Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.

The Asia Pacific Journal presents a link to an extraordinary 12-minute video by Matthew Carney of the Australian Broadcasting Corporation discussing the death penalty and the problem of wrongful convictions in Japanese criminal justice. This video explains what went wrong in three cases involving men who were victimized in the worst kind of way by Japan's criminal justice system, and it raises the possibility that these cases could stimulate reform in Japan's system of capital punishment and in the criminal justice system more generally.

Although psychopathic personality traits are widely reported to be related to reduced reactivity to emotion-eliciting situations, findings are not consistent. It has been argued that these differences could be related to variations in the way psychopathy is measured. To examine whether measurement variance resulting from the use of clinical assessment versus self-report assessment could be driving such differences, this systematic review and meta-analysis investigated the comparability of relations between psychopathic traits and responsiveness to emotion-inducing tasks for clinical versus self-report measures. The systematic review resulted in eight studies and 131 effect sizes, which included studies of emotion categorization, emotion regulation, decision-making, and executive functioning tasks. Robust Variance Estimation correlated effects models revealed no significant differences between effect sizes for clinical (PCL-R) versus self-report (PPI, SRP, and LSRP) assessment-based psychopathic traits and emotion tasks. Despite the small number of studies that included both clinical and self-report assessments of psychopathy, these results do not provide any evidence for an assessment-based difference in correlations with emotional responsiveness across tasks. The findings also show no associations between scores on emotional responsiveness and indices of psychopathy. Future research on emotional responsiveness in psychopathy should include both assessment types to be able to increase the research basis for the comparison.

We examined the association between influenza vaccination policies at acute care hospitals and influenza vaccination coverage among healthcare personnel for the 2021–22 influenza season. Mandatory vaccination and masking for unvaccinated personnel were associated with increased odds of vaccination. Hospital employees had higher vaccination coverage than licensed independent practitioners.

The spotted hyaena Crocuta crocuta is relatively understudied across its range despite evidence of widespread declines. It is therefore essential that robust baseline population density assessments are conducted to inform current management and future conservation policy. In Mozambique this is urgent as decades of armed conflict followed by unchecked poaching have resulted in large-scale wildlife declines and extirpations. We conducted the first robust population density estimate for a spotted hyaena population in Mozambique using spatially explicit capture–recapture methodologies. We recorded a relatively low population density of 0.8–2.1 hyaenas/100 km2 in the wildlife management area Coutada 11 in the Zambezi Delta of central Mozambique in 2021. These densities are well below the estimated carrying capacity for the landscape and are comparable to published densities in high human-impact, miombo woodland-dominated and arid environments. The combination of historical armed conflict, marginal trophy hunting and bushmeat poaching using wire snares and gin traps (with physical injuries evident in 9% of identified individuals) presents persistent anthropogenic pressure, limiting the post-war recovery of this resident hyaena population. We provide insights into the dynamics of hyaena population status and recovery in such post-war landscapes, adding to mounting evidence that the species is less resilient to severe anthropogenic disturbances than previously believed. We recommend long-term monitoring of this and other carnivore populations in post-war landscapes to ascertain demographic trends and implement effective conservation interventions for population recovery.

Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

This paper provides quantitative evidence on interbank transmission of financial distress in the Panic of 1907 and ensuing recession. Originating in New York City, the panic led to payment suspensions and emergency currency issuance in many cities. Data on the universe of interbank connections show that (1) suspension was more likely in cities whose banks had closer ties to banks at the center of the panic, (2) banks with such links were more likely to close in the panic and recession, and (3) banks responded to the panic by rearranging their correspondent relationships, with implications for network structure.

Young stellar objects (YSOs) are protostars that exhibit bipolar outflows fed by accretion disks. Theories of the transition between disk and outflow often involve a complex magnetic field structure thought to be created by the disk coiling field lines at the jet base; however, due to limited resolution, these theories cannot be confirmed with observation and thus may benefit from laboratory astrophysics studies. We create a dynamically similar laboratory system by driving a $\sim$1 MA current pulse with a 200 ns rise through a $\approx$2 mm-tall Al cylindrical wire array mounted to a three-dimensional (3-D)-printed, stainless steel scaffolding. This system creates a plasma that converges on the centre axis and ejects cm-scale bipolar outflows. Depending on the chosen 3-D-printed load path, the system may be designed to push the ablated plasma flow radially inwards or off-axis to make rotation. In this paper, we present results from the simplest iteration of the load which generates radially converging streams that launch non-rotating jets. The temperature, velocity and density of the radial inflows and axial outflows are characterized using interferometry, gated optical and ultraviolet imaging, and Thomson scattering diagnostics. We show that experimental measurements of the Reynolds number and sonic Mach number in three different stages of the experiment scale favourably to the observed properties of YSO jets with $Re\sim 10^5\unicode{x2013}10^9$ and $M\sim 1\unicode{x2013}10$, while our magnetic Reynolds number of $Re_M\sim 1\unicode{x2013}15$ indicates that the magnetic field diffuses out of our plasma over multiple hydrodynamical time scales. We compare our results with 3-D numerical simulations in the PERSEUS extended magnetohydrodynamics code.

Debate surrounds the early peopling of the Arabian Peninsula. The first evidence of the Levallois lithic technology in the Huqf area of south-eastern Arabia now extends the Middle Palaeolithic record of hominin activity into central Oman and helps to diversify the picture of Arabian prehistory.

We synthesize sea-level science developments, priorities and practitioner needs at the end of the 10-year World Climate Research Program Grand Challenge ’Regional Sea-Level Change and Coastal Impacts’. Sea-level science and associated climate services have progressed but are unevenly distributed. There remains deep uncertainty concerning high-end and long-term sea-level projections due to indeterminate emissions, the ice sheet response and other climate tipping points. These are priorities for sea-level science. At the same time practitioners need climate services that provide localized information including median and curated high-end sea-level projections for long-term planning, together with information to address near-term pressures, including extreme sea level-related hazards and land subsidence, which can greatly exceed current rates of climate-induced sea-level rise in some populous coastal settlements. To maximise the impact of scientific knowledge, ongoing co-production between science and practitioner communities is essential. Here we report on recent progress and ways forward for the next decade.

Migrants and refugees face elevated risks for mental health problems but have limited access to services. This study compared two strategies for training and supervising nonspecialists to deliver a scalable psychological intervention, Group Problem Management Plus (gPM+), in northern Colombia. Adult women who reported elevated psychological distress and functional impairment were randomized to receive gPM+ delivered by nonspecialists who received training and supervision by: 1) a psychologist (specialized technical support); or 2) a nonspecialist who had been trained as a trainer/supervisor (nonspecialized technical support). We examined effectiveness and implementation outcomes using a mixed-methods approach. Thirteen nonspecialists were trained as gPM+ facilitators and three were trained-as-trainers. We enrolled 128 women to participate in gPM+ across the two conditions. Intervention attendance was higher in the specialized technical support condition. The nonspecialized technical support condition demonstrated higher fidelity to gPM+ and lower cost of implementation. Other indicators of effectiveness, adoption and implementation were comparable between the two implementation strategies. These results suggest it is feasible to implement mental health interventions, like gPM+, using lower-resource, community-embedded task sharing models, while maintaining safety and fidelity. Further evidence from fully powered trials is needed to make definitive conclusions about the relative cost of these implementation strategies.

Newly elevated to species rank, the Bahama Nuthatch Sitta insularis is or was a bark- and twig-gleaning insectivore only known in life from the pine forests of Grand Bahama in the Bahamas archipelago. It became increasingly difficult to find in the past 50 years, seemingly in part in response to multiple hurricanes in this century. In spring (June–April) 2018, when it was still known to be extant, we divided the island into seven sections and carried out point count transects with playback and measured habitat variables at 464 locations in pine forest across Grand Bahama. We made only six observations at six locations, all in the region of Lucayan North and each involving a single nuthatch (possibly all the same individual). Fourteen count points were within 500 m of the six locations, and tree size at these sites was greater in height and girth than at sites with no observations and indeed than at other sites within Lucayan North. Count points within 500 m of nuthatch records in 2004–2018 had larger trees and more snags than survey points over 500 m away from previous detections, while count points within 500 m of our 2018 nuthatch records tallied more snags than did those within 500 m of the 2004–2007 records. Declines in habitat quality, habitat extent, nesting substrate, and food availability (driven by logging, attritional island development, and the direct and indirect effects of hurricanes), plus speculated increases in populations of invasive predators/competitors and in major mortality events (hurricanes, increasing in force and frequency with climate change), are suspected to be the ultimate causes of the decline of the nuthatch, with Hurricanes Matthew and Dorian the proximate causes of its evident extinction in 2019.

Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.