Kallikrein 14 is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness

Kallikrein 14 (KLK14) has been proposed as a useful prognostic marker in prostate cancer, with expression reported to be associated with tumour characteristics such as higher stage and Gleason score. KLK14 tumour expression has also shown the potential to predict prostate cancer patients at risk of disease recurrence after radical prostatectomy. The KLKs are a remarkably hormone-responsive family of genes, although detailed studies of androgen regulation of KLK14 in prostate cancer have not been undertaken to date. Using in vitro studies, we have demonstrated that unlike many other prostatic KLK genes that are strictly androgen responsive, KLK14 is more broadly expressed and inversely androgen regulated in prostate cancer cells. Given these results and evidence that KLK14 may play a role in prostate cancer prognosis, we also investigated whether common genetic variants in the KLK14 locus are associated with risk and/or aggressiveness of prostate cancer in approximately 1200 prostate cancer cases and 1300 male controls. Of 41 single nucleotide polymorphisms assessed, three were associated with higher Gleason score (≥7): rs17728459 and rs4802765, both located upstream of KLK14, and rs35287116, which encodes a p.Gln33Arg substitution in the KLK14 signal peptide region. Our findings provide further support for KLK14 as a marker of prognosis in prostate cancer.

Next-generation sequencing of cervical DNA detects human papillomavirus types not detected by commercial kits

Background Human papillomavirus (HPV) is the aetiological agent for cervical cancer and genital warts. Concurrent HPV and HIV infection in the South African population is high. HIV positive (+) women are often infected with multiple, rare and undetermined HPV types. Data on HPV incidence and genotype distribution are based on commercial HPV detection kits, but these kits may not detect all HPV types in HIV + women. The objectives of this study were to (i) identify the HPV types not detected by commercial genotyping kits present in a cervical specimen from an HIV positive South African woman using next generation sequencing, and (ii) determine if these types were prevalent in a cohort of HIV-infected South African women. Methods Total DNA was isolated from 109 cervical specimens from South African HIV + women. A specimen within this cohort representing a complex multiple HPV infection, with 12 HPV genotypes detected by the Roche Linear Array HPV genotyping (LA) kit, was selected for next generation sequencing analysis. All HPV types present in this cervical specimen were identified by Illumina sequencing of the extracted DNA following rolling circle amplification. The prevalence of the HPV types identified by sequencing, but not included in the Roche LA, was then determined in the 109 HIV positive South African women by type-specific PCR. Results Illumina sequencing identified a total of 16 HPV genotypes in the selected specimen, with four genotypes (HPV-30, 74, 86 and 90) not included in the commercial kit. The prevalence's of HPV-30, 74, 86 and 90 in 109 HIV positive South African women were found to be 14.6 %, 12.8 %, 4.6 % and 8.3 % respectively. Conclusions Our results indicate that there are HPV types, with substantial prevalence, in HIV positive women not being detected in molecular epidemiology studies using commercial kits. The significance of these types in relation to cervical disease remains to be investigated.

The evolutionary value of recombination is constrained by genome modularity

Genetic recombination is a fundamental evolutionary mechanism promoting biological adaptation. Using engineered recombinants of the small single-stranded DNA plant virus, Maize streak virus (MSV), we experimentally demonstrate that fragments of genetic material only function optimally if they reside within genomes similar to those in which they evolved. The degree of similarity necessary for optimal functionality is correlated with the complexity of intragenomic interaction networks within which genome fragments must function. There is a striking correlation between our experimental results and the types of MSV recombinants that are detectable in nature, indicating that obligatory maintenance of intragenome interaction networks strongly constrains the evolutionary value of recombination for this virus and probably for genomes in general.

Rapid host adaptation by extensive recombination

Experimental investigations into virus recombination can provide valuable insights into the biochemical mechanisms and the evolutionary value of this fundamental biological process. Here, we describe an experimental scheme for studying recombination that should be applicable to any recombinogenic viruses amenable to the production of synthetic infectious genomes. Our approach is based on differences in fitness that generally exist between synthetic chimaeric genomes and the wild-type viruses from which they are constructed. In mixed infections of defective reciprocal chimaeras, selection strongly favours recombinant progeny genomes that recover a portion of wild-type fitness. Characterizing these evolved progeny viruses can highlight both important genetic fitness determinants and the contribution that recombination makes to the evolution of their natural relatives. Moreover, these experiments supply precise information about the frequency and distribution of recombination breakpoints, which can shed light on the mechanistic processes underlying recombination. We demonstrate the value of this approach using the small single-stranded DNA geminivirus, maize streak virus (MSV). Our results show that adaptive recombination in this virus is extremely efficient and can yield complex progeny genomes comprising up to 18 recombination breakpoints. The patterns of recombination that we observe strongly imply that the mechanistic processes underlying rolling circle replication are the prime determinants of recombination breakpoint distributions found in MSV genomes sampled from nature. © 2009 SGM.

Strategies for the prevention of cervical cancer by human papillomavirus vaccination

As cervical cancer is causally associated with 14 high-risk types of human papillomavirus (HPV), a successful HPV vaccine will have a major impact on this disease. Although some persistent HPV infections progress to cervical cancer, host immunity is generally able to clear most HPV infections. Both cell-mediated and antibody responses have been implicated in influencing the susceptibility, persistence or clearance of genital HPV infection. There have been two clinical trials that show that vaccines based on virus-like particles (VLPs) made from the major capsid protein, L1, are able to type specifically protect against cervical intra-epithelial neoplasia and infection. However, there is no evidence that even a mixed VLP vaccine will protect against types not included in the vaccine, and a major challenge that remains is how to engineer protection across a broader spectrum of viruses. Strategies for production of HPV vaccines using different vaccine vectors and different production systems are also reviewed. © 2005 Elsevier Ltd. All rights reserved.

Inhibition of maize streak virus (MSV) replication by transient and transgenic expression of MSV replication-associated protein mutants

Maize streak disease is a severe agricultural problem in Africa and the development of maize genotypes resistant to the causal agent, Maize streak virus (MSV), is a priority. A transgenic approach to engineering MSV-resistant maize was developed and tested in this study. A pathogen-derived resistance strategy was adopted by using targeted deletions and nucleotide-substitution mutants of the multifunctional MSV replication-associated protein gene (rep). Various rep gene constructs were tested for their efficacy in limiting replication of wild-type MSV by co-bombardment of maize suspension cells together with an infectious genomic clone of MSV and assaying replicative forms of DNA by quantitative PCR. Digitaria sanguinalis, an MSV-sensitive grass species used as a model monocot, was then transformed with constructs that had inhibited virus replication in the transient-expression system. Challenge experiments using leafhopper-transmitted MSV indicated significant MSV resistance - from highly resistant to immune - in regenerated transgenic D. sanguinalis lines. Whereas regenerated lines containing a mutated full-length rep gene displayed developmental and growth defects, those containing a truncated rep gene both were fertile and displayed no growth defects, making the truncated gene a suitable candidate for the development of transgenic MSV-resistant maize. © 2007 SGM.

Can a parent do too much for their child? An examination by parenting professionals of the concept of overparenting

Is there a point where parental effort can be too much? While the link between parenting effort and the wellbeing of children has been firmly established, contemporary discussion has proposed that extreme levels of parental protection of and responsiveness to children could be counterproductive. Research has not yet addressed this phenomenon to ascertain if overparenting is a genuinely different type of parenting approach. The purpose of the present study was to gain insight into the parenting actions considered by parenting professionals (psychologists and school guidance counsellors) to be overparenting. One hundred and twenty-eight professionals responded to an online survey about their observations of overparenting, with eighty-six respondents providing lists of the types of actions they believed were behavioural examples of the term. The survey data revealed that certain types of actions were considered to be indicative of overparenting, and that particular beliefs and outcomes may be involved in this parenting approach. Implications for parenting advice and education programs, and further research are discussed.

Review: "Transfigured Stages : Major Practitioners and Theatre Aesthetics in Australia" by Margaret Hamilton

In Transfigured Stages: Major Practitioners and Theatre Aesthetics in Australia, Margaret Hamilton traces the emergence of a postdramatic performance aesthetic in Australian theatre in the 1980s, 1990s and early 2000s through what she characterizes as an ‘analysis’ (p. 15) or ‘critique’ (p. 16)of a series of pivotal productions. For Hamilton, the transfigured aesthetic in the spotlight here is one typified by a focus on memory, imagination, desire, fear or disgust as facets of the human condition; by a visual, televisual or interactive dramaturgy; and, most critically, by a metatheatrical tendency to make tensions in the theatre-making process part and parcel of the tensions in the performance itself (pp.18–20)...

Intended and actual avoidance of road use situations by older drivers and pedestrians, by gender and age

• The Queensland context • Rationale and aims • Method • Demographics and basic data • Avoidance of driving and walking situations • Success of intended avoidance • Further analyses (preliminary results) • Implications

The impact of a model of nurse education to improve knowledge and recognition of delirium in older persons by registered nurses

Introduction: Delirium is a serious issue associated with high morbidity and mortality in older hospitalised people. Early recognition enables diagnosis and treatment of underlying cause/s, which can lead to improved patient outcomes. However, research shows knowledge and accurate nurse recognition of delirium and is poor and lack of education appears to be a key issue related to this problem. Thus, the purpose of this randomised controlled trial (RCT) was to evaluate, in a sample of registered nurses, the usability and effectiveness of a web-based learning site, designed using constructivist learning principles, to improve acute care nurse knowledge and recognition of delirium. Prior to undertaking the RCT preliminary phases involving; validation of vignettes, video-taping five of the validated vignettes, website development and pilot testing were completed. Methods: The cluster RCT involved consenting registered nurse participants (N = 175) from twelve clinical areas within three acute health care facilities in Queensland, Australia. Data were collected through a variety of measures and instruments. Primary outcomes were improved ability of nurses to recognise delirium using written validated vignettes and improved knowledge of delirium using a delirium knowledge questionnaire. The secondary outcomes were aimed at determining nurse satisfaction and usability of the website. Primary outcome measures were taken at baseline (T1), directly after the intervention (T2) and two months later (T3). The secondary outcomes were measured at T2 by participants in the intervention group. Following baseline data collection remaining participants were assigned to either the intervention (n=75) or control (n=72) group. Participants in the intervention group were given access to the learning intervention while the control group continued to work in their clinical area and at that time, did not receive access to the learning intervention. Data from the primary outcome measures were examined in mixed model analyses. Results: Overall, the effect of the online learning intervention over time comparing the intervention group and the control group were positive. The intervention groups‘ scores were higher and the change over time results were statistically significant [T3 and T1 (t=3.78 p=<0.001) and T2 and T1 baseline (t=5.83 p=<0.001)]. Statistically significant improvements were also seen for delirium recognition when comparing T2 and T1 results (t=2.58 p=0.012) between the control and intervention group but not for changes in delirium recognition scores between the two groups from T3 and T1 (t=1.80 p=0.074). The majority of the participants rated the website highly on the visual, functional and content elements. Additionally, nearly 80% of the participants liked the overall website features and there were self-reported improvements in delirium knowledge and recognition by the registered nurses in the intervention group. Discussion: Findings from this study support the concept that online learning is an effective and satisfying method of information delivery. Embedded within a constructivist learning environment the site produced a high level of satisfaction and usability for the registered nurse end-users. Additionally, the results showed that the website significantly improved delirium knowledge & recognition scores and the improvement in delirium knowledge was retained at a two month follow-up. Given the strong effect of the intervention the online delirium intervention should be utilised as a way of providing information to registered nurses. It is envisaged that this knowledge would lead to improved recognition of delirium as well as improvement in patient outcomes however; translation of this knowledge attainment into clinical practice was outside the scope of this study. A critical next step is demonstrating the effect of the intervention in changing clinical behaviour, and improving patient health outcomes.

Seeking inclusion : views from ‘vulnerable’ communities about reporting by the Australian news media

This conference paper reports on the findings of the 'Vulnerability and the News Media’ project about news reporting on communities that are commonly regarded as ‘vulnerable’ by virtue of their issues or circumstances. The project focuses on news reporting of Indigenous and ethnically diverse communities, as well as people affected by mental health issues, people with disabilities, and survivors of crime and traumatic events. Numerous educational initiatives have tried to improve the quality of media reports about these communities and their issues. Despite this, the project’s research with stakeholders from those communities has found that they continue to raise the same concerns that have been expressed about the news media since the 1970s. In focus group research, stakeholders from these communities expressed concern about their continuing under-representation or omission from the news media. They felt that voices, experiences, perspectives and issues from their communities rarely appeared, or if they did appear, it was in limited contexts – often in circumstances that portrayed them as vulnerable or disruptive. They also pointed to ongoing media misrepresentation, such as stereotyping, inappropriate framing, and over-reliance on ‘usual suspects’ to talk about their communities. A common theme that they voiced was their need for greater inclusiveness in the media. Participants wished that journalists would better represent the diversity of life experiences and perspectives within their communities. Stakeholders also wanted an increased in representation of their political frameworks, such as stories about the difficulties they encountered in dealing with social and bureaucratic systems, and their understandings of causes and potential solutions for issues affecting their communities.

Automatic particle picking of biological molecules imaged by electron microscopy

One of the next great challenges of cell biology is the determination of the enormous number of protein structures encoded in genomes. In recent years, advances in electron cryo-microscopy and high-resolution single particle analysis have developed to the point where they now provide a methodology for high resolution structure determination. Using this approach, images of randomly oriented single particles are aligned computationally to reconstruct 3-D structures of proteins and even whole viruses. One of the limiting factors in obtaining high-resolution reconstructions is obtaining a large enough representative dataset ($>100,000$ particles). Traditionally particles have been manually picked which is an extremely labour intensive process. The problem is made especially difficult by the low signal-to-noise ratio of the images. This paper describes the development of automatic particle picking software, which has been tested with both negatively stained and cryo-electron micrographs. This algorithm has been shown to be capable of selecting most of the particles, with few false positives. Further work will involve extending the software to detect differently shaped and oriented particles.

Telephone support to rural and remote patients with heart failure : the Chronic Heart failure Assessment by Telephone (CHAT) study

Background Heart failure (HF) remains a condition with high morbidity and mortality. We tested a telephone support strategy to reduce major events in rural and remote Australians with HF, who have limited healthcare access. Telephone support comprised an interactive telecommunication software tool (TeleWatch) with follow-up by trained cardiac nurses. Methods Patients with a general practice (GP) diagnosis of HF were randomised to usual care (UC) or UC and telephone support intervention (UC+I) using a cluster design involving 143 GPs throughout Australia. Patients were followed for 12 months. The primary end-point was the Packer clinical composite score. Secondary end-points included hospitalisation for any cause, death or hospitalisation, as well as HF hospitalisation. Results Four hundred and five patients were randomised into CHAT. Patients were well matched at baseline for key demographic variables. The primary end-point of the Packer Score was not different between the two groups (P=0.98), although more patients improved with UC+I. There were fewer patients hospitalised for any cause (74 versus 114, adjusted HR 0.67 [95% CI 0.50-0.89], p=0.006) and who died or were hospitalised (89 versus 124, adjusted HR 0.70 [95% CI 0.53 – 0.92], p=0.011), in the UC+I vs UC group. HF hospitalisations were reduced with UC+I (23 versus 35, adjusted HR 0.81 [95% CI 0.44 – 1.38]), although this was not significant (p=0.43). There were 16 deaths in the UC group and 17 in the UC+I group (p=0.43). Conclusions Although no difference was observed in the primary end-point of CHAT (Packer composite score), UC+I significantly reduced the number of HF patients hospitalised amongst a rural and remote cohort. These data suggest that telephone support may be an efficacious approach to improve clinical outcomes in rural and remote HF patients.

Variation in risk seeking behavior in a natural experiment following a large negative wealth shock induced by a natural disaster

An ongoing challenge in behavioral economics is to understand the variations observed in risk attitudes as a function of their environmental context. Of particular interest is the effect of wealth on risk attitudes. The research in this area has however faced two constraints: the difficulty to study the causal effects of large changes in wealth, and the causal effects of losses on risk behavior. The present paper address this double limitation by providing evidence of the variation of risk attitude after large losses using a natural disaster (Brisbane floods) as the setting for a natural experiment.

Comparing the availability, price, variety and quality of fruits and vegetables across retail outlets and by area level socioeconomic position

Abstract Objective: To explore whether area-level socioeconomic position or the form of retail stream (conventional versus farmers’ market) are associated with differences in the price, availability, variety and quality of a range of fresh fruit and vegetables. Design: A multi-site cross-sectional pilot study of farmers’ markets, supermarkets and independent fruit and vegetable retailers. Each was surveyed to assess the price, availability, variety and quality of 15 fruit and 18 vegetable items. Setting: Retail outlets were located in South-East Queensland. Subjects: Fifteen retail outlets were surveyed (five of each retail stream). Results: Average basket prices were not significantly different across the socioeconomic spectrum however prices in low socioeconomic areas were cheapest. Availability, variety, and quality did not differ across levels of socioeconomic position however the areas with the most socioeconomic disadvantage scored poorest for quality and variety. Supermarkets had significantly better fruit and vegetable availability than farmers’ markets however price, variety and quality scores were not different across retail streams. Results demonstrate a trend to fruit and vegetable prices being more expensive at farmers’ markets, with the price of the Fruit basket being significantly greater at the organic farmer’s market compared with the non-organic farmers’ markets. Conclusions: Neither area-level socioeconomic position nor the form of retail stream was significantly associated with differences in the availability, price, variety and quality of fruit and vegetables, except for availability which was higher in supermarkets than farmers’ markets. Further research is needed to determine what role farmers’ markets can play in affecting fruit and vegetable intake.