OBJECTIVES/GOALS: Assess the association of PK-related single nucleotide variants (SNVs) with the risk of bleeding from DOACs in non-valvular AF patients. METHODS/STUDY POPULATION: A retrospective cohort study was carried out with 2,364 Caucasians with non-valvular AF and treated with rivaroxaban or apixaban. Patients were genotyped as part of the genomic biobank at the University of Michigan Health System. The primary endpoint was a composite of major and clinically relevant non-major (CRNM) bleeding. Cox proportional hazards regression with time-varying analysis assessed the association of 8 SNVs in 5 PK genes (ABCB1, ABCG2, CYP3A4, CYP3A5, CYP2J2) with the risk of bleeding from DOACs in unadjusted and covariate-adjusted models. Six tests were performed as 3 of the SNVs are in the same haplotype. P-values below the Bonferroni-corrected level of 8.33e-3 were considered statistically significant. RESULTS/ANTICIPATED RESULTS: A total of 412 (17.4%) major and CRNM bleeding events occurred over 2.27 ± 2.03 years of follow-up. None of the PK SNVs were significantly associated with bleeding risk on DOACs in both unadjusted and covariate-adjusted Cox regression models. DISCUSSION/SIGNIFICANCE: The effects of these eight genetic variants on exposure to DOACs may not be strong enough to translate into differences in clinical outcomes. Especially if the genetic inheritance underlying the risk of bleeding from DOACs is polygenic, reinforcing the need for further genomic studies on this subject.

Observational evidence in space and astrophysical plasmas with a long collisional mean free path suggests that more massive charged particles may be preferentially heated. One possible mechanism for this is the turbulent cascade of energy from injection to dissipation scales, where the energy is converted to heat. Here we consider a simple system consisting of a magnetized plasma slab of electrons and a single ion species with a cross-field density gradient. We show that such a system is subject to an electron drift wave instability, known as the universal instability, which is stabilized only when the electron and ion thermal speeds are equal. For unequal thermal speeds, we find from quasilinear analysis and nonlinear simulations that the instability gives rise to turbulent energy exchange between ions and electrons that acts to equalize the thermal speeds. Consequently, this turbulent heating tends to equalize the component temperatures of pair plasmas and to heat ions to much higher temperatures than electrons for conventional mass-ratio plasmas.

In bioassays, rice (Oryza sativa L.) recovery from metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide] injury tended to be slower in flooded rice, but was not significantly different from the recovery rate in a nonflooded rice. In soils treated with 1 ppm (w/w) metolachlor and incubated in constant-temperature chambers, the half-life of metolachlor was shorter at 40 C than at 30 C. The degradation rate of metolachlor was not significantly correlated with declining moisture potentials in the range of −30 to −80 kPa. The CO2 evolution from metolachlor-treated soil was negatively correlated with incubation time and positively correlated to declining moisture levels. In a field study, metolachlor, as determined by bioassay, was mobile in a Taloka silt loam soil profile. After being incorporated to 7.5 cm, it became evenly distributed in the top 15 cm of the soil profile within 18 days. Metolachlor adsorption was positively correlated with clay and organic carbon content.