The organisation of action in complex neurobiological systems

This chapter elucidates key ideas behind neurocomputational and ecological dynamics and perspectives of understanding the organisation of action in complex neurobiological systems. The need to study the close link between neurobiological systems and their environments (particularly their sensory and movement subsystems and the surrounding energy sources) is advocated. It is proposed how degeneracy in complex neurobiological systems provides the basis for functional variability in organisation of action. In such systems processes of cognition and action facilitate the specific interactions of each performer with particular task and environmental constraints.

Realistic yet humanitarian? The comprehensive plan of action and refugee policy in Southeast Asia

The 1989 Comprehensive Plan of Action (CPA) has recently been described as a successful example of how to manage large protracted refugee flows. However, this article revisits the circumstances surrounding the CPA used to resolve the prolonged Indo-Chinese refugee crisis to highlight that part of its development was linked to the fact that Southeast Asian states refused to engage with proposed solutions, which did not include repatriation for the majority of the Indo-Chinese asylum seekers who were deemed to be ‘non-genuine’1 ( UNGA, 1989a) refugees. This resulted in the CPA often forcibly repatriating ‘non-genuine’ refugees, particularly near the end of its program. This article reviews the CPA in order to assess whether its practices and results should be repeated.

iRAP Malaysia training course : decade of action for road safety

The International Road Assessment Program (iRAP) is a not-for-profit organisation that works in partnership with governments and non-government organisations in all parts of the world to make roads safe. The iRAP Malaysia pilot study on 3700km of road identified the potential to prevent 31,800 deaths and serious injuries over the next 20 years from proven engineering improvements. To help ensure the iRAP data and results are available to planners and engineers, iRAP, together with staff from the Centre for Accident Research and Road Safety – Queensland (CARRS-Q) and the Malaysian Institute of Road Safety Research (MIROS), developed a five-day iRAP training course that covers the background, theory and practical application of iRAP protocols, with a special focus on Malaysian case studies. Funding was provided by a competitive grant from the Australia-Malaysia Institute.

Symposium of action learning: introduction

Action learning / research is a broad field of research with deep roots in the 20th century. Unlike futures studies, which is more content oriented (i.e., the futures of health, peace futures, global futures), action learning / research is process and methodology oriented – addressing the manner in which research is done, rather than what is researched. At its core it is collaborative learning for social change. This is particularly important because, in this age of heterogenous changes and multi-fold social challenges, we need to be able to bridge learning about our futures with action and innovation in the present, in a way that is effective and accessible for lay communities and organisations, not just experts. [Introduction]

Moments of action provide insight into critical times for advection–diffusion–reaction processes

In 2010 Berezhkovskii and coworkers introduced the concept of local accumulation time (LAT) as a finite measure of the time required for the transient solution of a reaction diffusion equation to effectively reach steady state(Biophys J. 99, L59 (2010); Phys Rev E. 83, 051906 (2011)). Berezhkovskii’s approach is a particular application of the concept of mean action time (MAT) that was introduced previously by McNabb (IMA J Appl Math. 47, 193 (1991)). Here, we generalize these previous results by presenting a framework to calculate the MAT, as well as the higher moments, which we call the moments of action. The second moment is the variance of action time; the third moment is related to the skew of action time, and so on. We consider a general transition from some initial condition to an associated steady state for a one–dimensional linear advection–diffusion–reaction partial differential equation(PDE). Our results indicate that it is possible to solve for the moments of action exactly without requiring the transient solution of the PDE. We present specific examples that highlight potential weaknesses of previous studies that have considered the MAT alone without considering higher moments. Finally, we also provide a meaningful interpretation of the moments of action by presenting simulation results from a discrete random walk model together with some analysis of the particle lifetime distribution. This work shows that the moments of action are identical to the moments of the particle lifetime distribution for certain transitions.

Information practices of teen content creators : the intersection of action and experiences a grounded theory study

What are the information practices of teen content creators? In the United States over two thirds of teens have participated in creating and sharing content in online communities that are developed for the purpose of allowing users to be producers of content. This study investigates how teens participating in digital participatory communities find and use information as well as how they experience the information. From this investigation emerged a model of their information practices while creating and sharing content such as film-making, visual art work, story telling, music, programming, and web site design in digital participatory communities. The research uses grounded theory methodology in a social constructionist framework to investigate the research problem: what are the information practices of teen content creators? Data was gathered through semi-structured interviews and observation of teen’s digital communities. Analysis occurred concurrently with data collection, and the principle of constant comparison was applied in analysis. As findings were constructed from the data, additional data was collected until a substantive theory was constructed and no new information emerged from data collection. The theory that was constructed from the data describes five information practices of teen content creators. The five information practices are learning community, negotiating aesthetic, negotiating control, negotiating capacity, and representing knowledge. In describing the five information practices there are three necessary descriptive components, the community of practice, the experiences of information and the information actions. The experiences of information include information as participation, inspiration, collaboration, process, and artifact. Information actions include activities that occur in the categories of gathering, thinking and creating. The experiences of information and information actions intersect in the information practices, which are situated within the specific community of practice, such as a digital participatory community. Finally, the information practices interact and build upon one another and this is represented in a graphic model and explanation.

Dimensions of the venture creation process : amount, dynamics, and sequences of action in nascent entrepreneurship

This research examines the entrepreneurship phenomenon, and the question: Why are some venture attempts more successful than others? This question is not a new one. Prior research has answered this by describing those that engage in nascent entrepreneurship. Yet, this approach yielded little consensus and offers little comfort for those newly considering venture creation (Gartner, 1988). Rather, this research considers the process of venture creation, by focusing on the actions of nascent entrepreneurs. However, the venture creation process is complex (Liao, Welsch, & Tan, 2005), and multi-dimensional (Davidsson, 2004). The process can vary in the amount of action engaged by the entrepreneur; the temporal dynamics of how action is enacted (Lichtenstein, Carter, Dooley, and Gartner 2007); or the sequence in which actions are undertaken. And little is known about whether any, or all three, of these dimensions matter. Further, there exists scant general knowledge about how the venture creation process influences venture creation outcomes (Gartner & Shaver, 2011). Therefore, this research conducts a systematic study of what entrepreneurs do as they create a new venture. The primary goal is to develop general principles so that advice may be offered on how to ‘proceed’, rather than how to ‘be’. Three integrated empirical studies were conducted that separately focus on each of the interrelated dimensions. The basis for this was a randomly sampled, longitudinal panel, of nascent ventures. Upon recruitment these ventures were in the process of being created, but yet to be established as new businesses. The ventures were tracked one year latter to follow up on outcomes. Accordingly, this research makes the following original contributions to knowledge. First, the findings suggest that all three of the dimensions play an important role: action, dynamics, and sequence. This implies that future research should take a multi-dimensional view of the venture creation process. Failing to do so can only result in a limited understanding of a complex phenomenon. Second, action is the fundamental means through which venture creation is achieved. Simply put, more active venture creation efforts are more likely more successful. Further, action is the medium which allows resource endowments their effect upon venture outcomes. Third, the dynamics of how venture creation plays out over time is also influential. Here, a process with a high rate of action which increases in intensity will more likely achieve positive outcomes. Forth, sequence analysis, suggests that the order in which actions are taken will also drive outcomes. Although venture creation generally flows in sequence from discovery toward exploitation (Shane & Venkataraman, 2000; Eckhardt & Shane, 2003; Shane, 2003), processes that actually proceed in this way are less likely to be realized. Instead, processes which specifically intertwine discovery and exploitation action together in symbiosis more likely achieve better outcomes (Sarasvathy, 2001; Baker, Miner, & Eesley, 2003). Further, an optimal venture creation order exists somewhere between these sequential and symbiotic process archetypes. A process which starts out as symbiotic discovery and exploitation, but switches to focus exclusively on exploitation later on is most likely to achieve venture creation. These sequence findings are unique, and suggest future integration between opposing theories for order in venture creation.

Linking the fifth pillar to the first in the UN Decade of Action

The UN Decade of Action outlines five pillars of activity within a safe system framework to achieve the goal of slowing and then reversing the global growth in road traffic fatalities, especially in low-income and middle-income countries. The first four pillars - road safety management, safer roads and mobility, safer vehicles, and safer road users – have a strong focus on prevention of road traffic crashes and mitigation of energy exchange when a crash occurs. The fifth pillar – post-crash response – is far more specific, focusing only on crash victims in the event of a safe system failure. The victims appear to be relevant to the first four pillars only insofar as their numbers can be used to evaluate the success of road safety programs and identify the target groups and contributing factors. This paper argues that a better understanding of the lived experience of long term disability from traffic crashes has the potential to provide a feedback loop from the fifth pillar to the first. Research conducted in Thailand with male crash victims with spinal injury demonstrates that patterns of attribution and social and cultural factors have important implications for road safety management and for interventions aimed at influencing behaviour. In addition, the mobility constraints experienced by people with long term disability can point to systemic issues that might otherwise go unnoticed. The UN Decade of Action can benefit from a more thorough exploration of the experiences and circumstances of people with long term disability as the result of a road traffic crash. Rather than being evidence of the failure of the safe system, they can inform the development of more effective road safety management on low-income and middle-income countries.

Exercise-induced alterations in neutrophil degranulation and respiratory burst activity : possible mechanisms of action

Neutrophils constitute 50-60% of all circulating leukocytes; they present the first line of microbicidal defense and are involved in inflammatory responses. To examine immunocompetence in athletes, numerous studies have investigated the effects of exercise on the number of circulating neutrophils and their response to stimulation by chemotactic stimuli and activating factors. Exercise causes a biphasic increase in the number of neutrophils in the blood, arising from increases in catecholamine and cortisol concentrations. Moderate intensity exercise may enhance neutrophil respiratory burst activity, possibly through increases in the concentrations of growth hormone and the inflammatory cytokine IL-6. In contrast, intense or long duration exercise may suppress neutrophil degranulation and the production of reactive oxidants via elevated circulating concentrations of epinephrine (adrenaline) and cortisol. There is evidence of neutrophil degranulation and activation of the respiratory burst following exercise-induced muscle damage. In principle, improved responsiveness of neutrophils to stimulation following exercise of moderate intensity could mean that individuals participating in moderate exercise may have improved resistance to infection. Conversely, competitive athletes undertaking regular intense exercise may be at greater risk of contracting illness. However, there are limited data to support this concept. To elucidate the cellular mechanisms involved in the neutrophil responses to exercise, researchers have examined changes in the expression of cell membrane receptors, the production and release of reactive oxidants and more recently, calcium signaling. The investigation of possible modifications of other signal transduction events following exercise has not been possible because of current methodological limitations. At present, variation in exercise-induced alterations in neutrophil function appears to be due to differences in exercise protocols, training status, sampling points and laboratory assay techniques.

iRAP Malaysia training course: Decade of Action for Road Safety. Report to Department of Foreign Affairs and Trade, Australia-Malaysia Institute

The International Road Assessment Program (iRAP) is a not-for-profit organisation that works in partnership with governments and non-government organisations in all parts of the world to make roads safe. The iRAP Malaysia pilot study on 3,700km of road identified the potential to save 31,800 deaths and serious injuries over the next 20 years from proven engineering improvements. To help ensure the iRAP data and results are available to planners and engineers, iRAP, together with staff from the Centre for Accident Research and Road Safety – Queensland (CARRS-Q) and the Malaysian Institute of Road Safety Research (MIROS) developed a 5-day iRAP training course that covers the background, theory and practical application of iRAP protocols, with a special focus on Malaysian case studies. Funding was provided by a competitive grant from the Australian-Malaysia Institute.

The function and mechanisms of action of ghrelin and obestatin in ovarian cancer

In this study, we have demonstrated that the preproghrelin derived hormones, ghrelin and obestatin, may play a role in ovarian cancer. Ghrelin and obestatin stimulated an increase in cell migration in ovarian cancer cell lines and may play a role in cancer progression. Ovarian cancer is the leading cause of death among gynaecological cancers and is the sixth most common cause of cancer-related deaths in women in developed countries. As ovarian cancer is difficult to diagnose at a low tumour grade, two thirds of ovarian cancers are not diagnosed until the late stages of cancer development resulting in a poor prognosis for the patient. As a result, current treatment methods are limited and not ideal. There is an urgent need for improved diagnostic markers, as well better therapeutic approaches and adjunctive therapies for this disease. Ghrelin has a number of important physiological effects, including roles in appetite regulation and the stimulation of growth hormone release. It is also involved in regulating the immune, cardiovascular and reproductive systems and regulates sleep, memory and anxiety, and energy metabolism. Over the last decade, the ghrelin axis, (which includes the hormones ghrelin and obestatin and their receptors), has been implicated in the pathogenesis of many human diseases and it may t may also play an important role in the development of cancer. Ghrelin is a 28 amino acid peptide hormone that exists in two forms. Acyl ghrelin (usually referred to as ghrelin), has a unique n-octanoic acid post-translational modification (which is catalysed by ghrelin O-acyltransferase, GOAT), and desacyl ghrelin, which is a non-octanoylated form. Octanoylated ghrelin acts through the growth hormone secretagogue receptor type 1a (GHSR1a). GHSR1b, an alternatively spliced isoform of GHSR, is C-terminally truncated and does not bind ghrelin. Ghrelin has been implicated in the pathophysiology of a number of diseases Obestatin is a 23 amino acid, C-terminally amidated peptide which is derived from preproghrelin. Although GPR39 was originally thought to be the obestatin receptor this has been disproven, and its receptor remains unknown. Obestatin may have as diverse range of roles as ghrelin. Obestatin improves memory, inhibits thirst and anxiety, increases pancreatic juice secretion and has cardioprotective effects. Obestatin also has been shown to regulate cell proliferation, differentiation and apoptosis in some cell types. Prior to this study, little was known regarding the functions and mechanisms of action ghrelin and obestatin in ovarian cancer. In this study it was demonstrated that the full length ghrelin, GHSR1b and GOAT mRNA transcripts were expressed in all of the ovarian-derived cell lines examined (SKOV3, OV-MZ-6 and hOSE 17.1), however, these cell lines did not express GHSR1a. Ovarian cancer tissue of varying stages and normal ovarian tissue expressed the coding region for ghrelin, obestatin, and GOAT, but not GHSR1a, or GHSR1b. No correlations between cancer grade and the level of expression of these transcripts were observed. This study demonstrated for the first time that both ghrelin and obestatin increase cell migration in ovarian cancer cell lines. Treatment with ghrelin (for 72 hours) significantly increased cell migration in the SKOV3 and OV-MZ-6 ovarian cancer cell lines. Ghrelin (100 nM) stimulated cell migration in the SKOV3 (2.64 +/- 1.08 fold, p <0.05) and OV-MZ-6 (1.65 +/- 0.31 fold, p <0.05) ovarian cancer cell lines, but not in the representative normal cell line hOSE 17.1. This increase in migration was not accompanied by an increase in cell invasion through Matrigel. In contrast to other cancer types, ghrelin had no effect on proliferation. Ghrelin treatment (10nM) significantly decreased attachment of the SKOV3 ovarian cancer cell line to collagen IV (24.7 +/- 10.0 %, p <0.05), however, there were no changes in attachment to the other extracellular matrix molecules (ECM) tested (fibronectin, vitronectin and collagen I), and there were no changes in attachment to any of the ECM molecules in the OV-MZ-6 or hOSE 17.1 cell lines. It is, therefore, unclear if ghrelin plays a role in cell attachment in ovarian cancer. As ghrelin has previously been demonstrated to signal through the ERK1/2 pathway in cancer, we investigated ERK1/2 signalling in ovarian cancer cell lines. In the SKOV3 ovarian cancer cell line, a reduction in ERK1/2 phosphorylation (0.58 fold +/- 0.23, p <0.05) in response to 100 nM ghrelin treatment was observed, while no significant change in ERK1/2 signalling was seen in the OV-MZ-6 cell line with treatment. This suggests that this pathway is unlikely to be involved in mediating the increased migration seen in the ovarian cancer cell lines with ghrelin treatment. In this study ovarian cancer tissue of varying stages and normal ovarian tissue expressed the coding region for obestatin, however, no correlation between cancer grade and level of obestatin transcript expression was observed. In the ovarian-derived cell lines studied (SKOV3, OV-MZ-6 and hOSE 17.1) it was demonstrated that the full length preproghrelin mRNA transcripts were expressed in all cell lines, suggesting they have the ability to produce mature obestatin. This is the first study to demonstrate that obestatin stimulates cell migration and cell invasion. Obestatin induced a significant increase in migration in the SKOV3 ovarian cancer cell line with 10 nM (2.80 +/- 0.52 fold, p <0.05) and 100 nM treatments (3.12 +/- 0.68 fold, p <0.05) and in the OV-MZ-6 cancer cell line with 10 nM (2.04 +/- 0.10 fold, p <0.01) and 100 nM treatments (2.00 +/- 0.37 fold, p <0.05). Obestatin treatment did no affect cell migration in the hOSE 17.1normal ovarian epithelial cell line. Obestatin treatment (100 nM) also stimulated a significant increase in cell invasion in the OV-MZ-6 ovarian cancer cell line (1.45 fold +/- 0.13, p <0.05) and in the hOSE17.1 normal ovarian cell line cells (1.40 fold +/- 0.04 and 1.55 fold +/- 0.05 respectively, p <0.01) with 10 nM and 100 nM treatments. Obestatin treatment did not stimulate cell invasion in the SKOV3 ovarian cancer cell line. This lack of obestatin-stimulated invasion in the SKOV3 cell line may be a cell line specific result. In this study, obestatin did not stimulate cell proliferation in the ovarian cell lines and it has previously been shown to have no effect on cell proliferation in the BON-1 pancreatic neuroendocrine and GC rat somatotroph tumour cell lines. In contrast, obestatin has been shown to affect cell proliferation in gastric and thyroid cancer cell lines, and in some normal cell lines. Obestatin also had no effect on attachment of any of the cell lines to any of the ECM components tested (fibronectin, vitronectin, collagen I and collagen IV). The mechanism of action of obestatin was investigated further using a two dimensional-difference in gel electrophoresis (2D-DIGE) proteomic approach. After treatment with obestating (0, 10 and 100 nM), SKOV3 ovarian cancer and hOSE 17.1 normal ovarian cell lines were collected and 2D-DIGE analysis and mass spectrometry were performed to identify proteins that were differentially expressed in response to treatment. Twenty-six differentially expressed proteins were identified and analysed using Ingenuity Pathway Analysis (IPA). This linked 16 of these proteins in a network. The analysis suggested that the ERK1/2 MAPK pathway was a major mediator of obestatin action. ERK1/2 has previously been shown to be associated with obestatin-stimulated cell proliferation and with the anti-apoptotic effects of obestatin. Activation of the ERK1/2 signalling pathway by obestatin was, therefore, investigated in the SKOV3 and OV-MZ-6 ovarian cancer cell lines using anti-active antibodies and Western immunoblots. Obestatin treatment significantly decreased ERK1/2 phosphorylation at higher obestatin concentrations in both the SKOV3 (100 nM and 1000 nM) and OV-MZ-6 (1000 nM) cell lines compared to the untreated controls. Currently, very little is known about obestatin signalling in cancer. This thesis has demonstrated for the first time that the ghrelin axis may play a role in ovarian cancer migration. Ghrelin and obestatin increased cell migration in ovarian cancer cell lines, indicating that they may be a useful target for therapies that reduce ovarian cancer progression. Further studies investigating the role of the ghrelin axis using in vivo ovarian cancer metastasis models are warranted.

A simplified approach for calculating the moments of action for linear reaction-diffusion equations

The mean action time is the mean of a probability density function that can be interpreted as a critical time, which is a finite estimate of the time taken for the transient solution of a reaction-diffusion equation to effectively reach steady state. For high-variance distributions, the mean action time under-approximates the critical time since it neglects to account for the spread about the mean. We can improve our estimate of the critical time by calculating the higher moments of the probability density function, called the moments of action, which provide additional information regarding the spread about the mean. Existing methods for calculating the nth moment of action require the solution of n nonhomogeneous boundary value problems which can be difficult and tedious to solve exactly. Here we present a simplified approach using Laplace transforms which allows us to calculate the nth moment of action without solving this family of boundary value problems and also without solving for the transient solution of the underlying reaction-diffusion problem. We demonstrate the generality of our method by calculating exact expressions for the moments of action for three problems from the biophysics literature. While the first problem we consider can be solved using existing methods, the second problem, which is readily solved using our approach, is intractable using previous techniques. The third problem illustrates how the Laplace transform approach can be used to study coupled linear reaction-diffusion equations.

Ginger - mechanism of action in chemotherapy-induced nausea and vomiting: A review

Despite advances in anti-emetic therapy, chemotherapy-induced nausea and vomiting (CINV) still poses a significant burden to patients undergoing chemotherapy. Nausea, in particular, is still highly prevalent in this population. Ginger has been traditionally used as a folk remedy for gastrointestinal complaints and has been suggested as a viable adjuvant treatment for nausea and vomiting in the cancer context. Substantial research has revealed ginger to possess properties that could exert multiple beneficial effects on chemotherapy patients who experience nausea and vomiting. Bioactive compounds within the rhizome of ginger, particularly the gingerol and shogaol class of compounds, interact with several pathways that are directly implicated in CINV in addition to pathways that could play secondary roles by exacerbating symptoms. These properties include 5-HT3, substance P and acetylcholine receptor antagonism; anti-inflammatory properties; and modulation of cellular redox signalling, vasopressin release, gastrointestinal motility, and gastric emptying rate. This review outlines these proposed mechanisms by discussing the results of clinical, in vitro and animal studies both within the chemotherapy context and in other relevant fields. The evidence presented in this review indicates that ginger possesses multiple properties that could be beneficial in reducing chemotherapy-induced nausea and vomiting.

The 1989 Comprehensive Plan of Action (CPA) and refugee policy in Southeast Asia : twenty years forward what has changed?

In 2012, the only South East Asian countries that have ratified the 1951 Convention relating to the Status of Refugees and the 1967 Protocol Relating to the Status of Refugees (hereafter referred to as the 1951 Convention and 1967 Protocol) is Philippines (signed 1954), Cambodia (signed 1995) and Timor Leste (signed 2001). Countries such as Indonesia, Malaysia and Thailand have annual asylum seeking populations from Myanmar, South Asia and Middle East, that are estimated to be at 15 000-20 000 per country (UNHCR 2012). The lack of a permanent and formal asylum processing process in these countries means that that asylum-seeking populations in the region are reliant on the local offices of the United Nations High Commission for Refugees based in the region to process their claims. These offices rely upon the good will of these governments to have a presence near detection camps and in capital cities to process claims of those who manage to reach the UNHCR representative office. The only burden sharing mechanism within the region primarily exists under the Bali Process on People Smuggling, Trafficking in Persons and Related Transnational Crime (the Bali Process), introduced in 2002. The Bali Process refers to an informal cooperative agreement amongst the states from the Asia-Pacific region, with Australia and Indonesia as the co-chairs, which discusses its namesake: primarily anti-people smuggling activities and migration protocols. There is no provision within this process to discuss the development of national asylum seeking legislation, processes for domestic processing of asylum claims or burden sharing in contrast to other regions such as Africa and South America (i.e. 2009 African Union Convention for the Protection and Assistance of the Internally Displaced, 1969 African Union Convention Governing the Specific Aspects of Refugee Problems in Africa and 1984 Cartagena Declaration on Refugees [Americas]) (PEF 2010: 19).