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Konzo is a neglected paralytic neurological disease associated with food (cassava) poisoning that affects the worlds poorest children and women of childbearing ages across regions of sub-Saharan Africa. Despite understanding the dietary factors that lead to konzo, the molecular markers and mechanisms that trigger this disease remain unknown. To identify potential protein biomarkers associated with a disease status, plasma was collected from two independent Congolese cohorts, a discovery cohort (n = 60) and validation cohort (n = 204), sampled 10 years apart and subjected to multiple high-throughput assays. We identified that Glutathione Peroxidase 3 (GPx3), a critical plasma-based antioxidant enzyme, was the sole protein examined that was both significantly and differentially abundant between affected and non-affected participants in both cohorts, with large reductions observed in those affected with konzo. Our findings raise the notion that reductions in key antioxidant mechanisms may be the biological risk factor for the development of konzo, particularly those mediated through pathways involving the glutathione peroxidase family.

The fundamental trade-off between current and future reproduction has long been considered to result in a tendency for species that can grow large to begin reproduction at a larger size. Due to the prolonged time required to reach maturity, estimates of tree maturation size remain very rare and we lack a global view on the generality and the shape of this trade-off. Using seed production from five continents, we estimate tree maturation sizes for 486 tree species spanning tropical to boreal climates. Results show that a species' maturation size increases with maximum size, but in a non-proportional way: the largest species begin reproduction at smaller sizes than would be expected if maturation were simply proportional to maximum size. Furthermore, the decrease in relative maturation size is steepest in cold climates. These findings on maturation size drivers are key to accurately represent forests' responses to disturbance and climate change.

BACKGROUND: Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero. METHODS: In this prospective cohort study, we included infants from two cohorts of normocephalic children born in León and Managua, Nicaragua during the 2016 Zika epidemic. In León, all women pregnant during the two enrolment periods were eligible. In Managua, mother-child pairs were included from three districts in the municipality of Managua: all women who became pregnant before June 15, 2016, and had a due date of Sept 15, 2016 or later were eligible. Infants were serologically classified as Zika virus-exposed or Zika virus-unexposed in utero and were followed up prospectively until age 48 months. At 36 months and 48 months of age, the Mullen Scales of Early Learning (MSEL) assessment was administered. Primary outcomes were MSEL early learning composite (ELC) scores at 30-48 months in León and 36-48 months in Managua. We used an inverse probability weighting generalised estimating equations model to assess the effect of Zika virus exposure on individual MSEL cognitive domain scores and ELC scores, adjusted for maternal education and age, poverty status, and infant sex. FINDINGS: The initial enrolment period for the León cohort was between Jan 31 and April 5, 2017 and the second was between Aug 30, 2017, and Feb 22, 2018. The enrolment period for the Managua cohort was between Oct 24, 2019, and May 5, 2020. 478 mothers (482 infants) from the León cohort and 615 mothers (609 infants) from the Managua cohort were enrolled, of whom 622 children (303 from the León cohort; 319 from the Managua cohort) were included in the final analysis; four children had microcephaly at birth and thus were excluded from analyses, two from each cohort. 33 (11%) of 303 children enrolled in León and 219 (69%) of 319 children enrolled in Managua were exposed to Zika virus in utero. In both cohorts, no significant differences were identified in adjusted mean ELC scores between Zika virus-exposed and unexposed infants at 36 months (between-group difference 1·2 points [95% CI -4·2 to 6·5] in the León cohort; 2·8 [-2·4 to 8·1] in the Managua cohort) or at 48 months (-0·9 [-10·8 to 8·8] in the León cohort; 0·1 [-5·1 to 5·2] in the Managua cohort). No differences in ELC scores between Zika virus-exposed and unexposed infants exceeded 6 points at any time between 30 months and 48 months in León or between 36 months and 48 months in Managua, which was considered clinically significant in other settings. INTERPRETATION: We found no significant differences in neurodevelopmental scores between normocephalic children with in-utero Zika virus exposure and Zika virus-unexposed children at age 36 months or 48 months. These findings are promising, supporting typical neurodevelopment in Zika virus-exposed normocephalic children, although additional follow-up and research is warranted. FUNDING: National Institute of Child Health and Development, National Institute of Allergy and Infectious Diseases, and Fogarty International Center. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

The present study investigated whether distinct developmental patterns of externalizing behaviors (EBs: hyperactivity-impulsivity, noncompliance, physical aggression) based on parent reports were repeatedly and differentially associated with separate dimensions of internalizing problems such as general anxiety, separation anxiety, and depressive symptoms across the early, middle, and late preschool years in a population birth cohort (N = 2,057, 50.7% boys). Six high trajectory classes obtained by latent growth modeling were used as longitudinal indicators of single EB and co-occurrent EBs. Children following low or moderate trajectories for all EBs served as the reference class. Results revealed that children in trajectory classes reflecting high levels of co-occurring EBs showed higher levels of general anxiety, separation anxiety, and depressive symptoms across the preschool years. In contrast, children in trajectory classes reflecting single EB manifested higher levels of some, but not all, dimensions of internalizing problems. In addition, their scores varied from one period to another. No sex differences were observed in the above associations. These results underline the need for comprehensive assessments across distinct types of EBs and internalizing problems to better reflect the characteristics that distinguish individual children. Finally, results suggest that children showing early co-occurrent EBs and internalizing symptoms may be an important group to target for in-depth assessment and possibly preventive intervention.

Starting in fall of 2020, two faculty created and facilitated a book study with teacher candidates the semester before they entered student teaching. They read "This Book is Anti-Racist" by Tiffany Jewell and viewed the content through their own personal journey lenses and also applied the ideas to how they hope to bring anti-racism and multiculturalism into their teaching practice. In the spring of 2022, they conducted a pilot study to gauge the effectiveness in increasing teacher candidates' confidence in bringing anti-racism and cultural responsiveness to their teaching. Their initial findings showed promising results with a small sample size. They have progressed to over tripling their sample size during the fall 2022 semester with the hypothesis of seeing the promising pilot results further confirmed. This study has inspired ideas for future study and considerations for programmatic improvements, all with making anti-racism the norm for the teaching profession.

We investigated whether child temperament (negative emotionality, 5 months) moderated the association between maternal stimulation (5 months--2½ years) and academic readiness and achievement (vocabulary, mathematics, and reading). We applied structural equation modeling to the data from the Quebec Longitudinal Study of Child Development (N = 1121-1448; mostly Whites; 47% girls). Compared to children with low negative emotionality, those with high negative emotionality had higher levels of academic readiness (6 years) and mathematics achievement (7 years) when exposed to high levels of maternal stimulation ([Beta] = 3.17, p < 0.01 and [Beta] = 2.91, p < 0.01, respectively). The results support the differential susceptibility model whereby highly emotionally negative children were more susceptible to the influences of low and high levels of maternal stimulation in academic readiness and mathematics achievement's developments.

According to the failure model (Patterson & Capaldi, 1990), peer rejection is the intermediary link between problem behaviors and internalizing symptoms. The present study tested the model with 464 monozygotic and same-sex dizygotic twin pairs (234 female, 230 male dyads). Teacher-reported reactive aggression and internalizing symptoms, and peer-reported peer rejection were collected at ages 6, 7, and 10 (from 2001 to 2008). Support for the failure model emerged in conventional non-genetically controlled analyses, but not twin-difference score analyses (which remove shared environmental and genetic contributions). Univariate biometric models attributed minimal variance in failure model variables to shared environmental factors, suggesting that genetic factors play an important unacknowledged role in developmental pathways historically ascribed to nonshared experiences in the failure model.

High-energy (above a few hundred GeV) atmospheric muons are a natural probe for geophysical studies. They can travel through kilometres of rock allowing for a radiography of the density distribution within large structures, like mountains or volcanoes. A collaboration between volcanologists, astroparticle and particle physicists, Tomuvol was formed in 2009 to study tomographic muon imaging of volcanoes with high-resolution, large-scale tracking detectors. We report on two campaigns of measurements at the flank of the Puy de Dôme using glass resistive plate chambers (GRPCs) developed for particle physics, within the CALICE collaboration.

One of the main sources of background for the radiography of volcanoes using atmospheric muons comes from the accidental coincidences produced in the muon telescopes by charged particles belonging to the air shower generated by the primary cosmic ray. In order to quantify this background effect, Monte Carlo simulations of the showers and of the detector are developed by the TOMUVOL collaboration. As a first step, the atmospheric showers were simulated and investigated using two Monte Carlo packages, CORSIKA and GEANT4. We compared the results provided by the two programs for the muonic component of vertical proton-induced showers at three energies: 1, 10 and 100 TeV. We found that the spatial distribution and energy spectrum of the muons were in good agreement for the two codes.

Muon imaging of volcanoes and of geological structures in general is actively being developed by several groups in the world. It has the potential to provide 3-D density distributions with an accuracy of a few percent. At this stage of development, comparisons with established geophysical methods are useful to validate the method. An experiment has been carried out in 2011 and 2012 on a large trachytic dome, the Puy de Dôme volcano, to perform such a comparison of muon imaging with gravimetric tomography and 2-D electrical resistivity tomography. Here, we present the preliminary results for the last two methods. North–south and east–west resistivity profiles allow us to model the resistivity distribution down to the base of the dome. The modelling of the Bouguer anomaly provides models for the density distribution within the dome that are directly comparable with the results from the muon imaging. Our ultimate goal is to derive a model of the dome using the joint interpretation of all sets of data.

Introduction: Epinephrine continues to be a fundamental part of the Advanced Cardiac Life Support algorithm despite a lack of evidence that it improves neurologically intact survival. Our aim was both to identify a potential upper limit of epinephrine use in resuscitations and to demonstrate real-world epinephrine use in different patient subgroups.Methods: This was a single-center, retrospective cohort study, conducted between August 1, 2016–July 1, 2021, of patients with medical cardiac arrest who were administered a known number of epinephrine doses. The primary outcome was neurologically intact discharge defined by a modified Rankin scale ≤3, with secondary outcomes of comparing epinephrine doses by age, rhythm, and emergency medical services vs emergency department administration of epinephrine.Results: The study included 1,330 patients, with 184 patients (13.8%) surviving to neurologically intact discharge. The primary outcome of neurologically intact discharge was found in 89 (65.4%) patients in the zero epinephrine dose group, 75 (20.0%) in the 1-3 dose group, 15 (4.3%) in the 4-6 dose group, and one (0.002%) in the ≥7 dose group (P < 0.001). Patients received similar amounts of epinephrine when stratified by age, while patients with shockable rhythms received more epinephrine than patients with non-shockable rhythms.Conclusion: There was a significant decrease in neurologically intact discharge with increasing number of epinephrine doses, and our data suggests that seven or more doses of epinephrine is almost always futile. While further prospective studies are needed, clinicians should consider epinephrine doses when weighing the futility or benefit of continued resuscitation efforts.

While schools are the center of attention in many regards throughout the COVID-19 pandemic, programs that prepare educators have not received nearly as much attention. How has the reliance on technology, shifts in daily norms with health precautions, and other pandemic-related changes affected how colleges and universities are preparing teachers for their careers? This article walks the reader through the pandemic, from spring 2020, when the virus first shut down the US in most ways, to the winter of 2021. The authors, two educator preparation faculty members from both public and private higher education institutions in Massachusetts, reflect on their experiences navigating the challenges and enriching insights the pandemic brought to their work. Considerations for future implications for the field of teacher-preparation are delineated to think about the long-term effects this pandemic could have on higher education and K-12 education.