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.#

Evidence indicates hypervitaminosis A may be attributed to overconsumption of natural preformed vitamin A (VA) and overlapping VA intervention strategies. Hypervitaminosis A can disrupt metabolic processes; however, the extent and mechanisms of these impacts are not well understood. This study aims to assess metabolic differences related to hypervitaminosis A and VA supplementation by performing metabolomics analysis. A subsample of South African preschoolers participating in the country’s VA supplementation programme was selected. Participants were divided into two groups: adequate VA (n 15; 0·59–0·99 µmol/g total liver reserve and high VA (n 15; ≥ 1·0 µmol/g total liver reserve). Serum samples were collected at baseline and 28 d after consuming a 200 000 IU VA supplement. Lipidomics and oxylipins assays were conducted using ultraperformance LC-MS. At baseline, unsaturated lysophosphatidylcholines and unsaturated phosphatidylcholines were significantly lower in the high VA group (P < 0·05). A group-by-time interaction with VA supplementation was observed for polyunsaturated lysophosphatidylcholines and polyunsaturated phosphatidylcholines (P < 0·05). Additionally, a group effect was noted for oxylipins, and a time effect in response to VA supplementation was seen with decreased arachidonic acid and lipoxygenase- and non-enzymatically derived oxylipins (P < 0·05). Hypervitaminosis A is associated with modifications in lipids involved in cell structure and signalling, particularly unsaturated lysophosphatidylcholines and phosphatidylcholines. Further research is needed to identify the mechanisms behind these modifications, their physiological effects and their potential as biomarkers of elevated vitamin A status.

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.

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.

Two reports follow on the vast, and vastly expensive, Tokyo International Conference on African Development designed to showcase Japan's aid to Africa. The conference, held in Yokohama with the presence of 51 of 53 African nations, was attended by 40 Presidents of African nations. The first report by Ramesh Jaura concentrates on the proposed Japanese aid package, as Japan proposes to double both trade and investment in Africa within five years. The second report by the Yomiuri Shimbun's Kawakami Osamu highlights the real stakes for Japan: the effort to outbid China whose burgeoning trade, investment and presence in Africa is a cause of Japanese, and the continued pursuit of the chimera of a Japanese UN security council seat. Neither report mentions either oil and energy or military strategic issues. MS

Quantum field theory predicts a nonlinear response of the vacuum to strong electromagnetic fields of macroscopic extent. This fundamental tenet has remained experimentally challenging and is yet to be tested in the laboratory. A particularly distinct signature of the resulting optical activity of the quantum vacuum is vacuum birefringence. This offers an excellent opportunity for a precision test of nonlinear quantum electrodynamics in an uncharted parameter regime. Recently, the operation of the high-intensity Relativistic Laser at the X-ray Free Electron Laser provided by the Helmholtz International Beamline for Extreme Fields has been inaugurated at the High Energy Density scientific instrument of the European X-ray Free Electron Laser. We make the case that this worldwide unique combination of an X-ray free-electron laser and an ultra-intense near-infrared laser together with recent advances in high-precision X-ray polarimetry, refinements of prospective discovery scenarios and progress in their accurate theoretical modelling have set the stage for performing an actual discovery experiment of quantum vacuum nonlinearity.

Corn (Zea mays L.) is an important crop that contributes to global food security, but understanding how farm management practices and soil health affect corn grain nutrient analysis and therefore human health is lacking. Leveraging Rodale Institute's Farming Systems Trial—a long-term field experiment established in 1981 in Kutztown, PA, USA—this study was conducted to assess the impact of different agricultural management systems on corn grain nutrient profiles in a long-term trial that has resulted in differences in soil health indicators between treatments as a result of long-term management. The main plot factor was two tillage practices (intensive and reduced) and the subplot factor was four cropping systems (non-diversified conventional [nCNV], diversified conventional [dCNV], legume-based organic [ORG-LEG], and manure-based organic [ORG-MNR]). Generally, the levels of amino acids, vitamins, and protein in corn grain were greatest in the ORG-MNR system, followed by the ORG-LEG and dCNV systems, and finally the nCNV system. It is important to consider that the observed difference between the organic and conventionally grown grain could be due to variations in corn hybrids that were used in those systems. However, nutrient composition of corn differed within cropping systems but between management practices (diversified crop rotation and cover cropping) which also contributed to differences in soil health indicators (soil compaction, soil protein, and organic C levels) that may also influence grain nutrient concentrations. With the exception of methionine, nutrient concentration in corn grain was not affected by different tillage regimes. These findings provide novel information on corn grain nutritional quality of organic and conventional cropping systems after long-term management and give insights into how system-specific components affect nutrient composition of corn grain.

This study investigated the helminths of the mixed invasive population of Darevskia armeniaca and D. dahli, collected during two field trips in Denyshy, Zhytomyr region, Ukraine, in 2023. In total, 67 adult lizards (35 D. armeniaca and 32 D. dahli) were examined. Molecular and morphological approaches were used to identify the parasites. The analyses revealed six helminth species, including four nematodes (Toxocara cati, Strongyloides darevskyi, Oswaldocruzia sp., and Spirurida gen. sp.), one trematode (Pleurogenes claviger), and one cestode (Mesocestoides litteratus). Toxocara cati had the highest prevalence, found in cysts located primarily on the liver and in the body cavity of the hosts. The qualitative and quantitative comparative assessment of the helminth community suggests that, due to the introduction of these lizards, most helminth species from their native range have been lost. Additionally, most local helminth species have not yet adapted to parasitising these lizards as normal hosts of their life cycle.

We present a higher-order spectral element method (SEM) for analyzing eccentric anisotropic multilayered waveguides. The formulation uses conformal transformation optics to map the original eccentric waveguide to an equivalent concentric one. This transformation is extended to handle anisotropic non-reciprocal media characterized by non-symmetric and non-Hermitian tensors. In the transformed concentric domain, higher-order two-dimensional basis functions associated with the zeros of the completed Lobatto polynomial are used to expand the fields. To simulate radially unbounded problems, we employ a complex-stretched perfectly matched layer to mimic open space. The method is validated with radially bounded two-layer and three-layer waveguides and radially unbounded three-layer waveguides. Comparisons with the finite element method (FEM) demonstrate that our SEM approach requires significantly fewer degrees of freedom than FEM.

Turbulence self-organization is studied in the flux-driven regime by means of the reduced model Tokam1D. Derived in the electrostatic and isothermal limit but keeping finite electron and ion temperatures, it features two instabilities that are suspected to dominate turbulent transport at the edge of L-mode tokamak plasmas: interchange (a reduced version of the resistive ballooning modes) and collisional drift waves, governed respectively by an effective gravity parameter $g$ and the adiabaticity parameter $C$. The usual properties of these two instabilities are recovered in the linear regime. The nonlinear study focuses on the self-organization of collisional drift-wave turbulence at $g=0$. It is found that the energy stored in zonal flows (ZFs) decreases smoothly at small $C$ due to the reduction of both electric and diamagnetic stresses. Conversely to gradient-driven simulations, no sharp collapse is observed due to the self-consistent evolution of the equilibrium density profile. The ZFs are found to structure into staircases at small and large $C$. These structures exhibit a rich variety of dynamics but are found to be robust to large perturbations. Their nucleation is found to be critically governed by the phase dynamics. Finally, the staircase structures are lost in the gradient-driven regime, when the system is prevented from storing turbulent energy into the equilibrium density (pressure) profile.

In many species with encapsulated larval development, the larvae play an active role in hatching. However, the factors that control when the larvae hatch from each egg-capsule within an egg-mass are largely unknown. Advanced egg-masses of the gastropod Crepipatella peruviana were used to determine the hatching time of capsules from each egg-mass. After each female was detached, the egg-mass was also removed from the substrate and all capsules were then counted and measured. All capsules were examined to determine the time of hatching and the order in which capsules hatched from each egg-mass. Larvae were collected from each hatched egg-capsule and the number, size and weight of larvae from each capsule were determined. After 50–60% of the capsules from each egg-mass had hatched, the same characteristics of the remaining unhatched larvae from sister capsules were documented. Larvae were found to have hatched when they reached a size of 354 ± 22 μm (n = 245). Larvae from capsules within the same egg-mass hatched over a period of up to 12-days. The order of hatching in capsules from the same egg-mass was determined by larval content: capsules with fewer larvae and smaller capsules with heavier larvae hatched first. The hatching from one capsule in any given egg-mass did not induce the hatching of its sister capsules. Furthermore, hatching also occurred successfully in the mother absence, suggesting that this process is largely or completely controlled by the encapsulated larvae, although a possible maternal role in synchronizing hatching cannot be excluded.