In vitro primary cell culture as a physiologically relevant method for preclinical testing of human oncolytic adenovirus

Ad[I/PPT-E1A] is an oncolytic adenovirus that specifically kills prostate cells via restricted replication by a prostate-specific regulatory element. Off-target replication of oncolytic adenoviruses would have serious clinical consequences. As a proposed ex vivo test, we describe the assessment of the specificity of Ad[I/PPT-E1A] viral cytotoxicity and replication in human nonprostate primary cells. Four primary nonprostate cell types were selected to mimic the effects of potential in vivo exposure to Ad[I/PPT-E1A] virus: bronchial epithelial cells, urothelial cells, vascular endothelial cells, and hepatocytes. Primary cells were analyzed for Ad[I/PPT-E1A] viral cytotoxicity in MTS assays, and viral replication was determined by hexon titer immunostaining assays to quantify viral hexon protein. The results revealed that at an extreme multiplicity of infection of 500, unlikely to be achieved in vivo, Ad[I/PPT-E1A] virus showed no significant cytotoxic effects in the nonprostate primary cell types apart from the hepatocytes. Transmission electron microscopy studies revealed high levels of Ad[I/PPT-E1A] sequestered in the cytoplasm of these cells. Adenoviral green fluorescent protein reporter studies showed no evidence for nuclear localization, suggesting that the cytotoxic effects of Ad[I/PPT-E1A] in human primary hepatocytes are related to viral sequestration. Also, hepatocytes had increased amounts of coxsackie adenovirus receptor surface protein. Active viral replication was only observed in the permissive primary prostate cells and LNCaP prostate cell line, and was not evident in any of the other nonprostate cells types tested, confirming the specificity of Ad[I/PPT-E1A]. Thus, using a relevant panel of primary human cells provides a convenient and alternative preclinical assay for examining the specificity of conditionally replicating oncolytic adenoviruses in vivo.

Gene expression profile of primary prostate epithelial and stromal cells in response to sulforaphane or iberin exposure

BACKGROUND: Broccoli consumption has been associated with a reduced risk of prostate cancer. Isothiocyanates (ITCs) derived from glucosinolates that accumulate in broccoli are dietary compounds that may mediate these health effects. Sulforaphane (SF, 4-methylsulphinylbutyl ITC) derives from heading broccoli (calabrese) and iberin (IB, 3-methylsulphinypropyl ITC) from sprouting broccoli. While there are many studies regarding the biological activity of SF, mainly undertaken with cancerous cells, there are few studies associated with IB. METHODS: Primary epithelial and stromal cells were derived from benign prostatic hyperplasia tissue. Affymetrix U133 Plus 2.0 whole genome arrays were used to compare global gene expression between these cells, and to quantify changes in gene expression following exposure to physiologically appropriate concentrations of SF and IB. Ontology and pathway analyses were used to interpret results. Changes in expression of a subset of genes were confirmed by real-time RT-PCR. RESULTS: Global gene expression profiling identified epithelial and stromal-specific gene expression profiles. SF induced more changes in epithelial cells, whereas IB was more effective in stromal cells. Although IB and SF induced different changes in gene expression in both epithelial and stromal cells, these were associated with similar pathways, such as cell cycle and detoxification. Both ITCs increased expression of PLAGL1, a tumor suppressor gene, in stromal cells and suppressed expression of the putative tumor promoting genes IFITM1, CSPG2, and VIM in epithelial cells. CONCLUSION: These data suggest that IB and SF both alter genes associated with cancer prevention, and IB should be investigated further as a potential chemopreventative agent.

Asian-Australian Children’s Literature and Publishing (AACLAP)

Led by Queensland University of Technology, the Asian-Australian Children’s Literature and Publishing (AACLAP)research project investigates and records details of Australian children’s literature that is set in Asia and/or that represents Asian-Australian cultures and experiences and literature that is published in selected Asian languages. This includes East Asia, Southeast Asia, South Asia, and the Bay of Bengal. The AACLAP dataset is a comprehensive collection of agent and work records related to ’Asia’, including, but not limited to, autobiography, fiction, criticism, poetry, drama, short stories, and picture books, published during a forty-year period from 1970 to 2010. The dataset provide valuable primary and secondary sources that are important for developing literature-focused educational programs in line with the national government’s push for Asia Literacy. AACLAP is a subset of AustLit, the virtual research environment and information resource for Australian literary, print, and narrative culture scholars, students, and the public.

Differentiating first episode substance induced and primary psychotic disorders with concurrent substance use in young people

Objective: Substance use is common in first-episode psychosis, and complicates the accurate diagnosis and treatment of the disorder. The differentiation of substance-induced psychotic disorders (SIPD) from primary psychotic disorders (PPD) is particularly challenging. This cross-sectional study compares the clinical, substance use and functional characteristics of substance using first episode psychosis patients diagnosed with a SIPD and PPD. Method: Participants were 61 young people (15-24 years) admitted to a psychiatric inpatient service with first episode psychosis, reporting substance use in the past month. Diagnosis was determined using the Psychiatric Research Interview for DSM-IV Substance and Mental disorders (PRISM-IV). Measures of clinical (severity of psychotic symptoms, level of insight, history of trauma), substance use (frequency/quantity, severity) and social and occupational functioning were also administered. Results: The PRISM-IV differentially diagnosed 56% of first episode patients with a SIPD and 44% with a PPD. Those with a SIPD had higher rates of substance use and disorders, higher levels of insight, were more likely to have a forensic and trauma history and had more severe hostility and anxious symptoms than those with a PPD. Logistic regression analysis indicated a family history of psychosis, trauma history and current cannabis dependence were the strongest predictors of a SIPD. Almost 80% of diagnostic predictions of a SIPD were accurate using this model. Conclusions: This clinical profile of SIPD could help to facilitate the accurate diagnosis and treatment of SIPD versus PPD in young people with first episode psychosis admitted to an inpatient psychiatric service.

Immigrants and the utilization of hospital emergency departments

BACKGROUND: Immigrants with language barriers are at high risk of having poor access to health care services. However, several studies have indicated that immigrants tend to use emergency departments (EDs) as their primary source of care at the expense of primary care. This may place an additional burden on already overcrowded EDs and lead to a low level of patient satisfaction with ED care. The study was to review if immigrants utilize ED care differently from host populations and to assess immigrants’ satisfaction with ED care. DATA SOURCES: Studies about immigrants' utilization of EDs in Australia and worldwide were reviewed. RESULTS: There are confl icting results in the literature about the pattern of ED care use among immigrants. Some studies have shown higher utilization by immigrants compared to host populations and others have shown lower utilization. Overall, immigrants use ED care heavily, make inappropriate visits to EDs, have a longer length of stay in EDs, and are less satisfi ed with ED care as compared to host populations. CONCLUSIONS: Immigrants might use ED care differently from host populations due to language and cultural barriers. There is sparse Australian literature regarding immigrants' access to health care including ED care. To ensure equity, further research is needed to inform policy when planning health care provision to immigrants. KEY WORDS: Emergency department; Health service; Immigrants; Language; Utilization

What if you're really different? Case studies of children with high functioning autism participating in the Get REAL programme who had atypical learning trajectories.

Evaluation of the Get REAL programme in an inclusive primary school setting has indicated its effectiveness in promoting pro-social behaviour for children with high functioning Autism. However, two children with co-morbid diagnoses and complex personal circumstances showed less consistent improvements. In order to explain their unique trajectories, not readily derived from quantitative studies, an exploratory case study approach was used to examine contextual influences on patterns of progress. Multiple data sources included coded video footage from the Get REAL programme, school reports on conduct, and parents and classroom teacher reports using the Strengths and Difficulties Questionnaire. While results provide support for the efficacy of the Get REAL programme for the two children, they also highlight the value of co-ordinated strategies and collaborative individualised approaches in more complex cases. This paper outlines the Get REAL intervention and a range of other school and support agency strategies impacting progress.

'These are my photos of when I was little' : Locating Media Arts in the Primary School Curriculum

‘Media Arts’ has been included as a fifth area of the Arts for the Australian Curriculum which will become mandatory learning for all Australian children from pre-school to Year Six (Y6) from 2014. The current curriculum design is underpinned by an approach familiar to media educators who combine creative practice and critical response to develop students’ media literacies. Media Arts within the Australian Curriculum will place Australia at the forefront of international efforts to promote media education as an entitlement for all children. Even with this mandated endorsement, however, there remains ongoing debate about where to locate media education in school curricula. Historically, media education in Australia has been approached through diverse curriculum activities at the secondary school level. These include subject English’s critical literacy objectives; vocationally oriented media and technology education or ICTs education; and Arts courses using new media technologies for creativity. In this chapter we consider the possibilities and challenges for Media Arts, specifically for primary school student learning. We draw on empirical evidence from a research project that has trialled a Media Arts curriculum with students attending a primary school in a low socio-economic status and culturally diverse community on the outskirts of Brisbane, Queensland.

Practical insights into curricula integration for primary science

As indicated in a previous Teaching Science article, effective planning for curricula integration requires using standards from two (or more) subject areas (e.g., science and English, science and art or science and mathematics), which also becomes the assessment foci for teaching and learning. Curricula integration of standards into an activity necessitates pedagogical knowledge for developing students’ learning in both subject areas. For science education, the skills and tools for curricula integration include the use of other key learning areas (KLAs). A balance between teacher and student-centred science education programs that draw on democratic processes (e.g., Beane, 1997) can be used to make real-world links to target students’ individual needs. This article presents practical ways to commence thinking about curricula integration towards using Australian curriculum standards.

The Yonder project : literacy and social competency development in primary school students through co-creation of live performance

Since 2007 Kite Arts Education Program (KITE), based at Queensland Performing Arts Centre (QPAC), has been engaged in delivering a series of theatre-based experiences for children in low socio-economic primary schools in Queensland. The artist in residence (AIR) project titled Yonder includes performances developed by the children with the support and leadership of teacher artists from KITE for their community and parents/carers,supported by a peak community cultural institution. In 2009,Queensland Performing Arts Centre partnered with Queensland University of Technology (QUT) Creative Industries Faculty (Drama) to conduct a three-year evaluation of the Yonder project to understand the operational dynamics, artistic outputs and the educational benefits of the project. This paper outlines the research findings for children engaged in the Yonder project in the interrelated areas of literacy development and social competencies. Findings are drawn from six iterations of the project in suburban locations on the edge of Brisbane city and in regional Queensland.

Introducing ICT to a primary school in a developing country : a Fijian experience

One aspect of quality education in the 21st century is the availability of digital resources in schools. Many developing countries need to build this capability – not just in terms of technology but teacher capability as well. One of the ways to achieve such capacity is through knowledge sharing between teachers and educators in developed and developing countries. Over time such collaboration can have a lasting impact on all participants on both sides of the digital divide. This paper reports on how such collaboration can occur. It focuses on the initial stages of a long-term initiative where our primary objective is to develop models, which demonstrate how we (in developed countries) can engage productively and meaningfully with schools in developing countries to build their ICT capacity. As part of this initiative, we introduced laptops and LEGO robotics tool kits to a rural primary school in Fiji. We developed ICT activities that aligned with the curriculum in a number of subjects. In addition, we worked with the teachers over two weeks to build their expertise.

Bayesian algorithms with applications

Advances in algorithms for approximate sampling from a multivariable target function have led to solutions to challenging statistical inference problems that would otherwise not be considered by the applied scientist. Such sampling algorithms are particularly relevant to Bayesian statistics, since the target function is the posterior distribution of the unobservables given the observables. In this thesis we develop, adapt and apply Bayesian algorithms, whilst addressing substantive applied problems in biology and medicine as well as other applications. For an increasing number of high-impact research problems, the primary models of interest are often sufficiently complex that the likelihood function is computationally intractable. Rather than discard these models in favour of inferior alternatives, a class of Bayesian "likelihoodfree" techniques (often termed approximate Bayesian computation (ABC)) has emerged in the last few years, which avoids direct likelihood computation through repeated sampling of data from the model and comparing observed and simulated summary statistics. In Part I of this thesis we utilise sequential Monte Carlo (SMC) methodology to develop new algorithms for ABC that are more efficient in terms of the number of model simulations required and are almost black-box since very little algorithmic tuning is required. In addition, we address the issue of deriving appropriate summary statistics to use within ABC via a goodness-of-fit statistic and indirect inference. Another important problem in statistics is the design of experiments. That is, how one should select the values of the controllable variables in order to achieve some design goal. The presences of parameter and/or model uncertainty are computational obstacles when designing experiments but can lead to inefficient designs if not accounted for correctly. The Bayesian framework accommodates such uncertainties in a coherent way. If the amount of uncertainty is substantial, it can be of interest to perform adaptive designs in order to accrue information to make better decisions about future design points. This is of particular interest if the data can be collected sequentially. In a sense, the current posterior distribution becomes the new prior distribution for the next design decision. Part II of this thesis creates new algorithms for Bayesian sequential design to accommodate parameter and model uncertainty using SMC. The algorithms are substantially faster than previous approaches allowing the simulation properties of various design utilities to be investigated in a more timely manner. Furthermore the approach offers convenient estimation of Bayesian utilities and other quantities that are particularly relevant in the presence of model uncertainty. Finally, Part III of this thesis tackles a substantive medical problem. A neurological disorder known as motor neuron disease (MND) progressively causes motor neurons to no longer have the ability to innervate the muscle fibres, causing the muscles to eventually waste away. When this occurs the motor unit effectively ‘dies’. There is no cure for MND, and fatality often results from a lack of muscle strength to breathe. The prognosis for many forms of MND (particularly amyotrophic lateral sclerosis (ALS)) is particularly poor, with patients usually only surviving a small number of years after the initial onset of disease. Measuring the progress of diseases of the motor units, such as ALS, is a challenge for clinical neurologists. Motor unit number estimation (MUNE) is an attempt to directly assess underlying motor unit loss rather than indirect techniques such as muscle strength assessment, which generally is unable to detect progressions due to the body’s natural attempts at compensation. Part III of this thesis builds upon a previous Bayesian technique, which develops a sophisticated statistical model that takes into account physiological information about motor unit activation and various sources of uncertainties. More specifically, we develop a more reliable MUNE method by applying marginalisation over latent variables in order to improve the performance of a previously developed reversible jump Markov chain Monte Carlo sampler. We make other subtle changes to the model and algorithm to improve the robustness of the approach.

Integrating robotics in primary school activities

This article outlines the integration of robotics in two settings in a primary school. This initiative was part of an Australian Research Council project which was undertaken at this school. The article highlights how robotics was integrated in a technology unit in a year four class. It also explains how it was embedded into an after-school program which catered for students from years five to seven. From these experiences further possibilities of engaging with robotics are also discussed.

From vision to reality : views of primary school principals on inclusive education in New South Wales, Australia

This paper discusses the findings of a research study that used semi-structured interviews to explore the views of primary school principals on inclusive education in New South Wales, Australia. Content analysis of the transcript data indicates that principals’ attitudes towards inclusive education and their success in engineering inclusive practices within their school are significantly affected by their own conception of what “inclusion” means, as well as the characteristics of the school community, and the attitudes and capacity of staff. In what follows, we present two parallel conversations that arose from the interview data to illustrate the main conceptual divisions existing between our participants’ conceptions of inclusion. First, we discuss the act of “being inclusive” which was perceived mainly as an issue of culture and pedagogy. Second, we consider the mechanics of “including,” which reflected a more instrumentalist position based on perceptions of individual student deficit, the level of support they may require and the amount of funding they can attract.

Problem solving in the primary school (K-2)

This article focuses on problem solving activities in a first grade classroom in a typical small community and school in Indiana. But, the teacher and the activities in this class were not at all typical of what goes on in most comparable classrooms; and, the issues that will be addressed are relevant and important for students from kindergarten through college. Can children really solve problems that involve concepts (or skills) that they have not yet been taught? Can children really create important mathematical concepts on their own – without a lot of guidance from teachers? What is the relationship between problem solving abilities and the mastery of skills that are widely regarded as being “prerequisites” to such tasks?Can primary school children (whose toolkits of skills are limited) engage productively in authentic simulations of “real life” problem solving situations? Can three-person teams of primary school children really work together collaboratively, and remain intensely engaged, on problem solving activities that require more than an hour to complete? Are the kinds of learning and problem solving experiences that are recommended (for example) in the USA’s Common Core State Curriculum Standards really representative of the kind that even young children encounter beyond school in the 21st century? … This article offers an existence proof showing why our answers to these questions are: Yes. Yes. Yes. Yes. Yes. Yes. And: No. … Even though the evidence we present is only intended to demonstrate what’s possible, not what’s likely to occur under any circumstances, there is no reason to expect that the things that our children accomplished could not be accomplished by average ability children in other schools and classrooms.