Lewy body dementias (LBD) are the second most common dementia. Several genes have been associated with LBD, but little is known about their contributions to LBD pathophysiology. Each gene may transcribe multiple RNA, and LBD brains have extensive RNA splicing dysregulation. Hence, we completed the first transcriptome-wide transcript-level differential expression analysis of post-mortem LBD brains for gaining more insights into LBD molecular pathology that are essential for facilitating discovery of novel therapeutic targets and biomarkers for LBD. We completed transcript-level quantification of next-generation RNA-sequencing data from post-mortem anterior cingulate (ACC) and dorsolateral prefrontal cortices (DLPFC) of people with pathology-verified LBD (LBD = 14; Controls = 7) using Salmon. We identified differentially expressed transcripts (DET) using edgeR and investigated their functional implications using DAVID. We performed transcriptome-wide alternative splicing analysis using DRIMseq. We identified 74 DET in ACC and 96 DET in DLPFC after Benjamini-Hochberg false discovery rate (FDR) correction (5%). There were 135 and 98 FDR-corrected alternatively spliced genes in ACC and DLPFC of LBD brains, respectively. Identified DET may contribute to LBD pathology by altering DNA repair, apoptosis, neuroplasticity, protein phosphorylation, and regulation of RNA transcription. We confirm widespread alternative splicing and absence of chronic neuroinflammation in LBD brains. Transcript-level differential expression analysis can reveal specific DET that cannot be detected by gene-level expression analyses. Therapeutic and diagnostic biomarker potential of identified DET, especially those from TMEM18, MICB, MPO, and GABRB3, warrant further investigation. Future LBD blood-based biomarker studies should prioritise measuring the identified DET in small extracellular vesicles.

The maintenance of cross-cultural variation and arbitrary traditions in human populations is a key question in cultural evolution. Conformist transmission, the tendency to follow the majority, was previously considered central to this phenomenon. However, recent theory indicates that cognitive biases can greatly reduce its ability to maintain traditions. Therefore, we expanded prior models to investigate two other ways that cultural variation can be sustained: payoff-biased transmission and norm reinforcement. Our findings predict that both payoff-biased transmission and reinforcement can enhance conformist transmission's ability to maintain traditions. However, payoff-biased transmission can only sustain cultural variation if it is functionally related to environmental factors. In contrast, norm reinforcement readily generates and maintains arbitrary cultural variation. Furthermore, reinforcement results in path-dependent cultural dynamics, meaning that historical traditions influence current practices, even though group behaviours have changed. We conclude that environmental variation probably plays a role in functional cultural traditions, but arbitrary cultural variation is more plausibly due to the reinforcement of norm compliance.

This article presents the results of the 2008 excavation in the ancient theatre of Sparta conducted by the British School at Athens and the Ephorate of Antiquities of Laconia. Focused on the west side of the cavea, work aimed to locate the southern edge of the Late Antique settlement between the theatre and the sanctuary of Athena Chalkioikos; to establish the northern limits of the Late Antique settlement over the former orchestra; and to establish a more precise ceramic characterisation and chronology for the Early–Middle Byzantine period in Sparta. The area between settlement clusters on the acropolis and over the former orchestra was essentially open, with just a Byzantine terrace wall and path recorded. In the north-west part of the former cavea, a tomb built in the late eighth or early ninth century AD was used at least until the late thirteenth century for the burial of c. 29 individuals. This article presents the first results of a bioarchaeological study of the human remains, and studies of Byzantine pottery from the tomb interior and from the backfill of the pit in which the tomb was built (the latter including a notable quantity of Early Byzantine domestic ware). The 2008 findings are set in the larger context of research on post-antique phases in the theatre (drawing on the British School at Athens Archive) and on the material culture and urban topography of Byzantine Sparta. Almost all excavated contexts contained residual material of all periods. The article concludes with short catalogues of material which pre-dates the construction of the theatre and of inscriptions of all periods.

While humans are highly cooperative, they can also behave spitefully. Yet spite remains understudied. Spite can be normatively driven and while previous experiments have found some evidence that cooperation and punishment may spread via social learning, no experiments have considered the social transmission of spiteful behaviour. Here we present an online experiment where, following an opportunity to earn wealth, we asked participants to choose an action towards an anonymous partner across a full spectrum of social behaviour, from spite to altruism. In accordance with cultural evolutionary theory, participants were presented with social information that varied in source and content. Across six conditions, we informed participants that either the majority or the highest earner had chosen to behave spitefully, neutrally or altruistically. We found an overall tendency towards altruism, but at lower levels among those exposed to spite compared with altruism. We found no difference between social information that came from the majority or the highest earner. Exploratory analysis revealed that participants’ earnings negatively correlated with altruistic behaviour. Our results contrast with previous literature that report high rates of spite in experimental samples and a greater propensity for individuals to copy successful individuals over the majority.

Understanding the distribution and extent of suitable habitats is critical for the conservation of endangered and endemic taxa. Such knowledge is limited for many Central African species, including the rare and globally threatened Grey-necked Picathartes Picathartes oreas, one of only two species in the family Picathartidae endemic to the forests of Central Africa. Despite growing concerns about land-use change resulting in fragmentation and loss of forest cover in the region, neither the extent of suitable habitat nor the potential species’ distribution is well known. We combine 339 (new and historical) occurrence records of Grey-necked Picathartes with environmental variables to model the potential global distribution. We used a Maximum Entropy modelling approach that accounted for sampling bias. Our model suggests that Grey-necked Picathartes distribution is strongly associated with steeper slopes and high levels of forest cover, while bioclimatic, vegetation health, and habitat condition variables were all excluded from the final model. We predicted 17,327 km2 of suitable habitat for the species, of which only 2,490 km2 (14.4%) are within protected areas where conservation designations are strictly enforced. These findings show a smaller global distribution of predicted suitable habitat forthe Grey-necked Picathartes than previously thought. This work provides evidence to inform a revision of the International Union for Conservation of Nature (IUCN) Red List status, and may warrant upgrading the status of the species from “Near Threatened” to “Vulnerable”.

A numerical investigation is undertaken on the development of linear disturbances in the rotating disk boundary layer, in which a time-periodic modulation is applied to the disk rotation rate. The model gives a prototypical example of a three-dimensional oscillatory boundary layer, by adding a Stokes layer to the von Kármán flow that develops on a steady disk. The study extends the Floquet analysis of Morgan et al. (J. Fluid Mech., vol. 925, 2021, A20), who showed that disk modulation stabilises the stationary convective instabilities found on the steady rotating disk. Using a radial homogeneous flow approximation, whereby the radial dependence of the basic state is ignored, disturbance development is simulated for several modulation settings, with flow conditions matched to both convective and absolute forms of linear instability. Disturbances excited via a stationary periodic wall forcing display behaviour consistent with that found using Floquet theory; time-periodic modulation stabilises the cross-flow instability by reducing the radial growth rate. In addition, convective and absolute instabilities, generated by an impulsive wall forcing, are both stabilised by the introduction of modulation to the disk rotation rate. Modulation establishes a significant reduction in both the temporal growth rate and the disturbance amplitude as it propagates away from the impulse origin. Moreover, greater stabilising control benefits are realised as the modulation amplitude increases.

Background: Bacterial coinfections with COVID-19 appear to be rare, yet antibiotic use in this population is high. Limited guidance is available regarding the use of antibiotics in these patients. In response, a multidisciplinary group of physicians and pharmacists from 5 VISN9 facilities developed a guideline for the use of antibiotics with COVID-19 in July 2021. This guideline created a network-wide standard for antibiotic use and facilitates the assessment of antibiotic appropriateness in hospitalized veterans with COVID-19. Methods: In this observational, cross-sectional study, we reviewed veterans diagnosed with COVID-19 from August 1 through September 30, 2021, who were admitted to VISN9 facilities. Use of antibiotics was assessed during the first 4 days of admission. If antibiotics were prescribed, their use was determined to be appropriate or inappropriate based on the presence or absence of a finding concerning for bacterial coinfection as outlined in the guideline (Table 1). Additional data including procalcitonin results as well as positive sputum cultures were collected. Results: In total, 377 veterans were admitted for COVID-19 during the study period. Among them, 42 veterans (11%) received antibiotics for nonrespiratory infections and were removed from this analysis. Of the remaining 335 veterans, 229 (68%) received antibiotics and 116 (51%) of those met guideline criteria that were concerning for bacterial coinfection. Additionally, 32 (14%) of the 229 veterans who received antibiotics had >1 finding concerning for bacterial coinfection. Procalcitonin levels were obtained in 97 (42%) of 229. Only 33 veterans (14%) who received antibiotics had an elevated procalcitonin, and only 19 (8%) had a positive sputum culture. Conclusions: Antibiotic use was common in hospitalized veterans with COVID-19 in VISN9 facilities. This results are comparable to findings in the published literature. Among those receiving antibiotics early in their hospitalization, half were considered appropriate based on our guideline. Quality improvement initiatives are needed to improve implementation of the network guideline to reduce the overuse of antibiotics for management of COVID-19. Additionally, procalcitonin may be a helpful tool for hospitalized veterans with COVID-19.

Funding: None

Disclosures: None

OBJECTIVES/GOALS: The Fulkerson Home Food Inventory (HFI) is widely used to assess the home food environment, a key target of behavioral weight loss trials. However, no standardized report is available. We created publicly available procedures to automate and standardize HFI reporting, yielding a personalized report to enhance this measures clinical utility. METHODS/STUDY POPULATION: Parents in the TEENS adolescent behavioral weight loss trial complete the HFI at 0-, 2-, 4-, 8-, and 12m and receive personalized reports at each timepoint. In REDCap, participants identify foods available in their home. HFI syntax is applied to calculate the obesogenic home food availability score. Categories of foods found are identified, with specific guidance provided to enhance their home food environment. Prior to automation, procedures were time intensive and error prone. To address this, HFI data are exported into Excel by a PowerShell (v7.2) command-line script using Python (v3.10) with the REDCap API. Results are calculated with F# (v6.0) using Microsoft Excel Interop API and inserted into a report template with F# using the Microsoft Publisher Interop API. This process is repeated at each timepoint. RESULTS/ANTICIPATED RESULTS: The new automated procedures significantly reduce time to generate reports and enhance accuracy. Procedures yield a 2-page individualized report that includes the obesogenic home food environment score and identifies categories of healthy items found (e.g., fruits, vegetables, whole grains) as well as areas of improvement (e.g., high-fat dairy products, processed meats). Specific items found in each category are identified. The report identifies food found in the home (e.g., chicken nuggets) with suggested healthier substitutions (e.g., lean chicken breast). This syntax and commands will be made publicly available for use in the scientific and clinical community. DISCUSSION/SIGNIFICANCE: These publicly available procedures optimize, automate, and standardize reporting for the HFI. Procedures improve efficiency within large-scale clinical trials and yield a personalized report to enhance the clinical utility of this measure and empower participants to make informed decisions about their health behaviors.

The control of stationary convective instabilities in the rotating disk boundary layer via a time-periodic modulation of the disk rotation rate is investigated. The configuration provides an archetypal example of a three-dimensional temporally periodic boundary layer, encompassing both the von Kármán and Stokes boundary layers. A velocity–vorticity formulation of the governing perturbation equations is deployed, together with a numerical procedure that utilises the Chebyshev-tau method. Floquet theory is used to determine the linear stability properties of these time-periodic flows. The addition of a time-periodic modulation to the otherwise steady disk rotation rate establishes a stabilising effect. In particular, for a broad range of modulation frequencies, the growth of the stationary convective instabilities is suppressed and the critical Reynolds number for the onset of both the cross-flow and Coriolis instabilities is raised to larger values than that found for the steady disk without modulation. An energy analysis is undertaken, where it is demonstrated that time-periodic modulation induces a reduction in the Reynolds stress energy production and an increase in the viscous dissipation across the boundary layer. Comparisons are made with other control techniques, including distributed surface roughness and compliant walls.

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.

Humans are remarkable in their reliance on cultural inheritance, and the ecological success this has produced. Nonetheless, we lack a thorough understanding of how the cognitive underpinnings of cultural transmission affect cultural adaptation across diverse tasks. Here, we use an agent-based simulation to investigate how different learning mechanisms (both social and asocial) interact with task structure to affect cultural adaptation. Specifically, we compared learning through refinement, recombination or both, in tasks of different difficulty, with learners of different asocial intelligence. We find that for simple tasks all learning mechanisms are roughly equivalent. However, for hard tasks, performance was maximised when populations consisted of highly intelligent individuals who nonetheless rarely innovated and instead recombined existing information. Our results thus show that cumulative cultural adaptation relies on the combination of individual intelligence and ‘blind’ population-level processes, although the former may be rarely used. The counterintuitive requirement that individuals be highly intelligent, but rarely use this intelligence, may help resolve the debate over the role of individual intelligence in cultural adaptation.

What promised to be a refreshing addition to cumulative cultural evolution, by moving the focus from cultural transmission to technological innovation, falls flat through a lack of thoroughness, explanatory power, and data. A comprehensive theory of cumulative cultural change must carefully integrate all existing evidence in a cohesive multi-level account. We argue that the manuscript fails to do so convincingly.