Background: Antibodies directed against acetylcholine receptor (AChR) are absent in approximately 15% of patients with gMG. Approved treatment options represent an unmet need in the AChR-antibody (Ab)- gMG population. Efgartigimod is an immunoglobulin G1 (IgG1) antibody Fc fragment that selectively reduces IgG levels by blocking neonatal Fc receptor (FcRn)-mediated IgG recycling. Here, we describe efgartigimod efficacy in AChR-Ab- participants with gMG receiving either efgartigimod IV or subcutaneous (SC) efgartigimod PH20 (coformulated with recombinant human hyaluronidase PH20) across clinical studies. Methods: Post hoc analyses were conducted to examine efficacy and safety of efgartigimod IV and/or efgartigimod PH20 SC in AChR-Ab- participants in ADAPT/ADAPT+ and ADAPT-SC/ADAPT-SC+ trials. Results: Among pooled AChR-Ab- participants (n=56), mean (SE) MG-ADL total score improvement from baseline to Week 3 was -3.7 (Cycle 1: 0.44 [n=55]). Consistent MG-ADL improvements occurred with repeated cycles. Clinically meaningful improvements (CMI; ≥2-point MG-ADL decrease) occurred in 76.4% (n=42/55) of participants (Cycle 1, Week 3). In Cycle 1, 23.2% (n=13/56) of participants achieved minimal symptom expression (MG-ADL 0-1). Similar efficacy results occurred across all cycles. Overall safety profile was similar between AChR-Ab+ and AChR-Ab- participants. Conclusions: Both efgartigimod IV and efgartigimod PH20 SC were well tolerated and led to CMI in participants with AChR-Ab- gMG.

Background: RAISE-XT (NCT04225871; Phase 3 study) showed clinically meaningful and sustained improvements in myasthenia gravis (MG)-specific outcomes with zilucoplan, a macrocyclic peptide complement component 5 inhibitor, in patients with acetylcholine receptor autoantibody-positive generalised MG. Methods: Adults self-administered once-daily subcutaneous zilucoplan 0.3mg/kg. This post hoc analysis assessed durability of response to Week 120 in MG-Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) responders at Week 1 of two double-blind studies (NCT03315130, NCT04115293). Responder definitions: improvements of ≥3-points (MG-ADL) or ≥5-points (QMG) (interim data cut: 11 November 2023). Results: 93 patients were randomised to zilucoplan 0.3mg/kg in the double-blind studies; 43.0% (n=40/93) and 33.3% (n=31/93) were MG-ADL and QMG responders, respectively, at Week 1. Week 1 responders spent a median #of 98.9% (5.8–99.2) and 99.0% (2.5–99.2) time in response up to Week 120 for MG-ADL and QMG. Week 1 non-responders spent# a median #of 84.6% (0.0–98.3) and 66.7% (0.0–98.9) time in response up to Week 120 for MG-ADL and QMG, with most responding later in the study. Conclusions: Among early (Week 1) zilucoplan responders, time in response remained high (99%) up to Week 120. These data demonstrate rapid and sustained efficacy with long-term zilucoplan treatment.#

Background: The efficacy and safety of lecanemab have previously been evaluated in the Phase 3 randomized clinical trial, Clarity AD (NCT03887455). Methods: A Markov cohort model was developed to estimate the cost-effectiveness of lecanemab versus standard of care (SoC) in patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD), with confirmed beta-amyloid (Aβ) pathology, from a Canadian societal perspective. Health states were determined by Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. Transitions between health states during month 0-18 were estimated from Clarity AD. Beyond month 18, relative efficacy for lecanemab in the form of the hazard ratio for time-to-worsening of CDR-SB was applied to literature-based transition probabilities. The model included the effects of lost productivity and impact on carer health-related quality of life. Results: The incremental cost-effectiveness ratio (ICER) for lecanemab vs SoC was estimated to be CAD 62,751 per QALY gained. The probability that lecanemab was cost-effective at a threshold of CAD 100,000 was estimated to be 88.5%. Conclusions: Lecanemab represents a cost-effective option for the treatment for early AD from the Canadian societal perspective. The results of this analysis can be used to inform clinical and economic decision making.

Background: This study explored whether Myelin Water imaging could detect myelin injury in Anti-NMDA receptor autoimmune encephalitis (NMDAr-AIE), where traditional neuroimaging is often normal. Myelin Water Fraction (MWF) quantifies myelin content by distinguishing myelin sheath water from other brain water compartments. Methods: Adult participants with confirmed NMDAr-AIE diagnoses and healthy controls (HC) underwent 3T brain MRI including MWF mapping. Participants were recruited after discharge from the hospital. Mean MWF was calculated for 4 white matter regions of interest (ROI). Patient demographics, clinical assessments, treatment, and outcomes were collected. Results: Five participants with NMDAr-AIE (4F/1M, mean age 30, SD 7) and four HC (3F/1M, mean age 36, SD 6) were included. All NMDAr-AIE participants had normal or non-specific T2 hyperintensities on initial imaging and had received immunotherapy. The mean Modified Rankin Score (MRS) on discharge was 2. MWF (mean ± SD) for normal-appearing white matter, corpus callosum, corticospinal tract, and superior longitudinal fasciculus were 0.10±0.02, 0.12±0.02, 0.15±0.03, 0.12±0.02, which were very similar to HC at 0.09±0.02, 0.11±0.01, 0.15±0.02, and 0.11±0.02, respectively. Conclusions: Myelin Water imaging showed no myelin pathology in five NMDAr-AIE patients, with MWF values comparable to HC. This suggests that myelin pathways are relatively preserved post-recovery from AIE.

Background: Ocular point-of-care ultrasound (POCUS) may be a clinically useful method to evaluate shunt dysfunction for children with hydrocephalus in the emergency department (ED). We assessed whether a change in optic nerve sheath diameter (ONSD) from prior asymptomatic baseline is associated with shunt failure. Methods: This prospective single center cohort study included asymptomatic shunted children (age 0-18 years). Baseline ocular POCUS was performed in the outpatient neurosurgery clinic; a second POCUS was performed if the patient subsequently presented to the ED with symptoms of shunt failure. Shunt failure was defined by intraoperative confirmation of inadequate CSF flow through the shunt within 96 hours from ED presentation. Results: The primary outcome of intra-operatively confirmed shunt failure occurred in 14/76 (18%) ED patient presentations. ΔONSD in patients with and without shunt failure was 0.89mm and 0.16mm respectively; the mean difference was 0.73mm (95%CI: 0.34-1.12), p=0.0012. The area under the receiver operating characteristic curve was 0.86, with an optimal cutoff of ≥+0.4mm, corresponding to sensitivity of 0.93, specificity of 0.73, PPV of 0.43, NPV of 0.98. Conclusions: ΔONSD was strongly associated with shunt failure. We found ΔONSD of <+0.4 in symptomatic children with CSF shunts may identify a population that had low likelihood of true shunt failure.

Background: Studies have found similar rates of functional independence for men and women after endovascular thrombectomy (EVT). Less is known regarding EVT-related procedural complications and symptomatic intracerebral hemorrhage (sICH) between sexes. Methods: Using the OPTIMISE registry including data from 20 comprehensive stroke centers across Canada between 1/1/2018 and 12/31/2022, we performed a retrospective descriptive analysis of patients divided between men and women. Hemorrhagic transformation on follow-up imaging with associated clinical deterioration was required to define sICH. Results: 3631 patients were included (1778 men and 1853 women) for analysis. Female patients were older (71.8±14.6 vs 68.0±13.1 years, p<0.001). There were no differences in sICH rates (2.5% men vs. 2% women, p= 0.388}. Procedural complication rates were not different between men and women (5.8 vs 5.6% p=0.76): dissection {26 (1.5%) vs. 30 (1.6%), p=0.804}, perforation {11 (0.6%) vs. 7 (0.4%), p=0.426}, embolization {25 (1.4%) vs. 25 (1.3%), p=0.996} and arterial access complications {45 (2.5%) vs. 43 (2.3%), p=0.761}. Conclusions: In this large multicentre registry of stroke patients undergoing EVT, men and women had similarly low and reassuring rates of sICH and procedural complications. This complements previous data showing similar functional outcomes for men and women after EVT.

Background: Transcranial doppler ultrasound (TCD) in a pediatric neurocritical setting can determine cerebral hemodynamics by assessing the blood flow velocity in main cerebral arteries. In large vessel occlusions (LVO) that require endovascular thrombectomy (EVT), TCD can monitor recanalization and arterial re-occlusion. We describe one case in a previously healthy 13-year-old girl with a right M1 middle cerebral artery occlusion. Methods: Analysis was done via a retrospective case review. Results: Our patient underwent a successful endovascular thrombectomy (EVT) six hours after symptom onset. Follow up TCDs done at 4, 8, and 24 hours showed stable peak systolic velocities (PSV) on the narrowing of right M1 ranging from 245 to 270 cm/s with stable pre-stenotic PSV around 110 cm/s, indicating focal and stable narrowing of M1 without reocclusion. No high transient signals (HITS) were identified on sub 10 minute TCDs. An urgent echocardiogram revealed a bicuspid aortic valve with vegetations, with later confirmation of infective endocarditis. The patient made an impressive recovery with only mild deficits. Conclusions: TCD can be an effective tool in a pediatric neurocritical setting in guiding initial recanalization after EVT and monitoring for arterial re-occlusion, HITS and hyperperfusion. TCD monitoring also decreases the amount of radiation exposure via CTA.

Almost 12% of the human population have insufficient access to food and hence are at risk from nutrient deficiencies and related conditions, such as anaemia and stunting. Ruminant meat and milk are rich in protein and micronutrients, making them a highly nutritious food source for human consumption. Conversely, ruminant production contributes to methane (CH4) emissions, a greenhouse gas (GHG) with a global warming potential (GWP) 27-30 times greater than that of carbon dioxide (CO2). Nonetheless, ruminant production plays a crucial role in the circular bioeconomy in terms of upcycling agricultural products that cannot be consumed by humans, into valuable and nutritional food, whilst delivering important ecosystem services. Taking on board the complexities of ruminant production and the need to improve both human and planetary health, there is increasing emphasis on developing innovative solutions to achieve sustainable ruminant production within the ‘One Health’ framework. Specifically, research and innovation will undoubtedly continue to focus on 1) Genetics and Breeding; 2) Animal nutrition and 3) Animal Health, to achieve food security and human health, whilst limiting environmental impact. Implementation of resultant innovations within the agri-food sector will require several enablers, including large-scale investment, multi-actor partnerships, scaling, regulatory approval and importantly social acceptability. This review outlines the grand challenges of achieving sustainable ruminant production and likely research and innovation landscape over the next 15 years and beyond, specifically outlining the pathways and enablers required to achieve sustainable ruminant production within the One Health framework.

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.

The scatter in global atomic hydrogen (Hi) scaling relations is partly attributed to differences in how Hi and stellar properties are measured, with Hi reservoirs typically extending beyond the inner regions of galaxies where star formation occurs. Using pilot observations from the Widefield ASKAP L-band Legacy All-sky Blind Survey (WALLABY), we present the first measurements of Hi mass enclosed within the stellar-dominated regions of galaxies for a statistical sample of 995 local gas-rich systems, investigating the factors driving its variation. We examine how global Hi scaling relations change when measurements are restricted to $R_{\text{25}}$ and $R_{\text{24}}$ – the isophotal radii at 25 and 24 mag arcsec$^{-2}$ in the i-band – and explore how the fraction of Hi mass and Hi surface density within these radii correlate with other galaxy properties. On average, 68% of the total Hi mass is enclosed within $R_{\text{25}}$ and 54% within $R_{\text{24}}$, though significant variation exists between galaxies, ranging from $\sim$20% to 100%. The fraction of Hi mass within $R_{\text{25}}$ shows a mild correlation with stellar properties, with galaxies of higher stellar mass, greater stellar surface density, or redder colours enclosing a larger fraction of their Hi reservoirs. These correlations do not significantly strengthen when considering $R_{\text{24}}$. Conversely, global Hi surface densities show no significant correlation with stellar mass or stellar surface density, but trends start emerging when these are measured within the inner regions of galaxies. The strongest correlation is observed with optical colour, with bluer galaxies having higher average Hi surface densities within $R_{\text{25}}$. This trend of the average Hi surface density with optical colour strengthens when we restrict from $R_{\text{25}}$ to $R_{\text{24}}$, suggesting a closer connection between inner Hi reservoirs and star formation. This study underscores the value of (at least marginally) resolved Hi surveys of statistical samples for advancing our understanding of the gas-star formation cycle in galaxies.

Low vegetable intake is a key contributor to the health burden experienced by young adults in rural communities(1). Digital interventions provide an accessible delivery model that can be personalised to meet the diverse preferences of young adults(2). This study aimed to determine the feasibility, acceptability and efficacy of a personalised digital intervention to increase vegetable intake (Veg4Me), co-designed to meet the needs of young adults living in rural Australian communities(3). A 12-week assessor-blinded, two-arm, parallel randomised controlled trial was undertaken from August 2023 until April 2024. Young adults (18–35 years; consuming < 5 serves of vegetables/day; with an internet-connected device) living in Loddon Campaspe or Colac Otway Shire in Victoria, Australia, were recruited via social media and local government networks. Participants were randomised to receive 12 weeks of personalised (intervention) or non-personalised (control) support via a free web application (app; Veg4Me). Key features included 1) recipes personalised to users’ dietary and cooking preferences, 2) geo-located food environment map, 3) healthy eating resources, 4) goal-setting portal and 5) personalised e-newsletters. The primary outcome was feasibility: recruitment, participation and retention rate. Secondary outcomes were usability and user experience, perceived changed in vegetable intake, self-reported vegetable intake, and confidence to cook fresh green and root vegetables. Regression analyses (adjusted for baseline) were used to test for significant differences between groups. A total of n = 536 individuals registered on the Veg4Me website. After excluding fraudulent and duplicate responses (n = 289), n = 124 were eligible and provided consent to participate, n = 116 were randomised and n = 83 completed postintervention data collection. The recruitment rate was 47%, participation rate was 93% and retention rate was 72%. Compared to the control, more intervention participants were satisfied with Veg4Me (76% vs 52%). Most intervention participants reported that access to personalised recipes gave them confidence to eat a wider variety of vegetables (83%), while 76% accessed the food environment map, 63% accessed the healthy eating resources, 78% accessed the goal-setting function and 90% reported that the e-newsletters prompted them to access Veg4Me. Compared to the control, more intervention participants perceived that their vegetable intake had changed in the last 12 weeks (85% vs 57%; p = 0.013). Mean vegetable intake at 12 weeks in intervention and control participants was 2.7 (SD 1.0) and 2.7 (SD 1.4) serves/day, respectively (p = 0.67). Confidence to cook fresh green vegetables at 12 weeks in intervention and control participants was 93% and 91%, respectively (p = 0.24), while for root vegetables this was 88% and 81%, respectively (p = 0.11). Findings demonstrate the feasibility and acceptability of the Veg4Me intervention, and some evidence of efficacy. This study introduces a new strategy that has promise for addressing diet and health inequities experienced by young adults living in rural communities.

In the early morning of February 11, around 4 a.m., a devastating fire swept through the locked cells of a migrant worker detention center in the South Korean city of Yeosu, killing 10 detainees and wounding many others. The center staff tried to put out the flames by spraying fire extinguishers through the bars of the cells, but in an act that can only be described as barbaric, did not unlock the cell doors to free those trapped inside, out of fear that they would escape. Migrant workers behind the locked doors and barred windows were forced to breath in the toxic fumes emitted from burning mattresses. These fumes were the cause of most of the deaths and injuries. The cause of the fire is still under investigation, but the reality is that the roots of the tragedy lie with the Korean government's inhumane policy towards migrant workers.

Herbaceous perennials must annually rebuild the aboveground photosynthetic architecture from carbohydrates stored in crowns, rhizomes, and roots. Knowledge of carbohydrate utilization and storage can inform management decisions and improve control outcomes for invasive perennials. We monitored the nonstructural carbohydrates in a population of the hybrid Bohemian knotweed [Polygonum ×bohemicum (J. Chrtek & Chrtková) Zika & Jacobson [cuspidatum × sachalinense]; syn.: Fallopia ×bohemica (Chrtek and Chrtková) J.P. Bailey] and in Japanese knotweed [Polygonum cuspidatum Siebold & Zucc.; syn.: Fallopia japonica (Houtt.) Ronse Decr.]. Carbohydrate storage in crowns followed seasonal patterns typical of perennial herbaceous dicots corresponding to key phenological events. Starch was consistently the highest nonstructural carbohydrate present. Sucrose levels did not show a consistent inverse relationship with starch levels. Lateral distribution of starch in rhizomes and, more broadly, total nonstructural carbohydrates sampled before dormancy break showed higher levels in rhizomes compared with crowns. Total nonstructural carbohydrate levels in crowns reached seasonal lows at an estimated 22.6% of crown dry weight after accumulating 1,453.8 growing degree days (GDD) by the end of June, mainly due to depleted levels of stored starch, with the estimated minimum of 12.3% reached by 1,220.3 GDD accumulated by mid-June. Depletion corresponded to rapid development of vegetative canopy before entering the reproductive phase in August. Maximum starch accumulation in crowns followed complete senescence of aboveground tissues by mid- to late October. Removal of aboveground shoot biomass in late June to early July with removal of vegetation regrowth in early September before senescence would optimize the use of time and labor to deplete carbohydrate reserves. Additionally, foliar-applied systemic herbicide translocation to belowground tissue should be maximized with applications in late August through early fall to optimize downward translocation with assimilate movement to rebuild underground storage reserves. Fall applications should be made before loss of healthy leaf tissue, with the window for control typically ending by late September in Minnesota.

Objectives/Goals: Ischemic stroke treatments assist in restoring blood flow, but do not guarantee good outcomes. Since extracellular vesicles (EVs) able to cross the blood brain barrier, total (nonspecific) and astrocyte enriched EVs (TEVs, AEVs, respectively) from plasma may emerge as plasma biomarkers for prognostication and targeted therapeutics. Methods/Study Population: “Blood and Clot Thrombectomy Registry and Collaboration” (BACTRAC; NCT03153683) is a human stroke biobank at the University of Kentucky that collects samples at the time of mechanical thrombectomy during emergent large vessel occlusions (ELVO; ischemic stroke). EVs were isolated, via size exclusion chromatography, from unbanked plasma and concentrated resulting in TEVs. AEVs were immunoprecipitated with anti-EAAT1 (GLAST), an astrocyte-specific transmembrane glycoprotein. Isolated protein was sent to Olink and ran on their metabolic panel. Demographics and medical histories of the subjects were exported from REDcap and investigators were blinded during EV analysis. Results/Anticipated Results: ELVO subjects (8 females/ 5 males) were an average age of 71.1 ± 11.7 years. Lower TEV enolase 2, a neuronal glycolysis enzyme, associated with increased stroke severity (NIHSS; rs =  -0.7819, p = 0.0476). Higher systemically TEV quinoid dihydropteridine reductase (QDPR), essential co-factor enzyme, was associated with more severe strokes (NIHSS; rs =  0.8486, p = 0.0123) and lower cognition (MoCA; r2 =  0.7515, p = 0.0254). Interestingly, higher intracranial AEVs QDPR was associated with lower infarct volumes (rs =  -0.7333, p = 0.0202), less severe strokes (NIHSS; rs =  -0.6095, p = 0.0388), and better cognition (MoCA; r2 =  0.6095, p = 0.0388). Increased AEV nicotinamide adenine dinucleotide kinase another essential co-factor enzyme, intracranially also correlated to higher cognition (MoCA; rs =  0.8356, p = 0.0298). Discussion/Significance of Impact: Plasma TEV and AEV metabolic proteins correlate with the progression of stroke outcomes and should be investigated as target therapies during MT to improve outcomes.