Age of blood and recipient factors determine the severity of transfusion-related acute lung injury (TRALI)

Introduction Critical care patients frequently receive blood transfusions. Some reports show an association between aged or stored blood and increased morbidity and mortality, including the development of transfusion-related acute lung injury (TRALI). However, the existence of conflicting data endorses the need for research to either reject this association, or to confirm it and elucidate the underlying mechanisms. Methods Twenty-eight sheep were randomised into two groups, receiving saline or lipopolysaccharide (LPS). Sheep were further randomised to also receive transfusion of pooled and heat-inactivated supernatant from fresh (Day 1) or stored (Day 42) non-leucoreduced human packed red blood cells (PRBC) or an infusion of saline. TRALI was defined by hypoxaemia during or within two hours of transfusion and histological evidence of pulmonary oedema. Regression modelling compared physiology between groups, and to a previous study, using stored platelet concentrates (PLT). Samples of the transfused blood products also underwent cytokine array and biochemical analyses, and their neutrophil priming ability was measured in vitro. Results TRALI did not develop in sheep that first received saline-infusion. In contrast, 80% of sheep that first received LPS-infusion developed TRALI following transfusion with "stored PRBC." The decreased mean arterial pressure and cardiac output as well as increased central venous pressure and body temperature were more severe for TRALI induced by "stored PRBC" than by "stored PLT." Storage-related accumulation of several factors was demonstrated in both "stored PRBC" and "stored PLT", and was associated with increased in vitro neutrophil priming. Concentrations of several factors were higher in the "stored PRBC" than in the "stored PLT," however, there was no difference to neutrophil priming in vitro. Conclusions In this in vivo ovine model, both recipient and blood product factors contributed to the development of TRALI. Sick (LPS infused) sheep rather than healthy (saline infused) sheep predominantly developed TRALI when transfused with supernatant from stored but not fresh PRBC. "Stored PRBC" induced a more severe injury than "stored PLT" and had a different storage lesion profile, suggesting that these outcomes may be associated with storage lesion factors unique to each blood product type. Therefore, the transfusion of fresh rather than stored PRBC may minimise the risk of TRALI.

A Systems-level approach to building sustainable assessment cultures : moderation, quality task design and dependability of judgement

This paper considers the conditions that are necessary at system and local levels for teacher assessment to be valid, reliable and rigorous. With sustainable assessment cultures as a goal, the paper examines how education systems can support local level efforts for quality learning and dependable teacher assessment. This is achieved through discussion of relevant research and consideration of a case study involving an evaluation of a cross-sectoral approach to promoting confidence in school-based assessment in Queensland, Australia. Building on the reported case study, essential characteristics for developing sustainable assessment cultures are presented, including: leadership in learning; alignment of curriculum, pedagogy and assessment; the design of quality assessment tasks and accompanying standards, and evidence-based judgement and moderation. Taken together, these elements constitute a new framework for building assessment capabilities and promoting quality assurance.

Development of network-level project screening methods supporting the 4-Year pavement management plan in Texas

The Texas Department of Transportation (TxDOT) is concerned about the widening gap between pavement preservation needs and available funding. Thus, the TxDOT Austin District Pavement Engineer (DPE) has investigated methods to strategically allocate available pavement funding to potential projects that improve the overall performance of the District and Texas highway systems. The primary objective of the study presented in this paper is to develop a network-level project screening and ranking method that supports the Austin District 4-year pavement management plan development. The study developed candidate project selection and ranking algorithms that evaluated pavement conditions of each project candidate using data contained in the Pavement Management Information system (PMIS) database and incorporated insights from Austin District pavement experts; and implemented the developed method and supporting algorithm. This process previously required weeks to complete, but now requires about 10 minutes including data preparation and running the analysis algorithm, which enables the Austin DPE to devote more time and resources to conducting field visits, performing project-level evaluation and testing candidate projects. The case study results showed that the proposed method assisted the DPE in evaluating and prioritizing projects and allocating funds to the right projects at the right time.

Integrating driving and traffic simulators to study railway level crossing safety interventions : a methodology

Safety at Railway Level Crossings (RLXs) is an important issue within the Australian transport system. Crashes at RLXs involving road vehicles in Australia are estimated to cost $10 million each year. Such crashes are mainly due to human factors; unintentional errors contribute to 46% of all fatal collisions and are far more common than deliberate violations. This suggests that innovative intervention targeting drivers are particularly promising to improve RLX safety. In recent years there has been a rapid development of a variety of affordable technologies which can be used to increase driver’s risk awareness around crossings. To date, no research has evaluated the potential effects of such technologies at RLXs in terms of safety, traffic and acceptance of the technology. Integrating driving and traffic simulations is a safe and affordable approach for evaluating these effects. This methodology will be implemented in a driving simulator, where we recreated realistic driving scenario with typical road environments and realistic traffic. This paper presents a methodology for evaluating comprehensively potential benefits and negative effects of such interventions: this methodology evaluates driver awareness at RLXs , driver distraction and workload when using the technology . Subjective assessment on perceived usefulness and ease of use of the technology is obtained from standard questionnaires. Driving simulation will provide a model of driving behaviour at RLXs which will be used to estimate the effects of such new technology on a road network featuring RLX for different market penetrations using a traffic simulation. This methodology can assist in evaluating future safety interventions at RLXs.

Methodology to assess safety effects of future Intelligent Transport Systems on railway level crossings

There is consistent evidence showing that driver behaviour contributes to crashes and near miss incidents at railway level crossings (RLXs). The development of emerging Vehicle-to-Vehicle and Vehicle-to-Infrastructure technologies is a highly promising approach to improve RLX safety. To date, research has not evaluated comprehensively the potential effects of such technologies on driving behaviour at RLXs. This paper presents an on-going research programme assessing the impacts of such new technologies on human factors and drivers’ situational awareness at RLX. Additionally, requirements for the design of such promising technologies and ways to display safety information to drivers were systematically reviewed. Finally, a methodology which comprehensively assesses the effects of in-vehicle and road-based interventions warning the driver of incoming trains at RLXs is discussed, with a focus on both benefits and potential negative behavioural adaptations. The methodology is designed for implementation in a driving simulator and covers compliance, control of the vehicle, distraction, mental workload and drivers’ acceptance. This study has the potential to provide a broad understanding of the effects of deploying new in-vehicle and road-based technologies at RLXs and hence inform policy makers on safety improvements planning for RLX.

Low cost railway level crossings

The Cooperative Research Centre (CRC) for Rail Innovation is conducting a tranche of industry-led research projects looking into safer rail level crossings. This paper will provide an overview of the Affordable Level Crossings project, a project that is performing research in both engineering and human factors aspects of low-cost level crossing warning devices (LCLCWDs), and is facilitating a comparative trial of these devices over a period of 12 months in several jurisdictions. Low-cost level crossing warning devices (LCLCWDs) are characterised by the use of alternative technologies for high cost components including train detection and connectivity (e.g. radar, acoustic, magnetic induction train detection systems and wireless connectivity replacing traditional track circuits and wiring). These devices often make use of solar power where mains power is not available, and aim to make substantial savings in lifecycle costs. The project involves trialling low-cost level crossing warning devices in shadow-mode, where devices are installed without the road-user interface at a number of existing level crossing sites that are already equipped with conventional active warning systems. It may be possible that the deployment of lower-cost devices can provide a significantly larger safety benefit over the network than a deployment of expensive conventional devices, as the lower cost would allow more passive level crossing sites to be upgraded with the same capital investment. The project will investigate reliability and safety integrity issues of the low-cost devices, as well as evaluate lifecycle costs and investigate human factors issues related to warning reliability. This paper will focus on the requirements and safety issues of LCLCWDs, and will provide an overview of the Rail CRC projects.

Wolbachia-mediated resistance to dengue virus infection and death at the cellular level

Dengue is currently the most important arthropod-borne viral disease of humans. Recent work has shown dengue virus displays limited replication in its primary vector, the mosquito Aedes aegypti, when the insect harbors the endosymbiotic bacterium Wolbachia pipientis. Wolbachia-mediated inhibition of virus replication may lead to novel methods of arboviral control, yet the functional and cellular mechanisms that underpin it are unknown.

Prostate cancer biomarkers and the emerging proteomic techniques used in biomarker research

Prostate cancer (CaP) is the second leading cause of cancer-related deaths in North American males and the most common newly diagnosed cancer in men world wide. Biomarkers are widely used for both early detection and prognostic tests for cancer. The current, commonly used biomarker for CaP is serum prostate specific antigen (PSA). However, the specificity of this biomarker is low as its serum level is not only increased in CaP but also in various other diseases, with age and even body mass index. Human body fluids provide an excellent resource for the discovery of biomarkers, with the advantage over tissue/biopsy samples of their ease of access, due to the less invasive nature of collection. However, their analysis presents challenges in terms of variability and validation. Blood and urine are two human body fluids commonly used for CaP research, but their proteomic analyses are limited both by the large dynamic range of protein abundance making detection of low abundance proteins difficult and in the case of urine, by the high salt concentration. To overcome these challenges, different techniques for removal of high abundance proteins and enrichment of low abundance proteins are used. Their applications and limitations are discussed in this review. A number of innovative proteomic techniques have improved detection of biomarkers. They include two dimensional differential gel electrophoresis (2D-DIGE), quantitative mass spectrometry (MS) and functional proteomic studies, i.e., investigating the association of post translational modifications (PTMs) such as phosphorylation, glycosylation and protein degradation. The recent development of quantitative MS techniques such as stable isotope labeling with amino acids in cell culture (SILAC), isobaric tags for relative and absolute quantitation (iTRAQ) and multiple reaction monitoring (MRM) have allowed proteomic researchers to quantitatively compare data from different samples. 2D-DIGE has greatly improved the statistical power of classical 2D gel analysis by introducing an internal control. This chapter aims to review novel CaP biomarkers as well as to discuss current trends in biomarker research from two angles: the source of biomarkers (particularly human body fluids such as blood and urine), and emerging proteomic approaches for biomarker research.

Drugs affecting blood

25. Drugs affecting blood 25.1 Introduction 25.2 Important dysfunctions of the blood system 25.3 Drugs used in to correct dysfunctions of the blood 25.3.1 Anti-thrombosis treatments 25.3.1.1 Platelet aggregation inhibitors 25.3.1.2 Anticoagulants 25.3.1.3 Thrombolytics 25.3.2 Treatments for anaemia 25.3.3 Treatments for bleeding disorders

Evidence of unique genotypes of Beak and feather disease virus in Southern Africa

Psittacine beak and feather disease (PBFD), caused by Beak and feather disease virus (BFDV), is the most significant infectious disease in psittacines. PBFD is thought to have originated in Australia but is now found worldwide; in Africa, it threatens the survival of the indigenous endangered Cape parrot and the vulnerable black-cheeked lovebird. We investigated the genetic diversity of putative BFDVs from southern Africa. Feathers and heparinized blood samples were collected from 27 birds representing 9 psittacine species, all showing clinical signs of PBFD. DNA extracted from these samples was used for PCR amplification of the putative BFDV coat protein (CP) gene. The nucleotide sequences of the CP genes of 19 unique BFDV isolates were determined and compared with the 24 previously described sequences of BFDV isolates from Australasia and America. Phylogenetic analysis revealed eight BFDV lineages, with the southern African isolates representing at least three distinctly unique genotypes; 10 complete genome sequences were determined, representing at least one of every distinct lineage. The nucleotide diversity of the southern African isolates was calculated to be 6.4% and is comparable to that found in Australia and New Zealand. BFDVs in southern Africa have, however, diverged substantially from viruses found in other parts of the world, as the average distance between the southern African isolates and BFDV isolates from Australia ranged from 8.3 to 10.8%. In addition to point mutations, recombination was found to contribute substantially to the level of genetic variation among BFDVs, with evidence of recombination in all but one of the genomes analyzed.

High level protein expression in plants through the use of a novel autonomously replicating geminivirus shuttle vector

We constructed a novel autonomously replicating gene expression shuttle vector, with the aim of developing a system for transiently expressing proteins at levels useful for commercial production of vaccines and other proteins in plants. The vector, pRIC, is based on the mild strain of the geminivirus Bean yellow dwarf virus (BeYDV-m) and is replicationally released into plant cells from a recombinant Agrobacterium tumefaciens Ti plasmid. pRIC differs from most other geminivirus-based vectors in that the BeYDV replication-associated elements were included in cis rather than from a co-transfected plasmid, while the BeYDV capsid protein (CP) and movement protein (MP) genes were replaced by an antigen encoding transgene expression cassette derived from the non-replicating A. tumefaciens vector, pTRAc. We tested vector efficacy in Nicotiana benthamiana by comparing transient cytoplasmic expression between pRIC and pTRAc constructs encoding either enhanced green fluorescent protein (EGFP) or the subunit vaccine antigens, human papillomavirus subtype 16 (HPV-16) major CP L1 and human immunodeficiency virus subtype C p24 antigen. The pRIC constructs were amplified in planta by up to two orders of magnitude by replication, while 50% more HPV-16 L1 and three- to seven-fold more EGFP and HIV-1 p24 were expressed from pRIC than from pTRAc. Vector replication was shown to be correlated with increased protein expression. We anticipate that this new high-yielding plant expression vector will contribute towards the development of a viable plant production platform for vaccine candidates and other pharmaceuticals. © 2009 Blackwell Publishing Ltd.

Comparison of cervical and blood T-cell responses to human papillomavirus-16 in women with human papillomavirus-associated cervical intraepithelial neoplasia

Human papillomaviruses (HPVs) are obligate epithelial pathogens and typically cause localized mucosal infections. We therefore hypothesized that T-cell responses to HPV antigens would be greater at sites of pathology than in the blood. Focusing on HPV-16 because of its association with cervical cancer, the magnitude of HPV-specific T-cell responses at the cervix was compared with those in the peripheral blood by intracellular cytokine staining following direct ex vivo stimulation with both virus-like particles assembled from the major capsid protein L1, and the major HPV oncoprotein, E7. We show that both CD4 + and CD8 + T cells from the cervix responded to the HPV-16 antigens and that interferon-γ (IFN-γ) production was HPV type-specific. Comparing HPV-specific T-cell IFN-γ responses at the cervix with those in the blood, we found that while CD4 + and CD8 + T-cell responses to L1 were significantly correlated between compartments (P = 0.02 and P = 0.05, respectively), IFN-γ responses in both T-cell subsets were significantly greater in magnitude at the cervix than in peripheral blood (P = 0.02 and P = 0.003, respectively). In contrast, both CD4 + and CD8 + T-cell IFN-γ responses to E7 were of similar magnitude in both compartments and CD8 + responses were significantly correlated between these distinct immunological compartments (P = 0.04). We therefore show that inflammatory T-cell responses against L1 (but not E7) demonstrate clear compartmental bias and the magnitude of these responses do reflect local viral replication but that correlation of HPV-specific responses between compartments indicates their linkage.

A micro-level indexing model for assessing urban ecosystem sustainability

Purpose – As a consequence of rapid urbanisation and globalisation, cities have become the engines of population and economic growth. Hence, natural resources in and around the cities have been exposed to externalities of urban development processes. This paper introduces a new sustainability assessment approach that is tested in a pilot study. The paper aims to assist policy-makers and planners investigating the impacts of development on environmental systems, and produce effective policies for sustainable urban development. Design/methodology/approach – The paper introduces an indicator-based indexing model entitled “Indexing Model for the Assessment of Sustainable Urban Ecosystems” (ASSURE). The ASSURE indexing model produces a set of micro-level environmental sustainability indices that is aimed to be used in the evaluation and monitoring of the interaction between human activities and urban ecosystems. The model is an innovative approach designed to assess the resilience of ecosystems towards impacts of current development plans and the results serve as a guide for policymakers to take actions towards achieving sustainability. Findings – The indexing model has been tested in a pilot case study within the Gold Coast City, Queensland, Australia. This paper presents the methodology of the model and outlines the preliminary findings of the pilot study. The paper concludes with a discussion on the findings and recommendations put forward for future development and implementation of the model. Originality/value – Presently, there is a few sustainability indices developed to measure the sustainability at local, regional, national and international levels. However, due to challenges in data collection difficulties and availability of local data, there is no effective assessment model at the microlevel that the assessment of urban ecosystem sustainability accurately. The model introduced in this paper fills this gap by focusing on parcel-scale and benchmarking the environmental performance in micro-level.