Background: Nipocalimab (a fully human, effectorless anti-neonatal Fc receptor (FcRn) monoclonal antibody) may ameliorate gMG disease manifestations by selectively targeting FcRn IgG recycling and lowering IgG, including pathogenic autoantibodies in generalized myasthenia gravis (gMG). The objective was to evaluate the effectiveness and safety of intravenous nipocalimab added to background standard-of-care therapy in adolescents with gMG. Methods: Seropositive patients (12-<18 years) with gMG (MGFA Class II-IV) on stable therapy but inadequately controlled, were enrolled in a 24-week open label study. Nipocalimab was administered as a 30 mg/kg IV loading dose followed by 15 mg/kg IV every 2 Weeks. Results: Seven adolescents were enrolled; 5 completed 24-weeks of dosing. The mean(SD) age was 14.1(1.86) years; seven were anti-AChR+, six were female. Mean(SD) baseline MG-ADL/QMG scores were 4.29(2.430)/12.50(3.708). Nipocalimab showed a significant reduction in total serum IgG at week-24; the mean(SD) change from baseline to week-24 for total serum IgG was -68.98%(7.561). The mean(SD) change in MG-ADL/QMG scores at week-24 was -2.40(0.418)/-3.80(2.683); 4 of 5 patients achieved minimum symptom expression (MG-ADL score 0-1) by week-24. Nipocalimab was well-tolerated; there were no serious adverse events. There were no clinically meaningful laboratory changes. Conclusions: Nipocalimab demonstrated efficacy and safety in this 6-month trial in seropositive adolescents with gMG.

Background: TeleStroke can improve access to stroke care in rural areas. We aim to evaluate the safety and effectiveness of intravenous thrombolysis in our TeleStroke system. Methods: The Manitoba TeleStroke program was rolled out across 7 sites between November 2014 and January 2019. We retrospectively analyzed prospectively collected consecutive acute stroke patients’ data in this duration. The primary outcome was safety and effectiveness measured in terms of 90-day modified Rankin score (mRs). The number of acute ischemic stroke (AIS) patients receiving thrombolysis and endovascular thrombectomy [EVT] and process metrics were also analyzed. R/RStudio version-4.3.2 was used (p<0.05). Results: Of the 1,748 TeleStroke patients (age 71 years [IQR 58-81], female 810[46.3%]), 696 were identified as AIS. Of these, 265(38.1%) received thrombolysis and 48(6.9%) EVT. Ninety-day mortality was 53(20.0%) among those receiving thrombolysis and 117(44.2%) had a favorable outcome (mRs ≤2). Of those who received intravenous thrombolysis, 9 patients (4.2%) were found to have symptomatic intracranial hemorrhage. The median last-seen-normal (LSN)-to-door was121 minutes and the median door-to-needle, 55 minutes. Conclusions: Intravenous thrombolysis was found to be effective with acceptable safety. TeleStroke improved overall access to stroke care and played an important role in identifying AIS patients eligible for thrombolysis and EVT.

Riboswitches are RNA elements with a defined structure found in noncoding sections of genes that allow the direct control of gene expression by the binding of small molecules functionally related to the gene product. In most cases, this is a metabolite in the same (typically biosynthetic) pathway as an enzyme (or transporter) encoded by the gene that is controlled. The structures of many riboswitches have been determined and this provides a large database of RNA structure and ligand binding. In this review, we extract general principles of RNA structure and the manner or ligand binding from this resource.

This research builds on the work of D.K. Gode and Shyam Sunder who demonstrated the existence of a strong relationship between market institutions and the ability of markets to seek equilibrium—even when the agents themselves have limited intelligence and behave with substantial randomness. The question posed is whether or not market institutions account for the operation of the law of supply and demand in markets populated by humans with no role required of human rationality. Are institutions responsible for the operations of the law of supply and demand or are behavioral principles also at work? Experiments with humans and simulations with robots both conducted in conditions in which major institutional and structural aids to convergence were removed, produced clear answers. Human markets converge, while robot markets do not. The structural and institutional features certainly facilitate convergence under conditions of substantial irrationality, but they are not necessary for convergence in markets in which agents have the rationality of humans.

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.

In recent years, the rapid convergence of artificial intelligence (AI) and low-altitude flight technology has driven significant transformations across various industries. These advancements have showcased immense potential in areas such as logistics distribution, urban air mobility (UAM) and national defense. By adopting the AI technology, low-altitude flight technology can achieve high levels of automation and operate in coordinated swarms, thereby enhancing efficiency and precision. However, as these technologies become more pervasive, they also raise pressing ethical or moral concerns, particularly regarding privacy, public safety, as well as the risks of militarisation and weaponisation. These issues have sparked extensive debates. In summary, while the integration of AI and low-altitude flight presents revolutionary opportunities, it also introduces complex ethical challenges. This article will explore these opportunities and challenges in depth, focusing on areas such as privacy protection, public safety, military applications and legal regulation, and will propose strategies to ensure that technological advancements remain aligned with ethical or moral principles.

Echocardiographic Z-score models play a crucial role in defining cardiac pathology in paediatric patients. There are multiple models that practitioners utilize in the United States without guiding principles to standardize their use. Discrepant interpretations can occur depending on the model chosen, even if standardized Z-score cutoffs are applied. In this study, a survey was developed to assess pediatric cardiologists’ use of Z-score systems when evaluating and treating patients with isolated bicuspid aortic valve. The majority of respondents reported using Z-score cutoffs to evaluate the degree of aortic root and ascending aorta dilation. For the aortic root, mild, moderate, and severe dilation averaged at 2.13 (SD = 0.32), 3.59 (SD = 0.49), and 5.11 (SD = 0.84), respectively. Similar cutoffs were reported for determining ascending aorta dilation. A large proportion of respondents primarily used the Boston system (36%, 18/50) or Boston and Pediatric Heart Network systems together (36%, 18/50). There were also differences in management decisions, such as implementing competitive sports restrictions, based on Z-scores and the 2015 Task Force 7 Bethesda exercise guidelines. These survey results demonstrate variability that exists among paediatric cardiologists in their use of Z-scores for describing aortic root and ascending aorta dilation in patients with isolated bicuspid aortic valve and suggests the need for implementation of national guidelines for Z-score usage.

Metabolic enzymes are the catalysts that drive the biochemical reactions essential for sustaining life. Many of these enzymes are tightly regulated by feedback mechanisms. To fully understand their roles and modulation, it is crucial to investigate the relationship between their structure, catalytic mechanism, and function. In this perspective, by using three examples from our studies on Mycobacterium tuberculosis (Mtb) isocitrate lyase and related proteins, we highlight how an integrated approach combining structural, activity, and biophysical data provides insights into their biological functions. These examples underscore the importance of employing fast-fail experiments at the early stages of a research project, emphasise the value of complementary techniques in validating findings, and demonstrate how in vitro data combined with chemical, biochemical, and physiological knowledge can lead to a broader understanding of metabolic adaptations in pathogenic bacteria. Finally, we address the unexplored questions in Mtb metabolism and discuss how we expand our approach to include microbiological and bioanalytical techniques to further our understanding. Such an integrated and interdisciplinary strategy has the potential to uncover novel regulatory mechanisms and identify new therapeutic opportunities for the eradication of tuberculosis. The approach can also be broadly applied to investigate other biochemical networks and complex biological systems.

Transit-time damping (TTD) is a process in which the magnetic mirror force – induced by the parallel gradient of magnetic field strength – interacts with resonant plasma particles in a time-varying magnetic field, leading to the collisionless damping of electromagnetic waves and the resulting energization of those particles through the perpendicular component of the electric field, $E_\perp$. In this study, we utilize the recently developed field–particle correlation technique to analyse gyrokinetic simulation data. This method enables the identification of the velocity-space structure of the TTD energy transfer rate between waves and particles during the damping of plasma turbulence. Our analysis reveals a unique bipolar pattern of energy transfer in the velocity-space characteristic of TTD. By identifying this pattern, we provide clear evidence of TTD's significant role in the damping of strong plasma turbulence. Additionally, we compare the TTD signature with that of Landau damping (LD). Although they both produce a bipolar pattern of phase-space energy density loss and gain about the parallel resonant velocity of the Alfvénic waves, they are mediated by different forces and exhibit different behaviours as the perpendicular velocity $v_\perp \to 0$. We also explore how the dominant damping mechanism varies with ion plasma beta $\beta _i$, showing that TTD dominates over LD for $\beta _i > 1$. This work deepens our understanding of the role of TTD in the damping of weakly collisional plasma turbulence and paves the way to seek the signature of TTD using in situ spacecraft observations of turbulence in space plasmas.

We introduce a low-order dynamical system to describe thermal convection in an annular domain. The model derives systematically from a Fourier–Laurent truncation of the governing Navier–Stokes Boussinesq equations and accounts for spatial dependence of the flow and temperature fields. Comparison with fully resolved direct numerical simulations (DNS) shows that the model captures parameter bifurcations and reversals of the large-scale circulation (LSC), including states of (i) steady circulating flow, (ii) chaotic LSC reversals and (iii) periodic LSC reversals. Casting the system in terms of the fluid's angular momentum and centre of mass (CoM) reveals equivalence to a damped pendulum with forcing that raises the CoM above the fulcrum. This formulation offers a transparent mechanism for LSC reversals, namely the inertial overshoot of a forced pendulum, and it yields an explicit formula for the frequency $f^*$ of regular LSC reversals in the high-Rayleigh-number (Ra) limit. This formula is shown to be in excellent agreement with DNS and produces the scaling law $f^* \sim {Ra}^{0.5}$.

Marine litter poses a complex challenge in Indonesia, necessitating a well-informed and coordinated strategy for effective mitigation. This study investigates the seasonality of plastic concentrations around Sulawesi Island in central Indonesia during monsoon-driven wet and dry seasons. By using open data and methodologies including the HYCOM and Parcels models, we simulated the dispersal of plastic waste over 3 months during both the southwest and northeast monsoons. Our research extended beyond data analysis, as we actively engaged with local communities, researchers and policymakers through a range of outreach initiatives, including the development of a web application to visualize model results. Our findings underscore the substantial influence of monsoon-driven currents on surface plastic concentrations, highlighting the seasonal variation in the risk to different regional seas. This study adds to the evidence provided by coarser resolution regional ocean modelling studies, emphasizing that seasonality is a key driver of plastic pollution within the Indonesian archipelago. Inclusive international collaboration and a community-oriented approach were integral to our project, and we recommend that future initiatives similarly engage researchers, local communities and decision-makers in marine litter modelling results. This study aims to support the application of model results in solutions to the marine litter problem.

Ultrafast optical probing is a widely used method of underdense plasma diagnostic. In relativistic plasma, the motion blur limits spatial resolution in the direction of motion. For many high-power lasers the initial pulse duration of 30–50 fs results in a 10–15 μm motion blur, which can be reduced by probe pulse post-compression. Here we used the compression after compressor approach [Phys.-Usp. 62, 1096 (2019); JINST 17 P07035 (2022)], where spectral broadening is performed in thin optical plates and is followed by reflections from negative-dispersion mirrors. Our initially low-intensity probe beam was down-collimated for a more efficient spectral broadening and higher probe-to-self-emission intensity ratio. The setup is compact, fits in a vacuum chamber and can be implemented within a short experimental time slot. We proved that the compressed pulse retained the high quality necessary for plasma probing.

We find that division managers who are connected to the CEO are substantially less likely than others to depart from the firm and are more likely to be promoted. Connected managers are protected when performance is poor, and they display no special ability to improve performance given this protection. Connections matter more in weak governance/incentive environments, and the external labor market and stock market appear skeptical of connected managers’ talents. While much of the evidence suggests inefficient favoritism, connected managers are protected more in peripheral segments, suggesting a possible efficiency benefit in helping to resolve intrafirm information problems.