Influence of donor age, sex and ethnicity on high-titre anti-A and -B: Review of 6 million donations from two national blood providers.

BACKGROUND AND OBJECTIVES: Some blood operators routinely screen blood donations for high-titre (HT) anti-A/B to reduce the risk of a haemolytic transfusion reaction due to out-of-group plasma-rich components. We assessed donor factors associated with an increased likelihood of screening positive and compared routine data between England and Australia. MATERIALS AND METHODS: Data were assessed from HT screening during 2018-2020 in Australia and 2018-2021 in England, totalling nearly 6 million blood donations. Screening was performed using a Beckman Coulter PK7300 analyser with a micro-titre plate saline direct agglutination test in both countries, although different reagent red cells were chosen. HT-positive was defined as testing positive at a titre of 128 or above. RESULTS: The likelihood of a donor testing HT-positive was greater for females than males, declined with age and was dependent on the ABO group. However, the proportion of donors testing HT-positive was consistently higher in Australia than in England: overall, 14% of group O donations and 5% of group A donations in England tested HT-positive, compared with 51% and 22%, respectively in Australia. English data also showed that donors from Black, Asian or mixed ethnic backgrounds were more likely to test HT-positive than White donors. CONCLUSION: These data demonstrate that donor sex, age, ABO group and ethnicity affect the likelihood of testing HT-positive. Differences in testing methods likely had a significant impact on the proportion of donors testing as HT-positive or -negative rather than any differences in donor populations.

Frequency of red blood cell phenotypes from genotyped Australian blood donors.

BACKGROUND: Australian Red Cross Lifeblood (Lifeblood) performs human erythrocyte antigen (HEA) genotyping for a subset of repeat whole-blood donors through preferential selection which aims to maximise variation of results and possibility of identifying donors lacking high frequency red cell antigens. MATERIALS AND METHODS: The HEA Molecular Bead chip™ assay is used by Lifeblood for donor genotyping. A review of all donor HEA genotype data from March 2019 to May 2022 (3 years) was conducted. RESULTS: HEA genotyping was performed for 20,185donors. Due to selective genotyping of donors, a higher frequency of R1R1 predicted phenotype was identified. However, frequencies of other red cell phenotypes were relatively similar to previous reported in the Australian population. A small number of donors with rare red cell phenotypes was identified. CONCLUSION: Genotyping of blood donors provides an available pool of extended matched red blood cell products for matching to recipients. Additionally genotyping can improve the identification of donors with rare phenotypes. Whilst limitations exist, genotyping may reduce the need for labour intensive serotyping, improve blood inventory management, and may be useful in donor recruitment and retention.

Platelets retain function and can be stored following disruption of human leucocyte antigens.

BACKGROUND AND OBJECTIVES: Antibodies to human leucocyte antigen (HLA) Class-I antigens can lead to refractoriness to platelet transfusion. Although this can be overcome by transfusion of HLA-compatible platelets, they are not always available. Disruption of HLA antigens on platelets by acid treatment may be a suitable alternative when no other components are available. The aim of this study was to assess the effect of HLA disruption and subsequent storage of platelet components. MATERIALS AND METHODS: Platelet components were treated with 0.9% saline or citric acid solution (pH 3.0), and then stored until expiry (Day 7). HLA and platelet glycoprotein expression, platelet viability, activation and sialylation were measured by flow cytometry. Release of soluble factors was measured by ELISA and metabolism by biochemistry analyser. Reactivity to patient anti-sera containing anti-HLA antibodies was measured using platelet immunofluorescence tests (PIFTs) and monoclonal antibody immobilization of platelet antigen (MAIPA) assays. Platelet function was measured using aggregometry and thromboelastography (TEG). RESULTS: Acid treatment reduced detection of HLA Class-I on platelets by 75%, with significant reductions in reactivity to patient anti-sera. Acid treatment reduced platelet content and viability, increased platelet activation and accelerated metabolism. Glycan cleavage was increased by acid treatment. Treatment reduced platelet activation following agonist stimulation by ADP and TRAP-6, but platelets remained functional, displaying increased aggregation response and reduced time to clot formation by TEG. CONCLUSION: Although HLA disruption had some detrimental effects, acid-treated platelets remained functional, retaining their capacity to respond to agonists and form clots, and with further development could be used to support refractory patients.

Equity in blood transfusion precision services.

BACKGROUND: Blood collection agencies are integrating precision medicine techniques to improve and individualise blood donor and recipient outcomes. These organisations have a role to play in ensuring equitable application of precision medicine technologies for both donors and transfusion recipients. BODY: Precision medicine techniques, including molecular genetic testing and next generation sequencing, have been integrated in transfusion services to improve blood typing and matching with the aim to reduce a variety of known transfusion complications. Internationally, priorities in transfusion research have aimed to optimise services through the use of precision medicine technologies and consider alternative uses of genomic information to personalise transfusion experiences for both recipients and donors. This has included focusing on the use of genomics when matching blood products for transfusion recipients, to personalise a blood donor's donation type or frequency, and longitudinal donor research utilising blood donor biobanks. CONCLUSION: Equity in precision services and research must be of highest importance for blood collection agencies to maintain public trust, especially when these organisations rely on volunteer donors to provide transfusion services. The investment in implementing equitable precision medicine services, including development of blood donor biobanks, has the potential to optimise and personalise services for both blood donors and transfusion recipients.

Rethinking the transfusion pathway in myelodysplastic syndromes: Study protocol for a novel randomized feasibility n-of-1 trial of weekly-interval red cell transfusion in myelodysplastic syndromes.

BACKGROUND: Anemia in myelodysplastic syndromes (MDS) is associated with poorer health-related quality of life (HRQoL) and physical function, and is frequently treated with transfusions. The current common practice of transfusing multiple red blood cells (RBC) units every 2-4 weeks may result in peaks/troughs in hemoglobin (Hb) level, yet maintaining a stable Hb may better improve HRQoL. We describe a study protocol aiming to investigate the feasibility of weekly low-dose RBC transfusion in MDS patients, including assessing HRQoL and physical function outcomes. STUDY DESIGN AND METHODS: In this n-of-1 pilot study, patients receive two treatment arms, with randomly allocated treatment sequence: arm A (patient's usual transfusion schedule) and arm B (weekly transfusion, individualized per patient). To facilitate timely delivery of weekly transfusion, extended-matched RBCs are provided, with transfusion based upon the previous week's Hb/pre-transfusion testing results to eliminate delays of awaiting contemporaneous cross-matching. Primary outcome is the feasibility of delivering weekly transfusion. Secondary outcomes include HRQoL, functional activity measurements, RBC usage, and alloimmunization rates. A qualitative substudy explores patient and staff experiences. RESULTS: The trial is open in Australia, Netherlands, and UK. The first patient was recruited in 2020. Inter-country differences in providing RBCs are observed, including patient genotyping versus serological phenotyping to select compatible units. DISCUSSION: This pilot trial evaluates a novel personalized transfusion approach of weekly matched RBC transfusion and challenges the dogma of current routine pre-transfusion matching practice. Findings on study feasibility, HRQoL, and physical functional outcomes and the qualitative substudy will inform the design of a larger definitive trial powered for clinical outcomes.

Feasibility for non-invasive prenatal fetal blood group and platelet genotyping by massively parallel sequencing: A single test system for multiple atypical red cell, platelet and quality control markers.

Non-invasive prenatal tests (NIPT) to predict fetal red cell or platelet antigen status for alloimmunised women are provided for select antigens. This study reports on massively parallel sequencing (MPS) using a red cell and platelet probe panel targeting multiple nucleotide variants, plus individual identification single nucleotide polymorphisms (IISNPs). Maternal blood samples were provided from 33 alloimmunised cases, including seven with two red cell antibodies. Cell-free and genomic DNA was sequenced using targeted MPS and bioinformatically analysed using low-frequency variant detection. The resulting maternal genomic DNA allele frequency was subtracted from the cell-free DNA counterpart. Outcomes were matched against validated phenotyping/genotyping methods, where available. A 2.5% subtractive allele frequency threshold was set after comparing MPS predictions for K, RhC/c, RhE/e and Fya /Fyb against expected outcomes. This threshold was used for subsequent predictions, including HPA-15a, Jka /Jkb , Kpa /Kpb and Lua . MPS outcomes were 97.2% concordant with validated methods; one RhC case was discordantly negative and lacked IISNPs. IISNPs were informative for 30/33 cases as controls. NIPT MPS is feasible for fetal blood group genotyping and covers multiple blood groups and control targets in a single test. Noting caution for the Rh system, this has the potential to provide a personalised service for alloimmunised women.

A case of haemolytic disease of the fetus and newborn attributed to a novel antigen in the RHAG blood group system.

BACKGROUND AND OBJECTIVES: A newborn presented with jaundice in Thailand. The cord red cells tested positive by direct antiglobulin test (DAT) for an unknown maternal red cell antibody. Initial blood group sequencing suggested that the infant carried a novel variant RHAG c.140T>C, responsible for a low-prevalence antigen in the RHAG blood group system (ISBT 030). We report here on testing of samples from the infant's parents and older sibling to define a new antigen in the RHAG system. MATERIALS AND METHODS: Massive parallel sequencing (MPS) using a custom-designed panel was performed on all four family members. Extended serological testing was also performed to determine whether family members with the same variant as the infant showed reactivity with the antibody in the maternal plasma. RESULTS: We identified a novel single nucleotide variant (SNV) (RHAG c.140T>C, p.[Phe47Ser]) in samples from three of the four family members tested (the infant, the older sibling and the father). The variant was not detected in the mother's sample. Maternal plasma showed positive agglutination with all family members tested; however, when tested with routine panel cells, no reactivity was observed. CONCLUSION: This case study showed that the presence of the novel variant (RHAG c.140T>C), encoding a p.(Phe47Ser) change in the RhAG glycoprotein, was the apparent cause of incompatibility between maternal plasma and that of red cells from the proband, father and older sibling of the proband. We propose this variant to be a new low-prevalence antigen in the RHAG blood group system.

Repurposing Metformin for periodontal disease management as a form of oral-systemic preventive medicine.

BACKGROUND: Despite the improvements in treatment over the last decades, periodontal disease (PD) affects millions of people around the world and the only treatment available is based on controlling microbial load. Diabetes is known to increase the risk of PD establishment and progression, and recently, glucose metabolism modulation by pharmaceutical or dietarian means has been emphasised as a significant modulator of non-communicable disease development. METHODS: The impact of pharmaceutically controlling glucose metabolism in non-diabetic animals and humans (REBEC, UTN code: U1111-1276-1942) was investigated by repurposing Metformin, as a mean to manage periodontal disease and its associated systemic risk factors. RESULTS: We found that glucose metabolism control via use of Metformin aimed at PD management resulted in significant prevention of bone loss during induced periodontal disease and age-related bone loss in vivo. Metformin also influenced the bacterial species present in the oral environment and impacted the metabolic epithelial and stromal responses to bacterial dysbiosis at a single cell level. Systemically, Metformin controlled blood glucose levels and age-related weight gain when used long-term. Translationally, our pilot randomized control trial indicated that systemic Metformin was safe to use in non-diabetic patients and affected the periodontal tissues. During the medication window, patients showed stable levels of systemic blood glucose, lower circulating hsCRP and lower insulin levels after periodontal treatment when compared to placebo. Finally, patients treated with Metformin had improved periodontal parameters when compared to placebo treated patients. CONCLUSION: This is the first study to demonstrate that systemic interventions using Metformin in non-diabetic individuals aimed at PD prevention have oral-systemic effects constituting a possible novel form of preventive medicine for oral-systemic disease management.

Implementation of evidence-based primary cancer prevention interventions in MA community health centers: an explanatory sequential mixed methods study.

BACKGROUND: More than half of cancers could be prevented by employing evidence-based interventions (EBIs), including prevention interventions targeting nutrition, physical activity, and tobacco. Federally qualified health centers (FQHCs) are the primary source of patient care for over 30 million Americans - making them an optimal setting for ensuring evidence-based prevention that advances health equity. The aims of this study are to (1) determine the degree to which primary cancer prevention EBIs are being implemented within Massachusetts FQHCs and (2) describe how these EBIs are implemented internally and via community partnerships. METHODS: We used an explanatory sequential mixed methods design to assess the implementation of cancer prevention EBIs. First, we collected 34 quantitative surveys from staff at 16 FQHCs across Massachusetts to determine the frequency of EBI implementation. We followed up with 12 qualitative one-on-one interviews among a sample of staff to understand how the EBIs selected on the survey were implemented. Exploration of contextual influences on implementation and use of partnerships was guided by the Consolidated Framework for Implementation Research (CFIR). Quantitative data were summarized descriptively, and qualitative analyses used reflexive, thematic approaches, beginning deductively with codes from CFIR, then inductively coding additional categories. RESULTS: All FQHCs indicated they offered clinic-based tobacco interventions, such as clinician-delivered screening practices and prescription of tobacco cessation medications. Quitline interventions and some diet/physical activity EBIs were available at all FQHCs, but staff perceptions of penetration were low. Only 38% of FQHCs offered group tobacco cessation counseling and 63% referred patients to mobile phone-based cessation interventions. We found multilevel factors influenced implementation across intervention types - including the complexity of intervention trainings, available time and staffing, motivation of clinicians, funding, and external policies and incentives. While partnerships were described as valuable, only one FQHC reported using clinical-community linkages for primary cancer prevention EBIs. CONCLUSIONS: Adoption of primary prevention EBIs in Massachusetts FQHCs is relatively high, but stable staffing and funding are required to successfully reach all eligible patients. FQHC staff are enthusiastic about the potential of community partnerships to foster improved implementation-providing training and support to build these relationships will be key to fulfilling that promise.

Use of Evidence-Based Interventions to Promote Healthy Weight, Nutrition, and Physical Activity in Community Health Improvement Plans from Large Local Health Departments.

We sought to identify evidence-based healthy weight, nutrition, and physical activity strategies related to obesity prevention in large local health department (LHD) Community Health Improvement Plans (CHIPs). We analyzed the content of the most recent, publicly available plans from 72 accredited LHDs serving a population of at least 500 000 people. We matched CHIP strategies to the County Health Rankings and Roadmaps' What Works for Health (WWFH) database of interventions. We identified 739 strategies across 55 plans, 62.5% of which matched a "WWFH intervention" rated for effectiveness on diet and exercise outcomes. Among the 20 most commonly identified WWFH interventions in CHIPs, 10 had the highest evidence for effectiveness while 4 were rated as likely to decrease health disparities according to WWFH. Future prioritization of strategies by health agencies could focus on strategies with the strongest evidence for promoting healthy weight, nutrition, and physical activity outcomes and reducing health disparities.

Embedding community-engaged research principles in implementation science: The implementation science center for cancer control equity.

Gaps in the implementation of effective interventions impact nearly all cancer prevention and control strategies in the US including Massachusetts. To close these implementation gaps, evidence-based interventions must be rapidly and equitably implemented in settings serving racially, ethnically, socioeconomically, and geographically diverse populations. This paper provides a brief overview of The Implementation Science Center for Cancer Control Equity (ISCCCE) and describes how we have operationalized our commitment to a robust community-engaged center that aims to close these gaps. We describe how ISCCCE is organized and how the principles of community-engaged research are embedded across the center. Principles of community engagement have been operationalized across all components of ISCCCE. We have intentionally integrated these principles throughout all structures and processes and have developed evaluation strategies to assess whether the quality of our partnerships reflects the principles. ISCCCE is a comprehensive community-engaged infrastructure for studying efficient, pragmatic, and equity-focused implementation and adaptation strategies for cancer prevention in historically and currently disadvantaged communities with built-in methods to evaluate the quality of community engagement. This engaged research center is designed to maximize the impact and relevance of implementation research on cancer control in community health centers.

Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health.

Retromer controls cellular homeostasis through regulating integral membrane protein sorting and transport and by controlling maturation of the endo-lysosomal network. Retromer dysfunction, which is linked to neurodegenerative disorders including Parkinson's and Alzheimer's diseases, manifests in complex cellular phenotypes, though the precise nature of this dysfunction, and its relation to neurodegeneration, remain unclear. Here, we perform an integrated multi-omics approach to provide precise insight into the impact of Retromer dysfunction on endo-lysosomal health and homeostasis within a human neuroglioma cell model. We quantify widespread changes to the lysosomal proteome, indicative of broad lysosomal dysfunction and inefficient autophagic lysosome reformation, coupled with a reconfigured cell surface proteome and secretome reflective of increased lysosomal exocytosis. Through this global proteomic approach and parallel transcriptomic analysis, we provide a holistic view of Retromer function in regulating lysosomal homeostasis and emphasise its role in neuroprotection.

Data sharing in the context of community-engaged research partnerships.

Over the past 20 years, the National Institutes for Health (NIH) has implemented several policies designed to improve sharing of research data, such as the NIH public access policy for publications, NIH genomic data sharing policy, and National Cancer Institute (NCI) Cancer Moonshot public access and data sharing policy. In January 2023, a new NIH data sharing policy has gone into effect, requiring researchers to submit a Data Management and Sharing Plan in proposals for NIH funding (NIH. Supplemental information to the, 2020b; NIH. Final policy for data, 2020a). These policies are based on the idea that sharing data is a key component of the scientific method, as it enables the creation of larger data repositories that can lead to research questions that may not be possible in individual studies (Alter and Gonzalez, 2018; Jwa and Poldrack, 2022), allows enhanced collaboration, and maximizes the federal investment in research. Important questions that we must consider as data sharing is expanded are to whom do benefits of data sharing accrue and to whom do benefits not accrue? In an era of growing efforts to engage diverse communities in research, we must consider the impact of data sharing for all research participants and the communities that they represent. We examine the issue of data sharing through a community-engaged research lens, informed by a long-standing partnership between community-engaged researchers and a key community health organization (Kruse et al., 2022). We contend that without effective community engagement and rich contextual knowledge, biases resulting from data sharing can remain unchecked. We provide several recommendations that would allow better community engagement related to data sharing to ensure both community and researcher understanding of the issues involved and move toward shared benefits. By identifying good models for evaluating the impact of data sharing on communities that contribute data, and then using those models systematically, we will advance the consideration of the community perspective and increase the likelihood of benefits for all.

Out of the ESCPE room: Emerging roles of endosomal SNX-BARs in receptor transport and host-pathogen interaction.

Several functions of the human cell, such as sensing nutrients, cell movement and interaction with the surrounding environment, depend on a myriad of transmembrane proteins and their associated proteins and lipids (collectively termed "cargoes"). To successfully perform their tasks, cargo must be sorted and delivered to the right place, at the right time, and in the right amount. To achieve this, eukaryotic cells have evolved a highly organized sorting platform, the endosomal network. Here, a variety of specialized multiprotein complexes sort cargo into itineraries leading to either their degradation or their recycling to various organelles for further rounds of reuse. A key sorting complex is the Endosomal SNX-BAR Sorting Complex for Promoting Exit (ESCPE-1) that promotes the recycling of an array of cargos to the plasma membrane and/or the trans-Golgi network. ESCPE-1 recognizes a hydrophobic-based sorting motif in numerous cargoes and orchestrates their packaging into tubular carriers that pinch off from the endosome and travel to the target organelle. A wide range of pathogens mimic this sorting motif to hijack ESCPE-1 transport to promote their invasion and survival within infected cells. In other instances, ESCPE-1 exerts restrictive functions against pathogens by limiting their replication and infection. In this review, we discuss ESCPE-1 assembly and functions, with a particular focus on recent advances in the understanding of its role in membrane trafficking, cellular homeostasis and host-pathogen interaction.

Implementation of evidence-based primary cancer prevention interventions in MA community health centers: an explanatory sequential mixed methods study.

Background More than half of cancers could be prevented by employing evidence-based interventions (EBIs), including prevention interventions targeting nutrition, physical activity, and tobacco. Federally qualified health centers (FQHCs) are the primary source of patient care for over 30 million Americans - making them an optimal setting for ensuring evidence-based prevention that advances health equity. The aims of this study are to: 1) determine the degree to which primary cancer prevention EBIs are being implemented within Massachusetts FQHCs and 2) describe how these EBIs are implemented internally and via community partnerships. Methods We used an explanatory sequential mixed methods design to assess the implementation of cancer prevention EBIs. First, we used quantitative surveys of FQHC staff to determine the frequency of EBI implementation. We followed up with qualitative one-on-one interviews among a sample of staff to understand how the EBIs selected on the survey were implemented. Exploration of contextual influences on implementation and use of partnerships was guided by the Consolidated Framework for Implementation Research (CFIR). Quantitative data were summarized descriptively, and qualitative analyses used reflexive, thematic approaches, beginning deductively with codes from CFIR, then inductively coding additional categories. Results All FQHCs indicated they offered clinic-based tobacco interventions, such as clinician-delivered screening practices and prescription of tobacco cessation medications. Quitline interventions and some diet/physical activity EBIs were available at all FQHCs, but staff perceptions of penetration were low. Only 38% of FQHCs offered group tobacco cessation counseling and 63% referred patients to mobile phone-based cessation interventions. We found multilevel factors influenced implementation across intervention types - including the complexity of intervention trainings, available time and staffing, motivation of clinicians, funding, and external policies and incentives. While partnerships were described as valuable, only one FQHC reported using clinical-community linkages for primary cancer prevention EBIs. Conclusions Adoption of primary prevention EBIs in Massachusetts FQHCs is relatively high, but stable staffing and funding are required to successfully reach all eligible patients. FQHC staff are enthusiastic about the potential of community partnerships to foster improved implementation - providing training and support to build these relationships will be key to fulfilling that promise.

Evaluation of two temperature storage conditions for full blood count samples from Lifeblood's donors.

BACKGROUND AND OBJECTIVES: Lifeblood completes full blood count samples for selected donors to assess their suitability for future donations. Removing the current practice for refrigerated (2-8°C) storage and aligning with room temperature (20-24°C) storage of other donor blood samples would produce significant efficiencies in blood donor centres. This study aimed to compare full blood count results under two temperature conditions. MATERIALS AND METHODS: Paired full blood count samples were collected from 250 whole blood or plasma donors. These were stored either refrigerated or room temperature for testing on arrival at the processing centre and the following day. The primary outcomes of interest included differences between mean cell volume, haematocrit, platelet count, white cell and differential counts, and the need to produce blood films, based on existing Lifeblood criteria. RESULTS: A statistically significant (p < 0.05) difference for most full blood count parameters results was found between the two temperature conditions. The number of blood films required was similar under each temperature condition. CONCLUSION: The clinical significance of the small numerical differences in results is considered minimal. Furthermore, the number of blood films required remained similar under either temperature condition. Given the significant reductions in time, processing and costs associated with room temperature over refrigerated processing, we recommend a further pilot study to monitor the broader impacts, with the intent to implement national storage of full blood count samples at room temperature within Lifeblood.

The impact of revised definitions for transfusion-associated circulatory overload and transfusion-related acute lung injury on haemovigilance reporting.

BACKGROUND AND OBJECTIVES: Transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) are serious adverse transfusion reactions. Standardized surveillance definitions are important to ensure consistent reporting of cases. Recently, revised definitions have been developed for TACO and TRALI, the latter of which has not yet been widely implemented. This study aimed to assess the impact of the new TACO and TRALI definitions on haemovigilance reporting. MATERIALS AND METHODS: The Australian Red Cross Lifeblood Adverse Transfusion Reaction database was accessed to identify all cases of suspected or confirmed TACO and TRALI referred from 1 July 2015 to 30 June 2019. Cases were assessed against both the former and new definitions and the results were compared. RESULTS: A total of 73 cases were assessed. There were 48 TACO cases identified. Only 26 of 48 cases strictly met the former 2011 International Society of Blood Transfusion (ISBT) definition of TACO; 6 cases did not meet the definition and 16 cases lacked sufficient clinical details. In comparison, 46 cases met the revised 2018 ISBT definition, with only 2 cases having insufficient details. There were 24 cases of TRALI according to the existing 2004 Canadian Consensus Conference (CCC) definition compared with 25 cases according to the proposed 2019 revised definition. CONCLUSION: The revised TACO definition captured more cases than the former definition. No significant differences were observed in the number of TRALI cases under the proposed new definition. This is the first study to provide validation data for the revised TRALI definition.

Probabilistic mathematical modelling to predict the red cell phenotyped donor panel size.

In the last decade, Australia has experienced an overall decline in red cell demand, but there has been an increased need for phenotyped matched red cells. Lifeblood and mathematicians from Queensland universities have developed a probabilistic model to determine the percentage of the donor panel that would need extended antigen typing to meet this increasing demand, and an estimated timeline to achieve the optimum required phenotyped (genotyped) panel. Mathematical modelling, based on Multinomial distributions, was used to provide guidance on the percentage of typed donor panel needed, based on recent historical blood request data and the current donor panel size. Only antigen combinations determined to be uncommon, but not rare, were considered. Simulations were run to attain at least 95% success percentage. Modelling predicted a target of 38% of the donor panel, or 205,000 donors, would need to be genotyped to meet the current demand. If 5% of weekly returning donors were genotyped, this target would be reached within 12 years. For phenotyping, 35% or 188,000 donors would need to be phenotyped to meet Lifeblood's demand. With the current level of testing, this would take eight years but could be performed within three years if testing was increased to 9% of weekly returning donors. An additional 26,140 returning donors need to be phenotyped annually to maintain this panel. This mathematical model will inform business decisions and assist Lifeblood in determining the level of investment required to meet the desired timeline to achieve the optimum donor panel size.

Endosomes, receptors, and viruses.

Mechanisms of infection are deciphered at the host-pathogen interface.