Vaccination of healthy and diseased koalas (Phascolarctos cinereus) with a Chlamydia pecorum multi-subunit vaccine : evaluation of immunity and pathology

Chlamydial infections represent a major threat to the long-term survival of the koala and a successful vaccine would provide a valuable management tool. Vaccination however has the potential to enhance inflammatory disease in animals exposed to a natural infection prior to vaccination, a finding in early human and primate trials of whole cell vaccines to prevent trachoma. In the present study, we vaccinated both healthy koalas as well as clinically diseased koalas with a multi-subunit vaccine consisting of Chlamydia pecorum MOMP and NrdB mixed with immune stimulating complex as adjuvant. Following vaccination, there was no increase in inflammatory pathological changes in animals previously infected with Chlamydia. Strong antibody (including neutralizing antibodies) and lymphocyte proliferation responses were recorded in all vaccinated koalas, both healthy and clinically diseased. Vaccine induced antibodies specific for both vaccine antigens were observed not only in plasma but also in ocular secretions. Our data shows that an experimental chlamydial vaccine is safe to use in previously infected koalas, in that it does not worsen infection-associated lesions. Furthermore, the prototype vaccine is effective, as demonstrated by strong levels of neutralizing antibody and lymphocyte proliferation responses in both healthy and clinically diseased koalas. Collectively, this work illustrates the feasibility of developing a safe and effective Chlamydia vaccine as a tool for management of disease in wild koalas.

The open window of susceptibility to infection after acute exercise in healthy young male elite athletes

The 'open window' theory is characterised by short term suppression of the immune system following an acute bout of endurance exercise. This window of opportunity may allow for an increase in susceptibility to upper respiratory illness (URI). Many studies have indicated a decrease in immune function in response to exercise. However, many studies do not indicate changes in immune function past 2 hours after the completion of exercise, consequently failing to determine whether these immune cells numbers, or importantly their function, return to resting levels before the start of another bout of exercise. Ten male 'A' grade cyclists (age 24.2 +/- 5.3 years; body mass 73.8 +/- 6.5 kg; VO(2peak) 65.9 +/- 7.1 mL.kg(-1).min(-1)) exercised for two hours at 90% of their second ventilatory threshold. Blood samples were collected pre-, immediately post-, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours post-exercise. Immune variables examined included total leukocyte counts, neutrophil function (oxidative burst and phagocytic function), lymphocyte subset counts (CD4(+), CD8(+), and CD16(+)/56(+)), natural killer cell activity (NKCA), and NK phenotypes (CD56(dim)CD16(+), and CD56(bright)CD16(-)). There was a significant increase in total lymphocyte numbers from pre-, to immediately post-exercise (p<0.01), followed by a significant decrease at 2 hours post-exercise (p<0.001). CD4(+) T-cell counts significantly increased from pre-exercise, to 4 hours post- (p<0.05), and 6 hours post-exercise (p<0.01). However, NK (CD16(+)/56(+)) cell numbers decreased significantly from pre-exercise to 4 h post-exercise (p<0.05), to 6 h post-exercise (p<0.05), and to 8 h post-exercise (p<0.01). In contrast, CD56(bright)CD16- NK cell counts significantly increased from pre-exercise to immediately post-exercise (p<0.01). Neutrophil oxidative burst activity did not significantly change in response to exercise, while neutrophil cell counts significantly increased from pre-exercise, to immediately post-exercise (p<0.05), and 2 hours post-exercise (p<0.01), and remained significantly above pre-exercise levels to 8 hours post-exercise (p<0.01). Neutrophil phagocytic function significantly decreased from 2 hours post-exercise, to 6 hours post- (p<0.05), and 24 hours post-exercise (p<0.05). Finally, eosinophil cell counts significantly increased from 2 hours post to 6 hours post- (p<0.05), and 8 hours post-exercise (p<0.05). This is the first study to show changes in immunological variables up to 8 hours post-exercise, including significant NK cell suppression, NK cell phenotype changes, a significant increase in total lymphocyte counts, and a significant increase in eosinophil cell counts all at 8 hours post-exercise. Suppression of total lymphocyte counts, NK cell counts and neutrophil phagocytic function following exercise may be important in the increased rate of URI in response to regular intense endurance training.

In the bank or on the ground : an examination of financial reserves in Australian international aid organisations

This study contributes to the understanding of the contribution of financial reserves to sustaining nonprofit organisations. Recognising the limited recent Australian research in the area of nonprofit financial vulnerability, it specifically examines financial reserves held by signatories to the Code of Conduct of the Australian Council for International Development (ACFID) for the years 2006 to 2010. As this period includes the Global Financial Crisis, it presents a unique opportunity to observe the role of savings in a period of heightened financial threats to sustainability. The need for nonprofit entities to maintain reserves, while appearing intuitively evident, is neither unanimously accepted nor supported by established theoretic constructs. Some early frameworks attempt to explain the savings behaviour of nonprofit organisations and its role in organisational sustainability. Where researchers have considered the issue, its treatment has usually been either purely descriptive or alternatively, peripheral to a broader attempt to predict financial vulnerability. Given the importance of nonprofit entities to civil society, the sustainability of these organisations during times of economic contraction, such as the recent Global Financial Crisis, is a significant issue. Widespread failure of nonprofits, or even the perception of failure, will directly affect, not only those individuals who access their public goods and services, but would also have impacts on public confidence in both government and the sectors’ ability to manage and achieve their purpose. This study attempts to ‘shine a light’ on the paradox inherent in considering nonprofit savings. On the one hand, a public prevailing view is that nonprofit organisations should not hoard and indeed, should spend all of their funds on the direct achievement of their purposes. Against this, is the commonsense need for a financial buffer if only to allow for the day to day contingencies of pay rises and cost increases. At the entity level, the extent of reserves accumulated (or not) is an important consideration for Management Boards. The general public are also interested in knowing the level of funds held by nonprofits as a measure of both their commitment to purpose and as an indicator of their effectiveness. There is a need to communicate the level and prevalence of reserve holdings, balancing the prudent hedging of uncertainty against a sense of resource hoarding in the mind of donors. Finally, funders (especially governments) are interested in knowing the appropriate level of reserves to facilitate the ongoing sustainability of the sector. This is particularly so where organisations are involved in the provision of essential public goods and services. At a scholarly level, the study seeks to provide a rationale for this behaviour within the context of appropriate theory. At a practical level, the study seeks to give an indication of the drivers for savings, the actual levels of reserves held within the sector studied, as well as an indication as to whether the presence of reserves did mitigate the effects of financial turmoil during the Global Financial Crisis. The argument is not whether there is a need to ensure sustainability of nonprofits, but rather how it is to be done and whether the holding of reserves (net assets) is an essential element is achieving this. While the study offers no simple answers, it does appear that the organisations studied present as two groups, the ‘savers’ who build reserves and keep ‘money in the bank’ and ‘spender-delivers’ who put their resources ‘on the ground’. To progress an understanding of this dichotomy, the study suggests a need to move from its current approach to one which needs to more closely explore accounts based empirical donor attitude and nonprofit Management Board strategy.

Scaffolds for growth factor delivery as applied to bone tissue engineering

There remains a substantial shortfall in treatment of severe skeletal injuries. The current gold standard of autologous bone grafting from the same patient, has many undesirable side effects associated such as donor site morbidity. Tissue engineering seeks to offer a solution to this problem. The primary requirements for tissue engineered scaffolds have already been well established, and many materials, such as polyesters, present themselves as potential candidates for bone defects; they have comparable structural features, but they often lack the required osteoconductivity to promote adequate bone regeneration. By combining these materials with biological growth factors; which promote the infiltration of cells into the scaffold as well as the differentiation into the specific cell and tissue type, it is possible to increase the formation of new bone. However cost and potential complications associated with growth factors means controlled release is an important consideration in the design of new bone tissue engineering strategies. This review will cover recent research in the area of encapsulation and release of growth factors within a variety of different polymeric scaffolds.

In vitro physical stimulation of tissue-engineered and native cartilage

Because of the limited availability of donor cartilage for resurfacing defects in articular surfaces, there is tremendous interest in the in vitro bioengineering of cartilage replacements for clinical applications. However, attaining mechanical properties in engineered cartilaginous constructs that approach those of native cartilage has not been previously achieved when constructs are cultured under free-swelling conditions. One approach toward stimulating the development of constructs that are mechanically more robust is to expose them to physical environments that are similar, in certain ways, to those encountered by native cartilage. This is a strategy motivated by observations in numerous short-term experiments that certain mechanical signals are potent stimulators of cartilage metabolism. On the other hand, excess mechanical loading can have a deleterious effect on cartilage. Culture conditions that include a physical stimulation component are made possible by the use of specialized bioreactors. This chapter addresses some of the issues involved in using bioreactors as integral components of cartilage tissue engineering and in studying the physical regulation of cartilage. We first consider the generation of cartilaginous constructs in vitro. Next we describe the rationale and design of bioreactors that can impart either mechanical deformation or fluid-induced mechanical signals.

Micromarrows—Three-dimensional coculture of hematopoietic stem cells and mesenchymal stromal cells

Hematopoietic stem cell (HSC) transplant is a well established curative therapy for some hematological malignancies. However, achieving adequate supply of HSC from some donor tissues can limit both its application and ultimate efficacy. The theory that this limitation could be overcome by expanding the HSC population before transplantation has motivated numerous laboratories to develop ex vivo expansion processes. Pioneering work in this field utilized stromal cells as support cells in cocultures with HSC to mimic the HSC niche. We hypothesized that through translation of this classic coculture system to a three-dimensional (3D) structure we could better replicate the niche environment and in turn enhance HSC expansion. Herein we describe a novel high-throughput 3D coculture system where murine-derived HSC can be cocultured with mesenchymal stem/stromal cells (MSC) in 3D microaggregates—which we term “micromarrows.” Micromarrows were formed using surface modified microwells and their ability to support HSC expansion was compared to classic two-dimensional (2D) cocultures. While both 2D and 3D systems provide only a modest total cell expansion in the minimally supplemented medium, the micromarrow system supported the expansion of approximately twice as many HSC candidates as the 2D controls. Histology revealed that at day 7, the majority of bound hematopoietic cells reside in the outer layers of the aggregate. Quantitative polymerase chain reaction demonstrates that MSC maintained in 3D aggregates express significantly higher levels of key hematopoietic niche factors relative to their 2D equivalents. Thus, we propose that the micromarrow platform represents a promising first step toward a high-throughput HSC 3D coculture system that may enable in vitro HSC niche recapitulation and subsequent extensive in vitro HSC self-renewal.

Information support for health management in regional Sri Lanka : health managers’ perspectives

Good management, supported by accurate, timely and reliable health information, is vital for increasing the effectiveness of Health Information Systems (HIS). When it comes to managing the under resourced health systems of developing countries, information-based decision making is particularly important. This paper reports findings of a self-report survey that investigated perceptions of local health managers (HMs) of their own regional HIS in Sri Lanka. Data were collected through a validated, pre-tested postal questionnaire, and distributed among a selected group of HMs to elicit their perceptions of the current HIS in relation to information generation, acquisition and use, required reforms to the information system and application of information and communication technology (ICT). Results based on descriptive statistics indicated that the regional HIS was poorly organised and in need of reform; that management support for the system was unsatisfactory in terms of relevance, accuracy, timeliness and accessibility; that political pressure and community and donor requests took precedence over vital health information when management decisions were made; and use of ICT was unsatisfactory. HIS strengths included user-friendly paper formats, a centralised planning system and an efficient disease notification system; weaknesses were lack of comprehensiveness, inaccuracy, and lack of a feedback system. Responses of participants indicated that HIS would be improved by adopting an internationally accepted framework and introducing ICT applications. Perceived barriers to such improvements were high initial cost of educating staff to improve computer literacy, introduction of ICTs, and HIS restructure. We concluded that the regional HIS of Central Province, Sri Lanka had failed to provide much needed information support to HMs. These findings are consistent with similar research in other developing countries and reinforce the need for further research to verify causes of poor performance and to design strategic reforms to improve HIS in regional Sri Lanka.

Antigenic specificity of a monovalent versus polyvalent MOMP based Chlamydia pecorum vaccine in koalas (Phascolarctos cinereus)

Chlamydia continues to be a major pathogen of koalas. The bacterium is associated with ocular, respiratory and urogenital tract infections and a vaccine is considered the best option to limit the decline of mainland koala populations. Over the last 20 years, efforts to develop a chlamydial vaccine in humans have focussed on the use of the chlamydial major outer membrane protein (MOMP). Potential problems with the use of MOMP-based vaccines relate to the wide range of genetic diversity in its four variable domains. In the present study, we evaluated the immune response of koalas vaccinated with a MOMP-based C. pecorum vaccine formulated with genetically and serologically diverse MOMPs. Animals immunised with individual MOMPs developed strong antibody and lymphocyte proliferation responses to both homologous as well as heterologous MOMP proteins. Importantly, we also showed that vaccine induced antibodies which effectively neutralised various heterologous strains of koala C. pecorum in an in vitro assay. Finally, we also demonstrated that the immune responses in monovalent as well as polyvalent MOMP vaccine groups were able to recognise whole chlamydial elementary bodies, illustrating the feasibility of developing an effective MOMP based C. pecorum vaccine that could protect against a range of strains.

Evaluation of Eph receptor and ephrin expression within the human cornea and limbus

Eph receptor tyrosine kinases and their ligands, the ephrins, regulate the development and maintenance of multiple organs but little is known about their potential role within the cornea. The purpose of this study was to perform a thorough investigation of Eph/ephrin expression within the human cornea including the limbal stem cell niche. Initially, immunohistochemistry was performed on human donor eyes to determine the spatial distribution of Eph receptors and ephrins in the cornea and limbus. Patterns of Eph/ephrin gene expression in (1) immortalised human corneal endothelial (B4G12) or corneal epithelial (HCE-T) cell lines, and (2) primary cultures of epithelial or stromal cells established from the corneal limbus of cadaveric eye tissue were then assessed by reverse transcription (RT) PCR. Limbal epithelial or stromal cells from primary cultures were also assessed for evidence of Eph/ephrin-reactivity by immunofluorescence. Immunoreactivity for ephrinA1 and EphB4 was detected in the corneal endothelium of donor eyes. EphB4 was also consistently detected in the limbal and corneal epithelium and in cells located in the stroma of the peripheral cornea. Expression of multiple Eph/ephrin genes was detected in immortalised corneal epithelial and endothelial cell lines. Evidence of Eph/ephrin gene expression was also demonstrated in primary cultures of human limbal stromal (EphB4, B6; ephrinA5) and epithelial cells (EphA1, A2; ephrinA5, B2) using both RT-PCR and immunofluorescence. The expression of Eph receptors and ephrins within the human cornea and limbus is much wider than previously appreciated and suggests multiple potential roles for these molecules in the maintenance of normal corneal architecture.

Motivations and barriers to crowdfunding

This modest study is a snapshot of Australian donor motivations and donor barriers to crowdfunding, and provides some tentative recommendations to Artsupport Australia on ways crowdfunding uptake in Australia might increase. Limited qualitative data was gathered from 17 participants who have used crowdfunding in Australia such as: creative producers seeking funds; financial crowdfunding donors; Artsupport Australia mentors of artists who are using crowdfunding; and crowdfunding site stakeholders. These recommendations contribute ideas for development and implementation that align with the Australia Council for the Arts priorities, particularly to ‘build programs that support artists through all stages of their careers and to increase support for the arts from the business and general community through cultural philanthropy’ (Artsupport Australia website).

Could mobile telephony be harnessed for development in Papua New Guinea?

Could mobile telephony be harnessed for development in Papua New Guinea (PNG)? Could mobile phones be utilised to enhance the security and prosperity of rural communities? Could mobile phones be a useful tool in the achievement of the PNG 2050 Vision targets? This paper is based on literature review around use of mobile phones in development in Asia, Africa, and the Caribbean. It also draws on discussions with key players in PNG, such as NGOs, UN agencies, donor partners, telecommunication companies and the government of PNG. Anticipated benefits of mobile phone availability have not been fully realised in rural areas of PNG to date due to pricing, difficulties with recharging handset batteries in communities which do not have mains electricity supply, and also concerns about negative social changes related to mobile telephony, for example parental stress over youth forming unsuitable relationships. Nonetheless, there are manifest possible ways for mobile phone technology to change user communication patterns positively regarding economic output. In sectors as diverse as health, education and law and justice, discussions are currently underway to establish how mobile phones could be used to increase service delivery, particularly to rural and marginal communities.

Malaria antibody persistence correlates with duration of exposure

Background and Objectives  In Australia, the risk of transfusion-transmitted malaria is managed through the identification of ‘at-risk’ donors, antibody screening enzyme-linked immunoassay (EIA) and, if reactive, exclusion from fresh blood component manufacture. Donor management depends on the duration of exposure in malarious regions (>6 months: ‘Resident’, <6 months: ‘Visitor’) or a history of malaria diagnosis. We analysed antibody testing and demographic data to investigate antibody persistence dynamics. To assess the yield from retesting 3 years after an initial EIA reactive result, we estimated the proportion of donors who would become non-reactive over this period. Materials and Methods  Test results and demographic data from donors who were malaria EIA reactive were analysed. Time since possible exposure was estimated and antibody survival modelled. Results  Among seroreverters, the time since last possible exposure was significantly shorter in ‘Visitors’ than in ‘Residents’. The antibody survival modelling predicted 20% of previously EIA reactive ‘Visitors’, but only 2% of ‘Residents’ would become non-reactive within 3 years of their first reactive EIA. Conclusion  Antibody persistence in donors correlates with exposure category, with semi-immune ‘Residents’ maintaining detectable antibodies significantly longer than non-immune ‘Visitors’.

Building essential BPM capabilities to assist successful ICT deployment in the developing context : observations and recommendations from Sri Lanka

The role of Information and Communications Technology (ICT) has been identified as an important factor by the United Nations in achieving the millennium development goals (UNAPCICT, 2012)1. The potential for ICT has been identified as a means to reducing poverty, creating global communities by providing access to the internet and mobile networks to rural communities, improving education services, medical services, and information availability. As of today, significant amounts of funds have been invested by the governments and donor organizations in ‘Information and Communication Technologies for Development (ICT4D)’projects by establishing telecenters, e-villages, e-health, electronic and mobile banking, and egovernment systems for citizens in general, and more specifically, rural communities to bridge the digital divide (Heeks & Molla, 2009).

Plasma zinc and immune markers in runners in response to a moderate increase in training volume

Changes in plasma zinc concentration and markers of immune function were examined in a group of 10 male runners (n = 10) following a moderate increase in training over four weeks. Seven sedentary males acted as controls. Fasting blood samples were taken at rest, before (T0) and after (T4) four weeks of increased (+ 16 %) training and after two weeks of reduced (-31 %) training (T6). Blood was analysed for plasma zinc concentration, differential leucocyte counts, lymphocyte subpopulations and lymphocyte proliferation using incorporation of 3H-thymidine. The runners increased their training volume by 16 % over the four weeks. When compared with the nonathletes, the runners had lower concentrations of plasma zinc (p = 0.012), CD3 + (p = 0.042) and CD19 + lymphocytes (p = 0.010) over the four weeks. Lymphocyte proliferation in response to Concanavalin A stimulation was greater in the runners (p = 0.0090). Plasma zinc concentration and immune markers remained constant during the study. Plasma zinc concentration correlated with total leucocyte counts in the athletes at T6 (r = -0.72, p < 0.05) and with Pokeweed mitogen stimulation in the nonathletes at T6 (r = -0.92, p < 0.05). Therefore, athletes are unlikely to benefit from zinc supplementation during periods of moderately increased training volume.

Numerical solution of an optimal control model of dendritic cell treatment of a growing tumour

A new optimal control model of the interactions between a growing tumour and the host immune system along with an immunotherapy treatment strategy is presented. The model is based on an ordinary differential equation model of interactions between the growing tu- mour and the natural killer, cytotoxic T lymphocyte and dendritic cells of the host immune system, extended through the addition of a control function representing the application of a dendritic cell treat- ment to the system. The numerical solution of this model, obtained from a multi species Runge–Kutta forward-backward sweep scheme, is described. We investigate the effects of varying the maximum al- lowed amount of dendritic cell vaccine administered to the system and find that control of the tumour cell population is best effected via a high initial vaccine level, followed by reduced treatment and finally cessation of treatment. We also found that increasing the strength of the dendritic cell vaccine causes an increase in the number of natural killer cells and lymphocytes, which in turn reduces the growth of the tumour.