Availability of 8/8 HLA-allele matched unrelated donors (URDs) is a barrier for ethnic and racial minorities. We prospectively evaluated receipt of 8/8 HLA-allele matched URD or either 7/8 URD or cord blood (CB) transplants by patient ancestry from 2005 to 2017. Matched URDs were given priority if they were available. Of 1312 patients, 723 (55%) received 8/8 URD, 219 (17%) 7/8 URD, 319 (24%) CB, and 51 (4%) had no 7/8 or 8/8 URD or CB graft. Europeans were more likely to receive an 8/8 URD transplant than non-Europeans (67% vs 33%) and less likely to have no URD or CB graft (1% vs 9%). Southern Europeans received 8/8 URD transplants (41%) at rates similar to those of Asians (34%) and white Hispanics (35%); Africans were the least likely (18%) to undergo 8/8 URD transplantation. CB and 7/8 URDs extended transplant access to all groups. In 742 recent patients, marked racial disparity in 8/8 URD access between groups observed in earlier years persisted with only a modest increase in the percentage of 8/8 URD transplants. Of 78 recent African patients, 46% received a CB transplant and 14% had no 7/8 or 8/8 URD or CB graft. Increasing registry size has not resolved the racial disparity in URD access, which emphasizes the importance of alternative graft sources.
A strategy to rapidly determine if a matched unrelated donor (URD) can be secured for allograft recipients is needed. We sought to validate the accuracy of (1) HapLogic match predictions and (2) a resultant novel Search Prognosis (SP) patient categorization that could predict 8/8 HLA-matched URD(s) likelihood at search initiation. Patient prognosis categories at search initiation were correlated with URD confirmatory typing results. HapLogic-based SP categorizations accurately predicted the likelihood of an 8/8 HLA-match in 830 patients (1530 donors tested). Sixty percent of patients had 8/8 URD(s) identified. Patient SP categories (217 very good, 104 good, 178 fair, 33 poor, 153 very poor, 145 futile) were associated with a marked progressive decrease in 8/8 URD identification and transplantation. Very good to good categories were highly predictive of identifying and receiving an 8/8 URD regardless of ancestry. Europeans in fair/poor categories were more likely to identify and receive an 8/8 URD compared with non-Europeans. In all ancestries very poor and futile categories predicted no 8/8 URDs. HapLogic permits URD search results to be predicted once patient HLA typing and ancestry is obtained, dramatically improving search efficiency. Poor, very poor, andfutile searches can be immediately recognized, thereby facilitating prompt pursuit of alternative donors.
The relationship of carpal morphology to ecology and habitat is under studied in carnivorans and more generally in mammals. Here, we use 3D‐scanning techniques to assess the usefulness of a carpal bone, the scapholunar, in carnivorans to reflect ecology and habitat, and to reconstruct the ecology of five extinct carnivorans from two fossil sites: Rancho La Brea and Natural Trap Cave. We 3D‐scanned scapholunars and measured articular surface areas and angles between articular facets using GeoMagic and Rhino 3D‐software. We analyzed the difference in these metrics using multivariate analysis of variance and discriminant function analysis. Results show that the scapholunar reflects ecological signal, with clear groupings of cursorial carnivorans and grappling/climbing carnivorans; however, phylogenetic signal was also present in the results with hyaenids, canids, and large felids in distinct morphospaces. Extinct species Miracinonyx trumani (American cheetah) and Smilodon fatalis (sabertooth cat) showed surprising results with M. trumani grouping with pantherines instead of Acinonyx or Puma, suggesting it runs but still retains the ability to grapple prey. S. fatalis groups with pantherines, but also shows some unique adaptations, suggesting it had a different range of wrist motion than living cats. Overall, the scapholunar is a good indicator of ecology and functional morphology and can be another tool to use in modern and fossil carnivorans to reconstruct extinct ecologies and locomotor behaviors.
Genome wide association studies (GWAS) have been used to search for associations between genetic variants and a phenotypic trait of interest. New technologies, such as next-generation sequencing, hold the potential to revolutionize GWAS. However, millions of polymorphisms are identified with next-generation sequencing technology. Consequently, researchers must be careful when performing such a large number of statistical tests, and corrections are typically made to account for multiple testing. Additionally, for typical GWAS, the p value cutoff is set quite low (approximately <10−8). As a result of this p value stringency, it is likely that there are many true associations that do not meet this threshold. To account for this we have incorporated a priori biological knowledge to help identify true associations that may not have reached statistical significance. We propose the application of a pipelined series of statistical and bioinformatic methods, to enable the assessment of the association of genetic polymorphisms with a disease phenotype--here, hypertension--as well as the identification of statistically significant pathways of genes that may play a role in the disease process.
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