Determining the impact of current Canadian stem cell registry policy on donor availability via dynamic registry simulation.

BACKGROUND AND OBJECTIVES: When a haematopoietic stem cell registry size is constrained by limits on recruiting, as in Canada, identifying the right person to recruit is a critical determinant of effectiveness. The aim of this study was to evaluate the impact of changes to donor recruitment effort, within ethnic groups, on the matching effectiveness of the Canadian registry as it evolves over time. MATERIALS AND METHODS: Simulation methods are applied to create a cohort of donor recruits and patients over a 10-year time horizon. New recruits are added to the registry each year, while some existing donors 'age-out' upon reaching their 36th birthday. In a similar fashion, simulated patient lists are created. At the end of each simulated year, simulated patients are matched against the simulated registry. RESULTS: There are increased matches in non-White populations when diverse registrants are preferentially recruited, but there are larger decreases in the number of matches for Caucasian patients. Additionally, ethnic communities that have limited registrants in the Canadian registry in 2021 do not benefit from increased recruiting efforts as much as communities with a larger initial number of registrants. CONCLUSION: Preferentially recruiting from non-Caucasian populations reduces the number of matches from Canadian sources because increases in non-Caucasian populations will not fully counterbalance decreases to Caucasian patient matches. Nevertheless, more than 80% of all matches are for Caucasian patients, regardless of the donor recruiting effort within ethnic groups.

Evolutionary and Ecological Processes Underlying Geographic Variation in Innate Bird Songs.

AbstractEcological and evolutionary processes underlying spatial variation in signals involved in mate recognition and reproductive isolation are crucial to understanding the causes of population divergence and speciation. Here, to test hypotheses concerning the causes of song divergence, we examine how songs of two sister species of Atlantic Forest suboscine birds with innate songs, the Pyriglena fire-eye antbirds, vary across their ranges. Specifically, we evaluated the influence of isolation by distance and introgressive hybridization, as well as morphological and environmental variation, on geographic variation in male songs. Analyses based on 496 male vocalizations from 63 locations across a 2,200-km latitudinal transect revealed clinal changes in the structure of songs and showed that introgressive hybridization increases both the variability and the homogenization of songs in the contact zone between the two species. We also found that isolation by distance, morphological constraints, the environment, and genetic introgression independently predicted song variation across geographic space. Our study shows the importance of an integrative approach that investigates the roles of distinct ecological and evolutionary processes that influence acoustic signal evolution.

Modeling unrelated blood stem cell donor recruitment using simulated registrant cohorts: Assessment of human leukocyte antigen matching across ethnicity groups.

BACKGROUND: Human leukocyte antigen (HLA)-matched unrelated donors are not available for some patients considered for allogeneic hematopoietic cell transplantation, particularly among certain ethnic groups. Simulated recruitment modeling can inform efforts to find new matches for more patients. METHODS: Simulated recruits were generated by assigning a pair of donor HLA haplotypes from historical data files and matched against HLA data of patient searches in the Canadian Blood Services Stem Cell Registry. Recruitment cohorts reflected the proportion of five specific ethnic groups in the 2016 Canadian census data. RESULTS: Novel 8/8 HLA matches between simulated recruits and patients increased linearly with larger recruitment cohorts. The proportion of novel 8/8 HLA matches from Caucasian, Hispanic, and Native American/First Nations recruits was equal to or greater than their relative proportion in the recruited cohort (match to: recruit ratio (MRR) ≥ 1). In contrast, African American and Asian & Pacific Islander recruits represented a smaller proportion of novel matches relative to their percentage of the recruited cohort (MRR <1). The proportion of novel 7/8 HLA-matches from each ethnic group was approximately the same as their proportion in the recruited cohort (MRR ~ 1) and high rates of 7/8 HLA-matching already exist within the Canadian Blood Services registry for all ethnic groups. CONCLUSION: Continued large recruitment cohorts are needed to add new 8/8 HLA matches to registry inventories. Likelihoods of novel HLA matches varied across ethnic groups, reflecting varied HLA haplotype frequencies across groups. Simulated cohort modeling can inform recruitment strategies that will generate new donor options for patients.

The operational impact of introducing cold stored platelets.

BACKGROUND: Cold stored platelets (CSP) undergo physical changes that make them better at initiating a clot. While cold stored platelets are superior for reducing bleeding in actively bleeding patients, room temperature platelets (RTP) are better for increasing platelet count in patients requiring a prophylactic transfusion. However, whether the overhead required to maintain a dual platelet inventory of both RTP and CSP could be compensated by reduced platelet wastage resulting from the longer shelf life of CSP has not been determined. STUDY DESIGN AND METHODS: A simulation model of a regional blood supply was built, with focus on the operations of a case hospital. Two scenarios were considered: "No-CSP," in which the hospital issues only RTP, and "CSP," in which the hospital issues both RTP and CSP Within the CSP scenario, conditions were tested under which the hospital receives only RTP and converts some to cold stored platelets and a second strategy where the hospital receives CSP from the regional supplier in addition to converting RTP. RESULTS: A centralized supply of CSP is necessary since on-site conversion is limited by platelet age. Product shortages decrease with increased CSP inventory, but CSP wastage increases. It was also determined that, because relatively few RTP units can be converted on-site, RTP wastage is not significantly decreased with the introduction of CSP. CONCLUSION: Given the clinical benefits for treatment of trauma, CSP is a desirable addition to a blood formulary. However, it is unlikely that significant reductions in RTP wastage will occur because of the introduction of CSP.

Evaluating the inventory impact of utilizing low titer platelets in regional hospitals.

BACKGROUND: As a result of constrained supply, it is sometimes necessary to provide patients with ABO-mismatched platelets. Such practices increase the risk of acute hemolytic transfusion reaction (AHTR). Providing patients with platelets suspended in O plasma having low-titer Anti-A and Anti-B antibodies (LtABO) could reduce the incidence of AHTR. However, natural scarcity limits the number of such units that can be produced. In this paper we present a study to evaluate strategies for deploying LtABO at regional hospitals in Canada. STUDY DESIGN AND METHODS: Regional hospitals often experience demand for platelets on an irregular basis. They are, however, required to stock some number of platelets (typically one A-unit and one O-unit) for emergencies; outdates are common, with discard rates sometimes >>50%. A simulation study was completed to determine the impact of replacing a (1A, 1O) inventory with 2 or 3 units of LtABO at regional hospitals. RESULTS: A significant decreases in wastage and shortage can be expected by replacing a (1A, 1O) inventory policy with 2 units of LtABO. In tested cases, a 2-unit LtABO dominated a (1A, 1O) policy, resulting in statistically fewer outdates and instances of shortage. Holding 3 units of LtABO, increases product availability, but results in an increase in outdates when compared to a (1A, 1O) policy. CONCLUSION: Providing LtABO platelets to smaller, regional hospitals will lower wastage rates and improve patient access to care, when compared to existing (1A, 1O) inventory policies.

HLA-haplotype redundancy and rareness in Canadian Blood Services' Stem Cell Registry and Cord Blood Bank: Novel metrics for optimizing utility.

BACKGROUND: The utility of unrelated donor registries that support allogeneic hematopoietic cell transplantation could be optimized through greater understanding of redundancy and rareness of HLA phenotypes. METHODS: HLA phenotype rareness was determined using known HLA haplotype frequencies. Donor redundancy was determined through pairwise comparison of donor HLA profiles within an inventory. RESULTS: Among 61,730 registrants in the Canadian Blood Services (CBS) Stem Cell Registry (SCR) with high resolution HLA typing at 5 loci, 6.6% of HLA phenotypes were redundant with variation across ethnic groups (8.3% of Caucasian phenotypes; 8% of Native American/First Nations, 4.4% of Asia-Pacific Islanders (API), 2.1% of Hispanic, 0.7% of African-American (AFA), and 4.5% of other ethnicities). A total of 18.5% of registrants had redundant HLA phenotypes with variation across ethnic groups. All 3716 cord blood units in the CBS's cord blood bank (CBB) had high resolution HLA typing at 5 loci and 202 units were redundant (5.4%) comprising 78 HLA phenotypes, with varying rareness. Repeated HLA phenotypes were from Caucasian donors (77%), multiple ethnicity (13%), API (9%), and AFA (1%). Registrants and CBUs with AFA ethnicity had the rarest phenotypes while Caucasian ethnicity was associated with the most common HLA phenotypes. CONCLUSIONS: Redundancy was greater in the SCR compared to the CBB and was most common with CAU ethnicity. Recruiting non-Caucasian registrants and continued cord blood banking should reduce redundancy. A sub-inventory of redundant donors and cord blood units could support new uses for donor-supported cellular therapies that do not require HLA matching.

From demand forecasting to inventory ordering decisions for red blood cells through integrating machine learning, statistical modeling, and inventory optimization.

BACKGROUND: The demand and supply of blood are highly variable over time. Blood inventory management that relies heavily on experience-based decisions may not be adaptive to real demand, leading to high operational costs, wastage, and shortages. METHODS: We combined statistical modeling, machine learning, and optimization methods to develop a data-driven demand forecasting and inventory management strategy for red blood cells (RBCs). We then used the strategy to inform daily blood orders. A secondary semi-weekly (twice per week) ordering strategy was developed to handle the last-mile split delivery problem for blood suppliers, characterized by multi-deliveries to the same location multiple times during a short period of time. Both strategies were evaluated using the TRUST database including all patient data across four hospitals in Hamilton, Ontario. RESULTS: We identified 227,944 RBC transfusions for 40,787 patients in Hamilton, Ontario from 2012 to 2018. The predicted daily demand from the hybrid demand forecasting model was not significantly different from the actual daily demand (paired t-test p-value = 0.163); however, the proposed daily ordering quantity from the model was significantly lower than the actual ordering quantity (p-value <0.001). The proposed daily ordering strategy reduced inventory levels by 38.4% without risk of shortages, leading to an overall cost reduction of 43.0% (95% confidence interval [CI]: 42.3%, 43.7%) compared with the actual cost. The semi-weekly ordering strategy reduced ordering frequency by 62.6% (95% CI: 61.5%, 63.7%). CONCLUSION: The proposed data-driven ordering strategy combining demand forecasting and inventory optimization can achieve significant cost savings for healthcare systems and blood suppliers.

The impact of donor ferritin testing on blood availability in Canada.

BACKGROUND AND OBJECTIVES: Iron depletion is a side effect of blood donation. Agencies have developed policies to test donors and to extend inter-donation intervals (IDIs) for individuals with low ferritin levels. Ferritin testing, however, has an impact on product availability due to longer IDIs and the effect of test results on donor behaviour. In this paper we apply a model to evaluate the impact of ferritin testing in the Canadian donor population on whole blood donations. MATERIALS AND METHODS: A discrete event simulation was adopted for the study. The model represents a population of individuals that donate blood, are tested for ferritin levels, and may exit the system. Data for the simulation was derived from operational data, donor research studies from Canadian Blood Services and previously published sources. RESULTS: Red cell collections will decline by at least 3.1% and could decline by as much as 19.2% after ferritin testing is put in place. Requirements for new donors could rise by as much as 36.0%. CONCLUSION: The impact of ferritin testing on repeat donor behaviour, rather than extensions to the mandated inter-donation interval, is the largest factor influencing declines in whole blood donations. Because behaviour changes following the receipt of a low ferritin result, blood agencies must ensure that donors with low ferritin are motivated to modify their lifestyle and, when healthy, return to the donor pool.

Estimating the impact on the inventory of implementing pathogen-reduced platelets in Canada.

BACKGROUND: Pathogen reduction (PR) technology will be implemented in pooled platelets in Canada. It is anticipated that PR platelets will be licensed in Canada for a maximum shelf life of 5 days, while non-treated apheresis platelet products will continue to be licensed for 7 days. STUDY DESIGN AND METHODS: This study evaluates the impact on inventory, wastage, and shortages of implementing PR platelets. A custom-built simulation model was used to represent a regional distribution network. Experiments with the model were used to estimate product wastage and shortages when a 5-day PR pooled platelet product is introduced alongside a 7-day apheresis platelet product. RESULTS: Pooled platelet waste and shortages both increase as pooled shelf life decreases. Apheresis platelets, however, show a different response: While shortages of apheresis platelets increase as the shelf life of pooled units decreases, apheresis waste declines as pooled shelf life decreases. CONCLUSION: Additional platelet collections will be necessary to accommodate the shorter PR platelet shelf life and to cover increased patient transfusion needs due to a lower platelet yield in PR units. Increases of 9% for pooled units and 6% for apheresis units beyond expected demand, were found to be sufficient to ensure a non-inferior level of customer service while minimizing waste.

Modeling rare blood in Canada.

BACKGROUND: Many countries maintain rare blood programs to provide access to blood for patients with complex serologies. These include a process to screen donors and a registry to record information about rare donors; blood agencies may also freeze some units. However, frozen blood is much more expensive than liquid blood. STUDY DESIGN AND METHODS: A two-phase approach to analysis was used to evaluate how rare a blood type must be before a frozen inventory is necessary and what screening rates are required to support a rare blood program. A simulation model was employed to evaluate the impact of inventory on patient access. RESULTS: Results suggested that, for 27 of 29 phenotypes managed by Canadian Blood Services, insufficient donors had been identified to ensure a stable inventory. Analytic results showed the screening rate necessary to ensure a stable inventory and the time frame to build a rare donor base. Twenty-nine simulation scenarios were executed to evaluate patient access to rare blood against inventory levels. Results show that some amount of frozen inventory is necessary for phenotypes rarer than 1 in 3000. However, holding more than two units apiece of O-, O+, A-, and A+ did not improve patient access. CONCLUSION: While some level of frozen blood is needed for rare blood, large inventories do not improve access. Modest amounts of frozen inventory, combined with increased door screening, provides the greatest chance of maximizing patient access.

Self-Reported Pain Intensity and Depressive Symptoms Among Community-Dwelling Older Adults with Schizophrenia Spectrum Disorders.

Older adults with schizophrenia have some of the highest rates of both medical and psychiatric comorbidities. Despite this, little is known about comorbid pain and depressive symptoms in schizophrenia research. This study aimed to examine the associations between levels of pain intensity and depressive symptoms among community-dwelling adults aged 50 years and older with schizophrenia spectrum disorders. Recruited from U.S. community mental health centers, participants reported on pain and depressive symptoms at the onset of the Helping Older People Experience Success (HOPES) study. Unadjusted and adjusted regression analyses were conducted. Higher pain intensity was associated with elevated depressive symptoms in all analyses, which is consistent with other studies in the general population. Given the widespread efforts to manage pain and related mental health complications in older adults without serious mental illnesses, it is likewise important that community-based mental health professionals monitor and address intense pain and related depressive symptoms among older adults with schizophrenia.

Designing the blood supply chain: how much, how and where?

BACKGROUND: The topology of the blood supply chain network can take different forms in different settings, depending on geography, politics, costs, etc. Many developed countries are moving towards centralized networks. The goal for all blood distribution networks, regardless of topology, remains the same: to satisfy demand at minimal cost and minimal wastage. STUDY DESIGN AND METHODS: Mathematically, the blood supply system design can be viewed as a location-allocation problem, where the aim is to find the optimal location of collection and production facilities and to assign hospitals to them to minimize total system cost. However, most location-allocation models in the blood supply chain literature omit several important aspects of the problem, such as selecting amongst differing methods of collection and production. In this paper, we present a location-allocation model that takes these factors into account to support strategic decision-making at different levels of centralization. RESULTS: Our approach is illustrated by a case study (Colombia) to redesign the national blood supply chain under a range of realistic travel time limitations. For each scenario, an optimal supply chain configuration is obtained, together with optimal collection and production strategies. We show that the total costs for the most centralized scenario are around 40% of the costs for the least centralized scenario. CONCLUSION: Centralized systems are more efficient than decentralized systems. However, the latter may be preferred for political or geographical reasons. Our model allows decision-makers to redesign the supply network per local circumstances and determine optimal collection and production strategies that minimize total costs.

Perceived Mindfulness and Depressive Symptoms Among People with Chronic Pain.

The study purpose was to evaluate pain catastrophizing and psychological distress as mediators for the relationship between perceived mindfulness and depressive symptoms in people with chronic pain. We conducted an online cross-sectional survey with 211 adults with chronic musculoskeletal pain recruited from U.S. clinics and community networks. A serial multiple mediation analysis was performed using ordinary least-squares regressions and a bootstrap testing approach. Pain catastrophizing and psychological distress, independently and jointly, mediated the relationship between mindfulness and depressive symptoms. Rehabilitation counseling professionals should consider targeting mindfulness, pain catastrophizing, and psychological distress in psychosocial treatment for people with chronic pain.

Determining the inventory impact of extended-shelf-life platelets with a network simulation model.

BACKGROUND: The regulatory shelf life for platelets (PLTs) in many jurisdictions is 5 days. PLT shelf life can be extended to 7 days with an enhanced bacterial detection algorithm. Enhanced testing, however, comes at a cost, which may be offset by reductions in wastage due to longer shelf life. This article describes a method for estimating systemwide reductions in PLT outdates after PLT shelf life is extended. STUDY DESIGN AND METHODS: A simulation was used to evaluate the impact of an extended PLT shelf life within a national blood network. A network model of the Canadian Blood Services PLT supply chain was built and validated. PLT shelf life was extended from 5 days to 6, 7, and 8 days and runs were completed to determine the impact on outdates. RESULTS: Results suggest that, in general, a 16.3% reduction in PLT wastage can be expected with each additional day that PLT shelf life is extended. Both suppliers and hospitals will experience fewer outdating units, but wastage will decrease at a faster rate at hospitals. No effect was seen by blood group, but there was some evidence that supplier site characteristics influences both the number of units wasted and the site's ability to benefit from extended-shelf-life PLTs. CONCLUSION: Extended-shelf-life PLTs will reduce wastage within a blood supply chain. At 7 days, an improvement of 38% reduction in wastage can be expected with outdates being equally distributed between suppliers and hospital customers.

Host associations and turnover of haemosporidian parasites in manakins (Aves: Pipridae).

Parasites of the genera Plasmodium and Haemoproteus (Apicomplexa: Haemosporida) are a diverse group of pathogens that infect birds nearly worldwide. Despite their ubiquity, the ecological and evolutionary factors that shape the diversity and distribution of these protozoan parasites among avian communities and geographic regions are poorly understood. Based on a survey throughout the Neotropics of the haemosporidian parasites infecting manakins (Pipridae), a family of Passerine birds endemic to this region, we asked whether host relatedness, ecological similarity and geographic proximity structure parasite turnover between manakin species and local manakin assemblages. We used molecular methods to screen 1343 individuals of 30 manakin species for the presence of parasites. We found no significant correlations between manakin parasite lineage turnover and both manakin species turnover and geographic distance. Climate differences, species turnover in the larger bird community and parasite lineage turnover in non-manakin hosts did not correlate with manakin parasite lineage turnover. We also found no evidence that manakin parasite lineage turnover among host species correlates with range overlap and genetic divergence among hosts. Our analyses indicate that host switching (turnover among host species) and dispersal (turnover among locations) of haemosporidian parasites in manakins are not constrained at this scale.

Resource predictability and specialization in avian malaria parasites.

We tested the hypothesis that avian haemosporidian (malaria) parasites specialize on hosts that can be characterized as predictable resources at a site in Amazonian Ecuador. We incorporated host phylogenetic relationship and relative abundance in assessing parasite specialization, and we examined associations between parasite specialization and three host characteristics - abundance, mass and longevity - using quantile regression, phylogenetic logistic regression and t-tests. Hosts of specialist malaria parasite lineages were on average more abundant than hosts of generalist parasite lineages, but the relationship between host abundance and parasite specialization was not consistent across analyses. We also found support for a positive association between parasite specialization and host longevity, but this also was not consistent across analyses. Nonetheless, our findings suggest that the predictability of a host resource may play a role in the evolution of specialization. However, we also discuss two alternative explanations to the resource predictability hypothesis for specialization: (i) that interspecific interactions among the parasites themselves might constrain some parasites to a specialist strategy, and (ii) that frequent encounters with multiple host species, mediated by blood-sucking insects, might promote generalization within this system.

Seasonal patterns in δ2 H values of multiple tissues from Andean birds provide insights into elevational migration.

Elevational migration is a widespread phenomenon in tropical avifauna but it is difficult to identify using traditional approaches. Hydrogen isotope (δ2 H) values of precipitation decrease with elevation so δ2 H analysis of multiple bird tissues with different isotopic incorporation rates may be a reliable method for characterizing seasonal elevational migration. Here we compare δ2 H values in metabolically inert (feathers and claws) and metabolically active (whole blood) tissues to examine whether an upslope migration occurs prior to the breeding season in the Yungas Manakin (Chiroxiphia boliviana). We compare results from C. boliviana with data from a known elevational migrant, the Streak-necked Flycatcher (Mionectes striaticollis). Opposite to our expectations, tissue δ2 H values increased over time, largely reflecting seasonal patterns in precipitation δ2 H rather than elevational effects; linear mixed-effects models with strongest support included ordinal date, tissue type, and elevation. This seasonal increase in precipitation δ2 H is a general phenomenon in both tropical and temperate mountain ranges. We use these data to propose a hypothetical framework that predicts different patterns in tissue δ2 H values collected in different seasons from residents and elevational migrants. This framework can serve as a reference for future studies that assess elevational migration in birds and other animals.

Reciprocal specialization in multihost malaria parasite communities of birds: a temperate-tropical comparison.

How specialization of consumers with respect to resources varies with respect to latitude is poorly understood. Coexistence of many species in the tropics might be possible only if specialization also increases. Alternatively, lower average abundance of more diverse biotic resources in the tropics might force consumers to become more generalized foragers. We examine levels of reciprocal specialization in an antagonistic system-avian malaria-to determine whether the number of host species used and/or parasite lineages harbored differ between a temperate and a tropical assemblage. We evaluate the results of network analysis, which can incorporate both bird and parasite perspectives on specialization in one quantitative index, in comparison to null models. Specialization was significantly greater in both sample sites than predicted from null models. We found evidence for lower per-host species parasite diversity in temperate compared to tropical birds. However, specialization did not differ between the tropical and temperate sites from the parasite perspective. We supplemented the network analysis with estimates of specialization that incorporate phylogenetic relationships of associates and found no differences between sites. Thus, our analyses indicate that specialization within an antagonistic host-parasite (resource-consumer) system varies little between tropical and temperate localities.

Determining staffing requirements for blood donor clinics: the Canadian Blood Services experience.

BACKGROUND: Canadian Blood Services runs approximately 16,000 donor clinics annually. While there were more than 220 different clinic configurations used in 2011 and 2012, 67% of all clinic configurations followed one of 51 standard models. As part of operational planning for current and future configurations it was necessary for Canadian Blood Services to calculate staffing requirements for standard clinic models. STUDY DESIGN AND METHODS: In this article we present a method that incorporates both cost control and impact on donor experience. We calculate staffing requirements to minimize costs, but adjust using queuing theory to ensure donor wait time metrics are met. The method can be applied in a wide variety of situations. RESULTS: Although developed for a particular study, the methods described in this article can be applied in a wide variety of situations. A case study in which the model is used to review existing staffing arrangements at Canadian Blood Services is presented. CONCLUSION: The staffing model can be used to balance the requirements of minimizing staffing costs with that of ensuring that donors do not suffer unnecessary delays. Moreover, in an example application, savings of 3.4% were identified through the modeling process.

Yasuní--a hotspot for jaguars Panthera onca (Carnivora: Felidae)? Camera-traps and jaguar activity at Tiputini Biodiversity Station, Ecuador.

Jaguars (Panthera onca) are the largest predator in lowland forests of Amazonia but there have been few studies on their occurrence and activity in such forests. Here, we used camera traps to document the occurrence and activity of jaguars within a local area (-650ha) of lowland forest of Eastern Ecuador, over two sample periods (2005-2008, 7 222 trap days; 2010-2012, 6 199 trap days). We accumulated 151 independent photos of jaguars (189 total photographs) that represented 21 different individuals, including 11 males (114 photographs), seven females (32 photographs), and three that could not be assigned to a sex. Individual jaguars varied in the number of months they were recorded in the area; ten were photographed in only one month; five were photographed over periods of 8 to 22 months; and five from 45 to 81 months. Capture rates across all camera stations averaged 10.6/1 000 trap days; capture rates did not differ between the two sample periods. Male jaguars were more active during the day (06:00am-18:00pm; 71% of photographs), whereas females were equally active during the day and night. Monthly activity was variable but showed no consistent pattern. Although the study area is much smaller than typical home ranges of jaguars, the area is clearly visited by a large number of different individuals, some of whom repeatedly visit the area, indicating that it forms part of their home range. Other individuals likely were simply passing through the area. Based on the number of jaguars recorded during this study, it is clear that the region is an important area for conservation. Continued protection will be needed to ensure that populations ofjaguars and other species remain viable.