Optically Transparent Lead Halide Perovskite Polycrystalline Ceramics.

We utilize room-temperature uniaxial pressing at applied loads achievable with low-cost, laboratory-scale presses to fabricate freestanding CH3NH3PbX3 (X- = Br-, Cl-) polycrystalline ceramics with millimeter thicknesses and optical transparency up to ∼70% in the infrared. As-fabricated perovskite ceramics can be produced with desirable form factors (i.e., size, shape, and thickness) and high-quality surfaces without any postprocessing (e.g., cutting or polishing). This method should be broadly applicable to a large swath of metal halide perovskites, not just the compositions shown here. In addition to fabrication, we analyze microstructure-optical property relationships through detailed experiments (e.g., transmission measurements, electron microscopy, X-ray tomography, optical profilometry, etc.) as well as modeling based on Mie theory. The optical, electrical, and mechanical properties of perovskite polycrystalline ceramics are benchmarked against those of single-crystalline analogues through spectroscopic ellipsometry, Hall measurements, and nanoindentation. Finally, γ-ray scintillation from a transparent MAPbBr3 ceramic is demonstrated under irradiation from a 137Cs source. From a broader perspective, scalable methods to produce freestanding polycrystalline lead halide perovskites with comparable properties to their single-crystal counterparts could enable key advancements in the commercial production of perovskite-based technologies (e.g., direct X-ray/γ-ray detectors, scintillators, and nonlinear optics).

Flat-Knit, Flexible, Textile Metasurfaces.

Lightweight, low-cost metasurfaces and reflectarrays that are easy to stow and deploy are desirable for many terrestrial and space-based communications and sensing applications. This work demonstrates a lightweight, flexible metasurface platform based on flat-knit textiles operating in the cm-wave spectral range. By using a colorwork knitting approach called float-jacquard knitting to directly integrate an array of resonant metallic antennas into a textile, we realize two textile reflectarray devices, a metasurface lens (metalens) and a vortex-beam generator. Operating as a receiving antenna, the metalens focuses a collimated normal-incidence beam to a diffraction-limited, off-broadside focal spot. Operating as a transmitting antenna, the metalens converts the divergent emission from a horn antenna into a collimated beam with peak measured directivity, gain, and efficiency of 21.30 dB, 15.30 dB, and -6.00 dB (25.12%), respectively. The vortex-beam generating metasurface produces a focused vortex beam with a topological charge of m = 1 over a wide frequency range of 4.1-5.8 GHz. Strong specular reflection is observed for our textile reflectarrays, caused by wavy yarn floats on the backside of the float-jacquard textiles. Our work demonstrates a novel approach for scalable production of flexible metasurfaces by leveraging commercially available yarns and well-established knitting machinery and techniques. This article is protected by copyright. All rights reserved.

Punishment Leads to Greater Sensorimotor Learning But Less Movement Variability Compared to Reward.

When a musician practices a new song, hitting a correct note sounds pleasant while striking an incorrect note sounds unpleasant. Such reward and punishment feedback has been shown to differentially influence the ability to learn a new motor skill. Recent work has suggested that punishment leads to greater movement variability, which causes greater exploration and faster learning. To further test this idea, we collected 102 participants over two experiments. Unlike previous work, in Experiment 1 we found that punishment did not lead to faster learning compared to reward (n = 68), but did lead to a greater extent of learning. Surprisingly, we also found evidence to suggest that punishment led to less movement variability, which was related to the extent of learning. We then designed a second experiment that did not involve adaptation, allowing us to further isolate the influence of punishment feedback on movement variability. In Experiment 2, we again found that punishment led to significantly less movement variability compared to reward (n = 34). Collectively our results suggest that punishment feedback leads to less movement variability. Future work should investigate whether punishment feedback leads to a greater knowledge of movement variability and or increases the sensitivity of updating motor actions.

Reinforcement-based processes actively regulate motor exploration along redundant solution manifolds.

From a baby's babbling to a songbird practising a new tune, exploration is critical to motor learning. A hallmark of exploration is the emergence of random walk behaviour along solution manifolds, where successive motor actions are not independent but rather become serially dependent. Such exploratory random walk behaviour is ubiquitous across species' neural firing, gait patterns and reaching behaviour. The past work has suggested that exploratory random walk behaviour arises from an accumulation of movement variability and a lack of error-based corrections. Here, we test a fundamentally different idea-that reinforcement-based processes regulate random walk behaviour to promote continual motor exploration to maximize success. Across three human reaching experiments, we manipulated the size of both the visually displayed target and an unseen reward zone, as well as the probability of reinforcement feedback. Our empirical and modelling results parsimoniously support the notion that exploratory random walk behaviour emerges by utilizing knowledge of movement variability to update intended reach aim towards recently reinforced motor actions. This mechanism leads to active and continuous exploration of the solution manifold, currently thought by prominent theories to arise passively. The ability to continually explore muscle, joint and task redundant solution manifolds is beneficial while acting in uncertain environments, during motor development or when recovering from a neurological disorder to discover and learn new motor actions.

Curriculum in Neuro-Ophthalmic Principles for National Football League Game Officials: Comparison of Pretraining and Posttraining Ratings of Knowledge.

BACKGROUND: We hypothesize that creation of a structured curriculum in neuro-ophthalmology principles might improve self-rated learner satisfaction and knowledge base of National Football League (NFL) game officials. Our initial objective is to create the said curriculum in coordination with game official experts and staff at the NFL to increase levels of understanding of neuro-ophthalmology principles. We reviewed the prior published literature on applicable neuro-ophthalmic principles in professional sports. Major neuro-ophthalmic principles reviewed include both the efferent (e.g., saccadic and pursuit eye movements and vestibulo-ocular reflex) and afferent (visual field, dynamic visual acuity during body movement, and selective attention deficits). METHODS: A 6-question survey pertaining to levels of understanding, future applicability, relevance, satisfaction, and interest in additional training was then given to 26 individuals before and after a lecture given by Dr. Andrew Lee in Plano, TX. The primary outcome measure was the creation of the curriculum followed by real-world testing for face and content validity and ending with a self-rated assessment. RESULTS: Twenty-one individuals completed the prelecture and postlecture survey out of 26 individuals who attended. Prelecture means for the level of understanding of oculomotor terms and the likelihood of using said terms were 3.4 and 3.2, respectively. Postlecture means were 8.9 and 8.8, respectively. The lecture was rated 9.2 of 10 for relevance to coaching and teaching officials, and individuals rated their interest in further content as 9.4 of 10. CONCLUSIONS: This study found that NFL game officials are interested in learning more about the science behind play-calling in terms of neuro-ophthalmology principles and practices. In addition, from our pilot survey, it is evident that even one lecture can improve participants' level of understanding and likelihood of learning more about neuro-ophthalmic principles.

Visual accuracy dominates over haptic speed for state estimation of a partner during collaborative sensorimotor interactions.

We routinely have physical interactions with others, whether it be handing someone a glass of water or jointly moving a heavy object together. These sensorimotor interactions between humans typically rely on visual feedback and haptic feedback. Recent single-participant studies have highlighted that the unique noise and time delays of each sense must be considered to estimate the state, such as the position and velocity, of one's own movement. However, we know little about how visual feedback and haptic feedback are used to estimate the state of another person. Here, we tested how humans utilize visual feedback and haptic feedback to estimate the state of their partner during a collaborative sensorimotor task. Across two experiments, we show that visual feedback dominated haptic feedback during collaboration. Specifically, we found that visual feedback led to comparatively lower task-relevant movement variability, smoother collaborative movements, and faster trial completion times. We also developed an optimal feedback controller that considered the noise and time delays of both visual feedback and haptic feedback to estimate the state of a partner. This model was able to capture both lower task-relevant movement variability and smoother collaborative movements. Taken together, our empirical and modeling results support the idea that visual accuracy is more important than haptic speed to perform state estimation of a partner during collaboration.NEW & NOTEWORTHY Physical collaboration between two or more individuals involves both visual and haptic feedback. Here, we investigated how visual and haptic feedback is used to estimate the movements of a partner during a collaboration task. Our experimental and computational modeling results parsimoniously support the notion that greater visual accuracy is more important than faster yet noisier haptic feedback when estimating the state of a partner.

Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature.

BACKGROUND: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. METHODS: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). RESULTS: In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. CONCLUSIONS: MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health.

Exercising choice over feedback schedules during practice is not advantageous for motor learning.

The idea that there is a self-controlled learning advantage, where individuals demonstrate improved motor learning after exercising choice over an aspect of practice compared to no-choice groups, has different causal explanations according to the OPTIMAL theory or an information-processing perspective. Within OPTIMAL theory, giving learners choice is considered an autonomy-supportive manipulation that enhances expectations for success and intrinsic motivation. In the information-processing view, choice allows learners to engage in performance-dependent strategies that reduce uncertainty about task outcomes. To disentangle these potential explanations, we provided participants in choice and yoked groups with error or graded feedback (Experiment 1) and binary feedback (Experiment 2) while learning a novel motor task with spatial and timing goals. Across both experiments (N = 228 participants), we did not find any evidence to support a self-controlled learning advantage. Exercising choice during practice did not increase perceptions of autonomy, competence, or intrinsic motivation, nor did it lead to more accurate error estimation skills. Both error and graded feedback facilitated skill acquisition and learning, whereas no improvements from pre-test performance were found with binary feedback. Finally, the impact of graded and binary feedback on perceived competence highlights a potential dissociation of motivational and informational roles of feedback. Although our results regarding self-controlled practice conditions are difficult to reconcile with either the OPTIMAL theory or the information-processing perspective, they are consistent with a growing body of evidence that strongly suggests self-controlled conditions are not an effective approach to enhance motor performance and learning.

Lower Risk of Multisystem Inflammatory Syndrome in Children With the Delta and Omicron Variants of Severe Acute Respiratory Syndrome Coronavirus 2.

Little is known about the risk of multisystem inflammatory syndrome in children (MIS-C) with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. In southeast England, MIS-C rates per confirmed SARS-CoV-2 infections in children aged 0-16 years were 56% lower (rate ratio [RR], 0.34 [95% confidence interval {CI}, .23-.50]) during prevaccine Delta, 66% lower (RR, 0.44 [95% CI, .28-.69]) during postvaccine Delta, and 95% lower (RR, 0.05 [95% CI, .02-.10]) during the Omicron period.

CIITA promoter polymorphism impairs monocytes HLA-DR expression in patients with septic shock.

Low monocyte (m)HLA-DR expression is associated with mortality in sepsis. G-286A∗rs3087456 polymorphism in promoter III of HLA class II transactivator (CIITA), the master regulator of HLA, has been associated with autoimmune diseases but its role in sepsis has never been demonstrated. In 203 patients in septic shock, GG genotype was associated with 28-day mortality and mHLA-DR remained low whereas it increased in patients with AA or AG genotype. In ex vivo cells, mHLA-DR failed to augment in GG in comparison with AG or AA genotype on exposure to IFN-γ. Promoter III transcript levels were similar in control monocytes regardless of genotype and exposure to IFN-γ. Promoter III activity was decreased in GG genotype in monocyte cell line but restored after stimulation with IFN-γ. Hereby, we demonstrated that G-286A∗rs3087456 significantly impact mHLA-DR expression in patients with septic shock in part through CIITA promoter III activity, that can be rescued using IFN-γ.

Effect of the of 10-valent pneumococcal conjugate vaccine in Nepal 4 years after introduction: an observational cohort study.

BACKGROUND: In Nepal, Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial pneumonia in children, and is a major health concern. There are few data on the effect of vaccination on the disease or colonisation with pneumococci in the nasopharynx of children in this setting. The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine infant immunisation schedule in Nepal in 2015. We aimed to investigate the effect of the introduction of PCV10 on pneumococcal carriage and disease in children in Nepal. METHODS: We did an observational cohort study in children in Nepal. The hospital surveillance study took place in Patan Hospital, Kathmandu, and community studies in healthy children took place in Kathmandu and Okhaldhunga district. For the surveillance study, all children admitted to Patan Hospital between March 20, 2014, and Dec 31, 2019, aged between 2 months and 14 years with clinician-suspected pneumonia, were eligible for enrolment. For the community study, healthy children aged 0-8 weeks, 6-23 months, and 24-59 months were recruited from Kathmandu, and healthy children aged 6-23 months were recruited from Okhaldhunga. We assessed the programmatic effect of PCV10 introduction using surveillance for nasopharyngeal colonisation, pneumonia, and invasive bacterial disease from 1·5 years before vaccine introduction and 4·5 years after vaccine introduction. For the surveillance study, nasopharyngeal swabs, blood cultures, and chest radiographs were obtained from children admitted to Patan Hospital with suspected pneumonia or invasive bacterial disease. For the community study, nasopharyngeal swabs were obtained from healthy children in the urban and rural settings. Pneumonia outcomes were analysed using log-binomial models and adjusted prevalence ratios (aPR) comparing each calendar year after the introduction of the vaccine into the national programme with the pre-vaccine period (2014-15), adjusted for calendar month, age, and sex. FINDINGS: Between March 20, 2014, and Dec 31, 2019, we enrolled 2051 children with suspected pneumonia, and 11 354 healthy children (8483 children aged 6-23 months, 761 aged 24-59 months, and 2110 aged 0-8 weeks) to assess nasopharyngeal colonisation. Among clinical pneumonia cases younger than 2 years, vaccine serotype carriage declined 82% (aPR 0·18 [95% CI 0·07-0·50]) by 2019. There was no decrease in vaccine serotype carriage in cases among older unvaccinated age groups. Carriage of the additional serotypes in PCV13 was 2·2 times higher by 2019 (aPR 2·17 [95% CI 1·16-4·05]), due to increases in serotypes 19A and 3. Vaccine serotype carriage in healthy children declined by 75% in those aged 6-23 months (aPR 0·25 [95% CI 0·19-0·33]) but not in those aged 24-59 months (aPR 0·59 [0·29-1·19]). A decrease in overall vaccine serotype carriage of 61% by 2019 (aPR 0·39 [95% CI 0·18-0·85]) was also observed in children younger than 8 weeks who were not yet immunised. Carriage of the additional PCV13 serotypes in children aged 6-23 months increased after PCV10 introduction for serotype 3 and 19A, but not for serotype 6A. The proportion of clinical pneumonia cases with endpoint consolidation on chest radiographs declined from 41% in the pre-vaccine period to 25% by 2018, but rose again in 2019 to 36%. INTERPRETATION: The introduction of the PCV10 vaccine into the routine immunisation programme in Nepal has reduced vaccine serotype carriage in both healthy children and children younger than 2 years with pneumonia. Increases in serotypes 19A and 3 highlight the importance of continued surveillance to monitor the effect of vaccine programmes. This analysis demonstrates a robust approach to assessing vaccine effect in situations in which pneumococcal disease endpoint effectiveness studies are not possible. FUNDING: Gavi, the Vaccine Alliance and the World Health Organization.

Cellular and molecular mechanisms of IMMunE dysfunction and Recovery from SEpsis-related critical illness in adults: An observational cohort study (IMMERSE) protocol paper.

Sepsis is a common illness. Immune responses are considered major drivers of sepsis illness and outcomes. However, there are no proven immunomodulator therapies in sepsis. We hypothesised that in-depth characterisation of sepsis-specific immune trajectory may inform immunomodulation in sepsis-related critical illness. We describe the protocol of the IMMERSE study to address this hypothesis. We include critically ill sepsis patients without documented immune comorbidity and age-sex matched cardiac surgical patients as controls. We plan to perform an in-depth biological characterisation of innate and adaptive immune systems, platelet function, humoral components and transcriptional determinants of the immune system responses in sepsis. This will be done at pre-specified time points during their critical illness to generate an illness trajectory. The sample size for each biological assessment is different and is described in detail. In summary, the overall aim of the IMMERSE study is to increase the granularity of longitudinal immunology model of sepsis to inform future immunomodulation trials.

Effect of childhood vaccination and antibiotic use on pneumococcal populations and genome-wide associations with disease among children in Nepal: an observational study.

BACKGROUND: Pneumococcal disease is a leading cause of bacterial pneumonia and invasive bacterial disease among children globally. The reason some strains of pneumococci are more likely to cause disease, and how interventions such as vaccines and antibiotics affect pneumococcal strains is poorly understood. We aimed to identify genetic regions under selective pressure and those associated with disease through the analysis of pneumococcal whole-genome sequences. METHODS: Whole-genome sequencing was performed on pneumococcal isolates collected between January, 2005, and May, 2018, in Kathmandu, Nepal, which included programmatic ten-valent pneumococcal conjugate vaccine (PCV10) introduction in 2015. Isolates were from three distinct cohorts: nasopharyngeal swabs of healthy community-based children, nasopharyngeal swabs of children admitted to hospital with pneumonia, and sterile-site cultures from children admitted to hospital. Across these cohorts we examined serotype distribution, antibiotic resistance, strain distribution, and regions of recombination to determine genes that were undergoing diversifying selection. Genome-wide association studies comparing pneumonia and sterile-site isolates with healthy carriage were used to determine novel variants associated with disease. FINDINGS: After programmatic introduction of PCV10, there was a decline in vaccine covered serotypes; however, strains that had expressed these serotypes continued to exist in the post-PCV population. We identified GPSC9 to be a strain of concern due to its high prevalence in disease, multidrug resistance, and ability to switch to an unencapsulated phenotype via insertion of virulence factor pspC into the cps locus. Antibiotic resistance loci to co-trimoxazole were found to be prevalent (pre-PCV10 78% vs post-PCV10 81%; p=0·27) and increasingly prevalent to penicillin (pre-PCV10 15% vs post-PCV10 32%; p<0·0001). Regions with multiple recombinations were identified spanning the surface protein virulence factors pspA and pspC and antibiotic targets pbpX, folA, folC, folE, and folP. Furthermore, we identified variants in lacE2 to be strongly associated with isolates from children with pneumonia and PRIP to be strongly associated with isolates from sterile sites. INTERPRETATION: Our work highlights the effect of pneumococcal conjugate vaccines, antibiotics, and host-pathogen interaction in pneumococcal variation, and the pathogen's capability of adapting to these factors at both population-wide and strain-specific levels. Ongoing surveillance of disease-associated strains and further investigation of lacE2 and PRIP as serotype-independent targets for therapeutic interventions is required. FUNDING: Gavi, The Vaccine Alliance; WHO; Bill & Melinda Gates Foundation; Wellcome Sanger Institute; and US Centers for Disease Control and Prevention.

Humans utilize sensory evidence of others' intended action to make online decisions.

We often acquire sensory information from another person's actions to make decisions on how to move, such as when walking through a crowded hallway. Past interactive decision-making research has focused on cognitive tasks that did not allow for sensory information exchange between humans prior to a decision. Here, we test the idea that humans accumulate sensory evidence of another person's intended action to decide their own movement. In a competitive sensorimotor task, we show that humans exploit time to accumulate sensory evidence of another's intended action and utilize this information to decide how to move. We captured this continuous interactive decision-making behaviour with a drift-diffusion model. Surprisingly, aligned with a 'paralysis-by-analysis' phenomenon, we found that humans often waited too long to accumulate sensory evidence and failed to make a decision. Understanding how humans engage in interactive and online decision-making has broad implications that spans sociology, athletics, interactive technology, and economics.

Increased perceptions of autonomy through choice fail to enhance motor skill retention.

There has been growing research interest in the effects that motivation plays in motor learning, and specifically how autonomy, competence, and social relatedness may directly benefit the learning process. Here, we present a preregistered manipulation of autonomy-support by providing learners with choice during the practice of a speed cup-stacking task. One group was given control over when a video demonstration was provided and the viewing speed. A yoked control group received an identical demonstration schedule, but without choice (as their schedule was matched to a participant with choice). Critically, we addressed a gap in the literature by adding a yoked group who was explicitly told that they were being denied choice and that their schedule was chosen by another participant. We found no statistically significant learning differences between groups, despite finding evidence that providing choice increased perceived autonomy. Equivalence tests further showed that although the groups were not statistically equivalent, the effect size is likely too small to practically study the effects of autonomy-support through choice in most motor learning labs. These findings add to a growing body of research that questions a causal role of autonomy-support on motor learning, and the robustness of the so-called self-controlled learning advantage. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Childhood Invasive Bacterial Disease in Kathmandu, Nepal (2005-2013).

BACKGROUND: Invasive bacterial disease (IBD; including pneumonia, meningitis, sepsis) is a major cause of morbidity and mortality in children in low-income countries. METHODS: We analyzed data from a surveillance study of suspected community-acquired IBD in children <15 years of age in Kathmandu, Nepal, from 2005 to 2013 before introduction of pneumococcal conjugate vaccines (PCV). We detailed the serotype-specific distribution of invasive pneumococcal disease (IPD) and incorporated antigen and PCR testing of cerebrospinal fluid (CSF) from children with meningitis. RESULTS: Enhanced surveillance of IBD was undertaken during 2005-2006 and 2010-2013. During enhanced surveillance, a total of 7956 children were recruited of whom 7754 had blood or CSF culture results available for analysis, and 342 (4%) had a pathogen isolated. From 2007 to 2009, all 376 positive culture results were available, with 259 pathogens isolated (and 117 contaminants). Salmonella enterica serovar Typhi was the most prevalent pathogen isolated (167 cases, 28% of pathogens), followed by Streptococcus pneumoniae (98 cases, 16% pathogens). Approximately, 73% and 78% of pneumococcal serotypes were contained in 10-valent and 13-valent PCV, respectively. Most cases of invasive pneumococcal disease (IPD) were among children ≥5 years of age from 2008 onward. Antigen and PCR testing of CSF for pneumococci, Haemophilus influenzae type b and meningococci increased the number of these pathogens identified from 33 (culture) to 68 (culture/antigen/PCR testing). CONCLUSIONS: S. enterica serovar Typhi and S. pneumoniae accounted for 44% of pathogens isolated. Most pneumococcal isolates were of serotypes contained in PCVs. Antigen and PCR testing of CSF improves sensitivity for IBD pathogens.

Treatment of Multisystem Inflammatory Syndrome in Children.

BACKGROUND: Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS: We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS: Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS: We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).

Degradation of the Endothelial Glycocalyx Contributes to Metabolic Acidosis in Children Following Cardiopulmonary Bypass Surgery.

OBJECTIVES: Cardiopulmonary bypass surgery is complicated by metabolic acidosis, microvascular dysfunction, and capillary leak. The glycocalyx-a layer of proteins and sugars lining the vascular endothelium-is degraded during cardiopulmonary bypass. We aimed to describe the kinetics of glycocalyx degradation during and following cardiopulmonary bypass. We hypothesized that cleavage of negatively charged fragments of the glycocalyx would directly induce metabolic acidosis through changes in the strong ion gap (defined using Stewart's physicochemical approach to acid-base chemistry). We also investigated whether glycocalyx degradation was associated with failure of endothelial function and cardiovascular dysfunction. DESIGN: Single-center prospective cohort study. SETTING: Twenty-two bed surgical/medical PICU. PATIENTS: Twenty-seven term infants and children requiring cardiopulmonary bypass surgery for the correction/palliation of congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We recruited 27 patients, 5 days to 57 months old. We prospectively sampled plasma prior to, during, and following cardiopulmonary bypass at predefined time points. We measured plasma concentrations of interleukin-6 (inflammatory marker), heparan sulfate (negatively charged glycocalyx glycosaminoglycan), and syndecan-1 (neutrally charged glycocalyx protein). We defined the following outcome measures: metabolic acidosis (strong ion gap), renal dysfunction (fold change in creatinine), capillary leak (fluid bolus volume), cardiovascular dysfunction (Vasoactive Inotropic Score), and length of ventilation. In linear regression models, maximum measured heparan sulfate concentration (negatively charged) was associated with metabolic acidosis (p = 0.016), renal dysfunction (p = 0.009), and length of ventilation (p = 0.047). In contrast, maximum measured syndecan-1 concentration (neutrally charged) was not associated with these clinical endpoints (p > 0.30 for all). CONCLUSIONS: Our data show that metabolic acidosis (increased strong ion gap) is associated with plasma concentration of heparan sulfate, a negatively charged glycosaminoglycan cleaved from the endothelial glycocalyx during cardiopulmonary bypass. In addition, cleavage of heparan sulfate was associated with renal dysfunction, capillary leak, and global markers of cardiovascular dysfunction. These data highlight the importance of designing translational therapies to protect the glycocalyx in cardiopulmonary bypass.