Quantitative Trait Loci for CD4:CD8 Lymphocyte Ratio Are Associated with Risk of Type 1 Diabetes and HIV-1 Immune Control

Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We tested 2.3 million variants for association with five lymphocyte subsets, measured in 2538 individuals from the general population, including CD4+ T cells, CD8+ T cells, CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We identified two regions of strong association. The first was located in the major histocompatibility complex (MHC), with multiple SNPs strongly associated with CD4:CD8 ratio (rs2524054, p = 2.1 × 10−28). The second region was centered within a cluster of genes from the Schlafen family and was associated with NK cell levels (rs1838149, p = 6.1 × 10−14). The MHC association with CD4:CD8 replicated convincingly (p = 1.4 × 10−9) in an independent panel of 988 individuals. Conditional analyses indicate that there are two major independent quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one is located in the class I cluster and influences CD8 levels, whereas the second is located in the class II cluster and regulates CD4 levels. Jointly, both QTL explained 8% of the variance in CD4:CD8 ratio. The class I variants are also strongly associated with durable host control of HIV, and class II variants are associated with type-1 diabetes, suggesting that genetic variation at the MHC may predispose one to immune-related diseases partly through disregulation of T cell homeostasis.

Variation in the walking time to bus stop by the degree of transit captivity

Measures of transit accessibility are important in evaluating transit services, planning for future services and investment on land use development. Existing tools measure transit accessibility using averaged walking distance or walking time to public transit. Although the mode captivity may have significant implications on one’s willingness to walk to use public transit, this has not been addressed in the literature to date. Failed to distinguish transit captive users may lead to overestimated ridership and spatial coverage of transit services. The aim of this research is to integrate the concept of transit captivity into the analysis of walking access to public transit. The conventional way of defining “captive” and “choice” transit users showed no significant difference in their walking times according to a preliminary analysis. A cluster analysis technique is used to further divide “choice” users by three main factors, namely age group, labour force status and personal income. After eliminating “true captive” users, defined as those without driver’s licence or without a car in respective household, “non-true captive” users were classified into a total of eight groups having similar socio-economic characteristics. The analysis revealed significant differences in the walking times and patterns by their level of captivity to public transit. This paper challenges the rule-of-thumb of 400m walking distance to bus stops. In average, people’s willingness to walk dropped drastically at 268m and continued to drop constantly until it reached the mark of 670m, where there was another drastic drop of 17%, which left with only 10% of the total bus riders willing to walk 670m or more. This research found that mothers working part time were the ones with lowest transit captivity and thus most sensitive to the walking time, followed by high-income earners and the elderly. The level of captivity increases when public transit users earned lesser income, such as students and students working part time.

The radical in arts education research

Arts education research, as an interdisciplinary field, has developed in the shadows of a number of research traditions. However amid all the methodological innovation, I believe there is one particular, distinctive and radical research strategy which arts educators have created to research the practice of arts education: namely arts-based research. For many, and Elliot Eisner from Stanford University was among the first, arts education needed a research approach which could deal with the complex dynamics of arts education in the classroom. What was needed was ‘an approach to the conduct of educational research that was rooted in the arts and that used aesthetically crafted forms to reveal aspects of practice that mattered educationally’ (Eisner 2006: 11). While arts education researchers were crafting the principles and practices of arts-based research, fellow artist/researchers in the creative arts were addressing similar needs and fashioning their own exacting research strategies. This chapter aligns arts-based research with the complementary research practices established in creative arts studios and identifies the shared and truly radical nature of these moves. Finally, and in a contemporary turn many will find surprising, I will discuss how the radical aspects of these methodologies are now being held up as core elements of what is being called the fourth paradigm of scientific research, known as eScience. Could it be that the radical dynamics of arts-based research pre-figured the needs of eScience researchers who are currently struggling to manage the ‘deluge of Big Data’ which is disrupting their well-established scientific methods?

Developing a moderation community of practice

This paper reports on a study to evaluate technology-based processes for assessment moderation. The aim was to evaluate standard features found in an institutional Learning Management System, and their compatibility with the values and practices of a large teaching team. The process used an online discussion board forum for tutors, the paring of more experienced tutors with those new to the process, and further meetings conducted in both face-to-face and web conferencing environments. Online rubrics were used for assessing student work and the provision of feedback. A focus group conducted after marking was concluded and the analysis of the discussion board forum demonstrated a strong community of practice with a shared understanding of assessment requirements.

Perceptions of audio feedback in higher education assessment

The aim of this paper is to present results of research investigating the effectiveness of audio feedback in a third year undergraduate unit. While there is a large and growing body of literature about providing assessment feedback, there is little focussing on the use of audio media. This study employs a mixed method approach, involving semi-structured interviews with academic staff and a survey of students. Analysis of the interview data suggests that there are a number of issues surrounding acceptance of using audio feedback by lecturers. The next stage of the study is to examine the extent to which lecturers change their perceptions as they use audio feedback and to analyse the perceptions of the students (n=120), including the perceived importance of feedback, the ways in which they used the audio feedback and the extent to which they believe they control events that affect them. Ultimately, this study seeks to provide recommendations appropriate to the implementation of audio feedback in higher education.

'Take away from the dry sixties style marking': Lecturer and student perceptions and experiences of audio feedback

Providing audio feedback to assessment is relatively uncommon in higher education. However, published research suggests that it is preferred over written feedback by students but lecturers were less convinced. The aim of this paper is to examine further these findings in the context of a third year business ethics unit. Data was collected from two sources. The first is a series of in-depth, semi-structured interviews conducted with three lecturers providing audio feeback for the first time in Semester One 2011. The second source of data was drawn from the university student evaluation system. A total of 363 responses were used providing 'before' and 'after' perspectives about the effectiveness of audio feedback versus written feedback. Between 2005 and 2009 the survey data provided information about student attitudes to written assessment feedback (n=261). From 2010 onwards the data relates to audio (mp3) feedback (n=102). The analysis of he interview data indicated that introducing audio feedback should be done with care. The perception of the participating lecturers was mixed, ranging from sceptism to outright enthusiasm, but over time the overall approach became positive. It was found that particular attention needs to be paid to small (but important) technical details, and lecturers need to be convinced of its effectieness, especially that it is not necessarily more time consuming than providing written feedback. For students, the analysis revealed a clear preference for audio feedback. It is concluded that there is cause for concern and reason for optimism. It is a cause for concern because there is a possibility that scepticism on the part of academic staff seems to be based on assumptions about what students prefer and a concern about using the technology. There is reason for optimism because the evidence points towards students preferring audio feedback and as academic staff become more familiar with the technology the scepticism tends to evaporate. While this study is limited in scope, questions are raised about tackling negative staff perceptions of audio feedback that are worthy of further research.

Transforming higher education and student engagement through collaborative review to inform educational design

This paper reports on staff perceptions arising from a review process designed to assist staff in making informed decisions regarding educational design, approaches to engage students in learning, and the technology to support engagement in the classroom and across multiple locations and delivery modes. The aim of the review process was to transform the level of student engagement in the business faculty of an Australian university. The process took a collaborative approach through consultation with academic staff involved in the design and delivery of the units under review, and included targeted professional development as necessary. An institutional framework that characterises engagement indicator contexts and their attributes facilitated dialog during the review process. This paper reports on a mixed method study that included a survey of participants, and purposeful interviews to evaluate the effectiveness of the process. Although the study identified factors that hindered implementation and operationalization of review recommendations in some instances, study participants were generally of the view that recommendations would enhance student engagement. It is demonstrated that the bottom-up approach described in this paper is consistent with theoretical frameworks for transformational change in teaching and learning and the adoption of innovations.

Higher-resolution structure of the human insulin receptor ectodomain: Multi-modal inclusion of the insert domain

Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. However, only a low-resolution (3.8 Å) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding.

Understanding the civic impact of journalism

The importance of journalism to civil society is constantly proclaimed, but empirical evidence on journalism's impact, and how this operates, is surprisingly thin. Indeed, there is confusion even about what is meant by the term “impact”. Meanwhile, the issue of the role of journalism is becoming increasingly urgent as a consequence of the rapid changes engulfing the news media, brought about by technological change and the flow-on effect to the traditional advertising-supported business model. Assessing the impact of journalism has recently been the topic of debate among practitioners and scholars particularly in the United States, where philanthropists have responded to the perceived crisis in investigative journalism by funding not-for-profit newsrooms, with resulting new pressures being placed on journalists and editors to quantify their impact on society. These recent attempts have so far failed to achieve clarity or a satisfactory conclusion, which is not surprising given the complex web of causation within which journalism operates. In this paper, the authors propose a stratified definition of journalistic impact and function. They propose a methodology for studying impact drawing on realistic evaluation—a theory-based approach developed primarily to assess large social programmes occurring in open systems. The authors argue this could allow a conceptual and methodological advance on the question of media impacts, leading to research capable of usefully informing responses at a time of worrying change.

The death of newspapers: Have we reached the tipping point?

News Corp’s only substantial competitor in the print journalism sector may be on the brink of giving up the ghost, as has long been speculated even by its natural supporters such as Beecher. If it does, hundreds more jobs will go, along with the many hundreds of experienced, skilled journalists and editors already shown the door by the company.

Image, Political

Political communication scholars, journalists, and political actors alike, argue that the political process, and deliberative democracy (democracy founded on informed discussion inclusive of citizens), have lost their rational authenticity in that image and media spectacle have become more central to public opinion formation and electoral outcomes than policy. This entry examines the validity of that perception, and the extent to which “image” has emerged as a more significant factor in the political process. And if image is so important in political culture, what the impacts might be on the functioning of democratic processes.

Automatic wildfire detection and simulation using optical information from unmanned aerial systems

In many parts of the world, uncontrolled fires in sparsely populated areas are a major concern as they can quickly grow into large and destructive conflagrations in short time spans. Detecting these fires has traditionally been a job for trained humans on the ground, or in the air. In many cases, these manned solutions are simply not able to survey the amount of area necessary to maintain sufficient vigilance and coverage. This paper investigates the use of unmanned aerial systems (UAS) for automated wildfire detection. The proposed system uses low-cost, consumer-grade electronics and sensors combined with various airframes to create a system suitable for automatic detection of wildfires. The system employs automatic image processing techniques to analyze captured images and autonomously detect fire-related features such as fire lines, burnt regions, and flammable material. This image recognition algorithm is designed to cope with environmental occlusions such as shadows, smoke and obstructions. Once the fire is identified and classified, it is used to initialize a spatial/temporal fire simulation. This simulation is based on occupancy maps whose fidelity can be varied to include stochastic elements, various types of vegetation, weather conditions, and unique terrain. The simulations can be used to predict the effects of optimized firefighting methods to prevent the future propagation of the fires and greatly reduce time to detection of wildfires, thereby greatly minimizing the ensuing damage. This paper also documents experimental flight tests using a SenseFly Swinglet UAS conducted in Brisbane, Australia as well as modifications for custom UAS.

Prediction of individual genetic risk to prostate cancer using a polygenic score

BACKGROUND Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction. Prostate 75:1467–1474, 2015. © 2015 Wiley Periodicals, Inc.

Evaluation of polymeric nanomedicines targeted to PSMA: Effect of ligand on targeting efficiency

Targeted nanomedicines offer a strategy for greatly enhancing accumulation of a therapeutic within a specific tissue in animals. In this study, we report on the comparative targeting efficiency toward prostate-specific membrane antigen (PSMA) of a number of different ligands that are covalently attached by the same chemistry to a polymeric nanocarrier. The targeting ligands included a small molecule (glutamate urea), a peptide ligand, and a monoclonal antibody (J591). A hyperbranched polymer (HBP) was utilized as the nanocarrier and contained a fluorophore for tracking/analysis, whereas the pendant functional chain-ends provided a handle for ligand conjugation. Targeting efficiency of each ligand was assessed in vitro using flow cytometry and confocal microscopy to compare degree of binding and internalization of the HBPs by human prostate cancer (PCa) cell lines with different PSMA expression status (PC3-PIP (PSMA+) and PC3-FLU (PSMA−). The peptide ligand was further investigated in vivo, in which BALB/c nude mice bearing subcutaneous PC3-PIP and PC3-FLU PCa tumors were injected intravenously with the HBP-peptide conjugate and assessed by fluorescence imaging. Enhanced accumulation in the tumor tissue of PC3-PIP compared to PC3-FLU highlighted the applicability of this system as a future imaging and therapeutic delivery vehicle.