Recent genomic analysis of a skull fragment from Newgrange, Ireland, revealed a rare case of incest. Together with a wider network of distantly related passage tomb interments, this has bolstered claims of a social elite in later Neolithic Ireland. Here, the authors evaluate this social evolutionary interpretation, drawing on insecurities in context and the relative rarity of engendered status or resource restrictions in the archaeological record of prehistoric Ireland to argue that the status of individuals during this period is better understood through unstable identity negotiations. Inclusion in a passage tomb, while ‘special’, need not equate to a perpetual elite.

This paper re-evaluates recent kinship studies in Neolithic Ireland through a close analysis of biomolecular and fine-grained archaeological data. It outlines the rich possibilities these datasets offer when interwoven to enhance our understanding of diverse webs of social relationships. We synthesize a range of archaeological and scientific data to form a new model of kinship and its relationship to shifting traditions of megalith building and funerary and cosmological practices. This model is put in dialogue with recently published genetic data and used to test a variety of explanations for the patterns of biological relatedness revealed using these methods. We argue that the detected genetic patterning is best interpreted as reflecting a reconfiguration of social relations after 3600 bc linked to the consolidation of emergent social and religious communities.

The sustainable management of herbicides is critical to modern agriculture and the environment. This article examines the evolution and environmental implications of herbicide use in Saskatchewan, Canada, agriculture. It quantifies changes in herbicide use and their environmental impacts by analyzing farm-level herbicide use data from 1991 to 1994 and from 2016 to 2019 through the environmental impact quotient. Results confirm significant reductions in both environmental and toxicological impacts of herbicides used, underlining the pivotal shift from tillage-based weed control to herbicide-resistant cropping systems. The environmental impact of the top five herbicides (glufosinate, glyphosate, clethodim, imazamox, and 2,4-D) used from 2016 to 2019 is 65% lower than that for those herbicides (MCPA, 2,4-D, bromoxynil, diclofop-methyl, and trifluralin) used from 1991 to 1994, with a 45% reduction in the active ingredient applied per acre. Despite increased herbicide use due to more crop acres being seeded, the findings highlight a marked improvement in the sustainability of herbicide use, affirming the importance of technological advancements in agriculture. This research contributes valuable insights into long-term trends in herbicide use, offering a practical framework for informed decisions aligning with sustainable agricultural practices as well as reduced biodiversity impacts.

OBJECTIVES/GOALS: Platelets reside at the nexus of thrombosis and inflammation which make them an ideal target of investigation to understand mechanisms underlying chronic kidney disease (CKD)-related inflammatory and thrombotic dysregulation. Our objective is to determine whether a pro-inflammatory state in CKD is exacerbated by platelets. METHODS/STUDY POPULATION: Aim 1 will investigate effects of engineered reduction in the interaction of platelets with leukocytes [by disruption of one of the platelet surface receptor (GPIb-IX)] in the development of CKD in murine models. Aim 2 will investigate effects of platelet inhibitors on the development of CKD in murine models. RESULTS/ANTICIPATED RESULTS: We anticipate that the proposed studies in Aim 1 will demonstrate reduction in the interaction of platelets with leukocytes results in exacerbation of kidney injury upon CKD induction with cisplatin. We also anticipate that inhibition of platelets in Aim 2 with P2Y12 receptor inhibitors results in reduction in kidney injury upon CKD induction with cisplatin. DISCUSSION/SIGNIFICANCE: Upon successful completion of the proposed studies, we shall be able to better describe the role of platelets as modulators of inflammation in CKD. This will be a significant stride towards understanding the pathophysiology of a pro-inflammatory state in CKD and how platelets exacerbate inflammation and thrombosis in this population.

Zebra finches are often housed in monogamous pairs in small barren cages. In the present study it was investigated whether modest enrichment resulted in behavioural changes. Four plywood box cages of two different lengths were compared. A small and a large cage were used for the barren environment. Another small and large cage were used for the enriched environment, and included additional perches, twigs as well as sand and water baths. An ethogram consisting of 19 different behavioural patterns was used. The behaviour of the birds was studied using a combination of alternating (20s) one-zero and instantaneous sampling, one hour per day during a continuous four-week period.

Locomotor activity, vocalization and singing was significantly increased in the enriched cages and flying was more frequent in the large enriched cage than in any of the other cages. The study demonstrated the usefulness of behavioural analyses to determine to what extent simple enrichment allows the birds to exhibit a wider range of their natural behaviour.

Globally, internal medicine (IM) residents often feel they lack the knowledge and skills to approach patients presenting with neurologic issues. We conducted a multiple method needs assessment to determine the feasibility of a novel neurology flipped classroom (FC) curriculum for internal medicine residents. Our primary findings include participants: (1) finding neurology a useful rotation; (2) feeling uncomfortable with the neurological examination; and (3) endorsing flipped classroom as a potential alternative but with significant barriers. Our findings elucidate upon the various extrinsic/intrinsic motivators for resident education and illustrate the need to re-examine the way in which neurology is being taught to off-service residents.

Background: Rituximab is a B-cell-depleting monoclonal antibody whose off-label use is funded in Alberta by the Short-Term Exceptional Drug Therapy (STEDT) program. This study describes the use of rituximab for pediatric central nervous system (CNS) inflammatory disorders in Alberta. Methods: Rituximab applications for CNS inflammatory indications in patients < 18 years of age were identified from the STEDT database between January 1, 2012 – December 31, 2019. Patient information was linked to other provincial datasets, including the Discharge Abstract Database, Pharmaceutical Information Network, and provincial laboratory data. Analysis was descriptive. Results: 51 unique rituximab applications were identified, of which 50 were approved. New applications increased from one in 2012 to a high of 12 in 2018. The most common indication was autoimmune encephalitis (other than anti-NMDA receptor encephalitis; n=20, 39%). Most children were approved for a two-dose (n=33, 66%) or four-dose (n=16, 32%) induction regimen. Physician-reported outcomes were available for 24 patients, of whom 14 (58%) were felt to have fully met outcome targets. Conclusions: The use of rituximab for pediatric CNS inflammatory disorders has increased, particularly for the indication of autoimmune encephalitis. This study identified significant heterogeneity in dosing practices and laboratory monitoring, as well as regional disparities in use.

Advanced maternal age (AMA) is known to reduce fertility, increases aneuploidy in oocytes and early embryos and leads to adverse developmental consequences which may associate with offspring lifetime health risks. However, investigating underlying effects of AMA on embryo developmental potential is confounded by the inherent senescence present in maternal body systems further affecting reproductive success. Here, we describe a new model for the analysis of early developmental mechanisms underlying AMA by the derivation and characterisation of mouse embryonic stem cell (mESC-like) lines from naturally conceived embryos. Young (7–8 weeks) and Old (7–8 months) C57BL/6 female mice were mated with young males. Preimplantation embryos from Old dams displayed developmental retardation in blastocyst morphogenesis. mESC lines established from these blastocysts using conventional techniques revealed differences in genetic, cellular and molecular criteria conserved over several passages in the standardised medium. mESCs from embryos from AMA dams displayed increased incidence of aneuploidy following Giemsa karyotyping compared with those from Young dams. Moreover, AMA caused an altered pattern of expression of pluripotency markers (Sox2, OCT4) in mESCs. AMA further diminished mESC survival and proliferation and reduced the expression of cell proliferation marker, Ki-67. These changes coincided with altered expression of the epigenetic marker, Dnmt3a and other developmental regulators in a sex-dependent manner. Collectively, our data demonstrate the feasibility to utilise mESCs to reveal developmental mechanisms underlying AMA in the absence of maternal senescence and with reduced animal use.

The analysis of processing standards alongside samples for quality assurance in radiocarbon (14C) analyses is critical. Ideally, these standards should be similar both in nature and age to unknown samples. A new compound-specific approach was developed at the University of Bristol for dating pottery vessels using palmitic and stearic fatty acids extracted from within the clay matrix and isolated by preparative capillary gas chromatography. Obtaining suitable potsherds for use as processing standards in such analyses is not feasible, so we suggest that bog butter represents an ideal material for such purposes. We sampled ca. 450 g from two bog butter specimens and homogenized them by melting. We verified the homogeneity of both specimens by characterization of their lipid composition, δ13C values of individual lipids, and both bulk- and compound-specific radiocarbon analyses on 10 sub-samples of each bog butter specimen. The weighted means of all 14C measurements on the bog butter standards are 3777 ± 4 BP (IB33) and 338 ± 3 BP (IB38), thereby providing age-relevant standards for archaeological and historical fatty acids and ensuring the accuracy of radiocarbon determinations of lipids using a compound-specific approach. These new secondary standards will be subjected to an intercomparison exercise to provide robust consensus values.

The equation of state of Fo90 hydrous ringwoodite has been measured using X-ray powder diffraction to 45 GPa at the GSECARS beam line at the Advanced Photon Source synchrotron at Argonne National Laboratory. The sample was synthesized at 1400°C and 20 GPa in the 5000 ton multi anvil press at Bayerisches Geoinstitut in Bayreuth. The sample has the formula Mg1.70Fe0.19 2+ Fe0.02 3+H0.13- Si1.00O4 as determined by electron microprobe, Fourier transform infrared and Mössbauer spectroscopies, and contains ~0.79% H2O by weight. Compression of the sample had been been measured previously to 11 GPa by single crystal X-ray diffraction. A third-order Birch-Murnaghan equation of state fit to all of the data gives V 0 = 530.49±0.07 Å3, K 0 = 174.6±2.7 GPa and K ' = 6.2±0.6. The effect of 1% H incorporation in the structure on the bulk modulus is large and roughly equivalent to an increase in the temperature of ∼600°C at low pressure. The large value of K' indicates significant stiffening of the sample with pressure so that the effect of hydration decreases with pressure.

Thalénite-(Y), ideally Y3Si3O10F, is a heavy-rare-earth-rich silicate phase occurring in granite pegmatites that may help to illustrate rare-earth element (REE) chemistry and behaviour in natural systems. The crystal structure and mineral chemistry of thalénite-(Y) were analysed by electron microprobe analysis, X-ray diffraction and micro-Raman spectroscopy from a new locality in the peralkaline granite of the Golden Horn batholith, Okanogan County, Washington State, USA, in comparison with new analyses from the White Cloud pegmatite in the Pikes Peak batholith, Colorado, USA. The Golden Horn thalénite-(Y) occurs as late-stage sub-millimetre euhedral bladed transparent crystals in small miarolitic cavities in an arfvedsonite-bearing biotite granite. It exhibits growth zoning with distinct heavy-rare-earth element (HREE) vs. light-rare-earth element (LREE) enriched zones. The White Cloud thalénite-(Y) occurs in two distinct anhedral and botryoidal crystal habits of mostly homogenous composition. In addition, minor secondary thalénite-(Y) is recognized by its distinct Yb-rich composition (up to 0.8 atoms per formula unit (apfu) Yb). Single-crystal X-ray diffraction analysis and structure refinement reveals Y-site ordering with preferential HREE occupation of Y2 vs. Y1 and Y3 REE sites. Chondrite normalization shows continuous enrichment of HREE in White Cloud thalénite-(Y), in contrast to Golden Horn thalénite-(Y) with a slight depletion of the heaviest REE (Tm, Yb and Lu). The results suggest a hydrothermal origin of the Golden Horn miarolitic thalénite-(Y), compared to a combination of both primary magmatic followed by hydrothermal processes responsible for the multiple generations over a range of spatial scales in White Cloud thalénite-(Y).