The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT’s are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.

Despite advances in cancer genomics and the increased use of genomic medicine, metastatic cancer is still mostly an incurable and fatal disease. With diminishing returns from traditional drug discovery strategies, and high clinical failure rates, more emphasis is being placed on alternative drug discovery platforms, such as ex vivo approaches. Ex vivo approaches aim to embed biological relevance and inter-patient variability at an earlier stage of drug discovery, and to offer more precise treatment stratification for patients. However, these techniques also have a high potential to offer personalised therapies to patients, complementing and enhancing genomic medicine. Although an array of approaches are available to researchers, only a minority of techniques have made it through to direct patient treatment within robust clinical trials. Within this review, we discuss the current challenges to ex vivo approaches within clinical practice and summarise the contemporary literature which has directed patient treatment. Finally, we map out how ex vivo approaches could transition from a small-scale, predominantly research based technology to a robust and validated predictive tool. In future, these pre-clinical approaches may be integrated into clinical cancer pathways to assist in the personalisation of therapy choices and to hopefully improve patient experiences and outcomes.

Systematic, in-depth exploration of news media coverage of aggression and older adults remains sparse, with little attention to how and why particular frames manifest in coverage across differing settings and relationships. Frame analysis was used to analyze 141 English-language Canadian news media articles published between 2008 and 2019. Existing coverage tended towards stigmatizing, fear-inducing, and biomedical framings of aggression, yet also reflected and reinforced ambiguity, most notably around key differences between settings and relations of care. Mainstream news coverage reflects tensions in public understandings of aggression and older adults (e.g., as a medical or criminal issue), reinforced in particular ways because of the nature of news reporting. More nuanced coverage would advance understanding of differences among settings, relationships, and types of actions, and of the need for multifaceted prevention and policy responses based on these differences.

We study particle capture on an angled cylinder at a range of Péclet numbers. This system was inspired by the plumose antennae of certain species of male moths that intercept female pheromones at low Péclet numbers of 0.9–23. We use confocal microscopy to measure the branching patterns of 49 moths, spanning 12 families and two orders of magnitude in mass. Among the three levels of hierarchy in antennae, we find the middle level has a prevalent branching angle, $52^{\circ }\pm 12^{\circ }$ across our study set. Such intermediate branching angles are a surprising way to intercept molecules because they do not maximize the exposed surface area. To understand the benefits of angling cylinders into the flow, we study particle collection at high Péclet number using $10~\unicode[STIX]{x03BC}\text{m}$ drops that are several orders of magnitude larger than moth pheromones. Wind tunnel tests show that cylinders angled at $30^{\circ }{-}60^{\circ }$ are optimal for collection of particles, collecting 30 % more than when perpendicular to the flow. Simulations and smoke visualization show that angled cylinders bend incoming streamlines, creating a lingering effect near the cylinder that can enhance deposition by diffusion. We surmise that the optimal angle arises from a trade-off between the lingering effect, which decreases with increasing angle of the cylinder, and the cylinder’s increasing projected area as it is turned more perpendicular to the flow. Using a mathematical model, we show that only cylinders at low Péclet number show improved collection at intermediate angles. Thus, we cannot rationalize the high collection rates in our wind tunnel experiments at high Péclet number. We hope that our study will inspire more research into bio-inspired particle collection of angled surfaces, and find applications in sensors and filters.

Analysis of human remains and a copper band found in the center of a Late Archaic (ca. 5000–3000 cal BP) shell ring demonstrate an exchange network between the Great Lakes and the coastal southeast United States. Similarities in mortuary practices suggest that the movement of objects between these two regions was more direct and unmediated than archaeologists previously assumed based on “down-the-line” models of exchange. These findings challenge prevalent notions that view preagricultural Native American communities as relatively isolated from one another and suggest instead that wide social networks spanned much of North America thousands of years before the advent of domestication.

A controversy at the 2016 IUCN World Conservation Congress on the topic of closing domestic ivory markets (the 007, or so-called James Bond, motion) has given rise to a debate on IUCN's value proposition. A cross-section of authors who are engaged in IUCN but not employed by the organization, and with diverse perspectives and opinions, here argue for the importance of safeguarding and strengthening the unique technical and convening roles of IUCN, providing examples of what has and has not worked. Recommendations for protecting and enhancing IUCN's contribution to global conservation debates and policy formulation are given.

The Hell Gap National Historic Landmark, located on the northwestern plains of Wyoming, is one of the most important Paleoindian archaeological sites in North America because it contains a stratified sequence of occupations spanning nearly the entirety of the Paleoindian period. Although Hell Gap is central to archaeological knowledge concerning North American Paleoindian chronology, consistently assigning component ages has been problematic due to conflicting radiocarbon determinations from individual strata, stratigraphic age reversals in age-depth relationships, and other issues related to the stratified open campsite. Toward resolving the Hell Gap chronology, we devised a procedure for correcting age-depth relationships for incorporation in chronostratigraphic models and then used the Bayesian age-depth modeling qprocedures in Bchron to estimate the ages of 11 stratified components present at Hell Gap Locality 1. We present these age estimates and discuss their significance to Paleoindian chronology. Notable aspects of our chronology include a revised age estimate for the Goshen complex, the identification of three Folsom components spanning the entirety of the Folsom temporal range, and relatively young age estimates for the Late Paleoindian Frederick/Lusk component(s) at Locality 1. More broadly, our study demonstrates a procedure for creating chronometric models of stratigraphically complicated open stratified sites of any type.

Debates about the meaning of Southern symbols such as the Confederate battle emblem are sweeping the nation. These debates typically revolve around the question of whether such symbols represent “heritage or hatred:” racially innocuous Southern pride or White prejudice against Blacks. In order to assess these competing claims, we first examine the historical reintroduction of the Confederate flag in the Deep South in the 1950s and 1960s; next, we analyze three survey datasets, including one nationally representative dataset and two probability samples of White Georgians and White South Carolinians, in order to build and assess a stronger theoretical account of the racial motivations underlying such symbols than currently exists. While our findings yield strong support for the hypothesis that prejudice against Blacks bolsters White support for Southern symbols, support for the Southern heritage hypothesis is decidedly mixed. Despite widespread denials that Southern symbols reflect racism, racial prejudice is strongly associated with support for such symbols.

Black Mesa in northeastern Arizona exposes sediments of late Cenomanian–Turonian age deposited during the transgressive–regressive Greenhorn cyclothem. These sediments contain a diverse selachian fauna that consists of 21 taxa: Hybodus sp., Ptychodus whipplei, P. decurrens, P. cf. P. mammillaris, Chiloscyllium greeni, Chiloscyllium sp., Scapanorhynchus raphiodon, Cretodus semiplicatus, Cretolamna appendiculata, C. woodwardi, Cretoxyrhina mantelli, cf. Leptostyrax sp., Squalicorax falcatus, Rhinobatos sp., Pseudohypolophus mcnultyi, Protoplatyrhina hopii n. sp., Ischyrhiza schneideri, I. avonicola, Onchopristis dunklei, Ptychotrygon triangularis, P. rubyae n. sp., and five types of dermal denticles. Two selachian assemblages, a nearshore and a deeper water assemblage, are present in this fauna. Though there is some provincialism in North Africa, Europe, and North America during the Greenhorn marine cycle, the wide dispersion of some shark taxa and the great similarities between widely separated selachian faunas are striking.