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Abstract Globally, climate change represents the most significant threat to the environment and socio-economic development, endangering lives and livelihoods. Within the UN’s current 17 Sustainable Development Goals (SDGs), climate action is explicitly covered under Goal 13, “to take urgent action to combat climate change and its impacts”. This perspective considers how to re-frame the SDGs and their successor towards mainstreaming climate action within the targets and indicators of all the development goals.

Abstract Background Breast cancer, one of the most common forms of cancer, is associated with the highest cancer-related mortality among women worldwide. In comparison to other types of breast cancer, patients diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst outcome because current therapies do not produce long-lasting responses. Hence, innovative therapies that produce persisting responses are a critical need. We previously discovered that hyperactivating purinergic receptors (P2RXs) by increasing extracellular adenosine triphosphate (eATP) concentrations enhances TNBC cell lines’ response to chemotherapy. Heparan sulfate inhibits multiple extracellular ATPases, so it is a molecule of interest in this regard. In turn, heparanase degrades polysulfated polysaccharide heparan sulfate. Importantly, previous work suggests that breast cancer and other cancers express heparanase at high levels. Hence, as heparan sulfate can inhibit extracellular ATPases to facilitate eATP accumulation, it may intensify responses to chemotherapy. We postulated that heparanase inhibitors would exacerbate chemotherapy-induced decreases in TNBC cell viability by increasing heparan sulfate in the cellular microenvironment and hence, augmenting eATP. Methods We treated TNBC cell lines MDA-MB 231, Hs 578t, and MDA-MB 468 and non-tumorigenic immortal mammary epithelial MCF-10A cells with paclitaxel (cytotoxic chemotherapeutic) with or without the heparanase inhibitor OGT 2115 and/or supplemental heparan sulfate. We evaluated cell viability and the release of eATP. Also, we compared the expression of heparanase protein in cell lines and tissues by immunoblot and immunohistochemistry, respectively. In addition, we examined breast-cancer-initiating cell populations using tumorsphere formation efficiency assays on treated cells. Results We found that combining heparanase inhibitor OGT 2115 with chemotherapy decreased TNBC cell viability and tumorsphere formation through increases in eATP and activation of purinergic receptors as compared to TNBC cells treated with single-agent paclitaxel. Conclusion Our data shows that by preventing heparan sulfate breakdown, heparanase inhibitors make TNBC cells more susceptible to chemotherapy by enhancing eATP concentrations.

Abstract The efficient release of magnetic energy in astrophysical plasmas, such as during solar flares, can in principle be achieved through magnetic diffusion, at a rate determined by the associated electric field. However, attempts at measuring electric fields in the solar atmosphere are scarce, and none exist for sites where the magnetic energy is presumably released. Here, we present observations of an energetic event using the National Science Foundation’s Daniel K. Inouye Solar Telescope, where we detect the polarization signature of electric fields associated with magnetic diffusion. We measure the linear and circular polarization across the hydrogen Hε Balmer line at 397 nm at the site of a brightening event in the solar chromosphere. Our spectro-polarimetric modeling demonstrates that the observed polarization signals can only be explained by the presence of electric fields, providing conclusive evidence of magnetic diffusion, and opening a new window for the quantitative study of this mechanism in space plasmas.

In this article, we describe the conceptualization and development of the Secondary Transition Fidelity Assessment (STFA), a measure intended for use by high school leadership teams to examine secondary programs and practices demonstrated by research to lead to meaningful outcomes for secondary students with and without disabilities. We describe our conceptualization and development efforts, which resulted in a measure with six critical features: adolescent engagement, district-level capacity, school-level capacity, community engagement, family engagement, and professional capacity. Based on stakeholder feedback, we revised the STFA and developed an instruction manual and action planning guide to support the self-evaluation of secondary programs and practices using data from the STFA. Recommendations for the field related to research, policy, and practice are provided.

This cluster-randomized efficacy trial evaluated the impact of the Ready for Wages intervention, a classroom-based social skills program designed to improve the employability of youth living and being educated in juvenile justice settings. Fifteen juvenile justice facility schools participated. Data were collected from 118 classrooms: 59 treatment and 59 business-as-usual control. There were no statistically significant differences across conditions on the outcome measures, although differences favored the intervention group. Implementation was hampered by challenges associated with conducting research in authentic juvenile settings during the COVID-19 pandemic. Only half of the planned data collection could be completed. Despite the null findings of this study, more research in juvenile justice facilities is warranted to identify evidence-based practices that support prosocial behavior. Group intervention offers a cost-effective approach to reducing recidivism in a very high-risk population, with potential benefits for individuals and society in general.

The emerging literature on research-practice partnerships in education explains the conditions under which these partnerships operate to achieve the desired impact. This study adds to that literature base by exploring variation in the perceived impacts across three partnerships whose goal was improving achievement for multilingual learner students. To examine these partnerships, we posit a conceptual framework that defines partnership impacts and associated supportive dynamics within the partnership. We use this framework to guide our analysis of interviews and observations from three partnerships. Our study finds (1) practitioners and researchers' motivations to engage in the RPP are different but complementary; (2) practitioners and researchers perceive the RPP as impacting their capacity either to make decisions that change policy and practice or to develop research that is relevant for theory and practice; (3) both researchers and practitioners agree that consistent communication through meetings and reliable funding supports the RPP. Implications for the field and ideas for further research are discussed.

Abstract Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0–36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.

Abstract The sequencing platform and workflow strongly influence microbial community analyses through potential errors at each step. Effective diagnostics and experimental controls are needed to validate data and improve reproducibility. This cross-laboratory study evaluates sources of variability and error at three main steps of a standardized amplicon sequencing workflow (DNA extraction, polymerase chain reaction [PCR], and sequencing) using Oxford Nanopore MinION to analyze agricultural soils and a simple mock community. Variability in sequence results occurs at each step in the workflow with PCR errors and differences in library size greatly influencing diversity estimates. Common bioinformatic diagnostics and the mock community are ineffective at detecting PCR abnormalities. This work outlines several diagnostic checks and techniques to account for sequencing depth and ensure accuracy and reproducibility in soil community analyses. These diagnostics and the inclusion of a reference soil can help ensure data validity and facilitate the comparison of multiple sequencing runs within and between laboratories.

Abstract Respiratory infections caused by the human fungal pathogen Aspergillus fumigatus are a major cause of mortality for immunocompromised patients. Exposure to these pathogens occurs through inhalation, although the role of the respiratory epithelium in disease pathogenesis has not been fully defined. Employing a primary human airway epithelial model, we demonstrate that fungal melanins potently block the post-translational secretion of the chemokines CXCL1 and CXCL8 independent of transcription or the requirement of melanin to be phagocytosed, leading to a significant reduction in neutrophil recruitment to the apical airway both in vitro and in vivo. Aspergillus-derived melanin, a major constituent of the fungal cell wall, dampened airway epithelial chemokine secretion in response to fungi, bacteria, and exogenous cytokines. Furthermore, melanin muted pathogen-mediated calcium fluxing and hindered actin filamentation. Taken together, our results reveal a critical role for melanin interaction with airway epithelium in shaping the host response to fungal and bacterial pathogens.

Abstract Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [18F]F-AraG, a mitochondrial metabolic tracer capable of tracking activated lymphocytes and adipocytes simultaneously, we demonstrate, in models of glioblastoma and multiple sclerosis, the correlation between intracerebral immune infiltration and changes in brown- and bone marrow adipose tissue. Significantly, we show initial evidence that a neuroinflammation-adipose tissue link may also exist in humans. This study proposes the concept of an intricate immuno-neuro-adipose circuit, and highlights brown- and bone marrow adipose tissue as an intermediary in the communication between the immune and nervous systems. Understanding the interconnectedness within this circuitry may lead to advancements in the treatment and management of various conditions, including cancer, neurodegenerative diseases and metabolic disorders.

Water scarcity is increasingly driven by socio-economic dynamics, climate change, and population growth. Conflicts among water users, including states, complicate sustainable water management, necessitating collaborative solutions. Building on important studies in water resource management, this study integrates the Water Evaluation and Planning (WEAP) model with the Nash bargaining solution to develop a fair water allocation system, which we apply to the Lower Bari Doab area of Punjab, Pakistan. This case study area is characterized by high demands for agricultural, domestic, industrial, and environmental water. To ensure fair allocation of water resources, we analyze future water trends, anticipate demands, and address supply-demand gaps under various scenarios. Our findings demonstrate that by utilizing WEAP in conjunction with the Nash bargaining solution, we can effectively achieve a balance between water demand and supply. This approach enables us to compare various water-use strategies and ensures fair distribution among agricultural stakeholders, who often have lower priority compared to the domestic, industrial, and environmental sectors. More importantly, we demonstrate that Nash bargaining solutions can be mutually beneficial and can maximize overall coverage of water demand. This approach ensures that all agents are better off compared to a non-cooperative outcome, promoting fairness and equity by balancing the needs of all parties. This integrated approach provides a robust framework for sustainable water management and is applicable to other regions facing similar challenges.

Calls to identify, explore, and address ethical and social issues as part of the design and implementation of scientific research are now widespread. One way of doing so is through an embedded approach, where ethical, legal, and social implications (ELSI) researchers are situated within larger scientific research studies. We trace the emergence of the ‘embedded ELSI’ approach to integration alongside the development of genomic medicine. In particular, we conduct a conjunctural analysis that draws attention to contests and struggles over the forms and meanings of good science – in this case, genomics – and the role(s) of ELSI scholars and researchers in producing good science. We demonstrate that the embedded ELSI approach emerged from these contests, which left ELSI research and interventions constrained – institutionally, topically, and methodologically. We end by calling for an opening up of embedded approaches to integration so that they might better meet calls for justice and equity in the present conjuncture.

IntroductionAcute infectious disease represents a significant cause of mortality and morbidity in elderly individuals admitted to the hospital. In its extreme, it presents as sepsis, a systematic inflammatory and immunologic response responsible for self-injurious organ injury. As individuals age, a unique set of factors including immunosenescence predispose them to acquiring an infection and a worse clinical prognosis. This systematic review explores the relationship between cellular senescence, an age-related inflammatory phenomenon, with acute human infectious disease.MethodsEmbase via OVID, Scopus, Web of Science, Global Index Medicus, Cochrane Library via Wiley, and ClinicalTrials.gov were queried. Included studies must have compared at least one of the following measures of cellular senescence between patients with an infection and without an infection: cell cycle inhibition measured via levels of p16INK4a and/or p21CIP1, short telomere length, DNA damage via ɣH2AX, high senescence-associated β galactosidase activity, and inflammation via the detection of senescence associated secretory phenotype (SASP). Manuscripts were screened and data collected via two independent reviewers.ResultsA total of 15,828 studies were screened after duplicates were removed. One hundred and fifty-three full-text articles were assessed for eligibility and a total of 16 original articles were included in analysis. Of the 16 original articles included, 12 (75%) articles were centered on SARS-CoV-2, 2 (12.5%) articles utilized patients infected with Leishmania braziliensis, 1 (6.25%) with Plasmodium falciparum, and 1 (6.25%) with Hepatitis C.ConclusionCurrent literature demonstrates robust upregulation of markers of cellular senescence in the setting of acute SARS-CoV-2, P. falciparum, L. braziliensis, and hepatitis C virus, and that markers of senescence correlate with disease severity and persist for months after resolution. Limitations in the number and types of infectious organisms studied, low sample sizes, modest longitudinal sampling, and a lack of consistency in markers measured, the method of measurement, and the definition of normal values represent ongoing gaps in the literature.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=421473, Identifier CRD42023421473.

Background: There is conflicting evidence regarding the effect of residual transmitral mean pressure gradient (TMPG) after mitral transcatheter edge-to-edge repair (M-TEER). Different TMPG cutoffs have been employed in prior studies with varying results. Objectives: The purpose of this study was to examine the association between residual TMPG and M-TEER outcomes. Methods: Consecutive patients undergoing M-TEER at our institution between 2014 and 2022 were included and divided based on quartiles of predischarge TMPG. Outcomes were assessed using Kaplan-Meier analysis and Cox proportional hazard models. We performed subgroup analyses according to mitral regurgitation (MR) mechanism. The primary outcome was all-cause mortality or heart failure hospitalization. Results: We included 283 patients (age 76.7 ± 10.8 years, 42.8% women, 78.4% Caucasian, and baseline TMPG 2.4 ± 1.3 mm Hg). Higher baseline TMPG was a predictor of increased TMPG after M-TEER (coefficient 0.60 [95% CI: 0.40-0.70]; P

Objective: New echocardiographic definitions have been proposed for hemodynamic structural valve deterioration. We aimed to study their consistency in classifying structural valve deterioration after surgical aortic valve replacement. Methods: Data were used of patients undergoing surgical aortic valve replacement in a multicenter, prospective cohort study with a 5-year follow-up. All patients received the same stented bioprosthesis. Echocardiographic parameters were assessed by an independent core laboratory. Moderate or greater stenotic hemodynamic structural valve deterioration was defined according to Capodanno and colleagues, Dvir and colleagues, and the Valve Academic Research Consortium 3; regurgitation data were not considered in this analysis. Consistency was quantified on the basis of structural valve deterioration classification at subsequent time points. Results: A total of 1118 patients received implants. Patients’ mean age was 70 years, and 75% were male. Hemodynamic structural valve deterioration at any visit was present in 51 patients (4.6%), 32 patients (2.9%), and 34 patients (3.0%) according to Capodanno, Dvir, and Valve Academic Research Consortium 3. A total of 1064 patients (95%) were never labeled with structural valve deterioration by any definition. After the first classification with structural valve deterioration, 59%, 59%, and 65% had no subsequent structural valve deterioration classification according to Capodanno, Dvir, and Valve Academic Research Consortium 3, respectively. Conclusions: The current definitions of hemodynamic structural valve deterioration are strong negative predictors but inconsistent positive discriminators for the detection of stenotic hemodynamic structural valve deterioration. Although the diagnosis of structural valve deterioration may be categorical, echocardiographic indices lack this degree of precision in the first 5 years after surgical aortic valve replacement. The inconsistency of current structural valve deterioration definitions impedes the detection of true valve degeneration, which challenges the clinical usefulness of these definitions.

Abstract Background The Veterans Health Administration (VHA) is the United States largest learning health system. The Diffusion of Excellence (DoE) program is a large-scale model of diffusion that identifies and diffuses evidence-informed practices across VHA. During the period of 2016-2021, 57 evidence-informed practices were implemented across 82 VHA facilities. This setting provides a unique opportunity to understand sustainment determinants and pathways. Our objective was to characterize the longitudinal pathways of practices as they transition from initial implementation to long-term sustainment at each facility. Methods A longitudinal, mixed-methods evaluation of 82 VHA facilities. Eighty-two facility representatives, chosen by leadership as points-of-contact for 57 DoE practices, were eligible for post-implementation interviews and annual sustainment surveys. Primary outcomes (implementation, sustainment), and secondary outcomes (institutionalization, effectiveness, anticipated sustainment) at four time-points were collected. We performed descriptive statistics and directed content analysis using Hailemariam et al.’s factors influencing sustainment. Results After approximately five years post-implementation (e.g., 2021 sustainment outcomes), of the 82 facilities, about one-third fully sustained their practice compared to one-third that did not fully sustain their practice because it was in a “liminal” stage (neither sustained nor discontinued) or permanently discontinued. The remaining one-third of facilities had missing 2021 sustainment outcomes. A higher percentage of facilities (70%) had inconsistent primary outcomes (changing over time) compared to facilities (30%) with consistent primary outcomes (same over time). Thirty-four percent of facilities with sustained practices reported resilience since they overcame implementation and sustainment barriers. Facilities with sustained practices reported more positive secondary outcomes compared to those that did not sustain their practice. Key factors facilitating practice sustainment included: demonstrating practice effectiveness/benefit, sufficient organizational leadership, sufficient workforce, and adaptation/alignment with local context. Key factors hindering practice sustainment included: insufficient workforce, not able to maintain practice fidelity/integrity, critical incidents related to the COVID-19 pandemic, organizational leadership did not support sustainment of practice, and no ongoing support. Conclusions We identified diverse pathways from implementation to sustainment, and our data underscore that initial implementation outcomes may not determine long-term sustainment outcomes. This longitudinal evaluation contributes to understanding impacts of the DoE program, including return on investment, achieving learning health system goals, and insights into achieving high-quality healthcare in VHA.

Abstract Background Mucopolysaccharidosis (MPS) IIIB, also known as Sanfilippo Syndrome B, is a devastating childhood disease. Unfortunately, there are currently no available treatments for MPS IIIB patients. Yet, animal models of lysosomal storage diseases have been valuable tools in identifying promising avenues of treatment. Enzyme replacement therapy, gene therapy, and bone marrow transplant have all shown efficacy in the MPS IIIB model systems. A ubiquitous finding across rodent models of lysosomal storage diseases is that the best treatment outcomes resulted from intervention prior to symptom onset. Therefore, the aim of the current study was to identify early markers of disease in the MPS IIIB mouse model as well as examine clinically-relevant behavioral domains not yet explored in this model. Methods Using the MPS IIIB mouse model, we explored early developmental trajectories of communication and gait, and later social behavior, fear-related startle and conditioning, and visual capabilities. In addition, we examined brain structure and function via magnetic resonance imaging and diffusion tensor imaging. Results We observed reduced maternal isolation-induced ultrasonic vocalizations in MPS IIIB mice relative to controls, as well as disruption in a number of the spectrotemporal features. MPS IIIB also exhibited disrupted thermoregulation during the first two postnatal weeks without any differences in body weight. The developmental trajectories of gait were largely normal. In early adulthood, we observed intact visual acuity and sociability yet a more submissive phenotype, increased aggressive behavior, and decreased social sniffing relative to controls. MPS IIIB mice showed greater inhibition of startle in response to a pretone with a decrease in overall startle response and reduced cued fear memory. MPS IIIB also weighed significantly more than controls throughout adulthood and showed larger whole brain volumes and normalized regional volumes with intact tissue integrity as measured with magnetic resonance and diffusion tensor imaging, respectively. Conclusions Together, these results indicate disease markers are present as early as the first two weeks postnatal in this model. Further, this model recapitulates social, sensory and fear-related clinical features. Our study using a mouse model of MPS IIIB provides essential baseline information that will be useful in future evaluations of potential treatments.

Background and objective: Previous germline studies on renal cell carcinoma (RCC) have usually pooled clear and non–clear cell RCCs and have not adequately accounted for population stratification, which might have led to an inaccurate estimation of genetic risk. Here, we aim to analyze the major germline drivers of RCC risk and clinically relevant but underexplored germline variant types. Methods: We first characterized germline pathogenic variants (PVs), cryptic splice variants, and copy number variants (CNVs) in 1436 unselected RCC patients. To evaluate the enrichment of PVs in RCC, we conducted a case-control study of 1356 RCC patients ancestry matched with 16 512 cancer-free controls using approaches accounting for population stratification and histological subtypes, followed by characterization of secondary somatic events. Key findings and limitations: Clear cell RCC patients (n = 976) exhibited a significant burden of PVs in VHL compared with controls (odds ratio [OR]: 39.1, p = 4.95e-05). Non–clear cell RCC patients (n = 380) carried enrichment of PVs in FH (OR: 77.9, p = 1.55e-08) and MET (OR: 1.98e11, p = 2.07e-05). In a CHEK2-focused analysis with European participants, clear cell RCC (n = 906) harbored nominal enrichment of low-penetrance CHEK2 variants—p.Ile157Thr (OR: 1.84, p = 0.049) and p.Ser428Phe (OR: 5.20, p = 0.045), while non–clear cell RCC (n = 295) exhibited nominal enrichment of CHEK2 loss of function PVs (OR: 3.51, p = 0.033). Patients with germline PVs in FH, MET, and VHL exhibited significantly earlier age of cancer onset than patients without germline PVs (mean: 46.0 vs 60.2 yr, p

An 86-year-old male with multiple medical comorbidities was referred for an elective transcatheter aortic valve replacement (TAVR) for severe symptomatic aortic stenosis with an ejection fraction of 35%. A self-expanding valve was deployed successfully, but intraoperative transesophageal echocardiography (TEE) confirmed an acute type A aortic dissection (ATAAD), necessitating immediate intervention. Multiple intraoperative imaging modalities were utilized for deployment of a conformable GORE TAG (cTAG) stent graft for thoracic endovascular aortic repair (TEVAR). This case demonstrates TEVAR as an effective, minimally invasive option for immediate repair of ATAAD as a complication of TAVR in a high-risk surgical patient.

Linking score scales across different tests is considered speculative and fraught, even at the aggregate level. We introduce and illustrate validation methods for aggregate linkages, using the challenge of linking U.S. school district average test scores across states as a motivating example. We show that aggregate linkages can be validated both directly and indirectly under certain conditions such as when the scores for at least some target units (districts) are available on a common test (e.g., the National Assessment of Educational Progress). We introduce precision-adjusted random effects models to estimate linking error, for populations and for subpopulations, for averages and for progress over time. These models allow us to distinguish linking error from sampling variability and illustrate how linking error plays a larger role in aggregates with smaller sample sizes. Assuming that target districts generalize to the full population of districts, we can show that standard errors for district means are generally less than 0.2 standard deviation units, leading to reliabilities above 0.7 for roughly 90% of districts. We also show how sources of imprecision and linking error contribute to both within- and between-state district comparisons within versus between states. This approach is applicable whenever the essential counterfactual question--"what would means/variance/progress for the aggregate units be, had students taken the other test?"--can be answered directly for at least some of the units.

We use data from the Stanford Education Data Archive to describe district-level trends in average academic achievement between 2009 and 2019. Although on average school districts' test scores improved very modestly (by about 0.001 standard deviations per year), there is significant variation among districts. Moreover, we find that average test score disparities between nonpoor and poor students and between White and Black students are growing; those between White and Hispanic students are shrinking. We find no evidence of achievement-equity synergies or trade-offs: Improvements in overall achievement are uncorrelated with trends in achievement disparities. Finally, we find that the strongest predictors of achievement disparity trends are the levels and trends in within-district racial and socioeconomic segregation and changes in differential access to certified teachers.

Anxiety problems are common in children and can have profound adverse effects on personal, social and academic life. Almost 40% of anxiety disorders emerge before age 14, making primary schools invaluable settings for prevention and early support of child anxiety. Research indicates that school-based interventions can be costly and difficult to schedule, school staff lack confidence to deliver them effectively, and outcomes are mixed. One solution may be for school staff to adapt and enhance their day-to-day practices to better support children with anxiety. This systematic review aims to summarise what is known about the relationship between teachers' classroom management and anxiety in primary school-aged children. We searched ASSIA, British Education Index, Education Abstracts, Embase, ERIC, MEDLINE, PsycINFO and Scopus in December 2020 and June 2022, using a predefined strategy. We included studies of any design, published in peer-reviewed journals at any time, in any language, reporting associations between day-to-day classroom management strategies/methods and anxiety/internalising outcomes in children aged 4-11 years, taught in mainstream primary schools. Studies were assessed for quality/risk of bias. We identified eight studies (six quantitative, two qualitative) including 4505 children. We found some evidence that authoritarian, controlling and punitive classrooms may be linked to higher levels of anxiety, although, overall, existing evidence indicates either a weak or no association between classroom management and anxiety. This review highlights a paucity of research in this area. Furthermore, variability in design, measures and quality makes drawing firm conclusions difficult. Recommendations for future research are discussed.

Cross-national studies on socioeconomic status (SES) achievement gaps have focused on the size of the gap and given less attention to where in the SES distribution the achievement gap tends to be relatively large within a society, and whether this location varies across countries. We estimate the relative size of achievement gaps between students at the 50th and 10th percentiles versus the 90th and 50th percentiles of SES distribution within a society, using the Organisation for Economic Co-operation and Development (OECD) Programme for International Student Assessment (PISA) data. We find OECD countries vary in the size of the ratio of achievement gaps at lower-tail SES and upper-tail SES. Our multivariate analyses show that the ratio is positively associated with within-country patterns of economic inequality, measured by the ratio of income inequality and the ratio of segregation at lower-tail and upper-tail SES. We do not find evidence of an association between the achievement gap ratio and patterns of educational stratification.

Tumors develop in an oxidative environment characterized by peroxynitrite production and downstream protein tyrosine (Y) nitration. We showed that tyrosine nitration supports schwannoma cell proliferation and regulates cell metabolism in the inheritable tumor disorder NF2-related Schwannomatosis (NF2-SWN). Here, we identified the chaperone Heat shock protein 90 (Hsp90) as the first nitrated protein that acts as a metabolic switch to promote schwannoma cell proliferation. Doubling the endogenous levels of nitrated Hsp90 in schwannoma cells or supplementing nitrated Hsp90 into normal Schwann cells increased their proliferation. Metabolically, nitration on either Y33 or Y56 conferred Hsp90 distinct functions; nitration at Y33 (Hsp90NY33) down-regulated mitochondrial oxidative phosphorylation, while nitration at Y56 (Hsp90NY56) increased glycolysis by activating the purinergic receptor P2X7 in both schwannoma and normal Schwann cells. Hsp90NY33 and Hsp90NY56 showed differential subcellular and spatial distribution corresponding with their metabolic and proliferative functions in schwannoma three-dimensional cell culture models. Collectively, these results underscore the role of tyrosine nitration as a post-translational modification regulating critical cellular processes. Nitrated proteins, particularly nitrated Hsp90, emerge as a novel category of tumor-directed therapeutic targets.