Background: Late-onset Pompe disease (LOPD) is caused by a deficiency of acid α-glucosidase (GAA), leading to progressive muscle and respiratory decline. Cipaglucosidase alfa (cipa), a recombinant human GAA naturally enriched with bis-mannose-6-phosphate, exhibits improved muscle uptake but is limited by inactivation at near-neutral blood pH. Miglustat (mig), an enzyme stabiliser, binds competitively and reversibly to cipa, enhancing its stability and activity. Methods: In dose-finding studies, Gaa-/- mice were treated with cipa (20 mg/kg) +/- mig (10 mg/kg; equivalent human dose ~260 mg). Clinical study methodologies have been published (Schoser et al. Lancet Neurol 2021:20;1027–37; Schoser et al. J Neurol 2024:271;2810–23). Results: In Gaa-/- mice, cipa+mig improved muscle glycogen reduction more than cipa alone and grip strength to levels approaching wild-type mice. LOPD patients (n=11) treated with cipa alone showed dose-dependent decreases in hexose tetrasaccharide (Hex4) levels by ~15% from baseline, decreasing another ~10% with added mig (260 mg). In a head-to-head study, cipa+mig had a similar safety profile to alglucosidase alfa. Among 151 patients (three trials), mig-related adverse events occurred in 21 (13.9%), none serious. Conclusions: Mig stabilised cipa in circulation, improving cipa exposure, further reducing Hex4 levels and was well tolerated in clinical studies in patients with LOPD. Sponsored by Amicus Therapeutics, Inc.

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.

Plugging of a hydraulic fracture because of particle bridging in the fracture channel is ubiquitous in drilling operations and reservoir stimulations. The particles transported in the fluid and fracture can aggregate under certain conditions and finally form a plug. The plug reduces the permeability of the flow channel and blocks the fluid pressure from reaching the fracture front, leading to fracture arrest. In this paper, a numerical model is developed to describe the plugging process of a hydraulic fracture driven by a slurry of solid particles in a viscous fluid while accounting for the rock deformation, slurry flow in the fracture channel, fracture propagation, particle transport and bridging. Three dimensionless numbers are derived from the governing equations, which reveal two length scales that control the fracture propagation and particle transport behaviour, respectively. The difference in magnitude between the two length scales implies three limiting regimes for fracture propagation, i.e. static regime, fluid-driven regime and slurry-driven regime, which correspond to fracture arrest, fracture driven by clean fluid, and fracture driven by slurry, respectively. Numerical results show that the fracture will sequentially transition through the static regime, fluid-driven regime and slurry-driven regime as the fracture length increases. The transition between regimes is controlled by the ratio between the two length scales. Simulation results also reveal two plugging modes, with the plug located near the fracture tip region and at the fracture inlet. The transition between the two plugging modes is controlled by the ratio of the length scales and the injected particle concentration.

Objectives/Goals: Aspiration causes or aggravates lung diseases. While bedside swallow evaluations are not sensitive/specific, gold standard tests for aspiration are invasive, uncomfortable, expose patients to radiation, and are resource intensive. We propose the development and validation of an AI model that analyzes voice to noninvasively predict aspiration. Methods/Study Population: Retrospectively recorded [i] phonations from 163 unique ENT patients were analyzed for acoustic features including jitter, shimmer, harmonic to noise ratio (HNR), etc. Patients were classified into three groups: aspirators (Penetration-Aspiration Scale, PAS 6–8), probable (PAS 3–5), and non-aspirators (PAS 1–2) based on video fluoroscopic swallow (VFSS) findings. Multivariate analysis evaluated patient demographics, history of head and neck surgery, radiation, neurological illness, obstructive sleep apnea, esophageal disease, body mass index, and vocal cord dysfunction. Supervised machine learning using five folds cross-validated neural additive network modelling (NAM) was performed on the phonations of aspirator versus non-aspirators. The model was then validated using an independent, external database. Results/Anticipated Results: Aspirators were found to have quantifiably worse quality of sound with higher jitter and shimmer but lower harmonics noise ratio. NAM modeling classified aspirators and non-aspirators as distinct groups (aspirator NAM risk score 0.528+0.2478 (mean + std) vs. non-aspirator (control) risk score of 0.252+0.241 (mean + std); p Discussion/Significance of Impact: We report the use of voice as a novel, noninvasive biomarker to detect aspiration risk using machine learning techniques. This tool has the potential to be used for the safe and early detection of aspiration in a variety of clinical settings including intensive care units, wards, outpatient clinics, and remote monitoring.

State-owned enterprises (SOEs) in China play a critical role in national economic development and the country's positioning on the global stage. Chinese SOEs have undergone substantial transformations from traditional government-run entities to a variety of corporate forms exhibiting different levels of state involvement. Despite their substantial influence, the internal diversity of SOEs – from wholly state-owned to mixed-ownership – has not been thoroughly examined. This paper provides an overview of SOEs' critical roles in the Chinese economy, the relationship between SOEs and privately owned enterprises (POEs), and the challenges of SOEs in different stages of Chinese economic development. It then introduces five research papers that explore the institutional, strategic, and organizational perspectives on how SOEs manage the dual pressures of state and market logic, respond to policy adjustments, tackle leadership challenges, and navigate current global trends such as digital transformation, technological innovation, and environmental sustainability. In this paper, we provide important implications for policy and managerial practices and highlight a future research agenda for the heterogeneity of Chinese SOEs, and how SOEs respond to these challenges in the evolving geopolitical landscape, adapt their strategies, and manage relationships with foreign governments and enterprises under such conditions.

Neurocysticercosis is a poorly understood infection of the central nervous system with Taenia solium larva, and the treatment often fails to kill all the parasitic larva. Most research on this infection has used patient-level data, looking at summaries of the encysted parasitic cysticercus burden. Cyst-level analysis is needed to identify factors that impact individual cyst trajectories and how that may vary based on characteristics of the patient, infection and cyst being followed. We disaggregated data on 221 cysts from 117 patients who participated in a trial evaluating the impact of albendazole treatment to identify factors that impact cyst evolution over time from the active to the degenerating and calcified phases, and eventual resolution. We found that having calcified cysts at baseline was associated with a faster rate of transition from the degenerative phase to calcified phase or resolution. Age and sex were not associated with cyst evolution in the main effect analysis, but after stratifying on treatment we found that the direction of some associations by patient age and sex was reversed for patients in the albendazole arm compared to those in the placebo arm. These findings suggest that differences in host immune response by sex and age as well as by past exposure, potentially indicated by having calcified cysts together with active cysts at baseline, are important to cyst evolution and may be modified by treatment. Future research is needed to assess if these differences suggest distinct treatment recommendations.

This study addresses a significant knowledge gap in the literature by examining the relationship between religious involvement and subjective wellbeing (SWB) among older adults in Taiwan, a cultural context that has been underrepresented in existing research, with a focus on gender and age differences. Using data collected in Taichung City in 2017 (N = 645), this study measured religious involvement through religious affiliation, religiosity and frequency of religious participation, and assessed SWB via life satisfaction and happiness. Findings revealed no significant association between religious involvement and life satisfaction. However, religious participation was positively correlated with happiness. Gender differences were observed: Buddhism and Taoism were positively associated with life satisfaction among males, whereas religiosity and religious participation were significantly related to life satisfaction and happiness among females. Age disparities were also found, with religiosity significantly relating to both life satisfaction and happiness in the old-old group (70–89 years) but not in the young-old group (60–69 years). These findings highlight the nuanced associations between religious involvement and SWB, emphasising the importance of considering gender and age variations in future research. Future studies should further explore the cultural contexts that shape these relationships and examine other potential mediating factors to provide a more comprehensive understanding of how religious involvement influences wellbeing across different demographic groups.

The robots of tomorrow should be endowed with the ability to adapt to drastic and unpredicted changes in their environment and interactions with humans. Such adaptations, however, cannot be boundless: the robot must stay trustworthy. So, the adaptations should not be just a recovery into a degraded functionality. Instead, they must be true adaptations: the robot must change its behaviour while maintaining or even increasing its expected performance and staying at least as safe and robust as before. The RoboSAPIENS project will focus on autonomous robotic software adaptations and will lay the foundations for ensuring that they are carried out in an intrinsically trustworthy, safe and efficient manner, thereby reconciling open-ended self-adaptation with safety by design. RoboSAPIENS will transform these foundations into ‘first time right’-design tools and platforms and will validate and demonstrate them.

The reactivity of basal surfaces, steps and edges of muscovite was studied by imaging surface precipitates of PbCl2 using atomic force microscopy (AFM). We reacted PbCl2 solution with freshly cleaved muscovite surfaces and found that PbCl2 precipitates were formed on the basal surfaces, steps and edges. It was observed that PbCl2 precipitated preferentially along the steps compared to the basal surfaces and that PbCl2 precipitates at multiple-layer edges were needle-shaped and oriented in different directions. One of the muscovite samples we cleaved had muscovite fragments sitting on the freshly cleaved surfaces. These fragments resulted from previously formed cracks. Thus, we were able to compare the reactivity of the weathered surfaces with that of freshly cleaved surfaces. It was found that PbCl2 was not precipitated along the edges of previously cracked muscovite fragments. These results clearly demonstrated that the edges of freshly cleaved muscovite are the most reactive surface sites, whereas the edges of weathered muscovite are not as reactive. We believe that the surface reactivity of the edges of freshly cleaved muscovite is likely due to terminal or Al-OH1/2− groups on these crystalline surfaces, which favor adsorption of Pb2+ ions and the subsequent nucleation and precipitation reactions. We also investigated the effect of drying rate on the morphology of the surface precipitates. Fast drying resulted in a nearly complete covered surface with a leaflike morphology, whereas slow drying resulted in more isolated surface clusters.

The attitude-tracking problem of hypersonic morphing vehicles (HMVs) is investigated in this research. After introducing variable-span wings, the optimal aerodynamic shape is available throughout the entire flight mission. However, the morphing wings cause significant changes in aerodynamic coefficients and mass distribution, challenging the attitude control. Therefore, a complete design procedure for the flight control system is proposed to address the issue. Firstly, the original model and the control-oriented model of HMVs are built. Secondly, in order to eliminate the influence caused by the multisource uncertainties, an adaptive fixed-time disturbance observer combined with fuzzy control theory is established. Thirdly, the fixed-time control method is developed to stabilise hypersonic morphing vehicles based on a multivariable sliding mode manifold. The control input can be obtained directly. Finally, the effectiveness of the proposed method is proved with the help of the Lyapunov theory and simulation results.

The chemistry of Al transformation has been well documented, though little is known about the mechanisms of structural perturbation of Al precipitates by carbonates at a molecular level. The purpose of the present study was to investigate the structural perturbation of Al precipitates formed under the influence of carbonates. Initial carbonate/Al molar ratios (MRs) used were 0, 0.1, and 0.5 after aging for 32 days, then the samples were analyzed by X-ray absorption near edge structure spectroscopy (XANES), X-ray diffraction (XRD), Fourier-transform infrared absorption spectroscopy (FTIR), and chemical analysis. The XRD data were in accord with the FTIR results, which revealed that as the carbonate/Al MR was increased from 0 to 0.1, carbonate preferentially retarded the formation of gibbsite and had relatively little effect on the formation of bayerite. As the carbonate/Al MR was increased to 0.5, however, the crystallization of both gibbsite and bayerite was completely inhibited. The impact of carbonate on the nature of Al precipitates was also evident in the increase of adsorbed water and inorganic C contents with increasing carbonate/Al MR. The Al K- and L- edge XANES data provide the first evidence illustrating the change in the coordination number of Al from 6-fold to mixed 6- and 4-fold coordination in the structural network of short-range ordered (SRO) Al precipitates formed under the increasing perturbation of carbonate. The fluorescence yield spectra of the O K-edge show that the intensity of the peak at 534.5 eV assigned to σ* transitions of Al-O and O-H bonding decreased with increasing carbonate/Al MR. The XANES data, along with the evidence from XRD, FTIR, and chemical analysis showed clearly that carbonate caused the alteration of the coordination nature of the Al-O bonding through perturbation of the atomic bonding and structural configuration of Al hydroxides by complexation with Al in the SRO network of Al precipitates. The surface reactivity of an Al-O bond is related to its covalency and coordination geometry. The present findings were, therefore, of fundamental significance in understanding the low-temperature geochemistry of Al and its impacts on the transformation, transport, and fate of nutrients and pollutants in the ecosystem.

The effects of apparatus-induced dispersion on nonuniform, density-dependent flow in a cylindrical soil column were investigated using a finite-element model. To validate the model, the results with an analytical solution and laboratory column test data were analysed. The model simulations confirmed that flow nonuniformities induced by the apparatus are dissipated within the column when the distance to the apparatus outlet exceeds $3R/2$, where R represents the radius of the cylindrical column. Furthermore, the simulations revealed that convergent flow in the vicinity of the outlet introduces additional hydrodynamic dispersion in the soil column apparatus. However, this effect is minimal in the region where the column height exceeds $3R/2$. Additionally, it is found that an increase in the solution density gradient during the solute breakthrough period led to a decrease in flow velocity, which stabilized the flow and ultimately reduced dispersive mixing. Overall, this study provides insights into the behaviour of apparatus-induced dispersion in nonuniform, density-dependent flow within a cylindrical soil column, shedding light on the dynamics and mitigation of flow nonuniformities and dispersive mixing phenomena.

Political divisions have become a central feature of modern life. Here, we ask whether these divisions affect advice-taking from co- and counter-partisans in a nonpolitical context. In an incentivized task assessing the accuracy of nonpolitical news headlines, we find partisan bias in advice-taking: Democratic participants are less swayed by (accurate) information that comes from Republicans compared to the same information from Democrats (Republican participants display no such bias). We then adjudicate between two possible mechanisms for this biased advice-taking: a preference-based account, where participants are motivated to take less advice from counter-partisans because doing so is unpleasant; versus a belief-based account, where participants sincerely believe co-partisans are more competent at the task (even though this belief is incorrect). To do so, we examine the impact of a substantial increase in the stakes, which should increase accuracy motivations (and thereby reduce the relative impact of partisan motivations). We find that increasing the stakes does not reduce biased advice-taking, hence no evidence to support the bias is driven by preference. Consistent with the belief-based account, we find that Democratic participants (incorrectly) believe their co-partisans are better at the task, and this incorrect belief is much less severe among Republican participants. Further supporting the notion that the stated beliefs are sincere, raising the stakes of the belief elicitation of relative partisan competence does not affect the stated beliefs. Finally, participants—instead of ignoring the feedback—actually substantially update in favor of their counter-partisans given feedback that suggests counter-partisans are competent.

A 198.8 m deep borehole was drilled through ice to subglacial bedrock in the northwestern marginal part of Princess Elizabeth Land, ~12 km south of Zhongshan Station, in January–February 2019. Three years later, in February 2022, the borehole temperature profile was measured, and the geothermal heat flow (GHF) was estimated using a 1-D time-dependent energy-balance equation. For a depth corresponding to the base of the ice sheet, the GHF was calculated as 72.6 ± 2.3 mW m−2 and temperature −4.53 ± 0.27°C. The regional averages estimated for this area based, generally, on tectonic setting vary from 55 to 66 mW m−2. A higher GHF is interpreted to originate mostly from the occurrence of metamorphic complexes intruded by heat-producing elements in the subglacial bedrock below the drill site.

The control of a wing-in-ground craft (WIG) usually allows for many needs, like cruising, speed, survival and stealth. Various degrees of emphasis on these requirements result in different trajectories, but there has not been a way of integrating and quantifying them yet. Moreover, most previous studies on other vehicles’ multi-objective trajectory is planned globally, lacking for local planning. For the multi-objective trajectory planning of WIGs, this paper proposes a multi-objective function in a polynomial form, in which each item represents an independent requirement and is adjusted by a linear or exponential weight. It uses the magnitude of weights to demonstrate how much attention is paid relatively to the corresponding demand. Trajectories of a virtual WIG model above the wave trough terrain are planned using reward shaping based on the introduced multi-objective function and deep reinforcement learning (DRL). Two conditions are considered globally and locally: a single scheme of weights is assigned to the whole environment, and two different schemes of weights are assigned to the two parts of the environment. Effectiveness of the multi-object reward function is analysed from the local and global perspectives. The reward function provides WIGs with a universal framework for adjusting the magnitude of weights, to meet different degrees of requirements on cruising, speed, stealth and survival, and helps WIGs guide an expected trajectory in engineering.