Young stellar objects (YSOs) are protostars that exhibit bipolar outflows fed by accretion disks. Theories of the transition between disk and outflow often involve a complex magnetic field structure thought to be created by the disk coiling field lines at the jet base; however, due to limited resolution, these theories cannot be confirmed with observation and thus may benefit from laboratory astrophysics studies. We create a dynamically similar laboratory system by driving a $\sim$1 MA current pulse with a 200 ns rise through a $\approx$2 mm-tall Al cylindrical wire array mounted to a three-dimensional (3-D)-printed, stainless steel scaffolding. This system creates a plasma that converges on the centre axis and ejects cm-scale bipolar outflows. Depending on the chosen 3-D-printed load path, the system may be designed to push the ablated plasma flow radially inwards or off-axis to make rotation. In this paper, we present results from the simplest iteration of the load which generates radially converging streams that launch non-rotating jets. The temperature, velocity and density of the radial inflows and axial outflows are characterized using interferometry, gated optical and ultraviolet imaging, and Thomson scattering diagnostics. We show that experimental measurements of the Reynolds number and sonic Mach number in three different stages of the experiment scale favourably to the observed properties of YSO jets with $Re\sim 10^5\unicode{x2013}10^9$ and $M\sim 1\unicode{x2013}10$, while our magnetic Reynolds number of $Re_M\sim 1\unicode{x2013}15$ indicates that the magnetic field diffuses out of our plasma over multiple hydrodynamical time scales. We compare our results with 3-D numerical simulations in the PERSEUS extended magnetohydrodynamics code.

Dante Cicchetti’s earliest work, his studies of social-emotional development in infants and children with Down syndrome, set the stage for the emergence of the larger field of developmental psychopathology. By applying basic developmental principles, methodologies, and questions to the study of persons with Down syndrome, Dante took on the challenge of searching for patterns in atypical development. In doing so, he extended traditional developmental theory and introduced a more “liberal” approach that both continues to guide developmentally based research with persons with neurodevelopmental conditions (NDCs), including Down syndrome. We highlight five themes from Dante’s work: (1) appreciating the importance of developmental level; (2) prioritizing the organization of development; (3) examining whether developmental factors work similarly in those with known genetic conditions; (4) rethinking narratives about ways of being; and (5) examining the influence of multiple levels of the environment on the individual’s functioning. We highlight ways that these essential lessons anticipated present-day research with persons with a variety of NDCs, including Down syndrome, other genetic syndromes associated with intellectual disability, and autism. We conclude with visions to the future for research with these populations as well as for the field of developmental psychopathology more generally.

OBJECTIVES/GOALS: We aim to discover safer and more effective therapeutics for CNS disorders. Current therapeutic development is hindered by dosing out drugs for safe consumption. By identifying proteins with narrow functional roles in the brain (i.e., behavioral control), we can develop drugs targeting these proteins for improved treatment safety and efficacy. METHODS/STUDY POPULATION: We focused on an evolutionarily new, non-neuronal, non-synaptic glutamate signaling mechanism, system xc- (Sxc). Sxc activity was eliminated by mutating the gene Slc7a11 through pronuclear injection of zinc-finger nucleases into Sprague Dawley rat embryos to create a line of rats lacking Sxc (MSxc). To confirm Sxc mutation, we verified that tissue from MSxc rats had a complete lack of xCT, which is the regulatory subunit of Sxc that is encoded by Slc7a11. We also verified that astrocyte cultures generated from MSxc tissue lacked cystine-evoked glutamate release. Next, we measured development (body weight), CNS regulation of metabolism, and other indicators of generalized, non-specific brain function as well as behaviors that are reliant on behavioral control, such as impulse control and response inhibition. RESULTS/ANTICIPATED RESULTS: Eliminating Sxc was not lethal and did not impair development or produce widespread changes in brain function as is commonly observed when deleting other glutamate mechanisms. MSxc rats did not differ from wildtype in growth rate, central regulation of metabolism as reflected by absolute or diurnal changes in core body temperature, locomotor activity in a familiar or novel environment, or simple forms of cognition such as novel object recognition, or operant responding (food and cocaine-reinforced). In contrast, behaviors that rely on behavioral control were impaired. MSxc rats displayed deficits in impulse control and behavioral flexibility. We hypothesize that MSxc rats will also show deficits in response inhibition using the stop signal reaction time task, a common metric used in clinical populations. DISCUSSION/SIGNIFICANCE: Eliminating Sxc activity in rats produced deficits in behaviors reliant on impulse control, without impacting development or simple brain function. These results show the potential of targeting Sxc to restore behavioral control without generating therapeutically limiting adverse effects resulting from non-specific changes in brain function.

Biogeochemical analyses of organisms’ tissues provide direct proxies for diets, behaviors, and environmental interactions that have proven invaluable for studies of extant and extinct species. Applying these to Cretaceous ecosystems has at times produced anomalous results, however, as dinosaurs preserve unusually positive stable carbon isotope compositions relative to extant C3-feeding vertebrates. This has been hypothesized to be a unique property of dinosaur dietary physiology, with potential significance for our interpretations of their paleobiology. We test that hypothesis through multi-taxic stable carbon isotope analyses of a spatiotemporally constrained locality in the Late Cretaceous of Canada, and compare the results to a modern near-analogue environment in Louisiana. The stable carbon isotope anomaly is present in all sampled fossil vertebrates, dinosaur or not. This suggests another more widespread factor is responsible. Examinations of diagenetic effects suggest that, where present, they are insufficient to explain the isotope anomaly. The isotope anomaly is therefore not primarily the result of a unique dietary physiology of dinosaurs, but rather a mix of factors impacting all taxa, such as environmental and/or source-diet differences. Our study underscores the importance of multi-taxic samples from spatiotemporally constrained localities in testing hypotheses of extinct organisms and ecosystems, and in the use of modern data to “ground truth” when evaluating analogue versus non-analogue conditions in greenhouse paleoecosystems.

One of the longstanding debates in life-course epidemiology is whether an adverse intrauterine environment, often proxied by birth weight, causally increases the future risk of cardiometabolic disease. The use of a discordant twin study design, which controls for the influence of shared genetic and environmental confounding factors, may be useful to investigate whether this relationship is causal. We conducted a discordant twin study of 120 monozygotic (MZ) and 148 dizygotic (DZ) twin pairs from the UK Biobank to explore the potential causal relationships between birth weight and a broad spectrum of later-life cardiometabolic risk factors. We used a linear mixed model to investigate the association between birth weight and later-life cardiometabolic risk factors for twins, allowing for both within-pair differences and between-pair differences in birth weight. Of primary interest is the within-pair association between differences in birth weight and cardiometabolic risk factors, which could reflect an intrauterine effect on later-life risk factors. We found no strong evidence of association in MZ twins between the within-pair differences in birth weight and most cardiometabolic risk factors in later life, except for nominal associations with C-reactive protein and insulin-like growth factor 1. However, these associations were not replicated in DZ twin pairs. Our study provided no strong evidence for intrauterine effects on later-life cardiometabolic risk factors, which is consistent with previous large-scale studies of singletons testing the potential causal relationship. It does not support the hypothesis that adverse intrauterine environments increase the risk of cardiometabolic disease in later life.

OBJECTIVES/GOALS: We aim to determine whether non-neuronal, non-synaptic glutamate signaling mechanisms can be targeted to produce highly specific, narrow changes in brain function that would benefit CNS disorders. To do this, we investigated cognitive changes produced through manipulating the activity of the astrocytic glutamate release mechanism system xc-. METHODS/STUDY POPULATION: System xc- (Sxc) activity was eliminated by mutating the gene Slc7a11 through pronuclear injection of zinc-finger nucleases into Sprague Dawley rat embryos to create a line of rats lacking Sxc (MSxc rats). To confirm a lack of Sxc activity, we verified that tissue from MSxc rats had a complete lack of xCT, which is the regulatory subunit of Sxc that is encoded by Slc7a11. We also verified that astrocyte cultures generated from MSxc tissue lacked cystine-evoked glutamate release. Next, we measured development (body weight), CNS regulation of metabolism, and other indicators of generalized, non-specific brain function as well as behaviors that are reliant on executive function, such as cognitive flexibility, impulse control, decision-making, and response inhibition. RESULTS/ANTICIPATED RESULTS: Eliminating Sxc was not lethal and did not impair development or produce widespread changes in brain function as is commonly observed when deleting other glutamate mechanisms. MSxc rats did not differ from wildtype in growth rate, central regulation of metabolism as reflected by absolute or diurnal changes in core body temperature, locomotor activity in a familiar or novel environment, or simple forms of cognition such as novel object recognition, or operant responding (food and cocaine-reinforced). In contrast, behaviors that rely on executive function were impaired. MSxc rats displayed deficits in cocaine reinstatement and attentional set-shifting. We anticipate MSxc rats to also show impairments in decision-making in the rat gambling task and response inhibition in the stop-signal reaction time task. DISCUSSION/SIGNIFICANCE: Eliminating Sxc activity in rats produced deficits in behaviors reliant on executive function without impacting development or simple brain function. These results highlight the potential of targeting Sxc to enhance cognition without generating therapeutically limiting adverse effects resulting from non-specific changes in brain function.

Studies of introduced subject matter in rock-art assemblages typically focus on themes of cross-cultural interaction, change and continuity, power and resistance. However, the economic frameworks guiding or shaping the production of an assemblage have often been overlooked. In this paper we use a case study involving a recently recorded assemblage of introduced subject matter from Marra Country in northern Australia's southwest Gulf of Carpentaria region to explore their production using a hybrid economy framework. This framework attempts to understand the nature of the forces that shape people's engagement with country and subsequently how it is being symbolically marked as adjustments to country occur through colonization. We argue that embedding these motifs into a hybrid economy context anchored in the pastoral industry allows for a more nuanced approach to cross-cultural interaction studies and adds another layer to the story of Aboriginal place-marking in colonial contexts. This paper aims to go beyond simply identifying motifs thought to represent introduced subject matter, and the cross-cultural framework(s) guiding their interpretation, and instead to direct attention to the complex network of relations that potentially underpin the production of such motifs.

The end-Cretaceous (K/Pg) mass extinction event is the most recent and well-understood of the “big five” and triggered establishment of modern terrestrial ecosystem structure. Despite the depth of research into this event, our knowledge of upper Maastrichtian terrestrial deposits globally relies primarily on assemblage-level data limited to a few well-sampled formations in North America, the Hell Creek and Lance Formations. These assemblages disproportionally affect our interpretations of this important interval. Multiple investigations have quantified diversity patterns within these assemblages, but the potential effect of formation-level size-dependent taphonomic biases and their implications on extinction dynamics remains unexplored. Here, the relationship between taphonomy and body size of the Hell Creek Formation and Lance Formation dinosaurs and mammals are quantitatively analyzed. Small-bodied dinosaur taxa (<70 kg) are consistently less complete, unlikely to be articulated, and delayed in their description relative to their large-bodied counterparts. Family-level abundance (particularly skeletons) is strongly tied to body mass, and the relative abundance of juveniles of large-bodied taxa similarly is underrepresented. Mammals show similar but nonsignificant trends. The results are remarkably similar to those from the Campanian-aged Dinosaur Park Formation, suggesting a widespread strong taphonomic bias against the preservation of small taxa, which will result in their seemingly depauperate diversity within the assemblage. This taphonomically skewed view of diversity and abundance of small-bodied taxa amid our best late Maastrichtian samples has significant implications for understanding speciation and extinction dynamics (e.g., size-dependent extinction selectivity) across the K/Pg boundary.

We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers $270 \,\mathrm{deg}^2$ of an area covered by the Dark Energy Survey, reaching a depth of 25–30 $\mu\mathrm{Jy\ beam}^{-1}$ rms at a spatial resolution of $\sim$ 11–18 arcsec, resulting in a catalogue of $\sim$ 220 000 sources, of which $\sim$ 180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.

The Hawaiian archipelago was formerly home to one of the most species-rich land snail faunas (> 752 species), with levels of endemism > 99%. Many native Hawaiian land snail species are now extinct, and the remaining fauna is vulnerable. Unfortunately, lack of information on critical habitat requirements for Hawaiian land snails limits the development of effective conservation strategies. The purpose of this study was to examine the plant host preferences of native arboreal land snails in Puʻu Kukui Watershed, West Maui, Hawaiʻi, and compare these patterns to those from similar studies on the islands of Oʻahu and Hawaiʻi. Concordant with studies on other islands, we found that four species from three diverse families of snails in Puʻu Kukui Watershed had preferences for a few species of understorey plants. These were not the most abundant canopy or mid canopy species, indicating that forests without key understorey plants may not support the few remaining lineages of native snails. Preference for Broussaisia arguta among various island endemic snails across all studies indicates that this species is important for restoration to improve snail habitat. As studies examining host plant preferences are often incongruent with studies examining snail feeding, we suggest that we are in the infancy of defining what constitutes critical habitat for most Hawaiian arboreal snails. However, our results indicate that preserving diverse native plant assemblages, particularly understorey plant species, which facilitate key interactions, is critical to the goal of conserving the remaining threatened snail fauna.

Recent studies have used Mendelian randomization (MR) to investigate the observational association between low birth weight (BW) and increased risk of cardiometabolic outcomes, specifically cardiovascular disease, glycemic traits, and type 2 diabetes (T2D), and inform on the validity of the Barker hypothesis. We used simulations to assess the validity of these previous MR studies, and to determine whether a better formulated model can be used in this context. Genetic and phenotypic data were simulated under a model of no direct causal effect of offspring BW on cardiometabolic outcomes and no effect of maternal genotype on offspring cardiometabolic risk through intrauterine mechanisms; where the observational relationship between BW and cardiometabolic risk was driven entirely by horizontal genetic pleiotropy in the offspring (i.e. offspring genetic variants affecting both BW and cardiometabolic disease simultaneously rather than a mechanism consistent with the Barker hypothesis). We investigated the performance of four commonly used MR analysis methods (weighted allele score MR (WAS-MR), inverse variance weighted MR (IVW-MR), weighted median MR (WM-MR), and MR-Egger) and a new approach, which tests the association between maternal genotypes related to offspring BW and offspring cardiometabolic risk after conditioning on offspring genotype at the same loci. We caution against using traditional MR analyses, which do not take into account the relationship between maternal and offspring genotypes, to assess the validity of the Barker hypothesis, as results are biased in favor of a causal relationship. In contrast, we recommend the aforementioned conditional analysis framework utilizing maternal and offspring genotypes as a valid test of not only the Barker hypothesis, but also to investigate hypotheses relating to the Developmental Origins of Health and Disease more broadly.

Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.

The scarcity of Romano-British human remains from north-west England has hindered understanding of burial practice in this region. Here, we report on the excavation of human and non-human animal remains1 and material culture from Dog Hole Cave, Haverbrack. Foetal and neonatal infants had been interred alongside a horse burial and puppies, lambs, calves and piglets in the very latest Iron Age to early Romano-British period, while the mid- to late Roman period is characterised by burials of older individuals with copper-alloy jewellery and beads. This material culture is more characteristic of urban sites, while isotope analysis indicates that the later individuals were largely from the local area. We discuss these results in terms of burial ritual in Cumbria and rural acculturation. Supplementary material is available online (https://doi.org/10.1017/S0068113X20000136), and contains further information about the site and excavations, small finds, zooarchaeology, human osteology, site taphonomy, the palaeoenvironment, isotope methods and analysis, and finds listed in Benson and Bland 1963.