The development of an effective vaccine against Chlamydia : utilisation of a non-toxic mucosal adjuvant to generate a protective mucosal response

Chlamydia is responsible for a wide range of diseases with enormous global economic and health burden. As the majority of chlamydial infections are asymptomatic, a vaccine has greatest potential to reduce infection and disease prevalence. Protective immunity against Chlamydia requires the induction of a mucosal immune response, ideally, at the multiple sites in the body where an infection can be established. Mucosal immunity is most effectively stimulated by targeting vaccination to the epithelium, which is best accomplished by direct vaccine application to mucosal surfaces rather than by injection. The efficacy of needle-free vaccines however is reliant on a powerful adjuvant to overcome mucosal tolerance. As very few adjuvants have proven able to elicit mucosal immunity without harmful side effects, there is a need to develop non-toxic adjuvants or safer ways to administered pre-existing toxic adjuvants. In the present study we investigated the novel non-toxic mucosal adjuvant CTA1-DD. The immunogenicity of CTA1-DD was compared to our "gold-standard" mucosal adjuvant combination of cholera toxin (CT) and cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN). We also utilised different needle-free immunisation routes, intranasal (IN), sublingual (SL) and transcutaneous (TC), to stimulate the induction of immunity at multiple mucosal surfaces in the body where Chlamydia are known to infect. Moreover, administering each adjuvant by different routes may also limit the toxicity of the CT/CpG adjuvant, currently restricted from use in humans. Mice were immunised with either adjuvant together with the chlamydial major outer membrane protein (MOMP) to evaluate vaccine safety and quantify the induction of antigen-specific mucosal immune responses. The level of protection against infection and disease was also assessed in vaccinated animals following a live genital or respiratory tract infectious challenge. The non-toxic CTA1-DD was found to be safe and immunogenic when delivered via the IN route in mice, inducing a comparable mucosal response and level of protective immunity against chlamydial challenge to its toxic CT/CpG counterpart administered by the same route. The utilisation of different routes of immunisation strongly influenced the distribution of antigen-specific responses to distant mucosal surfaces and also abrogated the toxicity of CT/CpG. The CT/CpG-adjuvanted vaccine was safe when administered by the SL and TC routes and conferred partial immunity against infection and pathology in both challenge models. This protection was attributed to the induction of antigen-specific pro-inflammatory cellular responses in the lymph nodes regional to the site of infection and rather than in the spleen. Development of non-toxic adjuvants and effective ways to reduce the side effects of toxic adjuvants has profound implications for vaccine development, particularly against mucosal pathogens like Chlamydia. Interestingly, we also identified two contrasting vaccines in both infection models capable of preventing infection or pathology exclusively. This indicated that the development of pathology following an infection of vaccinated animals was independent of bacterial load and was instead the result of immunopathology, potentially driven by the adaptive immune response generated following immunisation. While both vaccines expressed high levels of interleukin (IL)-17 cytokines, the pathology protected group displayed significantly reduced expression of corresponding IL-17 receptors and hence an inhibition of signalling. This indicated that the balance of IL-17-mediated responses defines the degree of protection against infection and tissue damage generated following vaccination. This study has enabled us to better understand the immune basis of pathology and protection, necessary to design more effective vaccines.

The getting of wisdom : the future of PM university education in Australia

The dynamic and complex nature of project management (PM) in Australia provides exciting opportunities for universities to that are willing to actively engage with their corporate partners and other key stakeholders to develop program and course offerings that simultaneously address the needs of students, employers, and other stakeholders and further the current body of PM knowledge and research. This article identifies key challenges and opportunities for the future direction of PM university education. This draws on descriptions of successful program models, examining teaching on PM skills on generic business and engineering degrees, dedicated graduate masters programs in PM, doctoral research programs in PM, and forms of effective collaboration between industry and academia.

Characterising one-to-one conservatoire teaching : Some implications of a quantitative analysis

Despite the significant recent growth in research relating to instrumental, vocal and composition tuition in higher education, little is known about the diversity of approaches that characterise one-to-one teaching in the Conservatoire, and what counts as optimal practice for educating 21st-century musicians. Through analysis of video-recorded one-to-one lessons that draws on a ‘bottom up’ methodology for characterising pedagogical practices (Taylor, 2012; Taylor et al, 2012), this paper provides empirical evidence about the nature of one-to-one pedagogy in one Australian institution. The research aims (1) to enable a better understanding of current one-to-one conservatoire teaching; and (2) to build and improve upon existing teaching practice using authentic insights gained through systematic investigation. The authors hope the research will lead to a better understanding of the diversity and efficacy of the pedagogical practice within the specific context in which the study was conducted, and beyond, to Conservatoire pedagogy generally.

Professional development on-site and in context at Narangba Valley SHS

The implementation of the National Professional Standards for Teachers (Australian Institute for Teaching and School Leadership (AITSL), 2011) will require all teachers to undertake 30 hours per year of professional development (PD) to maintain thei registration. However, defining what constitutes effective PD s complex. This article discusses an approach used by Narangba Valley State High School (SHS) in Queensland which involves effective on-site PD, resulting in improved student outcomes. In addition to the school-administered growth and learning (GAL) plans for each teacher, the school worked collaboratively with an external person (university lecturer) and implemented an effective, sustainable, whole-school approach to PD which was ongoing, on time, on task, on the mark, and on-the-spot (Jetnikoff & Smeed, 2012). The article unpacks an interview with Ross Mackay, the Narangba Valley SHS executive-principal and one of the authors of this paper, and provides practical advice for other school leaders wishing to implement a similar approach to PD.

Is intermittent intrapleural analgesia safe and effective following thoracoscopic anterior scoliosis correction surgery?

Introduction: Thoracoscopic anterior instrumented fusion (TASF) is a safe and viable surgical option for corrective stabilisation of progressive adolescent idiopathic scoliosis (AIS) [1-2]. However, there is a paucity of literature examining optimum methods of analgesia following this type of surgery. The aim of this study was to identify; if local anaesthetic bolus via an intrapleural catheter provides effective analgesia following thoracoscopic scoliosis correction; what pain levels may be expected; and any adverse effects associated with the use of intermittent intrapleural analgesia at our centre. Methods: A subset of the most recent 80 patients from a large single centre consecutive series of 201 patients (April 2000 to present) who had undergone TASF had their medical records reviewed. 32 patients met the inclusion criteria for the analysis (i.e. pain scores must have been recorded within the hour prior and within two hours following an intrapleural bolus being given). All patients received an intrapleural catheter inserted during surgery, in addition to patient-controlled opiate analgesia and oral analgesia as required. After surgery, patients received a bolus of 0.25% bupivacaine every four hours via the intrapleural catheter. Visual analogue pain scale scores were recorded before and after the bolus of local anaesthetic and the quantity and time of day that any other analgesia was taken, were also recorded. Results and Discussion: 28 female and four male patients (mean age 14.5 ± 1.5 years) had a total of 230 boluses of local anaesthetic administered intrapleurally, directly onto the spine, in the 96 hour period following surgery. Pain scores significantly decreased following the administration of a bolus (p<0.0001), with the mean pain score decreasing from 3.66 to 1.83. The quantity of opiates via patient-controlled analgesia after surgery decreased steadily between successive 24 hours intervals after an initial increase in the second 24 hour period when patients were mobilised. One intrapleural catheter required early removal at 26 hours postop due to leakage; there were no other associated complications with the intermittent intrapleural analgesia method. Post-operative pain following anterior scoliosis correction was decreased significantly with the administration of regular local anaesthetic boluses and can be reduced to ‘mild’ levels by combined analgesia regimes. The intermittent intrapleural analgesia method was not associated with any adverse events or complications in the full cohort of 201 patients.

Monocular vision based autonomous navigation for a cost-effective MAV in GPS-denied environments

In this paper, we present a monocular vision based autonomous navigation system for Micro Aerial Vehicles (MAVs) in GPS-denied environments. The major drawback of monocular systems is that the depth scale of the scene can not be determined without prior knowledge or other sensors. To address this problem, we minimize a cost function consisting of a drift-free altitude measurement and up-to-scale position estimate obtained using the visual sensor. We evaluate the scale estimator, state estimator and controller performance by comparing with ground truth data acquired using a motion capture system. All resources including source code, tutorial documentation and system models are available online.

Building the computer mediated distance learning community: Issues and observations drawn from teaching and learning

This paper discusses computer mediated distance learning on a Master's level course in the UK and student perceptions of this as a quality learning environment.