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Page 1: 2 RESEARCH AND DEVELOPMENT |ANNUAL REPORT€¦ · working party on transfusion transmitted disease. • Associate Professor Catherine Hyland is a member of the ISBT working party
Page 2: 2 RESEARCH AND DEVELOPMENT |ANNUAL REPORT€¦ · working party on transfusion transmitted disease. • Associate Professor Catherine Hyland is a member of the ISBT working party

2 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014

Photo credits:

Blood service photographs were taken by Tara Delia, Jemma Falkenmire, Genghis Lopez and Kate Sutherland

ADF photo used by permission

Micrographs were provided by Dr Margaret Veale

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RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 3

Table of Contents Table of Contents .................................................................................................................................. 3

EXECUTIVE SUMMARY ........................................................................................................................ 5

RESEARCH PROGRAM 2013-14 .......................................................................................................... 7

Researchers ........................................................................................................................................... 7

Applied and Developmental Research ................................................................................................ 9

Improved manufacturing efficiencies, systems and product characterisation ................................ 9

Frozen blood research .................................................................................................................... 9

Understanding pathogen reduction technologies.......................................................................... 11

Clinical Research ................................................................................................................................ 13

Product improvement .................................................................................................................... 13

Patient adverse event management ............................................................................................. 13

Donor adverse event management ............................................................................................... 15

Donor and Community Research ...................................................................................................... 17

Understanding donor motivation ................................................................................................... 17

Donor retention.............................................................................................................................. 17

Lapsed donor reactivation ............................................................................................................. 19

Transfusion Science Research .......................................................................................................... 21

Evidence based evaluation of emerging infectious risks to the safety of the blood supply .......... 21

Transfusion models ....................................................................................................................... 23

New strategies for blood grouping ................................................................................................ 23

Properties of stored red blood cells .............................................................................................. 23

APPENDIX 1: PUBLICATIONS AND INVITED PRESENTATIONS.................................................... 26

Peer reviewed journal articles ........................................................................................................... 26

Publications by Blood Service researchers ................................................................................... 26

Publications by Blood Service collaborators ................................................................................. 29

Peer reviewed published abstracts ................................................................................................... 29

Invited publications ............................................................................................................................ 31

Invited external presentations ........................................................................................................... 31

Internal presentations ......................................................................................................................... 33

Books and other materials ................................................................................................................. 33

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4 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 International database listings .......................................................................................................... 34

APPENDIX 2: GRANTS ....................................................................................................................... 35

Grants Active 2013-14 ......................................................................................................................... 35

Applied and Developmental Research .......................................................................................... 35

Donor and Community Research .................................................................................................. 35

Transfusion Science Research ..................................................................................................... 35

New Grant Applications: Successful ................................................................................................ 36

Clinical Research .......................................................................................................................... 37

Donor and Community Research .................................................................................................. 37

Transfusion Science Research ..................................................................................................... 37

New Grant applications: Submitted .................................................................................................. 38

Applied and Developmental Research .......................................................................................... 38

Clinical Research .......................................................................................................................... 38

Transfusion Science Research ..................................................................................................... 38

APPENDIX 3: ABSTRACTS ACCEPTED FOR CONFERENCE ORAL OR POSTER

PRESENTATIONS ................................................................................................................................ 39

Applied and Developmental Research .............................................................................................. 39

Clinical Research ................................................................................................................................ 39

Donor and Community Research ...................................................................................................... 40

Transfusion Science Research .......................................................................................................... 41

APPENDIX 4: CONFERENCE ATTENDANCE ................................................................................... 44

International ......................................................................................................................................... 44

Applied and Developmental Research .......................................................................................... 44

Transfusion Science Research ..................................................................................................... 44

Domestic .............................................................................................................................................. 44

Applied and Developmental Research .......................................................................................... 44

Clinical Research .......................................................................................................................... 45

Donor and Community Research .................................................................................................. 45

Transfusion Science Research ..................................................................................................... 45

APPENDIX 5: STUDENT PROJECTS ................................................................................................. 46

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RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 5

EXECUTIVE SUMMARY The Australian Red Cross Blood Service (Blood Service) Research and Development (R&D) division has had a strong year embracing organisational change and strengthening its focus on research outcomes. Project outcomes have driven improvements in the Blood Service and the blood and health sector. There has been a strong focus on aligning research with strategic goals and translating research into changed business practice. A total of 57 projects were commenced, 26 were completed, 26 are ongoing, and five were abandoned.

The Research Advisory Committee has also been strengthened through the addition of three internationally recognised blood research experts.

The division has translated research into strong operational outcomes, some of which include:

The supply of a process for preparing deep frozen blood components for the Australian Defence Force (ADF) was the outcome from over five years’ research. The work extends the shelf-life of blood components to up to 10 years by adapting and developing technologies in freezing and thawing blood components. This will provide the ADF with life-saving blood components when deployed in remote locations or austere environments where fresh components are difficult to access.

The Motivating Lapsed Donors - Registry Project is being translated into practice through a collaboration between R&D and Donor Services. This project provides strong business results by reducing the cost per donor-contact for lapsed donors by almost 40 per cent, as well as improving the sustainability of the donor base. Blood Service researchers contributed to world-class genotyping research by identifying two new clinically significant antigens - SARA and Kip - which are now classified in the MNS blood group system. Using state-of-the-art gene sequencing technology, researchers have been able to narrow that discovery down to specific changes in particular blood group antigens, which explains the reason for a transfusion incompatibility observed clinically many years ago. The discovery will avoid problems of incompatibility in future, should this rare event recur.

The division has also built on long-term research partnerships by collaborating with leading research groups at the University of Queensland and The Prince Charles Hospital to investigate further the link between blood components’ storage conditions and Transfusion-Related Acute Lung Injury (TRALI). Patients with TRALI have breathing difficulties and low blood oxygen following a transfusion. Using sheep as a model to mimic the human condition, this research aims to understand the mechanisms of TRALI and ultimately to reduce its incidence.

The Research and Development division is a diverse and multidisciplinary team, with members active in the local and international blood research communities. Visiting scholars from China, Nepal and France have chosen to join the group this year, bringing added diversity and fresh insights to the group. Blood Service researchers have achieved recognition locally and internationally. Two senior members of the division, Associate Professor Catherine Hyland and Dr John-Paul Tung, were awarded Australian Red Cross Distinguished Staff Awards in June 2014. Researchers from the division have been invited to present the results of their work in at a variety of forums around the globe.

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6 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014

Leading-edge research:

A research team of 60 people in three cities

Dr Lacey Johnson

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RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 7

RESEARCH PROGRAM 2013-14 Researchers The R&D division consists of over 60 team members, conducting research and support activities in dedicated facilities in Brisbane, Sydney and Melbourne. Many research fellows hold adjunct appointments at universities, and 20 members have doctorates.

Research in the division is organised into four programs:

Applied and Developmental Research focuses on evaluating novel technologies that have the potential to improve the quality and safety of Blood Service products, as well as improving operational efficiency and donor wellbeing.

Clinical Research works to ensure the safety, efficacy and appropriate use of blood products through direct participation and/or collaboration with other research groups in human clinical trials, development, analysis and linkage of clinical registries and other research related to blood components transfused into patients.

Donor and Community Research examines methods to ensure there are adequate collections to meet clinical demand. It investigates donor safety, retention, recruitment, motivation and community attitudes towards whole blood, platelet and plasma donation.

Transfusion Science Research carries out research that can be translated into improved operational procedures or product characteristics. Research areas in this program include horizon scanning, research on emerging transfusion transmitted diseases, molecular genotyping to facilitate more accurate matching of donor and patient, and research on blood component storage conditions which can have an impact on transfusion outcomes.

R&D researchers continue to build strong reputations locally and internationally. This year, they produced over 30 peer-reviewed publications1, with their external collaborators won over $1.9 million in new external funding2, and have been invited to contribute their expertise internationally. Some examples are:

• Dr Helen Faddy was invited to join the International Society of Blood Transfusion (ISBT) working party on transfusion transmitted disease.

• Associate Professor Catherine Hyland is a member of the ISBT working party for red cell blood group nomenclature.

• PhD student, Ms Rhiannon Mc Bean, was invited to present at the ISBT working party on red cell immunogenetics and blood group terminology in Korea.

Two visiting scholars obtained competitive funding from their home country to fund their work with the R&D team in Brisbane. Dr John-Paul Tung received a bursary to attend the 2013 British Society for Blood Transfusion conference where he was honoured with the Margaret Kenwright Young Scientist Award.

Researchers in the division are also actively engaged in educating the next generation of scientists, through supervision of Honours and PhD research students. A listing of student projects is shown in

1 Details of publications appear in Appendix 1

2 Grants are listed in Appendix 2

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8 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 Appendix 5. Post-graduate students in R&D continue to benefit from the fundraising of the Home Hill Lions Club 40 years ago when Club members established the Alexander Steele Young Memorial Lions Foundation. Trustees of the foundation established the Alex Young Memorial Lions Scholarship in 2012, which provides “top up” scholarships to students with a primary scholarship. R&D has been able to attract some of the very best students to the Blood Service to carry out their post-graduate research projects.

Table 1: Awards presented to Blood Service researchers

Awards

Dr Helen Faddy Travel Awards for Young Scientists, International Society for Blood Transfusion (ISBT) Working Party on Transfusion Transmitted Infections (WP-TTID), November 2013

Ms Shauna French Australian Society of Thrombosis and Haemostasis Best Scientific Paper Award, Australian Society of Thrombosis and Haemostasis, October 2013 (Blood Service co-authors: Dr John-Paul Tung, Prof Robert Flower)

Associate Prof. Catherine Hyland

Australian Red Cross Distinguished Staff Award, Australian Red Cross Society, June 2014

Dr Lacey Johnson ANZSBT Travel Grant to attend the annual scientific meeting, ANZSBT, October 2013

Ms Rhiannon McBean University of Sydney (50 per cent university scholarship), Alex Young Memorial Lions ‘Top Up’ Scholarship

Mr Ashish Shrestha University of Queensland International (UQI) scholarship, 2013-2016

Dr John-Paul Tung Margaret Kenwright Young Scientist Award, British Blood Transfusion Society, October 2013 (other Blood Service co-authors: Prof Robert Flower, Dr Melinda Dean, Wesley Bierman);

Australian Red Cross Distinguished Staff Award, Australian Red Cross Society, June 2014

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RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 9

Applied and Developmental Research The Applied and Developmental Research team works closely with other Blood Service divisions to conduct applied research projects whose outcomes can be readily translated into operational procedures. In 2013-14, eleven projects were completed, and a further five are ongoing. All projects are listed by title below, including Blood Service researchers.

Projects within the Applied and Developmental Research Program are divided into three strategically aligned themes:

• Improved manufacturing efficiencies, systems and product characterisation • Frozen blood research • Understanding pathogen reduction technologies

Improved manufacturing efficiencies, systems and product characterisation

The improved manufacturing efficiencies research theme aligns with the priorities of the Blood Service through projects investigating novel ways to manufacture or store blood components in order to find efficiencies and to improve component quality, shelf-life or safety. Projects aim to develop and optimise robust protocols that can be translated into routine operational procedures within the Manufacturing division of the Blood Service.

Highlights from this research theme are the findings from the evaluation of washed red cells and the assessment of a new packaging system for serum eye drops. The evaluation of washed red cells has shown that automated washing is more efficient than the current manual washing method. The resulting red cells are of an equivalent quality. A new packaging system for serum eye drops will assist in streamlining current manufacturing protocols, creating a more efficient process which will be evaluated using cost-benefit analysis.

Data from platelet additive studies were presented to the Therapeutic Goods Authority (TGA) to support the Blood Service’s application to extend platelet shelf-life from five to seven days.

Frozen blood research

Cryopreservation is an attractive alternative method for blood component storage, enabling considerable extension of the component shelf-life compared with liquid storage. However, it is essential to understand any biochemical and functional alterations to blood components arising from this process, and to determine how any changes may influence their clinical utility when transfused. The frozen blood research theme assesses technologies and develops strategies to improve cryopreservation processes for platelets, red cells and plasma.

A major focus of this theme has been the successful technology transfer and subsequent validation of manufacturing processes for two blood components, deep frozen plasma and red cells, for supply to the Australian Defence Force (ADF). Following technology transfer, the Frozen Blood Project Team conducted the ADF frozen blood field trial, which demonstrated the successful transfer of processes initially developed in R&D to an external customer.

Methods for cryopreservation of the third blood component, platelets, are now being developed. Current research to understand the effects of cryopreservation on platelet quality will facilitate technology transfer of these procedures to Manufacturing and subsequently the ADF.

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Understanding pathogen reduction technologies

Working with the

ADF to supply frozen blood to remote defence

personnel

Dr Ryan Hyland and Ms Shereen Tan

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Understanding pathogen reduction technologies

Pathogen reduction technology (PRT) is designed to inactivate pathogens (viral, bacterial and parasitic) in blood components. The Applied and Developmental Research group has acquired substantial knowledge and expertise in this area and this research theme has been designed to build upon this expertise and assess the applicability of these technologies to the Australian context. Projects will lead to a more detailed understanding of the effects of PRT treatment on blood components and of the clinical outcomes for recipients of PRT-treated components. This will subsequently provide strong technical support for any future Blood Service reviews to consider whether PRT should be integrated into manufacturing procedures.

Projects have consolidated findings and expertise gained from previous PRT studies. Having built a strong international reputation in this field, Blood Service researchers were approached by MacoPharma (one of the commercial developers of PRT) to evaluate the efficacy of the THERAFLEX UVC-Platelets system for the inactivation of dengue virus and to examine the quality of platelets following UVC treatment. This research was performed on a contract basis and was fully cost-recovered. Additionally, the group received funding from the Australian and New Zealand Society for Blood Transfusion (ANZSBT) to investigate the interactions between PRT-treated platelets and neutrophils.

Table 2: Applied and Developmental Research projects, by theme

Improved manufacturing efficiencies, systems and product characterisation

Completed projects

Production of “dry” buffy coats Dr Kelly Winter, Dr Denese Marks

Production of reduced plasma buffy coats Dr Kelly Winter, Dr Lacey Johnson, Dr Denese Marks

Assessment of novel platelet additive solutions (PAS) for the maintenance of platelet quality over extended storage

Dr Lacey Johnson, Dr Denese Marks

To assess improvements in protein yield using Haemonetics high separation (HS) core in conjunction with Rev H software

Dr Denese Marks, Dr Kelly Winter, Dr Ryan Hyland

Assessment of bioactive substances in washed red cells prepared for neonatal transfusion

Dr Celine Loh and Dr Denese Marks

Ongoing projects

Evaluation of a new packaging system for serum eye drops Dr Joanne Tan, Dr Denese Marks

Anaerobic storage of red blood cells Dr Margaret Veale and Dr Denese Marks

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Frozen Blood

Completed projects

Assessment of alternate reconstitution solutions to improve platelet quality following cryopreservation (Aim 1B and 1C of the frozen blood research theme)

Dr Lacey Johnson, Dr Denese Marks

Evaluation of plasma quality following lyophilisation and reconstitution Dr Celine Loh, Dr Ryan Hyland and Dr Denese Marks

Optimisation and characterisation of deglycerolised red cell products (Part 1) Dr Kelly Winter, Dr Lacey Johnson and Dr Denese Marks

Ongoing projects

Stability testing of frozen blood products to determine shelf-life at minus 80°C (Aim 1A of the frozen blood research theme)

Dr Lacey Johnson, Dr Denese Marks

A preliminary evaluation of cryopreserved and PRT-treated platelet products using an in vitro microvascular transfusion model

Dr Margaret Veale, Dr Lacey Johnson, Dr Denese Marks

A pilot randomised, controlled, double-blind clinical trial of cryopreserved platelets vs. conventional liquid-stored platelets for the management of post-surgical bleeding

Dr Lacey Johnson, Dr Denese Marks, Prof David O Irving

Understanding pathogen reduction systems Completed projects

The effect of the THERAFLEX UV-Platelets system on the infectivity of dengue viruses

Dr Helen Faddy, Mr Jesse Fryk, Dr Denese Marks

The influence of pathogen reduction treatment on the immunomodulatory capacity of platelets: does it change the way they interact with neutrophils?

Dr Celine Loh and Dr Denese Marks

Evaluation of the in vitro quality of platelets treated with the THERAFLEX UV-Platelets pathogen reduction technology system

Dr Lacey Johnson, Dr Ryan Hyland and Dr Denese Marks

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Clinical Research The Clinical Research Program focuses on the safety of blood donors, and the safety, efficacy and appropriate use of transfused blood components. Work is conducted in collaboration with other research groups by carrying out human clinical trials, and development, analysis and linkage of clinical registries. In 2013-14, two projects were completed within this program, and a further seven are ongoing. Their titles and Blood Service investigators are listed below.

Projects within Clinical Research fall within three strategically aligned research themes:

• Product improvement • Patient adverse event management • Donor adverse event management.

Product improvement

This research focuses on extending and improving the range of Blood Service products.

The continuing increase in demand for IVIg is the primary driver for plasma collection at the Blood Service. One project within this theme aims to identify markers of efficacy of IVIg which are predictive of clinical outcome. If successfully identified, a set of markers may be used to determine whether an individual is likely to respond, and if so, to establish the minimal effective dose in an individual and ensure cost-effective use of this expensive product.

Patient adverse event management

In some cases transfusion can be life-threatening. This can be caused by many factors, including the patient’s response to the donor’s blood itself, or to substances that accumulate during storage of the blood component to be transfused. This theme investigates the usage of blood components and the resulting outcomes for patients in a clinical setting.

A highlight for the year was the completion of a retrospective study aimed at determining the incidence of leucocyte survival (transfusion-associated microchimerism) within Australian major trauma patients who were transfused between 2000 and 2012. This study determined that there is continued leucocyte survival in up to 10 per cent of major trauma patients transfused with four or more red cell units, despite the introduction of leucocyte filtration for all blood components manufactured by the Blood Service since October 2008. Furthermore, patients who are most at risk of microchimerism appear to present with spleen injury prior to transfusion. This data could be used by clinical practitioners to determine whether procedures such as irradiation should be used for patients such as these.

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Ensuring new mothers and babies have access to the blood they need

Dr Rena Hirani and Dr Wayne Dyer

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Donor adverse event management

Management of adverse events in donors allows the Blood Service to maintain donor health and safety as well as to ensure a reliable, ongoing supply of blood products and components. Adverse events range from feeling unwell at the time of donation, through to more complex immune responses such as those seen in the RhD program.

As part of a national Blood Service RhD Program, eligible RhD-negative individuals are actively immunised with RhD-positive red blood cells (RBCs) to stimulate an immune response to produce anti-D immunoglobulin. However, up to 50 per cent of donors newly enrolled into this program do not respond to immunisation. A screening test to identify these “non-responders” to foreign RBC antigens would be useful. In this context, a recent National Heart, Lung and Blood Institute working group has identified RBC alloimmunisation as a priority research area.

Table 3: Clinical Research projects by theme

Product Improvement

Completed projects

A prospective survey of donors commencing autologous serum eyedrops (manufactured by the Blood Service) to treat keratoconjunctivitis sicca (dry eye syndrome) and non-healing corneal ulcers (ASED II)

Ms Jenny Fisher, Dr Philip Mondy, Dr Tania Brama, Dr Daniel Waller, Ms Carley Gemelli, Dr Hugh Capper, Prof David O Irving

Ongoing projects

Clinical studies of evidence-based IVIg dosing in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and idiopathic thrombocytopenic purpura (ITP) patients.

Dr Wayne Dyer, Dr Joanne Tan

Patient adverse event management

Completed projects

Blood product safety in massive transfusion recipients: The effect of leucoreduction on the incidence on transfusion-associated microchimerism: A retrospective study.

Dr Rena Hirani

Ongoing projects

Blood product safety in massive transfusion recipients – The effect of leucoreduction on the incidence on transfusion-associated microchimerism: A prospective study.

Dr Rena Hirani

Perinatal Transfusion Outcomes Partnership (OBOE) – (NHMRC-funded Partnership grant)

Prof David O Irving and (until October 2013) Dr Hugh Capper

TRANSFUSE (NHMRC grant-funded) Prof David Irving, Dr Philip Mondy

TORC II – Transfusion Outcomes Research Collaborative (Blood Service – Monash University Collaborative)

Prof David O Irving, Prof Robert Flower, Dr Chris Hogan (TORC II Steering Committee members)

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Donor adverse event management

Ongoing projects

Genetic polymorphisms that predict response to RhD immunisation

Dr Joanne Tan

An open label three arm interventional study assessing the effect of vein visualisation technology on donation reactions and anxiety in donors aged 18-30 years.

Prof David O Irving, Dr Phillip Mondy, Dr Tania Brama, Ms Deborah Wall–Smith, Dr Daniel Waller, Ms Jenny Fisher.

Dr Rena Hirani

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Donor and Community Research Donor and Community Research employs behavioural and social science theory and methods to describe, explain, predict and influence blood donation behaviour to ensure the sustainability of Australia’s donor base. In 2013-14, three projects were completed in this research program, two were abandoned, and five are ongoing. Their titles and Blood Service investigators are listed below. Research themes in 2013-14 are:

• Understanding donor motivation • Supporting donor retention • Lapsed donor reactivation

Understanding donor motivation

This theme aims to investigate and explain the reasons why people choose to donate blood as well as the reasons why they choose not to participate in blood donation. Work involves practical application of strategies that aim to increase the donor base and thus ensure sustainability of supply.

Projects undertaken in the Understanding Donor Motivation theme include an Australian Research Council (ARC) Linkage Grant funded project that examines methods to motivate individuals from culturally diverse backgrounds (specifically, those from Sub-Saharan Africa) to donate blood. This is a three year project being conducted primarily by Blood Service collaborators in the university sector. Outcomes from this project are expected to inform business decisions in relation to the engagement of a broader range of culturally and linguistically diverse communities.

Two projects that had been originally included in R&D’s project commencement summary for 2013-14 were abandoned early in the year. These projects were deemed not to be sufficiently aligned to business requirements or timelines to be carried out at this time. These projects were:

• Knowledge and attitudes about donating blood and organs amongst school students less than 16 years old.

• Evaluating the new donor centre design: Donor and staff perspectives (complementary to Blood Service project).

Donor retention

The donor retention research theme encompasses research projects that focus on the adequacy and sustainability of the Australian blood supply. Proposed methods for promoting retention are diverse and include improving the donation experience and understanding social and demographic factors that impact on donor retention.

A highlight of this research theme has been the technological and logistical refinements to in-centre research methods. Use of face to face recruitment, tablet devices and automated data extractions

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Using new data collection methods to understand donors

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resulted in an 80 per cent response rate followed by 50 percent retention over a four week period. This sets up a strong model for future research projects.

Lapsed donor reactivation

This research theme focuses on interventions to reactivate blood donors who no longer donate, despite having a previous ongoing engagement and commitment to donate.

The Motivating Lapsed Donors - Registry Project sought to determine whether changing service interactions with lapsed donors could promote reactivation and retention of these people. It led to the testing and business development of a lapsed donor registry that reduces the cost per donation for lapsed donors by almost 40 per cent. The outcomes from this project, initiated in 2011-12 are now being incorporated into routine practice at the Blood Service.

Table 4: Donor and Community Research projects by theme

Understanding donor motivation

Completed projects

A pilot of Geographic Information Systems (GIS) to inform resource allocation within the Australian Red Cross Blood Service

Dr Daniel Waller, Dr Geoff Smith

Ongoing projects

Evaluating a model for culturally relevant interventions to increase blood donation and overcome perceived blood donation barriers among migrant communities: the case of African migrants and refugees (ARC Linkage Grant funded)

Ms Jane Hayman

Hospitals to hospitality Dr Geoff Smith until May 2014, then Ms Jane Hayman

Supporting donor retention

Completed projects

Understanding the emotional responses and service perceptions of Blood Donors: a National Study - consolidation of previous projects to collaborate with marketing and to inform development of targeted interventions

Dr Geoff Smith until May 2014, then Ms Jane Hayman

Ongoing projects

The initiation and maintenance of plasma and platelet donation in Australia: An analysis of the role of donor identity and commitment (ARC linkage grant funded)

Dr Geoff Smith until May 2014, then Ms Jane Hayman

Role of pride in motivating blood donations - a collaborative project with Blood Service Marketing and University of NSW (UNSW) to determine if new directions can be pursued

Dr Daniel Waller

Ms Amanda Thijsen

Towards a typology of referring blood service community members - collaborate with marketing to understand the value of

Ms Jane Hayman

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Lapsed donor reactivation

Completed projects

Motivating Lapsed Donors - Registry Project Dr Daniel Waller

Ms Carley Gemelli(L) and Ms Jane Hayman (R)

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Transfusion Science Research The Transfusion Science Research team collaborates with the Manufacturing and Medical, Transplantation and Quality Services divisions and external agencies to conduct leading-edge research to improve understanding of the clinical effects of blood and blood products which can be translated into improved operational procedures. A key component of this research is “horizon scanning” which enables the Blood Service to identify emerging threats and opportunities, and thus to target research to ensure a safe and sufficient blood supply into the future. This year ten projects were completed, nine are ongoing, and three were abandoned. The project titles and Blood Service investigators are listed below.

Projects are aligned to four strategic research themes:

• Evidence based evaluation of emerging infectious risks to the safety of the blood supply • in vivo and in vitro models of transfusion • New strategies for blood grouping • Properties of stored red blood cells.

Evidence based evaluation of emerging infectious risks to the safety of the blood supply

Australia has one of the safest blood supplies in the world. However, this record could be compromised without active research to:

• ensure emerging risks are identified • develop procedures to evaluate and control risk.

Concern still exists around transfusion-transmitted infections (TTIs), especially emerging threats. This research team investigates possible risks to the safety of the Australian blood supply, with a focus on infectious diseases.

A highlight of the year’s research was the evaluation of the risk to the Australian blood supply posed by Hepatitis E virus (HEV). There is increasing public health concern over HEV globally. In Australia, cases of diagnosed HEV are uncommon with an average of only 25 new cases a year. The virus can lead to acute hepatitis and death, particularly among vulnerable groups. While there have been no reported cases of transfusion-transmitted HEV in Australia to date, cases have been reported in the United Kingdom, Germany, France and Japan. As recently as 1 August 2014, the area of Hokkaido in Japan became the first to introduce routine HEV testing for all donations. In England, a recent study detected the virus in around one in 3000 donors.

Transfusion Science researchers have completed a project that looked at evidence of exposure to the virus in over 3000 Australian donor plasma samples. HEV exposure was demonstrated in 5.99 per cent of Australian donors, of whom 2.06 per cent were recently exposed to the virus. A higher rate of previous exposure was found in international travellers. A small proportion of donors (3.37 per cent) was identified with evidence of previous HEV exposure and who had not reported travel outside Australia. They may, therefore, have acquired HEV locally. This work has been accepted for publication in the journal Emerging Infectious Diseases. A larger study is planned to measure the rate of HEV viraemia in blood donations in order to estimate the risk this virus poses to the Australian blood supply.

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Dr John-Paul Tung

Keeping the blood supply safe by monitoring emerging diseases

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Transfusion models

These projects investigate how the factors in transfused blood components interact with a patient’s immune and vascular system. Donor variation, procedures for processing and storage of blood components and the presence of biological response modifiers are all investigated. Modelling of transfusion in the laboratory and in animal models enables detailed responses to be studied, in ways that are not possible in human patients. This research provides a better understanding of how transfusion influences patients’ clinical outcomes and will supply the Blood Service with evidence to underpin the development of safer blood products and improved transfusion safety.

New strategies for blood grouping

Demographic changes in the Australian population have led to variation in the frequency and type of blood groups, with consequences for transfusion practice. For some blood groups, reliable typing is only available using genetic technologies. In this research theme, data from new methods are compared with current data and used to evaluate strategies for more accurate and reliable matching of a full blood profile between donors and recipients.

Blood Service researchers contributed to world-class genotyping research by identifying two new clinically significant antigens - SARA and Kip - which are now classified in the MNS blood group system. This project is entitled Clinical utility of genotyping in solving complex red cell serology: benefit in the contemporary Australian population.

In studying the SARA antigen, massive parallel sequencing (also known as next generation sequencing) was used to characterise the genetic change in members of an Australian family carrying the blood group. This antigen has proven to be clinically significant, and was later identified in a Canadian family who had experienced haemolytic disease of the newborn.

The evidence for the existence of Kip was uncovered by Dr Ling Wei with the Blood Service R&D team in Australia. Dr Wei, a visiting scholar from China, reviewed the literature in relation to a case reported as “Kip positive” that had remained unresolved for 25 years. Dr Wei and the R&D team used gene sequencing to characterise the allele in stored samples from that donor. The allele is now recognised as GYP*KIP and the associated antigen, Kip, is recognised as MNS48.

The publication of the techniques used in making these discoveries provides a basis for laboratory tests to identify these blood groups in future investigations.

Properties of stored red blood cells

This research focuses on understanding the impact of storage on red blood cells and other blood products. Outcomes from this research measure changes in fresh blood components under different storage conditions. This research, previously carried out in Melbourne, was relocated to Brisbane as part of the restructure of the R&D division in late 2013.

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24 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 Table 5: Transfusion Science Research projects by theme

Evidence based evaluation of emerging TTI risk

Ongoing projects

Does Hepatitis E virus pose a risk to the safety of Australia’s blood supply?

Dr Helen Faddy, Mr Ashish Shrestha, Dr Clive Seed, Prof Robert Flower, Ms Kelly Rooks, Dr Anthony Keller, Dr Robert Harley, Dr Hiu-Tat Chan

A new multimodal assay for the detection of dengue contamination of blood (ARC Linkage Grant-funded with University of Queensland)

Dr Helen Faddy, Ms Thu Tran, Prof David O Irving, Prof Robert Flower

Dengue transmission under climate change in Northern Australia: linking ecological and population-based models to develop adaptive strategies (NHMRC grant funded)

Dr Helen Faddy

Does Babesia pose a risk to the safety of Australia’s blood supply?

Dr Helen Faddy, Dr Clive Seed, Prof Robert Flower, Ms Kelly Rooks, Dr Anthony Keller, Dr Robert Harley, Dr Hiu-Tat Chan

Transfusion models: immune biomarkers and murine model

Ongoing projects

Identification of biomarkers to predict patient outcomes to transfusion

Dr Melinda Dean, Prof Robert Flower, Ms Katrina Ki, Ms Kelly Rooks,Ms Alexis Perros

Investigation of blood physiology and haematological disease through analysis of mice with novel ENU-induced mutant phenotypes.

Dr Melinda Dean, Prof Robert Flower, Ms Katrina Kildey (supported by an APRA postgraduate scholarship), Ms Fenny Chong

Transfusion models: TRALI and Proteomics in ovine model

Completed projects

Extracorporeal membrane oxygenation (ECMO) (NHMRC/TPCHF/ASYLMF/ANZSBT/QEMRFgrants-funded)

Dr John-Paul Tung, Ms Gabriela Simonova, Ms Eunike McGowan

Is blood coagulation activated following transfusion of red blood cells (RBC) stored at 4ºC for an extended time? (NHMRC/TPCHF/ASYLMF/ANZSBT/QEMRF grants-funded)

Dr John-Paul Tung, Prof Robert Flower, Ms Htet Htet Aung

Optimisation and characterisation of deglycerolised red cell products (Part 1) Characterising the sheep red cell storage lesion to support the future development of an in vivo sheep model of homologous blood transfusion

(NHMRC/TPCHF/ASYLMF/ANZSBT/QEMRFgrants-funded)

Dr John-Paul Tung, Dr Kristen Glenister, Ms Gabriela Simonova

Ongoing projects

Ovine Transfusion Related Acute Lung Injury (TRALI) model: characterising antibody-mediated TRALI and Biological Response Modifier (BRM)-mediated TRALI

Dr John-Paul Tung, Dr Melinda Dean, Ms Gabriela Simonova, Ms Denisa Meka, Ms Eunike McGowan, Ms Annette Sultana, Prof Robert Flower

Investigating age of red cells in an ovine model of trauma- Dr John-Paul Tung, Ms Gabriela

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haemorrhage (formerly CRASH-2/CRASH-Plus) Simonova

Abandoned projects

Proteomic and metabolic evaluation of rejuvenated human and sheep red cells.

Dr Kristen Glenister, Dr John-Paul Tung

New Strategies for blood grouping

Completed projects

Improving transfusion safety: identification of phenotype/genotype anomalies in the reagent red cell donor panel

A/Prof Catherine A Hyland, Ms Rhiannon McBean and Prof Robert Flower

Evidence-based estimate of the risk of alloimmunisation as a result of transfusion of RhD negative recipient with very weak D red blood cell (DEL).

A/Prof Catherine Hyland, Dr Stacy Scott, Professor Robert Flower

Clinical utility of genotyping in solving complex red cell serology: benefit in the contemporary Australian population

A/Prof Catherine A Hyland, Ms Rhiannon McBean and Prof Robert Flower

Ongoing projects

NIPA translation: Non-invasive prenatal RHD genotyping as a guide to decision making in managing pregnancies for alloimmunised RhD negative pregnant women.

A/Prof Catherine Hyland, Ms Helen O’Brien, Ms Glenda Millard, Prof Robert Flower

Properties of stored red blood cells

Completed projects

Microparticles (MPs) in fresh frozen plasma, cryoprecipitate and red blood cell components

A/Prof Rosemary Sparrow

Donor-related factors and variability of stored RBC quality: towards a predictive tool for improved quality of RBC units

A/Prof Rosemary Sparrow

Properties of stored red blood cells: minimization of immune and vascular reactivity

A/Prof Rosemary Sparrow

Role of the P2X7 receptor, an ATP-gated cation channel, in the red cell storage lesion

Dr Kelly Winter, Dr Lacey Johnson, Dr Denese Marks

Abandoned projects

Evaluation of a new device to measure RBC mechanical fragility

Evaluation of polymer beads to improve the quality and reduce donor related variability of stored blood components

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26 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014

APPENDIX 1: PUBLICATIONS AND INVITED PRESENTATIONS3 Peer reviewed journal articles

Publications by Blood Service researchers

Aubron C, Bailey M, McQuilten Z, Pilcher D, Hegarty C, Martinelli A, Magrin G, Irving D, Cooper DJ, Bellomo R. Duration of red blood cells storage and outcome in critically ill patients. Journal of Critical Care 2014 Jun; 29:476 e1-8

Booth AO, Lim K, Capper H, Irving D, Fisher J, McNaughton SA, Riddell L, Keller A, Nowson CA. Iron status and dietary iron intake of female blood donors. Transfusion 2013 Jul 22. doi: 10.1111/trf.12347.

Chan, KS, Sparrow RL Microparticle profile and procoagulant activity of fresh-frozen plasma is affected by whole blood leukoreduction rather than 24-hour room temperature hold. Transfusion. 2014 Aug;54(8):1935-44. doi: 10.1111/trf.12602. Epub 2014 Mar 18

Chemonges S, Shekar K, Tung JP, Dunster KR, Diab S, Platts D, Watts RP, Gregory SD, Foley S, Simonova G, McDonald C, Hayes R, Bellapart J, Timms D, Chew M, Fung YL, Toon M, Maybauer MO, Fraser JF. Optimal Management of the Critically Ill: Anaesthesia, Monitoring, Data Capture, and Point-of-Care Technological Practices in Ovine Models of Critical Care. BioMed Research International. 2014; 468309. doi: 10.1155/2014/468309.

Chemonges S, Tung JP, Fraser JF. Proteogenomics of selective susceptibility to endotoxin using circulating acute phase biomarkers and bioassay development in sheep: a review. Proteome Sci. 2014 Mar 1;12(1):12.

Faddy H, Seed C, Lau C, Racloz V, Flower R, Smythe L, Burns M, Dohnt M, Craig S, Harley R P, Weinstein P Antibodies to Leptospira among blood donors in higher-risk areas of Australia: possible implications for transfusion safety. Blood Transfusion 19:1-5. doi: 10.2450/2014.0012-14.

Fung YL, Minchinton RM, Tung JP. How do you solve a problem like TRALI? ISBT Science Series 2014 9, 287–293

Fung YL, Tung JP, Foley SR, Simonova G, Thom O, Staib A, Collier J, Dunster K, Solano C, Shekar K, Chew MS, Fraser JF. Stored blood transfusion induces transient pulmonary arterial hypertension without impairing coagulation in an ovine model of non-traumatic haemorrhage. Vox Sanguinis. 2013; 105 (2):150-8.

Fung YL, Tung JP, Minchinton RM. Neutrophil Antibodies are Clinically Important. ISBT Science Series 2014; 9, 253–257

Hyland CA, Gardener GJ, O'Brien H, Millard G, Gibbons K, Tremellen A, Ochoa-Garay G, Flower RL, Hyett JA. Strategy for managing maternal variant RHD alleles in Rhesus D negative obstetric

3 Blood Service researchers are indicated in bold type

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populations during fetal RHD genotyping. Prenatal diagnosis. 2014 Jan; 34: 56-62. doi: 10.1002/pd.4253. Epub Nov 4, 2013

McVernon J, Laurie K, Faddy H, Irving D, Nolan T, Barr I, Kelso A. Seroprevalence of antibody to influenza A(H1N1)pdm09 attributed to vaccination or infection, before and after the second (2010) pandemic wave in Australia. Influenza Other Respir Viruses 2014;8:194-200.doi: 10.1111/irv.12225. Epub 2013 Dec 31. doi: 10.1111/irv.12225

Johnson L, Loh YS, Kwok M, Marks DC. In vitro assessment of buffy-coat derived platelet components suspended in SSP+ treated with the INTERCEPT Blood System. Transfusion Medicine 2013; 23: 121-9.

Johnson L, Reid S, Tan S, Vidovic D, Marks DC. PAS-G supports platelet reconstitution after cryopreservation in the absence of plasma. Transfusion 2013; 53: 2268-2277.

Kildey K, Flower RL, Tran TV, Tunningley R, Harris J, Dean MM. Characterization of ENU-induced Mutations in RBC Structural Proteins. Computational and Structural Biotechnology Journal. 2013; 6 (7): e20130312

Loh YS, Johnson L, Kwok M, Marks DC. Pathogen reduction treatment alters the immunomodulatory capacity of buffy-coat derived platelet concentrates. Transfusion 2014; 54: 577-584. doi: 10.1111/trf.12320. Epub 2013 Jul 5.

Lopez GH, McBean RS, Wilson B, Irwin DL, Liew YW, Hyland CA and Flower RL Molecular typing for the Indian blood group associated 252G>C single nucleotide polymorphism in a selected cohort of Australian blood donors Blood Transfusion 2014 Jun 5:1-8. doi: 10.2450/2014.0336-13. [Epub ahead of print]

Lucky TTA, Seed CR, Waller D, Lee, JF, McDonald A, Wand H, Wroth S, Shuttleworth G, Keller, AJ, Pink J, Wilson DP. Understanding noncompliance with selective donor deferral criteria for high-risk behaviors in Australian blood donors. Transfusion 2014; 54: 1739-49

Marks DC, Speedy J, Robinson KL, Brama T, Capper HR, Mondy P, Keller AJ An 8-week course of 45 mg of carbonyl iron daily reduces iron deficiency in female whole blood donors aged 18 to 45 years: results of a prospective randomized controlled trial. Transfusion 2014; 54: 780-788. doi: 10.1111/trf.12464. Epub 2013 Oct 28.

Masser B, Smith G, and Williams,L. Donor Research in Australia - Challenges and Promise. Transfusion Medicine and Hemotherapy. 2014; 41: 296–301.

McQuilten Z, Waters N, Polonsky M, Renzaho A. Blood donation by African migrants and refugees in Australia: the role of demographic and socio-economic factors. Vox Sanguinis 2014 Jan 106, 137–143.

Osthoff M, Yong HMA, Dean MM, Eisen DP. Significance of mannose-binding lectin deficiency and NOD2 polymorphisms in Staphylococcus aureus bloodstream infections. PLoS One 2013; 8 (9): e76218.

Patterson JA, Roberts CL, Bowen JR, Irving DO, Isbister JP, Morris JM, Ford JB. Blood transfusion during pregnancy, birth, and the postnatal period. Obstet Gynecol. 2014 ;123: 126-33.

Polonsky MJ, Renzaho AMN, Shahriar Ferdous A, McQuilten Z. African culturally and linguistically diverse communities’ blood donation intentions in Australia: integrating knowledge into the theory of planned behavior. Transfusion 2013; 53: 1475-1486.

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28 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 Reade M, Marks DC, Johnson L, Irving D, Holley A. Frozen platelets for rural Australia: the CLIP trial. Anaesthesia and Intensive Care 2013; 41, 804-805.

Salvin HE, Pasricha S-R, Marks DC, Speedy J. Iron deficiency in blood donors: a national cross-sectional study. Transfusion 2014 Apr 17. doi: 10.1111/trf.12647. [Epub ahead of print]

Seed CR, Lucky TTA, Waller D, Lee JF, Wroth S, McDonald A, Pink J, Wilson DP, Keller AJ Compliance with the current 12-month deferral for male-to-male sex in Australia. Vox Sanguinis 2014 Jan 106:14-22.

Simonova G, Tung JP, Fraser JF, Lien Do H, Staib A, Chew MS, Dunster KR, Glenister KM, Jackson D, Fung YL. A comprehensive ovine model of blood transfusion. Vox Sanguinis 2014; 106: 153-60.

Sparrow RL, Sran A, Healey G, Veale MF, Norris PJ. In vitro measures of membrane changes reveal differences between red blood cells stored in saline-adenine-glucose-mannitol and AS-1 additive solutions: a paired study. Transfusion 2014; 54: 56056-8. doi: 10.1111/trf.12344. Epub 2013 Jul 22.

Storry JR, Castilho L, Daniels G, Flegel WA, Garratty G, de Haas M, Hyland C, Lomas-Francis C, Moulds JM, Nogues N, Olsson ML, Poole J, Reid ME, Rouger P, van der Schoot E, Scott M, Tani, Y, Yu LC, Wendel S, Westhoff C, Yahalom V, Zelinski T International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology: Cancun report (2012) Vox Sanguinis 2014; 107: 190-96; doi: 10.1111/vox.12127 Epub date 2014/01/01

Tran HB, Hodge G, Holt P, Dean MM, Ahern J, Reynolds PN, Hodge S. Oxidative stress decreases functional airway mannose binding lectin in COPD. PLoS One 2014; ;9: e98571

Tsui NB, Hyland CA, Gardener GJ, Danon D, Fisk NM, Millard G, Flower RL, Lo YM. Noninvasive fetal RHD genotyping by microfluidics digital PCR using maternal plasma from two alloimmunized women with the variant RHD(IVS3+1G>A) allele. Prenatal Diagnosis 2013; 33:1214-6. doi: 10.1002

Veale MF, Healey G, Sparrow RL. Longer storage of red blood cells is associated with increased in vitro erythrophagocytosis. Vox Sanguinis 2014; 106: 219-226. doi: 10.1111/vox.12095. Epub 2013 Oct 9.

Viennet E, Knope K, Faddy H, Williams C, Harley D. Assessing the threat of chikungunya virus emergence in Australia. Communicable Diseases Intelligence 2013, 37:E136-43.

Williams S, Richards J, Faddy H ,Leydon J, Moran R, Nicholson S, Perry F, Paskin, R, Catton M, Lester R, MacKenzie J. Opportunistic seroprevalence study for Murray Valley Encephalitis and Kunjin viruses in Victoria, Australia 2011. Australian and New Zealand Journal of Public Health. 2013; 37:427-33.

Winter KM, Johnson L, Kwok M, Vidovic D, Hyland R, Mufti M, Erickson A, Marks DC. Red cell in vitro quality and function is maintained following S-303 Pathogen Inactivation Treatment. Transfusion 2014; 54: 1798-807.

Yuan FF, Velickovic Z, Ashton LJ, Dyer WB, Geczy AF, Dunckley H, Lynch G, Sullivan JS. Influence of HLA gene polymorphisms on susceptibility and outcome post infection with the SARS-CoV virus. Virol Sinica 2014 (DOI) 10.1007/s12250-014-3398-x.

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Publications which have been epublished ahead of print during the reporting period, 1 July 2013-30 June 2014. These publications will appear in print in the following reporting period:

Chan, KS, Sparrow RL Microparticle profile and procoagulant activity of fresh-frozen plasma is affected by whole blood leukoreduction rather than 24-hour room temperature hold. Transfusion. 2014 Aug;54(8):1935-44. doi: 10.1111/trf.12602. Epub 2014 Mar 18

Johnson L, Coorey C, Marks DC. The hemostatic activity of cryopreserved platelets is mediated by phosphatidylserine-expressing platelets and platelet microparticles. Transfusion. 2014 Aug;54(8):1917-26. Epub 2014 Feb 17, ahead of print DOI: 10.1111/trf.12578. * Invited for journal cover artwork *

Scott SA, Nagl L, Tilley L, Liew YW, Condon J, Flower R, Hyland CA The RHD(1227G>A) DEL-associated allele is the most prevalent DEL allele in Australian D- blood donors with C+ and/or E+ phenotypes. Transfusion. 2014 Jun 4. doi: 10.1111/trf.12701. [Epub ahead of print]

Publications by Blood Service collaborators

Bove LL, Bagot,KL, Masser BM, White KM. Resisting a status downgrade: The role of messaging in impeding donor flexibility. American Marketing Association International Service Research Conference. Thessaloniki, Greece; 06/2014.

Renzaho AMN, Polonsky MJ The influence of acculturation, medical mistrust, and perceived discrimination on knowledge about blood donation and blood donation status. Transfusion 2013; 53: 162S-171S.

Slonim R, Wang C, Garbarino E. The Market for Blood: Past, Present and Future. Journal of Economic Perspectives. Journal of Economic Perspectives 2014; 28: 177-196.

Peer reviewed published abstracts Dean MM, Ki KK, Tran TV, Baidya S, Christensen AM, Flower RL. Packed Red Blood Cells Modulate Expression of Dendritic Cell Signal Transduction and Antigen Presentation Pathways. Blood; 2013; 122 (21): 1156.

Dean MM, Kildey K, Tran TV, Rooks K, Baidya S, Flower RL.Single Nucleotide Variations in Spectrin-1β Accentuate The Red Blood Cell Storage Lesion. Blood 2013; 122 : 3422.

Dean MM, Samson LD, Rooks K, Fryk J, Baidya S, Flower RL. Donor Variation in Biological Mediators During Storage of Packed Red Blood Cells. Blood 2013; 122: 3655.

Faddy H, Allison K, Margaritis A, Ismay S, Marks D. The effect of freezing and thawing samples stored in plasma preparation tubes (PPTs) for up to 18 months on the ability to detect HIV, HCV and HBV. Vox Sanguinis 2014;107 (Suppl. 1): 15,.

Faddy H, Fryk J, Young P, Watterson D, Tolksdorf F, Sumian C, Gravemann U, Seltsam A, Marks D. The Theraflex UV-Platelets technology effectively inactivates dengue viruses in platelet concentrates. Vox Sanguinis 2014;107 (Suppl. 1): 125.

Faddy H, Racloz V, Lau C, Flower R & Weinstein P. Sero-prevalence of antibodies to Leptospira among blood donors in high-risk areas of Queensland. Transfusion Medicine 2013; 23: 292

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30 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 Faddy H, Ranzoni A, Watterson D, Chong, KC S, Tran T, Jones M, Lebani K, Flower R, Irving D, Mahler S, Young P, Cooper M. Development of the first integrated multimodal assay for the sensitive detection of dengue virus in blood donations. Vox Sanguinis 2014; 107 (Suppl. 1): 165

Faddy H, Shrestha A, Seed C, Rooks K, Harley R, Chan H, Holmberg J, Flower R. Hepatitis E virus seroprevalence in Australian donors. Vox Sanguinis 2014; 107 (Suppl. 1): 161

Flower RL, Kildey K, Tran TV, Dean MM. Variation in Blood component storage in an animal model related to single nucleotide variants in spectrin gene spnb1. Vox Sanguinis 2013; 105 (s2): 12

Fung YL, Tung JP. What’s new with TRALI? Vox Sanguinis 2013; 105 (s2): 42

Hyland C, Lopez G, McBean R, Liew Y-W, Condon J, Flower R. Duffy blood group typing: Is genotype more accurate than phenotype for Duffy blood grouping? Vox Sanguinis 2014; 107: s1 37

Johnson L, Tan S, Coorey C, Marks DC. Evaluation of alternate solutions for the reconstitution of cryopreserved platelets to improve post-thaw recovery. Journal of Military and Veterans’ Health 2013; 21: 33-34

Loh YS, Dean MM, Johnson L, Marks DC. Pathogen reduction treatment and subsequent storage of buffy-coat derived platelets alters production of monocyte inflammatory mediators in a whole blood transfusion model. Vox Sanguinis 2013;105 (s2): 12.

Loh YS, Stark MJ, Kwok M, Tan S, Marks DC. Washing of red cells, age at the time of processing and subsequent storage influence the in vitro quality and bioactive substances in the red cell supernatant. Vox Sanguinis 2013; 105 (s2): 17

Marks DC. Pathogen Reduction Technology. Vox Sanguinis 2013; 105 (s2): 3

McBean R, Hyland C and Flower R. Molecular Genotyping Platforms for Blood Group Antigen Prediction. Pathology 2014; 46: S87.

McBean R, Hyland C, Roscioli T and Flower R. The low frequency SARAH blood group antigen: Evidence for a new MNS antigen. Vox Sanguinis 2014; 107: S1, 17

McBean R, Hyland C, Roscioli T and Flower R. Next Generation Sequencing of an Australian Family to Identify the Genetic Basis of a Rare Blood Group Antigen. Pathology 2014; 46: S87

Scott S, Tilley L, McBean R, Flower R and Hyland C. DEL-Associated Alleles, Including Novel RHD DEL Alleles, Detected in 2.17% of RhD Negative Blood Donors with the RhC and/or RhE Haplotypes. Transfusion 2013; 53: 167A.

Simonova G, Fung YL, Glenister KM, Tung JP. The Ovine Packed Red Blood Cell Storage Lesion: Characterisation And Comparison To That Of Human Packed Red Blood Cells. Vox Sanguinis 2013; 105 (s1): P-245.

Speedy J, Marks DC, Brama T, Bell B, Bower M. A new era for youth donors: supporting the community’s need for blood through advocacy. Vox Sanguinis 2014; 107 (s1): 57-248

Tran HB, Ahern J, Hodge G, Holt P, Dean MM, Reynolds PN, Hodge S; Oxidative changes to sub-cellular localisation and function of mannose binding lectin on alveolar macrophages may contribute to decreased phagocytosis in COPD. Respirology; 2014; 19 (S2): 45.

Tung JP, Bierman W, Knauth C, Flower RL, Dean MM. Divergent in vitro inflammatory responses to antibodies relevant to transfusion-related acute lung injury. Transfusion Medicine; 2013; 23 (s2): YS04.

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Tung JP, Simonova G, Glenister K, Fraser JF, Fung YL. The sheep as a transfusion model: Comparison of the storage lesion of human and ovine red blood cell units. Transfusion Medicine; 2013; 23 (s2).

Veale MF, Healey G, Johnson L and Marks DC. Thrombus formation and adhesion of cryopreserved platelets to collagen and endothelial cells under shear stress. Vox Sanguinis, 2014; 107 (Suppl. s1): 1-56.

Young M, Cripps A, Nimmo G, Ji Y, Fryk J, Faddy H, Flower R.Sero-Prevalence of Antibodies to Hepatitis A Virus among Australian Blood Donors. Pathology 46, S87, 2014

Invited publications Hodge S, Dean MM, Eisen DP; Lectins as potential adjunct therapeutics for COPD/emphysema? Invited Editorial; Journal of Pulmonary & Respiratory Medicine; July 2013.

Invited external presentations Dean MM, Faddy H, Tung JP; Introduction to Blood Transfusion and Research and Development at the Blood Service; Queensland University of Technology; June 2013.

Dean MM Myeloid Dendritic Cells in Blood Transfusion; Invited Speaker, DC Down Under Symposium; Sydney Australia; August 2013.

Dean MM Session Chair: Age of Red Cells. Annual Scientific Meeting of HAA. Gold Coast, Australia. 20-23 October, 2013.

Faddy HM The Australian Perspective on the Emerging Threat of Hepatitis E Virus. Grifols Symposium, International Society for Blood Transfusion, Seoul, June 2014.

Faddy HM Emerging threats to the safety of the blood supply. Queensland branch HSANZ meeting, Brisbane, March 2014.

Faddy HM Seroprevalence of antibodies to hepatitis A virus among Australian blood donors. DiaSorin Australia Infectious Disease Scientific User Group Meeting, Noosa, March 2014.

Faddy HM Seroprevalence of hepatitis E virus in Australia. International Society for Blood Transfusion Working Party on Transfusion Transmitted infectious diseases, Kuala Lumpur, December 2013.

Faddy HM. Emerging threats to the Australian blood supply. HAA, Gold Coast, October 2013.

Flower, R Approaches to determination of a full profile of blood group genotypes: single nucleotide variant mapping and massively parallel sequencing; Invited speaker, BIT’s 5th Annual World DNA and Genome Day, Dalien, China; April 2014.

Flower RL, Transfusion Update: Changing population demographics: genotyping to measure new antigen patterns, Melbourne 14-16 May 2014

Fung YL, Minchinton RM, Tung JP. How do you solve a problem like TRALI? State of the Art Presentations, 24th Regional Congress of the ISBT – Asia, Kuala Lumpur, Malaysia, 1–4 December 2013 – presentation by Yoke Ling Fung

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32 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 Fung YL, Tung JP, Minchinton RM. Neutrophil Antibodies are Clinically Important. State of the Art Presentations, 24th Regional Congress of the ISBT – Asia, Kuala Lumpur, Malaysia, 1–4 December 2013 – presentation by Yoke Ling Fung

Hyland CA, Gardener G, Tremellen A, Gibbons K, O’Brien H, Millard G & Flower R. Non-invasive Fetal RHD Genotyping HSANZ/ANZSBT/ASTH Annual Scientific Meeting:, Gold Coast, 20 October 2013

Hyland CA, Laboratory Testing Challenges: RHD variant case study, Transfusion Update Melbourne 14-16 May 2014

Hirani, R; The effect of leucoreduction on the incidence of transfusion associated microchimerism.

• Concord Hospital, ER and Burns unit staff, 2014 • Royal North Shore Hospital, ER and trauma staff, 2014 • John Hunter Hospital, Trauma research division April 2014 • Westmead hospital week, Trauma symposium, August 2013

Johnson L, My career as a senior research fellow at the Australian Red Cross Blood Service, Autumn Networking Session 2014, Medical Society (MedSoc) of the University of Technology, Sydney (UTS), 28 May 2014

Johnson L. Evaluation of alternate solutions for the reconstitution of cryopreserved platelets to improve post-thaw recovery. Australasian Military Medicine Association/Repat Foundation Joint Conference, Adelaide, 1 November 2013.

Marks DC. Are 7 day platelets as good as 5 day platelets? Therapeutic Goods Authority/Blood Service Liaison Meeting, via Webinar, 1 June 2014

Marks, DC. Are 7 day platelets as good as 5 day platelets? Transfusion Update, Melbourne, 16 May 2014

Marks, DC Platelet storage: could we extend the platelet shelf-life? Australian Institute of Medical Scientists North Coast Division Annual Conference; Arrawarra, NSW: 1-3 November 2013

Marks, DC. Pathogen Reduction Technology. ISBT Academy Day, 24th Regional Congress of the ISBT, Kuala Lumpur, Malaysia, December 1-4 2013

McBean RS, Hyland CA, Roscioli T and Flower RL The low frequency SARAH blood group antigen: evidence for a new MNS antigen: ISBT International Society of Blood Transfusion Working Party on Red Cell Immunogenetics and Blood Group Terminology We recommended that SARAH be assigned to the MNS blood group system: The recommendation was ratified by the ISBT WP Committee and the antigen assigned the number MNS 0047 under the ISBT nomenclature system. Seoul, South Korea, Saturday 31 May 2014

Tung JP Animal Models of Transfusion-Related Acute Lung Injury (TRALI). Annual Scientific Meeting of HAA. Gold Coast, Australia. 20-23 October 2013

Tung JP Research and Development at the Australian Red Cross Blood Service: Animal models of blood transfusion. Royal Veterinary College, London, UK. 9 October, 2013

Wei Ling, Robert Flower, Ji Yan-Li, Luo Guang-Ping, Genghis Lopez and Catherine Hyland GP.Kip: rediscovered & redefined: ISBT International Society of Blood Transfusion Working Party on Red Cell Immunogenetics and Blood Group Terminology, We recommended that GP.Kip be assigned to the MNS blood group system. This also was ratified by the Committee and a

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unique antigen found on this glycophorin assigned the number MNS 0048. Seoul, South Korea Saturday 31 May 2014.

Internal presentations The effective translation of research results into business practice depends on collaboration and communication between researchers and the broader business. Formal communication channels exist through management for initiation and translation of research projects which are relevant to the business. However, less formal communication between business divisions has the potential to generate new ideas and increase employee engagement. Communication forums include presentations such as “Pulse” in Brisbane, which aims to communicate research projects to a general audience within the Blood Service, while specific seminars provide more in-depth knowledge of research findings to key internal stakeholders (eg Blood User’s Group, Donor Centre in-services, etc).

The following list provides some examples of such internal presentations by R & D staff in 2013/14.

Hirani, R. The effect of leucoreduction on the incidence of transfusion associated microchimerism. Research and Development, Clinical team update, Jan 2014

Hirani, R. Current Blood Service Research and Development activities. Newcastle Donor Centre, April 2014

Hirani, R. The effect of leucodepletion on the incidence of transfusion-associated microchimerism. Research and Development, Laboratory peer update, April 2014

Loh YS. Pathogen Reduction Treatment And Subsequent Storage Of Buffy-Coat Derived Platelets Alters Production Of Monocyte Inflammatory Mediators In A Whole Blood Transfusion Model Australian Red Cross Blood Service, Pulse Presentation, Brisbane 26th June, 2014

Tan JCG, Bondar N, Armstrong NJ, Yuan FF, Flower RL, Capper H, Dyer WB Genetic polymorphisms associated with different responder profiles of RhD-immunised blood donors Clinicians’ Consultative Committee Meeting, Sydney Processing Centre, Blood Service, 7 August 2013

Tan JCG, Bondar N, Armstrong NJ, Yuan FF, Flower RL, Capper H, Dyer WB Genetic polymorphisms associated with different responder profiles of RhD-immunised blood donors NSW Blood User Group Meeting, Sydney Processing Centre, Blood Service, 29 October 2013

Tan JCG. Genetic polymorphisms that predict response to RhD and other red blood cell antigens Research and Development Leadership Team Meeting, Sydney Processing Centre, Blood Service, 18 December 2013

Books and other materials Master of Applied Science Thesis, Lisa Nagl, 2014, Improving the detection of donations with in the RhD negative blood donor panel which weakly express the RhD antigen. Queensland University of Technology.

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34 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014

International database listings Eight novel alleles of blood group genes were described and allelic designations were assigned by the International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group Terminology.

When a new variant of a gene is discovered it is important that this information is available to inform genetic analysis and establish discovery. In this reporting period, a number of novel variants of blood group genes were discovered by the R &D team and were published in Genbank, the most widely accessed and recognised repository of genetic information. All entries in Genbank are reviewed and curated by independent experts to ensure their novelty and accuracy.

GenBank Accession Numbers as follows:

GenBank Accession Number KF784871 Lopez,G.H., Condon,J.A., Wilson,B., Martin,J.R., Liew,Y.W., Flower,R.L. and Hyland,CA. 2014 A novel FY*A allele with the 265T and 298A SNPs formerly associated exclusively with the FY*B allele and weak Fy(b) antigen expression: implication for genotyping interpretative algorithms. Novel allele: FY*01W.02

GenBank Accession Number KC924823 Lopez,G.H., Morrison J, Condon,J.A., Wilson,B., Martin,J.R., Liew,Y.W., Flower,R.L. and Hyland,CA. 2014 Silencing mutations on the FY*01N (FY*A) alleles confound SNP based genotyping predictions for samples with Fy(a-n-) phenotypes: Is SNP based genotyping more accurate than phenotyping? Novel allele: FY*01N.07.

GenBank Accession Number KC290447 Scott SA, Nagl L, Tilley L, Liew YW, Condon J, Flower R, Hyland CA 2014 The RHD(1227G>A) DEL-associated allele is the most prevalent DEL allele in Australian D- blood donors with C+ and/or E+ phenotypes Novel alleles for D/negative 297del23 allele RHD*01N.37.

GenBank Accession Number KC290445. Scott SA, Liew YW, Hyland CA. and Flower RL. D negative/possible DEL variant with inactive Splice site IVS6+2T>A; RHD*01N.38.

GenBank Accession Number KC290446. Scott SA, Tilley L, Liew, YW, Condon J, Hyland CA and Flower RL. DEL Phenotype Inactive Splice site IVS1+5G>C, RHD*01EL.21.

GenBank Accession Number KC341996. Scott S., Liew YW, Nagl L, Hyland CA and Flower RL .DEL Phenotype Inactive Splice site IVS2-2delA RHD*01EL.22.

GenBank Accession Number KF 973190. McBean R, Hyland CA, Roscioli T, Flower RL 2014 The low SARAH blood group antigen:evidence for a new MNS antigen: GYPA*47.

GenBank Accession Number KF501485. Wei L., Lopez GH, Ji Y-L, Hyland CA, Flower, RL 2013 MNS hybrid glycophorins: GP.Kip and GP.Yak are the same, 2013: GYP*48

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APPENDIX 2: GRANTS Grants Active 2013-14

Applied and Developmental Research

$70 000 Evaluation of alternate solutions for the reconstitution of cryopreserved platelets to improve post-thaw recovery. Defence Health Foundation; Chief Investigator: Lacey Johnson; Co-investigator: Denese Marks

$25 000 The influence of pathogen reduction treatment on the immunomodulatory capacity of platelets: does it change the way they interact with neutrophils? Australian & New Zealand Society of Blood Transfusion ; Chief Investigator: Yen Siew Loh; Co-investigator: Denese Marks

$85 656 A pilot multicentre blinded randomised controlled clinical trial of cryopreserved platelets vs. conventional liquid-stored platelets for the management of post-surgical bleeding Australian New Zealand College of Anaesthetists (ANZCA) Academic Enhancement Grant;Chief Investigator: Michael Reade (University of Queensland) Blood Service co-investigators: Denese Marks, Lacey Johnson, David Irving Other co-investigators: Anthony Holley, Rinaldo Bellomo, David Gattas

Donor and Community Research

$371 000 The initiation and maintenance of plasma and platelet donation in Australia: An analysis of the role of donor identity and commitment. Australian Research Council Linkage Grant; Dr Barbara Masser (University of Queensland)

$229 905 Evaluating a Model for Culturally Relevant Interventions to Increase Blood Donation and Overcome Perceived Blood Donation Barriers Among Migrant Communities: The Case of African Migrants and Refugees. Australian Research Council Linkage Grant; Dr Michael Polonsky (Deakin University)

$40 250 Social influence and registry design to motivate blood donations. Science of Philanthropy Initiative/Research Support; Dr Robert Slonim (University of Sydney)

$392 000 Field experiments motivated by behavioral economics to understand prosocial behaviour and improve blood supply. Australian Research Council Discovery Grant; Dr Robert Slonim (University of Sydney)

$1 500 Behavioural Exchange 2014 Conference Sloan Conference Grant; Dr Daniel Waller (Blood Service)

Transfusion Science Research

$84 300 How effective is frozen blood in the treatment of severe trauma? Australian Defence Health Foundation Booster Grant; Fraser JF, Reade M, Shekar K, Fung YL, Bhaskar B, Tung JP.

$200 000 Adding “Insult to Injury” – The effect of fresh and aged blood to oxygenation, metabolism and organ function in a clinically relevant trauma/sepsis model.

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Queensland Emergency Medicine Research Foundation (QEMRF); Staib A, Fraser JF, Fung YL, Shekar K, Chew MS, Reade M, Tung JP, McDonald C, Collier J, Dunster KD, Diab S, Barnett AG.

$96 297 Towards optimisation of tissue oxygenation in the critically ill. The effect of fresh and aged blood in infection and trauma. TPCH Foundation Research Grant; Fraser JF, Chew MS, Reade M, Shekar K, Fung YL, Molenaar P, Tung JP, Dunster KD, Edleman J, Thomson O, Staib A.

$929 299 The unholy alliance between extracorporeal circuitry and transfusion medicine: characterising inflammation and injury NHMRC project grant; Chief Investigators: Fraser JF, Fung YL, Semple JW, Bidstrup B, Schiebler A. Associate Investigators: Barnett AG, Bhaskar B, Claydon K, Colebourne K, Dunster K, Flower R, McDonald C, Mullany D, Nataatnadja M, Pellegrino V, Platts, D, Prevolous AC, Punctuerere B, Traber D, Tung JP, Walker G.

$450 000 The first integrated multimodal assay for the ultrasensitive detection of dengue contamination of blood. Australian Research Council; Chief Investigators: Matthew Cooper, Paul Young, Stephen Mahler; Partner Investigators: Helen Faddy, David Irving, Robert Flower.

$430 000 Dengue transmission under climate change in Northern Australia: linking ecological and population-based models to develop adaptive strategies. NHMRC: Chief Investigators: David Harley, Scott Ritchie, Craig Williams, Keith Dear, Anthony McMichael; Associate Investigators: Helen Faddy, Ivan Hanigan.

$12 000 Identification of biomarkers to predict transfusion-related dendritic cell immune dysfunction. Australian & New Zealand Society of Blood Transfusion; Chief Investigator: Dean MM; Co-investigators: Ki KK, Flower RL.

Ms Fenny Chong (L) and Ms Katrina Ki (R) Ms Kelly Rooks

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New Grant Applications: Successful

Clinical Research

$7 000 Propensity of alloantibody formation in transfusion-dependent patients Australian & New Zealand Society of Blood Transfusion; Tan JCG, Mondy PJ

Donor and Community Research

$392 000 The Role of Affect in Donor Retention. Australian Research Council Linkage Grant; Dr Barbara Masser (University of Queensland)

Transfusion Science Research

$599 995 Advanced Cardio-respiratory Therapies Improving OrgaN Support (ACTIONS). TPCH Foundation Program Grant; Chief Investigators: Fraser JF, Gregory S, Shekar K, Olive C, Tansley G, Platts D, Tung JP, McGiffin D, Thomson B, Bull T; Associate Investigators; Barnett A, Bannon P, Marasco S, Anstey C, Timms D, Brodie D, Moore J, Fanning J, Spooner A, Simmonds M, Molenaar P, Robins E.

$17 728 Do processing- and/or donor- associated parameters contribute to biological variation in biological response modifiers (BRMs) in packed red blood cells? ANZSBT Research Fund; Chief Investigator: Dean MM, Tung JP, Flower RL.

$3 400 The Endothelial Glycocalyx in Acute Traumatic Coagulopathy. Intensive Care Foundation Trainee Formal Project Grant; Milford E, Fraser JF, Reade M, Tung JP.

$949 279 Understanding tissue responses to fluid resuscitation and blood transfusion during ovine sepsis to improve outcomes. National Health and Medical Research Council (NHMRC) project grant; Chief investigators: Fraser JF, Maitland K, Shekar K, Chew MS, Reade M, Fung YL, Tung JP. Associate Investigators: Barnett AG, Nichol A, Sim B, Platts D, Moore J, Turnbridge M, Singer M, Ng M, Bellomo R.

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38 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014

New Grant applications: Submitted

Applied and Developmental Research

$16 000 Characterisation of the platelet and platelet microparticle proteome following platelet cryopreservation; Johnson L, Marks DC.

$13 000 The use of liposomes to improve freezing and thawing of cryopreserved RBCs Australian & New Zealand Society of Blood Transfusion; Veale MF, Marks DC.

Clinical Research

$42 756 Immune biomarkers for evidence-based efficacy of intravenous immunoglobulin (IVIg) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Australian & New Zealand Society of Blood Transfusion ; Wayne Dyer, Joanne Tan, Phillip Mondy.

Transfusion Science Research

$420 000 Improving the efficacy of macrophage-targeted lectins in treating chronic lung disease. NHMRC; Chief Investigators: Hodge S, Hodge G, Eisen D, Renoylds P, Dean MM.

$500 000 Is AMPD3 the red cell longevity clock? NHMRC; Chief Investigators: Foote S, Burgio G, McMorran B, Karuso P, Irving D, Flower RL, Dean MM.

$401 000 Culture-free detection and identification of clinical bacterial infections in less than two hours. NHMRC development grant: Chief Investigators: Matthew Cooper, David Paterson, Andrea Ranzoni, Mark Schembri, Mark Blaskovich, Helen Faddy; Associate Investigators: Graeme Nimmo, Hanna Sidjabat, Melinda Dean.

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APPENDIX 3: ABSTRACTS ACCEPTED FOR CONFERENCE ORAL OR POSTER PRESENTATIONS Applied and Developmental Research Johnson L, Coorey C, Marks DC. Platelet microparticles contribute to the procoagulant activity of cryopreserved platelets. HAA 2013 (HSANZ/ANZSBT/ASTH Joint Scientific Meeting), Gold Coast Convention and Exhibition Centre, Gold Coast, Queensland, Australia, 20-23 October 2013. (Oral)

Johnson L, Tan S, Coorey C, Marks DC. Evaluation of alternate solutions for the reconstitution of cryopreserved platelets to improve post-thaw recovery. Australasian Military Medicine Association/Repat Foundation Joint Conference, Adelaide, 1-3 November, 2014. (Oral)

Kwok M, Johnson L, Marks DC. ERYSEP: whole blood separation using hollow-fibre filtration. HAA 2013 (HSANZ/ANZSBT/ASTH Joint Scientific Meeting), Gold Coast Convention and Exhibition Centre, Gold Coast, Queensland, Australia, 20-23 October 2013. (Poster)

Loh YS, Dean MM, Johnson L, Marks DC. Pathogen reduction treatment and subsequent storage of buffy-coat derived platelets alters production of monocyte inflammatory mediators in a whole blood transfusion model. 24th Regional Congress of the ISBT, Kuala Lumpur, Malaysia. 1-4 December, 2013 (Oral)

Loh YS, Stark MJ, Kwok M, Tan S, Marks DC. Washing of red cells, age at the time of processing and subsequent storage influence the in vitro quality and bioactive substances in the red cell supernatant. 24th Regional Congress of the ISBT, Kuala Lumpur, Malaysia. 1-4 December, 2013 (Oral)

Marks, DC. Pathogen Reduction Technology. 24th Regional Congress of the ISBT, Kuala Lumpur, Malaysia. 1-4 December, 2013 (Oral)

Speedy J, Marks DC, Brama T, Bell B, Bower M. A new era for youth donors: supporting the community’s need for blood through advocacy. 33rd International Congress of the ISBT, Seoul, Korea. 31 May -5 June, 2014 (Poster)

Veale MF, Healey G, Johnson L and Marks DC. Thrombus formation and adhesion of cryopreserved platelets to collagen and endothelial cells under shear stress. 33rd International Congress of the ISBT, Seoul, Korea. 31 May -5 June, 2014 (Oral)

Clinical Research Hirani, R. The effect of leucoreduction on the incidence of transfusion associated microchimerism, Singapore trauma conference, April 2014 (submitted as oral, accepted as poster) - conference not attended

Hirani, R. The effect of leucoreduction on the incidence of transfusion associated microchimerism, ASMR, 2013 (poster) – conference not attended

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40 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 Mondy P, Brama T, Fisher J, Capper H, Waller D,., & Gemelli, C.N. Prospective study of Autologous Serum Eye Drops (ASED) confirms sustained benefits after a rapid initial response in Keratoconjunctivitis Sicca and Non-Healing Corneal Ulcers. The International Symposium on Ocular Pharmacology and Therapeutics, Reykjavik, Iceland; June 2014. (Oral)

Tan JCG, Armstrong NJ, Yuan FF, Flower RL, Dyer WB, Capper H Genetic polymorphisms and immune response pathways associated with different responder profiles of RhD-immunised blood donors 23rd Regional Meeting of the International Society of Blood Transfusion Amsterdam, The Netherlands, 2-5 June 2013 (Oral)

Tan JCG, Bondar N, Armstrong NJ, Yuan FF, Flower RL, Capper H, Dyer WB Factors influencing red cell alloimmunisation: A study of RhD-immunised blood donors and beyond Combined Meetings of the Haematology Society of Australia and New Zealand (HSANZ), the Australian & New Zealand Society of Blood Transfusion (ANZSBT) and the Australasian Society of Thrombosis and Haemostasis (ASTH) Gold Coast, QLD, 20-23 October 2013 (Oral)

Tan JCG, Hirani R, Dean MM, Capper H, Dyer WB Identification of immune cell biomarkers associated with response to intravenous immunoglobulin therapy Combined Meetings of the Haematology Society of Australia and New Zealand (HSANZ), the Australian & New Zealand Society of Blood Transfusion (ANZSBT) and the Australasian Society of Thrombosis and Haemostasis (ASTH) Gold Coast, QLD, 20-23 October 2013 (Poster)

Donor and Community Research Brown M, Coote L, Sampson S, & Waller D. Structural Choice Modelling of Embedded Experiments: A Case Study of a Voluntary Blood Donation System. Institute for Choice Seminar Series Sydney; April 2014. (Oral)

Garbarino E, Irving DO, Slonim R, Smith G, Waller D, & Wang C. Blood Donation Registry – A Cost-effective Mechanism of Regaining ‘Lost’ Donors. American Association of Blood Banks Annual Meeting, Denver, Colorado; October 2013. (Poster)

Seed C, Lucky T, Waller D, Lee J, Wroth S, McDonald A, Wilson DP, Pink J & Keller AJ. Low Prevalence of Non-Compliance to the Current 12 Month Deferral for Male-to-Male Sex in Australia. 23rd Regional Congress of the International Society of Blood Transfusion, Amsterdam, Netherlands; June 2013. (Oral)

Waller D, Garradd A, & Cheah S. Investigating Enthusiasm for a Donate Blood For Research Program among Australian-deferred Blood Donors: Examining the attitudes of a sample of Variant Creutzfeldt-Jakob disease (vCJD) risk deferred donors. American Association of Blood Banks Annual Meeting, Denver, Colorado; October 2013. (Poster)

Williams L, & Waller D. Proud to be a donor: Pride uniquely predicts pre-donation intention and behaviour. Conference of the Society of Australasian Social Psychologists, Canberra; April 2014. (Oral Presentation)

Williams L, Waller D, & Garradd A. Positive Social Emotions and Blood Donation. University of Otago Colloqium, Otago; August 2014 (Oral).

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Transfusion Science Research Allison K, Faddy H, Margaritis A, Ismay S, Marks D. The effect of freezing and thawing samples stored in plasma preparation tubes (PPT) for detection of HIV, HCV and HBV. HAA Joint Scientific Meeting, 20 – 23 October 2013 (Poster)

Dean MM, Bierman W, Knauth C, Flower RL, Tung JP. Stored Blood Products Augment Inflammation in a Two-event Model of Transfusion Related Acute Lung Injury (TRALI). Annual Scientific Meeting of HAA. 20-23 October 2013. Gold Coast, Australia. (Poster)

Dean MM, Ki KK, Tran TV, Baidya S, Christensen AM, Flower RL; Packed Red Blood Cells Modulate Expression of Dendritic Cell Signal Transduction and Antigen Presentation Pathways. American Society of Haematology Annual Meeting. 7 - 10 December 2013. New Orleans, USA. (Poster)

Dean MM, Kildey K, Tran TV, Rooks K, Baidya S, Flower RL; Single Nucleotide Variations in Spectrin-1β Accentuate The Red Blood Cell Storage Lesion. American Society of Haematology Annual Meeting. 7-10 December 2013. New Orleans, USA. (Poster)

Dean MM, Samson LD, Rooks K, Fryk J, Baidya S, Flower RL; Donor Variation in Biological Mediators During Storage of Packed Red Blood Cells. American Society of Haematology Annual Meeting. 7 -10 December 2013. New Orleans, USA. (Poster)

Faddy H, Allison K, Margaritis A, Ismay S, Marks D. The effect of freezing and thawing samples stored in plasma preparation tubes (PPTs) for up to 18 months on the ability to detect HIV, HCV and HBV. ISBT 2014, 31 May -5 June 2014 (Oral)

Faddy H, Fryk, J, Young P, Watterson D, Tolksdorf F, Sumian C, Gravemann U, Seltsam A, Marks D. The Theraflex UV-Platelets technology effectively inactivates dengue viruses in platelet concentrates. ISBT 2014, 31 May -5 June 2014 (Poster)

Faddy H, Ranzoni A, Watterson D, Chong F, KC S, Tran T, Jones M, Lebani K, Flower R, Irving D, Mahler S, Young P, Cooper M. Development of the first integrated multimodal assay for the sensitive detection of dengue virus in blood donations. ISBT 2014, 31 May -5 June 2014 (Poster)

Faddy H, Shrestha A, Seed C ,Rooks K, Harley R, Chan H, Holmberg J, Flower R. Hepatitis E virus seroprevalence in Australian donors. ISBT 2014, 31 May -5 June 2014 (Poster)

Flower RL, Kildey K, Tran TV, Dean MM. Variation in Blood component storage in an animal model related to single nucleotide variants in spectrin gene spnb1. International Society of Blood Transfusion Regional Congress. 1– 4 December 2013. Kuala Lumpur, Malaysia. (Oral)

French S, Tung JP, Flower RL, Pecheniuk N. Storage of Red Blood Cells increases Thrombin Generation in Normal Pooled Plasma. Annual Scientific Meeting of HAA. 20th -23rd Oct 2013. Gold Coast, Australia. Awarded best laboratory based poster for the ASTH Stream (Poster)

Harley D, Viennet E, Dear K, Faddy H, Hanigan I,McMichael AJ, Ritchie SA, Williams C. Mosquitoes, mobility and meteorology: The epidemiology of Dengue in North Queensland. Australian Society of Infectious Diseases Annual Scientific meeting. 26 – 29 March 2014 (Oral)

Hyland CA, Lopez G, McBean R, Liew YW, Condon J and Flower RL Duffy blood group typing: is genotype more accurate than phenotype for Duffy blood grouping? 33rd International Congress of the International Society of Blood Transfusion 31 May -5 June 2014 (Oral)

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42 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 Knauth C, Dean MM, Bierman W, Flower RL, Tung JP. Neutrophil Oxidative Burst is Primed by Supernatant from Stored Red Cells: Implications for Transfusion-Related Acute Lung Injury (TRALI). Annual Scientific Meeting of HAA. 20 – 23 October 2013. Gold Coast, Australia. (Poster)

Kildey K, Harris J, Flower RL, Tran TV, Dean MM. Bad blood: Identifying the factors responsible for reducing the viability of blood bank stocks. IHBI Inspires 2013. 28– 29 November 2013. Brisbane, Australia. (Oral)

Ki KK, Tran TV, Flower RL, Christensen AM, Dean MM; Packed Red Blood Cells Modulate Expression of Dendritic Cell Signal Transduction and Antigen Presentation Pathways. Annual Scientific Meeting of HAA. 20 – 23 October 2013. Gold Coast, Australia. (Poster)

Kildey K, Flower RL, Tran TV, Dean MM. Single Nucleotide Variants (SNV) in RBC structural proteins: Implications for blood component storage. Annual Scientific Meeting of HAA. 20 – 23 October 2013. Gold Coast, Australia. (Poster)

McBean RS, Hyland CA, Flower RLP (2014) Molecular Genotyping Platforms for Blood Group Antigen Prediction. RCPA Pathology Update (Poster)

McBean RS, Hyland CA, Roscioli T and Flower RL The low frequency SARAH blood group antigen: evidence for a new MNS antigen 33rd International Congress of the International Society of Blood Transfusion 31 May-5 June 2014 (Oral)

McBean RS, Roscioli A, Hyland CA, Flower RLP (2014) Next Generation Sequencing of an Australian Family to Identify the Genetic Basis of a Rare Blood Group Antigen. RCPA Pathology Update (Poster)

McBean RS, Hyland CA, Millard G and Flower RL Phenotype Genotype Non-concordance in Duffy & Rh Systems Detected in Reagent Red Cell Donors HAA Annual Scientific Meeting, 20 – 23 October 2013, (Poster)

McBean RS, Roscioli T, Hyland CA, and Flower RL Next Generation Sequencing of an Australian Family to Identify the Genetic Basis of a Rare Blood Group Antigen Kolling-RNSH-USYD-UTS Annual Scientific Meeting, 18-20 November 2013 (Poster)

Osthoff M, Ngian GS, Dean MM, Eisen D, Sahhar J. The lectin pathway of complement – a potential role in the pathogenesis and disease manifestations of systemic sclerosis. Australian Rheumatology Association. 17th - 20th May 2014. Hobart, Australia. (Poster)

Pecheniuk N, Aung HH, Mardiasmo D, Tung JP, Flower RL. Packed red blood cell storage tips the coagulation balance in favour of procoagulant activity. Annual Scientific Meeting of HAA. 20- 23 October 2013. Gold Coast, Australia. (Poster)

Ranzoni A, Watterson D, Chong F, KC S, Jones M, Lebani K, Mahler S, Tran T, Faddy H, Irving D, Young P and Cooper MA. The first integrated multimodal assay for sensitive detection of dengue contamination of blood. 24th Anniversary World Congress on Biosensors, 27 – 30 May 2014. (Poster)

Shrestha A, Faddy H, Rooks K, Flower R. Hepevirus: Does locally acquired infection occur more frequently than we think? Australian Society for Microbiology (ASM) Annual Scientific Meeting and Exhibition, 6 – 9 July 2014 (Poster).

Simonova G, Fung YL, Glenister KM, Fraser JF, Tung JP. A Comparison of the Storage Lesions of Ovine and Human Packed Red Blood Cell Units. Annual Scientific Meeting of HAA. 20 – 23 October 2013. Gold Coast, Australia. (Poster)

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Simonova G, Fung YL, Glenister KM, Fraser JF, Tung JP. Sheep Red Blood Cells for Transfusion: Is the storage lesion comparable to human red blood cells? ANZICS/ACCCN Intensive Care Annual Scientific Meeting. 17 – 19 October 2013. Hobart, Australia. (Poster)

Tran HB, Ahern J, Hodge G, Holt P, Dean MM, Reynolds PN, Hodge S; Oxidative changes to sub-cellular localisation and function of mannose binding lectin on alveolar macrophages may contribute to decreased phagocytosis in COPD. The Thoracic Society of Australia and New Zealand Annual Scientific Meeting. 4– 9 April 2014. Adelaide, Australia. (Oral)

Tung JP, Bierman W, Knauth C, Flower RL, Dean MM. Divergent in vitro inflammatory responses to antibodies relevant to transfusion-related acute lung injury. British Blood Transfusion Society (BBTS) Annual Meeting. 17 October, 2013. Birmingham, UK. – Margaret Kenwright Young Scientist Award (Oral)

Tung JP, Simonova G, Glenister KM Fraser JF, Fung YL. The sheep as a transfusion model: Comparison of the storage lesion of human and ovine red blood cell units. BBTS Annual Meeting. 16 -18 October 2013. Birmingham, UK. (Poster)

Viennet E, Dear K, Faddy H, Hanigan I, McMichael AJ, Ritchie SA, Williams C, Harley D. Dengue Transmission in a High-Income Country: Descriptive and spatio-temporal Analysis. 9th conference Louis Pasteur Emerging Infectious diseases. 9-11 April 2014 (Poster)

Young M, Cripps A, Nimmo G, Ji Y, Fryk J, Faddy H, Flower R. Sero-prevalence of antibodies to hepatitis A virus among Australian blood donors. RCPA Pathology update, 21 – 23 February 2014 (Poster).

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APPENDIX 4: CONFERENCE ATTENDANCE International

Applied and Developmental Research

Denese Marks, Celine Loh. 24th Regional Congress of the ISBT, Kuala Lumpur, Malaysia. 1-4,December 2013

Margaret Veale 33rd International Congress of the ISBT, Seoul, Korea. 31 May -5 June 2014

Transfusion Science Research

A/ Prof Catherine A. Hyland, Rhiannon McBean: 33rd International Congress of the International Society of Blood Transfusion (ISBT) Seoul, Republic of Korea, 31 May -5 June 2014

Rhiannon McBean: AABB Annual Meeting, Denver, USA, 12-15 October 2103.

Dr John-Paul Tung: British Blood Transfusion Society (BBTS) 2013 Annual Meeting. Birmingham, UK. 16-18 October 2013

Dr Melinda Dean: American Society of Haematology Annual Meeting. 7-10 December 2013. New Orleans, USA.

Dr Helen Faddy: 33rd international Congress of the International Society Blood Transfusion (ISBT), Seoul, Korea. 31 May -5 June 2014.

Prof Robert Flower, Dr Helen Faddy: 24th Regional Congress of the International Society Blood Transfusion (ISBT), Kuala Lumpur, Malaysia. 1 – 4 December 2013

Domestic

Applied and Developmental Research

Lacey Johnson: Australasian Military Medicine Association/Repat Foundation Joint Conference, Adelaide, 1-3 November, 2014.

Lacey Johnson, Matthew Kwok, Dr Joanne Tan: Combined Meetings of the Haematology Society of Australia and New Zealand (HSANZ), the Australian & New Zealand Society of Blood Transfusion (ANZSBT) and the Australasian Society of Thrombosis and Haemostasis (ASTH), Gold Coast, QLD, 20-23October, 2013

Denese Marks, Celine Loh, Joanne Tan: Transfusion Update, Melbourne VIC, 14-16 May, 2014

Joanne Tan: Association of Regulatory and Clinical Scientists Scientific Congress, Randwick, NSW, 3-4 June 2014

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Clinical Research

Joanne Tan: Dendritic Cell Down Under Symposium, Concord Repatriation General Hospital, NSW, 15-16 August 2013

Dr Rena Hirani critical appraisal workshop, Sydney, October 2013

Dr Rena Hirani Concept development workshop for trials and translational research studies, Australian Red Cross Blood Service, Sydney, October 2013

Dr Rena Hirani CLEAR study collaborators meeting, Cancer Council NSW, Sydney, December

2013

Dr Rena Hirani SAX collaborators meeting, SAX Institute, Sydney, October 2013

Donor and Community Research

Dr Daniel Waller: Behavioural Exchange International Behavioural Insights Conference Sydney, June 2014

Transfusion Science Research

A/Prof Catherine A Hyland and G Millard Transfusion Update. Melbourne 14-16 May, 2014

Rhiannon McBean: RCPA Pathology Update, Melbourne, Australia, 21-23 February 2014

Rhiannon McBean: Kolling-RNSH-USYD-UTS Annual Scientific Meeting, Sydney, Australia, 18-21 November, 2013

A/Prof Catherine A Hyland and E McGowan Dr John-Paul Tung, Dr Melinda Dean, Gabriela Simonova, Denisa Meka, Eunike McGowan, Katrina Kildey, Katrina Ki: Annual Scientific Meeting of HSANZ (Haematology Society of Australia and New Zealand), ANZSBT (Australian and New Zealand Society of Blood Transfusion) and ASTH (Australasian Society of Thrombosis and Haemostasis) (HAA). Gold Coast, Australia. 20-23 October, 2013

Katrina Kildey: IHBI Inspires 2013. 28-29 November 2013. Brisbane, Australia.

Dr Melinda Dean, Katrina Ki: DC Down Under Symposium; Sydney Australia; August 2013.

Dr Helen Faddy, Ms Kirsty Allison, Mr Jesse Fryk, Ms Kelly Rooks (shared registration): HAA Joint Scientific Meeting, Gold Coast, Australia. 20 – 23 October 2013.

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APPENDIX 5: STUDENT PROJECTS R&D team members collaborate with universities, research institutes and hospitals to support students undertaking original research under the supervision of senior Blood Service Researchers.

During the 2103/14 year, there were six PhD students including four who are full time. Katrina Kildey and Katrina Ki are supported by Australian Postgraduate Research Awards, Rhiannon Mc Bean has a scholarship from Sydney University, and Ashish Shrestha is supported by a University of Queensland International (UQI) Scholarship. The other two PhD students are studying part time, working principally at Prince Charles Hospital, part supervised by Dr John-Paul Tung. Elissa Mylford is a Medical Officer doing a PhD, and Monica Ng is pursuing her PhD concurrently with studies in medicine. For the last two years, two new PhD students have joined the group each year and the first completions are scheduled for 2015. Lisa Nagl was awarded her Master of Applied Science in June 2014, and at the same time Yu Ji commenced a Master’s degree at University of Queensland. Three Honours students completed their project during the reporting periods, and a further nine are in progress.

A full listing of students and their project titles appears on the following pages.

From the top: Ms Ji Yu, Ms Sarah Raynel, Ms Htet Htet Aung

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RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014 47

Student name Project title Institution Degree

Htet Htet Aung Routine storage of packed red blood cells: Generation of microparticles and their impact on coagulation

Queensland University of Technology

BBiomedSc (Hons)

Anna Coghlan The effect of temporary exclusion of blood donors exposed to emerging infections while travelling

University of Queensland

MBBS (Hons)

Courtney Edwards

What motivates people to donate blood and to what extent are these motivations satisfied?

University of Canberra Psychology (Hons)

Yu Ji Genetic factors associated with donation career: iron metabolism and storage

University of Queensland

MSc

Katrina Ki Transfusion Related Immune Modulation: The Role of Dendritic Cell C-type Lectin Receptors LOX-1 and Clec9A

University of Queensland

PhD

Katrina Kildey Investigation of blood physiology and hematological disease through analysis of mice with novel ENU-induced mutant phenotypes

Queensland University of Technology

PhD

Daniel Lancini CMV seroepidemiology in Australian blood donors and CMV-seronegative blood supply

University of Queensland

MBBS (Hons)

Rhiannon McBean

Relationship between genotype and phenotype: a study of blood group gene polymorphisms

University of Sydney PhD Due for completion March 2015

Eunike McGowan Investigation of a novel assay to characterise inflammation in an ovine model of extracorporeal support and transfusion

Queensland University of Technology

BBiomedSc (Hons IIA) completed

Denisa Meka Investigating the role of biological response modifiers in transfusion-related acute lung injury

Queensland University of Technology

BBiomedSc

(Hons I) completed

Elissa Milford Effects of commonly used and emerging resuscitation fluids on end organ function in severe trauma

University of Queensland

(based at Prince Charles Hospital/Critical Care Research Group)

PhD

Lisa Nagl Improving the detection of donations within the RhD negative blood donor panel which weakly express the RhD antigen

Queensland University of Technology

MAppSc Completed June 2014

Monica Ng Mortality and morbidity after stored packed red blood cell transfusion:

a meta-analysis and systematic review

University of Queensland

(based at Prince Charles Hospital/Critical Care

MBBS (Hons) (completing)

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48 RESEARCH AND DEVELOPMENT |ANNUAL REPORT 2013-2014

Research Group)

Monica Ng The double whammy: impact of activated endothelium and stored blood transfusion on microparticle formation and thrombosis

University of Queensland

(based at Prince Charles Hospital/Critical Care Research Group)

PhD (commencing)

Alexis Perros Investigation of transfusion-related immune modulation of dendritic cell function in cardiac surgery patients

Queensland University of Technology

BBiomedSc (Hons)

Sarah Raynel Characterisation of the platelet and platelet microparticle proteome following platelet cryopreservation

University of Technology Sydney

BBiomedSc

(Hons) Due for completion Nov 2014

Ashish Shrestha Evaluating the risks posed by emerging transfusion-transmitted infectious diseases to the safety of Australia’s blood supply

The University of Queensland

PhD

Annette Sultana Transfusion-related acute lung injury (TRALI): Do antibodies and biological response modifiers synergistically modulate inflammatory responses?

Queensland University of Technology

BBiomedSc (Hons)