Background: A phase 3 trial, ADVANCE (NCT03777059), demonstrated that atogepant, an oral, CGRP receptor antagonist dosed once daily, results in clinically meaningful reductions in mean monthly migraine days. This open-label extension for ADVANCE trial completers evaluated long-term safety and tolerability of atogepant over 40-weeks. Methods: Participants in this trial (NCT03939312), rolled over from the ADVANCE trial, were treated with atogepant 60mg once daily for 40-weeks, with a 4-week safety follow-up. Only safety data were collected. Results: 685 participants took at least one dose of study drug, 74.6% completed the 40-week treatment period; mean age of 41.8 years, 88.2% female, 84.4% white, and mean BMI of 30.58 kg/m2. Mean (SD) treatment duration was 233.6 (89.32) days. 62.5% of participants experienced a treatment-emergent adverse event (TEAE), with 8.8% considered treatment-related by the investigator; serious adverse events (SAEs) occurred in 3.4% of participants, none were treatment-related. The most frequent AEs leading to discontinuation was nausea (0.4%, n=3); the most frequent TEAEs observed included upper respiratory tract infection (5.5%, n=38) and urinary tract infection (5.3%, n=36). No deaths or hepatic safety issues were observed. Conclusions: Safety results are consistent with known safety profile of atogepant and support long-term safety and tolerability of once daily dosing of atogepant 60mg.

Attitudinal differences between urban and rural voters in America have been in the spotlight in recent years and engaging rural populations politically has been growing in importance, particularly since the 2016 presidential election. Meanwhile, social and geographic sorting is increasing the salience of a rural identity that drives distinct policy preferences. While recent research has examined how rural identities drive social and economic policy preferences, rural Americans are also particularly relevant to the fate of environmental policy. Farmers, ranchers, and forest landowners manage huge portions of American lands and watersheds and are important stakeholders in the implementation of environmental policies. Despite this, the environmental policy preferences of rural Americans have received little attention from the research community. This study fills a gap in the literature by investigating how collective identities among rural Americans drive environmental policy preferences. Through eight focus groups and thirty-five interviews with rural voters across America (total n=105), this study explores how four components of rural American identity—connection to nature, resentment/disenfranchisement, rootedness, and self-reliance—inform specific rural perspectives on environmental policy. The findings have implications for how to best design, communicate, and implement environmental policies in a way that can better engage rural Americans on this issue.

In this paper, we describe the system design and capabilities of the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope at the conclusion of its construction project and commencement of science operations. ASKAP is one of the first radio telescopes to deploy phased array feed (PAF) technology on a large scale, giving it an instantaneous field of view that covers $31\,\textrm{deg}^{2}$ at $800\,\textrm{MHz}$. As a two-dimensional array of 36$\times$12 m antennas, with baselines ranging from 22 m to 6 km, ASKAP also has excellent snapshot imaging capability and 10 arcsec resolution. This, combined with 288 MHz of instantaneous bandwidth and a unique third axis of rotation on each antenna, gives ASKAP the capability to create high dynamic range images of large sky areas very quickly. It is an excellent telescope for surveys between 700 and $1800\,\textrm{MHz}$ and is expected to facilitate great advances in our understanding of galaxy formation, cosmology, and radio transients while opening new parameter space for discovery of the unknown.

The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with $\sim$ 15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination $+41^\circ$ made over a 288-MHz band centred at 887.5 MHz.

In this paper we examine the role of weak magnetic fields in breaking Kelvin’s circulation theorem and in vortex breakup in two-dimensional magnetohydrodynamics for the physically important case of a fluid with low magnetic Prandtl number (low $Pm$). We consider three canonical inviscid solutions for the purely hydrodynamical problem, namely a Gaussian vortex, a circular vortex patch and an elliptical vortex patch. We examine how magnetic fields lead to an initial loss of circulation $\unicode[STIX]{x1D6E4}$ and attempt to derive scaling laws for the loss of circulation as a function of field strength and diffusion as measured by two non-dimensional parameters. We show that for all cases the loss of circulation depends on the integrated effects of the Lorentz force, with the patch cases leading to significantly greater circulation loss. For the case of the elliptical vortex, the loss of circulation depends on the total area swept out by the rotating vortex, and so this leads to more efficient circulation loss than for a circular vortex.

Background: Approximately 12-15% of patients with intracranial aneurysms (IA) have affected first-degree relatives, and are considered to have familial intracranial aneurysms (FIA). Individuals with FIA are at higher risk for aneurysm formation and subarachnoid hemorrhage. THSD1 is the only gene to be associated with nonsyndromic FIA at this time. Our study aims to find rare DNA variants that are major risk factors for FIA in our cohort of patients. Methods: To date we have enrolled 37 affected and 31 unaffected people from 16 families. We have done exome or genome sequencing on at least 1 person from each of 12 families. Results: A rare p.(R686W) variant in THSD1 was found in 1/12 families, but did not cosegregate fully with disease. While less attractive as the primary cause of FIA, we cannot rule out the potential modifying effects of THSD1 p.(R686W) in this family. A second candidate, an extracellular matrix gene within a chromosomal region previously implicated by familial mapping studies, contains rare variants in 4/12 of our families. All four variants are predicted to be damaging. Conclusions: Alongside environmental risk factors, individual FIA families may also have complex rare variant contributions to their disease, such as digenic and multi-locus contributions.

A generalization of Serre’s Conjecture asserts that if $F$ is a totally real field, then certain characteristic $p$ representations of Galois groups over $F$ arise from Hilbert modular forms. Moreover, it predicts the set of weights of such forms in terms of the local behaviour of the Galois representation at primes over $p$. This characterization of the weights, which is formulated using $p$-adic Hodge theory, is known under mild technical hypotheses if $p>2$. In this paper we give, under the assumption that $p$ is unramified in $F$, a conjectural alternative description for the set of weights. Our approach is to use the Artin–Hasse exponential and local class field theory to construct bases for local Galois cohomology spaces in terms of which we identify subspaces that should correspond to ones defined using $p$-adic Hodge theory. The resulting conjecture amounts to an explicit description of wild ramification in reductions of certain crystalline Galois representations. It enables the direct computation of the set of Serre weights of a Galois representation, which we illustrate with numerical examples. A proof of this conjecture has been announced by Calegari, Emerton, Gee and Mavrides.