Distinguishing early domesticates from their wild progenitors presents a significant obstacle for understanding human-mediated effects in the past. The origin of dogs is particularly controversial because potential early dog remains often lack corroborating evidence that can provide secure links between proposed dog remains and human activity. The Tumat Puppies, two permafrost-preserved Late Pleistocene canids, have been hypothesized to have been littermates and early domesticates due to a physical association with putatively butchered mammoth bones. Through a combination of osteometry, stable isotope analysis, plant macrofossil analysis, and genomic and metagenomic analyses, this study exploits the unique properties of the naturally mummified Tumat Puppies to examine their familial relationship and to determine whether dietary information links them to human activities. The multifaceted analysis reveals that the 14,965–14,046 cal yr BP Tumat Puppies were littermates who inhabited a dry and relatively mild environment with heterogeneous vegetation and consumed a diverse diet, including woolly rhinoceros in their final days. However, because there is no evidence of mammoth consumption, these data do not establish a link between the canids and ancient humans.

Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.

The Society for Healthcare Epidemiology of America, the Association of Professionals in Infection Control and Epidemiology, the Infectious Diseases Society of America, and the Pediatric Infectious Diseases Society represent the core expertise regarding healthcare infection prevention and infectious diseases and have written multisociety statement for healthcare facility leaders, regulatory agencies, payors, and patients to strengthen requirements and expectations around facility infection prevention and control (IPC) programs. Based on a systematic literature search and formal consensus process, the authors advocate raising the expectations for facility IPC programs, moving to effective programs that are:

• Foundational and influential parts of the facility’s operational structure

• Resourced with the correct expertise and leadership

• Prioritized to address all potential infectious harms

This document discusses the IPC program’s leadership—a dyad model that includes both physician and infection preventionist leaders—its reporting structure, expertise, and competencies of its members, and the roles and accountability of partnering groups within the healthcare facility. The document outlines a process for identifying minimum IPC program medical director support. It applies to all types of healthcare settings except post-acute long-term care and focuses on resources for the IPC program. Long-term acute care hospital (LTACH) staffing and antimicrobial stewardship programs will be discussed in subsequent documents.

Commercial targeted sprayer systems allow producers to reduce herbicide inputs but risks the possibility of not treating emerging weeds. Currently, targeted applications with the John Deere system have five spray sensitivity settings, and no published literature discusses the effects of these settings on detecting and spraying weeds of varying species, sizes, and positions in crops. Research was conducted in Arkansas, Illinois, Indiana, Mississippi, and North Carolina on plantings of corn, cotton, and soybean to determine how various factors might influence the ability of targeted applications to treat weeds. These data included 21 weed species aggregated to six classes with height, width, and densities ranging from 25 to 0.25 cm, 25 to 0.25 cm, and 14.3 to 0.04 plants m−2, respectively. Crop and weed density did not influence the likelihood of treating the weeds. As expected, the sensitivity setting alters the ability to treat weeds. Targeted applications (across sensitivity settings, median weed height and width, and density of 2.4 plants m−2) resulted in a treatment success of 99.6% to 84.4% for Convolvulaceae, 99.1% to 68.8% for decumbent broadleaf weeds, 98.9% to 62.9% for Malvaceae, 99.1% to 70.3% for Poaceae, 98.0% to 48.3% for Amaranthaceae, and 98.5% to 55.8% for yellow nutsedge. Reducing the sensitivity setting reduced the ability to treat weeds. The size of weeds aided targeted application success, with larger weeds being more readily treated through easier detection. Based on these findings, various conditions can affect the outcome of targeted multinozzle applications. Additionally, the analyses highlight some of the parameters to consider when using these technologies.

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.

Objectives/Goals: Transmission-blocking vaccines hold promise for malaria elimination by reducing community transmission. But a major challenge that limits the development of efficacious vaccines is the vast parasite’s genetic diversity. This work aims to assess the genetic diversity of the Pfs25 vaccine candidate in complex infections across African countries. Methods/Study Population: We employed next-generation amplicon deep sequencing to identify nonsynonymous single nucleotide polymorphisms (SNPs) in 194 Plasmodium falciparum samples from four endemic African countries: Senegal, Tanzania, Ghana, and Burkina Faso. The individuals aged between 1 and 74 years, but most of them ranged from 1 to 19 years, and all presented symptomatic P. falciparum infection. The genome amplicon sequencing was analyzed using Geneious software and P. falciparum 3D7 as a reference. The SPNs were called with a minimum coverage of 500bp, and for this work, we used a very sensitive threshold of 1% variant frequency to determine the frequency of SNPs. The identified SNPs were threaded to the crystal structure of the Pfs25 protein, which allowed us to predict the impact of the novel SNP in the protein or antibody binding. Results/Anticipated Results: We identified 26 SNPs including 24 novel variants, and assessed their population prevalence and variant frequency in complex infections. Notably, five variants were detected in multiple samples (L63V, V143I, S39G, L63P, and E59G), while the remaining 21 were rare variants found in individual samples. Analysis of country-specific prevalence showed varying proportions of mutant alleles, with Ghana exhibiting the highest prevalence (44.6%), followed by Tanzania (12%), Senegal (11.8%), and Burkina Faso (2.7%). Moreover, we categorized SNPs based on their frequency, identifying dominant variants (>25%), and rare variants (Discussion/Significance of Impact: We identified additional SNPs in the Pfs25 gene beyond those previously reported. However, the majority of these newly discovered display low variant frequency and population prevalence. Further research exploring the functional implications of these variations will be important to elucidate their role in malaria transmission.

Starting in late September 1872, horses started falling ill with a severe respiratory complaint in the countryside about a dozen miles north of Toronto, Ontario. Veterinary experts swiftly diagnosed the malady, which paralyzed street transportation, commerce, and everyday life in Toronto itself during the first weeks of October, as influenza. Over the next year, an equine plague that most contemporaries referred to as the epizootic—and which I call the Great Horse Flu in the book I am completing on this outbreak—spread throughout southern Canada, every reach of the United States, and parts of Cuba, Mexico, and Central America. The novel influenza virus responsible for this outbreak sickened between ninety and ninety-nine percent of horses, donkeys, and mules across this vast swath of the northern Americas.1 Our best guess is that the Great Horse Flu killed between one and four percent of the equines it afflicted—a case fatality rate roughly not unlike those recorded by the Great Influenza Pandemic of 1918–1920 and the COVID Pandemic. In less than a year, an estimated 112,500 to 554,000 horses and ponies perished alongside tens or hundreds of thousands of mules and donkeys.2

The nature and extent of interactions between the distant regions and cultures of Mesoamerica remain open to much debate. Close economic and political ties developed between Teotihuacan and the lowland Maya during the Early Classic period (AD 250–550), yet the relationship between these cultures continues to perplex scholars. This article presents an elaborately painted altar from an elite residential group at the lowland Maya centre of Tikal, Guatemala. Dating to the fifth century AD, the altar is unique in its display of Teotihuacan architectural and artistic forms, adding to evidence not only for cultural influence during this period, but also for an active Teotihuacan presence at Tikal.

Overbidding in sealed-bid second-price auctions (SPAs) has been shown to be persistent and associated with cognitive ability. We study experimentally to what extent cross-game learning can reduce overbidding in SPAs, taking into account cognitive skills. Employing an order-balanced design, we use first-price auctions (FPAs) to expose participants to an auction format in which losses from high bids are more salient than in SPAs. Experience in FPAs causes substantial cross-game learning for cognitively less able participants but does not affect overbidding for the cognitively more able. Vice versa, experiencing SPAs before bidding in an FPA does not substantially affect bidding behavior by the cognitively less able but, somewhat surprisingly, reduces bid shading by cognitively more able participants, resulting in lower profits in FPAs. Thus, ‘cross-game learning’ may rather be understood as ‘cross-game transfer’, as it has the potential to benefit bidders with lower cognitive ability whereas it has little or even adverse effects for higher-ability bidders.

Planktonic foraminifera are extremely well suited to studying evolutionary change in the fossil record due to their abundant deposits and global distribution. Species are typically conservative in their shell morphology, with the same geometric shapes appearing repeatedly through iterative evolution, but the mechanisms behind the architectural limits on foraminiferal shell shape are still not well understood. To determine how these developmental constraints arise, we study morphological change leading up to the origination of the unusually ornate species Globigerinoidesella fistulosa. We measured the size and circularity of more than 900 specimens of G. fistulosa, its ancestor the Trilobatus sacculifer plexus, and intermediate forms from a site in the western equatorial Pacific. Our results show that the origination of G. fistulosa from the T. sacculifer plexus involved a combination of two heterochronic expressions: earlier onset of protuberances (pre-displacement) and a steeper allometric slope (acceleration) as compared with its ancestor. Our work provides a case study of the complex morphological and developmental changes required to produce unusual shell shapes and highlights the importance of developmental deviations in evolutionary origination.

A concept for a femtosecond pulse compressor based on underdense plasma prisms is presented. An analytical model is developed to calculate the spectral phase incurred and the expected pulse compression. A 2D particle-in-cell simulation verifies the analytical model. Simulated intensities (${\sim} {10}^{16}$ W/cm2) were orders of magnitude higher than the damage threshold for conventional gratings used in chirped pulse amplification. Theoretical geometries for compact (tens of cm scale) compressors for 1, 10 and 100 PW power levels are proposed.

Interval estimates of the Pearson, Kendall tau-a and Spearman correlations are reviewed and an improved standard error for the Spearman correlation is proposed. The sample size required to yield a confidence interval having the desired width is examined. A two-stage approximation to the sample size requirement is shown to give accurate results.

In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes in the baseline neurovascular state can result in significant modulations of the BOLD signal that are independent of changes in neural activity. This paper introduces some of the normalization and calibration methods that have been proposed for making the BOLD signal a more accurate reflection of underlying brain activity for human fMRI studies.