Transcriptional changes involved in neuronal recovery after sports-related concussion (SRC) may be obscured by inter-individual variation in mRNA expression and nonspecific changes related to physical exertion. Using a co-twin study, the objective of this study was to identify important differences in mRNA expression among a single pair of monozygotic (MZ) twins discordant for concussion. A pair of MZ twins were enrolled as part of a larger study of concussion biomarkers among collegiate athletes. During the study, Twin A sustained SRC, allowing comparison of mRNA expression to the nonconcussed Twin B. Twin A clinically recovered by Day 7. mRNA expression was measured pre-injury and at 6 h and 7 days postinjury using Affymetrix HG-U133 Plus 2.0 microarray. Changes in mRNA expression from pre-injury to each postinjury time point were compared between the twins; differences >1.5-fold were considered important. Kyoto Encyclopedia of Genes and Genomes identified biologic networks associated with important transcripts. Among 38,000 analyzed genes, important changes were identified in 153 genes. The ErbB (epidermal growth factor receptor) signaling pathway was identified as the top transcriptional network from pre-injury to 7 days postinjury. Genes in this pathway with important transcriptional changes included epidermal growth factor (2.41), epiregulin (1.73), neuregulin 1 (1.54) and mechanistic target of rapamycin (1.51). In conclusion, the ErbB signaling pathway was identified as a potential regulator of clinical recovery in a MZ twin pair discordant for SRC. A co-twin study design may be a useful method for identifying important gene pathways associated with concussion recovery.

Recent reports implicate both the liver fluke Opisthorchis viverrini as a reservoir of Helicobacter pylori within the human gastrointestinal tract and H. pylori in the pathogenesis of opisthorchiasis-associated cholangiocarcinoma. We postulated that adherence of bacterial ligands to host receptors initiates colonization of the live fluke by H. pylori and here we aimed to assess the molecular interaction between O. viverrini and H. pylori by investigating host receptors for H. pylori in the fluke. Several known receptors of H. pylori including Lewis B, sialyl-Lewis X, Toll-like receptor 4 and L-fucose were detected immunohistochemically and histochemically by focusing analysis on the gut epithelium and tegument of the adult stage of the fluke. The frequency of detection of Lewis B, sialyl-Lewis X, TLR4 and L-fucose in 100 individual worms was 3, 3, 19 and 70%, respectively. Detection of H. pylori by a diagnostic ureA gene-based PCR assay revealed the presence of H. pylori in individual O. viverrini worms in 41 of 49 (79%) worms examined. In addition, numbers of bacteria decreased in a dose- and time-dependent fashion following exposure to fucosidase. These findings suggested that L-fucose represents a tractable receptor for H. pylori that can mediate bacterial colonization of the gut of O. viverrini.

This study aimed to explore the association between hyperglycemia in pregnancy (type 2 diabetes (T2D) and gestational diabetes mellitus (GDM)) and child developmental risk in Europid and Aboriginal women.

PANDORA is a longitudinal birth cohort recruited from a hyperglycemia in pregnancy register, and from normoglycemic women in antenatal clinics. The Wave 1 substudy included 308 children who completed developmental and behavioral screening between age 18 and 60 months. Developmental risk was assessed using the Ages and Stages Questionnaire (ASQ) or equivalent modified ASQ for use with Aboriginal children. Emotional and behavioral risk was assessed using the Strengths and Difficulties Questionnaire. Multivariable logistic regression was used to assess the association between developmental scores and explanatory variables, including maternal T2D in pregnancy or GDM.

After adjustment for ethnicity, maternal and child variables, and socioeconomic measures, maternal hyperglycemia was associated with increased developmental “concern” (defined as score ≥1 SD below mean) in the fine motor (T2D odds ratio (OR) 5.30, 95% CI 1.77–15.80; GDM OR 3.96, 95% CI 1.55–10.11) and problem-solving (T2D OR 2.71, 95% CI 1.05–6.98; GDM OR 2.54, 95% CI 1.17–5.54) domains, as well as increased “risk” (score ≥2 SD below mean) in at least one domain (T2D OR 5.33, 95% CI 1.85–15.39; GDM OR 4.86, 95% CI 1.95–12.10). Higher maternal education was associated with reduced concern in the problem-solving domain (OR 0.27, 95% CI 0.11–0.69) after adjustment for maternal hyperglycemia.

Maternal hyperglycemia is associated with increased developmental concern and may be a potential target for intervention so as to optimize developmental trajectories.

An antiviral effect of lithium has been proposed, but never investigated for coronavirus disease 2019 (COVID-19). Using electronic health records of 26 554 patients with documented serum lithium levels during the pandemic, we show that the 6-month COVID-19 infection incidence was lower among matched patients with ‘therapeutic’ (0.50–1.00) versus ‘subtherapeutic’ (0.05–0.50) lithium levels (hazard ratio (HR) = 0.82, 95% CI 0.69–0.97, P = 0.017) and among patients with ‘therapeutic’ lithium levels versus matched patients using valproate (HR = 0.79, 95% CI 0.67–0.92, P = 0.0023). Lower rates of infection were observed for both new COVID-19 diagnoses and positive polymerase chain reaction tests, regardless of underlying psychiatric diagnosis and vaccination status.

Early psychosocial adversities exist at many levels, including caregiving-related, extrafamilial, and sociodemographic, which despite their high interrelatedness may have unique impacts on development. In this paper, we focus on caregiving-related early adversities (crEAs) and parse the heterogeneity of crEAs via data reduction techniques that identify experiential cooccurrences. Using network science, we characterized crEA cooccurrences to represent the comorbidity of crEA experiences across a sample of school-age children (n = 258; 6–12 years old) with a history of crEAs. crEA dimensions (variable level) and crEA subtypes (subject level) were identified using parallel factor analysis/principal component analysis and graph-based Louvain community detection. Bagging enhancement with cross-validation provided estimates of robustness. These data-driven dimensions/subtypes showed evidence of stability, transcended traditional sociolegally defined groups, were more homogenous than sociolegally defined groups, and reduced statistical correlations with sociodemographic factors. Finally, random forests showed both unique and common predictive importance of the crEA dimensions/subtypes for childhood mental health symptoms and academic skills. These data-driven outcomes provide additional tools and recommendations for crEA data reduction to inform precision medicine efforts in this area.

Among bilinguals, language-related variables such as first and second language proficiency and balance may be related to important cognitive and academic outcomes, but approaches to characterizing these variables are inconsistent, particularly among at-risk samples of children. The current study employed comprehensive language assessment of English and Spanish language skills and contrasted various approaches to the characterization of language among at-risk ELs in middle school (N = 161). Specifically, we contrasted variable-centered and person-centered approaches, and convergence between objective and self-report measures. Findings support a two-factor structure of English and Spanish language skills in this population, three profiles of students (balanced, moderately unbalanced-higher Spanish, and very unbalanced-higher English), convergence between variable-centered and person-centered approaches, and mixed support for subjective indices of usage. Results provide a foundation from which to examine the roles of L1 and L2 proficiency as well as balance in important cognitive and academic outcomes in this at-risk and understudied population.

Anisotropic heat conduction in a plasma embedded in a magnetic field with irregular, possibly chaotic, field lines is discussed. If the collisional mean free path exceeds the electron gyroradius, the heat conductivity is much larger along the field lines than across them, and this enhances the transport across a domain where good flux surfaces do not exist. Recognising that anisotropic heat conduction may be cast in a variational form, and by constructing increasingly sophisticated trial functions that are based on invariant and almost-invariant structures under the magnetic field-line flow, bounds are derived on this enhancement and on the temperature variation along the magnetic field. In this way, remarkably accurate approximations for the temperature can be rapidly constructed without solving the diffusion equation, even in the small perpendicular-diffusion limit when the solution for the temperature is dominated by the fractal structure the magnetic field lines.

In England, the dominant policy narrative recognises no association between spending on children’s services and quality and a limited association between quality and deprivation. We combined 374 inspection outcomes between 2011 and 2019 with data on preventative and safeguarding expenditure and Indices of Multiple Deprivation (IMD) scores. A multilevel logistic regression model predicting ‘good’ or ‘outstanding’ judgements suggests each £100 increase in preventative spending per child was associated with a 69 per cent increase (95 per cent CI: 27.5 per cent, 124 per cent) in the odds of a positive inspection. A one-decile increase in deprivation was associated with a 16 per cent (95 per cent CI: −25 per cent, −5.7 per cent) decrease. Safeguarding expenditure was not associated with outcomes. Deprived communities have worse access to good-quality children’s services and government policies that have increased poverty and retrenched preventative services have likely exacerbated this inequality. Further, inattention to socioeconomic context in inspections raises concerns about their use in ‘take over’ policies.

Veterinary healthcare workers are in close contact with many different animals and might be at an increased risk of acquiring Clostridioides difficile. In this cross-sectional study, we assessed the prevalence and risk factors of C. difficile carriage in Dutch veterinary healthcare workers. Participants provided a faecal sample and filled out a questionnaire covering potential risk factors for C. difficile carriage. C. difficile culture positive isolates were polymerase chain reaction (PCR) ribotyped and the presence of toxin genes tcdA, tcdB and cdtA/cdtB was determined. Eleven of 482 [2.3%; 95% confidence interval (CI) 1.3–4.0] veterinary healthcare workers were carriers of C. difficile. Three persons carried C. difficile ribotype 078 (0.6%; 95% CI 0.2–1.8). Risk factors for carriage were health/medication and hygiene related, including poor hand hygiene after patient (animal) contact, and did not include occupational contact with certain animal species. In conclusion, the prevalence of C. difficile carriage in veterinary healthcare workers was low and no indications were found that working in veterinary care is a risk for C. difficile carriage.

Youth in the juvenile justice system evince high rates of mental health symptoms, including anxiety and depression. How these symptom profiles change after first contact with the justice system and – importantly – how they are related to re-offending remains unclear. Here, we use latent growth curve modeling to characterize univariate and multivariate growth of anxiety, depression, and re-offending in 1216 male adolescents over 5 years following their first arrest. Overall, the group showed significant linear and quadratic growth in internalizing symptoms and offending behaviors over time such that levels decreased initially after first arrest followed by a small but significant upturn occurring a few years later. Crucially, multivariate growth models revealed strong positive relationships between the rates of growth in internalizing symptoms and offending behaviors such that improvements in mental health related to greater decreases in offending, and vice versa. These results highlight the reciprocal nature of internalizing and externalizing problems in adolescence, underscoring the importance of considering mental health alongside offending in the juvenile justice system.

Given the large anisotropy of transport processes in magnetized plasmas, the magnetic field structure can strongly impact heat diffusion: magnetic surfaces and cantori form barriers to transport while chaotic layers and island structures can degrade confinement. When a small but non-zero amount of perpendicular diffusion is included, the structure of the magnetic field becomes less important, allowing pressure gradients to be supported across chaotic regions and island chains. We introduce a metric for the effective volume over which the local parallel diffusion dominates based on the solution to the anisotropic heat diffusion equation. To validate this metric, we consider model fields with a single island chain and a strongly chaotic layer for which analytic predictions of the relative parallel and perpendicular transport can be made. We also analyse critically chaotic fields produced from different sets of perturbations, highlighting the impact of the mode number spectrum on the heat transport. Our results indicate that this metric coincides with the effective volume of non-integrability in the limit $\kappa _{\perp } \rightarrow 0$, where $\kappa_{\perp}$ is the perpendicular diffusion coefficient. We propose that this metric be used to assess the impact of non-integrability on the heat transport in stellarator equilibria.

Adjoint methods can speed up stellarator optimisation by providing gradient information more efficiently compared with finite-difference evaluations. Adjoint methods are herein applied to vacuum magnetic fields, with objective functions targeting quasi-symmetry and a rotational transform value on a surface. To measure quasi-symmetry, a novel way of evaluating approximate flux coordinates on a single flux surface without the assumption of a neighbourhood of flux surfaces is proposed. The shape gradients obtained from the adjoint formalism are evaluated numerically and verified against finite-difference evaluations.

Wiggle matching is an important and powerful technique in radiocarbon dating that can be used to improve the precision of calendar age estimates. All radiocarbon determinations require calibration to provide calendar age estimates. This calibration is achieved by comparing the determinations against a calibration curve $\mu ( \cdot )$ to calculate the probability the sample arises from any particular calendar age t. Wiggle matching involves the calibration of a set of radiocarbon determinations taken from samples with known separations between their calendar ages. Since the calendar age separations between samples are known, all the calendar ages are known functions of one particular age, ${T_1}$ — commonly the most recent calendar age. Dating the sequence then reduces to considering $p({T_1} = {t_1}|data)$, the probability of the calendar age ${t_1}$ given the set of radiocarbon determinations. In previous work, a Bayesian approach has been used to derive a nice formula for this quantity under the assumption we have independent pointwise estimates of the calibration curve $\mu (t)$. In this paper, we derive a generalization of this formula showing how to incorporate covariance information from the calibration curve under an assumption of multivariate normality.