Directional Effects Research Articles

Microsphere Photonic Superlens for a Highly Emissive Flexible Upconversion-Nanoparticle-Embedded Film

Increasing upconversion luminescence (UCL) to overcome the intrinsically low conversion efficiency of upconversion nanoparticles (UCNPs) poses a fundamental challenge. Photonic nanostructures are the efficient approaches for UCL enhancement by tailoring the local electromagnetic fields. Unfortunately, such nanostructures are sensitive to environmental conditions, and the regulation strength is varied in flexible applications. Here, we report giant UCL enhancement from a flexible UCNP-embedded film coupled with a microsphere photonic superlens (MPS), by which the enhancement ratio of UCL is over 104-fold under 808 nm excitation down to 0.72 mW. The enhancement pathways of MPS-enhanced UCL are attributed to Mie-resonant nanofocusing for high excitation-photon density, optical whispering-gallery modes (WGMs) for fast radiative decay, and the directional antenna effect for far-field emission confinement. The contribution of optical resonance in the MPS to suppressing the phonon-induced nonradiative transition and thermal quenching is experimentally validated. The UCL quantum yield is therefore improved by 3-fold to 4.20% under 120 mW/cm2 near-infrared excitation, consistent with the enhancement ratio via the Purcell effect of WGMs. Furthermore, the MPS demonstrates the robust optical regulation capability toward flexible applications, opening up new opportunities for facilitating multiphoton upconversion in wearable optoelectrical devices for nanoimaging, biosensing, and energy conversion in the future.

Longitudinal associations of parental monitoring and delinquent peer affiliation: The potential influence of parental solicitation and monitoring rules.

Poor parental monitoring has been theorized as a key risk factor for an adolescent's association with deviant peers. However, measurements of parental monitoring often only measure parental knowledge rather than parental monitoring actions, leaving the true longitudinal associations between parental monitoring and peer delinquency unclear. The current sample consisted of 1095 male justice-involved adolescents (13-17 years old at baseline collected between 2011 and 2013) from across the United States who provided survey data every 6 months for 3 years. Longitudinal associations between parental monitoring constructs (i.e., parental solicitation and monitoring rules) and peer delinquency were tested using random intercept cross-lagged panel models to investigate both between-individual associations and within-individual bidirectional effects. Although parental monitoring and peer delinquency were negatively related at a between-individual level, very few within-individual directional effects were found. The few within-individual effects present indicated that parental solicitation predicted greater peer delinquency and peer delinquency predicted fewer parental monitoring rules over time. Current findings indicate that, while greater overall parental monitoring is associated with less peer delinquency, there is little evidence that changes in parental monitoring lead to reductions in peer delinquency over time. Results support previous findings suggesting parental monitoring should not be the sole target of intervention for reducing peer delinquency.

The Relationship Between Sleep Duration and Blood Lipids Among Chinese Middle-Aged and Older Adults: Cross-Lagged Path Analysis From CHARLS.

This study used data from the China Health and Retirement Longitudinal Study to investigate the temporal relationship between blood lipids and sleep duration in Chinese middle-aged and older adults. We used medical examinations and questionnaire data of 5,016 Chinese middle-aged and older adults (age 45+) in 2011 and 2015. Cross-lagged path analysis was performed to examine the bidirectional relationships between blood lipids and sleep duration. Sleep duration and lipids data were analyzed as continuous variables. Temporal relationships between sleep duration and HDL-cholesterol, LDL-cholesterol, total cholesterol, and triglycerides were different. Sleep duration was negatively associated with HDL-cholesterol 4 year later (β1 = −0.171, P = 0.005), and HDL-cholesterol was negatively associated with sleep duration 4 year later (β2 = −0.006, P = 0.002). Longer sleep duration was associated lower levels of LDL-cholesterol (β1 = −0.275, P = 0.097) and total cholesterol (β1 = −0.329, P = 0.096) 4 year later. There was a positive correlation between triglycerides and sleep duration. The path coefficient from triglycerides to sleep duration 4 year later (β2 = 0.001, P = 0.018) was greater than that from sleep duration to triglycerides 4 year later (β1 = 0.109, P = 0.847), with P = 0.030 for the difference between β1 and β2. In stratified analysis, we found that the strength and direction of the relationships may be related to age and BMI. Effects of sleep duration on blood lipids were only observed among participants aged <60 years, while the effect in the opposite direction was observed in older adults (age 60+), and the cross-lagged path coefficients were more significant in adults with BMI > 25.

Screening: From tornado diagrams to effective dimensions

Popular sensitivity analysis techniques such as Tornado Diagrams or the Morris method are based on one-at-a-time input variations (local main effects, henceforth). We evidence a link between local main effects of screening methods and global sensitivity measures. The link allows analysts to obtain insights on interactions on the local and global scales simultaneously. We evidence a mirroring effect according to which a local main effect calculated from the base case to the sensitivity case is equal in magnitude to the local total effect in the opposite direction, and their difference yields an overall local interaction index. We then obtain the exact relationship between Morris sensitivity measures and Sobol’ total indices and discuss its implications on the choice of the sampling scheme. We show that the non-diagonal elements of the variance-covariance matrix of main effects computed at randomized locations yield Liu and Owen’s global interaction indices. Asymptotic results are derived with particular reference to confidence intervals for the mean dimension. We illustrate findings and insights through numerical experiments on two well known simulators.

Identification of shared loci associated with both Crohn's disease and leprosy in East Asians.

Genome-wide association studies (GWAS) of Crohn's disease (CD) in European and leprosy in Chinese population have shown that CD and leprosy share genetic risk loci. As these shared loci were identified through cross-comparisons across different ethnic populations, we hypothesized that meta-analysis of GWAS on CD and leprosy in East Asian populations would increase power to identify additional shared loci. We performed a cross-disease meta-analysis of GWAS data from CD (1621 cases and 4419 controls) and leprosy (2901 cases 3801 controls) followed by replication in additional datasets comprising 738 CD cases and 488 controls and 842 leprosy cases and 925 controls. We identified one novel locus at 7p22.3, rs77992257 in intron 2 of ADAP1, shared between CD and leprosy with genome-wide significance (P = 3.80 × 10-11) and confirmed 10 previously established loci in both diseases: IL23R, IL18RAP, IL12B, RIPK2, TNFSF15, ZNF365-EGR2, CCDC88B, LACC1, IL27, NOD2. Phenotype variance explained by the polygenic risk scores derived from Chinese leprosy data explained up to 5.28% of variance of Korean CD, supporting similar genetic structures between the two diseases. Although CD and leprosy shared a substantial number of genetic susceptibility loci in East Asians, the majority of shared susceptibility loci showed allelic effects in the opposite direction. Investigation of the genetic correlation using cross-trait linkage disequilibrium score regression also showed a negative genetic correlation between CD and leprosy (rg [SE] = -0.40[0.13], P = 2.6 × 10-3). These observations implicate the possibility that CD might be caused by hyper-sensitive reactions toward pathogenic stimuli.

Linear array analysis of passive surface waves combined with mini-Sosie technique

SUMMARY Mini-Sosie, which is convenient and environmentally friendly with high energy output, is gaining increasing attention as a seismic exploration source. Passive surface wave survey using ambient noise have become a powerful tool for exploration in urban areas due to the advantages of being efficient and non-destructive. A 2-D or pseudo-1D array that can attenuate phase velocity overestimation due to directional noise are the optimal choice, but such arrays are limited by the complex environment of the experimental site on the one hand and the need to ensure that the medium beneath the array meets the assumption of lateral isotropy on the other. However, the fully 1-D linear array as an alternative lacks the ability to suppress the directional effect of the noise source. In this study, we develop a novel approach for linear array analysis of passive surface waves combined with mini-Sosie technique, called LAPSS. We use the mini-Sosie technique with fixed-frequency impact in the in-line direction to provide the theoretical phase velocity values at several frequency points as a reference for the biased dispersion image obtained from the linear array analysis, so as to estimate the azimuth of the noise source and to perform the correction of the biased dispersion image. We present the detailed workflow of LAPSS and compare the performance of LAPSS with PLAS (which has proven to be superior to the frequency–wavenumber method, spatial autocorrelation method, refraction microtremor and multichannel analysis of passive surface waves) in achieving unbiased dispersion image with different noise source distributions through synthetic tests. The results show that the accuracy of the two methods is comparable, but LAPSS greatly improves the computational efficiency, has stronger generalizability and depends on weaker assumptions. Finally, a field experiment is conducted to verify the feasibility and effectiveness of LAPSS in obtaining unbiased dispersion images using a fully linear array.

Causal Effects of Genetically Predicted Cystatin C on Osteoporosis: A Two-Sample Mendelian Randomization Study.

Objectives: Although it has long been reported that high levels of cystatin C could contribute to the development of osteoporosis in some studies, no evidence has established a causal association between them thus far. Methods: A Mendelian randomization (MR) study was conducted to determine the causal effect of cystatin C on osteoporosis based on public databases obtained from separately published genome-wide association studies (GWASs). The single-nucleotide polymorphisms (SNPs) for cystatin C were extracted from the MR-Base (CKDGen, 33,152 participants), and the SNPs for osteoporosis were extracted from the United Kingdom Biobank project (United Kingdom Biobank, including 5,266 osteoporosis cases and 331,893 controls). We defined the odds ratio (OR) of IVW methods as the primary outcome. In addition, weighted median and MR–Egger regressions were used in the sensitivity analysis. Results: In IVW, we found that genetically predicted cystatin C was causally associated with the risk of osteoporosis with an OR of 1.02 [95% confidence interval (CI) = 1.003–1.025, p = 0.01]. In the further sensitivity analysis, weighted median regression also showed directionally similar estimates (OR = 1.02, 95% CI = 1.005–1.03, p = 0.005), and MR–Egger regression (OR = 1.02, 95% CI = 1.000–1.036, p = 0.15) revealed similar estimates but with lower precision. The funnel plot, MR–Egger intercept, and MR-PRESSO all indicate that no directional pleiotropic effect was observed. Conclusion: In conclusion, our MR study showed evidence of a causal association between serum cystatin C levels and osteoporosis, which also needs to be verified by studies with larger sample sizes in the future. Early monitoring of cystatin C may enable us to prevent osteoporosis-related diseases.

The importance of modeling the effects of trend and anisotropy on soil fertility maps

• Restricted Maximum Likelihood has a higher accuracy in Fields with higher anisotropy. • Kriging with Method of Moments has higher accuracy in areas with lower anisotropy. • Spatial variability in soil chemical fertility used in Precision Agriculture must be modeled. • Directional effects in geospatial data must be considered in variogram modeling. • Synthetic data with variable levels of trend and anisotropy were simulated. Precision Agriculture (PA) commonly uses interpolation to generate maps for site-specific management. Semivariogram modeling with kriging interpolation considerers several parameters such as trend and anisotropy, which require proper estimation to return reliable maps. Often present in agricultural fields, these directional effects can also account for machine traffic and crop/soil management. Despite modeling trend and anisotropy being desirable for creating soil fertility maps, these effects are often disregarded during semivariogram modeling. Hence, this study evaluates whether semivariogram modeling considering anisotropy and trend influences the improvement of maps used in precision agriculture. Predicted performance and trends identified in the data when modeling anisotropy were evaluated considering two sampling grid densities, using the method of moments (MoM) and restricted maximum likelihood (REML) to estimate semivariogram parameters. Different levels of trend and anisotropy were tested on four types of virtual fields with 100 repetitions, and two experimental fields. Data were processed in an automated manner for virtual field generation, sampling extraction, semivariogram modeling, kriging, and cross-validation. Metrics were then subjected to bootstrapping and the differences were compared using confidence intervals. Results indicate that modeling directional effects improved the accuracy of kriging-generated maps. REML resulted in the best variability estimation in strong anisotropy, whereas MoM was more efficient in fields with weaker anisotropy. Modeling anisotropy was particularly useful in experimental fields, where trend was considered a function of spatial covariates. Consequently, semivariogram modeling must consider both directional effects to provide accurate soil fertility maps for precision agriculture.

Dynamic interplay of cognitive functioning and depressive symptoms in patients with Parkinson's disease.

We examine the trajectories of and the dynamic interplay between cognitive functioning and depressive symptoms in patients with Parkinson's disease (PD) in comparison to healthy controls (HC) from an intraindividual perspective. The DeNoPa study is a single-center, observational, longitudinal study with biennial follow-ups over 8 years. The present analyses are based on 123 PD (79 male) and 107 HC (64 male) with a mean age of 64.1 years (SD = 8.3). PD and HC completed a battery of neuropsychological tests and scales assessing depressive symptoms. We used a random-intercept cross-lagged panel model (RI-CLPM) to study their trajectories and the dynamic interplay. Cognitive abilities of PD were on average d = -0.67 worse at baseline and d = -1.22 at 8-years follow-up in comparison to HC. Depressive symptoms in PD showed large variability and followed a U-shaped trajectory. From an intraindividual perspective, greater impairments in cognitive abilities were subsequently associated with increased depressive symptoms (b = -0.60, p = .03), whereas the effect in the opposite direction was not significant. We found indication that a decline on a global composite scale of cognition can be seen as a precursor of depressive symptoms in patients with PD. To counter cognitive losses and the subsequent mood deterioration, patient education and early cognitive (and behavioral) enrichment seem promising candidates for treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Longer screen time utilization is associated with the polygenic risk for Attention-deficit/hyperactivity disorder with mediation by brain white matter microstructure.

SummaryBackgroundAttention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with longer screen time utilization (STU) at the behavioral level. However, whether there are shared neural links between ADHD symptoms and prolonged STU is not clear and has not been explored in a single large-scale dataset.MethodsLeveraging the genetics, neuroimaging and behavioral data of 11,000+ children aged 9–11 from the Adolescent Brain Cognitive Development cohort, this study investigates the associations between the polygenic risk and trait for ADHD, STU, and white matter microstructure through cross-sectionally and longitudinal analyses.FindingsChildren with higher polygenic risk scores for ADHD tend to have longer STU and more severe ADHD symptoms. Fractional anisotropy (FA) values in several white matter tracts are negatively correlated with both the ADHD polygenic risk score and STU, including the inferior frontal-striatal tract, inferior frontal-occipital fasciculus, superior longitudinal fasciculus and corpus callosum. Most of these tracts are linked to visual-related functions. Longitudinal analyses indicate a directional effect of white matter microstructure on the ADHD scale, and a bi-directional effect between the ADHD scale and STU. Furthermore, reduction of FA in several white matter tracts mediates the association between the ADHD polygenic risk score and STU.InterpretationThese findings shed new light on the shared neural overlaps between ADHD symptoms and prolonged STU, and provide evidence that the polygenic risk for ADHD is related, via white matter microstructure and the ADHD trait, to STU.FundingThis study was mainly supported by NSFC and National Key R&D Program of China.

Wind Fetch and Direction Effects on Langmuir Turbulence in a Coastal Ocean

AbstractMixing processes in the upper ocean play a key role in transferring heat, momentum, and matter in the ocean. These mixing processes are significantly enhanced by wave‐driven Langmuir turbulence (LT). Based on a paired analysis of observations and simulations, this study investigates wind fetch and direction effects on LT at a coastal site south of the island Martha’s Vineyard (MA, USA). Our results demonstrate that LT is strongly influenced by wind fetch and direction in coastal oceans, both of which contribute to controlling turbulent coastal transport processes. For northerly offshore winds, land limits the wind fetch and wave development, whereas southerly winds are associated with practically infinite fetch. Observed and simulated two‐dimensional wave height spectra reveal persistent southerly swell and substantially more developed wind‐driven waves from the south. For oblique offshore winds, waves develop more strongly in the alongshore direction with less limited fetch, resulting in significant wind and wave misalignments. Observations of coherent near‐surface crosswind velocities indicate that LT is only present for sufficiently developed waves. The fetch‐limited northerly winds inhibit wave developments and the formation of LT. In addition to limited fetch, strong wind–wave misalignments prevent LT development. Although energetic and persistent, swell waves do not substantially influence LT activity during the observation period because these relatively long swell waves are associated with small Stokes drift shear. These observational results agree well with turbulence‐resolving large eddy simulations (LESs) based on the wave‐averaged Navier–Stokes equation, validating the LES approach to coastal LT in the complex wind and wave conditions.

Association and Path Analysis of Yield and Its Component Traits for Yield Maximization in Green Gram (Vigna radiata L. Wilczek)

The present investigation was undertaken to estimate the correlation coefficients among thirteen quantitative traits and to study the direct and indirect effects of various yield contributing traits on grain yield by path analysis. Ten genetically diverse genotypes of green gram (Vigna radiata L.) were used as parents in line x tester mating design in addition to their twenty four F2 lines at Educational and Research farm, Department of Genetics and Plant Breeding, Brahmanand P.G. College, Rath (Hamirpur), Uttar Pradesh during zaid, 2019 in a randomized block design with three replications each. The results of association study revealed that grain yield per plant showed highly significant and positive correlation, at both genotypic and phenotypic levels, with number of days to flowering, number of pods per cluster, number of clusters per plant, number of pods per plant and biological yield per plant (g) indicating possibility of simultaneous improvement for these traits. However, yield per plant for parents showed significant negative correlation with primary branches per plant and harvest index at both genotypic and phenotypic levels. In contrast, only clusters per plant, pods per cluster, pods per plant, biological yield per plant, seeds per pod, seed weight per pod and 100 seed weight exhibited significant positive association in F2 generation, indicating existence of linkage. Harvest index had negative association with most of the traits at genotypic as well as phenotypic levels. Path analysis revealed that, biological yield per plant; harvest index and seeds per pod recorded the high direct effect in desirable direction. Their association with grain yield was also significant and positive except with harvest index, indicating true and perfect association between these traits at both genotypic and phenotypic levels. Therefore, direct selection for these characters would help in isolating high yielding genotypes from highly segregating population. Among the traits showing negative direct effects were days to 50% flowering, branches per plant, plant height, pods per plant and seed weight per pod, however, these trait had positive association with yield. Hence, biological yield per plant, harvest index, seeds per pod and clusters per plant may be improved to enhance seed yield per plant and hybridization followed by direct and indirect selection for these traits may be undertaken for breeding high yielding cultivars.

A Multi-Parameter Integrated Sensor Based on Selectively Filled D-Shaped Photonic Crystal Fiber.

We propose and numerically investigate a multi-parameter integrated sensor based on a selectively filled D-shaped photonic crystal fiber (PCF). The simple structure can be used to comprehensively detect refractive index, magnetic field, temperature, and voltage. According to the surface plasmon resonance and directional coupling effect, the PCF is coated with a gold nano-film to detect the refractive index of the external environment. In addition, magnetic fluid (water-based Fe3O4), toluene, and nematic liquid crystal (NLC E7) are selectively filled into different cladding air holes of the D-shaped PCF to realize the different sensing of the magnetic field, temperature, and voltage. The measurement of refractive index, magnetic field, temperature, and voltage are independent of each other, so these four parameters can be measured simultaneously. The sensing characteristics of the proposed structure are investigated systematically by the finite element method. The results show that the sensitivities of refractive index, magnetic field, temperature, and voltage are 4600 nm/RIU, 1.375 nm/Oe, 15.143 nm/°C, and 0.971 nm/V, respectively. The presented design based on materials selectively filled with D-shaped PCF might enable promising application in multi-parameter optical sensing.

Defect-induced asymmetrical mechanical behavior in shape memory zirconia: A phase-field investigation

An elastoplastic phase-field model is used to investigate the deformation mechanisms of yttria stabilized tetragonal zirconia in presence of defects. A remarkable tension-compression asymmetry is detected. A higher strength and a lower degree of transformation are observed in compression than in tension. Also, deformation mechanism is asymmetric depending on the crystal orientation. For some cases (other cases), phase transformation is absent in tension (in compression), while both transformation and plasticity are present in compression (in tension). Such tension-compression asymmetry is attributed to activation of different monoclinic variants with different Eigen strain tensors in tension versus compression. Results also reveal a higher degree of transformation and plasticity with lower onset stresses as the void size increases. Elliptic voids exhibit a directional effect with a maximum stress intensity factor of 5.6 MPa m1/2 when the long semi-axis is diagonally oriented with respect to the loading direction, and this prediction is comparable to experiments.

Tibial internal and external rotation taping for improving pain in patients with patellofemoral pain syndrome

ObjectivesThe aim of this study was to assess the effects of two rigid taping methods, tibial internal rotation taping and external rotation taping, on knee pain during three clinical function tests in individuals with patellofemoral pain syndrome. DesignRepeated measures study. MethodsFifteen participants (male, height 174.9 ± 5.8 cm, weight 68.3 ± 10.2 kg) with unilateral patellofemoral pain syndrome were treated by applying internal rotation taping and external rotation taping, in randomized order. While taped, participants were asked to perform three clinical tests in random order: single-leg squat, double-leg squat, and quadriceps maximum isometric contraction. Pain was scored using a Visual Analog Scale. ResultsCompared with no taping, both internal rotation taping and external rotation taping significantly improved pain during each of the three clinical tests (F = 224.10, p < 0.001, partial η² = 0.94). Furthermore, there was a tape direction effect, where external rotation taping was more effective than internal rotation taping (F = 4.90, p = 0.044, partial η² = 0.26). For each test, the amount of pain improvement after taping was positively correlated with initial pain level (0.539 ≤ rho ≤ 0.921, all p < 0.05). ConclusionsBoth internal rotation taping and external rotation taping were effective in improving pain in individuals with patellofemoral pain syndrome, and external rotation taping was more effective than internal rotation taping. The significant correlations observed between initial pain levels and pain improvement after taping suggest that those with greater patellofemoral pain achieve greater relief from tibial rotation taping.

Flexible microsphere‐coupled surface‐enhanced Raman spectroscopy (McSERS) by dielectric microsphere cavity array with random plasmonic nanoparticles

AbstractSurface‐enhanced Raman spectroscopy (SERS) is a powerful tool for nondestructive and ultrasensitive optical trace‐detection. However, the sophisticated fabrication processes and performance degradation on flexible substrates block SERS for practical uses. Here, we report a facile flexible microsphere‐coupled SERS (McSERS) substrate composed of a dielectric microsphere cavity array (MCA) and random gold nanoparticles (AuNPs) capping on a polydimethylsiloxane (PDMS) film (MCA/AuNPs/PDMS) for giant Raman enhancement. The random distribution of AuNPs provides a hydrophilic surface against to the coffee‐ring effect for uniform localized surface plasmon resonance (LSPR) response. The MCA capped on the AuNPs boosts the Raman intensity via the multiple optical manipulation processes, in which the photonic nanojet (PNJ) confines the excitation intensity near the AuNPs, whispering‐gallery mode (WGM) facilitates the energy transfer from microsphere cavities to AuNP gaps for LSPR boosting, and directional antenna effect converts near‐field Raman signals into far‐field with a small divergence. Therefore, the Raman scattering is dramatically improved with the enhancement factor (EF) to 107 for the limit of detection (LoD) of 4‐nitrobenzenethiol (4‐NBT) molecules down to 0.1 nM, two orders of magnitude higher via MCA coupling. Moreover, the flexible McSERS substrate exhibits outstanding durability and compatibility as an ultrasensitive Raman test strip, by which the thiram concentration is detectable down to 2.42 ng/cm2 on apple peels. The present work provides a facile strategy to fabricate SERS substrates with high flexibility for optical trace‐detection in real‐world applications.

Coughing Intensity and Wind Direction Effects on the Transmission of Respiratory Droplets: A Computation with Euler–Lagrange Method

Studies on droplet transmission are needed to understand the infection mechanism of SARS-CoV-2. This research investigated the effects of coughing intensity and wind direction on respiratory droplets transportation using the Euler–Lagrange method. The results revealed that both coughing intensity and wind conditions considerably influence the transmission of small and medium droplets but had little effect on large droplets. A stronger coughing intensity resulted in small and medium droplets traveling farther in a calm wind and spreading widely and rapidly in a windy environment. The droplets do not travel far in the absence of ambient wind, even with stronger coughing. Medium droplets spread in clusters, and small droplets drifted out of the domain in the band area in different wind conditions except for 60° and 90° wind directions, in which cases, the droplets were blown directly downstream. In 0° wind direction, many droplets were deposited on the human body. The fast and upward movement of particles in 60° and 90° directions could cause infection risk with short exposure. In 180° wind direction, droplets spread widely and traveled slowly because of the reverse flow downstream, prolonged exposure can result in a high risk of infection.

Social withdrawal and academic achievement, intertwined over years? Bidirectional effects from primary to upper secondary school.

Socially withdrawn children tend to perform poorer academically than their peers. What remains unknown, is the temporal ordering of the two phenomena. Also, substantial gender differences exist in both social withdrawal and academic achievement; thus, it is conceivable that the strength of the relation between them is gendered as well. To investigate cross-sectional correlates and test directional effects of social withdrawal and academic achievement from primary to upper secondary school, and to examine potential gendered effects. Prospective associations were analysed from age 6 to age 14 using biannual teacher ratings of children's social withdrawal and academic achievement in a representative community sample (n=845), by means of random intercept cross-lagged panel modelling. In boys, increased academic achievement at ages 8 and 12 forecasted decreased social withdrawal 2years later, whereas increased social withdrawal at age 10 predicted reduced academic achievement at age 12. No such effects were seen in girls. Social withdrawal and academic achievement are bidirectionally related among boys, but not girls. Results are discussed in light of need-to-belong theory, and practical implications for schools and teachers are illuminated.

Efficacy and Safety of Intravenous Iron Therapy for Treating Anaemia in Critically ill Adults: A Rapid Systematic Review With Meta-Analysis.

Our objective was to systematically evaluate the efficacy and safety of intravenous (IV) iron therapy for treating anaemia in critically ill adults (>16 years) admitted to intensive care or high dependency units. We excluded quasi-RCTs and other not truly randomised trials. We searched 7 electronic databases (including CENTRAL, MEDLINE, and Embase) using a pre-defined search strategy from inception to June 14, 2021. One reviewer screened, extracted, and analysed data, with verification by a second reviewer of all decisions. We used Cochrane risk of bias (ROB) 1 and GRADE to assess the certainty of the evidence. We reported 3 comparisons across 1198 patients, in 8 RCTs: (1) IV iron vs control (7 RCTs, 748 participants); our primary outcome (hemoglobin (Hb) concentration at 10 to 30 days) was reported in 7 of the 8 included trials. There was evidence of an effect (very-low certainty) in favour of IV iron over control in the main comparison only (6 RCTs, n=528, mean difference (MD) 0.52g/dL [95%CI 0.23, 0.81], P=.0005). For the remaining outcomes there was no evidence of an effect in either direction (low certainty of evidence for Hb concentration at <10 days; very-low certainty of evidence for hospital duration, ICU duration, hospital readmission, infection, mortality; HRQoL outcomes were not GRADED). (2) IV iron+subcutaneous erythropoietin (EPO) vs control (2 RCTs, 104 participants); reported outcomes showed no evidence of effect in either direction, based on very-low certainty evidence (Hb concentration at 10-30 days, and <10 days, infection, mortality). (3) Hepcidin-guided treatment with IV iron or iron+ EPO vs standard care (1 RCT, 399 participants) reported evidence of an effect in favour of the intervention for 90-day mortality (low certainty of evidence), but no other group differences for the reported outcomes (low certainty evidence for Hb concentration at 10-30 days, hospital duration; HRQoL was not GRADED). The evidence across all comparisons was downgraded for high and unclear ROB for lack of blinding, incomplete outcome data, baseline imbalance, and imprecision around the estimate (wide CIs and small sample size). In conclusion, the current evidence continues to support further investigation into the role for iron therapy in increasing Hb in critically ill patients. Recent, small, trials have begun to focus on patient-centred outcomes but a large, well conducted, and adequately powered trial is needed to inform clinical practice.

3D-organoid culture supports differentiation of human CAR+ iPSCs into highly functional CAR Tcells.

Unlimited generation of chimeric antigen receptor (CAR) Tcells from human-induced pluripotent stem cells (iPSCs) is an attractive approach for "off-the-shelf" CAR Tcell immunotherapy. Approaches to efficiently differentiate iPSCs into canonical αβ Tcell lineages, while maintaining CAR expression and functionality, however, have been challenging. We report that iPSCs reprogramed from CD62L+ naive and memory Tcells followed by CD19-CAR engineering and 3D-organoid system differentiation confers products with conventional CD8αβ-positive CAR Tcell characteristics. Expanded iPSC CD19-CAR Tcells showed comparable antigen-specific activation, degranulation, cytotoxicity, and cytokine secretion compared with conventional CD19-CAR Tcells and maintained homogeneous expression of the TCR derived from the initial clone. iPSC CD19-CAR Tcells also mediated potent antitumor activity invivo, prolonging survival of mice with CD19+ human tumor xenografts. Our study establishes feasible methodologies to generate highly functional CAR Tcells from iPSCs to support the development of "off-the-shelf" manufacturing strategies.