Background: Epstein-Barr virus (EBV) infection is believed to be a critical prerequisite for the development of multiple sclerosis (MS). This study aims to investigate whether anti-EBV titres are elevated before the onset of MS symptoms in people with radiologically isolated syndrome (pwRIS) and to evaluate their association with markers of adverse clinical outcomes. Methods: Epstein-Barr nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) titres were quantified in a cohort of 47 pwRIS and 24 healthy controls using Enzyme-Linked Immuno-Sorbent Assay. Plasma glial fibrillary acidic protein (GFAP) and neurofilament light protein (NfL) were measured using single-molecule array. MRI lesion metrics and the development of MS symptoms over time were also evaluated. Results: EBNA1 titres were higher pwRIS compared to healthy controls (p=0.038), while VCA titres were not (p=0.237). A positive correlation was observed between EBNA1 titres and plasma GFAP in pwRIS (p=0.005). Neither EBNA1 nor VCA titres correlated with NfL. MRI lesion measures and the development of MS symptoms did not show any significant relationship with EBNA1 or VCA titres. Conclusions: Eelevated EBNA1 titres are detectable prior to MS symptom onset and correlate with GFAP, a biomarker associated with worse clinical outcomes. However, their role in disease progression and clinical outcomes requires further investigation.

Background: Radiologically isolated syndrome (RIS) is characterized by incidental MRI findings suggestive of multiple sclerosis in asymptomatic individuals. Emerging blood biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and chitinase 3-like 1 protein (CHI3L1) are promising tools for evaluating neuroinflammation and neurodegeneration. Methods: This cross-sectional analysis included 47 individuals with RIS who underwent MRI and plasma biomarker assessments. Plasma levels of CHI3L1, NfL, and GFAP were measured using highly sensitive assays. Correlations between biomarkers and MRI markers, including T1-black holes (BHs), central vein sign (CVS) positive lesions, paramagnetic rim lesions (PRLs), choroid plexus volume (CPV), and thalamic and hippocampal volumes, were analyzed using linear regression. Results: Plasma CHI3L1 levels correlated with increased CPV (β = 0.347, p = 0.017) and reduced thalamic (β = -0.309, p = 0.035) and hippocampal (β = -0.535, p < 0.001) volumes. Plasma GFAP levels were associated with BHs, CVS, and PRLs, whereas plasma NfL showed no correlations with MRI measures. Conclusions: Plasma CHI3L1 correlates with subcortical grey matter atrophy and CPV increase in RIS, distinct from correlations observed with GFAP or NfL. This suggests that plasma CHI3L1 may reflect neurodegeneration and inflammation in RIS and provide insights into disease activity not captured by other biomarkers.

The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.

Spirometra is a genus of zoonotic cestodes with an ambiguous species-level taxonomic history. Previously, Spirometra mansonoides was considered the only species present in North America. However, recent molecular data revealed the presence of at least three distinct species in the USA: Spirometra sp. 2 and 3, and Spirometra mansoni. This study aimed to elucidate the diversity and potential host associations of Spirometra species among companion animals in the USA. Samples (N = 302) were examined from at least 13 host species, including mammals, amphibians and reptiles. Sample types included eggs isolated from faeces (n = 222), adult specimens (n = 71) and plerocercoids (n = 9) from 18 different states and 2 territories across the USA. Extracted genomic DNA was subjected to PCR targeting a fragment of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. Generated sequences (n = 136) were included in a phylogenetic analysis. Spirometra mansoni was detected in domestic cats (n = 76), dogs (n = 12), a White’s tree frog (n = 1), a Cuban knight anole (n = 1), a green iguana (n = 1) and a serval (n = 1) across 15 states and Puerto Rico. Spirometra sp. 2 was found only in dogs (n = 3) from Florida and Spirometra sp. 3 was found only in cats (n = 41) from 17 states. All plerocercoid samples were consistent with S. mansoni. The results confirm that at least three distinct Spirometra species are present and established in companion animals, such as dogs and cats, and likely are using various native and exotic species as paratenic hosts within the USA.

Low birthweight is a risk factor for type 2 diabetes. We hypothesised that differential associations between birthweight and clinical characteristics in persons with and without type 2 diabetes may provide novel insights into the role of birthweight in type 2 diabetes and its progression. We analysed UK Biobank data from 9,442 persons with and 254,446 without type 2 diabetes. Associations between birthweight, clinical traits, and genetic predisposition were assessed using adjusted linear and logistic regression, comparing the lowest and highest 25% of birthweight to the middle 50%. Each kg increase in birthweight was associated with higher BMI, waist, and hip circumference, with stronger effects in persons with versus without type 2 diabetes (BMI: 0.74 [0.58, 0.90] vs. 0.21 [0.18, 0.24] kg/m2; waist: 2.15 [1.78, 2.52] vs. 1.04 [0.98, 1.09] cm; hip: 1.65 [1.33, 1.97] vs. 1.04 [1.04, 1.09] cm). Family history of diabetes was associated with higher birthweight regardless of diabetes status, albeit with a twofold higher effect estimate in type 2 diabetes. Low birthweight was further associated with prior myocardial infarction regardless of type 2 diabetes status (OR 1.33 [95% CI 1.11, 1.60] for type 2 diabetes; 1.23 [95% CI 1.13, 1.33] without), and hypertension (OR 1.25 [1.23, 1.28] and stroke 1.24 [1.14, 1.34]) only among persons without type 2 diabetes. Differential associations between birthweight and cardiometabolic traits in persons with and without type 2 diabetes illuminate potential causal inferences reflecting the roles of pre- and postnatal environmental versus genetic aetiologies and disease mechanisms.

We present the first results from a new backend on the Australian Square Kilometre Array Pathfinder, the Commensal Realtime ASKAP Fast Transient COherent (CRACO) upgrade. CRACO records millisecond time resolution visibility data, and searches for dispersed fast transient signals including fast radio bursts (FRB), pulsars, and ultra-long period objects (ULPO). With the visibility data, CRACO can localise the transient events to arcsecond-level precision after the detection. Here, we describe the CRACO system and report the result from a sky survey carried out by CRACO at 110-ms resolution during its commissioning phase. During the survey, CRACO detected two FRBs (including one discovered solely with CRACO, FRB 20231027A), reported more precise localisations for four pulsars, discovered two new RRATs, and detected one known ULPO, GPM J1839 $-$10, through its sub-pulse structure. We present a sensitivity calibration of CRACO, finding that it achieves the expected sensitivity of 11.6 Jy ms to bursts of 110 ms duration or less. CRACO is currently running at a 13.8 ms time resolution and aims at a 1.7 ms time resolution before the end of 2024. The planned CRACO has an expected sensitivity of 1.5 Jy ms to bursts of 1.7 ms duration or less and can detect $10\times$ more FRBs than the current CRAFT incoherent sum system (i.e. 0.5 $-$2 localised FRBs per day), enabling us to better constrain the models for FRBs and use them as cosmological probes.

Two studies were conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to determine the optimal granular ammonium sulfate (AMS) rate and application timing for pyroxasulfone-coated AMS. In the rate study, AMS rates included 161, 214, 267, 321, 374, 428, and 481 kg ha−1, equivalent to 34, 45, 56, 67, 79, 90, and 101 kg N ha−1, respectively. All rates were coated with pyroxasulfone at 118 g ai ha−1 and topdressed onto 5- to 7-leaf cotton. In the timing study, pyroxasulfone (118 g ai ha−1) was coated on AMS and topdressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf, 9- to 11-leaf, and first bloom cotton. In both studies, weed control and cotton tolerance to pyroxasulfone-coated AMS were compared to pyroxasulfone applied POST and POST-directed. The check in both studies received non-herbicide-treated AMS (321 kg ha−1). Before treatment applications, all plots (including the check) were maintained weed-free with glyphosate and glufosinate. In both studies, pyroxasulfone applied POST was most injurious (8% to 16%), while pyroxasulfone-coated AMS resulted in ≤4% injury. Additionally, no differences in cotton lint yield were observed in either study. With the exception of the lowest rate of AMS (161 kg ha−1; 79%), all AMS rates coated with pyroxasulfone controlled Palmer amaranth ≥83%, comparably to pyroxasulfone applied POST (92%) and POST-directed (89%). In the timing study, the application method did not affect Palmer amaranth control; however, applications made at the mid- and late timings outperformed early applications. These results indicate that pyroxasulfone-coated AMS can control Palmer amaranth comparably to pyroxasulfone applied POST and POST-directed, with minimal risk of cotton injury. However, the application timing could warrant additional treatment to achieve adequate late-season weed control.

Multi-site and multi-organizational teams are increasingly common in epidemiologic research; however, there is a lack of standards or best practices for achieving success in collaborative research networks in epidemiology. We summarize our experiences and lessons learned from the Diabetes Location, Environmental Attributes, and Disparities (LEAD) Network, a collaborative agreement between the Centers for Disease Control and Prevention and research teams at Drexel University, New York University, Johns Hopkins University and Geisinger, and the University of Alabama at Birmingham. We present a roadmap for success in collaborative epidemiologic research, with recommendations focused on the following areas to maximize efficiency and success in collaborative research agreements: 1) operational and administrative considerations; 2) data access and sharing of sensitive data; 3) aligning network research aims; 4) harmonization of methods and measures; and 5) dissemination of findings. Future collaborations can be informed by our experiences and ultimately dedicate more resources to achieving scientific aims and efficiently disseminating scientific work products.

An experiment was conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to evaluate residual herbicide-coated fertilizer for cotton tolerance and Palmer amaranth control. Treatments included acetochlor, atrazine, dimethenamid-P, diuron, flumioxazin, fluometuron, fluridone, fomesafen, linuron, metribuzin, pendimethalin, pyroxasulfone, pyroxasulfone + carfentrazone, S-metolachlor, and sulfentrazone. Each herbicide was individually coated on granular ammonium sulfate (AMS) and top-dressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf cotton. The check plots received the equivalent rate of nonherbicide-treated AMS. Before top-dress, all plots (including the check) were treated with glyphosate and glufosinate to control previously emerged weeds. All herbicides except metribuzin resulted in transient cotton injury. Cotton response to metribuzin varied by year and location. In 2022, metribuzin caused 11% to 39% and 8% to 17% injury at the Clayton and Rocky Mount locations, respectively. In 2023, metribuzin caused 13% to 32% injury at Clayton and 73% to 84% injury at Rocky Mount. Pyroxasulfone (91%), pyroxasulfone + carfentrazone (89%), fomesafen (87%), fluridone (86%), flumioxazin (86%), and atrazine (85%) controlled Palmer amaranth ≥85%. Pendimethalin and fluometuron were the least effective treatments, resulting in 58% and 62% control, respectively. As anticipated, early season metribuzin injury translated into yield loss; plots treated with metribuzin yielded 640 kg ha−1 and were comparable to yields after linuron (790 kg ha−1) was used. These findings suggest that with the exception of metribuzin, residual herbicides coated onto AMS may be suitable and effective in cotton production, providing growers with additional modes of action for late-season control of multiple herbicide–resistant Palmer amaranth.

We present the Pilot Survey Phase 2 data release for the Wide-field ASKAP L-band Legacy All-sky Blind surveY (WALLABY), carried-out using the Australian SKA Pathfinder (ASKAP). We present 1760 H i detections (with a default spatial resolution of 30′′) from three pilot fields including the NGC 5044 and NGC 4808 groups as well as the Vela field, covering a total of $\sim 180$ deg$^2$ of the sky and spanning a redshift up to $z \simeq 0.09$. This release also includes kinematic models for over 126 spatially resolved galaxies. The observed median rms noise in the image cubes is 1.7 mJy per 30′′ beam and 18.5 kHz channel. This corresponds to a 5$\sigma$ H i column density sensitivity of $\sim 9.1\times10^{19}(1 + z)^4$ cm$^{-2}$ per 30′′ beam and $\sim 20$ km s$^{-1}$ channel and a 5$\sigma$ H i mass sensitivity of $\sim 5.5\times10^8 (D/100$ Mpc)$^{2}$ M$_{\odot}$ for point sources. Furthermore, we also present for the first time 12′′ high-resolution images (“cut-outs”) and catalogues for a sub-sample of 80 sources from the Pilot Survey Phase 2 fields. While we are able to recover sources with lower signal-to-noise ratio compared to sources in the Public Data Release 1, we do note that some data quality issues still persist, notably, flux discrepancies that are linked to the impact of side lobes associated with the dirty beams due to inadequate deconvolution. However, in spite of these limitations, the WALLABY Pilot Survey Phase 2 has already produced roughly a third of the number of HIPASS sources, making this the largest spatially resolved H i sample from a single survey to date.

Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25–26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs. Prominent themes surfaced, including competing research priorities and incentives, inadequate representation of patient population in clinical trials, opportunities to better leverage existing technology and infrastructure in trial design, and a need for heightened transparency and accountability in research practices. The group determined that together these elements contribute to an inefficient and costly clinical research enterprise, amplifying disparities in population health and sustaining gaps in evidence that impede advancements in equitable healthcare delivery and outcomes. The goal of addressing the identified challenges is to ultimately make clinical trials faster, more inclusive, and more efficient across diverse communities and settings.

The surface charge density of mica (001) cleavages was determined by counting the number of fission particle tracks in a given area of a 6-mm muscovite disc replica with optical and scanning electron microscopy after saturation of the layer charge by washing with 0.5 M UO2(NO3)2 solution, dilution of the excess salt by washing with 0.01 M UO2(NO3)2 in 0.005 M HNO3 (pH 2.4), blotting off the excess liquid, thermal neutron activation in contact with the muscovite disc, etching the muscovite, and counting the 235U fission tracks/cm2. In initial studies, the uranyl cations were found to hydrolyze from the cleavage surface continuously during the washings with water, ethanol or acetone to remove excess salts, but the uranyl cations in the interlayers near broken edges and crystallographical steps were strongly retained even against washings with 0.5 M CaCl2 solution. The hydrolysis of UO22 + from the smooth portions of the flake surfaces was avoided by the use of three 1-hr final washings with the 0.01 M UO2(NO3)2 in 0.005 M HNO3 solution. Each flake was pressed between filter papers three times to remove the excess solution. A negligible amount of excess salt remained on the cover glass controls. The UO22 + cations retained (mean, 3.6 ± 0.2 × 10−7 mequiv./cm2) on the cleavage surfaces of various micas were nearly equivalent to the theoretical surface charge (cation exchange capacity, 3.5 × 10−7 mequiv./cm2), showing that hydrolysis was prevented. The uranium on the unblemished mica planar surfaces increased with increasing uranyl concentrations in the final washing solution, indicating that the excess salt remaining on the surfaces had become significant. With a given UO22 + salt concentration, the uranium on the surface increased on increasing the solution pH from 2.5 to 3.5, attributable to the formation of polymeric ions such as U2O52 + and U3O82 + with higher uranium retention per unit positive charge equivalent to the fixed negative charge of the mineral surface. Uranyl cations replaced much of the interlayer cations from vermiculites even after K, Rb and Cs presaturation and drying from 110°C were employed. Strong adsorption of uranyl cations (in a form not replaced by washings with a neutral salt solution), which occurred in the defects of micaceous minerals, is important in the interpretation of actinide element retention in soils and sediments wherein these minerals are abundant.

The layer structure of kaolinite from Twiggs, Georgia and fire-clay type kaolinite (Frantex B, from France), particle size separates 2–0·2 μm was studied by high resolution electron microscopy after embedment in Spurr low-viscosity Epoxy media and thin sectioning normal to the (001) planes by an ultramicrotome. Images of the (001) planes (viewed edge-on) of both kaolinites were spaced at 7 Å and generally aligned in parallel, with occasional bending into more widely spaced images of about 10 Å interval. Some of the 10 Å images converged to 7 Å at one or both ends, forming ellipse-shaped islands 80 to 130 Å thick and 300 to 500 Å long. The island areas and interleaved 10 Å layers between 7 Å layers may represent a residue of incomplete weathering of mica to kaolinite.

The proportions of micaccous occlusions were too small and the layer sequences too irregular to be detected by X-ray diffraction. The lateral continuity of the layers through the 7-10-7 Å sequence in a kaolinite particle would partially interrupt or prevent expansion in dimethyl sulfoxide (DMSO) and other kaolinite intercalating media. Discrete mica particles were also observed with parallel images at 10 Å, as impurities in both kaolinites. The small K content of the chemical analyses of the kaolinite samples is accounted for as interlayer K, not only in discrete mica particles but also in the micaceous occlusions.

Background: Hyperacute stroke care demands rapid, coordinated care. Traditional metrics like Door-to-Needle time are pivotal but insufficient for capturing the complexity of endovascular stroke interventions. The SMILES collaboration aims to standardize and optimize protocols for door-to-intervention times, incorporating Crew Resource Management (CRM). Methods: The multidisciplinary initiative integrates both hospitals, ED, neurology, and QI teams. We employed a comprehensive approach: stakeholder engagement, simulation-based learning, process mapping, and literature review. Emphasis was placed on enhancing situational awareness, triage and prioritization, cognitive load management, role clarity, effective communication, and debriefing. Results: The collaboration led to PDSA cycles and development of refined stroke protocols. Interventions included: 1) A ’zero point survey’ for team pre-arrival briefings, enhancing situational awareness and role clarity; 2) Streamlined patient registration to reduce cognitive load and improve triage efficiency; 3) Direct transfer of patients to imaging. Additionally, digital tools were implemented to facilitate communication. Simulation sessions reinforced CRM principles, leading to improved team cohesion and operational performance. Conclusions: The SMILES initiative is grounded in CRM principles by standardizing protocols and emphasizing non-technical skills crucial for high-stakes environments. This improves outcomes but also fosters a culture of safety and efficiency. Future directions include an evaluation of these protocols’ impact on patient factors.

OBJECTIVES/GOALS: Our objective is to develop a Telenephrology dashboard for the 150,000 Veterans that obtain care through the Iowa City Veterans Affairs Health Care System. Our goal is to create a comprehensive and user-friendly tool for monitoring kidney health and facilitating remote nephrology consultations. METHODS/STUDY POPULATION: We structured our intervention according to the five stages of human-centered design: (1) Empathize, (2) Define, (3) Ideate, (4) Prototype and (5) Test. During the empathy stage, the principal investigator spent 10 hours immersed in the clinical setting observing how nephrologists approach a remote nephrology consultation. These observations were augmented by unstructured interviews with clinicians and patients to better understand the process and dynamics. Following this, a rapid ideation workshop was convened to generate creative solutions that balance technical requirements with the needs of clinicians and patients. These led to rapid prototyping and testing to identify what elements of the prototypes worked and which needed improvement. RESULTS/ANTICIPATED RESULTS: Through the empathy and define stages, three needs were identified: (1) clarity in visualizing data, (2) accuracy of information, and (3) balancing standardization with individualization. During the rapid ideation workshop, the concept of a four-frame dashboard was settled upon. This led to the creation of five prototypes, which were tested. These were reconciled and modified to make a final product. This final product, the Telenephrology Dashboard, contains 5 elements that support nephrologists and supporting staff: (1) a graph of kidney function over time, (2) tables synthesizing lab data, (3) options to drill down events to specific times, (4) customization of views, and (5) integration of kidney disease progression models. DISCUSSION/SIGNIFICANCE: A Telenephrology dashboard was created to facilitate remote nephrology consultations through a Human-Centered Design process. Our next steps include determining if this dashboard may improve end-user satisfaction, referring clinician satisfaction, access to specialist care, and patient outcomes.