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: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP). The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) and open-label extension ADHERE+ (NCT04280718) trials (interim analysis cutoff: February 16, 2024) assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to efgartigimod or placebo for ≤48 weeks (stage-B). Participants with clinical deterioration in stage-B or who completed ADHERE entered ADHERE+. Week 36 changes from run-in baseline (CFB) in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), and grip strength scores were evaluated. Results: Of 322 stage-A participants, 221 were randomized and treated in stage-B, and 99% entered ADHERE+. Mean CFB (SE) in aINCAT, I-RODS, and grip strength scores were -1.2 (0.15) and 8.8 (1.46) and 17.5 (2.02), respectively, at ADHERE+ Week 36 (N=150). Half the participants with clinical deterioration during ADHERE stage-B restabilized on efgartigimod from ADHERE+ Week 4. Conclusions: Interim results from ADHERE+ indicate long-term effectiveness of efgartigimod PH20 SC in clinical outcomes in participants with CIDP.

Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP), a rare, progressive, immune-mediated disease that can lead to irreversible disability. The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) trial assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to weekly efgartigimod or placebo for ≤48 weeks (stage-B). This posthoc analysis evaluated changes from run-in baseline (study enrollment) to stage-B last assessment and items of the Inflammatory Rasch-built Overall Disability Scale (I-RODS). Results: Of 322 participants who entered stage-A, 221 were randomized and treated in stage-B, and 191/221 had data for run-in baseline and post–stage-B timepoints. Mean (SE) I-RODS change at stage-B last assessment vs run-in baseline was 5.7 (1.88) and -4.9 (1.82) in participants randomized to efgartigimod and placebo, respectively. 37/97 (38.1%) and 24/92 (26.1%) participants randomized to efgartigimod and placebo, respectively, experienced ≥4-point improvements in I-RODS score. Efgartigimod-treated participants improved ≥1 point in I-RODS items of clinical interest. Conclusions: Participants who received efgartigimod in stage-B experienced improvements in I-RODS score from study enrollment to stage-B last assessment.

We investigated the effects of maternal vitamin and mineral supplementation throughout gestation on gene expression in the jejunal mucosa of neonatal calves. Crossbred Angus heifers (n = 14) were estrus synchronized, bred to female-sexed semen, and randomly assigned to a basal diet (Control, CON; n = 7) or the basal diet plus vitamin and mineral supplement (Treatment, VTM; n = 7). After parturition, calves were removed from their dams before suckling, fed colostrum replacer, and euthanized 30 h after the first feeding. A subsample of the mucosa of the mid-jejunum was collected, and total RNA was isolated. Gene expression was measured using RNA-Seq, and differentially expressed genes (DEGs) were identified using DESeq2. We identified 528 DEGs from the jejunal mucosa between the VTM and CON calves (P ≤ 0.05 and |log2FC| ≥ 0.5). The DEGs were associated with nutrient transport, lipid metabolism, and immune-related biological processes and pathways. Interestingly, genes underlying the complement and coagulation cascades were mostly downregulated in calves born to VTM dams. On the other hand, the cytokine-cytokine receptor interaction KEGG pathway showed most genes upregulated (LIFR, KDR, TNFRSF4, TNFSF18, FLT1, and TNFRSF12A). Our results show that vitamin and mineral supplementation throughout gestation affects genes underlying tissue structure, nutrient transport and metabolism, and immune system pathways in neonates. The implications of such changes and the long-term outcomes on herd health and performance warrant further research.

Avocado is a delicious fruit crop having great economic importance. Understanding the extent of variability present in the existing germplasm is important to identify genotypes with specific traits and their utilization in crop improvement. The information on genetic variability with respect to morphological and biochemical traits in Indian avocados is limited and as it has hindered genetic improvement of the crop. In the current study, 83 avocado accessions from different regions of India were assessed for important 17 morphological and 8 biochemical traits. The results showed the existence of wide variability for traits such as fruit weight (75.88–934.12 g), pulp weight (48.08–736.19 g), seed weight (6.37–32.62 g), FRAP activity (27.65–119.81 mg AEAC/100 g), total carotenoids (0.96–7.17 mg/100 g), oil content (4.91–25.49%) and crude fibre (6.85–20.75%) in the studied accessions. The first three components of principal component analysis explained 54.79 per cent of total variance. Traits such as fruit weight, pulp weight, seed weight, moisture and oil content contributed more significantly towards total variance compared to other traits. The dendrogram constructed based on Euclidean distance wards minimum variance method divided 83 accessions into two major groups and nine sub clusters suggesting wide variability in the accessions with respect to studied traits. In this study, superior accessions for important traits such as fruit size (PA-102, PA-012), high pulp recovery (PA-036, PA-082,), thick peel (PA-084, PA-043, PA-011, PA-008), high carotenoids (PA-026, PA-096) and high oil content (PA-044, PA-043, PA-046, PA-045) were identified which have potential utility in further crop improvement programmes.

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 Australian SKA Pathfinder (ASKAP) offers powerful new capabilities for studying the polarised and magnetised Universe at radio wavelengths. In this paper, we introduce the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), a groundbreaking survey with three primary objectives: (1) to create a comprehensive Faraday rotation measure (RM) grid of up to one million compact extragalactic sources across the southern $\sim50$% of the sky (20,630 deg$^2$); (2) to map the intrinsic polarisation and RM properties of a wide range of discrete extragalactic and Galactic objects over the same area; and (3) to contribute interferometric data with excellent surface brightness sensitivity, which can be combined with single-dish data to study the diffuse Galactic interstellar medium. Observations for the full POSSUM survey commenced in May 2023 and are expected to conclude by mid-2028. POSSUM will achieve an RM grid density of around 30–50 RMs per square degree with a median measurement uncertainty of $\sim$1 rad m$^{-2}$. The survey operates primarily over a frequency range of 800–1088 MHz, with an angular resolution of 20” and a typical RMS sensitivity in Stokes Q or U of 18 $\mu$Jy beam$^{-1}$. Additionally, the survey will be supplemented by similar observations covering 1296–1440 MHz over 38% of the sky. POSSUM will enable the discovery and detailed investigation of magnetised phenomena in a wide range of cosmic environments, including the intergalactic medium and cosmic web, galaxy clusters and groups, active galactic nuclei and radio galaxies, the Magellanic System and other nearby galaxies, galaxy halos and the circumgalactic medium, and the magnetic structure of the Milky Way across a very wide range of scales, as well as the interplay between these components. This paper reviews the current science case developed by the POSSUM Collaboration and provides an overview of POSSUM’s observations, data processing, outputs, and its complementarity with other radio and multi-wavelength surveys, including future work with the SKA.

The legitimacy of armed forces in the eyes of civilians is increasingly recognized as crucial not only for battlefield effectiveness but also for conflict resolution and peace building. However, the concept of “military legitimacy” remains under-theorized and its determinants poorly understood. We argue that perceptions of military legitimacy are shaped by two key dimensions of warfare: just cause and just conduct. Leveraging naturally occurring variation during one of the deadliest urban battles in recent history—the multinational campaign to defeat the Islamic State in Mosul, Iraq—we evaluate our theory using a mixed-methods design that combines original survey data, satellite imagery, and interviews. Civilians living in neighborhoods where armed forces were less careful to protect civilians view those forces as less legitimate than civilians elsewhere. Surprisingly, these results persist after conditioning on personal experiences of harm, suggesting that perceptions are influenced not only by victimization—consistent with previous studies—but also by beliefs about the morality of armed forces’ conduct and the cause for which they are fighting.

The Society for Healthcare Epidemiology of America, the Association of Professionals in Infection Control and Epidemiology, the Infectious Diseases Society of America, and the Pediatric Infectious Diseases Society represent the core expertise regarding healthcare infection prevention and infectious diseases and have written multisociety statement for healthcare facility leaders, regulatory agencies, payors, and patients to strengthen requirements and expectations around facility infection prevention and control (IPC) programs. Based on a systematic literature search and formal consensus process, the authors advocate raising the expectations for facility IPC programs, moving to effective programs that are:

• Foundational and influential parts of the facility’s operational structure

• Resourced with the correct expertise and leadership

• Prioritized to address all potential infectious harms

This document discusses the IPC program’s leadership—a dyad model that includes both physician and infection preventionist leaders—its reporting structure, expertise, and competencies of its members, and the roles and accountability of partnering groups within the healthcare facility. The document outlines a process for identifying minimum IPC program medical director support. It applies to all types of healthcare settings except post-acute long-term care and focuses on resources for the IPC program. Long-term acute care hospital (LTACH) staffing and antimicrobial stewardship programs will be discussed in subsequent documents.

The description and delineation of trematode species is a major ongoing task. Across the field there has been, and currently still is, great variation in the standard of this work and in the sophistication of the proposal of taxonomic hypotheses. Although most species are relatively unambiguously distinct from their congeners, many are either morphologically very similar, including the major and rapidly growing component of cryptic species, or are highly variable morphologically despite little to no molecular variation for standard DNA markers. Here we review challenges in species delineation in the context provided to us by the historical literature, and the use of morphological, geographical, host, and molecular data. We observe that there are potential challenges associated with all these information sources. As a result, we encourage careful proposal of taxonomic hypotheses with consideration for underlying species concepts and frank acknowledgement of weaknesses or conflict in the data. It seems clear that there is no single source of data that provides a wholly reliable answer to our taxonomic challenges but that nuanced consideration of information from multiple sources (the ‘integrated approach’) provides the best possibility of developing hypotheses that will stand the test of time.

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.

The fossil record of dinosaurs in Scotland mostly comprises isolated highly fragmentary bones from the Great Estuarine Group in the Inner Hebrides (Bajocian–Bathonian). Here we report the first definite dinosaur body fossil ever found in Scotland (historically), having been discovered in 1973, but not collected until 45 years later. It is the first and most complete partial dinosaur skeleton currently known from Scotland. NMS G.2023.19.1 was recovered from a challenging foreshore location in the Isle of Skye, and transported to harbour in a semi-rigid inflatable boat towed by a motor boat. After manual preparation, micro-CT scanning was carried out, but this did not aid in identification. Among many unidentifiable elements, a neural arch, two ribs and part of the ilium are described herein, and their features indicate that this was a cerapodan or ornithopod dinosaur. Histological thin sections of one of the ribs support this identification, indicating an individual at least eight years of age, growing slowly at the time of death. If ornithopodan, as our data suggest, it could represent the world's oldest body fossil of this clade.