Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders

The impact that stressful encounters have upon long-lasting behavioural phenotypes is varied. Whereas a significant proportion of the population will develop "stress-related" conditions such as post-traumatic stress disorder or depression in later life, the majority are considered "resilient" and are able to cope with stress and avoid such psychopathologies. The reason for this heterogeneity is undoubtedly multi-factorial, involving a complex interplay between genetic and environmental factors. Both genes and environment are of critical importance when it comes to developmental processes, and it appears that subtle differences in either of these may be responsible for altering developmental trajectories that confer vulnerability or resilience. At the molecular level, developmental processes are regulated by epigenetic mechanisms, with recent clinical and pre-clinical data obtained by ourselves and others suggesting that epigenetic differences in various regions of the brain are associated with a range of psychiatric disorders, including many that are stress-related. Here we provide an overview of how these epigenetic differences, and hence susceptibility to psychiatric disorders, might arise through exposure to stress-related factors during critical periods of development.

Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300

It is well established that the coordinated regulation of activity-dependent gene expression by the histone acetyltransferase (HAT) family of transcriptional coactivators is crucial for the formation of contextual fear and spatial memory, and for hippocampal synaptic plasticity. However, no studies have examined the role of this epigenetic mechanism within the infralimbic prefrontal cortex (ILPFC), an area of the brain that is essential for the formation and consolidation of fear extinction memory. Here we report that a postextinction training infusion of a combined p300/CBP inhibitor (Lys-CoA-Tat), directly into the ILPFC, enhances fear extinction memory in mice. Our results also demonstrate that the HAT p300 is highly expressed within pyramidal neurons of the ILPFC and that the small-molecule p300-specific inhibitor (C646) infused into the ILPFC immediately after weak extinction training enhances the consolidation of fear extinction memory. C646 infused 6 h after extinction had no effect on fear extinction memory, nor did an immediate postextinction training infusion into the prelimbic prefrontal cortex. Consistent with the behavioral findings, inhibition of p300 activity within the ILPFC facilitated long-term potentiation (LTP) under stimulation conditions that do not evoke long-lasting LTP. These data suggest that one function of p300 activity within the ILPFC is to constrain synaptic plasticity, and that a reduction in the function of this HAT is required for the formation of fear extinction memory.

Assessment of cone beam CT registration for prostate radiation therapy : fiducial marker and soft tissue methods

Introduction This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCTFM) and the soft tissue prostate (CBCTST). Methods Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCTFM and CBCTST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland–Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoAmean) were defined as ±2.0 mm for CBCTFM and ±3.0 mm for CBCTST. Differences between CBCTST alignment and the observer-averaged CBCTFM (AvCBCTFM) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCTST and AvCBCTFM. Results CBCTFM and CBCTST alignments were performed for 185 images. The CBCTFM 95% LoAmean were within ±2.0 mm in all planes. CBCTST 95% LoAmean were within ±3.0 mm in all planes. Comparison of CBCTST with AvCBCTFM resulted in 95% LoA of −4.9 to 2.6, −1.6 to 2.5 and −4.7 to 1.9 mm in the superior–inferior, left–right and anterior–posterior planes, respectively. Conclusions Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy.

Revisiting the adoption of innovative products on Australian road infrastructure projects

Construction product innovation can exert a positive influence on project and industry performance. However, guidance is scarce on product innovation diffusion for road infrastructure, in contrast to the large body of literature on the manufacturing industry. A conceptual framework is proposed to understand these processes. Advice is given to managers based on the framework and a large quantitative survey. The framework focuses on contextual characteristics that influence the decision to adopt new-to-industry product innovation, as part of a diffusion process. Case study data are interpreted within the revised framework to test its value and disaggregate the broad obstacles to innovation. A large quantitative survey was then conducted to rank the relative importance of the obstacles constraining the adoption of innovative products on road construction projects. The three most important obstacles were found to be: (1) overemphasis on up-front project costs during tender stage; (2) disagreement over who carries the risk of new product failure; and (3) adversarial contract relations. The results suggest refinements to the conceptual framework to make it a more powerful tool for categorizing and analysing construction innovation obstacles. Results also suggest well-resourced repeat interactions within complementary procurement and regulatory systems will enhance the project teams’ ability to recognize and address innovation obstacles. Further, improved relationships are expected to decrease the need for an overly conservative approach to product approval and prescriptive specifications.

Simultaneous localization and planning on multiple map hypotheses

This paper presents a novel method to rank map hypotheses by the quality of localization they afford. The highest ranked hypothesis at any moment becomes the active representation that is used to guide the robot to its goal location. A single static representation is insufficient for navigation in dynamic environments where paths can be blocked periodically, a common scenario which poses significant challenges for typical planners. In our approach we simultaneously rank multiple map hypotheses by the influence that localization in each of them has on locally accurate odometry. This is done online for the current locally accurate window by formulating a factor graph of odometry relaxed by localization constraints. Comparison of the resulting perturbed odometry of each hypothesis with the original odometry yields a score that can be used to rank map hypotheses by their utility. We deploy the proposed approach on a real robot navigating a structurally noisy office environment. The configuration of the environment is physically altered outside the robots sensory horizon during navigation tasks to demonstrate the proposed approach of hypothesis selection.

Corporate Environmental and Economic Performance of Japanese Manufacturing Firms: Empirical Study for Sustainable Development

This study examines the relationship between environmental performance and economic performance in Japanese manufacturing firms. The environmental performance indicators include CO2 emissions and the aggregate toxic risk associated with chemical emissions relative to sales. Return on assets (ROA) is used as an indicator of economic performance. We demonstrate that there is a significant inverted U-shaped relationship between ROA and environmental performance calculated by aggregated toxic risk. We also find that the environmental performance increases ROA through both returns on sales and improved capital turnover. However, we observe a significant positive relationship between financial performance and environmental performance based on CO2 emissions. These findings may provide evidence for the consequences of firms' environmental behavior and sustainable development. © 2012 John Wiley & Sons, Ltd and ERP Environment.

What is the apparent angle of a Kelvin ship wave pattern?

While the half-angle which encloses a Kelvin ship wave pattern is commonly accepted to be 19.47 degrees, recent observations and calculations for sufficiently fast-moving ships suggest that the apparent wake angle decreases with ship speed. One explanation for this decrease in angle relies on the assumption that a ship cannot generate wavelengths much greater than its hull length. An alternative interpretation is that the wave pattern that is observed in practice is defined by the location of the highest peaks; for wakes created by sufficiently fast-moving objects, these highest peaks no longer lie on the outermost divergent waves, resulting in a smaller apparent angle. In this paper, we focus on the problems of free surface flow past a single submerged point source and past a submerged source doublet. In the linear version of these problems, we measure the apparent wake angle formed by the highest peaks, and observe the following three regimes: a small Froude number pattern, in which the divergent waves are not visible; standard wave patterns for which the maximum peaks occur on the outermost divergent waves; and a third regime in which the highest peaks form a V-shape with an angle much less than the Kelvin angle. For nonlinear flows, we demonstrate that nonlinearity has the effect of increasing the apparent wake angle so that some highly nonlinear solutions have apparent wake angles that are greater than Kelvin's angle. For large Froude numbers, the effect on apparent wake angle can be more dramatic, with the possibility of strong nonlinearity shifting the wave pattern from the third regime to the second. We expect our nonlinear results will translate to other more complicated flow configurations, such as flow due to a steadily moving closed body such as a submarine.

Evaluation of assessment in the context of work-based learning: Qualitative perspectives of new graduates

Aim Evaluation or assessment of competence is an important step to ensure the safety and efficacy of health professionals, including dietitians. Most competency-based assessment studies are focussed on valid and reliable methods of assessment for the preparation of entry-level dietitians, few papers have explored student dietitians’ perceptions of these evaluations. This study aimed to explore the perceptions of recent graduates from accredited nutrition and dietetics training programs in Australia. It also aimed to establish the relevance of competency-based assessment to adequately prepare them for entry-level work roles. Methods A purposive sample of newly-graduated dietitians with a range of assessment experiences and varied employment areas was recruited. A qualitative approach, using in-depth interviews with 13 graduates, with differing assessment experiences was undertaken. Graduates were asked to reflect upon their competency-based assessment experiences whilst a student. Data was thematically analysed by multiple authors. Results Four themes emerged from the data analysis: (i) Transparency and consistency are critical elements of work-based competency assessment. (ii) Students are willing to take greater responsibility in their assessment process. (iii) Work-based competency assessment prepares students for employment. (iv) The relationship between students and their assessors can impact on the student experience and their assessment performance. Conclusions Understanding this unique perspective of students can improve evaluation of future health professionals and assist in designing valid competency-based assessment approaches.

Stop-signal task difficulty and the right inferior frontal gyrus

The stop-signal paradigm is increasingly being used as a probe of response inhibition in basic and clinical neuroimaging research. The critical feature of this task is that a cued response is countermanded by a secondary ‘stop-signal’ stimulus offset from the first by a ‘stop-signal delay’. Here we explored the role of task difficulty in the stop-signal task with the hypothesis that what is critical for successful inhibition is the time available for stopping, that we define as the difference between stop-signal onset and the expected response time (approximated by reaction time from previous trial). We also used functional magnetic resonance imaging (fMRI) to examine how the time available for stopping affects activity in the putative right inferior frontal gyrus and presupplementary motor area (right IFG-preSMA) network that is known to support stopping. While undergoing fMRI scanning, participants performed a stop-signal variant where the time available for stopping was kept approximately constant across participants, which enabled us to compare how the time available for stopping affected stop-signal task difficulty both within and between subjects. Importantly, all behavioural and neuroimaging data were consistent with previous findings. We found that the time available for stopping distinguished successful from unsuccessful inhibition trials, was independent of stop-signal delay, and affected successful inhibition depending upon individual SSRT. We also found that right IFG and adjacent anterior insula were more strongly activated during more difficult stopping. These findings may have critical implications for stop-signal studies that compare different patient or other groups using fixed stop-signal delays.

The knowledge: a project by Boxcopy at Post-Museum, Singapore

‘The Knowledge’ was part of the Next Wave/Asialink project 'Invisible Structures: Australian artist collectives in Tokyo, Singapore and Yogyakarta' in January 2011. For this project, Brisbane ARI Boxcopy undertook a two-week residency at Post Musuem in Singapore. In this project, the Boxcopy artists Channon Goodwin, Joseph Breikers, Timothy P Kerr, Daniel McKewen, Raymonde Rajkowski, Tim Woodward, attempted to acquire an intimate knowledge of the city of Singapore by forming a free delivery company, The Boxcopy Publics Carriage Office of Singapore (BPCOS), which provided services around the city by foot, bike and public transport. In addition to committing to memory and documenting the streets and sites of Singapore, the BPCOS team also performed tasks such as delivering goods or messages, travel a particular route or visit a site, as requested by the people of Singapore. The project comprised this process of public interaction as well as an exhibition and website.