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: Stroke survivors have a higher risk of depression and suicide, but how hospitalization for major depression modifies the risk of suicide after stroke is not well-known. Methods: We conducted a population-based matched cohort study of adults hospitalized with first-ever stroke between 2008 to 2017 matched 1:1 to the general Ontario population on age, sex, neighbourhood-level income, rurality, and comorbidities. Patients with major depression or deliberate self-harm prior to index event were excluded from both groups. We used cause-specific proportional hazards models to evaluate the association between stroke and suicide (defined as self-harm or death by suicide) and used an interaction term to assess effect modification of depression on stroke-suicide association. Results: We included 64,719 matched pairs of patients with stroke and without (45.5% female, mean age 71.4 years). Compared to matched controls, stroke survivors had a higher rate of suicide (11.1 vs. 3.2, HR 2.87 [2.35-3.51]). Depression was associated with a higher rate of suicide in both groups (HR 13.8 [8.82-21.61]). The interaction between stroke and depression was not significant (Pstroke*depression = 0.51). Conclusions: Hospitalization for depression does not modify the rate of suicide after stroke, suggesting the need to better understand the pathways leading to suicide after stroke.

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.

It is known that interval type-2 fuzzy logic controllers (IT2FLC) with footprint of uncertainty (FOU) in terms of membership function (MF) have been developed as an effective control method to ensure control in systems where uncertainties and nonlinear situations are high, such as quadrotor control, and have been the subject of many studies. Designing and optimising parameters of IT2FLC controllers is complex and time-consuming. To overcome this situation, an optimisation method based on NSGA-II (Non-dominated Sorting Genetic Algorithm) was applied. ITAE (Integral Time Absolute Error) was chosen as the performance criterion. IT2FLC-NSGA-PID and NSGA-PID controllers were compared and it was observed that the IT2FLC-NSGA-PID controller gave better results. As a result, the superiority of the proposed controller over the other controllers is a better overshoot ratio, a faster settling time, a lower steady state error and a robust system response against uncertainties and disturbances in nonlinear systems.

Parasite biodiversity is underestimated or unknown in many regions, yet information on parasites is critical to understanding ecosystem structure and how this will change into the future. Understanding the diversity and role of parasites is especially important in regions exposed to anthropogenic pressures, such as aquatic ecosystems, as their interactions with other stressors can either exacerbate or mediate negative impacts. Water scarcity in the Brazilian semi-arid has led to a proliferation of reservoirs for human use. These artificial waterbodies host a diversity of taxa, including a large number of fish species; however, fish parasite diversity remains undocumented. This study investigated the parasitological diversity of fishes from reservoirs in the Paraíba and Mamanguape River basins in the Caatinga domain, Brazil – one of the most populated semi-arid regions worldwide. Eight reservoirs were studied, with fish sampled across the two phases of the hydrological cycle (dry and rainy seasons) using gillnets, cast nets, and trawl nets. Endo- and ecto-parasites were identified and enumerated, and parasitological indices (prevalence, intensity, and abundance) were calculated. In total, 1,170 individuals of 21 fish species were examined. Of these individuals, 42% were parasitized with at least one of 54 parasite taxa. We recorded 32 new geographical occurrences of parasites and 23 new fish-parasite interactions, expanding our understanding of ichthyoparasite diversity in the Brazilian semi-arid. Moving forward, it is important to develop knowledge around how anthropogenic changes (e.g., biological invasions, climate, and land use change) influence host-parasite structure and dynamics and ecosystem functioning in these ecosystems.

Turbofan engines are having a growing role in modern aircraft maintenance. Due to this increase, estimation of remaining useful life (RUL) of these engines is an important area of study in the field of reliability and maintenance optimisation. In this work, we propose a hybrid approach that combines deep learning models with similarity-based methods for accurate RUL estimation. For a better comparison, we evaluate four architectures: dropout long short-term memory (LSTM), bidirectional LSTM, convolutional neural network 1D (CNN 1D), and multi-layer LSTM. The FD002 subset of NASA’s Commercial Modular Aero-Propulsion System Simulation dataset is used in the case study. Root mean square error (RMSE) and mean absolute error (MAE) were used for performance metrics. The main output of the study suggests that the dropout LSTM model achieves the best prediction accuracy with an RMSE score of 26.547 and a MAE score of 18.749. It is worth noting that these are achieved despite requiring higher computational resources compared to multi-layer LSTM. Furthermore, all models had difficulties with smaller test trajectory lengths such as 50–100 due to training data imbalance. Overall, the findings highlight the promise of hybrid deep learning and similarity-based approaches for RUL prediction. However, potential advancements such as hyperparameter optimisation and data augmentation still hold potential for further improvements.

Bargaining scholars predict rapid power shifts cause preventive war. But cases with rapidly shifting power often remain peaceful. To explain the dogs that don’t bark, we introduce instant, repeated, costly militarization into Powell’s (1999) conventional-weapons power transition model. First, we rationalize preventive war during long, slow, complete-information power shifts. Second, we find that where past research into conventional shifts predicts war, a grand bargain backed by the decliner’s threat of war emerges as a second equilibrium. Because war and a grand bargain both prevent power from shifting, declining powers deploy them under the same conditions. Our grand bargain survives war-causing hazards, and some latent shifts. It occurs after incremental militarization causes repeated appeasement-like concessions, and when power shifts are instant, slow or fast, and perfectly observed; suggesting conventional shifts induce grand bargains under surprising conditions. The Great Game’s end fits our grand bargain, but that British elites seriously considered war.

Norm-based accounts of social behavior in economics typically reflect tradeoffs between maximization of own consumption utility and conformity to social norms. Theories of norm-following tend to assume that there exists a single, stable, commonly known injunctive social norm for a given choice setting and that each person has a stable propensity to follow social norms. We collect panel data on 1468 participants aged 11–15 years in Belfast, Northern Ireland and Bogotá, Colombia in which we measure norms for the dictator game and norm-following propensity twice at 10 weeks apart. We test these basic assumptions and find that norm-following propensity is stable, on average, but reported norms show evidence of change. We find that individual-level variation in reported norms between people and within people across time has interpretable structure using a series of latent transition analyses (LTA) which extend latent class models to a panel setting. The best fitting model includes five latent classes corresponding to five sets of normative beliefs that can be interpreted in terms of what respondents view as “appropriate” (e.g. equality vs. generosity) and how they view deviations (e.g. deontological vs. consequentialist). We also show that a major predictor of changing latent classes over time comes from dissimilarity to others in one’s network. Our application of LTA demonstrates how researchers can engage with heterogeneity in normative perceptions by identifying latent classes of beliefs and deepening understanding of the extent to which norms are shared, stable, and can be predicted to change. Finally, we contribute to the nascent experimental literature on the economic behavior of children and adolescents.

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.

Limited evidence on relative effectiveness is common in Health Technology Assessment (HTA), often due to sparse evidence on the population of interest or study-design constraints. When evidence directly relating to the policy decision is limited, the evidence base could be extended to incorporate indirectly related evidence. For instance, a sparse evidence base in children could borrow strength from evidence in adults to improve estimation and reduce uncertainty. In HTA, indirect evidence has typically been either disregarded (‘splitting’; no information-sharing) or included without considering any differences (‘lumping’; full information-sharing). However, sophisticated methods that impose moderate degrees of information-sharing have been proposed. We describe and implement multiple information-sharing methods in a case-study evaluating the effectiveness, cost-effectiveness and value of further research of intravenous immunoglobulin for severe sepsis and septic shock. We also provide metrics to determine the degree of information-sharing. Results indicate that method choice can have significant impact. Across information-sharing models, odds ratio estimates ranged between 0.55 and 0.90 and incremental cost-effectiveness ratios between £16,000–52,000 per quality-adjusted life year gained. The need for a future trial also differed by information-sharing model. Heterogeneity in the indirect evidence should also be carefully considered, as it may significantly impact estimates. We conclude that when indirect evidence is relevant to an assessment of effectiveness, the full range of information-sharing methods should be considered. The final selection should be based on a deliberative process that considers not only the plausibility of the methods’ assumptions but also the imposed degree of information-sharing.

Traditional wavefront control in high-energy, high-intensity laser systems usually lacks real-time capability, failing to address dynamic aberrations. This limits experimental accuracy due to shot-to-shot fluctuations and necessitates long cool-down phases to mitigate thermal effects, particularly as higher repetition rates become essential, for example, in inertial fusion research. This paper details the development and implementation of a real-time capable adaptive optics system at the Apollon laser facility. Inspired by astronomical adaptive optics, the system uses a fiber-coupled 905 nm laser diode as a pilot beam that allows for spectral separation, bypassing the constraints of pulsed lasers. A graphics processing unit-based controller, built on the open-source Compute And Control for Adaptive Optics framework, manages a loop comprising a bimorph deformable mirror and a high-speed Shack–Hartmann sensor. Initial tests showed excellent stability and effective aberration correction. However, integration into the Apollon laser revealed critical challenges unique to the laser environment that must be resolved to ensure safe operation with amplified shots.

Variation exists in our attitude and behaviour towards food and exercise, resulting in different degrees of health and ill health. Cultural and economic factors contribute to this, alongside personal choices, leading to a spectrum from normative eating, through disordered eating to the extremes of eating disorders (EDs). Understanding the intricate interplay between biological, psychological, and sociocultural factors to eating, exercise and body image is paramount to understand the current state regarding EDs and to deliver/develop multifaceted and individualised treatments. Significant service developments have occurred following the launch of the Irish Health Service Executive Model of Care for EDs in 2018. However, incomplete roll out and surge in EDs referrals post Covid-19 require generic child and adolescent mental health services (CAMHS) to be competent in assessment of EDs, and to keep abreast of clinical updates in order to offer effective treatment.

This review provides an evidenced based update on eating related difficulties, outlines a useful assessment framework, offers information on appropriate clinical management, and highlights exciting clinically relevant research developments.

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.