Identifying candidate gene effects by restricting search space in a multivariate genetic analysis of white matter microstructure

Several genetic variants are thought to influence white matter (WM) integrity, measured with diffusion tensor imaging (DTI). Voxel based methods can test genetic associations, but heavy multiple comparisons corrections are required to adjust for searching the whole brain and for all genetic variants analyzed. Thus, genetic associations are hard to detect even in large studies. Using a recently developed multi-SNP analysis, we examined the joint predictive power of a group of 18 cholesterol-related single nucleotide polymorphisms (SNPs) on WM integrity, measured by fractional anisotropy. To boost power, we limited the analysis to brain voxels that showed significant associations with total serum cholesterol levels. From this space, we identified two genes with effects that replicated in individual voxel-wise analyses of the whole brain. Multivariate analyses of genetic variants on a reduced anatomical search space may help to identify SNPs with strongest effects on the brain from a broad panel of genes.

The good student: Subjectivities, power and schooling

Schools are places where student subjectivities are negotiated and contested in a variety of spaces. This paper argues that schools organise the possibilities for student subjectivities through a set of discourses that construct idealised notions of the good student. Whilst some discourses occur across educational sites, in practice these sets of discourses construct a unique vision of the good student in each specific school site. This vision is articulated in a variety of ways in each school, however, the result is that each student is enmeshed within a complex nexus of power relations that they can contest, negotiate or accept. Most of the time, students engage in a swirling set of subjectivities that encompasses these possibilities in various ways at various times. This paper problematises commonsense notions of the good student at one school site. One intent is to give voice to the lived experience of students who find themselves the site of these technologies of power. These technologies construct a set of commonsense expectations of schools - amongst which is the desire to produce the good student. Another is to use a Foucaultean analysis that rejects the good/bad binary that underpins many commonsense understandings of what students should be.

A decision-analysis-based framework for analysing stakeholder behaviour in scenario planning

Scenario planning is a method widely used by strategic planners to address uncertainty about the future. However, current methods either fail to address the future behaviour and impact of stakeholders or they treat the role of stakeholders informally. We present a practical decision-analysis-based methodology for analysing stakeholder objectives and likely behaviour within contested unfolding futures. We address issues of power, interest, and commitment to achieve desired outcomes across a broad stakeholder constituency. Drawing on frameworks for corporate social responsibility (CSR), we provide an illustrative example of our approach to analyse a complex contested issue that crosses geographic, organisational and cultural boundaries. Whilst strategies can be developed by individual organisations that consider the interests of others – for example in consideration of an organisation's CSR agenda – we show that our augmentation of scenario method provides a further, nuanced, analysis of the power and objectives of all concerned stakeholders across a variety of unfolding futures. The resulting modelling framework is intended to yield insights and hence more informed decision making by individual stakeholders or regulators.

Generating benefits and negotiating tensions through an international doctoral forum: A sociological analysis

Workshops and seminars are widely-used forms of doctoral training. However, research with a particular focus on these forms of doctoral training is sporadic in the literature. There is no, if any, such research concerning the international context and participants’ own voices. Mindful of these lacunae in the literature, we write the current paper as a group of participants in one of a series of doctoral forums co-organised annually by Beijing Normal University, China and Queensland University of Technology, Australia. The paper voices our own experiences of participation in the doctoral forum. Data were drawn from reflections, journals, and group discussions of all 12 student and academic participants. These qualitative data were organised and analysed through Bourdieu’s notions of capital and field. Findings indicate that the doctoral forum created enabling and challenging social fields where participants accrued and exchanged various forms of capital and negotiated transient and complex power relations. In this respect, the sociological framework used provides a distinctive theoretical tool to conceptualise and analyse the benefits and tensions of participation in the doctoral forum. Knowledge built and lessons learned through our paper will provide implications and recommendations for future planning of, and participation in, the doctoral forum series and similar activities elsewhere.

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.

Laser capture microdissection and multiplex-tandem PCR analysis of proximal tubular epithelial cell signaling in human kidney disease

Interstitial fibrosis, a histological process common to many kidney diseases, is the precursor state to end stage kidney disease, a devastating and costly outcome for the patient and the health system. Fibrosis is historically associated with chronic kidney disease (CKD) but emerging evidence is now linking many forms of acute kidney disease (AKD) with the development of CKD. Indeed, we and others have observed at least some degree of fibrosis in up to 50% of clinically defined cases of AKD. Epithelial cells of the proximal tubule (PTEC) are central in the development of kidney interstitial fibrosis. We combine the novel techniques of laser capture microdissection and multiplex-tandem PCR to identify and quantitate “real time” gene transcription profiles of purified PTEC isolated from human kidney biopsies that describe signaling pathways associated with this pathological fibrotic process. Our results: (i) confirm previous in-vitro and animal model studies; kidney injury molecule-1 is up-regulated in patients with acute tubular injury, inflammation, neutrophil infiltration and a range of chronic disease diagnoses, (ii) provide data to inform treatment; complement component 3 expression correlates with inflammation and acute tubular injury, (iii) identify potential new biomarkers; proline 4-hydroxylase transcription is down-regulated and vimentin is up-regulated across kidney diseases, (iv) describe previously unrecognized feedback mechanisms within PTEC; Smad-3 is down-regulated in many kidney diseases suggesting a possible negative feedback loop for TGF-β in the disease state, whilst tight junction protein-1 is up-regulated in many kidney diseases, suggesting feedback interactions with vimentin expression. These data demonstrate that the combined techniques of laser capture microdissection and multiplex-tandem PCR have the power to study molecular signaling within single cell populations derived from clinically sourced tissue.

Data driven modeling for power transformer lifespan evaluation

Large sized power transformers are important parts of the power supply chain. These very critical networks of engineering assets are an essential base of a nation’s energy resource infrastructure. This research identifies the key factors influencing transformer normal operating conditions and predicts the asset management lifespan. Engineering asset research has developed few lifespan forecasting methods combining real-time monitoring solutions for transformer maintenance and replacement. Utilizing the rich data source from a remote terminal unit (RTU) system for sensor-data driven analysis, this research develops an innovative real-time lifespan forecasting approach applying logistic regression based on the Weibull distribution. The methodology and the implementation prototype are verified using a data series from 161 kV transformers to evaluate the efficiency and accuracy for energy sector applications. The asset stakeholders and suppliers significantly benefit from the real-time power transformer lifespan evaluation for maintenance and replacement decision support.