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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.

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.

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.

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.

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 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.

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).]

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.