549 resultados para complex response
Resumo:
The Oceania region is an area particularly prone to natural disasters such as cyclones, tsunamis, floods, droughts, earthquakes and volcanic eruptions. Many of the nations in the region are Small Island Developing States (SIDS), yet even within wealthy states such as Australia and New Zealand there are groups which are vulnerable to disaster. Vulnerability to natural disaster can be understood in human rights terms, as natural disasters threaten the enjoyment of a number of rights which are guaranteed under international law, including rights to health, housing, food, water and even the right to life itself. The impacts of climate change threaten to exacerbate these vulnerabilities, yet, despite the foreseeability of further natural disasters as a result of climate change, there currently exists no comprehensive international framework for disaster response offering practical and/or legally reliable mechanisms to assist at‐risk states and communities. This paper sets out to explore the human rights issues presented by natural disasters and examine the extent to which these issues can be addressed by disaster response frameworks at the international, regional and national levels.
Resumo:
A finely-tuned innate immune response plays a pivotal role in protecting host against bacterial invasion during periodontal disease progression. Hyperlipidemia has been suggested to exacerbate periodontal health condition. However, the underlying mechanism has not been addressed. In the present study, we investigated the effect of hyperlipidemia on innate immune responses to periodontal pathogen Porphyromonas gingivalis infection. Apolipoprotein E-deficient and wild-type mice at the age of 20 weeks were used for the study. Peritoneal macrophages were isolated and subsequently used for the study of viable P. gingivalis infection. ApoE−/− mice demonstrated inhibited iNOS production and impaired clearance of P. gingivalis in vitro and in vivo; furthermore, ApoE−/− mice displayed disrupted cytokine production pattern in response to P. gingivalis, with a decreased production of tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β and monocyte chemotactic protein-1. Microarray data demonstrated that Toll-like receptor (TLR) and NOD-like receptor (NLR) pathway were altered in ApoE−/− mice macrophages; further analysis of pattern recognition receptors (PRRs) demonstrated that expression of triggering receptors on myeloid cells-1 (TREM-1), an amplifier of the TLR and NLR pathway, was decreased in ApoE−/− mice macrophages, leading to decreased recruitment of NF-κB onto the promoters of the TNF-α and IL-6. Our data suggest that in ApoE−/− mice hyperlipidemia disrupts the expression of PRRs, and cripples the host’s capability to generate sufficient innate immune response to P. gingivalis, which may facilitate immune evasion, subgingival colonization and establishment of P. gingivalis in the periodontal niche.
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As highlighted by previous work in Normal Accident Theory1 and High Reliability Organisations, 2 the ability of a system to be flexible is of critical importance to its capability to prepare for, respond to, and recover from disturbance and disasters. This paper proposes that the research into ‘edge organisations’3 and ‘agility’4 is a potential means to operationalise components that embed high reliable traits in the management and oversight of critical infrastructure systems. Much prior work has focused on these concepts in a military frame whereas the study reported on here examines the application of these concepts to aviation infrastructure, specifically, a commercial international airport. As a commercial entity functions in a distinct manner from a military organisation this study aims to better understand the complementary and contradictory components of the application of agility work to a commercial context. Findings highlight the challenges of making commercial operators of infrastructure systems agile as well as embedding traits of High Reliability in such complex infrastructure settings.
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Indonesia is a country spread across wide-ranging archipelago, located in South East Asia between two oceans, the Indian and the Pacific. Indonesia is well known as an active tectonic region because it lies on top of three major active tectonic plates: the Eurasian in the North, the Indian Ocean-Australian in the South, and the Pacific plate in the East. The southern and eastern part of the country features a range of volcanic arcs, volcanic mountains, and lowlands with 500 young volcanoes, of which 128 are active and thus representing 15% of the world’s active volcanoes. In the period 2002-2007, approximately 1782 disasters occurred, with hundreds of thousands of lives lost and billions of rupiah in losses incurred: (Floods - 1183 instances, cyclones - 272 instances, and landslides - 252 instances). Of these, the 2004 Aceh tsunami and the 2006 central Java earthquake (impacting predominantly city and suburbs of Yogyakarta) were the most significant. Even so, disaster management experts believe lessons learnt from the two major natural disasters needs to be formalised into laws and institutions before another disaster occurs, regardless of the type of natural disaster – i.e. Volcano eruption or landslide; as opposed to tsunami or earthquake. Following in the wake of disasters occurring in Yogyakarta, many of its community members responded by banding together as one, with the determination of rebuilding its villages and cities through the spirit of ‘gotong royong’. The idea of social interaction; in particular as a collective, consensual, and cooperative nation; has predominantly formed the ideological basis of Indonesia’s societal nature. Many Indonesian terms cohere to this ideology, such as: ‘koperasi” (cooperatives as the basis of economic interactions), ‘musyawarah’ (consensual nature in decision making), and ‘gotong royong’ (mutual assistance). ‘Gotong royong’ has become a key cultural operator in Indonesia, in particular In Jogjakarta. Appropriately so as ‘gotong royong’ is depicted from the traditional Javanese village, where labour is accomplished through reciprocal exchange and the villagers are motivated by a general ethos of selfishness and concern for the common good. The culture of ‘gotong royong’ promotes positive values such as social harmony and mutual reciprocation in disaster-affected areas provides the necessary spirit needed to endure the hardships and for all involved. While gotong royong emphasises the positive notions of mutual family support and deep community level activity there is a potential for contrast against government lead disaster response and recovery management activities especially in settings where sporadic governance mechanisms exist and transparency and accountability in the recovery process of public infrastructure assets have been questioned. This paper thus questions whether Gotong Royong is a double-edged sword, and explores the potential marriage of community values and governance mechanisms for future disaster management planning and practice.
Resumo:
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.
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The Life Drama program is a theatre-based experiential learning program developed in Papua New Guinea over the past seven years. The Life Drama team recognises that a significant proportion of “education” for learners of all ages takes place outside formal education systems, particularly in developing nations such as Papua New Guinea. If arts education principles and practices are to contribute meaningfully and powerfully to resolving social and cultural challenges, it is important to recognise that many learners and educators will encounter and use these principles and practices outside of school or university settings. This paper briefly describes the Life Drama program and its context, highlights its two streams of operation (community educators and teacher educators) and indicates some ways in which an arts-based education initiative like Life Drama contributes to Goal 3 of the Seoul Agenda:“Apply arts education principles and practices to contribute to resolving the social and cultural challenges facing today‟s world.” In particular, the project addresses sub-goal 3b:“Recognize and develop the social and cultural well-being dimensions of arts education”.
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Health educators face an unusual challenge in relation to HIV: the need to convey two emotionally contradictory messages. On the one hand, there is currently no cure for HIV, which eventually leads to death (emotionally negative message). On the other hand, people with HIV can live long, healthy and productive lives (emotionally positive message). In developing countries where HIV prevalence is high, it is imperative that both messages are conveyed effectively. This article reports on a specific form, Dancing Diseases, implemented as one component of the Life Drama pilot study on Karkar Island, Papua New Guinea. Life Drama is an applied theatre and performance approach to HIV education. The article discusses Dancing Diseases as an example of applied theatre and performance practice, reflects on the participant group’s engagement with the form, and offers some ways in which the form could be refined and used in other health education contexts.
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Background Recent initiatives within an Australia public healthcare service have seen a focus on increasing the research capacity of their workforce. One of the key initiatives involves encouraging clinicians to be research generators rather than solely research consumers. As a result, baseline data of current research capacity are essential to determine whether initiatives encouraging clinicians to undertake research have been effective. Speech pathologists have previously been shown to be interested in conducting research within their clinical role; therefore they are well positioned to benefit from such initiatives. The present study examined the current research interest, confidence and experience of speech language pathologists (SLPs) in a public healthcare workforce, as well as factors that predicted clinician research engagement. Methods Data were collected via an online survey emailed to an estimated 330 SLPs working within Queensland, Australia. The survey consisted of 30 questions relating to current levels of interest, confidence and experience performing specific research tasks, as well as how frequently SLPs had performed these tasks in the last 5 years. Results Although 158 SLPs responded to the survey, complete data were available for only 137. Respondents were more confident and experienced with basic research tasks (e.g., finding literature) and less confident and experienced with complex research tasks (e.g., analysing and interpreting results, publishing results). For most tasks, SLPs displayed higher levels of interest in the task than confidence and experience. Research engagement was predicted by highest qualification obtained, current job classification level and overall interest in research. Conclusions Respondents generally reported levels of interest in research higher than their confidence and experience, with many respondents reporting limited experience in most research tasks. Therefore SLPs have potential to benefit from research capacity building activities to increase their research skills in order to meet organisational research engagement objectives. However, these findings must be interpreted with the caveats that a relatively low response rate occurred and participants were recruited from a single state-wide health service, and therefore may not be representative of the wider SLP workforce.
Resumo:
Work design operates as the system of arrangements and procedures for organizing work to achieve organizational goals. These systems are commonly established in periods of environmental and organizational stability and formulated to achieve efficiencies in resources, employee and team configuration. However, organizations charged with responding to disasters need to be prepared to respond to unexpected events on a large scale, and disaster response planning needs to accommodate a broad range of possible disasters. When the disaster state occurs, enactment of the specific organizational response is devolved to group or individual level managers. While this enactment presents a range of risks, it also provides a potential avenue for innovation. Employees ultimately are the foundation of change and innovation, as it is people who develop, respond, change and implement new ideas. This study analyzes motivational characteristics of work design at an Australian humanitarian organization encompassing normal operations and periods of disaster activation. The study will identify the paradox of dual work designs and the implications for organizational innovation.
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Achilles tendinopathy is a common disorder involving physically active and sedentary individuals alike. Although the processes underlying its development are poorly understood, tendinopathy is widely regarded as an ‘overuse’ injury in which the tendon fails to adapt to prevalent loading conditions. Paradoxically, there is emerging evidence that heavy eccentric loading of the Achilles tendon may be an effective conservative approach for treatment of tendinopathy, with success rates of 60–80% reported. Interestingly, loading exercises involving other forms of muscle action, such as concentric activation, have been shown to be less effective treatment options. However, little is known about the acute response of tendon to exercise at present, and there are few plausible explanatory mechanisms for the observed beneficial effects of eccentric exercise, as opposed to other forms of strain stimuli. This paper presents the findings from a series of experiments undertaken to evaluate the effect of various strain stimuli on the time-dependent response of human Achilles tendon in vivo. It was shown for the first time, that heavy resistive ankle plantarflexion/ dorsiflexion exercises induced an immediate and significant decrease in Achilles tendon thickness (~15%). While thickness returned to pre-exercise levels within 24 hours, the recovery was exponential, with primary recovery occurring in less than 6 hours post-exercise. We proposed that such a diametral strain response with tensile loading reflects collagen realignment, Poison’s effects and radial extrusion of water from the tendon core. With unloading, the recovery of tendon dimensions likely reflects the re-diffusion of water via osmotic and/or inflammatory driven processes. Interestingly, prolonged walking was found to induce a similar diametral strain response. In subsequent studies, we demonstrated that eccentric exercise resulted in a greater reduction (-21%) in Achilles tendon thickness than isolated concentric exercise alone (-5%), despite a similar loading impulse. These novel findings, coupled with observations of a reduced diametral strain response with tendon pathology, highlight the importance of fluid movement to tendon function, nutrition and health. They also provide new insights into potential mechanisms underlying Achilles tendinopathy that impact rehabilitation strategies.
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Increases in functionality, power and intelligence of modern engineered systems led to complex systems with a large number of interconnected dynamic subsystems. In such machines, faults in one subsystem can cascade and affect the behavior of numerous other subsystems. This complicates the traditional fault monitoring procedures because of the need to train models of the faults that the monitoring system needs to detect and recognize. Unavoidable design defects, quality variations and different usage patterns make it infeasible to foresee all possible faults, resulting in limited diagnostic coverage that can only deal with previously anticipated and modeled failures. This leads to missed detections and costly blind swapping of acceptable components because of one’s inability to accurately isolate the source of previously unseen anomalies. To circumvent these difficulties, a new paradigm for diagnostic systems is proposed and discussed in this paper. Its feasibility is demonstrated through application examples in automotive engine diagnostics.
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Interferon gamma (IFNγ) is a key Th1 cytokine, with a principal role in the immune response against intracellular organisms such as Chlamydia. Along with being responsible for significant morbidity in human populations, Chlamydia is also responsible for wide spread infection and disease in many animal hosts, with reports that many Australian koala subpopulations are endemically infected. An understanding of the role played by IFNγ in koala chlamydial diseases is important for the establishment of better prophylactic and therapeutic approaches against chlamydial infection in this host. A limited number of IFNγ sequences have been published from marsupials and no immune reagents to measure expression have been developed. Through preliminary analysis of the koala transcriptome, we have identified the full coding sequence of the koala IFNγ gene. Transcripts were identified in spleen and lymph node tissue samples. Phylogenetic analysis demonstrated that koala IFNγ is closely related to other marsupial IFNγ sequences and more distantly related to eutherian mammals. To begin to characterise the role of this important cytokine in the koala's response to chlamydial infection, we developed a quantitative real time PCR assay and applied it to a small cohort of koalas with and without active chlamydial disease, revealing significant differences in expression patterns between the groups. Description of the IFNγ sequence from the koala will not only assist in understanding this species' response to its most important pathogen but will also provide further insight into the evolution of the marsupial immune system
Resumo:
Members of the insulin-like growth factor (IGF) family have been shown to play critical roles in normal growth and development, as well as in tumour biology. The IGF system is complex and the biological effects of the IGFs are determined by their diverse interactions between many molecules, including their interactions with extracellular matrix (ECM) proteins. Recent studies have demonstrated that IGFs associate with the ECM protein vitronectin (VN) through IGF-binding proteins (IGFBP) and that this interaction modulates IGF-stimulated biological functions, namely cell migration and cell survival through the cooperative involvement of the type-I IGF receptor (IGF-1R) and VN-binding integrins. Since IGFs play important roles in the transformation and progression of breast cancer and VN has been found to be over-expressed at the leading edge of breast tumours, this project aimed to describe the effects of IGF-I:VN interactions on breast cell function. This was undertaken to dissect the molecular mechanisms underlying IGF-I:VN-induced responses and to design inhibitors to block the effects of such interactions. The studies described herein demonstrate that the increase in migration of MCF-7 breast cancer cells in response to the IGF-I:IGFBP-5:VN complex is accompanied by differential expression of genes known to be involved in migration, invasion and/or survival, including Tissue-factor (TF), Stratifin (SFN), Ephrin-B2, Sharp-2 and PAI-1. This „migration gene signature‟ was confirmed using real-time PCR analysis. Substitution of the native IGF-I within the IGF-I:IGFBP:VN complex with the IGF-I analogue, \[L24]\[A31]-IGF-I, which has a reduced affinity for the IGF-1R, failed to stimulate cell migration and interestingly, also failed to induce the differential gene expression. This supports the involvement of the IGF-1R in mediating these changes in gene expression. Furthermore, lentiviral shRNA-mediated stable knockdown of TF and SFN completely abrogated the increased cell migration induced by IGF-I:IGFBP:VN complexes in MCF-7 cells. Indeed, when these cells were grown in 3D Matrigel™ cultures a decrease in the overall size of the 3D spheroids in response to the IGF-I:IGFBP:VN complexes was observed compared to the parental MCF-7 cells. This suggests that TF and SFN have a role in complex-stimulated cell survival. Moreover, signalling studies performed on cells with the reduced expression of either TF or SFN had a decreased IGF-1R activation, suggesting the involvement of signalling pathways downstream of IGF-1R in TF- and/or SFN-mediated cell migration and cell survival. Taken together, these studies provide evidence for a common mechanism activated downstream of the IGF-1R that induces the expression of the „migration gene signature‟ in response to the IGF-I:IGFBP:VN complex that confers breast cancer cells the propensity to migrate and survive. Given the functional significance of the interdependence of ECM and growth factor (GF) interactions in stimulating processes key to breast cancer progression, this project aimed at developing strategies to prevent such growth factor:ECM interactions in an effort to inhibit the downstream functional effects. This may result in the reduction in the levels of ECM-bound IGF-I present in close proximity to the cells, thereby leading to a reduction in the stimulation of IGF-1R present on the cell surface. Indeed, the inhibition of IGF-I-mediated effects through the disruption of its association with ECM would not alter the physiological levels of IGF-I and potentially only exert effects in situations where abnormal over expression of ECM proteins are found; namely carcinomas and hyperproliferative diseases. In summary, this PhD project has identified novel, innovative and realistic strategies that can be used in vitro to inhibit the functions exerted by the IGF-I:IGFBP:VN multiprotein complexes critical for cancer progression, with a potential to be translated into in vivo investigations. Furthermore, TF and SFN were found to mediate IGF-I:IGFBP:VN-induced effects, thereby revealing their potential to be used as therapeutic targets or as predictive biomarkers for the efficacy of IGF-1R targeting therapies in breast cancer patients. In addition to its therapeutic and clinical scope, this PhD project has significantly contributed to the understanding of the role of the IGF system in breast tumour biology by providing valuable new information on the mechanistic events underpinning IGF-I:VN-mediated effects on breast cell functions. Furthermore, this is the first instance where favourable binding sites for IGF-II, IGFBP-3 and IGFBP-5 on VN have been identified. Taken together, this study has functionally characterised the interactions between IGF-I and VN and through innovative strategies has provided a platform for the development of novel therapies targeting these interactions and their downstream effects.