CTA1-DD is an effective adjuvant for targeting anti-chlamydial immunity to the murine genital mucosa

Chlamydia trachomatis is a significant human pathogen with potentially severe disease sequelae in the genital tract, including infertility. A successful vaccine will need to effectively target immunity to the genital mucosa. Intranasal immunisation with cholera toxin (CT) can target immunity to the genital tract, but has the potential to cause neurological side effects. CTA1-DD is a non-toxic potent mucosal adjuvant which combines the enzymatic properties of CT, with a B cell targeting moiety. Here, we demonstrate that intranasal immunisation with CTA1-DD and chlamydial Major Outer Membrane Protein (MOMP) results in the induction of neutralising systemic and mucosal antibodies, and reduces the level of chlamydial shedding following intravaginal challenge with Chlamydia muridarum. Thus, CTA1-DD is an effective adjuvant for vaccine development against Chlamydia trachomatis, and possibly also a range of other genital pathogens.

Thermal requirements, field mortality and population phenology modelling of Paropsis atomaria Olivier, an emergent pest in subtropical hardwood plantations

Paropsis atomaria is a recently emerged pest of eucalypt plantations in subtropical Australia. Its broad host range of at least 20 eucalypt species and wide geographical distribution provides it the potential to become a serious forestry pest both within Australia and, if accidentally introduced, overseas. Although populations of P. atomaria are genetically similar throughout its range, population dynamics differ between regions. Here, we determine temperature-dependent developmental requirements using beetles sourced from temperate and subtropical zones by calculating lower temperature thresholds, temperature-induced mortality, and day-degree requirements. We combine these data with field mortality estimates of immature life stages to produce a cohort-based model, ParopSys, using DYMEX™ that accurately predicts the timing, duration, and relative abundance of life stages in the field and number of generations in a spring–autumn (September–May) field season. Voltinism was identified as a seasonally plastic trait dependent upon environmental conditions, with two generations observed and predicted in the Australian Capital Territory, and up to four in Queensland. Lower temperature thresholds for development ranged between 4 and 9 °C, and overall development rates did not differ according to beetle origin. Total immature development time (egg–adult) was approximately 769.2 ± S.E. 127.8 DD above a lower temperature threshold of 6.4 ± S.E. 2.6 °C. ParopSys provides a basic tool enabling forest managers to use the number of generations and seasonal fluctuations in abundance of damaging life stages to estimate the pest risk of P. atomaria prior to plantation establishment, and predict the occurrence and duration of damaging life stages in the field. Additionally, by using local climatic data the pest potential of P. atomaria can be estimated to predict the risk of it establishing if accidentally introduced overseas. Improvements to ParopSys’ capability and complexity can be made as more biological data become available.

An empirical study of data collection protocols for wireless sensor networks

In the past few years, numerous data collection protocols have been developed for wireless sensor networks (WSNs). However, there has been no comparison of their relative performance in realistic environments. Here we report the results of an empirical study using a Fleck3 sensor network testbed for four different data collection protocols: One phase pull Directed Diffusion (DD), Expected Number of Transmissions (ETX), ETX with explicit acknowledgment (ETX-eAck), and ETX with implicit acknowledgment (ETX-iAck). Our empirical study provides useful insights for future sensor network deployments. When the required application end-to-end reliability is not strict (e.g., 70%) and link quality is good, DD and ETX are the best options because of their simplicity and low routing overhead. Both ETX-eAck and ETX-iAck achieve more than 90% end-to-end reliability when the link quality is reasonable (less than 25% packet loss). When the link quality is good, ETX-iAck introduces significantly less routing overhead (up to 50%) than ETX-eAck. However, if the radio transceiver supports variable packet length, ETX-eAck can outperform ETX-iAck when the link quality is poor. The important message from this paper is that choice of data collection protocol should come after the operating environment is understood. This understanding must include the characteristics of the radio transceiver, and link loss statistics from a long-term (across seasons and weather variation) radio survey of the site.

Deliberative assessment of surrogate consent in dementia research

Background Research involving incapacitated persons with dementia entails complex scientific, legal, and ethical issues, making traditional surveys of layperson views on the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD), involving balanced, detailed education and peer deliberation, on the views of those responsible for persons with dementia. Methods One hundred and seventy-eight community-recruited caregivers or primary decision-makers for persons with dementia were randomly assigned to either an all-day DD session group or a control group. Educational materials used for the DD session were vetted for balance and accuracy by an interdisciplinary advisory panel. We assessed the acceptability of family-surrogate consent for dementia research (“surrogate-based research”) from a societal policy perspective as well as from the more personal perspectives of deciding for a loved one or for oneself (surrogate and self-perspectives), assessed at baseline, immediately post-DD session, and 1 month after DD date, for four research scenarios of varying risk-benefit profiles. Results At baseline, a majority in both the DD and control groups supported a policy of family consent for dementia research in all research scenarios. The support for a policy of family consent for surrogate-based research increased in the DD group, but not in the control group. The change in the DD group was maintained 1 month later. In the DD group, there were transient changes in attitudes from surrogate or self-perspectives. In the control group, there were no changes from baseline in attitude toward surrogate consent from any perspective. Conclusions Intensive, balanced, and accurate education, along with peer deliberation provided by democratic deliberation, led to a sustained increase in support for a societal policy of family consent in dementia research among those responsible for dementia patients.

Here’s a story : using student podcasts to raise awareness of language

Thirty-five years ago, a landmark article entitled 'What The "Good Language Learner" Can Teach Us' suggested that if more was known about what 'successful learners' did, then those strategies could be taught to poorer learners to enhance learning (Rubin, 1975, p. 42). Since publication of Rubin's article, language instruction has begun to encompass technological applications (Chinnery, 2006) through mobile-assisted language learning (MALL or m-learning) like podcasts. Podcasting extends the classroom, offers convenience for diverse learners, and provides authentic listening opportunities. Although the effects of podcasting in higher education have yet to be investigated (Educause, 2007), this article describes how action research lead to the creation of a student learning strategy webpage featuring peer podcasts and successful language learning strategies in higher education.

‘Moments of disruption’ and the development of expatriate TESOL teachers

TESOL teachers, like mainstream teachers, often experience key incidents in their professional development. In expatriate TESOL however, unfamiliar cultural and linguistic contexts may disrupt teachers’ sense of both professional and personal identity. In this paper, narratives constructed from interviews of teacher experiences document a selection of critical events and discuss their implications for professional development in TESOL. Teachers reported that deep reflection on their experiences led to a re-conceptualisation of their professional and cultural identities. The analysis of their reflections may have significant implications for TESOL work in the context of the global and the local.

From frustration to satisfaction : using NLP to improve self-expression

How often do students tell us they are frustrated at being unable to express themselves, and more specifically, their true, deep and complex thoughts? We reassure them that language learning takes time, and that, with concerted effort, they will learn English. And mostly they do, but being able to fulfil various forms of academic assessment does not necessarily mean that non-native speakers can express, to their complete satisfaction, the depth and subtleties of their true thoughts and feelings such as is possible in their own language. Neuro-linguistic programming (NLP) is making an impact on English language teaching, and may just offer one solution to this problem. By drawing upon the notion of preferred representational systems, this paper suggests that expressing oneself with satisfaction may be as simple as understanding how one processes and stores information.

Alleviating poverty by engaging in microenterprise : how can INGOs in Vietnam help microenterprises overcome market constraints?

Microenterprise programs (MEPs) that aim to help poor communities engage in micro businesses have contributed significantly to poverty reduction in developing countries. However, a review of the literature suggests that the current approach adopted by MEPs has mainly provided services to microenterprises (MEs) based on what MEPs can supply rather than on what MEs actually need and what the market demands. Therefore, MEPs’ approaches are more likely to be supply driven. Yet when there are market constraints, such as high competition or low demand, this approach has been linked to the failure of MEs in their infancy. The alternative is a demand driven approach, in which MEPs provide MEs with support based on what MEs need, and what markets demand. However, research examining the application of this approach is limited. In order to gain an understanding of the approaches of MEPs, to identify whether these approaches are demand or supply driven, and to discover how these approaches are used to help MEs operate under market constraints, this study examined the operation of International Non-Government Organisations (INGOs) operating in Vietnam. This exploratory study involved in-depth interviews with senior executives from 10 INGOs. Thematic analysis was used to analyse data collected from the in-depth interviews. The results were further verified with publicly available data from the INGOs. The findings of this research indicate that the demand driven approach is dominant in most approaches of INGOs in Vietnam, and has become a key approach in helping MEs deal with market constraints. Further, rather than explaining the demand and supply driven dichotomy, the findings highlight that MEPs’ approaches can be viewed in two dimensions: a participant-demand driven approach focusing on the basic needs and capabilities of the extremely poor, irrespective of market demands; and a market-demand driven approach focusing on the capabilities of poor communities, while also accommodating market demands. This research provides contemporary and practical insights into the DD and SD approaches, and a better understanding of MEPs’ approaches to MED in Vietnam.

Factors affecting two- and five-year re-offence rates in Queensland drink drivers

Risk factors for repeat drink driving, an important road safety issue, are well known, but estimates of Australian recidivism rates by risk factors, apart from a recent NSW study, are not. Driving records of a cohort of Queensland drink drivers matched by age, region, BAC level and prior offence to participants in a drink driving rehabilitation program were used to estimate sex-specific two- and five-year re-offence rates overall and by these factors. Estimates of the proportion of Queensland drink drivers with a prior DD offence in 2004 were used to standardise rates to the Queensland drink driving population. Rates were higher in remote areas, as were rates in males, young drivers, drivers with high BAC levels and in drivers with one and especially with at least two prior DD convictions. Five-year rates for Queensland were estimated as 21.8% in males and 16.4% in females, appreciably higher than in NSW.

Nurses’ role in caring for people with a comorbidity of mental illness and intellectual disability : A literature review

This article examines literature on the role of the nurse caring for people with a dual disability (DD) of intellectual disability and mental illness. A search of the literature between 2000 and 2010 resulted in a total of 21 articles that met the inclusion criteria. Seven key categories of the role of the nurse were identified: (i) advocacy/health promotion (including working with family); (ii) assessment/case management; (iii) behavioural interventions; (iv) communication; (v) leadership and the nurse’s role within the multidisciplinary team; (vi) functions regarding medication administration; and (vii) safety/risk management. There is a paucity of research about the role of nurses working with people with DD, although a number of opinion-based articles exist. This article identifies a need for the role of the nurse working in DD to be more clearly articulated and for the development of evidence to guide best practice.

Prescribing practices of Australian dispensing doctors

Background: In response to health workforce shortages policymakers have considered expanding the roles that a health professional may perform. A more traditional combination of health professional roles is that of a dispensing doctor (DD) who routinely prescribes and dispenses pharmaceuticals. A systematic review conducted on mainly overseas DDs’ practices found that DDs tended to prescribe more items per patients, less often generically, and showed poorer adherence to best practice. Convenience for patients was cited by both patients and DDs as the main reason for dispensing. In Australia, rural doctors are allowed to dispense Pharmaceutical Benefit Scheme (PBS) subsidised pharmaceutical benefits if there is no reasonable pharmacy coverage. Little was known about the practices of these Australian DDs. Objectives: To examine the PBS prescribing patterns of dispensing with matched non-dispensing doctors and identify factors that influence prescribing behaviour. Method: A sequential explanatory (QUAN-->qual) mixed methodology was utilised. Firstly, rurality-matched DDs’ and non-DDs’ PBS data for fiscal years 2005-7 were analysed against criteria distilled from a systematic review and stakeholder consultations. Secondly, structured interviews were conducted with a purposive sample of DDs to examine the quantitative findings. Key findings: DDs prescribed significantly fewer PBS prescriptions per patients but used Regulation 24 significantly more than non-DDs. Regulation 24 biased the prescribing data. DDs prescribed proportionally more penicillin type antibiotics, adrenergic inhalants and non-steroidal anti-inflammatories as compared to non-DDs. Reasons offered by DD-respondents highlighted that prescribing was influenced by an awareness of cost to the patients, peer pressure and confidential prescriber feedback provided on a regular basis. Implications: This innovative census study does not support international data that DDs are less judicious in their prescribing. There is some evidence that DDs might reduce health inequity between rural and urban Australian, and that the DD health model is valuable to patients in isolated communities.

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.

Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility

Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00–2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15–4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47–5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease.

Differential gene expression in breast cancer cell lines and stroma-tumor differences in microdissected breast cancer biopsies revealed by display array analysis

To examine gene-expression patterning in late-stage breast cancer biopsies, we used a microdissection technique to separate tumor from the surrounding breast tissue or stroma. A DD-PCR protocol was then used to amplify expressed products, which were resolved using PAGE and used as probe to hybridize with representative human arrays and cDNA libraries. The probe derived from the tumor–stroma comparison was hybridized with a gene array and an arrayed cDNA library derived from a GCT of bone; 21 known genes or expressed sequence tags were detected, of which 17 showed differential expression. These included factors associated with epithelial to mesenchymal transition (vimentin), the cargo selection protein (TIP47) and the signal transducer and activator of transcription (STAT3). Northern blot analysis was used to confirm those genes also expressed by representative breast cancer cell lines. Notably, 6 genes of unknown function were restricted to tumor while the majority of stroma-associated genes were known. When applied to transformed breast cancer cell lines (MDA-MB-435 and T47D) that are known to have different metastatic potential, DD array analysis revealed a further 20 genes; 17 of these genes showed differential expression. Use of microdissection and the DD-PCR array protocol allowed us to identify factors whose localized expression within the breast may play a role in abnormal breast development or breast carcinogenesis.