Bayer (Germany)

The continuous growth in both the number of phenotypic records and the range of traits included in beef cattle genetic evaluations poses substantial statistical and computational challenges for the estimation of genetic and residual (co)variance matrices required for breeding value estimation. Structural equation models (SEM), implemented using either factor analysis (FA) or recursive model (REC) structures, provide a flexible framework to model genetic and residual (co)variance matrices while yielding more parsimonious and computationally efficient parameterizations. Here, SEM was applied to estimate parameters for growth and ultrasound-measured carcass traits in beef cattle. The dataset comprised 2942 animals, and six traits were evaluated using standard multiple-trait mixed models (SMTM) and SEM. We considered FA and REC models implemented with six alternative parameterizations, in which random effects were represented as linear combinations of fewer unobservable random variables. Relative to the SMTM, both the model with two factors in the genetic covariance matrix (FA2G) and the model in which six recursive effects were constrained to zero in the residual covariance matrix (REC1) demonstrated a strong ability to capture genetic variability, as reflected by comparable heritability estimates. Correlations between estimated breeding values (EBV) for the same traits across models were consistently high, ranging from 0.94 to 1.00, indicating strong agreement among model estimates. The FA2G model was the most parsimonious in terms of the effective number of parameters (pD), with 431.2 pD, corresponding to a reduction of 25.3 parameters relative to the SMTM. The REC1 model also emerged as a competitive alternative for this dataset, exhibiting a lower pD (443.6) than the SMTM (456.5) and the most favorable deviance information criterion among all models evaluated (e.g., 37,868.6 for REC1 versus 37,874.7 for SMTM). Overall, these results demonstrate that mixed-effects multi-trait models for beef cattle genetic evaluation can be effectively implemented using FA or REC structures, which provide parsimonious representations of the underlying covariance patterns while maintaining high agreement in EBV.

Introduction: The Phase III OCEANIC-STROKE trial (NCT05686070) investigates whether the activated Factor XI inhibitor asundexian combined with antiplatelet therapy (APT) reduces the risk of recurrent IS in patients with non-cardioembolic IS (NCIS) or high-risk TIA compared with APT alone. The objective of the present investigation was to describe the characteristics and outcomes of patients compatible with the OCEANIC-STROKE trial population among patients hospitalized for a first-ever NCIS or TIA in real-world settings in Japan. Methods: ASTRIS Japan was a retrospective cohort study using a Japanese nationwide hospital database (RWD Co.). Adults with a first hospitalization for NCIS or TIA between Jan 1, 2015 and Oct 29, 2022 were identified. Among them, a subset of patients compatible with the OCEANIC-STROKE trial population was selected by applying the emulated eligibility criteria of the OCEANIC-STROKE trial. Clinical events were assessed after discharge of the index NCIS or TIA hospitalization. Events that occurred during the hospitalization for index stroke were not considered. Results: In total, 18,719 patients with NCIS or TIA were identified. Of these, 5778 patients were identified for the OCEANIC-STROKE-compatible cohort (Fig 1). The median (Q1, Q3) length of follow-up was 715 (170.8, 1355.3) days. Table 1 shows the baseline characteristics of the OCEANIC-STROKE-compatible cohort. Mean±SD age was 73.1±11.9 years and 37.7% were female. Most (70.4%) patients initiated APT within 2 days of hospital admission. Single APT was used in 4830 (83.6%) patients and dual APT was used in 1991 (34.5%) patients, and were not mutually exclusive. Rates (per 1000 patient-years [95% CI]) of IS, hemorrhagic stroke, and major bleeding were 106.1 (100.0–112.1), 8.9 (7.3–10.5), and 47.2 (43.4–51.0), respectively. Compared with the overall NCIS or TIA cohort, a numerically higher rate of IS and a numerically lower rate of major bleeding were observed in the OCEANIC-STROKE-compatible cohort up to 5 years (Fig 2). Baseline characteristics of the overall NCIS or TIA and the OCEANIC-STROKE-compatible cohorts will be compared with those of patients in the OCEANIC-STROKE trial. Conclusions: In real-world settings, patients compatible with the enrolled OCEANIC-STROKE trial population had a high risk of IS recurrence following hospital discharge in Japan. Further improvements in secondary stroke prevention strategies are merited.