Immunogenicity and protective efficacy of an anti-Streptococcus pyogenes vaccine candidate in multiple animal species

Streptococcus pyogenes, also known as Group A Streptococcus (GAS) has been associated with a range of diseases from the mild pharyngitis and pyoderma to more severe invasive infections such as streptococcal toxic shock. GAS also causes a number of non-suppurative post-infectious diseases such as rheumatic fever, rheumatic heart disease and glomerulonephritis. The large extent of GAS disease burden necessitates the need for a prophylactic vaccine that could target the diverse GAS emm types circulating globally. Anti-GAS vaccine strategies have focused primarily on the GAS M-protein, an extracellular virulence factor anchored to GAS cell wall. As opposed to the hypervariable N-terminal region, the C-terminal portion of the protein is highly conserved among different GAS emm types and is the focus of a leading GAS vaccine candidate, J8-DT/alum. The vaccine candidate J8-DT/alum was shown to be immunogenic in mice, rabbits and the non-human primates, hamadryas baboons. Similar responses to J8-DT/alum were observed after subcutaneous and intramuscular immunization with J8-DT/alum, in mice and in rabbits. Further assessment of parameters that may influence the immunogenicity of J8-DT demonstrated that the immune responses were identical in male and female mice and the use of alum as an adjuvant in the vaccine formulation significantly increased its immunogenicity, resulting in a long-lived serum IgG response. Contrary to the previous findings, the data in this thesis indicates that a primary immunization with J8-DT/alum (50ƒÊg) followed by a single boost is sufficient to generate a robust immune response in mice. As expected, the IgG response to J8- DT/alum was a Th2 type response consisting predominantly of the isotype IgG1 accompanied by lower levels of IgG2a. Intramuscular vaccination of rabbits with J8-DT/alum demonstrated that an increase in the dose of J8-DT/alum up to 500ƒÊg does not have an impact on the serum IgG titers achieved. Similar to the immune response in mice, immunization with J8-DT/alum in baboons also established that a 60ƒÊg dose compared to either 30ƒÊg or 120ƒÊg was sufficient to generate a robust immune response. Interestingly, mucosal infection of naive baboons with a M1 GAS strain did not induce a J8-specific serum IgG response. As J8-DT/alum mediated protection has been previously reported to be due to the J8- specific antibody formed, the efficacy of J8-DT antibodies was determined in vitro and in vivo. In vitro opsonization and in vivo passive transfer confirmed the protective potential of J8-DT antibodies. A reduction in the bacterial burden after challenge with a bioluminescent M49 GAS strain in mice that were passively administered J8-DT IgG established that protection due to J8-DT was mediated by antibodies. The GAS burden in infected mice was monitored using bioluminescent imaging in addition to traditional CFU assays. Bioluminescent GAS strains including the ‘rheumatogenic’ M1 GAS could not be generated due to limitations with transformation of GAS, however, a M49 GAS strain was utilized during BLI. The M49 serotype is traditionally a ‘nephritogenic’ serotype associated with post-streptococcal glomerulonephritis. Anti- J8-DT antibodies now have been shown to be protective against multiple GAS strains such as M49 and M1. This study evaluated the immunogenicity of J8-DT/alum in different species of experimental animals in preparation for phase I human clinical trials and provided the ground work for the development of a rapid non-invasive assay for evaluation of vaccine candidates.

Road safety messages tailored for young adults : Using the Internet and encouraging protective passenger behaviour

Young drivers are at higher risk of crashes than other drivers when carrying passengers. Graduated Driver Licensing has demonstrated effectiveness in reducing fatalities however there is considerable potential for additional strategies to complement the approach. A survey with 276 young adults (aged 17-25 years, 64% females) was conducted to examine the potential and importance of strategies that are delivered via the Internet and potential strategies for passengers. Strategies delivered via the Internet represent opportunity for widespread dissemination and greater reach to young people at times convenient to them. The current study found some significant differences between males and females with regard to ways the Internet is used to obtain road safety information and the components valued in trusted road safety sites. There were also significant differences between males and females on the kinds of strategies used as passengers to promote driver safety and the context in which it occurred, with females tending to take more proactive strategies than males. In sum, young people see value in Internet delivery for passenger safety information (80% agreed/ strongly agreed) and more than 90% thought it was important to intervene while a passenger of a risky driver. Thus tailoring Internet road safety strategies to young people may differ for males and females however there is considerable potential for a passenger focus in strategies aimed at reducing young driver crashes.

Personalising teacher professional development : strategies enabling effective learning for educators of 21st century students

In the Knowledge Society, new demands are placed on teachers as they strive to empower young people to be global citizens, ready for the 21st century. Systemic shifts need to be made, however, to build capacity across the workforce to practise new ways of teaching and learning, including the personalisation of teacher professional development. This article argues new strategies and approaches for effective adult learning, including an individualised focus, context-based learning and an empowerment of teachers to develop their own personal learning networks. This article concludes with an analysis of the challenges facing professional development leaders in moving towards personalised teacher learning.

Strategies to engage engineering students in group project work

Project focused group work is significant in developing social and personal skills as well as extending the ability to identify, formulate and solve engineering problems. As a result of increasing undergraduate class sizes, along with the requirement for many students to work part-time, group projects, peer and collaborative learning are seen as a fundamental part of engineering education. Group formation, connection to learning objectives and fairness of assessment has been widely reported as major issues that leave students dissatisfied with group project based units. Several strategies were trialled including a study of formation of groups by different methods across two engineering disciplines over the past 2 years. Other strategies involved a more structured approach to assessment practices of civil and electrical engineering disciplines design units. A confidential online teamwork management tool was used to collect and collate student self and peer assessment ratings and used for both formative feedback as well as assessment purposes. Student satisfaction and overall academic results in these subjects have improved since the introduction of these interventions. Both student and staff feedback highlight this approach as enhancing student engagement and satisfaction, improved student understanding of group roles, reducing number of dysfunctional groups whilst requiring less commitment of academic resources.

Strategies for managing osteoarthritis

Background Although there are recommendations for the management of osteoarthritis (OA), little is known about how people with OA actually manage this chronic condition. Purpose The aims of this study were to identify the non-pharmacological and pharmacological therapies most commonly used for the management of hip or knee OA, in a community-based sample of adults, and to compare these with evidence-based recommendations. Methods A questionnaire was mailed to 2200 adult members of Arthritis Queensland living in Brisbane, Australia. It included questions about OA symptoms, management therapies and demographic characteristics. Results Of the 485 participants (192 men, 293 women) with hip or knee OA who completed the questionnaire, most had mild to moderate symptoms. Ninety-six percent of participants (aged 27–95 years) reported using at least one non-pharmacological therapy, and 78% reported using at least one pharmacological therapy. The most common currently used non-pharmacological strategy was range-of-motion exercises (men 52%, women 61%, p=0.05) and the most common frequently used pharmacological strategy was glucosamine/chondroitin (men 51%, women 60%, ns). For the most highly recommended strategies, 65% of men and 54% of women had never attended an information/education course (p=0.04), and fewer than half (46% of women and 42% of men, p=0.03) were frequent users of anti-inflammatory agents. Conclusion The findings suggest that many people with knee or hip OA do not follow the most highly endorsed of the OARSI (Osteoarthritis Research Society International) recommendations for management of OA. Health professionals should be encouraged to recommend evidence-based therapies to their patients.

Falls in Parkinson’s disease : evidence for altered stepping strategies on compliant surfaces

Background: Real-world environments comprise surfaces of different textures, densities and gradients, which can threaten postural stability and increase falls risk. However, there has been limited research that has examined how walking on compliant surfaces influences gait and postural stability in older people and PD patients. Methods: PD patients (n = 49) and age-matched controls (n = 32) were assessed using three dimensional motion analysis during self-paced walking on both firm and foam walkways. Falls were recorded prospectively over 12 months using daily falls calendars. Results: Walking on a foam surface influenced the temporospatial characteristics for all groups, but PD fallers adopted very different joint kinematics compared with controls. PD fallers also demonstrated reduced toe clearance and had increased mediolateral head motion(relative to walking velocity) compared with control participants. Conclusions: Postural control deficits in PD fallers may impair their capacity to attenuate surface-related perturbations and control head motion. The risk of falling for PD patients may be increased on less stable surfaces.

Enhancing student success and retention : an institution-wide strategy for peer programs

Higher Education's widening participation agenda prioritises improving access to university for low-SES students. Parallel with these ambitious national participation targets, is the challenge for universities to significantly improve student retention rates; hence, the need to implement strategies aimed to improve the quality of the student learning experience and build a 'sense of belonging'. Within the framework of the First Year Experience Program, Queensland University of Technology has embarked on establishing a whole-of-institution model for peer programs that aims to: 1) improve the student learning experience and outcomes; and, 2) establish quality assured and sustainable programs. This paper reports on the maturation university-wide peer program strategy and considers the challenges of implementing, evaluating and resourcing a sustainable and inclusive approach to peer programs.

Evaluation of an intervention to promote protective infant feeding practices to prevent childhood obesity : outcomes of the NOURISH RCT at 14 months of age and 6 months post the first of two intervention modules

OBJECTIVE: To evaluate a universal obesity prevention intervention, which commenced at infant age 4-6 months, using outcome data assessed 6-months after completion of the first of two intervention modules and 9 months from baseline. DESIGN: Randomised controlled trial of a community-based early feeding intervention. SUBJECTS AND METHODS: 698 first-time mothers (mean age 30±5 years) with healthy term infants (51% male) aged 4.3±1.0 months at baseline. Mothers and infants were randomly allocated to self-directed access to usual care or to attend two group education modules, each delivered over three months, that provided anticipatory guidance on early feeding practices. Outcome data reported here were assessed at infant age 13.7±1.3 months. Anthropometrics were expressed as z-scores (WHO reference). Rapid weight gain was defined as change in weight-for-age z-score (WAZ) > +0.67. Maternal feeding practices were assessed via self-administered questionnaire. RESULTS: There were no differences according to group allocation on key maternal and infant characteristics. At follow up (n=598 [86%]) the intervention group infants had lower BMIZ (0.42±0.85 vs 0.23±0.93, p=0.009) and infants in the control group were more likely to show rapid weight gain from baseline to follow up (OR=1.5 CI95%1.1-2.1, p=0.014). Mothers in the control group were more likely to report using non- responsive feeding practices that fail to respond to infant satiety cues such as encouraging eating by using food as a reward (15% vs 4%, p=0.001) or using games ( 67% vs 29%, p<0.001). CONCLUSIONS: These results provide early evidence that anticipatory guidance targeting the ‘when, what and how’ of solid feeding can be effective in changing maternal feeding practices and, at least in the short term, reducing anthropometric indicators of childhood obesity risk. Analyses of outcomes at later ages are required to determine if these promising effects can be sustained.

Falls after discharge from hospital : is there a gap between older peoples' knowledge about falls prevention strategies and the research evidence?

Purpose: The aim of this study was to examine whether older people are prepared to engage in appropriate falls prevention strategies after discharge from hospital. Design and Methods We used a semi-structured interview to survey older patients about to be discharged from hospital and examined their knowledge regarding falls prevention strategies to utilize in the post-discharge period. The study was part of a prospective cohort study, nested within a larger, randomized controlled trial. Participants (n = 333) were asked to suggest strategies to reduce their falls risk at home after discharge, and their responses were compared with current reported research evidence for falls prevention interventions.  Results Participants’ strategies (n = 629) were classified into 7 categories: behavioral, support while mobilizing, approach to movement, physical environment, visual, medical, and activities or exercise. Although exercise has been identified as an effective falls risk reduction strategy, only 2.9% of participants suggested engaging in exercises. Falls prevention was most often conceptualized by participants as requiring 1 (35.4%) or 2 (40.8%) strategies for avoiding an accidental event, rather than engaging in sustained multiple risk reduction behaviors.  Implications Results demonstrate that older patients have low levels of knowledge about appropriate falls prevention strategies that could be used after discharge in spite of their increased falls risk during this period. Findings suggest that health care workers should design and deliver falls prevention education programs specifically targeted to older people who are to be discharged from hospital.

A potential HIV epidemic among male street laborers in urban Vietnam

Background: Mass migration to Asian cities is a defining phenomenon of the present age, as hundreds of millions of people move from rural areas or between cities in search of economic prosperity. Although many do prosper, large numbers of people experience significant social disadvantage. This is especially the case among poorly educated, migrant unskilled unregistered male laborers who do much of the manual work throughout the cities. These men are at significant risk for many health problems, including HIV infection. However, to date there has been little research in developing countries to explain the determinants of this risk, and thereby to suggest feasible preventive strategies. Objectives and Methodology: Using combined qualitative and quantitative methods, the aim of this study was to explore the social contexts that affect health vulnerabilities and to develop conceptual models to predict risk behaviors for HIV [illicit drug use, unsafe sex, and non-testing for HIV] among male street laborers in Hanoi, Vietnam. Qualitative Research: Sixteen qualitative interviews revealed a complex variety of life experiences, beliefs and knowledge deficits that render these mostly poor and minimally educated men vulnerable to health problems including HIV infection. This study formed a conceptual model of numerous stressors related to migrants’ life experiences in urban space, including physical, financial and social factors. A wide range of coping strategies were adopted to deal with stressors – including problem-focused coping (PFC) and emotion-focused coping (EFC), pro-social and anti-social, active and passive. These men reported difficulty in coping with stressors because they had weak social networks and lacked support from formal systems. A second conceptual model emerged that highlighted equivalent influences of individual psychological factors, social integration, social barriers, and accessibility regarding drug use and sexual risk behavior. Psychological dimensions such as tedium, distress, fatalism and revenge, were important. There were strong effects of collective decision-making and fear of social isolation on shaping risk behaviors. These exploratory qualitative interviews helped to develop a culturally appropriate instrument for the quantitative survey and informed theoretical models of the factors that affect risk behaviors for HIV infection. Quantitative Research: The Information-Motivation-Behavioral Skills (IMB) model was adopted as the theoretical framework for a large-scale survey. It was modified to suit the contexts of these Vietnamese men. By doing a social mapping technique, 450 male street laborers were interviewed in Hanoi, Vietnam. The survey revealed that the risk of acquiring and transmitting HIV was high among these men. One in every 12 men reported homosexual or bisexual behavior. These men on average had 3 partners within the preceding year, and condom use was inconsistent. One third had had sex with commercial sex workers (CSW) and only 30% of them reported condom use; 17% used illicit drugs sometimes, with 66.7% of them frequently sharing injecting equipment with peers. Despite the risks, only 19.8% of men had been tested for HIV during the previous 12 months. These men have limited HIV knowledge and only moderate motivation and perceived behavioral skills for protective behavior. Although rural-to-urban migration was not associated with sexual risk behavior, three elements of the IMB model and depression associated with the process of mobility were significant determinants of sexual behavior. A modified model that incorporated IMB elements and psychosocial stress was found to be a better fit than the original IMB model alone in predicting protected sex behavior among the men. Men who were less psychologically and socially stressed, better informed and motivated for HIV prevention were more likely to demonstrate behavioral skills, and in turn were more likely to engage in safer sexual behavior. With regard to drug use, although the conventional model accounted for slightly less variance than the modified IMB model, data were of better fit for the conventional model. Multivariate analyses revealed that men who originated from urban areas, those who were homo- or bi-sexually identified and had better knowledge and skills for HIV prevention were more likely to access HIV testing, while men who had more sexual partners and those who did not use a condom for sex with CSW were least likely to take a test. The modified IMB model provided a better fit than the conventional model, as it explained a greater variance in HIV testing. Conclusions and Implications: This research helps to highlight a potential hidden HIV epidemic among street male, unskilled, unregistered laborers. This group has multiple vulnerabilities to HIV infection through both their partners and peers. However, most do not know their HIV status and have limited knowledge about preventing infection. This is the first application of a modified IMB model of risk behaviors for HIV such as drug use, condom use, and uptake of HIV testing to research with male street laborers in urban settings. The study demonstrated that while the extended IMB model had better fit than the conventional version in explaining the behaviors of safe sex and HIV testing, it was not so for drug use. The results provide interesting directions for future research and suggest ways to effectively design intervention strategies. The findings should shed light on culturally appropriate HIV preventive education and support programs for these men. As Vietnam has much in common with other developing countries in Southeast Asia, this research provides evidence for policy and practice that may be useful for public health systems in similar countries.

Investigating mothers' decisions about their child's sun-protective behaviour using the Theory of Planned Behaviour

This study tested the utility of the Theory of Planned Behaviour (TPB) to predict mothers’ decisions to ensure their child engages in sun-protective behaviours. Mothers (N = 162) of children aged four or five years completed standard TPB items (attitude, subjective norm, perceived behavioural control, intention) and additional variables of role construction, mothers’ own sun safe behaviour, planning and past behaviour. One week later, participants (N = 116) reported their behaviour. Results found support for the TPB constructs, role construction, past behaviour and the mediating role of planning. These findings can inform strategies to prevent skin cancer.

Microscopic traffic hysteresis in traffic oscillations : a behavioral perspective

This paper studies traffic hysteresis arising in traffic oscillations from a behavioral perspective. It is found that the occurrence and type of traffic hysteresis is closely correlated with driver behavior when experiencing traffic oscillations and with the time driver reaction begins relative to the starting deceleration wave. Statistical results suggest that driver behavior is different depending on its position along the oscillation. This suggests that different car-following models should be used inside the different stages of an oscillation in order to replicate realistic congestion features.

Towards an integration of the theory of planned behaviour and cognitive behavioural strategies : an example from a school-based injury prevention programme

Adolescent risk-taking behavior has potentially serious injury consequences and school-based behavior change programs provide potential for reducing such harm. A well-designed program is likely to be theory-based and ecologically valid however it is rare that the operationalisation process of theories is described. The aim of this paper is to outline how the Theory of Planned Behavior and Cognitive Behavioral Therapy informed intervention design in a school setting. Teacher interviews provided insights into strategies that might be implemented within the curriculum and provided detail used to operationalise theory constructs. Benefits and challenges in applying both theories are described with examples from an injury prevention program, Skills for Preventing Injury in Youth.

Self-regulation and mastery motivation in individuals with developmental disabilities : barriers, supports, and strategies

The development of the capacity for self-regulation represents an important achievement of childhood and is associated with social, behavioral, and academic competence (Bronson, 2001; Cleary & Zimmerman, 2004). Self-regulation evolves as individuals mature, with its final form integrating emotional, cognitive, and behavioral elements working together to achieve self-selected goals. This evolution is closely intertwined with the innate press to master the environment, labeled mastery motivation (Morgan, Harmon, & Maslin-Cole, 1990), as competence is the aim that underpins mastery motivation.