Current evidence underscores a need to transform how we do clinical research, shifting from academic-driven priorities to co-led community partnership focused programs, accessible and relevant career pathway programs that expand opportunities for career development, and design of trainings and practices to develop cultural competence among research teams. Failures of equitable research translation contribute to health disparities. Drivers of this failed translation include lack of diversity in both researchers and participants, lack of alignment between research institutions and the communities they serve, and lack of attention to structural sources of inequity and drivers of mistrust for science and research. The Duke University Research Equity and Diversity Initiative (READI) is a program designed to better align clinical research programs with community health priorities through community engagement. Organized around three specific aims, READI-supported programs targeting increased workforce diversity, workforce training in community engagement and cultural competence, inclusive research engagement principles, and development of trustworthy partnerships.

Drone technology and digital image analysis have enabled significant advances in precision agriculture, especially in site-specific treatment of weed escapes in crop fields. This study evaluated a pipeline for weed detection in multispectral drone imagery, along with site-specific herbicide application, using a remotely piloted aerial application system (RPAAS) targeting late-season weed escapes in rice with a selective postemergence rice herbicide, florpyrauxifen-benzyl. The efficacy of the RPAAS-based herbicide application with geocoordinates of weed escapes obtained manually or based on image analysis was compared with conventional backpack broadcast spray. The weed species targeted were barnyardgrass, Amazon sprangletop, yellow nutsedge, and hemp sesbania. A Python-based rice–weed detection model was developed using the canopy height model and spectral reflectance of weeds and rice plants. Results indicate that the accuracy of image-based detection for late-season weed escapes in rice was highest for hemp sesbania (95%), followed by Amazon sprangletop (87%) and yellow nutsedge (74%), with barnyardgrass showing the lowest accuracy at 62%. The study found that the backpack broadcast method had the highest efficacy in weed control, followed by the RPAAS method using manually obtained geocoordinates and those based on image analysis. Site-specific herbicide application using RPAAS resulted in a 45% reduction in herbicide compared to the broadcast backpack application. Moreover, the RPAAS site-specific application method for late-season treatment minimized the field area affected by herbicide injury and protected rice grain yields compared to the broadcast method. Overall, the utility of unmanned aerial sprayer–based detection and site-specific treatment of late-season weed escapes in rice has been demonstrated in this research, but further improvements in weed detection efficacy and the accuracy of targeting plants with RPAAS are necessary.

The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.

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.

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.

Since 1974, two out of every five constitutions (40.3%) were prepared via processes that included public consultation. The reasons for adopting these participatory mechanisms, however, are largely unexplored. I argue that public consultation is a tool for elite contestation of power. Introducing an original dataset of public consultations in constitution-making processes from 1974–2021 (n = 300), I find that in democracies, factional majorities and newcomer elites use public consultation to legitimate a break from the status quo. In autocracies, governing coalitions that depend on performance and enjoy greater party institutionalization push for public consultation to preserve favorable power-sharing arrangements.

Group A streptococcal or Streptococcus pyogenes infections have been increasing post-COVID-19 pandemic. We describe the epidemiology of S. pyogenes pharyngitis and invasive disease in Alberta, Canada 2018–2023. Positive pharyngitis specimens were identified from throat swabs collected from pharyngitis patients. Invasive S. pyogenes was defined as the isolation of S. pyogenes from a normally sterile site or severe skin infection. S. pyogenes isolates were emm typed. Pharyngitis and invasive disease displayed seasonal trends preceding the COVID-19 pandemic followed by a sharp decrease during COVID-19 intervention measures. After the lifting of interventions, rates of pharyngitis and invasive disease rose. There were 182 983 positive pharyngitis specimens between 2018 and 2023 for a positivity rate of 17.6%. The highest rates occurred in the 0–9 age group in 2023 (41.5%). Invasive disease increased in 2022–2023 driven by emm1 and 12 types. M1UK strain was the most frequent M1 type associated with invasive disease (59% of M1 isolates sequenced). Notably, out of 182 983 pharyngitis cases, there were 111 cases of invasive S. pyogenes detected for an invasive disease rate of 0.06%. This descriptive epidemiology of S. pyogenes pharyngitis and invasive S. pyogenes disease highlights the rapid increase in cases of S. pyogenes occurring in western Canada and illustrates the critical need for a vaccine.

Recent reports suggest the ON and OFF pathways are differentially susceptible to selective vision loss in glaucoma. Thus, perimetric assessment of ON- and OFF-pathway function may serve as a useful diagnostic. However, this necessitates a developed understanding of normal ON/OFF pathway function around the visual field and as a function of input intensity. Here, using electroencephalography, we measured ON- and OFF-pathway biased contrast response functions in the upper and lower visual fields. Using the steady-state visually evoked potential paradigm, we flickered achromatic luminance probes according to a saw-tooth waveform, the fast phase of which biased responses towards the ON or OFF pathways. Neural responses from the upper and lower visual fields were simultaneously measured using frequency tagging - probes in the upper visual field modulated at 3.75 Hz, while those in the lower visual field modulated at 3 Hz. We find that responses to OFF/decrements are larger than ON/increments, especially in the lower visual field. In the lower visual field, both ON and OFF responses were well described by a sigmoidal non-linearity. In the upper visual field, the ON pathway function was very similar to that of the lower, but the OFF pathway function showed reduced saturation and more cross-subject variability. Overall, this demonstrates that the relationship between the ON and OFF pathways depends on the visual field location and contrast level, potentially reflective of natural scene statistics.