We have previously argued thatbehavioral scientists have been testing and advocating individualistic (i-frame) solutions to policy problems that have systemic (s-frame) causes and require systemic solutions. Here, we consider the implications of adopting an s-frame approach for research. We argue that an s-frame approach will involve addressing different types of questions, which will, in turn, require a different toolbox of research methods.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental endocrine disruptor and model AhR agonist, is linked to skeletal abnormalities, cardiac edema, stunted growth rate, altered metabolism, and neurobehavioral deficits. We have previously reported transgenerational reproductive outcomes of developmental TCDD exposure in adult zebrafish (Danio rerio), an NIH-validated model for developmental and generational toxicology. Using the same paradigm of sublethal TCDD exposure (50 pg/ml) at both 3 and 7 weeks post fertilization (wpf), we investigated several novel endpoints, including longitudinal morphometrics and anxiety-linked behavior, in fish exposed as juveniles. We also assessed developmental abnormalities and neurobehavior in their F1 larval offspring. TCDD exposure induced timepoint-dependent decreases in several craniofacial and trunk morphometrics across juvenile development. In early adulthood, however, only exposed males underwent a transient period of compensatory growth, ending between 7 and 12 months post fertilization (mpf). At 12 mpf, exposed adult fish of both sexes displayed increased exploratory behaviors in a novel tank test. The F1 offspring of parents exposed at both 3 and 7 wpf were hyperactive, but neurobehavioral outcomes diverged depending on parental exposure window. F1 exposure-lineage larvae had increased rates of edema and skeletal abnormalities, but fewer unhatched larvae compared to controls. Parent- and timepoint-specific effects of exposure on abnormality rate were also evaluated; these outcomes were considerably less severe. Our novel behavioral findings expand current knowledge of the long-term and intergenerational consequences of early-life TCDD exposure in a zebrafish model, in addition to delineating minor longitudinal morphometric changes in exposed fish and abnormalities in larval offspring.

Childhood adversities have been linked to psychosocial outcomes, but it remains uncertain whether subtypes of adversity exert different effects on outcomes. Research is also needed to explore the dynamic interplay between adversity and psychosocial outcomes from childhood to mid-adolescence. This study aimed to investigate these relationships and their role in shaping adolescent wellbeing. Data were extracted from three timepoints of the UK Household Longitudinal Survey when participants (n = 646) were aged 10–15. Cross-lagged panel models were used to explore the relationship between cumulative adversities, and separately non-household (i.e., bullying victimization and adverse neighborhood) and household (i.e., sibling victimization, quarrelsome relationship with parents, financial struggles, and maternal psychological distress) adversities, and psychosocial outcomes (i.e., internalizing and externalizing problems, delinquency, and life satisfaction). Our results revealed that heightened cumulative adversity predicted psychosocial outcomes from childhood to mid-adolescence. Increased levels of household adversity predicted psychosocial outcomes throughout early to mid-adolescence, while non-household adversity only predicted psychosocial outcomes in early adolescence. Furthermore, worse psychosocial outcomes predicted higher levels of adversities during adolescence, highlighting bidirectionality between adversity and psychosocial outcomes. These findings underscore the varying impacts of adversity subtypes and the mutually reinforcing effects of adversities and psychosocial functioning from childhood to mid-adolescence.

As children advance through school, derived words become increasingly common in their reading materials. Previous studies have shown that children’s knowledge of derivational morphology develops relatively slowly, but there is more to learn about this development. This study examined differences in knowledge of the form and meaning of suffixes across grade levels (Grades 3, 5, and 8) and different types of derivational suffixes (adjectives and nominals). We assessed 309 English-speaking children on word reading and receptive vocabulary tests and two tasks designed to assess the form (orthographic knowledge) and meaning (semantic knowledge) of 28 derivational suffixes (14 adjectives and 14 nominals). Overall, our findings showed a significant improvement in identifying and understanding derivational suffixes from Grade 3 to Grade 5 and a smaller, but still significant, improvement from Grade 5 to Grade 8. Our findings regarding suffix types were mixed. While written forms of adjectives were identified more accurately than nominals across all grades, this advantage did not extend to the students’ understanding of the meaning of the suffixes. These results highlight the distinction between the identification of suffixes and the understanding of their meaning. We discuss our results in relation to suffix frequency in children’s reading materials.

There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.

Biodesign is a relatively new interdisciplinary field, which has grown rapidly over the last decade (as evidenced for example by the growth in student teams entering the Biodesign Challenge from 9 in 2016 to 52 in 2024).

Languages vary in the mapping of relational terms onto events. For instance, English motion descriptions favor manner (how something moves) verbs over path (where something move) verbs, whereas those of other languages, like Spanish, show the opposite pattern. While these lexicalization biases are malleable, adopting a novel lexicalization pattern can be slow for second language learners. One potential mechanism for learning non-native verb mappings is cross-situational statistical learning (CSSL). However, the application of CSSL to verbs is limited and does not explicitly examine how lexicalization biases may complicate adults’ ability to resolve the referential uncertainty of multiple referents. We ask English-speaking monolingual adults to learn the mappings of ten verbs via CSSL. Verbs mapped onto either manner or path of motion, with the other event component held constant. Adults in both conditions demonstrated successful learning of novel verbs, with adults learning the manner verbs showing more consistent performance across accepting correct referents and rejecting incorrect ones. Our results are the first to demonstrate adults’ use of CSSL to acquire verb meanings that both align with and cut against native lexicalization biases and suggest a limited influence of lexicalization biases on adults’ learning in idealized CSSL conditions.

An ab initio theoretical approach has been used to calculate optimized geometries and the relative energies of various compositional arrangements in structures of dioctahedral smectites based on models consisting of two unit-cells. These calculations indicate that the energy differences between structures having vacancies in sites with cis- or trans-OH coordination are small and that their relative energies vary with the chemical nature of the substitutions. For example, a cis-OH coordination for the vacancy was the most stable when the interlayer charge originated from substitution of Al for Si in the tetrahedral sheet, whereas the trans-coordination was the more stable for most cases of substitution in the octahedral sheet, an exception being Fe(II) for Al where the cis-OH coordination was favored. It seems likely, therefore, that long-range structural disorder will be a common phenomenon in natural phyllosilicate specimens.

In July 2021, Public Health Wales received two notifications of salmonella gastroenteritis. Both cases has attended the same barbecue to celebrate Eid al–Adha, two days earlier. Additional cases attending the same barbecue were found and an outbreak investigation was initiated. The barbecue was attended by a North African community’s social network. On same day, smaller lunches were held in three homes in the social network. Many people attended both a lunch and the barbecue. Cases were defined as someone with an epidemiological link to the barbecue and/or lunches with diarrhoea and/or vomiting with date of onset following these events. We undertook a cohort study of 36 people attending the barbecue and/or lunch, and a nested case-control study using Firth logistic regression. A communication campaign, sensitive towards different cultural practices, was developed in collaboration with the affected community. Consumption of a traditional raw liver dish, ‘marrara’, at the barbecue was the likely vehicle for infection (Firth logistic regression, aOR: 49.99, 95%CI 1.71–1461.54, p = 0.02). Meat and offal came from two local butchers (same supplier) and samples yielded identical whole genome sequences as cases. Future outbreak investigations should be relevant to the community affected by considering dishes beyond those found in routine questionnaires.

Negative pressure wound therapy (NPWT) has significantly advanced wound care and continues to find new applications. Its effects at a molecular level however, remain a subject of debate. The aim of this systematic review is to summarize the current evidence regarding the molecular mechanisms of action of NPWT. Medline, Embase, EBSCO databases and clinical trial registries were searched from inception to January 2023. Clinical studies, animal models or in-vitro studies that quantitatively or semi-quantitatively evaluated the influence of NPWT on growth factors, cytokine or gene-expression in the circulation or wound-bed were included. Risk of Bias assessment was performed using the RoBANS tool for non-randomized studies, the COCHRANE's Risk of Bias 2(ROB-2) tool for randomized clinical studies, OHAT tool for in-vitro studies or the SYRCLE tool for animal model studies. A descriptive summary was collated and the aggregated data is presented as a narrative synthesis. This review included 19 clinical studies, 11 animal studies and 3 in-vitro studies. The effects of NPWT on 43 biomarkers and 17 gene expressions were studied across included studies. NPWT stimulates modulation of numerous local and circulating cytokines and growth factor expressions to promote an anti-inflammatory profile. This is most likely achieved by downregulation of TNFα, upregulation of VEGF, TGF-β and fibronectin.

We present the third data release from the Parkes Pulsar Timing Array (PPTA) project. The release contains observations of 32 pulsars obtained using the 64-m Parkes ‘Murriyang’ radio telescope. The data span is up to 18 yr with a typical cadence of 3 weeks. This data release is formed by combining an updated version of our second data release with $\sim$3 yr of more recent data primarily obtained using an ultra-wide-bandwidth receiver system that operates between 704 and 4032 MHz. We provide calibrated pulse profiles, flux density dynamic spectra, pulse times of arrival, and initial pulsar timing models. We describe methods for processing such wide-bandwidth observations and compare this data release with our previous release.

OBJECTIVES/GOALS: Ebola virus infection causes severe disease and liver injury in humans. Macrophages contribute to inflammatory signaling and are prevalent in the liver. We assessed the activation status, including therapeutic target expression, of hepatic macrophages. METHODS/STUDY POPULATION: We compared formalin-fixed, paraffin-embedded liver tissue from terminal Ebola virus-infected and uninfected control cynomolgus macaques, a gold-standard model for human disease. We characterized region-specific protein and whole transcriptome expression in these tissues using GeoMx Digital Spatial Profiling. Macrophage (CD68+) and leukocyte (CD45+) accumulation in liver tissue was quantified by immunofluorescence image analysis using digital pathology software. RESULTS/ANTICIPATED RESULTS: Macrophage-specific (CD68+) regions in the liver of Ebola virus-infected macaques demonstrated a shift towards an inflammatory gene expression profile, as compared to those from healthy control tissue. These regions showed differential expression of monocyte/macrophage differentiation, antigen presentation, and T cell activation gene sets, which were associated with decreased MHC-II allele expression. Moreover, macrophage-specific regions in the infected macaques showed enriched expression of genes or proteins associated with known immunomodulatory therapeutics, including S100A9, IDO1, and CTLA-4. DISCUSSION/SIGNIFICANCE: These data demonstrate that hepatic macrophages express an inflammatory phenotype, that their ability to present antigens to the adaptive immune system may be impaired, and that they express therapeutically targetable markers for immunomodulation of these cells during Ebola virus infection.