Rýzmburk Castle is one of the largest and most important medieval castles in Bohemia, documented since 1250 AD. Its North tower is assumed to be built in 1260–1300 AD. To test this assumption, the surface layers of mortar were inspected for the presence of charcoals suitable for radiocarbon dating, and 10 charcoals were found. The charcoals probably originated from wood used for lime burning. The results of radiocarbon dating using accelerator mass spectrometry agree with the historical estimation. Single post-1287 sample indicates that the building date might be refined to 1287–1300 AD.

Organisational priorities for health care focus on efficiency as the health and care needs of populations increase. But evidence suggests that excessive planning can be counterproductive, leading to resistance from staff and patients, particularly those living with cognitive impairment. The current paper adds to this debate reporting an Institutional Ethnography of staff delivering care for older patients with cognitive impairment on acute orthopaedic wards in three National Health Service hospitals in the United Kingdom. A key problematic identified in this study is the point of disjuncture seen between the actualities of staff experience and intentions of protocols and policies. We identified three forms of disjuncture typified as: ‘disruptions’, where sequenced care was interrupted by patient events; ‘discontinuities’, where divisions in professional culture, space or time interrupted sequenced tasks; and ‘dispersions’, where displaced objects or people interrupted sequenced care flow. Arguably disruption is an integral characteristic of care work; it follows that to enable staff to flourish, organisations need to confer staff the autonomy to address systemic disruptions rather than attempt to eradicate them. Ultimately, organisational representations of ‘good practice’ as readily joined up, impose a care standard ‘stereotype’ that obscures rather than clarifies the interactional problems encountered by staff.

Phylogenetic analyses can be used to resolve taxonomic uncertainties and reconstruct a species’ evolutionary history. This can be combined with ecological data to predict missing life history traits which are important for creation of conservation management strategies. We investigated the evolutionary and life history of the ‘Critically Endangered’ Grenada Dove Leptotila wellsi by estimating its phylogenetic placement and using this new phylogeny to test the accuracy of phylogenetic comparative methods for estimating both documented and unknown life history traits. We extracted DNA from two Grenada Dove samples and obtained sequences from three mitochondrial markers: Cytochrome oxidase I (COI), NADH dehydrogenase 2 (ND2) and Cytochrome b (Cyt b); and one nuclear marker: β-Fibrinogen intron 7 (β-FIB). We present the first genetic data obtained for the Grenada Dove. Our data identify the Grey-Chested Dove Leptotila cassinii as the species which shares both a most recent common ancestor, with an estimated divergence of approximately 2.53 million years ago, and the smallest genetic distance (P = 0.0303) with the Grenada Dove. Life history trait values for the Grenada Dove predicted from our analyses using phylogenetic imputation are: clutch size = 2 (± 0.09) eggs; clutches per year = 1.4 (± 0.81); incubation time = 14.2 (± 0.75) days; hatching weight = 3.8 g (± 1.05) and single imputation: fledging age (genus median) = 15.5 days, longevity (genus median) = 8.6 years. This study contributes novel information regarding evolutionary history and life history characteristics to inform long-term conservation actions for a ‘Critically Endangered’ species.

This article analyses orthographic variation in the Linear B tablets from the Mycenaean palace of Pylos. Despite the general consistency in spelling found in Linear B texts from all sites, variation was in certain cases both permissible and entirely normal, even within the work of a single writer. Examining the patterns of orthographic variation found in the texts from Pylos, along with the factors which may have influenced this variation, sheds light on how the Mycenaean scribes were taught to write and how they applied this training in the process of creating their documents.

OBJECTIVES/GOALS: The goal was to develop foundational research knowledge and skills for clinicians interested in conducting clinical research. Emphasis was on the development of a research question and the iterative process necessary to transform a research question into a well-designed study and well-articulated research proposal for pilot grant funding. METHODS/STUDY POPULATION: The course took place over 10 sessions, May - September 2021. The application process required participants to provide an initial self-assessment of research skills and a proposed research question. 25 clinicians applied to the program, 11 were accepted, and 9 enrolled. All clinicians in the initial cohort were clinical faculty physicians. Because of the geographical distance of participants as well as the ongoing pandemic, the course used a blended learning approach with both synchronous and asynchronous learning. Participants viewed online lectures on core content coupled with live virtual sessions with opportunities for discussion and application of the content. Relevant CTSI and institutional resources were highlighted in each session. RESULTS/ANTICIPATED RESULTS: Of the 9 clinician participants who enrolled in Research 101, the average attendance per session was 67% or 6 people. 89% or 8 participants attended five or more sessions. 5 participants submitted a letter of intent for the annual CTSI Pilot grant program, and of the five, two were invited to submit a grant application. Formal evaluation of the program is currently ongoing and will close on November 30th, at which time full results will be available. Research competencies will be assessed through a pre-post comparison, each self-rated by course participants. Additionally, participants were asked to provide input on the most and least valuable components of the course, as well as any open-ended feedback. Research 101 leadership will use these results to improve the course for future participants. DISCUSSION/SIGNIFICANCE: A learning health system (LHS) is recognized as an essential means by which research evidence is translated into practice. Important to realizing the LHS vision is the engagement of clinicians into the generation and translation of research into practice. Research 101 is an important way to bolster clinician engagement in translational research.

Early psychosocial adversities exist at many levels, including caregiving-related, extrafamilial, and sociodemographic, which despite their high interrelatedness may have unique impacts on development. In this paper, we focus on caregiving-related early adversities (crEAs) and parse the heterogeneity of crEAs via data reduction techniques that identify experiential cooccurrences. Using network science, we characterized crEA cooccurrences to represent the comorbidity of crEA experiences across a sample of school-age children (n = 258; 6–12 years old) with a history of crEAs. crEA dimensions (variable level) and crEA subtypes (subject level) were identified using parallel factor analysis/principal component analysis and graph-based Louvain community detection. Bagging enhancement with cross-validation provided estimates of robustness. These data-driven dimensions/subtypes showed evidence of stability, transcended traditional sociolegally defined groups, were more homogenous than sociolegally defined groups, and reduced statistical correlations with sociodemographic factors. Finally, random forests showed both unique and common predictive importance of the crEA dimensions/subtypes for childhood mental health symptoms and academic skills. These data-driven outcomes provide additional tools and recommendations for crEA data reduction to inform precision medicine efforts in this area.

The Centers for Medicare and Medicaid mandated that nursing homes implement antibiotic stewardship programs (ASPs) by November 2017. We conducted surveys of Wisconsin nursing-home stewardship practices before and after this mandate. Our comparison of these surveys shows an overall increase in ASP implementation efforts, but it also highlights areas for further improvement.

The crosstalk between maternal stress exposure and fetal development may be mediated by epigenetic mechanisms, including DNA methylation (DNAm). To address this matter, we collect 32 cord blood samples from low-income Brazilian pregnant adolescents participants of a pilot randomized clinical intervention study (ClinicalTrials.gov, Identifier: NCT02807818). We hypothesized that the association between the intervention and infant neurodevelopmental outcomes at 12 months of age would be mediated by DNAm. First, we searched genome methylation differences between cases and controls using different approaches, as well as differences in age acceleration (AA), represented by the difference of methylation age and birth age. According to an adjusted p-value ≤ 0.05 we identified 3090 differentially methylated positions- CpG sites (DMPs), 21 differentially methylated regions (DMRs) and one comethylated module weakly preserved between groups. The intervention group presented a smaller AA compared to the control group (p = 0.025). A logistic regression controlled by sex and with gestational age indicated a coefficient of −0.35 towards intervention group (p = 0.016) considering AA. A higher cognitive domain score from Bayley III scale was observed in the intervention group at 12 months of age. Then, we performed a potential causal mediation analysis selecting only DMPs highly associated with the cognitive domain (adj. R2 > 0.4), DMRs and CpGs of hub genes from the weakly preserved comethylated module and epigenetic clock as raw values. DMPs in STXBP6, and PF4 DMR, mediated the association between the maternal intervention and the cognitive domain at 12 months of age. In conclusion, DNAm in different sites and regions mediated the association between intervention and cognitive outcome.

Caracterizar las estrategias de movilidad de las sociedades cazadoras-recolectoras-pescadoras en ambientes insulares y litorales es fundamental para comprender la interacción humano-ambiental en el pasado. Las prospecciones en el noreste de la isla Diego Portales, en el mar interior de Última Esperanza (Magallanes, Chile), han permitido documentar ocho yacimientos arqueológicos formados por uno o varios conchales. Todos ellos se hallan ubicados en áreas de la costa al resguardo del viento dominante y con fácil acceso mediante embarcación. Los trabajos arqueológicos en dos de estos yacimientos (Bahía Easter 1 y 2) indican una estrategia de subsistencia similar durante el Holoceno tardío final, basada en el aprovechamiento de la biodiversidad de este ambiente de ecotono, con más de una docena de recursos marinos y terrestres consumidos. Entre éstas destaca en abundancia el huemul (Hippocamelus bisulcus), probablemente cazado en el litoral continental. Teniendo en cuenta las dinámicas de poblamiento y movilidad propuestas desde la etnografía o la arqueología para otras áreas del archipiélago fuego-patagónico, los resultados permiten discutir la reocupación sucesiva de puntos estratégicos de la isla, particularmente en primavera-verano, cuando la encrucijada de caminos y recursos que representa el mar interior de Última Esperanza presentaba alicientes significativos para las comunidades canoeras.