Objectives/Goals: The identification of the cascade of molecular and cellular events occurring during the progression of focal segmental glomerulosclerosis in human kidney biopsies from kidney transplant (KTx) recipients (KTR) with normal function or recurrent FSGS to determine potential targets of intervention and therapy. Methods/Study Population: In this study, we evaluate the molecular and cellular events associated with primary FSGS in both native and transplant kidneys. We collected biopsy samples from the native normal kidney (nNK, n = 3), normal functioning allografts (NKTx, n = 3), primary FSGS in the native kidney (nFSGS, n = 1), recurrent FSGS (KTxFSGS, n = 5). KTxFSGS comprises a collection of longitudinal samples with biopsy also collected at the subsequent recurrence. Blood samples were collected during biopsy collection. Biopsies were preserved in RNAlater at the time of collection. 10X genomics chromium single nuclei RNA sequencing (snRNAseq) was performed using isolated nuclei. Data was analyzed using Seurat on R. Conditionally immortalized podocytes were treated with a patient serum to determine the change in expression observed in snRNAseq data. Results/Anticipated Results: Recurrence rates of primary FSGS are high in kidney allograft recipients up to 25–50% in first, and up to 80% in second transplants, often leading to graft loss. Our findings reveal that podocyte detachment is driven by metabolic and structural dysregulation rather than cell death, increasing VEGFA expression and disrupting glomerular endothelial cell growth and permeability. Parietal epithelial cells initially compensate by dedifferentiating toward podocytes but later increase collagen deposition, contributing to glomerular sclerosis. Increased interactions of glomerular cells with B cells exacerbate extracellular matrix deposition and scarring. We also observed tubular sclerosis and disruption of the regenerative potential of proximal tubular cells, with increased interaction with T cells. Discussion/Significance of Impact: These findings offer new insights into the pathogenesis of recurrent FSGS and suggest potential therapeutic targets and establishes a foundation for future studies to further evaluate the role of metabolic dysfunction as the cause of podocyte injury and loss.

Monetary incentives are a procedural pillar in experimental economics. By applying four distinct monetary incentive schemes in three experimental finance applications, we investigate the impact of an incentive scheme’s salience on results and elicit subjects’ perception of the experienced scheme. We find (1) no differences in results between salient schemes but a significant impact if the incentive scheme is non-salient. (2) The number of previous participations has a significant impact on the perception of the incentive scheme by subjects: it strongly correlates with subjects’ motives for participation, positively contributes to subjects’ understanding of the incentive scheme, but has no influence on subjects’ motivation within the experiment. (3) Subjects favor more salient over less- or non-salient schemes in the gain domain and negatively evaluate high salience in the loss domain.

In February 2023, 52 cases of gastrointestinal illness were reported in customers of Takeaway A, South Wales. Shigella flexneri serotype 2a was the causative organism. An outbreak investigation was conducted to determine the extent and vehicle of the outbreak.

Following descriptive summary and environmental investigations, a case–control study was completed. Participants completed a telephone questionnaire on food, travel, and environmental exposures. A multivariable logistic regression model was built, including exposures with p-values < 0.2 and interactions identified on stratified analysis. Staff faecal samples were screened for Shigella sp.

Thirty-one cases and 29 controls were included in the study. Eighty-seven per cent of cases and 76% of controls ate from Takeaway A on 10 February 2023. Coleslaw was the main factor associated with illness (aOR: 200, 95% CI: 12–3220) and an interaction with cabbage was identified (aOR: 886, 95% CI: 26–30034). Shigella sp. were not detected in any staff samples.

Coleslaw was the most likely vehicle. Though the contamination route is unknown, a food handler is the most likely source. This large outbreak differs from recent European outbreaks, which primarily have been associated with sexual transmission. Although uncommon in the UK, S. flexneri should be considered as a cause of foodborne outbreaks.

Ongoing policy negotiations, such as the negotiations for a future global plastics treaty, include calls for increased recycling of plastics. However, before recycling of plastics can be considered a safe practice, the flaws in today’s systems must be addressed. Plastics contain a vast range of chemicals, including monomers, polymers, processing agents, fillers, antioxidants, plasticizers, pigments, microbiocides and stabilizers. The amounts and types of chemicals in plastics products vary, and there are little requirements for transparency and reporting. Additionally, they are inherently contaminated with reaction by-products and other nonintentionally added substances (NIASs). As the chemical composition of plastics wastes is largely unknown, and many plastics chemicals are hazardous, they therefore hinder safe recycling since recyclers are not able to exclude materials that contain hazardous chemicals. To address this problem, we suggest the following policy strategies: 1) improved reporting, transparency and traceability of chemicals in plastics throughout their full life cycle; 2) chemical simplification and group-based approaches to regulating hazardous chemicals; 3) chemical monitoring, testing and quality control; 4) economic incentives that follow the waste hierarchy; and 5) support for a just transition to protect people, including waste pickers, impacted throughout the plastics life cycle.

We present results of frequency tripling experiments performed at the Hilase facility on a cryogenically gas cooled multi-slab ytterbium-doped yttrium aluminum garnet laser system, Bivoj/DiPOLE. The laser produces high-energy ns pulses at 10 Hz repetition rate, which are frequency doubled using a type-I phase-matched lithium triborate (LBO) crystal and consequently frequency summed using a type-II phase-matched LBO crystal. We demonstrated a stable frequency conversion to 343 nm at 50 J energy and 10 Hz repetition rate with conversion efficiency of 53%.

Ideally, survey respondents read and understand survey instructions, questions, and response scales, and provide answers that carefully reflect their beliefs, attitudes, or knowledge. However, respondents may also arrive at their responses using cues or heuristics that facilitate the production of a response, but diminish the targeted information content. We use eye-tracking data as covariates in a Bayesian switching-mixture model to identify different response behaviors at the item–respondent level. The model distinguishes response behaviors that are predominantly influenced either positively or negatively by the previous response, and responses that reflect respondents’ preexisting knowledge and experiences of interest. We find that controlling for multiple types of adaptive response behaviors allows for a more informative analysis of survey data and respondents.