An infection prevention bundle that consisted of the development of a response team, public–academic partnership, daily assessment, regular testing, isolation, and environmental controls was implemented in 26 skilled nursing facilities in Detroit, Michigan (March 2020–April 2021). This intervention was associated with sustained control of severe acute respiratory coronavirus virus 2 infection among residents and staff.

The Australian SKA Pathfinder (ASKAP) radio telescope has carried out a survey of the entire Southern Sky at 887.5 MHz. The wide area, high angular resolution, and broad bandwidth provided by the low-band Rapid ASKAP Continuum Survey (RACS-low) allow the production of a next-generation rotation measure (RM) grid across the entire Southern Sky. Here we introduce this project as Spectral and Polarisation in Cutouts of Extragalactic sources from RACS (SPICE-RACS). In our first data release, we image 30 RACS-low fields in Stokes I, Q, U at 25$^{\prime\prime}$ angular resolution, across 744–1032 MHz with 1 MHz spectral resolution. Using a bespoke, highly parallelised, software pipeline we are able to rapidly process wide-area spectro-polarimetric ASKAP observations. Notably, we use ‘postage stamp’ cutouts to assess the polarisation properties of 105912 radio components detected in total intensity. We find that our Stokes Q and U images have an rms noise of $\sim$80 $\unicode{x03BC}$Jy PSF$^{-1}$, and our correction for instrumental polarisation leakage allows us to characterise components with $\gtrsim$1% polarisation fraction over most of the field of view. We produce a broadband polarised radio component catalogue that contains 5818 RM measurements over an area of $\sim$1300 deg$^{2}$ with an average error in RM of $1.6^{+1.1}_{-1.0}$ rad m$^{-2}$, and an average linear polarisation fraction $3.4^{+3.0}_{-1.6}$ %. We determine this subset of components using the conditions that the polarised signal-to-noise ratio is $>$8, the polarisation fraction is above our estimated polarised leakage, and the Stokes I spectrum has a reliable model. Our catalogue provides an areal density of $4\pm2$ RMs deg$^{-2}$; an increase of $\sim$4 times over the previous state-of-the-art (Taylor, Stil, Sunstrum 2009, ApJ, 702, 1230). Meaning that, having used just 3% of the RACS-low sky area, we have produced the 3rd largest RM catalogue to date. This catalogue has broad applications for studying astrophysical magnetic fields; notably revealing remarkable structure in the Galactic RM sky. We will explore this Galactic structure in a follow-up paper. We will also apply the techniques described here to produce an all-Southern-sky RM catalogue from RACS observations. Finally, we make our catalogue, spectra, images, and processing pipeline publicly available.

Some charities are much more cost-effective than other charities, which means that they can save many more lives with the same amount of money. Yet most donations do not go to the most effective charities. Why is that? We hypothesized that part of the reason is that people underestimate how much more effective the most effective charities are compared with the average charity. Thus, they do not know how much more good they could do if they donated to the most effective charities. We studied this hypothesis using samples of the general population, students, experts, and effective altruists in five studies. We found that lay people estimated that among charities helping the global poor, the most effective charities are 1.5 times more effective than the average charity (Studies 1 and 2). Effective altruists, in contrast, estimated the difference to be factor 50 (Study 3) and experts estimated the factor to be 100 (Study 4). We found that participants donated more to the most effective charity, and less to an average charity, when informed about the large difference in cost-effectiveness (Study 5). In conclusion, misconceptions about the difference in effectiveness between charities is thus likely one reason, among many, why people donate ineffectively.

The Variables and Slow Transients Survey (VAST) on the Australian Square Kilometre Array Pathfinder (ASKAP) is designed to detect highly variable and transient radio sources on timescales from 5 s to $\sim\!5$ yr. In this paper, we present the survey description, observation strategy and initial results from the VAST Phase I Pilot Survey. This pilot survey consists of $\sim\!162$ h of observations conducted at a central frequency of 888 MHz between 2019 August and 2020 August, with a typical rms sensitivity of $0.24\ \mathrm{mJy\ beam}^{-1}$ and angular resolution of $12-20$ arcseconds. There are 113 fields, each of which was observed for 12 min integration time, with between 5 and 13 repeats, with cadences between 1 day and 8 months. The total area of the pilot survey footprint is 5 131 square degrees, covering six distinct regions of the sky. An initial search of two of these regions, totalling 1 646 square degrees, revealed 28 highly variable and/or transient sources. Seven of these are known pulsars, including the millisecond pulsar J2039–5617. Another seven are stars, four of which have no previously reported radio detection (SCR J0533–4257, LEHPM 2-783, UCAC3 89–412162 and 2MASS J22414436–6119311). Of the remaining 14 sources, two are active galactic nuclei, six are associated with galaxies and the other six have no multi-wavelength counterparts and are yet to be identified.

We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers $270 \,\mathrm{deg}^2$ of an area covered by the Dark Energy Survey, reaching a depth of 25–30 $\mu\mathrm{Jy\ beam}^{-1}$ rms at a spatial resolution of $\sim$ 11–18 arcsec, resulting in a catalogue of $\sim$ 220 000 sources, of which $\sim$ 180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.

The field of sclerochronology has long been known to paleobiologists. Yet, despite the central role of growth rate, age, and body size in questions related to macroevolution and evolutionary ecology, these types of studies and the data they produce have received only episodic attention from paleobiologists since the field's inception in the 1960s. It is time to reconsider their potential. Not only can sclerochronological data help to address long-standing questions in paleobiology, but they can also bring to light new questions that would otherwise have been impossible to address. For example, growth rate and life-span data, the very data afforded by chronological growth increments, are essential to answer questions related not only to heterochrony and hence evolutionary mechanisms, but also to body size and organism energetics across the Phanerozoic. While numerous fossil organisms have accretionary skeletons, bivalves offer perhaps one of the most tangible and intriguing pathways forward, because they exhibit clear, typically annual, growth increments and they include some of the longest-lived, non-colonial animals on the planet. In addition to their longevity, modern bivalves also show a latitudinal gradient of increasing life span and decreasing growth rate with latitude that might be related to the latitudinal diversity gradient. Is this a recently developed phenomenon or has it characterized much of the group's history? When and how did extreme longevity evolve in the Bivalvia? What insights can the growth increments of fossil bivalves provide about hypotheses for energetics through time? In spite of the relative ease with which the tools of sclerochronology can be applied to these questions, paleobiologists have been slow to adopt sclerochronological approaches. Here, we lay out an argument and the methods for a path forward in paleobiology that uses sclerochronology to answer some of our most pressing questions.

Debate about the nature of climate and the magnitude of ecological change across Australia during the last glacial maximum (LGM; 26.5–19 ka) persists despite considerable research into the late Pleistocene. This is partly due to a lack of detailed paleoenvironmental records and reliable chronological frameworks. Geochemical and geochronological analyses of a 60 ka sedimentary record from Brown Lake, subtropical Queensland, are presented and considered in the context of climate-controlled environmental change. Optically stimulated luminescence dating of dune crests adjacent to prominent wetlands across North Stradbroke Island (Minjerribah) returned a mean age of 119.9 ± 10.6 ka; indicating relative dune stability soon after formation in Marine Isotope Stage 5. Synthesis of wetland sediment geochemistry across the island was used to identify dust accumulation and applied as an aridification proxy over the last glacial-interglacial cycle. A positive trend of dust deposition from ca. 50 ka was found with highest influx occurring leading into the LGM. Complexities of comparing sedimentary records and the need for robust age models are highlighted with local variation influencing the accumulation of exogenic material. An inter-site comparison suggests enhanced moisture stress regionally during the last glaciation and throughout the LGM, returning to a more positive moisture balance ca. 8 ka.

OBJECTIVES/GOALS: Neuroblastoma (NB) is an embryonal cancer of the sympathetic nervous system that affects mostly infants and young children. The complex genetic background present across NB patients results in diverse clinical response and difficulty in individualizing therapy. Currently, NB patients undergo a regimen of genotoxic chemotherapeutics, radiation therapy, and new immunotherapy that, while effective, has significant side effects, including excruciating pain. One promising avenue for targeted therapy in neuroblastoma focuses on anaplastic lymphoma kinase (ALK), a cell surface neural receptor tyrosine kinase. We previously identified activating point mutations within the tyrosine kinase domain of ALK as the primary cause of hereditary NB, and we and others subsequently showed that these same alterations are the most common somatic single-nucleotide mutations in the sporadic forms of the disease. Crizotinib, a first-generation small molecule ATP-competitive inhibitor of the ALK tyrosine kinase, showed limited anti-tumor activity in patients with relapsed NB harboring ALK F1174 and F1245 mutations. We have demonstrated that lorlatinib, a novel ATP-competitive ALK inhibitor, overcomes this de novo resistance in preclinical models of ALK-driven NB. Recent clinical trials with lorlatinib in patients with non-small cell lung cancer harboring an ALK fusion, and in patients with NB harboring ALK mutations show the emergence of multiple or compound ALK mutations as a mechanism of resistance. We postulate that these compound mutations disrupt the interaction between and ALK and cause resistance. In this study, we employ a computational approach to model mutated ALK in complex with lorlatinib as well as ATP to understand whether the new mutations alter the affinity or mode of lorlatinib/ATP binding to ALK, and thus cause suboptimal ALK inhibition. METHODS/STUDY POPULATION: We employ methods in computational structural biology and drug design, primarily based on molecular modeling, molecular dynamics (MD), and molecular docking. Based on existing crystal structures of wildtype ALK, we model the mutations and perform MD simulations in order to characterize the activation state of the protein as well as perform ensemble docking calculations to assess the binding affinities and modes in ALK-lorlatinib and ALK-ATP complexes. RESULTS/ANTICIPATED RESULTS: We expect that the compound mutations cause resistance to lorlatinib either by lowering protein affinity for the drug or increasing the affinity for ATP. Alternatively, the compound mutations may disrupt the protein activation state, in which case ALK may no longer be active, and another protein/pathway could be driving the resistance. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study will enable the understanding of the mechanism of resistance to lorlatinib and facilitate the design of new ALK inhibitors, or help develop more optimal and mechanism-guided therapies aimed to overcome the resistance.

Caste has always generated political and scholarly controversy, but the forms that this takes today newly combine anti-caste activism with counter-claims that caste is irrelevant or non-existent, or claims to castelessness. Claims to castelessness are, in turn, viewed by some as a new disguise for caste power and privilege, while castlessness is also an aspiration for people subject to caste-based discrimination. This article looks at elite claims to “enclose” caste within religion, specifically Hinduism, and the Indian nation so as to restrict the field of social policy that caste applies to, to exempt caste-based discrimination from the law, and to limit the social politics of caste. It does so through a comparative analysis of two cases. The first is the exclusion of Christian and Muslim Dalits—members of castes subordinated as “untouchable”—from provisions and protections as Scheduled Castes in India. The other case is that of responses to the introduction of caste into anti-discrimination law in the UK. While Hindu organizations in the UK reject “caste” as a colonial and racist term and deploy postcolonial scholarship to deny caste discrimination, Dalit organizations, representing its potential victims, turn to scholarly discourse on caste, race, or human rights to support their cause. These are epistemological disputes about categories of description and how “the social” is made available for public debate, and especially for law. Such disputes engage with anthropology, whose analytical terms animate and change the social world that is their subject.

What place does the caste system have in modern India with its globally integrating market economy? The most influential anthropological approaches to caste have tended to emphasize caste as India's traditional religious and ritual order, or (treating such order as a product of the colonial encounter) as shaped politically, especially today by the dynamics of caste-based electoral politics. Less attention has been paid to caste effects in the economy. This article argues that the scholarly framing of caste mirrors a public-policy ‘enclosure’ of caste in the non-modern realm of religion and ‘caste politics’, while aligning modernity to the caste-erasing market economy. Village-level fieldwork in South India finds a parallel public narrative of caste either as ritual rank eroded by market relations or as identity politics deflected from everyday economic life. But, locally and nationally, the effects of caste are found to be pervasive in labour markets and the business economy. In the age of the market, caste is a resource, sometimes in the form of a network, its opportunity-hoarding advantages discriminating against others. Dalits are not discriminated by caste as a set of relations separate from economy, but by the very economic and market processes through which they often seek liberation. The caste processes, enclosures, and evasions in post-liberalization India suggest the need to rethink the modernity of caste beyond orientalist and post-colonial frameworks, and consider the presuppositions that shape understanding of an institution, the nature and experience of which are determined by the inequalities and subject positions it produces.

We employ Pan-STARRS photometry, Gaia trigonometric parallaxes, modern stellar evolution and atmosphere models, and our Bayesian fitting approach to determine cooling and total ages for 159,238 white dwarfs. In many cases we are able to derive precise ages (better than 5%) for individual white dwarfs. These results are meant for broad use within the white dwarf and stellar astrophysics communities and we plan to make available on-line the posterior distributions for cooling age, total age, initial stellar mass, and other parameters.