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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.
Children born very preterm (VPT; ≤32 weeks’ gestation) are at higher risk of developing behavioural problems, encompassing socio-emotional processing and attention, compared to term-born children. This study aimed to examine multi-dimensional predictors of late childhood behavioural and psychiatric outcomes in very preterm children, using longitudinal clinical, environmental, and cognitive measures.
Methods
Participants were 153 VPT children previously enrolled in the Evaluation of Preterm Imaging study who underwent neuropsychological assessments at 18–24 months, 4–7 years and 8–11 years as part of the Brain Immunity and Psychopathology following very Preterm birth (BIPP) study. Predictors of late childhood behavioural and psychiatric outcomes were investigated, including clinical, environmental, cognitive, and behavioural measures in toddlerhood and early childhood. Parallel analysis and exploratory factor analysis were conducted to define outcome variables. A prediction model using elastic-net regularisation and repeated nested cross-validation was applied to evaluate the predictive strength of these variables.
Results
Factor analysis revealed two key outcome factors in late childhood: externalising and internalising-socio-emotional problems. The strongest predictors of externalising problems were response inhibition, effortful control and internalising symptoms in early childhood (cross-validated R2=.256). The strongest predictors of internalising problems were autism traits and poor cognitive flexibility in early childhood (cross-validated R2=.123). Cross-validation demonstrated robust prediction models, with higher accuracy for externalising symptoms.
Conclusions
Early childhood cognitive and behavioural outcomes predicted late childhood behavioural and psychiatric outcomes in very preterm children. These findings underscore the importance of early interventions targeting cognitive development and behavioural regulation to mitigate long-term psychiatric risks in very preterm children.
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.
A previously developed modelling procedure for large eddy simulations (LESs) is extended to allow physical space implementations for inhomogeneous flows. The method is inspired by the well-established theoretical analyses and numerical investigations of homogeneous isotropic turbulence. A general procedure that focuses on recovering the full subgrid scale (SGS) dissipation from resolved fields is formulated, combining the advantages of both the structural and the functional strategy of SGS modelling. The interscale energy transfer is obtained from the test-filtered velocity field, corresponding to the subfilter scale (SFS) stress, or, equivalently, the similarity model is used to compute the total SGS dissipation. The energy transfer is then cast in the form of eddy viscosity, allowing the method to retain the desired total SGS dissipation in low resolution LES runs. The procedure also exhibits backscatter without causing numerical instabilities. The new approach is general and self-contained, working well for different filtering kernels, Reynolds numbers and grid resolutions.
This study examines the prospective associations of alcohol and drug misuse with suicidal behaviors among service members who have left active duty. We also evaluate potential moderating effects of other risk factors and whether substance misuse signals increased risk of transitioning from thinking about to attempting suicide.
Method
US Army veterans and deactivated reservists (N = 6,811) completed surveys in 2016–2018 (T1) and 2018–2019 (T2). Weights-adjusted logistic regression was used to estimate the associations of binge drinking, smoking/vaping, cannabis use, prescription drug abuse, illicit drug use, alcohol use disorder (AUD), and drug use disorder (DUD) at T1 with suicide ideation, plan, and attempt at T2. Interaction models tested for moderation of these associations by sex, depression, and recency of separation/deactivation. Suicide attempt models were also fit in the subgroup with ideation at T1 (n = 1,527).
Results
In models controlling for socio-demographic characteristics and prior suicidality, binge drinking, cannabis use, prescription drug abuse, illicit drug use, and AUD were associated with subsequent suicidal ideation (AORs = 1.42–2.60, ps < .01). Binge drinking, AUD, and DUD were associated with subsequent suicide plan (AORs = 1.23–1.95, ps < .05). None of the substance use variables had a main effect on suicide attempt; however, interaction models suggested certain types of drug use predicted attempts among those without depression. Additionally, the effects of smoking/vaping and AUD differed by sex. Substance misuse did not predict the transition from ideation to attempt.
Conclusions
Alcohol and drug misuse are associated with subsequent suicidal behaviors in this population. Awareness of differences across sex and depression status may inform suicide risk assessment.
A major subglacial lake, Lake Snow Eagle (LSE), was identified in East Antarctica by airborne geophysical surveys. LSE, contained within a subglacial canyon, likely hosts a valuable sediment record of the geological and glaciological changes of interior East Antarctica. Understanding past lake activity is crucial for interpreting this record. Here, we present the englacial radiostratigraphy in the LSE area mapped by airborne ice-penetrating radar, which reveals a localized high-amplitude variation in ice unit thickness that is estimated to be ∼12 ka old. Using an ice-flow model that simulates englacial stratigraphy, we investigate the origin of this feature and its relationship to changes in ice dynamical boundary conditions. Our results reveal that local snowfall redistribution initiated around the early Holocene is likely the primary cause, resulting from a short-wavelength (∼10 km) high-amplitude (∼20 m) ice surface slope variation caused by basal lubrication over a large subglacial lake. This finding indicates an increase in LSE water volume during the Holocene, illustrating the sensitivity in volume of a major topographically constrained subglacial lake across a single glacial cycle. This study demonstrates how englacial stratigraphy can provide valuable insight into subglacial hydrological changes before modern satellite observations, both for LSE and potentially at other locations.
Interlaminar delamination damage is a common and typical defect in the context of structural damage in carbon fiber-reinforced resin matrix composites. The technology to identify such damage is crucial for improving the safety and reliability of structures. In this paper, we fabricated carbon fiber-reinforced composite laminates with different degrees of delamination damage, conducted static load experiments on them and used femtosecond fiber Bragg grating sensors (fsFBG) to determine their structural state to investigate the effects of delamination damage on their performance. We constructed a model to identify damage based on the deep residual shrinkage network, and used experimental data to enable it to identify varying degrees of delamination damage to carbon fiber-reinforced composites with an accuracy of 97.98%.
Leader exemplification involves implicit and explicit claims of high moral values made by a leader. We employed a 2 × 3 experimental design with samples of 265 students in Study 1 and 142 working adults in Study 2 to examine the effects of leader exemplification (exemplification versus no exemplification) and ethical conduct (self-serving, self-sacrificial, and self-other focus) on perceived leader authenticity, trust in leader, and organizational advocacy. In Study 1, we found that exemplification produced elevated levels of perceived authenticity, trust, and advocacy in the form of employment and investment recommendations. We also showed that leader ethical conduct moderated this effect, as ratings were highest following a leader’s self-sacrificial conduct, lowest for self-serving conduct, and moderate for conduct reflecting self-other concerns. In Study 2, we replicated these findings for perceived authenticity and trust, but not organizational advocacy, which yielded mixed results. The leadership implications and future research directions are discussed.
We report on the pore size distribution and water retention of Beacon sandstone from Antarctica that harbours a cryptoendolithic community, predominantly lichens, just below the surface. We measured the pore size distribution, drying time and equilibrium relative humidity of sandstone samples that were colonized by lichens. The incremental pore volume distribution peaks at ~10 μm radius, but ~20% of the pore volume occurs for a radius < 0.02 μm. Water from snowmelt fills ~20% of the total pore volume. It takes ~4–5 days of evaporation to lose 90% of the water. As the rock loses water, the equilibrium relative humidity remains at 99% until an appreciable amount (80–90%) of the pore water is lost, after which the equilibrium relative humidity starts to decrease. The relative humidity remains at > 80% (68 h) long after the water content falls to < 98% (19 h) - the point at which liquid water is estimated no longer to be present. Lichens can remain active in air with high relative humidity (> 80%). Thus, the pore size distribution of the sandstone may play a role in explaining why lichens dominate these sandstones.
A stream of free-falling particles from a rectangular hopper, hereafter called a ‘curtain’, was characterised systematically using a well-resolved, non-intrusive optical shadowgraphic method, to reveal both an additional axial region and an additional dilute region distributed laterally on either side of the curtain, relative to those identified previously. The effects of particle size and hopper outlet thickness on the evolution of the particle curtain were separately isolated, whilst measuring particle mass flow rate. The curtains were characterised into four distinct axial regions, namely a near-field expansion region near to the hopper exit, a neck zone where the curtain contracts, a region of intermediate-field expansion and a far field with particles reaching terminal velocity. The initial expansion half-angle, $2.3^{\circ } \le \alpha \le 4.8^{\circ }$, was found to be insensitive to particle size, but to increase with hopper outlet thickness. The ‘trough’ in the neck zone was deduced to be caused by a pressure gradient driven by particle acceleration. The curtain expansion rate at the intermediate field was found to increase with a decrease in particle size and hopper outlet thickness. The outermost dilute-particle region was deduced to be caused by collisions, induced by gradients in the velocity profile near to the hopper exit. New dimensionless analysis reveals that the dynamics of curtains can be characterised broadly into two regimes, one in which the aerodynamics is dominant and the other where it is weak. Curtain transmittance was found to scale with the Froude number, highlighting the importance of particle momentum.
Ridge B is one of the least studied areas in Antarctica but has been considered to be a potential location for the oldest ice on Earth. Among important parameters for calculating where very old ice may exist, geothermal heat flux (GHF) is critical but poorly understood. Here, GHF is determined by quantifying the transitions between dry and wet basal conditions using a radioglaciological method applied to airborne radio-echo sounding data. GHF is then constrained by a thermodynamic model matched to the transitions. The results show that GHF in Ridge B varies locally and ranges from 48.5 to 65.1 mW m−2, with an average value of 58.0 mW m−2, which is consistent with the current known GHF constrained by subglacial lakes and derived from Vostok ice core temperature measurements. Our work highlights the value of considering local GHF when locating the oldest ice in this potential region or other regions.
Ice rises hold valuable records revealing the ice dynamics and climatic history of Antarctic coastal areas from the Last Glacial Maximum to today. This history is often reconstructed from isochrone radar stratigraphy and simulations focusing on Raymond arch evolution beneath the divides. However, this relies on complex ice-flow models where many parameters are unconstrained by observations. Our study explores quad-polarimetric, phase-coherent radar data to enhance understanding near ice divides and domes, using Hammarryggen Ice Rise (HIR) as a case study. Analysing a 5 km profile intersecting the dome, we derive vertical strain rates and ice-fabric properties. These align with ice core data near the summit, increasing confidence in tracing signatures from the dome to the flanks. The Raymond effect is evident, correlating with surface strain rates and radar stratigraphy. Stability is inferred over millennia for the saddle connecting HIR to the mainland, but dome ice-fabric appears relatively young compared to 2D model predictions. In a broader context, quad-polarimetric measurements provide valuable insights into ice-flow models, particularly for anisotropic rheology. Including quad-polarimetric data advances our ability to reconstruct past ice flow dynamics and climatic history in ice rises.
Leveraging the National COVID-19 Cohort Collaborative (N3C), a nationally sampled electronic health records repository, we explored associations between individual-level social determinants of health (SDoH) and COVID-19-related hospitalizations among racialized minority people with human immunodeficiency virus (HIV) (PWH), who have been historically adversely affected by SDoH.
Methods:
We retrospectively studied PWH and people without HIV (PWoH) using N3C data from January 2020 to November 2023. We evaluated SDoH variables across three domains in the Healthy People 2030 framework: (1) healthcare access, (2) economic stability, and (3) social cohesion with our primary outcome, COVID-19-related hospitalization. We conducted hierarchically nested additive and adjusted mixed-effects logistic regression models, stratifying by HIV status and race/ethnicity groups, accounting for age, sex, comorbidities, and data partners.
Results:
Our analytic sample included 280,441 individuals from 24 data partner sites, where 3,291 (1.17%) were PWH, with racialized minority PWH having higher proportions of adverse SDoH exposures than racialized minority PWoH. COVID-19-related hospitalizations occurred in 11.23% of all individuals (9.17% among PWH, 11.26% among PWoH). In our initial additive modeling, we observed that all three SDoH domains were significantly associated with hospitalizations, even with progressive adjustments (adjusted odds ratios [aOR] range 1.36–1.97). Subsequently, our HIV-stratified analyses indicated economic instability was associated with hospitalization in both PWH and PWoH (aOR range 1.35–1.48). Lastly, our fully adjusted, race/ethnicity-stratified analysis, indicated access to healthcare issues was associated with hospitalization across various racialized groups (aOR range 1.36–2.00).
Conclusion:
Our study underscores the importance of assessing individual-level SDoH variables to unravel the complex interplay of these factors for racialized minority groups.
With the in-depth study of thin-film structures, nonuniform thin films with rigid elements have been applied in the aerospace and flexible electronics industries. For thin-film structures with rigid elements, there is an interaction force between the rigid element and the thin film; therefore, the wrinkling mode of the thin film changes under the influence of the interaction force. In this study, a wrinkle model was developed to predict the wrinkle morphology of thin-film structures with rigid elements on the diagonal. First, the wrinkle patterns of the rigid elements were observed at different positions using tensile experiments. Then, the relationship between the tilt of the rigid element and the wrinkle wavelength was investigated using a finite-element eigenvalue buckling analysis. Finally, local wrinkling caused by the perturbed stress of the rigid element was introduced, and a wrinkling model of a square thin film with rigid elements on the diagonal under tension was established. The theoretical analysis results were compared with simulation and experimental results, demonstrating that the model can accurately describe the wrinkle patterns of thin-film structures containing rigid elements on the diagonal under tension.
This contribution focuses on the abatement with hydrogen of CO2 and non-CO2 emissions. It is agenda-setting in two respects. Firstly, it challenges the globally accepted hydrocarbon sustainable aviation fuel (SAF) pathway to sustainability and recommends that our industry accelerates along the hydrogen pathway to ‘green’ aviation. Secondly, it reports a philosophical and analytical investigation of appropriate accuracy on abatement strategies for nitrogen oxides and contrails of large hydrogen airliners. For the second contribution, a comparison is made of nitrogen oxide emissions and contrail avoidance options of two hydrogen airliners and a conventional airliner of similar passenger capacity. The hydrogen aircraft are representative of the first and second innovation waves where the main difference is the weight of the hydrogen tanks. Flights of 1000, 2000, 4000 and 8000 nautical miles are explored. Cranfield’s state of the art simulators for propulsion system integration and gas turbine performance (Orion and Turbomatch) were used for this. There are two primary contributions to knowledge. The first is a new set of questions to be asked of SAF and hydrogen decarbonising features. The second is the quantification of the benefits from hydrogen on non-CO2 emissions. For the second generation of long-range hydrogen-fuelled aircraft having gas turbine propulsion, lighter tanks (needing less thrust and lower gas temperatures) are anticipated to reduce NOx emissions by over 20%; in the case of contrails, the preliminary findings indicate that regardless of the fuel, contrails could largely be avoided with fuel-burn penalties of a few per cent. Mitigating action is only needed for a small fraction of flights. For conventional aircraft this penalty results in more CO2, while for hydrogen aircraft the additional emission is water vapour. The conclusion is that our research community should continue to consider hydrogen as the key ‘greening’ option for aviation, notwithstanding the very significant costs of transition.
A commercial bentonite (primarily smectite) from Fischer Scientific Company (F bentonite) and a natural bentonite from Peru (P bentonite) were used in the preparation of pillared clays with polyoxymetal cations of Al that were subsequently modified with Ce and La. Several Al/metal ratios (5 and 9) were used to investigate the effects on the thermal and hydrothermal stability of these synthetic clays. The structure of these materials was studied by X-ray diffraction. Isotherms were determined by N2 adsorption. Thermal stability was determined using thermogravimetric (TG) measurements and ara-monia-TPD (temperature programmed desorption) was used to obtain acidity data. These materials exhibited basal spacings from 16 to 20 Å, with surface areas from 239 to 347 m2g−1, with microporosity contributing from 50 to 80% of the total surface area. Pillared clays prepared from F bentonite generally showed larger basal spacings and surface areas than those prepared from P bentonite. Pillared clays modified with Ce or La did not show any apparent structural changes relative to the Al-pillared clays. Pillared clays modified with Ce and La had similar acid properties as Al-pillared clays. In contrast, the thermal and hydrothermal stabilities of these materials were greater than Al-pillared clays. However, Ce-pillared clay appears to be more effective than La-pillared clay in delaying the dehydroxylation of pillared clays with increasing temperature. The intercalation of Ce and La into Al-pillared clays improved the thermal stability, which may increase the utility of these materials as catalysts.
Bentonite- and sepiolite-supported copper catalysts have been prepared either by adsorption of Cu(II) from aqueous solutions of copper nitrate at pH ~4.5 or by adsorption of a [Cu(NH3)4]2+ complex from an ammonia solution of CuSO4 at pH ~9.5. The structure and composition of the calcined preparations have been studied by X-ray diffraction, chemical analysis, and energy dispersive X-rays. Textural characteristics have derived from the analysis of the adsorption-desorption isotherms of N2. All catalysts have been tested for the dehydrogenation of methanol to methyl formate. For this reaction, bentonite-based catalysts were found to have very little activity, which indicates that copper located in the inter-lamellar spaces is inaccessible to methanol molecules. On the contrary, copper-sepiolite catalysts showed a very high specific activity even for those catalysts with a very low copper content. The chemical state of copper in the catalysts on-stream has been revealed by X-ray photoelectron spectroscopy and X-ray-induced Auger techniques. In most of the catalysts Cu+ is the dominant copper species.
Ultra-processed plant-based foods, such as plant-based burgers, have gained in popularity. Particularly in the out-of-home (OOH) environment, evidence regarding their nutritional profile and environmental sustainability is still evolving. Plant-based burgers available at selected OOH sites were randomly sampled in Amsterdam, Copenhagen, Lisbon and London. Plant-based burgers (patty, bread and condiment) (n 41) were lab analysed for their energy, macronutrients, amino acids and minerals content per 100 g and serving and were compared with reference values. For the plant-based burgers, the median values per 100 g were 234 kcal, 20·8 g carbohydrates, 3·5 g dietary fibre and 12·0 g fat, including 0·08 g TFS and 2·2 g SFA. Protein content was 8·9 g/100 g, with low protein quality according to amino acid composition. Median Na content was 389 mg/100 g, equivalent to 1 g salt. Compared with references, the median serving provided 31% of energy intake based on a 2000 kcal per day and contributed to carbohydrates (17–28%), dietary fibre (42%), protein (40%), total fat (48%), SFA (26%) and Na (54%). One serving provided 15–23% of the reference values for Ca, K and Mg, while higher contributions were found for Zn, Mn, P and Fe (30–67%). The ultra-processed plant-based burgers provide protein, dietary fibre and essential minerals and contain relatively high levels of energy, Na and total fats. The amino acid composition indicated low protein quality. The multifaceted nutritional profile of plant-based burgers highlights the need for manufacturers to implement improvements to better support healthy dietary habits, including reducing energy, Na and total fats.
As nurse practitioners and physician assistants (APPs) become more prevalent in delivering pediatric care, their involvement in antimicrobial stewardship efforts increases in importance. This project aimed to create and assess the efficacy of a problem-based learning (PBL) approach to teaching APPs antimicrobial stewardship principles.
Methods:
A PBL education initiative was developed after communication with local APP leadership and focus group feedback. It was offered to all APPs associated with Lurie Children’s Hospital of Chicago. Participants completed a survey which assessed opinions on antimicrobial stewardship and included knowledge-based questions focused on antimicrobial stewardship. Prescriptions for skin and soft tissue infections associated with APPs were recorded via chart review before and after the education campaign.
Results:
Eighty APPs participated in the initial survey and teaching initiative with 44 filling out the 2-week follow-up and 29 filling out the 6-month follow-up. Subjective opinions of antimicrobial stewardship and comfort with basic principles of AS increased from pre-intervention. Correct responses to knowledge-based assessments increased from baseline after 2-week follow-up (p < 0.01) and were maintained at the 6-month follow-up (p = 0.03). Simple skin and soft tissue infection prescriptions for clindamycin went from 44.4% pre-intervention to 26.5% (p = 0.2) post-intervention.
Conclusions:
A PBL approach for APP education on antimicrobial stewardship can be effective in increasing knowledge and comfort with principles of antimicrobial stewardship. These changes are maintained in long-term follow-up. Changes in prescribing habits showed a strong trend towards recommended empiric therapy choice. Institutions should develop similar education campaigns for APPs.