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A relevant learning space for academics, especially junior researchers, is the academic conference. While conference participation has long been associated with personal attendance at the conference venue, virtual participation is becoming increasingly important. This study investigates the perceived value of a purely virtual academic conference for its participants by analyzing the evaluation feedback (N = 759) from three virtual and two face-to-face LAK conferences. For the purposes of this study, we derive a definition of conference value and identify factors contributing to the overall value rating of virtual academic conferences based on the existing literature. Results indicate a perceived value of virtual conferences comparable with that of face-to-face events, satisfaction with social interaction and topics of interest being the most important predictors. Our insights show that virtual conferences are valuable events for academic professional development and conference organizers can utilize these results to design a valuable event for their participants.

Abstract This study on severe malarial anemia (SMA: Hb < 6.0 g/dL), a leading global cause of childhood morbidity and mortality, compares the entire expressed whole blood host transcriptome between Kenyan children (3-48 mos.) with non-SMA (Hb ≥ 6.0 g/dL, n = 39) and SMA (n = 18). Differential expression analyses reveal 1403 up-regulated and 279 down-regulated transcripts in SMA, signifying impairments in host inflammasome activation, cell death, and innate immune and cellular stress responses. Immune cell profiling shows decreased memory responses, antigen presentation, and immediate pathogen clearance, suggesting an immature/improperly regulated immune response in SMA. Module repertoire analysis of blood-specific gene signatures identifies up-regulation of erythroid genes, enhanced neutrophil activation, and impaired inflammatory responses in SMA. Enrichment analyses converge on disruptions in cellular homeostasis and regulatory pathways for the ubiquitin-proteasome system, autophagy, and heme metabolism. Pathway analyses highlight activation in response to hypoxic conditions [Hypoxia Inducible Factor (HIF)−1 target and Reactive Oxygen Species (ROS) signaling] as a central theme in SMA. These signaling pathways are also top-ranking in protein abundance measures and a Ugandan SMA cohort with available transcriptomic data. Targeted RNA-Seq validation shows strong concordance with our entire expressed transcriptome data. These findings identify key molecular themes in SMA pathogenesis, offering potential targets for new malaria therapies.

Teaching reading to children whose language differs from the oral language of the classroom and from the linguistic structure of academic text adds an additional layer of complexity to reading instruction. There is a large and growing body of evidence indicating that language variation impacts reading, spelling, and writing in predictable ways. In particular, it has been demonstrated that mismatches between the language variety spoken by many African American children in their homes and communities and the written language variety encountered in books and other text can slow the development of reading and writing. The focus of this article is the impact of one language variety, African American English (AAE), on literacy development and on teaching, assessing, and learning. The goal is to describe aspects of instruction, curricula, and assessment that may create obstacles to literacy for African American children (compounding the effects of other factors, such as growing up in systemically under-resourced neighborhoods) and to share ways to modify instructional practices to benefit AAE speakers in significant ways.

Severe malarial anemia (SMA, Hb < 6.0 g/dL) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission zones. This study explored the entire expressed human transcriptome in whole blood from 66 Kenyan children with non-SMA (Hb ≥ 6.0 g/dL, n = 41) and SMA (n = 25), focusing on host immune response networks. RNA-seq analysis revealed 6862 differentially expressed genes, with equally distributed up-and down-regulated genes, indicating a complex host immune response. Deconvolution analyses uncovered leukocytic immune profiles indicative of a diminished antigenic response, reduced immune priming, and polarization toward cellular repair in SMA. Weighted gene co-expression network analysis revealed that immune-regulated processes are central molecular distinctions between non-SMA and SMA. A top dysregulated immune response signaling network in SMA was the HSP60-HSP70-TLR2/4 signaling pathway, indicating altered pathogen recognition, innate immune activation, stress responses, and antigen recognition. Validation with high-throughput gene expression from a separate cohort of Kenyan children (n = 50) with varying severities of malarial anemia (n = 38 non-SMA and n = 12 SMA) confirmed the RNA-seq findings. Proteomic analyses in 35 children with matched transcript and protein abundance (n = 19 non-SMA and n = 16 SMA) confirmed dysregulation in the HSP60-HSP70-TLR2/4 signaling pathway. Additionally, glutamine transporter and glutamine synthetase genes were differentially expressed, indicating altered glutamine metabolism in SMA. This comprehensive analysis underscores complex immune dysregulation and novel pathogenic features in SMA.

BackgroundProlactinomas (PRLs) are prevalent pituitary adenomas associated with metabolic changes and increased cardiovascular morbidity. This study examined clinical, endocrine, metabolic, and inflammatory profiles in PRL patients, aiming to identify potential prognostic markers.MethodsThe study comprised data from 59 PRL patients gathered in a registry at the University Hospital of Zurich. Diagnostic criteria included MRI findings and elevated serum prolactin levels. We assessed baseline and follow-up clinical demographics, metabolic markers, serum inflammation-based scores, and endocrine parameters. Treatment outcomes were evaluated based on prolactin normalization, tumor shrinkage, and cabergoline dosage.ResultsThe PRL cohort exhibited a higher prevalence of overweight/obesity, prediabetes/diabetes mellitus, and dyslipidemia compared to the general population. Significant correlations were found between PRL characteristics and BMI, HbA1c, and fT4 levels. Follow-up data indicated decreases in tumor size, tumor volume, prolactin levels, and LDL-cholesterol, alongside increases in fT4 and sex hormones levels. No significant associations were observed between baseline parameters and tumor shrinkage at follow-up. A positive association was noted between PRL size/volume and the time to achieve prolactin normalization, and a negative association with baseline fT4 levels.ConclusionThis study underscores the metabolic significance of PRL, with notable correlations between PRL parameters and metabolic indices. However, inflammatory markers were not significantly correlated with patient stratification or outcome prediction. These findings highlight the necessity for standardized follow-up protocols and further research into the metabolic pathogenesis in PRL patients.

Many characters in written Chinese incorporate components (radicals) that provide cues to meaning. These cues are often partial, and some are misleading because they are unrelated to the character's meaning. Previous studies have shown that radicals influence the reader's processing of the characters in which they occur (e.g., Feldman and Siok in J Memory Language 40(4):559-576, 1999). We investigated whether readers automatically activate the semantic information associated with a radical even when it is irrelevant to the character's meaning, using a modified version of the Van Orden (Memory Cogn 15(3):181-198, 1987) task with auditory semantic relatedness ratings on test items. Fifty-one Mandarin speakers participated in the study. On each trial they saw a reference category such as "animal" prior to seeing a character then indicated whether the target character was a member of that category. Decisions were slower and less accurate when a target that is not a member of the target category contained a radical that is. For example, if the category is "found in the kitchen," the answer for the target [character omitted] "ticket" is no; however the character contains the misleading radical [character omitted] "knife". These patterns suggest that readers process the semantics of the radical even when it is not relevant to the meaning of the character. The results further verify the role of radical semantics in character processing and raise questions as to whether repetitions of experience with the idiosyncrasies of the script may result in some of the irrelevant semantics influencing the meaning of the character.

IntroductionIn 2012, the World Health Organization revised treatment guidelines for childhood pneumonia with lower chest wall indrawing (LCWI) but no 'danger signs', to recommend home-based treatment. We analysed data from children hospitalized with LCWI pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) study to identify sub-groups with high odds of mortality, who might continue to benefit from hospital management but may not be admitted by staff implementing the 2012 guidelines. We compare the proportion of deaths identified using the criteria in the 2012 guidelines, and the proportion of deaths identified using an alternative set of criteria from our model.MethodsPERCH enrolled a cohort of 2189 HIV-negative children aged 2-59 months who were admitted to hospital with LCWI pneumonia (without obvious cyanosis, inability to feed, vomiting, convulsions, lethargy or head nodding) between 2011-2014 in Kenya, Zambia, South Africa, Mali, The Gambia, Bangladesh, and Thailand. We analysed risk factors for mortality among these cases using predictive logistic regression. Malnutrition was defined as mid-upper-arm circumference ResultsAmong 2189 cases, 76 (3·6%) died. Mortality was associated with oxygen saturation ConclusionsAlthough it focuses on treatment failure in hospital, this study supports the proposal for better risk stratification of children with LCWI pneumonia. Those who have hypoxaemia, any malnutrition or those who were born to HIV positive mothers, experience poorer outcomes than other children with LCWI pneumonia. Consistent identification of these risk factors should be prioritised and children with at least one of these risk factors should not be managed in the community.

There is now considerable evidence regarding the types of interventions that are effective at remediating reading disabilities on average. It is generally unclear, however, what predicts the magnitude of individual-level change following a given intervention. We examine new predictors of intervention gains that are theoretically grounded in computational models of reading and focus on individual differences in the functional organization of the reading system. Specifically, we estimate the extent to which children with reading disabilities (n = 118 3rd-4th graders) rely on two sources of information during an oral word reading task-print-speech correspondences and semantic imageability--before and after a phonologically-weighted intervention. We show that children who relied more on print-speech regularities and less on imageability preintervention had better intervention gains. In parallel, children who over the course of the intervention exhibited greater increases in their reliance on print-speech correspondences and greater decreases in their reliance on imageability, had better intervention outcomes. Importantly, these two factors were differentially related to specific reading task outcomes, with greater reliance on print-speech correspondences associated with pseudoword naming, while (lesser) reliance on imageability related to word reading and comprehension. We discuss the implications of these findings for theoretical models of reading acquisition and educational practice.

Background: The COVID-19 outbreak came with an unprecedented opportunity to investigate how the new reality of social distancing and limited international travel will affect the organization of academic conferences. Objectives: Drawing on conceptualization of academic conferences as professional learning spaces, in this study, we examine the factors associated with the perceived value of purely virtual academic conferences and how such perceptions differ between participants from different research fields. The aim was to gain knowledge about factors that should be considered when designing a virtual conference. Methods: Survey data from participants of three different virtual conferences were collected (N = 311). Kendall's rank correlation and X[superscript 2]-analyses were performed. Results and Conclusion: Results show satisfaction with social interaction, the extent to which presentations met participants' topics of interest and the perceived importance of learning and getting an overview on the research topic to be related to the value rating. Researchers from different research fields differ significantly in their opinion about the most appropriate conference format regarding getting an overview on the research topic. For some researchers, virtual participation might be a valuable alternative to attending a conference in person. The study serves as a first attempt to understand how and for which target groups virtual conferences serve as a valuable learning event. Further research on this conference format is needed.

Learning environments are rich with structure but learning that structure can take considerable effort. Given that thesequence with which knowledge is accumulated is important for development (Smith & Slone, 2017), we consider whetheroptimizing the sequence of training examples can accelerate learning, as evaluated by out of sample generalization. Toexamine this issue we used established connectionist networks that map an orthographic input to a phonological output(Cox, Cooper Borkenhagen, & Seidenberg, 2018; Plaut et al., 1996). Utilizing machine teaching (Sen et al., 2018; Zhu,2015) to optimize word selection for a 10,000 word sequence, we observe an 8% average gain (over 100 sequences) ongeneralization accuracy (from 51% to 59%) compared to matched random sequences. These findings have implicationsfor learning domains where generalization is critical, like reading development where the child needs to gain as muchknowledge as possible from limited experience.

As the COVID-19 pandemic revealed, rapid development of vaccines and therapeutic antibodies are crucial to guarantee a quick return to the status quo of society. In early 2020, we deployed our droplet microfluidic single-cell-based platform DROPZYLLA® for the generation of cognate antibody repertoires of convalescent COVID-19 donors. Discovery of SARS-CoV-2-specific antibodies was performed upon display of antibodies on the surface of HEK293T cells by antigen-specific sorting using binding to the SARS-CoV-2 spike and absence of binding to huACE2 as the sort criteria. This efficiently yielded antibodies within 3–6 weeks, of which up to 100% were neutralizing. One of these, MTX-COVAB, displaying low picomolar neutralization IC50 of SARS-CoV-2 and with a neutralization potency on par with the Regeneron antibodies, was selected for GMP manufacturing and clinical development in June 2020. MTX-COVAB showed strong efficacy in vivo and neutralized all identified clinically relevant variants of SARS-CoV-2 at the time of its selection. MTX-COVAB completed GMP manufacturing by the end of 2020, but clinical development was stopped when the Omicron variant emerged, a variant that proved to be detrimental to all monoclonal antibodies already approved. The present study describes the capabilities of the DROPZYLLA® platform to identify antibodies of high virus-neutralizing capacity rapidly and directly.

Learning to read English requires learning the complex statis-tical dependencies between orthography and phonology. Pre-vious research has focused on how these statistics are learnedin neural network models provided with as much training asneeded. Children, however, are expected to acquire this knowl-edge in a few years of school with only limited instruction. Weexamined how these mappings can be learned efficiently, de-fined by tradeoffs between the number of words that are explic-itly trained and the number that are correct by generalization.A million models were trained, varying the sizes of randomly-selected training sets. For a target corpus of about 3000 words,training sets of 200–300 words were most efficient, producinggeneralization to as many as 1800 untrained words. Composi-tion of the 300 word training sets also greatly affected general-ization. The results suggest directions for designing curriculathat promote efficient learning of complex material.

Background Paediatric community-acquired pneumonia (CAP) is a leading cause of paediatric morbidity. However, particularly for outpatients with paediatric CAP, data on aetiology and management are scarce. Methods The prospective pedCAPNETZ study multicentrically enrols children and adolescents with outpatient-treated or hospitalised paediatric CAP in Germany. Blood and respiratory specimens were collected systematically, and comprehensive analyses of pathogen spectra were conducted. Follow-up evaluations were performed until day 90 after enrolment. Results Between December 2014 and August 2020, we enrolled 486 children with paediatric CAP at eight study sites, 437 (89.9%) of whom had radiographic evidence of paediatric CAP. Median (interquartile range) age was 4.5 (1.6–6.6) years, and 345 (78.9%) children were hospitalised. The most prevalent symptoms at enrolment were cough (91.8%), fever (89.2%) and tachypnoea (62.0%). Outpatients were significantly older, displayed significantly lower C-reactive protein levels and were significantly more likely to be symptom-free at follow-up days 14 and 90. Pathogens were detected in 90.3% of all patients (one or more viral pathogens in 68.1%; one or more bacterial strains in 18.7%; combined bacterial/viral pathogens in 4.1%). Parainfluenza virus and Mycoplasma pneumoniae were significantly more frequent in outpatients. The proportion of patients with antibiotic therapy was comparably high in both groups (92.4% of outpatients versus 86.2% of hospitalised patients). Conclusion We present first data on paediatric CAP with comprehensive analyses in outpatients and hospitalised cases and demonstrate high detection rates of viral pathogens in both groups. Particularly in young paediatric CAP patients with outpatient care, antibiotic therapy needs to be critically debated.

Abstract Background Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in infants. Globally, RSV is responsible for approximately 3.2 million hospital admissions and about 60,000 in-hospital deaths per year. Methods Infection with RespIratory Syncytial Virus (IRIS) is an observational, multi-centre study enrolling infants with severe RSV infection and healthy controls. Inclusion criteria are age between 0 and 36 months and hospitalisation due to RSV infection at three German sites. Exclusion criteria are premature birth, congenital or acquired bronchopulmonary or cardiac diseases, and immunodeficiency. Healthy control probands are enrolled via recruitment of patients undergoing routine surgical procedures. Blood and respiratory specimens are collected upon admission, and RSV and other pathogens are analysed by multiplex polymerase chain reaction. Different biomaterials, including plasma, nasal lining fluid, blood cells, DNA, and RNA specimens, are sampled in a dedicated biobank. Detailed information on demographic characteristics and medical history is recorded, and comprehensive clinical data, including vital signs, medication, and interventions. Discussion The IRIS study aims to discover host and viral factors controlling RSV disease courses in infants. The approach including multi-omics characterisation in clinically well-characterized children with RSV bronchiolitis seeks to improve our understanding of the immune response against this virus. It may disclose novel diagnostic and treatment approaches for respiratory infections in infants. Trial registration: ClinicalTrials.gov, NCT04925310. Registered 01 October 2021—Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04925310?cond=NCT04925310&draw=2&rank=1

Can the science of reading contribute to improving educational practices, allowing more students to become skilled readers? Much has been learned about the behavioral and brain bases of reading, how students learn to read, and factors that contribute to low literacy. The potential to use research findings to improve literacy outcomes is substantial but remains largely unrealized. The lack of improvement in literacy levels, especially among students who face other challenges such as poverty, has led to new pressure to incorporate the science of reading in curricula, instructional practices, and teacher education. In the interest of promoting these efforts, the authors discuss three issues that could undermine them: the need for additional translational research linking reading science to classroom activities, the oversimplified way that the science is sometimes represented in the educational context, and the fact that theories of reading have become more complex and less intuitive as the field has progressed. Addressing these concerns may allow reading science to be used more effectively and achieve greater acceptance among educators.

Neural network models of reading provide a good account of many aspects of normal and disordered performance, butthe training procedures are unrealistically comprehensive. Unlike models, child learners have limited instructional timeand are explicitly taught only a small subset of the words they will regularly encounter. To address this discrepancy weinvestigated alternative learning procedures in a standard orthography-to-phonology multilayer network, to identify oneswhich involve a small, teachable subset of words that facilitate learning untrained words with less effort. We also asked,for any such set, whether the procedure can be improved by optimizing the training sequence. Candidate training setsand sequences were derived using a model-based procedure and from elementary reading curricula. The results indicatetradeoffs between the size and composition of the training set and generalization. These procedures suggest pedagogicalsolutions to the problem of learning more than there is time to teach.

Many Chinese characters consist of probabilistic cues to meaning or pronunciation. We investigated whether readersautomatically activate the semantics associated with a familiar phonetic even when it is putatively irrelevant. In a lexicaldecision task, primes were semantically related to the overall character, the sub-lexical component, or not related to either.Latencies were significantly faster when primes were related to the meaning of the phonetic and related to the meaningof the entire target as compared to unrelated prime-target pairs. The magnitudes of the priming effects were larger forlower frequency targets. Results indicate that readers activate the semantics of a phonetic even when it is unrelated to themeaning of the character. This suggests that the irrelevant semantics may influence the meaning of a character, and alsochallenges standard analyses in which such characters are considered morphemes because phonetics can also contribute tomeaning.

Background: Severe malarial anemia (SMA; Hb < 5.0 g/dl) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions such as western Kenya.Methods: We investigated the relationship between two novel complement component 5 (C5) missense mutations [rs17216529:C>T, p(Val145Ile) and rs17610:C>T, p(Ser1310Asn)] and longitudinal outcomes of malaria in a cohort of Kenyan children (under 60 mos, n = 1,546). Molecular modeling was used to investigate the impact of the amino acid transitions on the C5 protein structure.Results: Prediction of the wild-type and mutant C5 protein structures did not reveal major changes to the overall structure. However, based on the position of the variants, subtle differences could impact on the stability of C5b. The influence of the C5 genotypes/haplotypes on the number of malaria and SMA episodes over 36 months was determined by Poisson regression modeling. Genotypic analyses revealed that inheritance of the homozygous mutant (TT) for rs17216529:C>T enhanced the risk for both malaria (incidence rate ratio, IRR = 1.144, 95%CI: 1.059–1.236, p = 0.001) and SMA (IRR = 1.627, 95%CI: 1.201–2.204, p = 0.002). In the haplotypic model, carriers of TC had increased risk of malaria (IRR = 1.068, 95%CI: 1.017–1.122, p = 0.009), while carriers of both wild-type alleles (CC) were protected against SMA (IRR = 0.679, 95%CI: 0.542–0.850, p = 0.001).Conclusion: Collectively, these findings show that the selected C5 missense mutations influence the longitudinal risk of malaria and SMA in immune-naïve children exposed to holoendemic P. falciparum transmission through a mechanism that remains to be defined.

Abstract Objective To identity phenotypes of self‐reported symptoms of psychopathology and their correlates in patients with temporal lobe epilepsy (TLE). Method 96 patients with TLE and 82 controls were administered the Symptom Checklist 90‐Revised (SCL‐90‐R) to characterize emotional‐behavioral status. The nine symptom scales of the SCL‐90‐R were analyzed by unsupervised machine learning techniques to identify latent TLE groups. Identified clusters were contrasted to controls to characterize their association with sociodemographic, clinical epilepsy, neuropsychological, psychiatric, and neuroimaging factors. Results TLE patients as a group exhibited significantly higher (abnormal) scores across all SCL‐90‐R scales compared to controls. However, cluster analysis identified three latent groups: (1) unimpaired with no scale elevations compared to controls (Cluster 1, 42% of TLE patients), (2) mild‐to‐moderate symptomatology characterized by significant elevations across several SCL‐90‐R scales compared to controls (Cluster 2, 35% of TLE patients), and (3) marked symptomatology with significant elevations across all scales compared to controls and the other TLE phenotype groups (Cluster 3, 23% of TLE patients). There were significant associations between cluster membership and demographic (education), clinical epilepsy (perceived seizure severity, bitemporal lobe seizure onset), and neuropsychological status (intelligence, memory, executive function), but with minimal structural neuroimaging correlates. Concurrent validity of the behavioral phenotype grouping was demonstrated through association with psychiatric (current and lifetime‐to‐date DSM IV Axis 1 disorders and current treatment) and quality‐of‐life variables. Significance Symptoms of psychopathology in patients with TLE are characterized by a series of discrete phenotypes with accompanying sociodemographic, cognitive, and clinical correlates. Similar to cognition in TLE, machine learning approaches suggest a developing taxonomy of the comorbidities of epilepsy.

Abstract Many G protein-coupled receptors (GPCRs) are therapeutic targets, with most drugs acting at the orthosteric site. Some GPCRs also possess allosteric sites, which have become a focus of drug discovery. In the M2 muscarinic receptor, allosteric modulators regulate the binding and functional effects of orthosteric ligands through a mix of conformational changes, steric hindrance and electrostatic repulsion transmitted within and between the constituent protomers of an oligomer. Tacrine has been called an atypical modulator because it exhibits positive cooperativity, as revealed by Hill coefficients greater than 1 in its negative allosteric effect on binding and response. Radioligand binding and molecular dynamics simulations were used to probe the mechanism of that modulation in monomers and oligomers of wild-type and mutant M2 receptors. Tacrine is not atypical at monomers, which indicates that its atypical effects are a property of the receptor in its oligomeric state. These results illustrate that oligomerization of the M2 receptor has functional consequences.

We routinely encounter speakers with different accents andspeaking styles. The speech perception literature offersexamples of disruption of comprehension for unfamiliarspeech and also of listeners’ rapid accommodation tounfamiliar accents. Much of this research uses a singlemeasure and/or focuses on isolated word perception. Weinvestigated listeners’ abilities to comprehend and shadowconnected speech spoken in a familiar or unfamiliar accent.We found increases in shadowing latencies andcomprehension errors in the Dissimilar Speech relative toSimilar Speech conditions—especially for relatively informalrather than more academic style speech. Additionally, therewas less accommodation over time to Dissimilar than SimilarSpeech. These results suggest that there are costs both in theimmediate timescale of processing speech (necessary forshadowing) and in the longer time scale of listeningcomprehension when accent and other speech quality is verydifferent from one’s own speech.

Abstract Background Pediatric community acquired pneumonia (pedCAP) is one of the leading causes for childhood morbidity accounting for up to 20% of pediatric hospital admissions in high income countries. In spite of its high morbidity, updated epidemiological and pathogen data after introduction of preventive vaccination and novel pathogen screening strategies are limited. Moreover, there is a need for validated recommendations on diagnostic and treatment regimens in pedCAP. Through collection of patient data and analysis of pathogen and host factors in a large sample of unselected pedCAP patients in Germany, we aim to address and substantially improve this situation. Methods pedCAPNETZ is an observational, multi-center study on pedCAP. Thus far, nine study centers in hospitals, outpatient clinics and practices have been initiated and more than 400 patients with radiologically confirmed pneumonia have been enrolled, aiming at a total of 1000 study participants. Employing an online data base, information on disease course, treatment as well as demographical and socioeconomical data is recorded. Patients are followed up until day 90 after enrollment; Comprehensive biosample collection and a central pedCAPNETZ biobank allow for in-depth analyses of pathogen and host factors. Standardized workflows to assure sample logistics and data management in more than fifteen future study centers have been established. Discussion Through comprehensive epidemiological, clinical and biological analyses, pedCAPNETZ fills an important gap in pediatric and infection research. To secure dissemination of the registry, we will raise clinical and scientific awareness at all levels. We aim at participating in decision making processes for guidelines and prevention strategies. Ultimately, we hope the results of the pedCAPNETZ registry will help to improve care and quality of life in pedCAP patients in the future.

ObjectiveBenign epilepsy with centrotemporal spikes (BECTS), the most common focal childhood epilepsy, is associated with subtle abnormalities in cognition and possible developmental alterations in brain structure when compared to healthy participants, as indicated by previous cross-sectional studies. To examine the natural history of BECTS, we investigated cognition, cortical thickness, and subcortical volumes in children with new/recent onset BECTS and healthy controls (HC).MethodsParticipants were 8-15 years of age, including 24 children with new-onset BECTS and 41 age- and gender-matched HC. At baseline and 2 years later, all participants completed a cognitive assessment, and a subset (13 BECTS, 24 HC) underwent T1 volumetric magnetic resonance imaging (MRI) scans focusing on cortical thickness and subcortical volumes.ResultsBaseline cognitive abnormalities associated with BECTS (object naming, verbal learning, arithmetic computation, and psychomotor speed/dexterity) persisted over 2 years, with the rate of cognitive development paralleling that of HC. Baseline neuroimaging revealed thinner cortex in BECTS compared to controls in frontal, temporal, and occipital regions. Longitudinally, HC showed widespread cortical thinning in both hemispheres, whereas BECTS participants showed sparse regions of both cortical thinning and thickening. Analyses of subcortical volumes showed larger left and right putamens persisting over 2 years in BECTS compared to HC.SignificanceCognitive and structural brain abnormalities associated with BECTS are present at onset and persist (cognition) and/or evolve (brain structure) over time. Atypical maturation of cortical thickness antecedent to BECTS onset results in early identified abnormalities that continue to develop abnormally over time. However, compared to anatomic development, cognition appears more resistant to further change over time.

The discovery of human remains from the Lauricocha cave in the Central Andean highlands in the 1960's provided the first direct evidence for human presence in the high altitude Andes. The skeletons found at this site were ascribed to the Early to Middle Holocene and represented the oldest known population of Western South America, and thus were used in several studies addressing the early population history of the continent. However, later excavations at Lauricocha led to doubts regarding the antiquity of the site. Here, we provide new dating, craniometric, and genetic evidence for this iconic site. We obtained new radiocarbon dates, generated complete mitochondrial genomes and nuclear SNP data from five individuals, and re-analyzed the human remains of Lauricocha to revise the initial morphological and craniometric analysis conducted in the 1960's. We show that Lauricocha was indeed occupied in the Early to Middle Holocene but the temporal spread of dates we obtained from the human remains show that they do not qualify as a single contemporaneous population. However, the genetic results from five of the individuals fall within the spectrum of genetic diversity observed in pre-Columbian and modern Native Central American populations.

Background: Malaria remains one of the leading global causes of childhood morbidity and mortality. In holoendemic Plasmodium falciparum transmission regions, such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb) < 6.0 g/dl] is the primary form of severe disease. Ubiquitination is essential for regulating intracellular processes involved in innate and adaptive immunity. Although dysregulation in ubiquitin molecular processes is central to the pathogenesis of multiple human diseases, the expression patterns of ubiquitination genes in SMA remain unexplored.Methods: To examine the role of the ubiquitination processes in pathogenesis of SMA, differential gene expression profiles were determined in Kenyan children (n = 44, aged

Background: To respond to the Surgeon General's call to develop, disseminate, and evaluate messages to reduce indoor tanning (IT) in the 2014 Call to Action to Prevent Skin Cancer, an understanding of the IT communication environment is necessary. Purpose: The purpose of this study was to identify the most prevalent false or misleading IT claims. Methods: Pro-tanning websites (N = 78) were identified in a Google search. Using systematic quantitative content analysis, website characteristics were coded, as well as claims regarding health, safety, appearance/social, and mood/relaxation benefits of IT. All text appearing on the websites was reviewed and coded. Results: Two prominent types of claims emerged: health (86%) and IT safety (90%) benefits of IT. Within health, the most common claims were: (1) prevent health conditions (73%) and (2) a base tan provides protection from the sun (41%). Within safety, the most common claims were: (1) safe because it is controlled (81%) and (2) government regulation ensures safety (56%). Discussion: An abundance of misleading claims were identified, prompting concern from a public health perspective, because tanners may use these claims to justify their tanning behavior. Translation to Health Education Practice: By understanding the prevalence of these claims, prevention efforts may be more effective in creating a disruptive association between IT and many advertised "benefits" of engaging in this dangerous behavior.

This article reviews the important role of statistical learning for language and reading development. Although statistical learning--the unconscious encoding of patterns in language input--has become widely known as a force in infants' early interpretation of speech, the role of this kind of learning for language and reading comprehension in children has received less attention. In fact, the implicit learning of co-occurrences of words, sentence structures, and other components of language forms a critical part of children's language comprehension and fluent reading. Beyond introducing basic information about language statistics, the article offers a discussion of how variability in the amount and nature of language experience can affect language development and literacy, including variation owing to the amount of language input in the child's linguistic environment and the variable nature of input for children who are exposed to multiple languages or multiple dialects.

Despite anecdotal evidence of relative visuospatial processing strengths in individuals with reading disability (RD), only a few studies have assessed the presence or the extent of these putative strengths. The current study examined the cognitive and neural bases of visuospatial processing abilities in adolescents with RD relative to typically developing (TD) peers. Using both cognitive tasks and functional magnetic resonance imaging (fMRI) we contrasted printed word recognition with non-language visuospatial processing tasks. Behaviorally, lower reading skill was related to a visuospatial processing advantage (shorter latencies and equivalent accuracy) on a geometric figure processing task, similar to findings shown in two published studies. FMRI analyses revealed key group by task interactions in patterns of cortical and subcortical activation, particularly in frontostriatal networks, and in the distributions of right and left hemisphere activation on the two tasks. The results are discussed in terms of a possible neural tradeoff in visuospatial processing in RD.

ObjectiveAdults with juvenile myoclonic epilepsy (JME) have subtle brain structural abnormalities in the frontothalamocortical network, poorer cognitive function, and worse long-term social outcomes, even when their seizures are controlled and/or remitted. The natural history of JME and development of abnormalities in brain structure and cognition from epilepsy onset has not been studied.MethodsThe maturational trajectories of cognitive and brain development were prospectively compared between 19 children with new-onset JME in the first 2 years after diagnosis and 57 healthy controls.ResultsCognitive abilities of children with JME were similar to or worse than healthy controls at baseline but failed to reach the competence level of healthy controls at follow-up across most of the tested cognitive abilities. Abnormal patterns of brain development, as assessed by magnetic resonance imaging studies, were evident in children with JME and included attenuation of age-related decline in cortical volume, thickness, and surface area compared to typically developing children. The altered brain developmental trajectory in the JME group was evident in higher-association frontoparietotemporal brain regions (p < 0.05, corrected for multiple comparisons).InterpretationChildren with JME have abnormal structural brain development and impaired cognitive development early in the course of their epilepsy.

ObjectiveBirth weight is an important indicator of prenatal environment, and subtle variations of birth weight within the normal range have been associated with differential risk for cognitive and behavioral problems. Therefore, we aimed to determine if there are differences in birth weight between full-term children with uncomplicated new/recent-onset epilepsies and typically developing healthy controls. We further examined the relationships between birth weight and childhood/adolescent cognition, behavior, and academic achievement.MethodsOne hundred eight children with new-onset/recent-onset epilepsy and 70 healthy controls underwent neuropsychological assessment. All participants were born full-term (>37 weeks) without birth complications. Parents were interviewed regarding their child's gestation, birth, and neurodevelopmental history.ResultsBirth weight of children with epilepsy was significantly lower than healthy controls (p = 0.023). Whereas birth weight (covaried with age, sex, handedness, and mother's education) was significantly associated with cognition in controls in multiple domains (intelligence, language, aspects of academic achievement), this relationship was absent in children with epilepsy. Birth weight was not associated with clinical epilepsy variables (age of onset, epilepsy syndrome) and was not predictive of a variety of other academic or psychiatric comorbidities of epilepsy.SignificanceAlthough the origin of lower birth weight in children with epilepsy is unknown, these findings raise the possibility that abnormal prenatal environment may affect childhood-onset epilepsy. Furthermore, the positive relationship between birth weight and cognition evident in healthy controls was disrupted in children with epilepsy. However, birth weight was not related to academic and psychiatric comorbidities of childhood epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Reading disability is a brain-based difficulty in acquiring fluent reading skills that affects significant numbers of children. Although neuroanatomical and neurofunctional networks involved in typical and atypical reading are increasingly well characterized, the underlying neurochemical bases of individual differences in reading development are virtually unknown. The current study is the first to examine neurochemistry in children during the critical period in which the neurocircuits that support skilled reading are still developing. In a longitudinal pediatric sample of emergent readers whose reading indicators range on a continuum from impaired to superior, we examined the relationship between individual differences in reading and reading-related skills and concentrations of neurometabolites measured using magnetic resonance spectroscopy. Both continuous and group analyses revealed that choline and glutamate concentrations were negatively correlated with reading and related linguistic measures in phonology and vocabulary (such that higher concentrations were associated with poorer performance). Correlations with behavioral scores obtained 24 months later reveal stability for the relationship between glutamate and reading performance. Implications for neurodevelopmental models of reading and reading disability are discussed, including possible links of choline and glutamate to white matter anomalies and hyperexcitability. These findings point to new directions for research on gene-brain-behavior pathways in human studies of reading disability.

Barriers to global emergency care development include a critical lack of data in several areas, including limited documentation of the acute disease burden, lack of agreement on essential components of acute care systems, and a lack of consensus on key analytic elements, such as diagnostic classification schemes and regionally appropriate metrics for impact evaluation. These data gaps obscure the profound health effects of lack of emergency care access in low- and middle-income countries (LMICs). As part of the Academic Emergency Medicine consensus conference "Global Health and Emergency Care: A Research Agenda," a breakout group sought to develop a priority research agenda for data collection and management within global emergency care systems.

The chief complaint is a patient's self-reported primary reason for presenting for medical care. The clinical utility and analytical importance of recording chief complaints have been widely accepted in highly developed emergency care systems, but this practice is far from universal in global emergency care, especially in limited-resource areas. It is precisely in these settings, however, that the use of chief complaints may have particular benefit. Chief complaints may be used to quantify, analyze, and plan for emergency care and provide valuable information on acute care needs where there are crucial data gaps. Globally, much work has been done to establish local practices around chief complaint collection and use, but no standards have been established and little work has been done to identify minimum effective sets of chief complaints that may be used in limited-resource settings. As part of the Academic Emergency Medicine consensus conference, "Global Health and Emergency Care: A Research Agenda," the breakout group on data management identified the lack of research on emergency chief complaints globally-especially in low-income countries where the highest proportion of the world's population resides-as a major gap in global emergency care research. This article reviews global research on emergency chief complaints in high-income countries with developed emergency care systems and sets forth an agenda for future research on chief complaints in limited-resource settings.

Summary: Background: Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years. Methods: We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus–associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths. Findings: In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries. Interpretation: Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries. Funding: Bill & Melinda Gates Foundation.