics, chemistry, and physiology/medicine. We find that more collaboration with the same researcher is actually no better for advancing creativity: publications produced early in a sequence of repeated collaborations with a given coauthor tend to be published better and cited more than papers that come later in the collaboration with the same coauthor. Our results indicate that scientific collaboration involves conceptual complementarities that may erode over a sequence of repeated interactions.

A systematic review of instruments for assessment of capacity in activities of daily living in children with developmental co-ordination disorder

Children with developmental co-ordination disorder (DCD) face evident motor difficulties in activities of daily living (ADL). Assessment of their capacity in ADL is essential for diagnosis and intervention, in order to limit the daily consequences of the disorder. The aim of this study is to systematically review potential instruments for standardized and objective assessment of children's capacity in ADL, suited for children with DCD. As a first step, databases of MEDLINE, EMBASE, CINAHL and PsycINFO were searched to identify studies that described instruments with potential for assessment of capacity in ADL. Second, instruments were included for review when two independent reviewers agreed that the instruments: (1) are standardized and objective; (2) assess at activity level and comprise items that reflect ADL, and; (3) are applicable to school-aged children that can move independently. Out of 1507 publications, 66 publications were selected, describing 39 instruments. Seven of these instruments were found to fulfil the criteria and were included for review: the Bruininks-Oseretsky Test of Motor Performance-2 (BOT2); the Do-Eat (Do-Eat); the Movement Assessment Battery for Children-2 (MABC2); the school-Assessment of Motor and Process Skills (schoolAMPS); the Tuffts Assessment of Motor Performance (TAMP); the Test of Gross Motor Development (TGMD); and the Functional Independence Measure for Children (WeeFIM). As a third step, for the included instruments, suitability for children with DCD was discussed based on the ADL comprised, ecological validity and other psychometric properties. We concluded that current instruments do not provide comprehensive and ecologically valid assessment of capacity in ADL as required for children with DCD.

Participatory media and 'co-creative' storytelling

Distinguishing critical participatory media from other participatory media forms (for example user-generated content and social media) may be increasingly difficult to do, but nonetheless remains an important task if media studies is to remain relevant to the continuing development of inclusive social political and media cultures. This was one of a number of the premises for a national Australian Research Council-funded study that set out to improve the visibility of critical participatory media, and understand its use for facilitating media participation on a population wide basis (Spurgeon et. al. 2015). The term ‘co-creative’ media was adopted to make this distinction and to describe an informal system of critical participatory media practice that is situated between major public, Indigenous and community arts, culture and media sectors. Although the co-creative media system is found to be a site of innovation and engine for social change its value is still not fully understood. For this reason, this system continues to provide media and cultural studies scholars with valuable sites for researching the sociocultural transformations afforded by new media and communication technologies, as well as their limitations.

Complimentary collaborations: Teachers and researchers co-developing best practices in art education

Australia is currently experiencing a huge cultural shift as it moves from a State-based curriculum, to a national education system. The Australian State-based bodies that currently manage teacher registration, teacher education course accreditation, curriculum frameworks and syllabi are often complex organisations that hold conflicting ideologies about education and teaching. The development of a centralised system, complete with a single accreditation body and a national curriculum can be seen as a reaction to this complexity. At the time of writing, the Australian Curriculum is being rolled out in staggered phases across the states and territories of Australia. Phase one has been implemented, introducing English, Mathematics, History and Science. Subsequent phases (Humanities and Social Sciences, the Arts, Technologies, Health and Physical Education, Languages, and year 9-10 work studies) are intended to follow. Forcing an educational shift of this magnitude is no simple task; not least because the States and Territories have and continue to demonstrate varying levels of resistance to winding down their own curricula in favour of new content with its unfamiliar expectations and organisations. The full implementation process is currently far from over, and far from being fully resolved. The Federal Government has initiated a number of strategies to progress the implementation, such as the development of the Australian Institute for Teaching and School Leadership (AITSL) to aid professional educators to implement the new curriculum. AITSL worked with professional and peak specialist bodies to develop Illustrations of Practice (hereafter IoP) for teachers to access and utilise. This paper tells of the building of one IoP, where a graduate teacher and a university lecturer collaborated to construct ideas and strategies to deliver visual arts lessons to early childhood students in a low Socio- Economic Status [SES] regional setting and discusses the experience in terms of its potential for professional learning in art education.

Uncertainty based online planning for UAV target finding in cluttered and GPS-denied environments

There are some scenarios in which Unmmaned Aerial Vehicle (UAV) navigation becomes a challenge due to the occlusion of GPS systems signal, the presence of obstacles and constraints in the space in which a UAV operates. An additional challenge is presented when a target whose location is unknown must be found within a confined space. In this paper we present a UAV navigation and target finding mission, modelled as a Partially Observable Markov Decision Process (POMDP) using a state-of-the-art online solver in a real scenario using a low cost commercial multi rotor UAV and a modular system architecture running under the Robotic Operative System (ROS). Using POMDP has several advantages to conventional approaches as they take into account uncertainties in sensor information. We present a framework for testing the mission with simulation tests and real flight tests in which we model the system dynamics and motion and perception uncertainties. The system uses a quad-copter aircraft with an board downwards looking camera without the need of GPS systems while avoiding obstacles within a confined area. Results indicate that the system has 100% success rate in simulation and 80% rate during flight test for finding targets located at different locations.

Co-distribution and co-infection of chikungunya and dengue viruses

BACKGROUND Chikungunya and dengue infections are spatio-temporally related. The current review aims to determine the geographic limits of chikungunya, dengue and the principal mosquito vectors for both viruses and to synthesise current epidemiological understanding of their co-distribution. METHODS Three biomedical databases (PubMed, Scopus and Web of Science) were searched from their inception until May 2015 for studies that reported concurrent detection of chikungunya and dengue viruses in the same patient. Additionally, data from WHO, CDC and Healthmap alerts were extracted to create up-to-date global distribution maps for both dengue and chikungunya. RESULTS Evidence for chikungunya-dengue co-infection has been found in Angola, Gabon, India, Madagascar, Malaysia, Myanmar, Nigeria, Saint Martin, Singapore, Sri Lanka, Tanzania, Thailand and Yemen; these constitute only 13 out of the 98 countries/territories where both chikungunya and dengue epidemic/endemic transmission have been reported. CONCLUSIONS Understanding the true extent of chikungunya-dengue co-infection is hampered by current diagnosis largely based on their similar symptoms. Heightened awareness of chikungunya among the public and public health practitioners in the advent of the ongoing outbreak in the Americas can be expected to improve diagnostic rigour. Maps generated from the newly compiled lists of the geographic distribution of both pathogens and vectors represent the current geographical limits of chikungunya and dengue, as well as the countries/territories at risk of future incursion by both viruses. These describe regions of co-endemicity in which lab-based diagnosis of suspected cases is of higher priority.

Identification of a novel FGFRL1 MicroRNA target site polymorphism for bone mineral density in meta-analyses of genome-wide association studies

MicroRNAs (miRNAs) are critical post-transcriptional regulators. Based on a previous genome-wide association (GWA) scan, we conducted a polymorphism in microRNAs' Target Sites (poly-miRTS)-centric multistage meta-analysis for lumbar spine (LS)-, total hip (HIP)-, and femoral neck (FN)-bone mineral density (BMD). In stage I, 41,102 poly-miRTSs were meta-analyzed in 7 cohorts with a genome-wide significance (GWS) α=0.05/41,102=1.22×10-6. By applying α=5×10-5 (suggestive significance), 11 poly-miRTSs were selected, with FGFRL1 rs4647940 and PRR5 rs3213550 as top signals for FN-BMD (P-value=7.67×10-6 and 1.58×10-5) in gender-combined sample. In stage II in silico replication (two cohorts), FGFRL1 rs4647940 was the only signal marginally replicated for FN-BMD (P-value=5.08×10-3) at α=0.10/11=9.09×10-3. PRR5 rs3213550 was also selected based on biological significance. In stage III de novo genotyping replication (two cohorts), FGFRL1 rs4647940 was the only signal significantly replicated for FN-BMD (P-value=7.55×10-6) at α=0.05/2=0.025 in gender-combined sample. Aggregating three stages, FGFRL1 rs4647940 was the single stage I-discovered and stages II- and III-replicated signal attaining GWS for FN-BMD (P-value=8.87×10-12). Dual-luciferase reporter assays demonstrated that FGFRL1 3' untranslated region harboring rs4647940 appears to be hsa-miR-140-5p's target site. In a zebrafish microinjection experiment, dre-miR-140-5p is shown to exert a dramatic impact on craniofacial skeleton formation. Taken together, we provided functional evidence for a novel FGFRL1 poly-miRTS rs4647940 in a previously known 4p16.3 locus, and experimental and clinical genetics studies have shown both FGFRL1 and hsa-miR-140-5p are important for bone formation. © The Author 2015. Published by Oxford University Press. All rights reserved.

LRP5 regulates human body fat distribution by modulating adipose progenitor biology in a dose- and depot-specific fashion

Summary Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired β-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/β-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders. © 2015 The Authors.