Outdoor worker sun protection project : a comprehensive applied research project to demonstrate the effectiveness of sun protection measures which influence high risk outdoor workers in Queensland to adopt sun safe behaviour practices 2010 – 2013

The QUT Outdoor Worker Sun Protection (OWSP) project undertook a comprehensive applied health promotion project to demonstrate the effectiveness of sun protection measures which influence high risk outdoor workers in Queensland to adopt sun safe behaviours. The three year project (2010-2013) was driven by two key concepts: 1) The hierarchy of control, which is used to address risks in the workplace, advocates for six control measures that need to be considered in order of priority (refer to Section 3.4.2); and 2) the Ottawa Charter which recommends five action means to achieve health promotion (refer to Section 2.1). The project framework was underpinned by a participatory action research approach that valued peoples’ input, took advantage of existing skills and resources, and stimulated innovation (refer to Section 4.2). Fourteen workplaces (small and large) with a majority outdoor workforce were recruited across regional Queensland (Darling Downs, Northwest, Mackay and Cairns) from four industries types: 1) building and construction, 2) rural and farming, 3) local government, and 4) public sector. A workplace champion was identified at each workplace and was supported (through resource provision, regular contact and site visits) over a 14 to 18 month intervention period to make sun safety a priority in their workplace. Employees and employers were independently assessed for pre- and postintervention sun protection behaviours. As part of the intervention, an individualised sun safety action plan was developed in conjunction with each workplace to guide changes across six key strategy areas including: 1) Policy (e.g., adopt sun safety practices during all company events); 2) Structural and environmental (e.g., shade on worksites; eliminate or minimise reflective surfaces); 3) Personal protective equipment (PPE) (e.g., trial different types of sunscreens, or wide-brimmed hats); 4) Education and awareness (e.g., include sun safety in inductions and toolbox talks; send reminder emails or text messages to workers);5) Role modelling (e.g., by managers, supervisors, workplace champions and mentors); and 6) Skin examinations (e.g., allow time off work for skin checks). The participatory action process revealed that there was no “one size fits all” approach to sun safety in the workplace; a comprehensive, tailored approach was fundamental. This included providing workplaces with information, resources, skills, know how, incentives and practical help. For example, workplaces engaged in farming complete differing seasonal tasks across the year and needed to prepare for optimal sun safety of their workers during less labour intensive times. In some construction workplaces, long pants were considered a trip hazard and could not be used as part of a PPE strategy. Culture change was difficult to achieve and workplace champions needed guidance on the steps to facilitate this (e.g., influencing leaders through peer support, mentoring and role modelling). With the assistance of the project team the majority of workplaces were able to successfully implement the sun safety strategies contained within their action plans, up skilling them in the evidence for sun safety, how to overcome barriers, how to negotiate with all relevant parties and assess success. The most important enablers to the implementation of a successful action plan were a pro-active workplace champion, strong employee engagement, supportive management, the use of highly visual educational resources, and external support (provided by the project team through regular contact either directly through phone calls or indirectly through emails and e-newsletters). Identified barriers included a lack of time, the multiple roles of workplace champions, (especially among smaller workplaces), competing issues leading to a lack of priority for sun safety, the culture of outdoor workers, and costs or budgeting constraints. The level of sun safety awareness, knowledge, and sun protective behaviours reported by the workers increased between pre-and post-intervention. Of the nine sun protective behaviours that were assessed, the largest changes reported included a 26% increase in workers who “usually or always” wore a broad-brimmed hat, a 20% increase in the use of natural shade, a 19% increase in workers wearing long-sleeved collared shirts, and a 16% increase in workers wearing long trousers.

Outdoor Worker Sun Protection Project : a mixed methods intervention to improve sun safety among outdoor workers

Queensland, Australia has one of the highest rates of skin cancer in the world. Outdoor workers are regularly exposed to high doses of ultraviolet radiation, and are at increased risk to develop non-melanoma and melanoma skin cancers. In 2010, a health promotion intervention to improve sun protection among outdoor workers in Queensland commenced. The intervention employed a mixed methods approach and a participatory action research framework. Fourteen workplaces were recruited from building and construction, rural and farming, local government, and public sector organisations. Management and workers were engaged in cycles of assessment, reflection and discussion, planning, implementation and reassessing, over a 14-month intervention period. Overall, at least one workplace representative from each workplace (range 1-3) and in depth focus groups were held with a subset of workers (range 3-16) to assess sun safe behaviours pre and post intervention. Workers’ attitudes, beliefs, knowledge and willingness to engage in sun protection differed depending on workplace characteristics and support. A familiar theme among workers spoke of sun safety as being “common sense” and the “workers individual responsibility”. Often there was a discrepancy in the perceptions of the workers, compared to the view of workplace representatives and the workplaces position or policy on sun safety. In larger workplaces, especially Government Departments, workers were more aware and followed sun safe practices compared to smaller workplaces where sun safety was not a high priority. These results indicate that a workplace culture which places high values on safety and polices more broadly may also have a positive effect on sun safety among outdoor workers as well. In addition, the specific characteristics of the workplace and the outdoor work tasks influence workers willingness to engage in sun safety measures.

The duration of Chlamydia muridarum genital tract infection and associated chronic pathological changes are reduced in IL-17 knockout mice but protection is not increased further by immunization

IL-17 is believed to be important for protection against extracellular pathogens, where clearance is dependent on neutrophil recruitment and local activation of epithelial cell defences. However, the role of IL-17 in protection against intracellular pathogens such as Chlamydia is less clear. We have compared (i) the course of natural genital tract C. muridarum infection, (ii) the development of oviduct pathology and (iii) the development of vaccine-induced immunity against infection in wild type (WT) BALB/c and IL-17 knockout mice (IL-17-/-) to determine if IL-17-mediated immunity is implicated in the development of infection-induced pathology and/or protection. Both the magnitude and duration of genital infection was significantly reduced in IL-17-/- mice compared to BALB/c. Similarly, hydrosalpinx was also greatly reduced in IL-17-/- mice and this correlated with reduced neutrophil and macrophage infiltration of oviduct tissues. Matrix metalloproteinase (MMP) 9 and MMP2 were increased in WT oviducts compared to IL-17-/- animals at day 7 post-infection. In contrast, oviducts from IL-17-/- mice contained higher MMP9 and MMP2 at day 21. Infection also elicited higher levels of Chlamydia-neutralizing antibody in serum of IL-17-/- mice than WT mice. Following intranasal immunization with C. muridarum Major Outer Membrane Protein (MOMP) and cholera toxin plus CpG adjuvants, significantly higher levels of chlamydial MOMP-specific IgG and IgA were found in serum and vaginal washes of IL-17-/- mice. T cell proliferation and IFNγ production by splenocytes was greater in WT animals following in vitro re-stimulation, however vaccination was only effective at reducing infection in WT, not IL-17-/- mice. Intranasal or transcutaneous immunization protected WT but not IL-17-/- mice against hydrosalpinx development. Our data show that in the absence of IL-17, the severity of C. muridarum genital infection and associated oviduct pathology are significantly attenuated, however neither infection or pathology can be reduced further by vaccination protocols that effectively protect WT mice.

The role of immunoglobulins and their transporters in urogenital Chlamydial infections

Chlamydia trachomatis infections of the male and female reproductive tracts are the world's leading sexually transmitted bacterial disease, and can lead to damaging pathology, scarring and infertility. The resolution of chlamydial infection requires the development of adaptive immune responses to infection, and includes cell-mediated and humoral immunity. Whilst cluster of differentiation (CD)4+ T cells are known to be essential in clearance of infection [1], they are also associated with immune cell infiltration, autoimmunity and infertility in the testes [2-3]. Conversely, antibodies are less associated with inflammation, are readily transported into the reproductive tracts, and can offer lumenal neutralization of chlamydiae prior to infection. Antibodies, or immunoglobulins (Ig), play a supportive role in the resolution of chlamydial infections, and this thesis sought to define the function of IgA and IgG, against a variety of chlamydial antigens expressed during the intracellular and extracellular stages of the chlamydial developmental cycle. Transport of IgA and IgG into the mucosal lumen is facilitated by receptor-mediated transcytosis yet the expression profile (under normal conditions and during urogenital chlamydial infection) of the polymeric immunoglobulin receptor (pIgR) and the neonatal Fc receptor (FcRn) remains unknown. The expression profile of pIgR and FcRn in the murine male reproductive tract was found to be polarized to the lower and upper reproductive tract tissues respectively. This demonstrates that the two receptors have a tissue tropism, which must be considered when targeting pathogens that colonize different sites. In contrast, the expression of pIgR and FcRn in the female mouse was found to be distributed in both the upper and lower reproductive tracts. When urogenitally infected with Chlamydia muridarum, both male and female reproductive tracts up-regulated expression of pIgR and down-regulated expression of FcRn. Unsurprisingly, the up-regulation of pIgR increased the concentration of IgA in the lumen. However, down-regulation of FcRn, prevented IgG uptake and led to an increase or pooling of IgG in lumenal secretions. As previous studies have identified the importance of pIgR-mediated delivery of IgA, as well as the potential of IgA to bind and neutralize intracellular pathogens, IgA against a variety of chlamydial antigens was investigated. The protection afforded by IgA against the extracellular antigen major outer membrane protein (MOMP), was found to be dependent on pIgR expression in vitro and in vivo. It was also found that in the absence of pIgR, no protection was afforded to mice previously immunized with MOMP. The protection afforded from polyclonal IgA against the intracellular chlamydial antigens; inclusion membrane protein A (IncA), inclusion membrane proteins (IncMem) and secreted chlamydial protease-like activity factor (CPAF) were produced and investigated in vitro. Antigen-specific intracellular IgA was found to bind to the respective antigen within the infected cell, but did not significantly reduce inclusion formation (p > 0.05). This suggests that whilst IgA specific for the selected antigens was transported by pIgR to the chlamydial inclusion, it was unable to prevent growth. Similarly, immunization of male mice with intracellular chlamydial antigens (IncA or IncMem), followed by depletion CD4+ T cells, and subsequent urogenital C. muridarum challenge, provided minimal pIgR-mediated protection. Wild type male mice immunized with IncA showed a 57 % reduction (p < 0.05), and mice deficient in pIgR showed a 35 % reduction (p < 0.05) in reproductive tract chlamydial burden compared to control antigen, and in the absence of CD4+ T cells. This suggests that pIgR and secretory IgA (SIgA) were playing a protective role (21 % pIgR-mediated) in unison with another antigen-specific immune mechanism (36 %). Interestingly, IgA generated during a primary respiratory C. muridarum infection did not provide a significant amount of protection to secondary urogenital C. muridarum challenge. Together, these data suggest that IgA specific for an extracellular antigen (MOMP) can play a strong protective role in chlamydial infections, and that IgA targeting intracellular antigens is also effective but dependent on pIgR expression in tissues. However, whilst not investigated here, IgA targeting and blocking other intracellular chlamydial antigens, that are more essential for replication or type III secretion, may be more efficacious in subunit vaccines. Recently, studies have demonstrated that IgG can neutralize influenza virus by trafficking IgG-bound virus to lysosomes [4]. We sought to determine if this process could also traffic chlamydial antigens for degradation by lysosomes, despite Chlamydia spp. actively inhibiting fusion with the host endocytic pathway. As observed in pIgR-mediated delivery of anti-IncA IgA, FcRn similarly transported IgG specific for IncA which bound the inclusion membrane. Interestingly, FcRn-mediated delivery of anti-IncA IgG significantly decreased inclusion formation by 36 % (p < 0.01), and induced aberrant inclusion morphology. This suggests that unlike IgA, IgG can facilitate additional host cellular responses which affect the intracellular niche of chlamydial growth. Fluorescence microscopy revealed that IgG also bound the inclusion, but unlike influenza studies, did not induce the recruitment of lysosomes. Notably, anti-IncA IgG recruited sequestosomes to the inclusion membrane, markers of the ubiquitin/proteasome pathway and major histocompatibility complex (MHC) class I loading. To determine if the protection against C. muridarum infection afforded by IncA IgG in vitro translated in vivo, wild type mice and mice deficient in functional FcRn and MHC-I, were immunized, depleted of CD4+, and urogenitally infected with C. muridarum. Unlike in pIgR-deficient mice, the protection afforded from IncA immunization was completely abrogated in mice lacking functional FcRn and MHC-I/CD8+. Thus, both anti-IncA IgA and IgG can bind the inclusion in a pIgR and FcRn-mediated manner, respectively. However, only IgG mediates a higher reduction in chlamydial infection in vitro and in vivo suggesting more than steric blocking of IncA had occurred. Unlike anti-MOMP IgA, which reduced chlamydial infection of epithelial cells and male mouse tissues, IgG was found to enhance infectivity in vitro, and in vivo. Opsonization of EBs with MOMP-IgG enhanced inclusion formation of epithelial cells in a MOMP-IgG dose-dependent and FcRn-dependent manner. When MOMP-IgG opsonized EBs were inoculated into the vagina of female mice, a small but non-significant (p > 0.05) enhancement of cervicovaginal C. muridarum shedding was observed three days post infection in mice with functional FcRn. Interestingly, infection with opsonized EBs reduced the intensity of the peak of infection (day six) but protracted the duration of infection by 60 % in wild type mice only. Infection with EBs opsonized in IgG also significantly increased (p < 0.05) hydrosalpinx formation in the oviducts and induced lymphocyte infiltration uterine horns. As MOMP is an immunodominant antigen, and is widely used in vaccines, the ability of IgG specific to extracellular chlamydial antigens to enhance infection and induce pathology needs to be considered. Together, these data suggest that immunoglobulins play a dichotomous role in chlamydial infections, and are dependent on antigen specificity, FcRn and pIgR expression. FcRn was found to be highly expressed in upper male reproductive tract, whilst pIgR was dominantly expressed in the lower reproductive tract. Conversely, female mice expressed FcRn and pIgR in both the lower and upper reproductive tracts. In response to a normal chlamydial infection, pIgR is up-regulated increasing secretory IgA release, but FcRn is down-regulated preventing IgG uptake. Similarly to other studies [5-6], we demonstrate that IgA and IgG generated during primary chlamydial infections plays a minor role in recall immunity, and that antigen-specific subunit vaccines can offer more protection. We also show that both IgA and IgG can be used to target intracellular chlamydial antigens, but that IgG is more effective. Finally, IgA against the extracellular antigen MOMP can afford protection, whist IgG plays a deleterious role by increasing infectivity and inducing damaging immunopathology. Further investigations with additional antigens or combination subunit vaccines will enhance our understanding the protection afforded by antibodies against intracellular and extracellular pathogenic antigens, and help improve the development of an efficacious chlamydial vaccine.

System level tests of transformer differential protection using an IEC 61850 process bus

The IEC 61850 family of standards for substation communication systems were released in the early 2000s, and include IEC 61850-8-1 and IEC 61850-9-2 that enable Ethernet to be used for process-level connections between transmission substation switchyards and control rooms. This paper presents an investigation of process bus protection performance, as the in-service behavior of multi-function process buses is largely unknown. An experimental approach was adopted that used a Real Time Digital Simulator and 'live' substation automation devices. The effect of sampling synchronization error and network traffic on transformer differential protection performance was assessed and compared to conventional hard-wired connections. Ethernet was used for all sampled value measurements, circuit breaker tripping, transformer tap-changer position reports and Precision Time Protocol synchronization of sampled value merging unit sampling. Test results showed that the protection relay under investigation operated correctly with process bus network traffic approaching 100% capacity. The protection system was not adversely affected by synchronizing errors significantly larger than the standards permit, suggesting these requirements may be overly conservative. This 'closed loop' approach, using substation automation hardware, validated the operation of protection relays under extreme conditions. Digital connections using a single shared Ethernet network outperformed conventional hard-wired solutions.

Galectin-1 : a link between tumor hypoxia and tumor immune privilege

Purpose: To identify a 15-KDa novel hypoxia-induced secreted protein in head and neck squamous cell carcinomas (HNSCC) and to determine its role in malignant progression. Methods: We used surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and tandem MS to identify a novel hypoxia-induced secreted protein in FaDu cells. We used immunoblots, real-time polymerase chain reaction (PCR), and enzyme-linked immunoabsorbent assay to confirm the hypoxic induction of this secreted protein as galectin-1 in cell lines and xenografts. We stained tumor tissues from 101 HNSCC patients for galectin-1, CA IX (carbonic anhydrase IX, a hypoxia marker) and CDS (a T-cell marker). Expression of these markers was correlated to each other and to treatment outcomes. Results: SELDI-TOF studies yielded a hypoxia-induced peak at 15 kDa that proved to be galectin-1 by MS analysis. Immunoblots and PCR studies confirmed increased galectin-1 expression by hypoxia in several cancer cell lines. Plasma levels of galectin-1 were higher in tumor-bearing severe combined immunodeficiency (SCID) mice breathing 10% O 2 compared with mice breathing room air. In HNSCC patients, there was a significant correlation between galectin-1 and CA IX staining (P = .01) and a strong inverse correlation between galectin-1 and CDS staining (P = .01). Expression of galectin-1 and CDS were significant predictors for overall survival on multivariate analysis. Conclusion: Galectin-1 is a novel hypoxia-regulated protein and a prognostic marker in HNSCC. This study presents a new mechanism on how hypoxia can affect the malignant progression and therapeutic response of solid tumors by regulating the secretion of proteins that modulate immune privilege. © 2005 by American Society of Clinical Oncology.

Chronic immune activation and inflammation as the cause of malignancy

Several chronic infections known to be associated with malignancy have established oncogenic properties. However the existence of chronic inflammatory conditions that do not have an established infective cause and are associated with the development of tumours strongly suggests that the inflammatory process itself provides the prerequisite environment for the development of malignancy. This environment includes upregulation of mediators of the inflammatory response such as cyclo-oxygenase (COX)-2 leading to the production of inflammatory cytokines and prostaglandins which themselves may suppress cell mediated immune responses and promote angiogenesis. These factors may also impact on cell growth and survival signalling pathways resulting in induction of cell proliferation and inhibition of apoptosis. Furthermore, chronic inflammation may lead to the production of reactive oxygen species and metabolites such as malondialdehyde within the affected cells that may in turn induce DNA damage and mutations and, as a result, be carcinogenic. Here it is proposed that the conditions provided by a chronic inflammatory environment are so essential for the progression of the neoplastic process that therapeutic intervention aimed at inhibiting inflammation, reducing angiogenesis and stimulating cell mediated immune responses may have a major role in reducing the incidence of common cancers. © 2001 Cancer Research Campaign http://www.bjcancer.com.

The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease

Recent studies have demonstrated that angiogenesis and suppressed cell- mediated immunity (CMI) play a central role in the pathogenesis of malignant disease facilitating tumour growth, invasion and metastasis. In the majority of tumours, the malignant process is preceded by a pathological condition or exposure to an irritant which itself is associated with the induction of angiogenesis and/or suppressed CMI. These include: cigarette smoking, chronic bronchitis and lung cancer; chronic oesophagitis and oesophageal cancer; chronic viral infections such as human papilloma virus and ano-genital cancers, chronic hepatitis B and C and hepatocellular carcinoma, and Epstein- Barr virus (EBV) and lymphomas; chronic inflammatory conditions such as Crohn's disease and ulcerative colitis and colorectal cancer; asbestos exposure and mesothelioma and excessive sunlight exposure/sunburn and malignant melanoma. Chronic exposure to growth factors (insulin-like growth factor-I in acromegaly), mutations in tumour suppressor genes (TP53 in Li Fraumeni syndrome) and long-term exposure to immunosuppressive agents (cyclosporin A) may also give rise to similar environments and are associated with the development of a range of solid tumours. The increased blood supply would facilitate the development and proliferation of an abnormal clone or clones of cells arising as the result of: (a) an inherited genetic abnormality; and/or (b) acquired somatic mutations, the latter due to local production and/or enhanced delivery of carcinogens and mutagenic growth factors. With progressive detrimental mutations and growth-induced tumour hypoxia, the transformed cell, to a lesser or greater extent, may amplify the angiogenic process and CMI suppression, thereby facilitating further tumour growth and metastasis. There is accumulating evidence that long-term treatment with cyclo-oxygenase inhibitors (aspirin and indomethacin), cytokines such as interferon-α, anti-oestrogens (tamoxifen and raloxifene) and captopril significantly reduces the incidence of solid tumours such as breast and colorectal cancer. These agents are anti-angiogenic and, in the case of aspirin, indomethacin and interferon-α have proven immunomodulatory effects. Collectively these observations indicate that angiogenesis and suppressed CMI play a central role in the development and progression of malignant disease. (C) 2000 Elsevier Science Ltd.

What encourages sun protection among outdoor workers from four industries?

Objectives: We aimed to identify current practice of sun protection and factors associated with effective use in four outdoor worker industries in Queensland, Australia. Methods: Workplaces in four industries with a high proportion of outdoor workers (building/construction, rural/farming, local government, and public sector industries) were identified using an online telephone directory, screened for eligibility, and invited to participant via mail (n=15, recruitment rate 37%). A convenience sample of workers were recruited within each workplace (n=162). Workplaces’ sun protective policies and procedures were identified using interviews and policy analysis with workplace representatives, and discussion groups and computer-assisted telephone interviews with workers. Personal characteristics and sun protection knowledge, attitudes and behaviors were collated and analysed. Results: Just over half the workplaces had an existing policy which referred to sun protection (58%), and most provided at least some personal protective equipment (PPE), but few scheduled work outside peak sun hours (43%) or provided skin checks (21%). Several worker and workplace characteristics were associated with greater sun protection behaviour among workers, including having received education on the use of PPE (p<0.001), being concerned about being in the sun (p=0.002); and working in a smaller workplace (p=0.035). Conclusions: Uptake of sun protection by outdoor workers is affected by a complex interplay of both workplace and personal factors, and there is a need for effective strategies targeting both the workplace environment and workers’ knowledge, attitudes and behaviors to decrease harmful sun exposure further.

A single copy of a virus-derived transgene encoding hairpin RNA gives immunity to barley yellow dwarf virus

Barley yellow dwarf virus-PAV (BYDV-PAV) is the most serious and widespread virus of cereals worldwide. Natural resistance genes against this luteovirus give inadequate control, and previous attempts to introduce synthetic resistance into cereals have produced variable results. In an attempt to generate barley with protection against BYDV-PAV, plants were transformed with a transgene designed to produce hairpin (hp)RNA containing BYDV-PAV sequences. From 25 independent barley lines transformed with the BYDV-PAV hpRNA construct, nine lines showed extreme resistance to the virus and the majority of these contained a single transgene. In the progeny of two independent transgenic lines, inheritance of a single transgene consistently correlated with protection against BYDV-PAV. This protection was rated as immunity because the virus could not be detected in the challenged plants by ELISA nor recovered by aphid feeding experiments. In the field, BYDV-PAV is sometimes associated with the related luteovirus Cereal yellow dwarf virus-RPV (CYDV-RPV). When the transgenic plants were challenged with BYDV-PAV and CYDV-RPV together, the plants were susceptible to CYDV-RPV but immune to BYDV-PAV. This shows that the immunity is virus-specific and not broken down by the presence of CYDV. It suggests that CYDV-RPV does not encode a silencing-suppressor gene or that its product does not protect BYDV-PAV against the plant's RNAi-like defence mechanism. Either way, our results indicate that the BYDV-PAV immunity will be robust in the field and is potentially useful in minimizing losses in cereal production worldwide.

A flexible protection scheme for an islanded Multi-Microgrid

Multi-Microgrids (MMGs) have been proposed to connect distributed generators (DG), microgrids (MG), and medium-voltage (MV) loads with the distribution system. A flexible protection scheme that enables an islanded MMG to continue operation during fault conditions is yet to be developed. In this paper, a protection scheme for an islanded MMG that utilises MG controllers and communication links is proposed. The MMG model used includes two MGs connected to the distribution system. Each MG consists of diesel, wind, and photovoltaic (PV) microsources. The effectiveness of the proposed protection scheme is evaluated by simulation.

An improved protection strategy for microgrids

Microgrids (MG) enable the integration of low capacity renewable energy resources with distribution systems. A recently proposed protection scheme for MGs utilising undervoltage, High Impedance Fault (HIF) detection, directional protection modules, and communication links significantly reduces the fault clearing time compared to previous schemes. In this paper, the effect of replacing undervoltage protection with differential protection in a scheme that also contains HIF and directional protection modules is studied. The MG model used in this study includes a diesel, wind, and two photovoltaic (PV) microsources. The alternative protection schemes are evaluated by simulation. It is found that the protection scheme consisting of differential, HIF detection, and directional protection modules is more effective compared to the alternative in protecting the MG from some fault conditions such as the phase-A-to-ground, phase-B-to-C, and phase-B-to-C-to-ground.

Transcutaneous immunization with a novel lipid-based adjuvant protects against Chlamydia genital and respiratory infections

Mucosal adjuvants are important to overcome the state of immune tolerance normally associated with mucosal delivery and to enhance adaptive immunity to often-weakly immunogenic subunit vaccine antigens. Unfortunately, adverse side effects of many experimental adjuvants limit the number of adjuvants approved for vaccination. Lipid C is a novel, non-toxic, lipid oral vaccine-delivery formulation, developed originally for oral delivery of the live Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccine. In the present study, murine models of chlamydial respiratory and genital tract infections were used to determine whether transcutaneous immunization (TCI) with Lipid C-incorporated protein antigens could elicit protective immunity at the genital and respiratory mucosae. BALB/c mice were immunized transcutaneously with Lipid C containing the chlamydial major outer membrane protein (MOMP), with and without addition of cholera toxin and CpG-ODN 1826 (CT/CpG). Both vaccine combinations induced mixed cell-mediated and mucosal antibody immune responses. Immunization with Lipid C-incorporated MOMP (Lipid C/MOMP), either alone or with CT/CpG resulted in partial protection following live challenge with Chlamydia muridarum as evidenced by a significant reduction in recoverable Chlamydia from both the genital secretions and lung tissue. Protection induced by immunization with Lipid C/MOMP alone was not further enhanced by the addition of CT/CpG. These results highlight the potential of Lipid C as a novel mucosal adjuvant capable of targeting multiple mucosal surfaces following TCI. Protection at both the respiratory and genital mucosae was achieved without the requirement for potentially toxic adjuvants, suggesting that Lipid C may provide a safe effective mucosal adjuvant for human vaccination.

Australian domestic violence protection order legislation : a comparative quantitative content analysis of victim safety provisions

In Australia, protection orders are a key legal response to domestic violence, and are often viewed as a way of providing for victim safety. For instance, recently the joint Australian and New South Wales Law Reform Commissions recommended that a common core purpose of all state and territory domestic violence legislation should be ‘to ensure or maximise the safety and protection of persons who fear or experience family violence’ (2010:Recommendation 7-4). Drawing and building upon prior research in Australia and the United States (‘US’), this paper uses comparative quantitative content analysis to assess the victim safety focus of domestic violence protection order legislation in each Australian state and territory. The findings of this analysis show that the Northern Territory, South Australia and Victoria ‘stand out’ from the other jurisdictions, having the highest victim safety focus in their legislation. However, there remains sizeable scope for improvement in all Australian jurisdictions, in terms of the victim safety focus of their legislative provisions and the considerations of legislative inconsistency between jurisdictions.