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For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 × 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10(-8), 3.66 × 10(-9), and 3.04 × 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10(-6) and 1.42 × 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.

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Study Objective In this study, we evaluated (1) trauma under-triage by age group; (2) the association between age and serious injury after accounting for other field triage criteria and confounders; and (3) the potential impact of a mandatory age triage criterion for field triage. Methods This was a retrospective cohort study of injured children and adults transported by 48 EMS agencies to 105 hospitals in 6 regions of the Western U.S. from 2006 through 2008. We used probabilistic linkage to match EMS records to hospital records, including: trauma registries, state discharge databases and emergency department databases. The primary outcome measure was serious injury, as measured by an Injury Severity Score (ISS) ≥ 16. We assessed under-triage (ISS ≥ 16 and triage-negative or transport to a non-trauma center) by age decile and used multivariable logistic regression models to estimate the association (linear and non-linear) between age and ISS ≥ 16, adjusted for important confounders. We also evaluated the potential impact of age on triage efficiency and trauma center volume. Results 260,027 injured patients were evaluated and transported by EMS over the 3-year study period. Under-triage increased for patients over 60 years of age, reaching approximately 60% for those older than 90 years. There was a strong non-linear association between age and ISS ≥ 16. For patients not meeting other triage criteria, the probability of serious injury was most notable after 60 years. A mandatory age triage criterion would have decreased under-triage at the expense of over-triage, with one ISS ≥ 16 patient identified for every 60–65 additional patients transported to major trauma centers. Conclusion Trauma under-triage increases in patients older than 60 years. While the probability of serious injury increases among triage-negative patients with increasing age, the use of a mandatory age triage criterion appears inefficient for improving field triage.

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