Creation of forest edges has a global impact on forest vertebrates.

Forest edges influence more than half of the world's forests and contribute to worldwide declines in biodiversity and ecosystem functions. However, predicting these declines is challenging in heterogeneous fragmented landscapes. Here we assembled a global dataset on species responses to fragmentation and developed a statistical approach for quantifying edge impacts in heterogeneous landscapes to quantify edge-determined changes in abundance of 1,673 vertebrate species. We show that the abundances of 85% of species are affected, either positively or negatively, by forest edges. Species that live in the centre of the forest (forest core), that were more likely to be listed as threatened by the International Union for Conservation of Nature (IUCN), reached peak abundances only at sites farther than 200-400 m from sharp high-contrast forest edges. Smaller-bodied amphibians, larger reptiles and medium-sized non-volant mammals experienced a larger reduction in suitable habitat than other forest-core species. Our results highlight the pervasive ability of forest edges to restructure ecological communities on a global scale.

Approaches to understanding and interpreting the risks of red blood cell transfusion in neonates.

In this review, we explore how to assess potential harm related to neonatal transfusion practice. We consider different sources of information, including passive or active surveillance systems such as registries, observational studies, randomised trials and systematic reviews. Future research directions are discussed.

A time-driven, activity-based costing methodology for determining the costs of red blood cell transfusion in patients with beta thalassaemia major.

OBJECTIVES: To describe the methodology to estimate the total cost of administration of a single unit of red blood cells (RBC) in adults with beta thalassaemia major in an Australian specialist haemoglobinopathy centre. BACKGROUND: Beta thalassaemia major is a genetic disorder of haemoglobin associated with multiple end-organ complications and typically requiring lifelong RBC transfusion therapy. New therapeutic agents are becoming available based on advances in understanding of the disorder and its consequences. Assessment of the true total cost of transfusion, incorporating both product and activity costs, is required in order to evaluate the benefits and costs of these new therapies. METHODS: We describe the bottom-up, time-driven, activity-based costing methodology used to develop process maps to provide a step-by-step outline of the entire transfusion pathway. Detailed flowcharts for each process are described. Direct observations and timing of the process maps document all activities, resources, staff, equipment and consumables in detail. The analysis will include costs associated with performing these processes, including resources and consumables. Sensitivity analyses will be performed to determine the impact of different staffing levels, timings and probabilities associated with performing different tasks. RESULTS: Thirty-one process maps have been developed, with over 600 individual activities requiring multiple timings. These will be used for future detailed cost analyses. CONCLUSIONS: Detailed process maps using bottom-up, time-driven, activity-based costing for determining the cost of RBC transfusion in thalassaemia major have been developed. These could be adapted for wider use to understand and compare the costs and complexities of transfusion in other settings.

International haemovigilance: what have we learned and what do we need to do next?

The International Haemovigilance Network (IHN) defines haemovigilance as 'a set of surveillance procedures covering the whole transfusion chain (from the collection of blood and its components to the follow-up of recipients), intended to collect and assess information on unexpected or undesirable effects resulting from the therapeutic use of labile blood products, and to prevent their occurrence or recurrence'. IHN, the International Society of Blood Transfusion and World Health Organization work together to support both developing and established haemovigilance systems. Haemovigilance systems provide valuable data on a range of adverse events related to blood donation and clinical transfusion, from donor syncopal events to transfusion-transmitted infections, immunological complications and the impact of human errors. Harmonised definitions for most adverse reactions have been developed and validated internationally. Definitions of pulmonary complications are again under review. Haemovigilance data have resulted in changes in policy, products and practice, and can complement and inform clinical audit and research, leading to improved blood donor safety, optimised product use and better clinical outcomes after transfusion. However, more work is needed. Not all countries have haemovigilance systems in place. More robust data and careful analysis are required to improve the understanding of the causes, occurrence and clinical outcomes of these events. Wider dissemination of results will facilitate health policy development internationally, and implementation of haemovigilance recommendations will support further important progress in blood safety.

Day or overnight transfusion in critically ill patients: does it matter?

BACKGROUND AND OBJECTIVES: The timing of blood administration in critically ill patients is first driven by patients' needs. This study aimed to define the epidemiology and significance of overnight transfusion in critically ill patients. MATERIALS AND METHODS: This is a post hoc analysis of a prospective multicentre observational study including 874 critically ill patients receiving red blood cells, platelets, fresh frozen plasma (FFP) or cryoprecipitate. Characteristics of patients receiving blood only during the day (8 am up until 8 pm) were compared to those receiving blood only overnight (8 pm up until 8 am). Characteristics of transfusion were compared, and factors independently associated with major bleeding were analysed. RESULTS: The 287 patients transfused during the day only had similar severity and mortality to the 258 receiving blood products overnight only. Although bleeding-related admission diagnoses were similar, major bleeding was the indication for transfusion in 12% of patients transfused in daytime only versus 30% of patients transfused at night only (P < 0·001). Similar total amount of blood products were transfused at day and night (2856 versus 2927); however, patients were more likely to receive FFP and cryoprecipitate at night compared with daytime. Overnight transfusion was independently associated with increased odds of major bleeding (odds ratio, 3·16, 95% confidence interval, 2·00-5·01). CONCLUSION: Transfusion occurs evenly across day and night in ICU; nonetheless, there are differences in type of blood products administered that reflect differences in indication. Critically ill patients were more likely to receive blood for major bleeding at night irrespective of admission diagnosis.

Massive transfusions for critical bleeding: is everything old new again?

Massive transfusion or major haemorrhage protocols have been widely adopted in the treatment of critically bleeding patients. Following evidence that higher ratios of transfused plasma and platelets to red blood cells may offer survival benefits in military trauma patients, these ratios are now commonly incorporated into massive transfusion protocols. They more closely resemble the effects of whole blood transfusion, which in the second half of last century was largely replaced by individual blood component transfusion based on laboratory-guided indicators. However, high-quality evidence to guide transfusion support for critically bleeding patients across the range of bleeding contexts is lacking, including for both trauma and non-trauma patients. More data on major haemorrhage support and clinical outcomes are needed to inform guidelines and practice.

Descriptive characteristics and in-hospital mortality of critically bleeding patients requiring massive transfusion: results from the Australian and New Zealand Massive Transfusion Registry.

BACKGROUND AND OBJECTIVES: Critically bleeding patients requiring massive transfusion (MT) are clinically challenging, and limited data exist to support management decisions. This study describes patient characteristics, transfusion support and clinical outcomes from the Australian and New Zealand (NZ) Massive Transfusion Registry (ANZ-MTR). MATERIALS AND METHODS: Retrospective, cohort study of all adult patients receiving MT (≥5 units red blood cells [RBC] in 4 h) at participating ANZ-MTR hospitals, 2011-2015. Mortality information was collected from the Australian National Death Index and NZ Ministry of Health. Associations between patient characteristics and outcomes were modelled using logistic regression. RESULTS: A total of 3560 MT cases were identified. For in-hospital deaths, cardiothoracic surgery was the most frequent bleeding context (24·5%) followed by trauma (18·3%). Age (OR = 1·03; 95% CI: 1·02-1·04), more comorbidities (OR = 1·14; 95% CI: 1·09-1·21), larger volume of RBC in first 24 h from MT onset (OR = 1·04; 95% CI: 1·02-1·06), higher platelet to RBC ratio at 4 h (OR = 2·76; 95% CI: 1·14-6·65) and higher activated partial thromboplastin time (OR = 1·02; 95% CI: 1·01-1·03) were associated with in-hospital mortality. CONCLUSION: Patients with more comorbidities, older age, traumatic or surgical bleeding or requiring more blood components had higher in-hospital mortality. These findings provide a basis to evaluate and monitor practice relating to optimal use of blood products, variation in transfusion practices and patient outcomes, and also enable benchmarking of hospital performance for management of MT in specific patient groups.

Evaluation of clinical coding data to determine causes of critical bleeding in patients receiving massive transfusion: a bi-national, multicentre, cross-sectional study.

OBJECTIVES: To evaluate the use of routinely collected data to determine the cause(s) of critical bleeding in patients who receive massive transfusion (MT). BACKGROUND: Routinely collected data are increasingly being used to describe and evaluate transfusion practice. MATERIALS/METHODS: Chart reviews were undertaken on 10 randomly selected MT patients at 48 hospitals across Australia and New Zealand to determine the cause(s) of critical bleeding. Diagnosis-related group (DRG) and International Classification of Diseases (ICD) codes were extracted separately and used to assign each patient a cause of critical bleeding. These were compared against chart review using percentage agreement and kappa statistics. RESULTS: A total of 427 MT patients were included with complete ICD and DRG data for 427 (100%) and 396 (93%), respectively. Good overall agreement was found between chart review and ICD codes (78·3%; κ = 0·74, 95% CI 0·70-0·79) and only fair overall agreement with DRG (51%; κ = 0·45, 95% CI 0·40-0·50). Both ICD and DRG were sensitive and accurate for classifying obstetric haemorrhage patients (98% sensitivity and κ > 0·94). However, compared with the ICD algorithm, DRGs were less sensitive and accurate in classifying bleeding as a result of gastrointestinal haemorrhage (74% vs 8%; κ = 0·75 vs 0·1), trauma (92% vs 62%; κ = 0·78 vs 0·67), cardiac (80% vs 57%; κ = 0·79 vs 0·60) and vascular surgery (64% vs 56%; κ = 0·69 vs 0·65). CONCLUSION: Algorithms using ICD codes can determine the cause of critical bleeding in patients requiring MT with good to excellent agreement with clinical history. DRG are less suitable to determine critical bleeding causes.

The International Haemovigilance Network Database for the Surveillance of Adverse Reactions and Events in Donors and Recipients of Blood Components: technical issues and results.

BACKGROUND AND OBJECTIVES: The International Haemovigilance Network's ISTARE is an online database for surveillance of all adverse reactions (ARs) and adverse events (AEs) associated with donation of blood and transfusion of blood components, irrespective of severity or the harm caused. ISTARE aims to unify the collection and sharing of information with a view to harmonizing best practices for haemovigilance systems around the world. MATERIALS AND METHODS: Adverse reactionss and adverse events are recorded by blood component, type of reaction, severity and imputability to transfusion, using internationally agreed standard definitions. RESULTS: From 2006 to 2012, 125 national sets of annual aggregated data were received from 25 countries, covering 132.8 million blood components issued. The incidence of all ARs was 77.5 per 100 000 components issued, of which 25% were severe (19.1 per 100 000). Of 349 deaths (0.26 per 100 000), 58% were due to the three ARs related to the respiratory system: transfusion-associated circulatory overload (TACO, 27%), transfusion-associated acute lung injury (TRALI, 19%) and transfusion-associated dyspnoea (TAD, 12%). Cumulatively, 594 477 donor complications were reported (rate 660 per 100 000), of which 2.9% were severe. CONCLUSIONS: ISTARE is a well-established surveillance tool offering important contributions to international efforts to maximize transfusion safety.

Bacterial safety of cell-based therapeutic preparations, focusing on haematopoietic progenitor cells.

Bacterial safety of cellular preparations, especially haematopoietic progenitor cells (HPCs), as well as advanced therapy medicinal products (ATMPs) derived from stem cells of various origins, present a challenge for physicians, manufacturers and regulators. The article describes the background and practical issues in this area and illustrates why sterility of these products cannot currently be guaranteed. Advantages and limitations of approaches both for classical sterility testing and for microbiological control using automated culture systems are discussed. The review considers novel approaches for growth-based rapid microbiological control with high sensitivity and faster availability of results, as well as new methods for rapid bacterial detection in cellular preparations enabling meaningful information about product contamination within one to two hours. Generally, however, these direct rapid methods are less sensitive and have greater sampling error compared with the growth-based methods. Opportunities for pyrogen testing of cell therapeutics are also discussed. There is an urgent need for development of novel principles and methods applicable to bacterial safety of cellular therapeutics. We also need a major shift in approach from the traditional view of sterility evaluation (identify anything and everything) to a new thinking about how to find what is clinically relevant within the time frame available for the special clinical circumstances in which these products are used. The review concludes with recommendations for optimization of microbiological control of cellular preparations, focusing on HPCs.

Elucidating the clinical characteristics of patients captured using different definitions of massive transfusion.

BACKGROUND AND OBJECTIVES: The type and clinical characteristics of patients identified with commonly used definitions of massive transfusion (MT) are largely unknown. The objective of this study was to define the clinical characteristics of patients meeting different definitions of MT for the purpose of patient recruitment in observational studies. MATERIALS AND METHODS: Data were extracted on all patients who received red blood cell (RBC) transfusions in 2010 at three tertiary Australian hospitals. MT patients were identified according to three definitions: ≥10 units RBC in 24 h (10/24 h), ≥6 units RBC in 6 h (6/6 h) and ≥5 units RBC in 4 h (5/4 h). Clinical coding data were used to assign bleeding context. Data on in-hospital mortality were also extracted. RESULTS: Five hundred and forty-two patients met at least one MT definition, with 236 (44%) included by all definitions. The most inclusive definition was 5/4 h (508 patients, 94%) followed by 6/6 h (455 patients, 84%) and 10/24 h (251 patients, 46%). Importantly, 40-55% of most types of critical bleeding events and 82% of all obstetric haemorrhage cases were excluded by the 10/24 h definition. Patients who met both the 5/4 h and 10/24 h definitions were transfused more RBCs (19 vs. 8 median total RBC units; P < 0·001), had longer ventilation time (120 vs. 55 h; P < 0·001), median ICU (149 vs. 99 h; P < 0·001) and hospital length of stay (23 vs. 18 h; P = 0·006) and had a higher in-hospital mortality rate (23·3% vs. 16·4%; P = 0·050). CONCLUSION: The 5/4 h MT definition was the most inclusive, but combination with the 10/24 h definition appeared to identify a clinically important patient cohort.

Establishment of the first international repository for transfusion-relevant bacteria reference strains: ISBT working party transfusion-transmitted infectious diseases (WP-TTID), subgroup on bacteria.

BACKGROUND: Bacterial contamination of platelet concentrates (PCs) still remains a significant problem in transfusion with potential important clinical consequences, including death. The International Society of Blood Transfusion Working Party on Transfusion-Transmitted Infectious Diseases, Subgroup on Bacteria, organised an international study on Transfusion-Relevant Bacteria References to be used as a tool for development, validation and comparison of both bacterial screening and pathogen reduction methods. MATERIAL AND METHODS: Four Bacteria References (Staphylococcus epidermidis PEI-B-06, Streptococcus pyogenes PEI-B-20, Klebsiella pneumoniae PEI-B-08 and Escherichia coli PEI-B-19) were selected regarding their ability to proliferate to high counts in PCs and distributed anonymised to 14 laboratories in 10 countries for identification, enumeration and bacterial proliferation in PCs after low spiking (0·3 and 0·03 CFU/ml), to simulate contamination occurring during blood donation. RESULTS: Bacteria References were correctly identified in 98% of all 52 identifications. S. pyogenes and E. coli grew in PCs in 11 out of 12 laboratories, and K. pneumoniae and S. epidermidis replicated in all participating laboratories. The results of bacterial counts were very consistent between laboratories: the 95% confidence intervals were for S. epidermidis: 1·19-1·32 × 10(7) CFU/ml, S. pyogenes: 0·58-0·69 × 10(7) CFU/ml, K. pneumoniae: 18·71-20·26 × 10(7) CFU/ml and E. coli: 1·78-2·10 × 10(7) CFU/ml. CONCLUSION: The study was undertaken as a proof of principle with the aim to demonstrate (i) the quality, stability and suitability of the bacterial strains for low-titre spiking of blood components, (ii) the property of donor-independent proliferation in PCs, and (iii) their suitability for worldwide shipping of deep frozen, blinded pathogenic bacteria. These aims were successfully fulfilled. The WHO Expert Committee Biological Standardisation has approved the adoption of these four bacteria strains as the first Repository for Transfusion-Relevant Bacteria Reference Strains and, additionally, endorsed as a project the addition of six further bacteria strain preparations suitable for control of platelet contamination as the next step of enlargement of the repository.

Apollo 11: exposure of lower animals to lunar material.

Lunar material returned from the first manned landing on the moon was assayed for the presence of replicating agents possibly harmful to life on earth. Ten species of lower animals were exposed to lunar material for 28 days. No pathological effects attributable to contact with lunar material were detected.

Duffy antigen expression on reticulocytes does not alter following blood loss in an autologous donation model.

BACKGROUND: The Duffy blood group (Fy) antigen functions as the receptor whereby the malarial parasite Plasmodium vivax invades reticulocytes. In this study, we evaluated an autologous blood donation model to measure Fy expression during the anticipated response to blood loss. AIMS: This study aims to examine Fy expression following anticipated reticulocytosis in response to blood loss from autologous whole blood donation. METHOD: Subjects were healthy blood donors presenting for planned collection of two or three autologous units. Whole blood (450 ml +/- 10%) was collected and processed. Blood samples for Fy testing were obtained from the donations. These were assayed by flow cytometry by measuring binding of a phycoerythrin-labelled anti-Fy6 antibody and compared against reticulocyte numbers. Reticulocyte numbers were measured using thiazole orange. Results were compared from baseline (first donation) with samples at second and, if available, third, donations. Phenotyping for Fy a and b antigens was performed. RESULTS: Reticulocytes increased by a mean of 37% over baseline [0.93% (range 0.31-1.93) to 1.23% (0.32-3.51%)] following donation of two (n = 32) or three (n = 9) autologous whole blood units. Absolute reticulocyte count remained low. Mean and median Fy expression on mature red blood cells and reticulocytes did not change from baseline levels despite individual variation. No apparent relationship to serologically determined Fy a and/or b antigen status was present. CONCLUSION: Baseline expression of Fy antigen on mature red blood cells and reticulocytes is quite variable between individuals, but appears not to be greatly affected by mild to moderate reticulocytosis following blood loss in an autologous blood donation model.

A 'dangerous' group O donor: severe hemolysis in all recipients of organs from a donor with multiple red cell alloantibodies.

Alloimmune hemolysis is a recognized but infrequent complication of solid organ transplantation, particularly where there is incompatibility within the ABO blood group system. We describe severe hemolysis due to passenger lymphocyte syndrome (PLS) in all three recipients of organs from a single donor with multiple red cell (RC) alloantibodies. The first patient, a liver transplant recipient, required augmentation of immunosuppression to treat immune hemolysis due to anti-B, -D, -C and -Cellano (k). This is the first description of PLS caused by alloantibody to the high incidence RC antigen, k. The two single lung transplant recipients developed hemolysis due to anti-D. Both required escalation of immunosuppression and early transfusion support. Three months posttransplant, all three patients have ongoing evidence of compensated hemolysis. This series highlights the potential for severe non-ABO-mediated immune hemolysis following solid organ transplantation. A positive donor RC antibody screen should prompt careful monitoring of organ recipients for hemolysis.

Particle size distribution and composition in a mechanically ventilated school building during air pollution episodes.

UNLABELLED: Particle count-based size distribution and PM(2.5) mass were monitored inside and outside an elementary school in Salt Lake City (UT, USA) during the winter atmospheric inversion season. The site is influenced by urban traffic and the airshed is subject to periods of high PM(2.5) concentration that is mainly submicron ammonium and nitrate. The school building has mechanical ventilation with filtration and variable-volume makeup air. Comparison of the indoor and outdoor particle size distribution on the five cleanest and five most polluted school days during the study showed that the ambient submicron particulate matter (PM) penetrated the building, but indoor concentrations were about one-eighth of outdoor levels. The indoor:outdoor PM(2.5) mass ratio averaged 0.12 and particle number ratio for sizes smaller than 1 microm averaged 0.13. The indoor submicron particle count and indoor PM(2.5) mass increased slightly during pollution episodes but remained well below outdoor levels. When the building was occupied the indoor coarse particle count was much higher than ambient levels. These results contribute to understanding the relationship between ambient monitoring station data and the actual human exposure inside institutional buildings. The study confirms that staying inside a mechanically ventilated building reduces exposure to outdoor submicron particles. PRACTICAL IMPLICATIONS: This study supports the premise that remaining inside buildings during particulate matter (PM) pollution episodes reduces exposure to submicron PM. New data on a mechanically ventilated institutional building supplements similar studies made in residences.