Liverpool, United Kingdom
Liverpool, United Kingdom

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Robertson J.,NHSBT | Watson D.,Better Blood Transfusion Regional Lead | Iqbal A.,Durham University | Tinegate H.,NHSBT
Transfusion Medicine | Year: 2014

SUMMARY: Objectives: To record the fate of transfused platelet doses in the North of England, and thereby assist with demand-planning and help target teaching on appropriate use. Background: Platelet use has risen recently to the extent that donation practice has changed to meet demand. Two national comparative audits have shown inappropriate use and the 2010 audit concluded that current UK guidelines for platelet usage should be completely implemented at a local level. It is necessary to know how platelets are used and by whom in order to facilitate guideline concordance. Methods: All hospital trusts in the North East and Cumbria recorded data on all platelet doses transfused in two separate 4-week periods in 2012. Data were entered onto an electronic survey tool. Results: One thousand and five hundred and seventy-four reports were received, documenting 1937 transfused doses - 96% of total issues for the study periods. One thousand and forty-five platelet doses (54%) were given for haematological indications. The second commonest indication was cardiac surgery (201 doses, 10% of the total) followed by non-haematological oncology (127 doses, 6.5%), critical care (106 doses, 5%) and liver disease (50 doses, 2·5%). The commonest haematological indication was acute myeloid leukaemia, 310 doses, (16% of all platelet use), followed by stem cell transplantation, 271 doses (14%). Seventy-two percent of platelet doses were given prophylactically, the majority without any planned procedure. Conclusion: The commonest indication for platelet use, where reinforcement of guidelines will be productive, is prophylaxis in haematological disease. Use of platelets in cardiac surgery is also worthy of close scrutiny. © 2014 British Blood Transfusion Society.

Scorer T.,Institute of Naval Medicine | Doughty H.,NHSBT
Journal of the Royal Army Medical Corps | Year: 2016

Prehospital use of blood products may improve survival. However, transfusion support with frozen blood components is logistically burdensome and constrains the configuration of prehospital medical support. Alternatives to frozen plasma, including lyophilised plasma, offer the potential for advanced resuscitation in the prehospital environment. We describe the successful use of lyophilised plasma by a UK patrol in the prehospital environment during operations in Afghanistan in 2012 and reflect on recent military experience and the need for further developments. © 2016, Journal of the Royal Army Medical Corps. All Rights Reserved.

Eagle M.J.,NHSBT | Rooney P.,NHSBT | Kearney J.N.,NHSBT
Cell and Tissue Banking | Year: 2015

Demineralised bone matrix (DBM) is produced by grinding cortical bone into a powder, sieving the powder to obtain a desired size range and then demineralising the powder using acid. Protocols for the production of DBM powder have been published since 1965 and the powder can be used in lyophilised form or it can be mixed with a carrier to produce a paste or putty. The powder is generally produced from cortical bone which has been processed to remove blood, bone marrow and bone marrow components, including fat. Removal of fat is accomplished by incorporating incubation in an organic solvent, often chloroform, chloroform/methanol or acetone. The use of organic solvents in a clean room environment in a human tissue bank is problematic and involves operator exposure and the potential for the solvent to be trapped in air filters or recirculated throughout the clean room suite. Consequently, in this study, we have developed a cortical bone washing step which removes fat/lipid without the use of an organic solvent. Bone was prepared from six femoral shafts from three donors by dissecting soft tissue and bisecting the shaft, the shafts were then cut into ~9–10 cm lengths. These struts were then taken through a series of hot water washes at 56–59 °C, centrifugation and decontamination steps. Washed cortical struts were then lyophilised before being ground with a compressed air milling machine. The ground bone was sieved, demineralised, freeze-dried and terminally sterilised with a target dose of 25 kGy gamma irradiation. The DBM powder was evaluated for residual calcium content, in vitro cytotoxicity and osteoinductivity by implantation into the muscle of an athymic mouse. Data indicated that in addition to removing in excess of 97 % DNA and extractable soluble protein, the washing protocol reduced lipid 10,000-fold. The processed bone was easily ground without clogging the grinder; the sterilised DBM powder was not cytotoxic but was osteoinductive in the animal model. Therefore, we have developed a method of producing osteoinductive DBM without the need to use organic solvents. © 2014, Springer Science+Business Media Dordrecht.

Rooney P.,NHSBT | Eagle M.J.,NHSBT | Kearney J.N.,NHSBT
Cell and Tissue Banking | Year: 2015

Human tissue is shipped to surgeons in the UK in either a freeze-dried or frozen state. To ensure quality and safety of the tissue, frozen tissue must be shipped in insulated containers such that tissue is maintained at an appropriate temperature. UK Blood Transfusion Service regulations state “Transportation systems must be validated to show maintenance of the required storage temperature” and also state that frozen, non-cryopreserved tissue “must be transported… at −20 °C or lower” (Guidelines for the Blood Transfusion Services in the United Kingdom, 8th Edn. 2013). To maintain an expiry date for frozen tissue longer than 6 months, the tissue must be maintained at a temperature of −40 °C or below. The objective of this study was to evaluate and validate the capability of a commercially available insulated polystyrene carton (XPL10), packed with dry ice, to maintain tissue temperature below −40 °C. Tissue temperature of a single frozen femoral head or a single frozen Achilles tendon, was recorded over a 4-day period at 37 °C, inside a XPL10 carton with dry ice as refrigerant. The data demonstrate that at 37 °C, the XPL10 carton with 9.5 kg of dry ice maintained femoral head and tendon tissue temperature below −55 °C for at least 48 h; tissue temperature did not rise above −40 °C until at least 70 h. Data also indicated that at a storage temperature lower than 37 °C, tissue temperature was maintained for longer periods. © 2015, Springer Science+Business Media Dordrecht.

Eagle M.J.,NHSBT | Rooney P.,NHSBT | Kearney J.N.,NHSBT
Cell and Tissue Banking | Year: 2015

Shaped demineralised bone matrices (DBM) made from cancellous bone have important uses in orthopaedic and dental procedures, where the properties of the material allow its insertion into confined defects, therefore acting as a void filler and scaffold onto which new bone can form. The sponges are often small in size, <1.0 cm3. In this study, we report on an improved bone washing and demineralisation process that allows production of larger DBM sponges (3.375 or 8.0 cm3) from deceased donor bone. These sponges were taken through a series of warm water washes, some with sonication, centrifugation, 100 % ethanol and two decontamination chemical washes and optimally demineralised using 0.5 N hydrochloric acid under vacuum. Demineralisation was confirmed by quantitative measurement of calcium and qualitatively by compression. Protein and DNA removal was also determined. The DBM sponges were freeze dried before terminal sterilisation with a target dose of 25 kGy gamma irradiation whilst frozen. Samples of the sponges were examined histologically for calcium, collagen and the presence of cells. The data indicated lack of cells, absence of bone marrow and a maximum of 1.5 % residual calcium. © 2015, Springer Science+Business Media Dordrecht.

Blood platelets remained obscure until the early 20th century although from the 1880s claims that low numbers were associated with certain types of 'purpura' began to gain favour. This article re-appraises critically, but with due consideration to the limited technology of the times, the first remarkable in vivo demonstration of the effects of platelets demonstrated by the serial 'Bleeding Times' reported by William Duke in 1910, when fresh blood was transfused to two thrombocytopenic people. It also speculates on the possible causes of the thrombocytopenia with which Duke's main patient presented. © 2011 The Author. Transfusion Medicine © 2011 British Blood Transfusion Society.

Eagle M.J.,NHSBT | Rooney P.,NHSBT | Kearney J.N.,NHSBT
Journal of Biomedical Materials Research - Part B Applied Biomaterials | Year: 2015

Human demineralized bone matrix derived from cortical bone is used by surgeons due to its ability to promote bone formation. There is also a need for shaped demineralized bone matrices made from cancellous bone, where the properties of the material allow its insertion into defects, therefore acting as a void filler and scaffold onto which new bone can form. In this study, we report that demineralized bone sponges were prepared by dissecting and cutting knee bone into cancellous bone cubes of 1 cm3. These cubes were then taken through a series of warm water washes, some with sonication, centrifugation, and two decontamination chemical washes. The cubes were optimally demineralized into sponges with 0.5N hydrochloric acid under vacuum with constant pH measurement. Demineralization was confirmed by quantitative measurement of calcium and qualitatively by compression. The sponges were freeze dried before terminal sterilisation with a target dose of 25 kGy gamma radiation whilst frozen. Samples of the sponges were histologically examined for calcium and collagen and also tested for osteoinductivity. Data showed well defined collagen staining in the sponges, with little residual calcium. Sponges from two out of three donors demonstrated osteoinductivity when implanted into the muscle of an athymic mouse. © 2014 Wiley Periodicals, Inc.

Mamode N.,Guys Hospital | Johnson R.J.,NHSBT | Hadjianastassiou V.G.,Guys Hospital
Transplantation | Year: 2011

Background: Despite the apparent safety of laparoscopic kidney procurement (laparoscopic donor nephrectomy [LDN]) in adults, doubts have persisted about its use in pediatric recipients, following the publication of a United Network for Organ Sharing analysis, which suggested that rejection rates were higher after LDN when compared with open procurement (open donor nephrectomy [ODN]) for children. The aim of this study was to determine whether acute rejection rates, and graft and patient survival, were worse after LDN for pediatric recipients. The analysis included both short and medium term outcomes. METHODS.: The UK Transplant Registry, a validated database with mandatory reporting, was interrogated from 2000 to 2007 for outcomes of pediatric recipients. A total of 306 recipients were identified, 119 of which had LDN. RESULTS.: Acute rejection was higher in the ODN group, compared with LDN (40.6% vs. 24.3% P=0.007). Graft survival at 1 year (99.2% vs. 94.3% P=0.03) and 3 years (99.2% vs 91.4%, P=0.01) was worse after ODN. There were more deaths after ODN (4 vs. 0), but this did not reach statistical significance. Cox proportional hazards modeling showed that the negative effect of ODN on graft survival was reduced when adjusted for acute rejection. CONCLUSIONS.: LDN seems to be safe for pediatric recipients in both the short and longer terms. © 2011 by Lippincott Williams & Wilkins.

PubMed | Sheffield Childrens Hospital, Anthony Nolan, NHSBT, University of Nottingham and 13 more.
Type: Consensus Development Conference | Journal: British journal of haematology | Year: 2016

Allogeneic haemopoietic stem cell transplantation offers a potentially curative treatment option for a wide range of life-threatening malignant and non-malignant disorders of the bone marrow and immune system in patients of all ages. With rapidly emerging advances in the use of alternative donors, such as mismatched unrelated, cord blood and haploidentical donors, it is now possible to find a potential donor for almost all patients in whom an allograft is indicated. Therefore, for any specific patient, the transplant physician may be faced with a myriad of potential choices, including decisions concerning which donor to prioritize where there is more than one, the optimal selection of specific umbilical cord blood units and which conditioning and graft-versus-host disease prophylactic schedule to use. Donor choice may be further complicated by other important factors, such as urgency of transplant, the presence of alloantibodies, the disease status (homozygosity or heterozygosity) of sibling donors affected by inherited disorders and the cytomegalovirus serostatus of patient and donor. We report UK consensus guidelines on the selection of umbilical cord blood units, the hierarchy of donor selection and the preferred conditioning regimens for umbilical cord blood transplantation, with a summary of rationale supporting these recommendations.

News Article | November 17, 2016

As part of the BLUEPRINT project, scientists have discovered how variation in blood cell characteristics and numbers affects the risk of complex diseases such as heart disease and autoimmune diseases including rheumatoid arthritis and type 1 diabetes Today in Cell and associated journals, 24 research studies from the landmark BLUEPRINT project and IHEC consortia reveal how variation in blood cells' characteristics and numbers can affect a person's risk of developing complex diseases such as heart disease, and autoimmune diseases including rheumatoid arthritis, asthma, coeliac disease and type 1 diabetes. The papers, along with another 17 in other high-impact journals, are the culmination of a five-year, £25 million (€30 million) project that brought together 42 leading European universities, research institutes and industry partners. The project's goals were to explore and describe the range of epigenetic changes that take place in bone marrow as stem cells develop into different types of mature blood cell. It also sought to match epigenetic changes and genetic differences to the physical characteristics of each cell type and use this knowledge to understand how these can lead to blood disorders, cancer and other complex diseases*. As part of BLUEPRINT, Wellcome Trust Sanger Institute led two of the six papers being published in the journal Cell today. In the first study, Sanger Institute researchers worked closely with colleagues at the University of Cambridge and the University of Oxford to carry out the largest and most in-depth study of DNA and blood cell characteristics using the UK BioBank resource and the INTERVAL study**. By comparing almost 30 million DNA sequence differences in more than 173,000 people with variation in the physical properties of blood cells the scientists identified 2,500 previously undiscovered locations in the genome that influence blood cell characteristics and functions. Further work showed that genetic differences affecting some of these characteristics are linked to increased risk of heart attack, or to rheumatoid arthritis and other common autoimmune diseases. Dr William Astle, from the University of Cambridge said: "The scale, resolution and homogeneity of our work were vital. Because we examined so many people we were able to discover important 'rare and low frequency' genetic differences that are present in fewer than 10 per cent of the population. We found that these can have a much larger impact on the characteristics of blood cells than the common differences studied previously. Of the more than 300 rare and low frequency difference we found, 74 appear to affect the structure of proteins. These give us important clues as to which biological pathways are involved in controlling the production, function and characteristics of blood cells." The team found that genetic differences that cause people to have more young red blood cells in their peripheral bloodstreams also increase the risk they will have a heart attack. Dr Adam Butterworth, one of the study's senior authors, from the University of Cambridge said: "When mature red blood cells rupture in our blood the body replaces them with new, young red cells - a process known as haemolysis. So we think that increased haemolysis and increased risk of coronary heart disease are affected by the same biological pathways. Identifying these pathways may offer new treatment possibilities." In another new finding, the research team showed that genetic differences that increased the amount of certain white blood cells, known as eosinophils, also increased the risk of a person developing rheumatoid arthritis, asthma, coeliac disease and type 1 diabetes. In the second Cell paper, researchers collaborated with scientists at the University of Cambridge, McGill University in Canada and several UK and European institutions to explore the role that epigenetics plays in the development and function of three major human immune cell types: CD14+ monocytes, CD16+ neutrophils and naïve CD4+ T cells, from the genomes of 197 individuals. They studied the contributions of various genetic control mechanisms, including epigenetic changes such as methyl tags on promoter regions in the DNA and histone modifications, to understand how these different levels of regulation interacted with genetic differences to change the expression of genes, immune function and, ultimately, human disease. The team identified 345 regions of the genome where they could pinpoint the likely molecular causes underlying a person's predisposition to immune-related diseases such as inflammatory bowel disease, type 1 diabetes and multiple sclerosis. Dr Tomi Pastinen, senior author on the second study, from McGill University said: "We have created an expansive, high-resolution atlas of variations that deepens our understanding of the interplay between the genetic and epigenetic machinery that drives the three primary cells of the human immune system. We have identified hundreds of genetic variations associated with autoimmune diseases that appear to affect the activity of genes in specific regions of the genome, pointing to biological pathways that may be involved in disease and which, ultimately, may be treatable with medication." Professor Nicole Soranzo, senior author on both studies from the Sanger Institute and University of Cambridge, added: "The BLUEPRINT project has provided the worldwide research community with detailed insights and understandings that will form the basis of important blood cell research for many years to come. When integrated with large-scale genetic studies, these results and data inform understanding of how differences in the human genome and epigenome interact to cause devastating common diseases, and inform new avenues for treating these conditions." 1. Astle WJ et al. (2016) The allelic landscape of human blood cell trait variation and links to common complex disease. Cell http://dx. 2. Chen L et al. (2016) Genetic drivers of epigenetic and transcriptional variation in human immune cells. Cell http://dx. One of the great mysteries in biology is how the many different cell types that make up our bodies are derived from a single cell and from one DNA sequence, or genome. We have learned a lot from studying the human genome, but have only partially unveiled the processes underlying cell determination. The identity of each cell type is largely defined by an instructive layer of molecular annotations on top of the genome - the epigenome - which acts as a blueprint unique to each cell type and developmental stage. Unlike the genome the epigenome changes as cells develop and in response to changes in the environment. Defects in the factors that read, write and erase the epigenetic blueprint are involved in many diseases. The comprehensive analysis of the epigenomes of healthy and abnormal cells will facilitate new ways to diagnose and treat various diseases, and ultimately lead to improved health outcomes. A collection of 42 coordinated papers now published by scientists from across the International Human Epigenome Consortium (IHEC) sheds light on these processes, taking global research in the field of epigenomics a major step forward. A set of 24 manuscripts has been released as a package in Cell and Cell Press-associated journals, and an additional 17 papers have been published in other high-impact journals. These papers represent the most recent work of IHEC member projects from Canada, the European Union, Germany, Japan, Singapore, South Korea, and the United States. The collection of publications showcases the achievements and scientific progress made by IHEC in core areas of current epigenetic investigations. For a full list of all 42 participating centres participating in BLUEPRINT, please see: http://www. BLUEPRINT is a large-scale research project receiving close to 30 million euro funding from the EU and involving 41 leading European universities, research institutes and industry entrepreneurs. The BLUEPRINT project aims to further the understanding of how our genes are activated or repressed in both healthy and diseased human cells. It aims to generate at least 100 reference epigenomes and study them to advance and exploit knowledge of the underlying biological processes and mechanisms in health and disease. http://www. The International Human Epigenome Consortium (IHEC) is a global consortium with the primary goal of providing free access to high-resolution reference human epigenome maps for normal and disease cell types to the research community. The epigenome reference maps will be of great utility in basic and applied research. They are likely to have an immediate impact on the understanding of many diseases, and will hopefully lead to the discovery of new means to treat or manage them. In addition to this work, many members support related projects to improve epigenomic technologies, investigate epigenetic regulation in disease processes, and explore broader gene-environment interactions in human health. IHEC will facilitate communication among the members and offer a forum for coordination, with the objective of avoiding redundant research efforts, implementing high data quality standards, and thus maximizing efficiency among the scientists working to understand, treat, and prevent diseases. http://ihec-epigenomes. Coronary heart disease is the UK's single biggest killer. For over 50 years we've pioneered research that's transformed the lives of people living with heart and circulatory conditions. Our work has been central to the discoveries of vital treatments that are changing the fight against heart disease. But so many people still need our help. From babies born with life-threatening heart problems to the many Mums, Dads and Grandparents who survive a heart attack and endure the daily battles of heart failure. Join our fight for every heartbeat in the UK. Every pound raised, minute of your time and donation to our shops will help make a difference to people's lives. For more information visit https:/ With some 300 buildings, 40,000 students, 250,000 living alumni, and a reputation for excellence that reaches around the globe, McGill has carved out a spot among the world's greatest universities. https:/ NHS Blood and Transplant (NHSBT) is a joint England and Wales Special Health Authority. Its remit includes the provision of a reliable, efficient supply of blood, platelets, plasma and associated services to the NHS in England. It is also the organ donor organisation for the UK and is responsible for matching and allocating donated organs. http://www. UK Biobank is a major national and international health resource, and a registered charity in its own right, with the aim of improving the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses - including cancer, heart diseases, stroke, diabetes, arthritis, osteoporosis, eye disorders, depression and forms of dementia. UK Biobank recruited 500,000 people aged between 40-69 years in 2006-2010 from across the country to take part in this project. They have undergone measures, provided blood, urine and saliva samples for future analysis, detailed information about themselves and agreed to have their health followed. Over many years this will build into a powerful resource to help scientists discover why some people develop particular diseases and others do not. https:/ The mission of the University of Cambridge is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. To date, 90 affiliates of the University have won the Nobel Prize. Founded in 1209, the University comprises 31 autonomous Colleges, which admit undergraduates and provide small-group tuition, and 150 departments, faculties and institutions. Cambridge is a global university. Its 19,000 student body includes 3,700 international students from 120 countries. Cambridge researchers collaborate with colleagues worldwide, and the University has established larger-scale partnerships in Asia, Africa and America. The University sits at the heart of one of the world's largest technology clusters. The 'Cambridge Phenomenon' has created 1,500 hi-tech companies, 12 of them valued at over US$1 billion and two at over US$10 billion. Cambridge promotes the interface between academia and business, and has a global reputation for innovation. http://www. The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. http://www. Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. http://www.

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