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This brief analyzes 4-year graduation rates among students ever classified as English learners (ever-ELs) and those never classified as English learners (never-ELs) at the intersections of gender, race/ethnicity, and neighborhood income. We follow two cohorts of New York City students who entered ninth grade in 2013-2014 and 2014-2015 (N = 127,931). We find substantial variations in 4-year graduation among these subgroups, with differential predicted probabilities depending on the student's ever-EL status, race/ethnicity, and neighborhood income. These findings reveal important intersectional disparities in this diverse group of ELs--nuances that are lost when analyzing across a single social dimension and that push us to adopt an intersectional lens in quantitative research on ELs.

Abstract Serial macromolecular crystallography has become a powerful method to reveal room temperature structures of biological macromolecules and perform time-resolved studies. ID29, a flagship beamline of the ESRF 4th generation synchrotron, is the first synchrotron beamline in the world capable of delivering high brilliance microsecond X-ray pulses at high repetition rate for the structure determination of biological macromolecules at room temperature. The cardinal combination of microsecond exposure times, innovative beam characteristics and adaptable sample environment provides high quality complete data, even from an exceptionally small amount of crystalline material, enabling what we collectively term serial microsecond crystallography (SµX). After validating the use of different sample delivery methods with various model systems, we applied SµX to an integral membrane receptor, where only a few thousands diffraction images were sufficient to obtain a fully interpretable electron density map for the antagonist istradefylline-bound A2A receptor conformation, providing access to the antagonist binding mode. SµX, as demonstrated at ID29, will quickly find its broad applicability at upcoming 4th generation synchrotron sources worldwide and opens a new frontier in time-resolved SµX.

Abstract Coulomb explosion is an established momentum imaging technique, where the molecules are ionized multiple times on a femtosecond time scale before breaking up into ionized fragments. By measuring the momentum of all the ions, information about the initial molecular structure is theoretically available. However, significant geometric changes due to multiple ionizations occur before the explosion, posing a challenge in retrieving the ground-state structure of molecules from the measured momentum values of the fragments. In this work, we investigate theoretically and experimentally such a connection between the ground-state geometry of a polyatomic molecule (OCS) and the detected momenta of ionic fragments from the Coulomb explosion. By relying on time-dependent density functional theory (TDDFT), we can rigorously model the ionization dynamics of the molecule in the tunneling regime. We reproduce the energy release and the Newton plot momentum patterns of an experiment in which OCS is ionized to the 6+ charge state. Our results provide insight into the behavior of molecules during strong field multiple ionization, opening a way toward precision imaging of real-space molecular geometries using tabletop lasers.

BACKGROUND: Mu opioid receptors (MORs) are key for reward processing, mostly studied in dopaminergic pathways. MORs are also expressed in the dorsal raphe nucleus (DRN), which is central for the modulation of reward and mood, but MOR function in the DRN remains underexplored. Here, we investigated whether MOR-expressing neurons of the DRN (DRN-MOR neurons) participate in reward and emotional responses. METHODS: We characterized DRN-MOR neurons anatomically using immunohistochemistry and functionally using fiber photometry in responses to morphine and rewarding/aversive stimuli. We tested the effect of opioid uncaging on the DRN on place conditioning. We examined the effect of DRN-MOR neuron optostimulation on positive reinforcement and mood-related behaviors. We mapped their projections and selected DRN-MOR neurons projecting to the lateral hypothalamus for a similar optogenetic experimentation. RESULTS: DRN-MOR neurons form a heterogeneous neuronal population essentially composed of GABAergic (gamma-aminobutyric acidergic) and glutamatergic neurons. Calcium activity of DRN-MOR neurons was inhibited by rewarding stimuli and morphine. Local photo-uncaging of oxymorphone in the DRN produced conditioned place preference. DRN-MOR neuron optostimulation triggered real-time place preference and was self-administered, promoted social preference, and reduced anxiety and passive coping. Finally, specific optostimulation of DRN-MOR neurons projecting to the lateral hypothalamus recapitulated the reinforcing effects of total DRN-MOR neuron stimulation. CONCLUSIONS: Our data show that DRN-MOR neurons respond to rewarding stimuli and that their optoactivation has reinforcing effects and promotes positive emotional responses, an activity which is partially mediated by their projections to the lateral hypothalamus. Our study also suggests a complex regulation of DRN activity by MOR opioids, involving mixed inhibition/activation mechanisms that fine-tune DRN function.

Objectives: This study aimed to identify novel fosfomycin resistance genes across diverse environmental samples, ranging in levels of anthropogenic pollution. We focused on fosfomycin resistance, and given its increasing clinical importance, explored the prevalence of these genes within different environmental contexts. Methods: Metagenomic DNA was extracted from wastewater and sediment samples collected from sites in India, Sweden, and Antarctica. Class 1 integron gene cassette libraries were prepared, and resistant clones were selected on fosfomycin-supplemented media. Long-read sequencing was performed followed by bioinformatics analysis to identify novel fosfomycin resistance genes. The genes were cloned and functionally characterized in E. coli, and the impact of phosphonoformate on the enzymes was assessed. Results: Four novel fosfomycin resistance genes were identified. Phylogenetic analysis placed these genes within the FosX family, a group of metalloenzymes that hydrolyse fosfomycin without thiol conjugation. The genes were subsequently renamed fosE2, fosI2, fosI3, and fosP. Functional assays confirmed that these genes conferred resistance to fosfomycin in E. coli, with MIC ranging from 32 μg/ml to 256 μg/ml. Unlike FosA/B enzymes, these FosX-like proteins were resistant to phosphonoformate inhibitory action. A fosI3 homolog was identified in Pseudomonas aeruginosa, highlighting potential clinical relevance. Conclusions: This study expands the understanding of fosfomycin resistance by identifying new FosX family members across diverse environments. The lack of phosphonoformate inhibition underscores the clinical importance of these poorly studied enzymes, which warrant further investigation, particularly in pathogenic contexts.

Abstract Background Respiratory syncytial virus (RSV) is associated with substantial morbidity among infants. This study modelled the potential public health and economic impact of nirsevimab, a long-acting monoclonal antibody, as an immunoprophylactic strategy for all infants in Spain in their first RSV season. Methods A static decision-analytic model of the Spanish birth cohort during its first RSV season was developed to estimate the impact of nirsevimab on RSV-related health events and costs versus the standard of practice (SoP). Spain-specific costs and epidemiological data were used as model inputs. Modelled outcomes included RSV-related outpatient visits, emerging room (ER) visits, hospitalisations – including pediatric intensive care unit (PICU) admission, mechanical ventilation, and inpatient mortality. Results Under the current SoP, RSV caused 151,741 primary care visits, 38,798 ER visits, 12,889 hospitalisations, 1,412 PICU admissions, and 16 deaths over a single season, representing a cost of €71.8 million from a healthcare payer perspective. Universal immunisation of all infants with nirsevimab was expected to prevent 97,157 primary care visits (64.0% reduction), 24,789 ER visits (63.9%), 8,185 hospitalisations (63.5%), 869 PICU admissions (61.5%), and 9 inpatient deaths (52.6%), saving €47.8 million (62.4%) in healthcare costs. Conclusions These results suggest that immunisation with nirsevimab of all infants experiencing their first RSV season in Spain is likely to prevent thousands of RSV-related health events and save considerable costs versus the current SoP.

Abstract Introduction Respiratory syncytial virus (RSV) leads to significant morbidity in newborn infants in the United Kingdom (UK). Nirsevimab, a long-acting monoclonal antibody, received approval from the European Medicines Agency and has been licensed by the Medicines and Healthcare products Regulatory Agency for preventing RSV lower respiratory tract disease (LRTD) in neonates and infants during their first RSV season. The objective of this study was to assess the potential impact of nirsevimab on RSV-associated LRTDs, related costs, and loss of quality-adjusted life years (QALYs) in infants experiencing their first RSV season. Methods The impact of administering nirsevimab across all infant populations compared to palivizumab in the high-risk palivizumab-eligible population was assessed via a static decision-analytic model specified for a UK birth cohort experiencing their first RSV season. The RSV-related health events of interest included primary care (PC), accident and emergency (A&E) visits, hospitalizations [including hospitalizations alone and those resulting in intensive care unit (ICU) admissions], recurrent wheezing in infants who were previously hospitalized, and all-cause LRTD hospitalizations. Results Under the current standard of practice (SoP), RSV was estimated to result in 329,425 RSV LRTDs annually, including 24,381 hospitalizations and ICU admissions, representing £117.8 million (2024 GBP) in costs. Comparatively, universal immunization of all infants with nirsevimab could avoid 198,886 RSV LRTDs, including 16,657 hospitalizations and ICU admissions, resulting in savings of £77.2 million in RSV treatment costs. Considering the impact on all-cause LRTD of a universal immunization strategy, nirsevimab could be valued between £243 and £274, assuming willingness-to-pay (WTP) thresholds of £20,000 and £30,000 per QALY saved, respectively. Conclusions This analysis demonstrated that the health and economic burden of RSV would be substantially reduced in all infants experiencing their first RSV season in the UK (including term, preterm, and palivizumab-eligible infants) as a result of a universal immunization strategy with nirsevimab.

In this brief, we use a nationally representative sample of ever-English learners (ELs; N = 783) to examine relations between EL concentration within classrooms and reading growth between kindergarten and Grade 5. Piecewise growth models were used to estimate relations for four developmental periods (K-1, Grades 1-2, Grades 2-3, and Grades 3-5). Results indicate nonsignificant, trivially sized relations for classroom EL concentration across periods, with and without controls for school concentration and student characteristics. Results were robust across multiple specifications. Findings call into doubt the academic benefits of the common practice of grouping ELs together in particular classrooms.

Abstract Rural households in East Africa rely on local markets, but the influence of market food diversity and household food purchase diversity on diets has not been well‐characterized. We quantify the associations among market food diversity, household food purchase diversity and dietary diversity of mothers, fathers and children in rural Tanzania. This study uses baseline data from a randomized controlled trial, Engaging Fathers for Effective Child Nutrition and Development in Tanzania. We used the 10 food groups for women's dietary diversity to assess the seasonal availability of nutritious foods in 79 markets. Using data from 957 rural households in two districts in Mara, Tanzania, we measured household food purchase diversity over the previous month and dietary diversity among children (6–23 months), mothers and fathers. Overall, 63% of markets sold all 10 food groups throughout the year, indicating high‐market food diversity and minimal seasonality. However, only 33% of women and 35% of children met dietary diversity recommendations. Households that reported higher purchasing power (0.14, p

Background and aims Systemic sclerosis (SSc) is an autoimmune connective disease characterised by excessive extracellular matrix deposition and widespread skin and internal organ fibrosis including various cardiac manifestations. Heart involvement is one of the leading causes of death among patients with SSc. In this study, we aimed to assess the effect of various vasodilator treatments.Methods We used data from a national multicentric prospective study using the French SSc national database. We estimated the average treatment effect (ATE) of sildenafil, bosentan, angiotensin-converting enzyme (ACE) inhibitors and iloprost on diastolic dysfunction, altered ejection fraction

The circulation of seasonal influenza A viruses (IAVs) in humans relies on effective evasion and subversion of the host immune response. While the evolution of seasonal H1N1 and H3N2 viruses to avoid humoral immunity is well characterized, relatively little is known about the evolution of innate immune antagonism phenotypes in these viruses. Numerous studies have established that only a small subset of infected cells is responsible for initiating the type I and type III interferon (IFN) response during IAV infection, emphasizing the importance of single cell studies to accurately characterize the IFN response during infection. We developed a flow cytometry-based method to examine transcriptional changes in IFN and interferon stimulated gene (ISG) expression at the single cell level. We observed that NS segments derived from seasonal H3N2 viruses are more efficient at antagonizing IFN signaling but less effective at suppressing IFN induction, compared to the pdm2009 H1N1 lineage. We compared a collection of NS segments spanning the natural history of the current seasonal IAV lineages and demonstrate long periods of stability in IFN antagonism potential, punctuated by occasional phenotypic shifts. Altogether, our data reveal significant differences in how seasonal and pandemic H1N1 and H3N2 viruses antagonize the human IFN response at the single cell level.

This study examines differences in English language comprehension, reading fluency, and executive functions among Spanish-English bilinguals with reading difficulties. Reading difficulties examined included general reading difficulties, defined by low word reading and reading comprehension, and specific-reading comprehension difficulties, defined by low reading comprehension yet adequate word reading. Participants (N = 86) were categorized using multiple measures of reading comprehension and word reading in each of 6th, 7th, and 8th grade. Participants were also categorized based on persistent difficulties (i.e. remaining in the same group across multiple grades). On two measures of language comprehension, readers with either difficulty tended to demonstrate significant weaknesses relative to average readers. On passage reading fluency, readers with specific-reading comprehension difficulties performed worse than average readers but better than readers with general reading difficulties. On executive functions, readers with general reading difficulties demonstrated weaknesses relative to average readers, but there was little evidence that readers with specific-reading comprehension difficulties showed these weaknesses. These findings typically held when looking at readers with persistently defined difficulties. Longitudinal analyses indicated that 47% of students with S-RCD and 56% of students with GRD remained in their group across the three years, consistent with prior research. Findings highlight potential weaknesses in executive functions for children with general reading difficulties that should be considered when designing instruction for these students. These findings also support prior research on the importance of developing English language and reading fluency for Spanish-English bilingual children with reading difficulties. [This article was published in "Reading & Writing Quarterly" (EJ1344195).]

Organic–inorganic hybrid materials are explored for application as solid electrolytes for lithium-ion batteries. The material consists of a porous silica network, of which the pores are infiltrated by poly(ethylene oxide) and lithium perchlorate. The synthesis involves two steps: First, the inorganic backbone is created by the acid-catalyzed sol-gel synthesis of tetraethyl orthosilicate to ensure continuity of the backbone in three dimensions. In the second step, the polymer and salt are imbued into the porous backbone via solvent exchange. During drying, the cylindrical disk-shaped specimens shrink mainly in the radial direction, which results in spatially non-uniform structural developments. While this inhomogeneity is not discernible in the material's chemical compositional or thermal properties, it is manifest in its ionic conductivity and adiabatic elastic modulus. The ionic conductivity in the center of the specimens is projected to be between one and two orders of magnitude higher than the measured average across the sample diameter. The process that yields a structure with enhanced ionic mobility during post-synthesis physical conditioning is inferred from careful analysis and numerical interpretation of measurable quantities, and the implications for the design of nanostructured hybrid electrolytes with high ionic conductivity are discussed. [ABSTRACT FROM AUTHOR]

Abstract Remarkable advances in protocol development have been achieved to manufacture insulin-secreting islets from human pluripotent stem cells (hPSCs). Distinct from current approaches, we devised a tunable strategy to generate islet spheroids enriched for major islet cell types by incorporating PDX1+ cell budding morphogenesis into staged differentiation. In this process that appears to mimic normal islet morphogenesis, the differentiating islet spheroids organize with endocrine cells that are intermingled or arranged in a core-mantle architecture, accompanied with functional heterogeneity. Through in vitro modelling of human pancreas development, we illustrate the importance of PDX1 and the requirement for EphB3/4 signaling in eliciting cell budding morphogenesis. Using this new approach, we model Mitchell-Riley syndrome with RFX6 knockout hPSCs illustrating unexpected morphogenesis defects in the differentiation towards islet cells. The tunable differentiation system and stem cell-derived islet models described in this work may facilitate addressing fundamental questions in islet biology and probing human pancreas diseases.

The Dangkhar Landslide is an extremely large landslide located in the Spiti Valley of Himachal Pradesh, India. The landslide is situated in a remote high mountain desert within the Tethys Himalaya at elevations between 3400 m and 5600 m. It is amongst the five largest continental landslides on earth, covering an area of approximately 54 km2 and having an estimated volume of 15–20 km3. Geomechanical evaluations based on the block theory indicate that the Dangkhar Landslide formed as a result of unfavorable combinations of structural geological features and complex surface morphology. A massive kinematically removable block is created by a regional synclinal flexure that is crosscut and kinematically liberated by bounding side valleys. Three-dimensional block kinematics are necessary to permit the release of the giant block and its sliding along the synclinal flexure. Pseudostatic slope stability sensitivity analyses incorporating estimates of site seismicity and shear strength parameters suggest that earthquake shaking could have triggered instability if the static factor of safety was less than or in the range of about 1.5–1.9. Considering the glacial history of the region, ice debuttressing represents an additional potential triggering mechanism.

AbstractThe anterior cingulate cortex (ACC) processes the affective component of pain, whereas the primary somatosensory cortex (S1) is involved in its sensory-discriminative component. Injection of morphine in the ACC has been reported to be analgesic, and endogenous opioids in this area are required for pain relief. Mu opioid receptors (MORs) are expressed in both ACC and S1; however, the identity of MOR-expressing cortical neurons remains unknown. Using the Oprm1-mCherry mouse line, we performed selective patch clamp recordings of MOR+ neurons, as well as immunohistochemistry with validated neuronal markers, to determine the identity and laminar distribution of MOR+ neurons in ACC and S1. We found that the electrophysiological signatures of MOR+ neurons differ significantly between these 2 areas, with interneuron-like firing patterns more frequent in ACC. While MOR+ somatostatin interneurons are more prominent in ACC, MOR+ excitatory neurons and MOR+ parvalbumin interneurons are more prominent in S1. Our results suggest a differential contribution of MOR-mediated modulation to ACC and S1 outputs. We also found that females had a greater density of MOR+ neurons compared with males in both areas. In summary, we conclude that MOR-dependent opioidergic signaling in the cortex displays sexual dimorphisms and likely evolved to meet the distinct function of pain-processing circuits in limbic and sensory cortical areas.