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.

Japanese whalers use the electric lance as a secondary method of killing minke whales (Balaenoptera acutorostrata). The lances are dropped into the body, and currents varying between 2.2 and 14. OA, with a mean of 6.8A, are applied.

When currents of 5A were applied to the carcasses of dead whales, varying in size from 1.8 to 15.7m in length, no current densities induced in the target organs were sufficient to cause either insensibility (10mA cm−2 in the brain), or to cause ventricular fibrillation (0.5mA cm−2 in the heart), except in a few cases where electrodes were specifically placed to span the heart. When electrodes were placed in positions normally used in whaling operations, no current densities were produced which would have been sufficient to cause brain and cardiac dysfunction.

Further investigations on changes in current density with time post mortem after application of a controlled current of 5A showed, during a 60 hour period, a fourfold increase in the current density in the heart, and more than a twofold increase in the brain. Thus contrary to previous criticisms, if these studies had been carried out on live animals, all current densities would have been below threshold values.

There are no records of signs of epileptic form seizure, which are associated with an effective electrical stun, in whales subjected to the electric lance.

It is concluded that the electric lance as used in whaling operations is ineffective and likely to cause extra pain and suffering to an already distressed animal.

Valproate is widely used in psychiatry and neurology, including off-label use. Here we consider its potential benefits and risks, particularly for women of childbearing potential, and the evidence that clinical guidelines are adhered to. Finally, we consider the implications for clinical practice and research into its efficacy in off-label indications.

There is emerging evidence linking fruit and vegetable consumption and cognitive function. However, studies focusing on the nutrients underlying this relationship are lacking. We aim to examine the association between plasma nutrients and cognition in a population at risk for cognitive decline with a suboptimal diet. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial is a randomized controlled intervention that examines the effects of the MIND diet to prevent cognitive decline. The primary outcome is global cognition. A multivariate linear model was used to investigate the association between blood nutrients and global and/or domain-specific cognition. The model was adjusted for age, sex, education, study site, smoking status, cognitive activities and physical activities. High plasma α-carotene was associated with better global cognition. Participants in the highest tertile of plasma α-carotene had a higher global cognition z score of 0⋅17 when compared with individuals in the lowest tertile (P 0⋅002). Circulating α-carotene levels were also associated with higher semantic memory scores (P for trend 0⋅007). Lutein and zeaxanthin (combined) was positively associated with higher semantic memory scores (P for trend 0⋅009). Our study demonstrated that higher α-carotene levels in blood were associated with higher global cognition scores in a US population at risk for cognitive decline. The higher α-carotene levels in blood reflected greater intakes of fruits, other types of vegetables and lesser intakes of butter and margarine and meat. The higher circulating levels of lutein plus zeaxanthin reflected a dietary pattern with high intakes of fruits, green leafy, other vegetables and cheese, and low consumption of fried foods. Objective nutrient markers in the blood can better characterize dietary intake, which may facilitate the implementation of a tailored dietary intervention for the prevention of cognitive decline.

Recent research in American politics demonstrates that despite gender-based partisan sorting, gender gaps in policy preferences persist within political parties—particularly among Republicans. Republican women report significantly more moderate views than their male counterparts across a range of policy areas. These gaps are largely attributable to gender differences in beliefs about the appropriate scope of government and attitudes toward gender-based inequality. Arguably, gender has become a more salient feature of American elections in recent years, and this heightened salience raises questions about whether these within-party gender gaps are stable over time or vary across campaign contexts. We use survey data from the 2012 and 2016 American National Election Study to evaluate whether gender gaps in policy preferences are stable across elections or if the 2016 election context affected the magnitude of gender differences in policy preferences. We find that gender gaps in policy preferences within political parties are fairly stable across the two electoral periods.

This Research Reflection provides an overview of three interrelated topics: (i) lameness in dairy cows, demonstrating the underpinning importance of the condition, (ii) dairy farmer detection, diagnosis and treatment of lameness and associated foot lesions as well as dairy farmer perceptions towards the condition and (iii) lameness detection technologies, and their potential application on farm to automate the detection of lameness in commercial dairy herds. The presented literature clearly demonstrates that lameness is a major health issue in dairy herds, compromising dairy cow welfare and productivity, and resulting in significant economic implications for dairy farmers. Despite this, dairy farmers fail to perceive lameness as a serious threat to their dairy business. This restricted perception of the importance of lameness may be a product of limited ability to detect lame cows. Many automated lameness detection technologies have been proposed to assist dairy farmers in managing their herds. However, limitations such as cost, performance and dairy farmer perception of the usefulness of these technologies, has lead to poor uptake. It can, therefore, be concluded that there is a need to more thoroughly evaluate the effectiveness of these technologies under on-farm conditions, potentially in the form of a demonstration farm network. This will allow generation of the necessary data required to show dairy farmers that these technologies are reliable and are economically rational for their dairy business.

The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.

The dehydration of pure and waste gypsums has been examined using in situ synchrotron angledispersive X-ray diffraction. Pure gypsum was studied under a number of defined environments; various industrial waste gypsums were also studied under a common standard environment. It is found that the dehydration of gypsum to anhydrite proceeds via the hemihydrate and γ-anhydrite phases and the interplay and behaviour of these phases has been determined by full structural ‘Rietveld’ refinement. In the study of the pure gypsum system, the hemihydrate structure is shown to be preserved as water is lost. A ‘zero-water hemihydrate’ is observed before refinement in the higher symmetry γ-anhydrite cell is possible. The waste gypsum materials studied showed significant differences in the temperatures at which key transformation events occurred; these observations raise implications concerning the re-use of by-product gypsum materials. Finally, high temperature data are re-examined in the search for a variation of the anhydrite structure.

Spherical coordinate systems, which are ubiquitous in astronomy, cannot be shown without distortion on flat, two-dimensional surfaces. This poses challenges for the two complementary phases of visual exploration—making discoveries in data by looking for relationships, patterns, or anomalies—and publication—where the results of an exploration are made available for scientific scrutiny or communication. This is a long-standing problem, and many practical solutions have been developed. Our allskyVR approach provides a workflow for experimentation with commodity virtual reality head-mounted displays. Using the free, open source s2plot programming library, and the A-FrameWebVR browser-based framework, we provide a straightforward way to visualise all-sky catalogues on a user-centred, virtual celestial sphere. The allskyVR distribution contains both a quickstart option, complete with a gaze-based menu system, and a fully customisable mode for those who need more control of the immersive experience. The software is available for download from https://github.com/cfluke/allskyVR.