OBJECTIVES/GOALS: As the number of older adults (≥65 years) with T1D grows, there are limited data to guide care. In a six-month trial, CGM reduced hypoglycemia in older adults, yet there are challenges for widespread uptake. Our objective is to characterize older adults experiences with using CGM and define suboptimal responses signaling a need for resources or support. METHODS/STUDY POPULATION: The study will engage key stakeholders (i.e., older adults with T1D, caregivers [recruited as patient-caregiver dyads], and providers [endocrinologists, geriatricians, diabetes educators]) for a Group Model Building (GMB). GMB is a participatory approach to system dynamics in which participants share perceptions and experiences with a problem and collaboratively explore the system structure that shapes those trends. A series of 8 GMB workshops will be held with 3-8 participants. The final study n will be determined by thematic saturation. Workshops comprise 1) a questionnaire, 2) a GMB session, and 3) a focus group discussion. GMB will follow a replicable process to generate a model of the complex web of causal determinants affecting CGM-related experiences, including optimal and suboptimal CGM responses. RESULTS/ANTICIPATED RESULTS: To date, the study has enrolled 33 participants, including 28 older adults living with T1D and 5 caregivers (mean age = 74 years, range 67-83 years). Twenty-four patient participants will be active CGM users and 4 will be CGM non-users. The study will report on patient data capture from the questionnaire and EMR, including demographics, experiences, familiarity, and confidence surrounding CGM use; diabetes duration; insulin pump use; history of severe hypoglycemia. Analysis of aggregated data will generate causal loop diagrams that integrate pertinent theoretical frameworks, lived experiences, and CGM outcomes. Maps will be used to identify a set of suboptimal CGM responses (i.e., key outcome trajectories) that signal a need for action, with a diagram of factors that interact to produce each response. DISCUSSION/SIGNIFICANCE: Delivering CGM to older adults with T1D demands new approaches. This study will yield critical evidence to tailor support and resources for effective CGM use in older adults. Findings may be translated into suite of pragmatic interventions to bolster CGM use and matched to individual patients expected to benefit using a precision medicine framework.

Research among non-industrial societies suggests that body kinematics adopted during running vary between groups according to the cultural importance of running. Among groups in which running is common and an important part of cultural identity, runners tend to adopt what exercise scientists and coaches consider to be good technique for avoiding injury and maximising performance. In contrast, among groups in which running is not particularly culturally important, people tend to adopt suboptimal technique. This paper begins by describing key elements of good running technique, including landing with a forefoot or midfoot strike pattern and leg oriented roughly vertically. Next, we review evidence from non-industrial societies that cultural attitudes about running associate with variation in running techniques. Then, we present new data from Tsimane forager–horticulturalists in Bolivia. Our findings suggest that running is neither a common activity among the Tsimane nor is it considered an important part of cultural identity. We also demonstrate that when Tsimane do run, they tend to use suboptimal technique, specifically landing with a rearfoot strike pattern and leg protracted ahead of the knee (called overstriding). Finally, we discuss processes by which culture might influence variation in running techniques among non-industrial societies, including self-optimisation and social learning.

Seed retention, and ultimately seed shatter, are extremely important for the efficacy of harvest weed seed control (HWSC) and are likely influenced by various agroecological and environmental factors. Field studies investigated seed-shattering phenology of 22 weed species across three soybean [Glycine max (L.) Merr.]-producing regions in the United States. We further evaluated the potential drivers of seed shatter in terms of weather conditions, growing degree days, and plant biomass. Based on the results, weather conditions had no consistent impact on weed seed shatter. However, there was a positive correlation between individual weed plant biomass and delayed weed seed–shattering rates during harvest. This work demonstrates that HWSC can potentially reduce weed seedbank inputs of plants that have escaped early-season management practices and retained seed through harvest. However, smaller individuals of plants within the same population that shatter seed before harvest pose a risk of escaping early-season management and HWSC.

Northern Welsh is one of two main dialect families of Welsh (cym, ISO 693-3) spoken in Wales, the other being Southern Welsh. The Welsh counties of Anglesey, Gwynedd, Conwy, Denbighshire, Flintshire, and Wrexham in the United Kingdom are considered to comprise the unofficial region of North Wales shown in Figure 1 (as designated by StatsWales 2018). Within this area there are further dialectal differences that are beyond the scope of this analysis, which considers the general features of Northern Welsh as a whole. However, see Thomas & Thomas (1989) for an overview of differences between eastern and western varieties of Northern Welsh.

Americium is a man-made metal produced in very small quantities in nuclear reactors. Americium-241 is one of the radioactive isotopes of americium and has commercial applications, including use in smoke detectors. This is a case report of an occupational inhalation of americium-241, treated with both effective external decontamination and the use of diethylenetriamine pentaacetate to promote decorporation. This experience is significant because of the potential for americium or similar radionuclides to be used in “dirty” bombs or other radiological dispersion devices to cause large-scale radioactive contamination.

Environmental DNA (eDNA) surveying has potential to become a powerful tool for sustainable parasite control. As trematode parasites require an intermediate snail host that is often aquatic or amphibious to fulfil their lifecycle, water-based eDNA analyses can be used to screen habitats for the presence of snail hosts and identify trematode infection risk areas. The aim of this study was to identify climatic and environmental factors associated with the detection of Galba truncatula eDNA. Fourteen potential G. truncatula habitats on two farms were surveyed over a 9-month period, with eDNA detected using a filter capture, extraction and PCR protocol with data analysed using a generalized estimation equation. The probability of detecting G. truncatula eDNA increased in habitats where snails were visually detected, as temperature increased, and as water pH decreased (P < 0.05). Rainfall was positively associated with eDNA detection in watercourse habitats on farm A, but negatively associated with eDNA detection in watercourse habitats on farm B (P < 0.001), which may be explained by differences in watercourse gradient. This study is the first to identify factors associated with trematode intermediate snail host eDNA detection. These factors should be considered in standardized protocols to evaluate the results of future eDNA surveys.

While donor-conceived children have similar mental health outcomes compared to spontaneously conceived children, there is an inconsistency between studies investigating mental health outcomes of donor-conceived people in adulthood. This study is an online health survey that was completed by 272 donor sperm-conceived adults and 877 spontaneously conceived adults from around the world. Donor sperm-conceived adults had increased diagnoses of attention deficit disorder (P = 0.004), and autism (P = 0.044) in comparison to those conceived spontaneously. Donor sperm-conceived adults self-reported increased incidences of seeing a mental health professional (P < 0.001), identity formation problems (P < 0.001), learning difficulties (P < 0.001), panic attacks (P = 0.038), recurrent nightmares (sperm P = 0.038), and alcohol/drug dependency (P = 0.037). DASS-21 analysis revealed that donor sperm-conceived adults were also more stressed than those conceived spontaneously (P = 0.013). Both donor sperm and spontaneously conceived cohorts were matched for sex, age, height, alcohol consumption, smoking, exercise, own fertility, and maternal smoking. The increase in adverse mental health outcomes is consistent with some studies of donor-conceived adult mental health outcomes. These results are also consistent with the Developmental Origins of Health and Disease (DOHaD) phenomenon that has linked adverse perinatal outcomes, which have been observed in donor-conceived neonates, to increased risk of chronic disease, including mental health. Further work is required to reconcile our observations in adults to contrary observations reported in donor-conceived children.

ABSTRACT IMPACT: Melanoma leptomeningeal disease (LMD) is a devastating subtype of central nervous system (CNS) metastatic disease that is associated with limited treatment options and an extremely poor prognosis, thus requiring the development of preclinical models of LMD for therapeutic development. OBJECTIVES/GOALS:

1. 1. Develop an immunocompetent murine model of melanoma LMD with tumors bearing genetic mutations commonly found in patients, specifically BRAF(V600E)/PTEN-/-

2. 2. Assess the safety of intrathecal (IT) immunotherapy, specifically anti-PD1 antibody (aPD1)

3. 3. Evaluate the therapeutic efficacy of IT aPD1 checkpoint blockade in murine melanoma LMD METHODS/STUDY POPULATION: To develop BRAF(V600E)/PTEN-/- LMD models, we acquired BP, D4M, and D4M-UV2 (irradiated) murine melanoma cell lines and luciferase-tagged them. 1.5x10^4 cells were suspended in 10 uL serum-free media and injected into the cisterna magna of female C57BL/6 mice. Brain and spinal cord were harvested for histologic assessment once mice were moribund. To assess safety of IT aPD1, we injected IT control IgG or IT aPD1 (13 ug, 26 ug, 39 ug) and monitored weights or harvested at days 7 or 14 for IHC staining of inflammation markers. To evaluate therapeutic efficacy of IT aPD1, BP cells were directly injected as above. After 3 days, mice underwent imaging to confirm tumor uptake and randomization to receive 13 ug IT control IgG or aPD1 once + 200 ug systemic (Sys) control IgG or aPD1 (days 0, 3, and 5), and then monitored for survival. RESULTS/ANTICIPATED RESULTS: For LMD development, all mice survived cisternal injection of BP, D4M, and D4M-UV2 cells and median survival was 17, 19, and 30 days, respectively. Presence of leptomeningeal deposits was confirmed for all tumor-bearing mice by IHC for MART1. For safety of IT aPD1, all mice survived the procedure and no mice displayed morbidity or >10% weight loss over 14 days of observation. IHC assessment of brain and spinal cord samples from mice treated with 13 ug aPD1 revealed focal ischemia related to injection site and no other signs of neurological damage or inflammation. IT aPD1 treatment of mice with BP leptomeningeal tumors demonstrated no significant survival advantage, although both IT aPD1 +/- Sys aPD1 had mice live up to days 29 and 26, respectively, compared to both IT control IgG +/- Sys aPD1, for which all mice died by day 22. DISCUSSION/SIGNIFICANCE OF FINDINGS: We demonstrate that cisternal injection of murine BRAF(V600E)/PTEN-/- melanoma cell lines yield LMD with reproducible survival and that treatment with IT aPD1 in this model is feasible and safe. Together these findings establish a new model to facilitate the development of more effective immunotherapy strategies for melanoma patients with LMD.