Packed red blood cells suppress myeloid dendritic cell and monocyte inflammatory responses in a whole blood model of transfusion

Purpose/Objective: The basis for poor outcomes in some patients post transfusion remains largely unknown. Despite leukodepletion, there is still evidence of immunomodulatory effects of transfusion that require further study. In addition, there is evidence that the age of blood components transfused significantly affects patient outcomes. Myeloid dendritic cell (DC) and monocyte immune function were studied utilising an in vitro whole blood model of transfusion. Materials and methods: Freshly collected (‘recipient’) whole blood was cultured with ABO compatible leukodepleted PRBC at 25% blood replacement-volume (6hrs). PRBC were assayed at [Day (D) 2, 14, 28and 42 (date-of expiry)]. In parallel, LPS or Zymosan (Zy) were added to mimic infection. Recipients were maintained for the duration of the time course (2 recipients, 4 PRBC units, n = 8).Recipient DC and monocyte intracellular cytokines and chemokines (IL-6, IL-10, IL-12,TNF-a, IL-1a, IL-8, IP-10, MIP-1a, MIP-1b, MCP-1) were measured using flow cytometry. Changes in immune response were calculated by comparison to a parallel no transfusion control (Wilcoxin matched pairs). Influence of storage age was calculated using ANOVA. Results: Significant suppression of DC and monocyte inflammatory responses were evident. DC and monocyte production of IL-1a was reduced following exposure to PRBC regardless of storage age (P < 0.05 at all time points). Storage independent PRBC mediated suppression of DC and monocyte IL-1a was also evident in cultures costimulated with Zy. In cultures co-stimulated with either LPS or Zy, significant suppression of DC and monocyte TNF-a and IL-6 was also evident. PRBC storage attenuated monocyte TNF-a production when co-cultured with LPS (P < 0.01 ANOVA). DC and monocyte production of MIP-1a was significantly reduced following exposure to PRBC (DC: P < 0.05 at D2, 28, 42; Monocyte P < 0.05 all time points). In cultures co-stimulated with LPS and zymosan, a similar suppression of MIP-1a production was also evident, and production of both DC and monocyte MIP-1b and IP-10 were also significantly reduced. Conclusions: The complexity of the transfusion context was reflected in the whole blood approach utilised. Significant suppression of these key DC and monocyte immune responses may contribute to patient outcomes, such as increased risk of infection and longer hospital stay, following blood transfusion.

Bridging the biology of the ovine TRALI model – human inflammatory cell responses to TRALI inducing supernatants

Background Transfusion-related acute lung injury (TRALI) is a serious and potentially fatal consequence of transfusion. A two-event TRALI model demonstrated date-of-expiry - day (D) 5 platelet (PLT) and D42 packed red blood cell (PRBC) supernatants (SN) induced TRALI in LPS-treated sheep. We have adapted a whole blood transfusion culture model as an investigative bridge between the ovine TRALI model human responses to transfusion. Methods A whole blood transfusion model was adapted to replicate the ovine model - specifically +/- 0.23μg/mL LPS as the first event and 10% SN volume (transfusion) as the second event. Four pooled SN from blood products, previously used in the TRALI ovine model, were investigated: D1-PLT, D5-PLT, D1-PRBC, and D42-PRBC. Fresh human whole blood (recipient) was mixed with combinations of LPS and BP-SN stimuli and incubated in vitro for 6 hrs. Addition of golgi plug enabled measurement of monocyte cytokine production (IL-6, IL-8, IL-10, IL-12, TNF-α, IL-1α, CXCL-5, IP-10, MIP-1α, MCP-1) using multi-colour flow cytometry. Responses for 6 recipients were assessed. Results In the presence of LPS, D42-PRBC-SN significantly increased monocyte IL-6 (P=0.031), IL-8 (P=0.016) and IL-1α (P=0.008) production compared to D1-PRBC-SN. This response to D42-PRBC-SN was LPS-dependent, and was not evident in non-LPSstimulated controls. This response was also specific to D42-PRBC-SN, as similar changes were not evident for the D5-PLT-SN, compared to the D1-PLT-SN, regardless of the presence of LPS. D5-PLT-SN significantly increased IL-12 production (P=0.024) compared to D1-PLT-SN. This response was again LPS-dependent. Conclusions These data demonstrate a novel two-event mechanism of monocyte inflammatory response that was dependent upon both the presence of date-of-expiry blood product SN and LPS. Further, these results demonstrate different cytokines responses induced by date-of-expiry PLT-SN and PRBC-SN. These data are consistent with the evidence from the ovine TRALI model, and enhancing its relevance to transfusion related changes in humans.

The challenge of integrating climate change adaptation and disaster risk management : lessons from bushfire and flood inquiries in an Australian context

Emergency management and climate change adaptation will increasingly challenge all levels of government because of three main factors. First, Australia is extremely vulnerable to the impacts of climate change, particularly through the increasing frequency, duration and/or intensity of disasters such as floods and bushfires. Second, the system of government that divides powers by function and level can often act as a barrier to a well-integrated response. Third, policymaking processes struggle to cope with such complex inter-jurisdictional issues. This paper discusses these factors and explores the nature of the challenge for Australian governments. Investigations into the 2009 Victorian bushfires, the 2011 Perth Hills bushfires, and the 2011 Brisbane floods offer an indication of the challenges ahead and it is argued that there is a need to: improve community engagement and communication; refocus attention on resilience; improve interagency communication and collaboration; and, develop institutional arrangements that support continual improvement and policy learning. These findings offer an opportunity for improving responses as well as a starting point for integrating disaster risk management and climate change adaptation policies. The paper is based on the preliminary findings of an NCCARF funded research project: The Right Tool for the Job: Achieving climate change adaptation outcomes through improved disaster management policies, planning and risk management strategies involving Griffith University and RMIT. It should be noted from the outset that the purpose of this research project is not to criticise the actions of emergency service workers and volunteers who do an incredible job under extreme circumstances, often risking their own lives in the process. The aim is simply to offer emergency management agencies the opportunity to step back and rethink their overall approach to the challenge they face in the light of the impacts of climate change.

Study of a geo-multicast framework for efficient message dissemination at unmanned level crossings

Collisions among trains and cars at road/rail level crossings (LXs) can have severe consequences such as high level of fatalities, injuries and significant financial losses. As communication and positioning technologies have significantly advanced, implementing vehicular ad hoc networks (VANETs) in the vicinity of unmanned LXs, generally LXs without barriers, is seen as an efficient and effective approach to mitigate or even eliminate collisions without imposing huge infrastructure costs. VANETs necessitate unique communication strategies, in which routing protocols take a prominent part in their scalability and overall performance, through finding optimised routes quickly and with low bandwidth overheads. This article studies a novel geo-multicast framework that incorporates a set of models for communication, message flow and geo-determination of endangered vehicles with a reliable receiver-based geo-multicast protocol to support cooperative level crossings (CLXs), which provide collision warnings to the endangered motorists facing road/rail LXs without barriers. This framework is designed and studied as part of a $5.5 m Government and industry funded project, entitled 'Intelligent-Transport-Systems to improve safety at road/rail crossings'. Combined simulation and experimental studies of the proposed geo-multicast framework have demonstrated promising outcomes as cooperative awareness messages provide actionable critical information to endangered drivers who are identified by CLXs.

BIM : enabling sustainability and asset management through knowledge management

Building Information Modeling (BIM) is the use of virtual building information models to develop building design solutions and design documentation and to analyse construction processes. Recent advances in IT have enabled advanced knowledge management, which in turn facilitates sustainability and improves asset management in the civil construction industry. There are several important qualifiers and some disadvantages of the current suite of technologies. This paper outlines the benefits, enablers, and barriers associated with BIM and makes suggestions about how these issues may be addressed. The paper highlights the advantages of BIM, particularly the increased utility and speed, enhanced fault finding in all construction phases, and enhanced collaborations and visualisation of data. The paper additionally identifies a range of issues concerning the implementation of BIM as follows: IP, liability, risks, and contracts and the authenticity of users. Implementing BIM requires investment in new technology, skills training, and development of new ways of collaboration and Trade Practices concerns. However, when these challenges are overcome, BIM as a new information technology promises a new level of collaborative engineering knowledge management, designed to facilitate sustainability and asset management issues in design, construction, asset management practices, and eventually decommissioning for the civil engineering industry.

GO423 - the second Game On / brIGDA Independant Game Symposium

GO423 was initiated in 2012 as part of a community effort to ensure the vitality of the Queensland Games Sector. In common with other industrialised nations, the game industry in Australia is a reasonably significant contributor to Gross National Product (GNP). Games are played in 92% of Australian homes and the average adult player has been playing them for at least twelve years with 26% playing for more than thirty years (Brand, 2011). Like the games and interactive entertainment industries in other countries, the Australian industry has its roots in the small team model of the 1980s. So, for example, Beam Software, which was established in Melbourne in 1980, was started by two people and Krome Studios was started in 1999 by three. Both these companies grew to employing over 100 people in their heydays (considered large by Antipodean standards), not by producing their own intellectual property (IP) but by content generation for off shore parent companies. Thus our bigger companies grew on a model of service provision and tended not to generate their own IP (Darchen, 2012). There are some no-table exceptions where IP has originated locally and been ac-quired by international companies but in the case of some of the works of which we are most proud, the Australian company took on the role of “Night Elf” – a convenience due to affordances of the time zone which allowed our companies to work while the parent companies slept in a different time zone. In the post GFC climate, the strong Australian dollar and the vulnerability of such service provision means that job security is virtually non-existent with employees invariably being on short-term contracts. These issues are exacerbated by the decline of middle-ground games (those which fall between the triple-A titles and the smaller games often produced for a casual audience). The response to this state of affairs has been the change in the Australian games industry to new recognition of its identity as a wider cultural sector and the rise (or return) of an increasing number of small independent game development companies. ’In-dies’ consist of small teams, often making games for mobile and casual platforms, that depend on producing at least one if not two games a year and who often explore more radical definitions of games as designed cultural objects. The need for innovation and creativity in the Australian context is seen as a vital aspect of the current changing scene where we see the emphasis on the large studio production model give way to an emerging cultural sector model where small independent teams are engaged in shorter design and production schedules driven by digital distribution. In terms of Quality of Life (QoL) this new digital distribution brings with it the danger of 'digital isolation' - a studio can work from home and deliver from home. Community events thus become increasingly important. The GO423 Symposium is a response to these perceived needs and the event is based on the understanding that our new small creative teams depend on the local community of practice in no small way. GO423 thus offers local industry participants the opportunity to talk to each other about their work, to talk to potential new members about their work and to show off their work in a small intimate situation, encouraging both feedback and support.

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and -9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma (MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM (n = 35), inflamed pleura (IP, n = 12) and uninflammed pleura (UP, n = 14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan-Meier and Cox proportional hazard models. In MM, pro- and active MMP-2 levels were significantly greater than for MMP-9 (P = 0.006, P<0.001). Active MMP-2 was significantly greater in MM than in UP (P=0.04). MMP-2 activity was equivalent between IP and MM, but both pro- and active MMP-9 activities were greater in IP (P=0.02, P=0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P=0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P = 0.03, total MMP-2 P = 0.04). Total and pro-MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM. © 2003 Cancer Research UK.

Description of plant tRNA-derived RNA fragments (tRFs) associated with argonaute and identification of their putative targets

tRNA-derived RNA fragments (tRFs) are 19mer small RNAs that associate with Argonaute (AGO) proteins in humans. However, in plants, it is unknown if tRFs bind with AGO proteins. Here, using public deep sequencing libraries of immunoprecipitated Argonaute proteins (AGO-IP) and bioinformatics approaches, we identified the Arabidopsis thaliana AGO-IP tRFs. Moreover, using three degradome deep sequencing libraries, we identified four putative tRF targets. The expression pattern of tRFs, based on deep sequencing data, was also analyzed under abiotic and biotic stresses. The results obtained here represent a useful starting point for future studies on tRFs in plants. © 2013 Loss-Morais et al.; licensee BioMed Central Ltd.

Co-creating knowledge online : approaches for community artists

Forming peer alliances to share and build knowledge is an important aspect of community arts practice, and these co-creation processes are increasingly being mediated by the internet. This paper offers guidance for practitioners who are interested in better utilising the internet to connect, share, and make new knowledge. It argues that new approaches are required to foster the organising activities that underpin online co-creation, building from the premise that people have become increasingly networked as individuals rather than in groups (Rainie and Wellman 2012: 6), and that these new ways of connecting enable new modes of peer-to-peer production and exchange. This position advocates that practitioners move beyond situating the internet as a platform for dissemination and a tool for co-creating media, to embrace its knowledge collaboration potential. Drawing on a design experiment I developed to promote online knowledge co-creation, this paper suggests three development phases – developing connections, developing ideas, and developing agility – to ground six methods. They are: switching and routing, engaging in small trades of ideas with networked individuals; organising, co-ordinating networked individuals and their data; beta-release, offering ‘beta’ artifacts as knowledge trades; beta-testing, trialing and modifying other peoples ‘beta’ ideas; adapting, responding to technological disruption; and, reconfiguring, embracing opportunities offered by technological disruption. These approaches position knowledge co-creation as another capability of the community artist, along with co-creating art and media.

Stored blood products augment inflammation in a two-event model of Transfusion Related Acute Lung Injury (TRALI)

Aim/Background TRALI is hypothesised to develop via a two-event mechanism involving both the patieint's underlying morbidity and blood product factors. The storage of cellular products has been implicated in cases of non-antibody mediated TRALI, however the pathophysiological mechanisms are undefined. We investigated blood product storage-related modulation of inflmmatory cells and medicators involved in TRALI. Methods In an in vitro mode, fresh human whole blood was mixed with culture media (control) or LPS as a 1st event and "transfused" with 10% (v/v) pooled supernatant (SN) from Day 1 (d1, n=75) or Day 42 (D42, n=113) packed red blood cells (PRBCs) as a 2nd event. Following 6hrs, culture SN was used to assess the overall inflammatory response (cytometric bead array) and a duplicate assay containing protein transport inhibitor was used to assess neutrophil- and monocyte-specific inflmamatory responses using multi-colour flow cytometry. Panels: IL-6, IL-8, IL-10, IL-12, IL-1, TNF, MCP-1, IP-10, MIP-1. One-way ANOVA 95% CI. Results In the absence of LPS, exposure to D1 or D42 PRBC-SN reduced monocyte expression of IL-6, IL-8 and Il-10. D42 PRBC-SN also reduced monocyte IP-10, and the overall IL-8 production was increased. In the presence of LPS, D1-PRBC SN only modified overall IP-10 levels which were reduced. However, cf LPS alone, the combination of LPS and D42 PRBC-SN resulted in increased neutrophil and monocyte productionof IL-1 and IL-8 as well as reduced monocyte TNF production. Additionally, LPS and D42 PRBC-SN resulted in overall inflmmatory changes: elevated IL-8, <IP-1, IL-10 and MIP-1, and reduced TNF and IP-10. Conclusion In the absence of LPS, exposure to both fresh and stored PRBC-SN predominantly resulted in an anti-imflammatory response. However, in the presence of LPS, stored but not fresh PRBC-SN augmented a pro-inflammatory profile. These data support the two-event mechanism of TRALI pathogenesis, and highlights blood product storage duration as a factor contributing to the development of inflmamatory responses in non-antibody mediated TRALI.

An efficient proactive route maintenance process for reliable data transmissions in sensor networks

For industrial wireless sensor networks, maintaining the routing path for a high packet delivery ratio is one of the key objectives in network operations. It is important to both provide the high data delivery rate at the sink node and guarantee a timely delivery of the data packet at the sink node. Most proactive routing protocols for sensor networks are based on simple periodic updates to distribute the routing information. A faulty link causes packet loss and retransmission at the source until periodic route update packets are issued and the link has been identified as broken. We propose a new proactive route maintenance process where periodic update is backed-up with a secondary layer of local updates repeating with shorter periods for timely discovery of broken links. Proposed route maintenance scheme improves reliability of the network by decreasing the packet loss due to delayed identification of broken links. We show by simulation that proposed mechanism behaves better than the existing popular routing protocols (AODV, AOMDV and DSDV) in terms of end-to-end delay, routing overhead, packet reception ratio.

Evoking gesture in interactive art

In this paper, we describe an interactive artwork that uses large body gestures as its primary interactive mode. The artist intends the work to provoke active reflection in the audience by way of gesture and content. The technology is not the focus, rather the aim is to provoke memory, to elicit feelings of connective human experiences in a required-to-participate audience. We find the work provokes a diverse and contradictory set of responses. The methods used to understand this include qualitative methods common to evaluating interactive art works, as well as in-depth discussions with the artist herself. This paper is relevant to the Human - Centered Computing track because in all stages of the design of the work - as well as the evaluation - the focus is on the human aspect; the computing is designed to enable all-too-human responses.

Talk2Me : engaging interactive installation environments

In this research I explore what elements there may be in common between tangible interactive-technology works that successfully engage their participants. An exploration of existing methods for obtaining useful evaluations for non-use and ambiguous environments forms a part of the discussion.

The comparative behaviour of two combat boots under impact

Background Improvised explosive devices have become the characteristic weapon of conflicts in Iraq and Afghanistan. While little can be done to mitigate against the effects of blast in free-field explosions, scaled blast simulations have shown that the combat boot can attenuate the effects on the vehicle occupants of anti-vehicular mine blasts. Although the combat boot offers some protection to the lower limb, its behaviour at the energies seen in anti-vehicular mine blast has not been documented previously. Methods The sole of eight same-size combat boots from two brands currently used by UK troops deployed to Iraq and Afghanistan were impacted at energies of up to 518 J, using a spring-assisted drop rig. Results The results showed that the Meindl Desert Fox combat boot consistently experienced a lower peak force at lower impact energies and a longer time-to-peak force at higher impact energies when compared with the Lowa Desert Fox combat boot. Discussion This reduction in the peak force and extended rise time, resulting in a lower energy transfer rate, is a potentially positive mitigating effect in terms of the trauma experienced by the lower limb. Conclusion Currently, combat boots are tested under impact at the energies seen during heel strike in running. Through the identification of significantly different behaviours at high loading, this study has shown that there is rationale in adding the performance of combat boots under impact at energies above those set out in international standards to the list of criteria for the selection of a combat boot.

Smart material interfaces : a new form of physical interaction

Smart Material Interface (SMI) is the latest generation of user interface that makes use of engineered materials and leverages their special properties. SMIs are capable of changing their physical properties such as shape, size and color, and can be controlled under certain (external) conditions. We provide an example of such an SMI in the form of a prototype of a vacuum cleaner. The prototype uses schematic electrochromic polymer at the suction nozzle of the vacuum cleaner, which changes its color depending on the dust level on a floor. We emphasize on the new affordances and communication language supported by SMIs, which challenges the current metaphors of user interfaces in the field of HCI.