When the raters participating in a reliability study are a random sample from a larger population of raters, inferences about the intraclass correlation coefficient must be based on the three mean squares from the analysis of variance table summarizing the results: between subjects, between raters, and error. An approximate confidence interval for the parameter is presented as a function of these three mean squares.

Continuous analogues of the finite linear and stimulus sampling theories are developed for non-determinate reinforcement schedules. Closed-form expressions are derived for the asymptotic response distribution and certain sequential statistics. Computations for a target experiment are given to illustrate the character of the theoretical results.

Most infections with pandemic Vibrio cholerae are thought to result in subclinical disease and are not captured by surveillance. Previous estimates of the ratio of infections to clinical cases have varied widely (2 to 100 infections per case). Understanding cholera epidemiology and immunity relies on the ability to translate between numbers of clinical cases and the underlying number of infections in the population. We estimated the infection incidence during the first months of an outbreak in a cholera-naive population using a Bayesian vibriocidal antibody titer decay model combining measurements from a representative serosurvey and clinical surveillance data. 3,880 suspected cases were reported in Grande Saline, Haiti, between 20 October 2010 and 6 April 2011 (clinical attack rate 18.4%). We found that more than 52.6% (95% Credible Interval (CrI) 49.4-55.7) of the population ≥2 years showed serologic evidence of infection, with a lower infection rate among children aged 2-4 years (35.5%; 95%CrI 24.2-51.6) compared with people ≥5 years (53.1%; 95%CrI 49.4-56.4). This estimated infection rate, nearly three times the clinical attack rate, with underdetection mainly seen in those ≥5 years, has likely impacted subsequent outbreak dynamics. Our findings show how seroincidence estimates improve understanding of links between cholera burden, transmission dynamics and immunity.

Predation can have cascading, regulatory effects across ecological communities. Knowledge of the diet of predators can therefore provide important information regarding their ecology and conservation, as well as their impacts on prey populations. Using scats collected during 2019–2023 and estimates of prey abundance from aerial surveys, we characterized prey consumption and preferences of the Vulnerable African lion Panthera leo population in Tsavo, Kenya. Biomass models applied to prey frequencies in scats revealed that > 85% of lion diet comprised large ungulates weighing > 150 kg. The Critically Endangered hirola Beatragus hunteri and Endangered Grevy's zebra Equus grevyi (species that were introduced in Tsavo as part of ex situ conservation programmes in the 1960s) were amongst the seven prey species, of 16 detected, that were preferred by lions. Our results potentially indicate a disproportionate impact of lion predation on the small hirola and Grevy's zebra populations. Preferential predation, coupled with high availability of alternative prey, may trap the small populations of hirola and Grevy's zebra within a predator pit. Our findings provide a better understanding of lion diet, optimal foraging and the potential effects predators can have on threatened and rare prey species in an important conservation landscape. Based on our findings, we recommend an observational study of the predation ecology of lions and other predators in this system, to provide information on age- and sex-specific predation rates on hirola and Grevy's zebra for a population viability analysis, to support the management of these two threatened and rare herbivores in Tsavo.

How was trust created and reinforced between the inhabitants of medieval and early modern cities? And how did the social foundations of trusting relationships change over time? Current research highlights the role of kinship, neighbourhood, and associations, particularly guilds, in creating ‘relationships of trust’ and social capital in the face of high levels of migration, mortality, and economic volatility, but tells us little about their relative importance or how they developed. We uncover a profound shift in the contribution of family and guilds to trust networks among the middling and elite of one of Europe's major cities, London, over three centuries, from the 1330s to the 1680s. We examine almost 15,000 networks of sureties created to secure orphans’ inheritances to measure the presence of trusting relationships connected by guild membership, family, and place. We uncover a profound increase in the role of kinship – a re-embedding of trust within the family – and a decline of the importance of shared guild membership in connecting Londoners who secured orphans’ inheritances together. These developments indicate a profound transformation in the social fabric of urban society.

The impact of invasive species on biodiversity, food security and economy is increasingly noticeable in various regions of the globe as a consequence of climate change. Yet, there is limited research on how climate change affects the distribution of the invasive Asian citrus psyllid Diaphorina citri Kuwayama (Hemiptera:Liviidae) in Ghana. Using maxnet package to fit the Maxent model in R software, we answered the following questions; (i) what are the main drivers for D. citri distribution, (ii) what are the D. citri-specific habitat requirements and (iii) how well do the risk maps fit with what we know to be correctly based on the available evidence?. We found that temperature seasonality (Bio04), mean temperature of warmest quarter (Bio10), precipitation of driest quarter (Bio17), moderate resolution imaging spectroradiometer land cover and precipitation seasonality (Bio15), were the most important drivers of D. citri distribution. The results follow the known distribution records of the pest with potential expansion of habitat suitability in the future. Because many invasive species, including D. citri, can adapt to the changing climates, our findings can serve as a guide for surveillance, tracking and prevention of D. citri spread in Ghana.

This study aimed to parse between-person heterogeneity in growth of impulsivity across childhood and adolescence among participants enrolled in five childhood preventive intervention trials targeting conduct problems. In addition, we aimed to test profile membership in relation to adult psychopathologies. Measurement items representing impulsive behavior across grades 2, 4, 5, 7, 8, and 10, and aggression, substance use, suicidal ideation/attempts, and anxiety/depression in adulthood were integrated from the five trials (N = 4,975). We applied latent class growth analysis to this sample, as well as samples separated into nonintervention (n = 2,492) and intervention (n = 2,483) participants. Across all samples, profiles were characterized by high, moderate, low, and low-increasing impulsive levels. Regarding adult outcomes, in all samples, the high, moderate, and low profiles endorsed greater levels of aggression compared to the low-increasing profile. There were nuanced differences across samples and profiles on suicidal ideation/attempts and anxiety/depression. Across samples, there were no significant differences between profiles on substance use. Overall, our study helps to inform understanding of the developmental course and prognosis of impulsivity, as well as adding to collaborative efforts linking data across multiple studies to better inform understanding of developmental processes.

We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

We present analysis of the far ultraviolet (FUV) emission of sources in the central region of the Coma cluster ($z=0.023$) using the data taken by the UVIT aboard the multi-wavelength satellite mission AstroSat. We find a good correlation between the UVIT FUV flux and the fluxes in both wavebands of the Galex mission, for the common sources. We detect stars and galaxies, amongst which the brightest ($r \lesssim 17$ mag) galaxies in the field of view are mostly members of the Coma cluster. We also detect three quasars ($z = 0.38, 0.51, 2.31$), one of which is likely the farthest object observed by the UVIT so far. In almost all the optical and UV colour-colour and colour-magnitude planes explored in this work, the Coma galaxies, other galaxies and bright stars could be separately identified, but the fainter stars and quasars often coincide with the faint galaxies. We have also investigated galaxies with unusual FUV morphology which are likely to be galaxies experiencing ram-pressure stripping in the cluster. Amongst others, two confirmed cluster members which were not investigated in the literature earlier, have been found to show unusual FUV emission. All the distorted sources are likely to have fallen into the cluster recently, and hence have not virialised yet. A subset of our data have optical spectroscopic information available from the archives. For these sources (${\sim} 10\%$ of the sample), we find that 17 galaxies identify as star-forming, 18 as composite and 13 as host galaxies for active galactic nuclei, respectively on the emission-line diagnostic diagram.