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BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18. METHODS: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ2 test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity. FINDINGS: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%-73% for 28 years until 2010-18, when it increased to 87% (95% CI 82·1-90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8-96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5-87·0] and 85·4% [71·8-92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56-3·72; p

Objective To explore the relevant relationship and specificity between the implicit and explicit loyalty of military cadets in order to provide a theoretical basis and objective indicators for a more comprehensive and objective assessment for individual loyalty. Methods E-Prime 2.0, a classic implicit association paradigm was employed to construct an implicit association loyalty test for 64 military cadets. Simultaneously, an explicit loyalty measurement was conducted using the Chinese Military Personnel Loyalty Scale. Results ① Significant implicit effect was observed in the loyalty assessment of military cadets, indicating a general tendency to perceive higher levels of personal loyalty and lower levels of loyalty to external entities. ② Explicit loyalty assessment revealed that the participants had the highest loyalty score towards the Party, the Nation, and the People (4.79±0.34), followed by the loyalty score to their profession (4.38±0.53), and the relatively lower loyalty score towards the unit and leaders (4.03±0.83). Among the 3 dimensions of loyalty, the normative loyalty score ranked highest, while continuance loyalty score took lower. ③ There were no correlations among the scores of loyalty to the Party, the Nation, and the People (r=-0.030, P=0.823), to the profession (r=-0.047, P=0.728), to the unit (r=0.050, P=0.710), or to the leaders (r=0.043, P=0.749). Conclusion The implicit effect in the loyalty assessment is significant in military cadets, and there is no significant correlation between explicit and implicit loyalty measurements. Thus, we cannot rely solely on explicit measurements to assess their loyalty attitudes.

Objective To construct a theoretical model for cognitive domain information transmission (COIT) to promote the establishment of an attack and defense system for COIT, and further to validate it by simulating data in mathematical model. Methods A hub-susceptible-infected-recovery (HSIR) model was proposed theoretically to conceptualize COIT, and then the model was validated with Runge-Kutta nonlinear integral equation for mathematical simulation. Results Standard HSIR model showed when cognitive domain information was transmitted in a large population of 10 000 people, the peak transmission was observed at Day 46 and 7 480 members were covered, with a basic reproduction number of 1.3. Further, when some measures were taken to obstruct COIT at Days 8, 4 and 2, respectively, the number of peak infects people was decreased to 5 822, 4 892 and 4 126, with a peak transmission duration shortened by 92, 62 and 41 d, in order. Conclusion Basing on HSIR model, we bring forward a dynamic model of COPT, and primarily construct a defense system of COPI combat.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management.

Addressing the demand for high stability of beamline instruments at the SHINE facility, a high stability mirror regulating mechanism has been developed for mirror adjustments. Active mass damping was adopted to attenuate pitch angle vibrations of mirrors caused by structural vibrations. An internal absolute velocity feedback was used to reduce the negative impact of spillover effects and to improve performance. The experiment was conducted on a prototype structure of a mirror regulating mechanism, and results showed that the vibration RMS of the pitch angle was effectively attenuated from 47 nrad to 27 nrad above 1 Hz. [ABSTRACT FROM AUTHOR]

The nitrogen doping (N‐doping) treatment for niobium superconducting radio‐frequency (SRF) cavities is one of the key enabling technologies that support the development of more efficient future large accelerators. However, the N‐doping results have diverged due to a complex chemical profile under the nitrogen‐doped surface. Particularly, under industrial‐scale production conditions, it is difficult to understand the underlying mechanism thus hindering performance improvement. Herein, a combination of spatially resolved and surface‐sensitive approaches is employed to establish the detailed near‐surface phase composition of thermally processed niobium. The results show that intermediate phase segregations, particularly the nanometric carbon‐rich phase, can impede the nitridation process and limit the interactions between nitrogen and the niobium sub‐surface. In comparison, the removal of the carbon‐rich layer at the Nb surface leads to enhanced nitrogen binding at the Nb surface. Combining the RF test results, it is shown that the complex uniformity and grain boundary penetrations of impurity elements have a direct correlation with the mid‐field quench behavior in the N‐doped Nb cavities. Therefore, proper control of the nanometric intermediate phase formation in discrete thermal steps is critical in improving the ultimate performance and production yield of the Nb cavities. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro–micro‐molecular perspective from in vivo neuroimaging data. Methods: The "ADHD‐200 initiative" repository provided multi‐site high‐quality resting‐state functional connectivity (rsfc‐) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient‐transcriptional signatures of AHBA enrichment and meta‐analytic decoding. Results: Compared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition‐involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5‐HT2A receptors (all pBH <0.01) and co‐varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient‐transcriptional variants indicated the risk of both cell‐specific and chromosome‐ dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05). Conclusions: Our findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5‐HT systems as well brain‐derived enrichment of specific cellular/chromosomal expressions. [ABSTRACT FROM AUTHOR]

The purpose of this work was to investigate a novel aqueous dispersion (Eudragit® L100-55) f or e nteric c oating o f drugs. Three different casting solutions, Eudragit® L100-55 aqueous dispersion, Eudragit® L 100-55 o rganic s olution, and Eudragit® L30D-55 aqueous dispersion, were used to prepare free films by the casting method. Drug-loaded pellets, prepared by the extrusion-spheronization method, were coated with one of these three coating solutions using the fluidized-bed spray coating technology. Properties of the free films were thoroughly investigated. Films formed by Eudragit® L100-55 aqueous dispersions showed similar properties to those formed by Eudragit® L100-55 organic solution regarding thermodynamic properties, moisture permeability, solubility and acid tolerance ability. Furthermore, the performance of the novel film was better than that formed by Eudragit® L30D-55 aqueous dispersion. Among the three enteric coating solutions, Eudragit® L100- 55 aqueous dispersion will be a promising aqueous dispersion for enteric coating and can be used in the development of enteric-coated preparations.

To develop a novel water-in-oil-in-water (W/O/W) adjuvant and evaluate the effect on foot-and-mouth disease (FMD) inactivated vaccine, in this study, we prepared the novel nano-emulsion adjuvant based on QS-21 (BEA) which is composed of the mixture of mineral oil Marcol52, surfactant Tween80, oleate polyoxyethylene ether ester, polyoxyethylene palmitic acid ester and span80, cosurfactant polyethylene glycol and QS-21. The two-step emulsification method formed the W/O/W nano-emulsion with two films and three-phase structures. The effective particle diameter of the BEA was about 184 nm, and it has good thermal stability. Then, BEA was emulsified as an adjuvant to prepare for the inactivated FMDV vaccine, and BALB/c mice and pigs were immunized to evaluate its safety and immunization effect. The results showed that the inactivated BEA-FMDV vaccine significantly increased BALB/c mice and pigs' antibodies and cytokine IFN-γ in serum. Meanwhile, the pig-neutralizing antibodies were higher than control group. Safety tests found no symptoms of FMD or significant toxic reactions. After 28 days of immunization, the protection rate can reach 93.3%. The BEA vaccine had good stability at 4 °C, no stratification after 180 days, and the content of 146S in the vaccine did not decrease. In conclusion, the BEA prepared in this study is suitable for FMDV inactivated vaccine and is an effective adjuvant. [ABSTRACT FROM AUTHOR]

With the rapid development of intelligent robotics, the Internet of Things, and smart sensor technologies, great enthusiasm has been devoted to developing next-generation intelligent systems for the emulation of advanced perception functions of humans. Neuromorphic devices, capable of emulating the learning, memory, analysis, and recognition functions of biological neural systems, offer solutions to intelligently process sensory information. As one of the most important neuromorphic devices, Electrolyte-gated transistors (EGTs) have shown great promise in implementing various vital neural functions and good compatibility with sensors. This review introduces the materials, operating principle, and performances of EGTs, followed by discussing the recent progress of EGTs for synapse and neuron emulation. Integrating EGTs with sensors that faithfully emulate diverse perception functions of humans such as tactile and visual perception is discussed. The challenges of EGTs for further development are given. [ABSTRACT FROM AUTHOR]