In the present work, we extend the results of a previous investigation on the dynamics of electrons under the action of an inverse free-electron-laser scheme (Almansa et al., Phys. Plasmas, vol. 26, 2019, 033105). While the former work examined electrons as single test particles subject to the combined action of a modulated wiggler plus a laser field, we now look at electrons as composing a particle beam, where collective space-charge effects are relevant and included in the analysis. Our previous work showed that effective acceleration is achieved when the initial velocities of the particles are close enough to the phase velocity of the beat-wave mode formed by the laser and the wiggler fields. Electrons are then initially accelerated by a ponderomotive uphill effect generated by the beat mode and, once reaching the phase velocity of the beat, undergo a final strong resonant acceleration step resembling a catapult effect. The present work shows that, under proper conditions, space-charge effects play a similar role as the initial (or injected) velocity of the beam. Even if acceleration is absent when space charge is neglected, it may be present and effective when charge effects are taken into account. We also discuss how far the space charge can grow without affecting the sustainability of the acceleration process.

We question Spelke's key claim that the medium, in which contents from different core knowledge systems can be represented and combined, is language-based. Recalling an episodic memory, playing chess, and conducting mental rotation are tasks where core knowledge information is represented and combined. Although these tasks can be described by means of language, these tasks are not inherently language-based. Hence, language may be an important subset of an abstraction medium – not the medium as such.

Children hospitalised with severe malnutrition have high mortality and readmission rates post-discharge. Current milk-based formulations target restoring ponderal growth but not the modification of gut barrier integrity or microbiome which increases the risk of gram-negative sepsis and poor outcomes. We propose that legume-based feeds rich in fermentable carbohydrates will promote better gut health and improve overall outcomes. We conducted an open-label phase II trial at Mbale and Soroti Regional Referral Hospitals, Uganda, involving 160 children aged 6 months to 5 years with severe malnutrition (mid-upper arm circumference (MUAC) < 11·5 cm and/or nutritional oedema). Children were randomised to a lactose-free, chickpea-enriched legume paste feed (LF) (n 80) v. WHO standard F75/F100 feeds (n 80). Co-primary outcomes were change in MUAC and mortality to day 90. Secondary outcomes included weight gain (> 5 g/kg/d), de novo development of diarrhoea, time to diarrhoea and oedema resolution. Day 90 MUAC increase was marginally lower in LF v. WHO arm (1·1 cm (interquartile range (IQR) 1·1) v. 1·4 cm (IQR 1·40), P = 0·09); day 90 mortality was similar (11/80 (13·8 %) v. 12/80 (15 %), respectively, OR 0·91 (95 % CI 0·40, 2·07), P = 0·83). There were no differences in any of the other secondary outcomes. Owing to initial poor palatability of the LF, ten children switched to WHO feeds. Per-protocol analysis indicated a trend to lower day 90 mortality and readmission rates in the LF (6/60 (10 %) and 2/60(3 %)) v. WHO feeds (12/71(17·5 %) and 4/71(6 %)). Further refinement of LF and clinical trials are warranted, given the poor outcomes in children with severe malnutrition.

Background: We evaluated vorasidenib (VOR), a dual inhibitor of mIDH1/2, in patients with mIDH1/2 glioma (Phase 3; NCT04164901). Methods: Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (age ≥12; Karnofsky Performance Score ≥80; measurable non-enhancing disease; surgery as only prior treatment; not in immediate need of chemoradiotherapy). Patients were stratified by 1p19q status and baseline tumor size and randomized 1:1 to VOR 40 mg or placebo (PBO) daily in 28-day cycles. Endpoints included imaging-based progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), health-related quality of life (HRQoL), neurocognition and seizure activity. Results: 331 patients were randomized (VOR, 168; PBO, 163). The median age was 40.0 years. 172 and 159 patients had histologically confirmed oligodendroglioma and astrocytoma, respectively. Treatment with VOR significantly improved PFS and TTNI. Median PFS: VOR, 27.7 mos; PBO, 11.1 mos (P=0.000000067). Median TTNI: VOR, not reached; PBO, 17.8 mos (P=0.000000019). Treatment with VOR resulted in shrinkage of tumor volume. Post-treatment TGR: VOR, -2.5% (95% CI: -4.7, -0.2); PBO, 13.9% (95% CI: 11.1, 16.8). HRQoL and neurocognition were preserved and seizure control was maintained. VOR had a manageable safety profile. Conclusions: VOR was effective in mIDH1/2 diffuse glioma not in immediate need of chemoradiotherapy.

We present radio observations of the galaxy cluster Abell S1136 at 888 MHz, using the Australian Square Kilometre Array Pathfinder radio telescope, as part of the Evolutionary Map of the Universe Early Science program. We compare these findings with data from the Murchison Widefield Array, XMM-Newton, the Wide-field Infrared Survey Explorer, the Digitised Sky Survey, and the Australia Telescope Compact Array. Our analysis shows the X-ray and radio emission in Abell S1136 are closely aligned and centered on the Brightest Cluster Galaxy, while the X-ray temperature profile shows a relaxed cluster with no evidence of a cool core. We find that the diffuse radio emission in the centre of the cluster shows more structure than seen in previous low-resolution observations of this source, which appeared formerly as an amorphous radio blob, similar in appearance to a radio halo; our observations show the diffuse emission in the Abell S1136 galaxy cluster contains three narrow filamentary structures visible at 888 MHz, between $\sim$80 and 140 kpc in length; however, the properties of the diffuse emission do not fully match that of a radio (mini-)halo or (fossil) tailed radio source.

The U.S. Department of Veterans Affairs is actively transitioning away from a disease-centric model of healthcare to one that prioritizes disease prevention and the promotion of overall health and well-being. Described as Whole Health, this initiative aims to provide personalized, values-centered care that optimizes physical, behavioral, spiritual, and socioeconomic well-being. To inform this initiative, we analyzed cross-sectional data from a nationally representative sample of primarily older U.S. military veterans to estimate levels of well-being across these domains, and identify sociodemographic, military, and potentially modifiable health and psychosocial correlates of them. Results revealed that, overall, veterans reported high domain-specific well-being (average scores ranging from 6.7 to 8.3 out of 10), with the highest levels in the socioeconomic domain and lowest in the physical domain. Several modifiable factors, including purpose in life, resilience, and social support, were strongly associated with the examined well-being domains. Interventions targeting these constructs may help promote well-being among U.S. veterans.

This paper introduces DivFolio, a multiperiod portfolio selection and analytic software application that incorporates automated and user-determined divestment practices accommodating Environmental Social Governance (ESG) and portfolio carbon footprint considerations. This freely available portfolio analytics software tool is written in R with a GUI interface developed as an R Shiny application for ease of user experience. Users can utilize this software to dynamically assess the performance of asset selections from global equity, exchange-traded funds, exchange-traded notes, and depositary receipts markets over multiple time periods. This assessment is based on the impact of ESG investment and fossil-fuel divestment practices on portfolio behavior in terms of risk, return, stability, diversification, and climate mitigation credentials of associated investment decisions. We highlight two applications of DivFolio. The first revolves around using sector scanning to divest from a specialized portfolio featuring constituents of the FTSE 100. The second, rooted in actuarial considerations, focuses on divestment strategies informed by environmental risk assessments for mixed pension portfolios in the US and UK.

This paper argues for a new way of thinking about Early Celtic art in the context of changes taking place throughout Eurasia during the fifth and fourth centuries bce. It applies ideas of anthropologist Alfred Gell, among others, regarding art as a stimulus to action. It asks, in the spirit of papers by Chris Gosden and W.J.T. Mitchell, ‘what did the art do’? The paper argues that this complex new art can be understood in terms of agency contributing to and even stimulating aggressive attitudes and practices on the part of elites during the late fifth and early fourth centuries bce. The new worldviews that are apparent in the new style, and actions driven by them, played major roles in Iron Age Europeans’ participation in the so-called Axial Age of dynamic change throughout Eurasia.

Aquatic ecosystems - lakes, ponds and streams - are hotspots of biodiversity in the cold and arid environment of Continental Antarctica. Environmental change is expected to increasingly alter Antarctic aquatic ecosystems and modify the physical characteristics and interactions within the habitats that they support. Here, we describe physical and biological features of the peripheral ‘moat’ of a closed-basin Antarctic lake. These moats mediate connectivity amongst streams, lake and soils. We highlight the cyclical moat transition from a frozen winter state to an active open-water summer system, through refreeze as winter returns. Summer melting begins at the lakebed, initially creating an ice-constrained lens of liquid water in November, which swiftly progresses upwards, creating open water in December. Conversely, freezing progresses slowly from the water surface downwards, with water at 1 m bottom depth remaining liquid until May. Moats support productive, diverse benthic communities that are taxonomically distinct from those under the adjacent permanent lake ice. We show how ion ratios suggest that summer exchange occurs amongst moats, streams, soils and sub-ice lake water, perhaps facilitated by within-moat density-driven convection. Moats occupy a small but dynamic area of lake habitat, are disproportionately affected by recent lake-level rises and may thus be particularly vulnerable to hydrological change.

OBJECTIVES/GOALS: The primary research goal was to identify brain alterations reliably associated with obesity using coordinate-based meta-analysis. A secondary goal was to compare brain alterations in metabolically healthy (MHO) and unhealthy (MUO) obesity. METHODS/STUDY POPULATION: Source data were peer-reviewed studies reporting locations of gray-matter alterations in group-average, case-control contrasts (obese vs. non-obese) cohorts, performed in a whole-brain, voxel-wise manner. Both voxel-based morphometry and voxel-based physiology studies were included. Three coordinate-based meta-analyses were performed: Pooled (MUO + MHO), MHO, and MUO. RESULTS/ANTICIPATED RESULTS: Thirty-two studies reporting a total of 50 case-control contrasts (MHO, 23; MUO, 27) met inclusion criteria, representing 3,368 participants (obese, 1,781; non-obese, 1587). The pooled analysis yielded 8 cerebral foci (3 nuclear, 5 cortical) in regions implicated in reward-seeking, cognitive, and interoceptive behaviors. MHO yielded 7 cerebral foci (4 nuclear, 3 cortical), partially overlapping Pooled results, with similar behavioral loadings. The MUO pattern was distinct, with 3 cerebellar and 1 occipital foci. DISCUSSION/SIGNIFICANCE: Brain alterations occurred reliably in obesity. The dominant pattern (Pooled & MHO) involved cerebral reward-system circuits, evident even in metabolically healthy obesity. Cerebellar alterations occurred exclusively in metabolically unhealthy obesity, a pattern previously reported in metabolic syndrome.

OBJECTIVES/GOALS: Women and healthcare providers from underserved rural and urban communities participated in Community Engagement (CE) studios to offer perspectives for increasing research participation of women from diverse backgrounds prior to initiating recruitment for a randomized-controlled trial comparing treatments for urgency urinary incontinence. METHODS/STUDY POPULATION: CE studios are listening sessions to gather patient or community input on specific study areas of interest before implementation. Ten CE studios were held via Zoom at five study sites (Rhode Island, Washington DC, Alabama, New Mexico, and Southern California). Each site held two studios: 1) women living with urgency urinary incontinence, 2) clinicians providing care in their areas. Participants gave recommendations on ways to increase study participation of women from diverse racial and ethnic backgrounds with a focus on recruitment and retention, identification of barriers to participation, and suggested approaches to overcome those barriers. Summaries were compiled from each CE studio to identify similar and contrasting recommendations across sites. RESULTS/ANTICIPATED RESULTS: A total of 80 participants (47 community women experiencing urgency urinary incontinence, and 33 healthcare professionals) participated across all sites. Studio participants discussed anticipated barriers for participant recruitment and retention with a focus on solutions to those barriers. Based on these suggestions, we created recruitment materials using pictures, videos, and simple terminology. We created educational content to help providers with current best practices for urinary urgency incontinence. We have allowed most study visits to be conducted virtually, identified affiliated clinics in various locations to improve proximity to undeserved communities, and have earmarked additional funds to help offset travel costs including gas, public transportation, and childcare. DISCUSSION/SIGNIFICANCE: CE studios have provided pragmatic patient- and provider-centered recommendations that have been incorporated into functional strategies to improve research participation and diversity. CTSA CE core expertise can support successful CE studio planning and implementation.

Recent research has shown the potential of speleothem δ13C to record a range of environmental processes. Here, we report on 230Th-dated stalagmite δ13C records for southwest Sulawesi, Indonesia, over the last 40,000 yr to investigate the relationship between tropical vegetation productivity and atmospheric methane concentrations. We demonstrate that the Sulawesi stalagmite δ13C record is driven by changes in vegetation productivity and soil respiration and explore the link between soil respiration and tropical methane emissions using HadCM3 and the Sheffield Dynamic Global Vegetation Model. The model indicates that changes in soil respiration are primarily driven by changes in temperature and CO2, in line with our interpretation of stalagmite δ13C. In turn, modelled methane emissions are driven by soil respiration, providing a mechanism that links methane to stalagmite δ13C. This relationship is particularly strong during the last glaciation, indicating a key role for the tropics in controlling atmospheric methane when emissions from high-latitude boreal wetlands were suppressed. With further investigation, the link between δ13C in stalagmites and tropical methane could provide a low-latitude proxy complementary to polar ice core records to improve our understanding of the glacial–interglacial methane budget.