Objectives/Goals: Clinical relevance of preclinical animal models is commonly in question. Herein, we investigated locoregional tumor immune microenvironment (TIME) differences in tumor-bearing murine oral cancer models, unresponsive to traditional immunotherapy, and also developed an oral tumor resection model to ultimately enhance translational relevance. Methods/Study Population: Here, we utilized carcinogen-induced, HPV-negative preclinical oral cancer models. For TIME studies, ROC1 cells were maintained as published. ROC1 tumors were established in the murine flank and oral cavity of wildtype C57Bl/6 mice, and tumor growth kinetics were assessed at each site. At distinct stages of tumor growth, tumors were harvested, as well as their respective corresponding inguinal and cervical tumor-draining lymph nodes (tdLNs). Multiparameter 28-marker spectral flow cytometry was performed to analyze immune cell populations at each site. For tumor resection studies, MOC2 tumors were similarly maintained and established in the oral cavity. MOC2 tumors were accessed via midline transcervical incisions. Upon tumor excision, wounds were closed with multiple interrupted Vicryl sutures. Results/Anticipated Results: We anticipated no differences between heterotopic and orthotopic tumor sites. Both sites displayed an initial period of delayed ROC1 tumor growth followed by rapid progression. Comprehensive analyses revealed low T cell infiltration overall and increases in select myeloid cells (i.e., macrophages and dendritic cells) over time in both models. Other immune cell types, however, generally increased over time in the flank. Differences between corresponding tdLNs further indicate deviating changes in immunosuppressive phenotypes (i.e., regulatory T cells and macrophages) and immune checkpoint marker expression. Additionally, MOC2 oral tumors were successfully resected with no visible remaining tumor. No subsequent healing complications were observed, and tumor recurrence occurred within 1 week post-surgery. Discussion/Significance of Impact: Tissue-specific TIME and tdLN differences may impact antitumor treatment and response. Ability to resect orthotopic tumors allows for modeling of standard-of-care treatment for oral cancer. These studies can enable tailoring of therapeutic strategies and provide insight into model selection and data interpretation from translational studies.

We present a re-discovery of G278.94+1.35a as possibly one of the largest known Galactic supernova remnants (SNRs) – that we name Diprotodon. While previously established as a Galactic SNR, Diprotodon is visible in our new Evolutionary Map of the Universe (EMU) and GaLactic and Extragalactic All-sky MWA (GLEAM) radio continuum images at an angular size of $3{{{{.\!^\circ}}}}33\times3{{{{.\!^\circ}}}}23$, much larger than previously measured. At the previously suggested distance of 2.7 kpc, this implies a diameter of 157$\times$152 pc. This size would qualify Diprotodon as the largest known SNR and pushes our estimates of SNR sizes to the upper limits. We investigate the environment in which the SNR is located and examine various scenarios that might explain such a large and relatively bright SNR appearance. We find that Diprotodon is most likely at a much closer distance of $\sim$1 kpc, implying its diameter is 58$\times$56 pc and it is in the radiative evolutionary phase. We also present a new Fermi-LAT data analysis that confirms the angular extent of the SNR in gamma rays. The origin of the high-energy emission remains somewhat puzzling, and the scenarios we explore reveal new puzzles, given this unexpected and unique observation of a seemingly evolved SNR having a hard GeV spectrum with no breaks. We explore both leptonic and hadronic scenarios, as well as the possibility that the high-energy emission arises from the leftover particle population of a historic pulsar wind nebula.

We aimed to estimate the secondary attack rate of mpox among UK household contacts and determine factors associated with transmission to inform public health management of contacts, during the global outbreak in 2022. Information was collected via NHS and public health services and included age, gender, place of residence, setting, and type of contact. Aggregate information was summarized for the UK. Record level data was combined for England, Wales and Northern Ireland, and multivariable logistic regression was used to determine factors associated with transmission. The secondary attack rate among UK household mpox contacts was 4% (60/1 526). Sexual contact with the index case was associated with a 11-fold increase in adjusted odds of becoming a case in England, Wales, and Northern Ireland (95% CI 5.5–22, p < 0.001). Household contacts outside of London had increased odds compared to London residents (adjusted OR 2.9, 95%CI 1.6–5.4, p < 0.001), while female contacts had reduced odds of becoming a case (aOR: 0.41, 95% CI: 0.15–0.95). We found a low overall secondary attack rate among household mpox contacts with strong evidence of increased transmission risk associated with sexual contact. This evidence will inform the risk assessment of contacts and support prioritization of those with close intimate contact for follow up.

The authors report on ancient DNA data from two human skeletons buried within the chancel of the 1608–1616 church at the North American colonial settlement of Jamestown, Virginia. Available archaeological, osteological and documentary evidence suggest that these individuals are Sir Ferdinando Wenman and Captain William West, kinsmen of the colony's first Governor, Thomas West, Third Baron De La Warr. Genomic analyses of the skeletons identify unexpected maternal relatedness as both carried the mitochondrial haplogroup H10e. In this unusual case, aDNA prompted further historical research that led to the discovery of illegitimacy in the West family, an aspect of identity omitted, likely intentionally, from genealogical records.

Iron is essential for many physiological functions of the body, and it is required for normal growth and development. Iron deficiency (ID) is the most common form of micronutrient malnutrition and is particularly prevalent in infants and young children in developing countries. Iron supplementation is considered the most effective strategy to combat the risk of ID and ID anaemia (IDA) in infants, although iron supplements cause a range of deleterious gut-related problems in malnourished children. The purpose of this review is to assess the available evidence on the effect of iron supplementation on the gut microbiota during childhood ID and to further assess whether prebiotics offer any benefits for iron supplementation. Prebiotics are well known to improve gut-microbial health in children, and recent reports indicate that prebiotics can mitigate the adverse gut-related effects of iron supplementation in children with ID and IDA. Thus, provision of prebiotics alongside iron supplements has the potential for an enhanced strategy for combatting ID and IDA among children in the developing world. However, further understanding is required before the benefit of such combined treatments of ID in nutritionally deprived children across populations can be fully confirmed. Such enhanced understanding is of high relevance in resource-poor countries where ID, poor sanitation and hygiene, alongside inadequate access to good drinking water and poor health systems, are serious public health concerns.

We present source detection and catalogue construction pipelines to build the first catalogue of radio galaxies from the 270 $\rm deg^2$ pilot survey of the Evolutionary Map of the Universe (EMU-PS) conducted with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The detection pipeline uses Gal-DINO computer vision networks (Gupta et al. 2024, PASA, 41, e001) to predict the categories of radio morphology and bounding boxes for radio sources, as well as their potential infrared host positions. The Gal-DINO network is trained and evaluated on approximately 5 000 visually inspected radio galaxies and their infrared hosts, encompassing both compact and extended radio morphologies. We find that the Intersection over Union (IoU) for the predicted and ground-truth bounding boxes is larger than 0.5 for 99% of the radio sources, and 98% of predicted host positions are within $3^{\prime \prime}$ of the ground-truth infrared host in the evaluation set. The catalogue construction pipeline uses the predictions of the trained network on the radio and infrared image cutouts based on the catalogue of radio components identified using the Selavy source finder algorithm. Confidence scores of the predictions are then used to prioritise Selavy components with higher scores and incorporate them first into the catalogue. This results in identifications for a total of 211 625 radio sources, with 201 211 classified as compact and unresolved. The remaining 10 414 are categorised as extended radio morphologies, including 582 FR-I, 5 602 FR-II, 1 494 FR-x (uncertain whether FR-I or FR-II), 2 375 R (single-peak resolved) radio galaxies, and 361 with peculiar and other rare morphologies. Each source in the catalogue includes a confidence score. We cross-match the radio sources in the catalogue with the infrared and optical catalogues, finding infrared cross-matches for 73% and photometric redshifts for 36% of the radio galaxies. The EMU-PS catalogue and the detection pipelines presented here will be used towards constructing catalogues for the main EMU survey covering the full southern sky.

The COVID-19 pandemic in Australia has profoundly affected older adults, particularly in the state of Victoria, which experienced strict lockdown restrictions six times since the pandemic began in 2020; totalling 245 days over three years. This study explored the experiences of older adults living in retirement villages during the first three lockdowns in Victoria from March 2020 to February 2021. We draw on the concept of the ‘third age’ to explore how residents’ post-retirement social and lifestyle aspirations were disrupted by the pandemic and associated lockdowns. In-depth qualitative interviews were conducted with 14 residents during January and February 2021. All data were analysed using thematic mapping. Five key themes were identified: (1) benefits and frustrations of retirement village living during a pandemic; (2) the loss of amenities and activities; (3) heightened loneliness and social isolation; (4) reaching out to others; and (5) variable experiences of operators’ response. Although the COVID-19 pandemic has highlighted short-term and long-term issues around social isolation and the management of retirement villages, it has also demonstrated the resilience of residents and the strength of community ties and relationships. Retirement villages are promoted as age-friendly environments that enable an active and healthy post-retirement lifestyle. Yet our findings reveal heterogeneity within village populations. When services closed during lockdowns, this revealed a tension between the policy assumption that retirement villages are a housing consumption choice, and the unmet needs of those residents who depend on village services for day-to-day functioning.

Ice-contact lakes modify glacier geometry and dynamics by shifting the majority of mass loss from the ice surface to the terminus. Lake-terminating glaciers are known to experience greater thinning rates and higher velocities than land-terminating glaciers, but the controls on variability in surface elevation change and ice flow between lake-terminating glaciers in different regions remain poorly explored. We combined existing datasets of glacier velocity, surface elevation change and glacial lake area to characterise the evolution of 352 lake-terminating and land-terminating glaciers within three Himalayan sub-regions between 2000 and 2019. These analyses show that the influence of ice-contact lakes propagates up-glacier across only the lowermost 30% of the hypsometric distribution, even where lakes are well established. We find that ice-contact lakes only affect glacier behaviour when the lakes reach an advanced evolutionary stage; most clearly manifested in the Eastern Himalaya by statistically robust differences in glacier-wide surface elevation change between lake-terminating (–0.68 ± 0.05 m a–1) and land-terminating (–0.54 ± 0.04 m a–1) glaciers. These differences are driven by the presence of a greater number of well-developed ice-contact lakes in the Eastern Himalaya compared to in the Western and Central Himalaya, resulting from greater mass loss rates to date.

In 2003, Bohman, Frieze, and Martin initiated the study of randomly perturbed graphs and digraphs. For digraphs, they showed that for every $\alpha \gt 0$, there exists a constant $C$ such that for every $n$-vertex digraph of minimum semi-degree at least $\alpha n$, if one adds $Cn$ random edges then asymptotically almost surely the resulting digraph contains a consistently oriented Hamilton cycle. We generalize their result, showing that the hypothesis of this theorem actually asymptotically almost surely ensures the existence of every orientation of a cycle of every possible length, simultaneously. Moreover, we prove that we can relax the minimum semi-degree condition to a minimum total degree condition when considering orientations of a cycle that do not contain a large number of vertices of indegree $1$. Our proofs make use of a variant of an absorbing method of Montgomery.