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Virtually every teacher works with at least some and sometimes many, students who struggle to read on grade level. Recent research has demonstrated success in improving the reading level of students in grades 4-9 with reading difficulties. This practice guide, developed by the What Works Clearinghouse™ (WWC) in conjunction with an expert panel, distills this contemporary research into easily comprehensible and practical recommendations for educators to use when providing reading interventions. The recommendations outline evidence-based practices that can help teachers meet the needs of their students with reading difficulties. These recommendations will also help educators address the requirements of two federal laws, the Elementary and Secondary Education Act (ESEA) and the Individuals with Disabilities Education Act (IDEA), that favor the use of relevant evidence-based instructional practices relevant to students' needs. This practice guide grounds the four recommendations (multisyllabic word reading, fluency building, comprehension-building practices, and stretch texts) in high-quality evidence based on research studies focused on reading interventions. Each recommendation includes instructional practices and a short summary of the research evidence that supports the recommendation.

Recent intervention research has demonstrated success in raising the achievement level of students who are struggling with mathematics. This practice guide, developed by the What Works Clearinghouse™ (WWC) in conjunction with an expert panel, distills this contemporary mathematics intervention research into six easily comprehensible and practical recommendations for teachers to use when teaching elementary students in intervention settings. Two federal laws, the Elementary and Secondary Education Act (ESEA) and Individuals with Disabilities Education Act (IDEA), require use of instructional practices supported by evidence. The recommendations presented in the guide address these laws by translating the body of high-quality evidence into actionable practices for teachers to use with their students. Although this guide is an update of the 2009 guide, "Assisting Students Struggling with Mathematics: Response to Intervention (RtI) for Elementary and Middle School," it is narrower in scope, focusing only on practices and principles underlying effective small-group interventions in grades K-6. The practices that appear in this guide's recommendations highlight effective approaches to mathematics intervention that meet the needs of the students in small-group or one-on-one settings. Each of these practices move students toward more fluent performance of mathematics. Each recommendation includes features of intervention and/or instructional practices, with guidance on how to implement them, advice on how to overcome potential obstacles, and a short summary of the research evidence that supports the recommendation. This guide is designed to be used by teachers providing mathematics intervention to students who are struggling. This professional group includes special educators, mathematics general education teachers, mathematics specialists, and mathematics coaches. [For the 2009 edition of this guide, see ED504995.]

We use time-domain simulations of Jupiter observations to test and develop a beam reconstruction pipeline for the Simons Observatory Small Aperture Telescopes. The method relies on a mapmaker that estimates and subtracts correlated atmospheric noise and a beam fitting code designed to compensate for the bias caused by the mapmaker. We test our reconstruction performance for four different frequency bands against various algorithmic parameters, atmospheric conditions, and input beams. We additionally show the reconstruction quality as a function of the number of available observations and investigate how different calibration strategies affect the beam uncertainty. For all of the cases considered, we find good agreement between the fitted results and the input beam model within an ∼1.5% error for a multipole range l = 30-700 and an ∼0.5% error for a multipole range l = 50-200. We conclude by using a harmonic-domain component separation algorithm to verify that the beam reconstruction errors and biases observed in our analysis do not significantly bias the Simons Observatory r-measurement

The goal of this practice guide is to offer educators specific, evidence-based recommendations for teaching foundational reading skills to students in kindergarten through 3rd grade. This guide is a companion to the existing practice guide, "Improving Reading Comprehension in Kindergarten Through 3rd Grade", and as a set, these guides offer recommendations for preparing students to be successful readers. Both guides recommend some practices that can and should be implemented beginning in kindergarten, and both guides also suggest some instructional practices that can be implemented after students have mastered early reading skills. This guide synthesizes the best available research on foundational reading skills and shares practices that are supported by evidence. It is intended to be practical and easy for teachers to use. The guide includes many examples in each recommendation to demonstrate the concepts discussed. This guide provides teachers, reading coaches, principals, and other educators with instructional recommendations that can be implemented in conjunction with existing standards or curricula and does not recommend a particular curriculum. Teachers can use the guide when planning instruction to support the development of foundational reading skills among students in grades K-3 and in diverse contexts. Professional-development providers, program developers, and researchers can also use this guide. Professional-development providers can use the guide to implement evidence-based instruction and align instruction with state standards or to prompt teacher discussion in professional learning communities. Program developers can use the guide to create more effective early-reading curricula and interventions. Finally, researchers may find opportunities to test the effectiveness of various approaches to foundational reading education and explore gaps or variations in the reading-instruction literature. The following are appended: (1) Postscript from the Institute of Education Sciences; (2) About the Authors; (3) Disclosure of Potential Conflicts of Interest; and (4) Rationale for Evidence Ratings. A glossary is included. [For the companion guide, "Improving Reading Comprehension in Kindergarten through 3rd Grade: IES Practice Guide. NCEE 2010-4038," see ED512029.]

Mastering algebra is important for future math and postsecondary success. Educators will find practical recommendations for how to improve algebra instruction in the What Works Clearinghouse (WWC) practice guide, "Teaching Strategies for Improving Algebra Knowledge in Middle and High School Students". The methods and examples included in the guide focus on helping students analyze solved problems, recognize structure, and utilize alternative approaches to solving algebra problems. Each recommendation includes the level of supporting research evidence behind it, examples to use in class, and solutions to potential implementation roadblocks. Teachers can implement these strategies in conjunction with existing standards or curricula. In addition, these strategies can be utilized for all students learning algebra in grades 6-12 and in diverse contexts, including during both formative and summative assessment. Administrators and professional development providers can use the guide to implement evidence-based instruction and align instruction with state standards or to prompt teacher discussion in professional learning communities. Appended are: (1) Postscript from the Institute of Education Sciences; (2) About the Authors; (3) Disclosure of Potential Conflicts of Interest; and (4) Rationale for Evidence Ratings. A Glossary is included.

Technologies have been theorised to understand their powers to produce spacetimes – notably through Bernard Stiegler’s reading of technics as constitutive of human ontology. However, less attention has been paid to how technologies shape spacetimes according to their own distinct logics of evolution, the result being a tendency to reduce technological agency to a question of its effects on human being. The first half of the paper elaborates this problem in conversation with geographies of the digital turn. The second half introduces an alternative approach through Gilbert Simondon’s ontogenetic notion of technology characterised by its own logics of evolution – what I term techno-genesis.

We use time-domain simulations of Jupiter observations to test and develop a beam reconstruction pipeline for the Simons Observatory Small Aperture Telescopes. The method relies on a mapmaker that estimates and subtracts correlated atmospheric noise and a beam fitting code designed to compensate for the bias caused by the mapmaker. We test our reconstruction performance for four different frequency bands against various algorithmic parameters, atmospheric conditions, and input beams. We additionally show the reconstruction quality as a function of the number of available observations and investigate how different calibration strategies affect the beam uncertainty. For all of the cases considered, we find good agreement between the fitted results and the input beam model within an ∼1.5% error for a multipole range ℓ = 30–700 and an ∼0.5% error for a multipole range ℓ = 50–200. We conclude by using a harmonic-domain component separation algorithm to verify that the beam reconstruction errors and biases observed in our analysis do not significantly bias the Simons Observatory r-measurement

In Europe, increasing efforts on climate change mitigation, a sudden focus on energy independence after Russia’s invasion of Ukraine, and reported breakthroughs in nuclear fusion have sparked renewed interest in the potential of nuclear power. So-called small modular reactors (SMRs) are increasingly under development, and familiar promises about nuclear power’s potential are being revived. Nuclear power is routinely portrayed by proponents as the source of “limitless” amounts of carbonfree electricity. The rhetorical move from speaking about “renewable energy” to “fossil-free energy” is increasingly evident, and telling., Funding agencies: Svensk Kärnbränslehantering (grant no.24992), the Swedish Research Council (grants no. 2020-00623 and no. 2020-06548).

Compartments are a fundamental feature of life, based variously on lipid membranes, protein shells, or biopolymer phase separation. Here, this combines self-assembling bacterial microcompartment (BMC) shell proteins and liquid-liquid phase separation (LLPS) to develop new forms of compartmentalization. It is found that BMC shell proteins assemble at the liquid-liquid interfaces between either 1) the dextran-rich droplets and PEG-rich continuous phase of a poly(ethyleneglycol)(PEG)/dextran aqueous two-phase system, or 2) the polypeptide-rich coacervate droplets and continuous dilute phase of a polylysine/polyaspartate complex coacervate system. Interfacial protein assemblies in the coacervate system are sensitive to the ratio of cationic to anionic polypeptides, consistent with electrostatically-driven assembly. In both systems, interfacial protein assembly competes with aggregation, with protein concentration and polycation availability impacting coating. These two LLPS systems are then combined to form a three-phase system wherein coacervate droplets are contained within dextran-rich phase droplets. Interfacial localization of BMC hexameric shell proteins is tunable in a three-phase system by changing the polyelectrolyte charge ratio. The tens-of-micron scale BMC shell protein-coated droplets introduced here can accommodate bioactive cargo such as enzymes or RNA and represent a new synthetic cell strategy for organizing biomimetic functionality.

IntroductionThis study determined the safety and recommended phase 2 dose (RP2D) of the multikinase inhibitor cabozantinib in combination with trifluridine/tipiracil (FTD/TPI) in refractory metastatic colorectal carcinoma (mCRC).Patients and methodsSingle institution investigator-initiated phase 1 study using 3+3 design. Eligible mCRC patients had received prior standard regimens. Cabozantinib was given orally (p.o.) at 20 mg (dose level [DL] 0) or 40 mg (DL 1) daily on days 1-28, and FTD/TPI p.o. at 35 mg/m2 on days 1-5 and 8-12 every 28 days. Prophylactic growth-factor support was allowed.ResultsFifteen patients were enrolled. Median age 56 years (31-80), male (12/15), ECOG 0/1 = 9/6. Three patients were treated at DL 0 and another nine were treated at DL 1, none exhibiting a DLT. Most common any grade (G) treatment related adverse events (TRAE) were diarrhea (50%), nausea (42%), neutropenia (42%), fatigue (33%), and rash (25%). G3-4 TRAE were neutropenia (25%) and thrombocytopenia, hypokalemia, and weight loss (each 8%). No serious TRAE or G5 were reported. The RP2D was determined to be DL 1. Median PFS was 3.8 months (95% CI 1.9-6.8) and disease control rate was 86.7%.ConclusionThe combination of cabozantinib and FTD/TPI is feasible and tolerable at standard doses with the use of growth factors and showed encouraging clinical activity in refractory mCRC.ClinicaltrialsGOV: NCT04868773.

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies. Here we used 278 bronchoalveolar lavage (BAL) fluid samples to study the lung microenvironment in 229 pediatric patients who have undergone HCT treated at 32 childrens hospitals between 2014 and 2022. By leveraging paired microbiome and human gene expression data, we identified high-risk BAL compositions associated with in-hospital mortality (P = 0.007). Disadvantageous profiles included bacterial overgrowth with neutrophilic inflammation, microbiome contraction with epithelial fibroproliferation and profound commensal depletion with viral and staphylococcal enrichment, lymphocytic activation and cellular injury, and were replicated in an independent cohort from the Netherlands (P = 0.022). In addition, a broad array of previously occult pathogens was identified, as well as a strong link between antibiotic exposure, commensal bacterial depletion and enrichment of viruses and fungi. Together these lung-immune system-microorganism interactions clarify the important drivers of fatal lung injury in pediatric patients who have undergone HCT. Further investigation is needed to determine how personalized interpretation of heterogeneous pulmonary microenvironments may be used to improve pediatric HCT outcomes.

Donor-funded climate and disaster resilience programmes and projects aim to help build the capacities and resilience of communities. Measuring resilience is critical, therefore, in providing feedback, evidence, and accountability. This paper presents recent two-year time-series findings from an ongoing multi-partner academic and practical collaboration pertaining to a climate change adaption project with rural communities in Cambodia. To measure community resilience, the study used the Flood Resilience Measurement for Communities, which measures, using mixed methods, disaster resilience capacities across five key dimensions of resilience: human, social, physical, natural, and financial capitals. The study analysed and reported changes in these areas of resilience in the selected villages, generating insights into the strengths and weaknesses of flood resilience capacities in the region. This paper provides valuable guidance as to where investment can be most effective in different communities, confirming the usefulness of the tool in measuring resilience and assessing the effectiveness of the project concerned.

The laws of taxation, trusts, and estates are new fronts in the culture wars over abortion. After the Supreme Court's 2022 decision in Dobbs v. Jackson Women's Health Organization, some anti-abortion states enacted fetal personhood statutes that have the potential to unsettle and destabilize longstanding legal doctrines that otherwise create predictability and stability in the laws of taxation and succession. This Article makes three principal claims: descriptive, predictive, and normative. First, the Article explores how Dobbs opened the door for states like Georgia to treat zygotes-embryos-fetuses as “dependents” for state income tax purposes. Second, the Article identifies some of the most salient ways fetal personhood laws could upend longstanding rules concerning property ownership and taxpayers' determination of their fiscal obligations to the government. Unless carefully circumscribed, fetal personhood laws will disrupt the orderly transmission of property at death, the ability to administer a trust, and any durational limits on trusts. Third, the Article argues that state lawmakers should explicitly limit the scope of fetal personhood laws. Somewhat counterintuitively, both those with antiabortion views and those who wish to secure access to the procedure share an interest in narrowing these laws' applicability. For symbolic-political reasons, however, it is unlikely that lawmakers in anti-abortion states will place voluntary boundaries on the applicability of fetal personhood statutes. Therefore, the Article proposes rules of construction that judges should adopt in jurisdictions that have enacted fetal personhood laws. These include presumptions that a zygote-embryo-fetus is not the beneficiary of an estate or trust, disregarding in vitro embryos for purposes of the rule against perpetuities, and fixing the generational assignment of a zygote-embryo-fetus for generation-skipping transfer tax purposes at one generation below that of the intended parents. Th

This thesis explores topics of gender, sexuality, and male and female agency in Restoration literature and theatre, specifically Aphra Behn’s The Rover (1677) and The City Heiress (1682), William Wycherley’s The Country Wife (1675), and Sébastien Brémond’s Hattige; or the Amours of the Prince of Tamaran (1680). It explores how these authors understand and explore the ways in which both genders were confined by dominant models during this time period, while also navigating the fluidity and complexity of these models. This thesis focuses on how libertinism and its emphasis on sexuality relates to gender categories. Given that access to libertinism is dictated through social class, sexuality, and wit, certain aspects of libertinism can be available for women. While women cannot completely do this and dominate men in the same way, they can harness parts of this libertine role, although they still must be careful about their reputation and honour. This thesis explores topics of the libertine figure and other categories of gender in relation to that figure through its representation in popular genres of Restoration literature (comedy and amatory secret history), arguing that as represented in these texts, sexuality and gender are constitutive of one another.

INTRODUCTION: Co-design in health research involves patient and public involvement and engagement (PPIE) in intervention or service design. Traditionally, co-design is undertaken in-person; however, exploring online delivery is warranted. PPIE in co-design must be considered carefully, and assumptions that in-person approaches will transition automatically to an online environment should be avoided. Currently, there are a lack of evidence-informed approaches to facilitating co-design online. This study aimed to develop and evaluate a framework for authentically adapting health research co-design into an online environment. MATERIALS AND METHODS: The initial framework was developed through a literature review, synthesis of in-person co-design principles, and alignment of online strategies. The framework was then applied to a co-design project with 10 participants across relevant PPIE groups (end-users [n = 4], clinicians [n = 2], coaches [n = 2] and clinician-researchers [n = 2]). Participants' experiences of the online co-design process were evaluated via a mixed-methods design using surveys and semi-structured interviews. Evaluation data were analysed using descriptive statistics and reflexive thematic analysis to inform a revised framework. RESULTS: The developed framework, Partnership-focussed Principles-driven Online co-Design (P-POD) was used to design eight 90 min online co-design workshops. Evaluation data involved 46 survey responses, and eight participants were interviewed on project completion. Survey data indicated that the process was satisfying, engaging and adhered to the P-POD framework. Themes derived from interview data describe a respectful and collaborative online culture, valuing of diverse perspectives and space for healthy debate, how power was perceived as being shared but not equal and multiple definitions of success within and beyond the process. A final, refined P-POD framework is presented. CONCLUSION: With evaluation of the initial P-POD

A holistic review is given of the Southern Ocean dynamic system, in the context of the crucial role it plays in the global climate and the profound changes it is experiencing. The review focuses on connections between different components of the Southern Ocean dynamic system, drawing together contemporary perspectives from different research communities, with the objective of closing loops in our understanding of the complex network of feedbacks in the overall system. The review is targeted at researchers in Southern Ocean physical science with the ambition of broadening their knowledge beyond their specific field, and aims at facilitating better‐informed interdisciplinary collaborations. For the purposes of this review, the Southern Ocean dynamic system is divided into four main components: large‐scale circulation; cryosphere; turbulence; and gravity waves. Overviews are given of the key dynamical phenomena for each component, before describing the linkages between the components. The reviews are complemented by an overview of observed Southern Ocean trends and future climate projections. Priority research areas are identified to close remaining loops in our understanding of the Southern Ocean system.

BACKGROUND: Hip osteoarthritis (OA) is a leading cause of chronic pain and disability worldwide. Self-management is vital with education, exercise and weight loss core recommended treatments. However, evidence-practice gaps exist, and service models that increase patient accessibility to clinicians who can support lifestyle management are needed. The primary aim of this study is to determine the effectiveness of a telehealth-delivered clinician-supported exercise and weight loss program (Better Hip) on the primary outcomes of hip pain on walking and physical function at 6 months, compared with an information-only control for people with hip OA. METHODS: A two-arm, parallel-design, superiority pragmatic randomised controlled trial. 212 members from a health insurance fund aged 45 years and over, with painful hip OA will be recruited. Participants will be randomly allocated to receive: i) Better Hip; or ii) web-based information only (control). Participants randomised to the Better Hip program will have six videoconferencing physiotherapist consultations for education about OA, prescription of individualised home-based strengthening and physical activity programs, behaviour change support, and facilitation of other self-management strategies. Those with a body mass index > 27 kg/m2, aged < 80 years and no specific health conditions, will also be offered six videoconferencing dietitian consultations to undertake a weight loss program. Participants in the control group will be provided with similar educational information about managing hip OA via a custom website. All participants will be reassessed at 6 and 12 months. Primary outcomes are hip pain on walking and physical function. Secondary outcomes include measures of pain; hip function; weight; health-related quality of life; physical activity levels; global change in hip problem; willingness to undergo hip replacement surgery; rates of hip replacement; and use of oral pain medications. A health economic evaluation

A holistic review is given of the Southern Ocean dynamic system, in the context of the crucial role it plays in the global climate and the profound changes it is experiencing. The review focuses on connections between different components of the Southern Ocean dynamic system, drawing together contemporary perspectives from different research communities, with the objective of closing loops in our understanding of the complex network of feedbacks in the overall system. The review is targeted at researchers in Southern Ocean physical science with the ambition of broadening their knowledge beyond their specific field, and aims at facilitating better-informed interdisciplinary collaborations. For the purposes of this review, the Southern Ocean dynamic system is divided into four main components: large-scale circulation; cryosphere; turbulence; and gravity waves. Overviews are given of the key dynamical phenomena for each component, before describing the linkages between the components. The reviews are complemented by an overview of observed Southern Ocean trends and future climate projections. Priority research areas are identified to close remaining loops in our understanding of the Southern Ocean system.

MYCN oncogene amplification is frequently observed in aggressive childhood neuroblastoma. Using an unbiased large-scale mutagenesis screen in neuroblastoma-prone transgenic mice, we identify a single germline point mutation in the transcriptional corepressor Runx1t1, which abolishes MYCN-driven tumorigenesis. This loss-of-function mutation disrupts a highly conserved zinc finger domain within Runx1t1. Deletion of one Runx1t1 allele in an independent Runx1t1 knockout mouse model is also sufficient to prevent MYCN-driven neuroblastoma development, and reverse ganglia hyperplasia, a known pre-requisite for tumorigenesis. Silencing RUNX1T1 in human neuroblastoma cells decreases colony formation in vitro, and inhibits tumor growth in vivo. Moreover, RUNX1T1 knockdown inhibits the viability of PAX3-FOXO1 fusion-driven rhabdomyosarcoma and MYC-driven small cell lung cancer cells. Despite the role of Runx1t1 in MYCN-driven tumorigenesis neither gene directly regulates the other. We show RUNX1T1 forms part of a transcriptional LSD1-CoREST3-HDAC repressive complex recruited by HAND2 to enhancer regions to regulate chromatin accessibility and cell-fate pathway genes.

From ~24 months old, typically developing (TD) children often generalise names for solid objects to novel examples that are the same shape. This ‘shape bias’ can facilitate word learning by providing an attentional short-cut, allowing children to accurately generalise novel nouns. Autistic children often experience delays in language acquisition, and difficulty exploiting the shape bias may be a contributing factor. However, extant research findings are highly inconsistent, with autistic children exhibiting a shape bias in certain tasks but not others. Thus, the current research investigated whether variability in autistic children’s shape bias can be explained by methodological differences. Autistic children (aged 4 to 9 years) and TD children matched on receptive vocabulary (aged 30 months to 4 years) participated in five experiments measuring shape bias in both ‘forced-choice’ and ‘yes or no’ variants of a novel noun generalisation task (NNG). Each task included an ‘online’ condition, where children were asked to generalise a label from a visible standard item to a target, and an ‘offline’ condition where the standard was absent at test, and generalisation had to be completed from memory. Experiment 1 investigated whether the visibility of the standard affected autistic children’s shape bias in a forced-choice task with high contrast stimuli. We found that both autistic and TD groups generalised by shape regardless of standard visibility. Experiment 2 investigated whether shape was still preferred in a yes/no task, where children had the freedom to include any of the stimuli in the category rather than just the best example. In this task, autistic children were more likely to accept the differently shaped distractors than the TD group. Experiments 3 and 4 used the same tasks with low contrast stimuli to investigate whether the requirement to remember the standard had an impact when object shapes were more similar. Both groups again exhibited a shape bias in the f

Publication date: April 30, 2024

BackgroundStaining tissue samples to visualise cellular detail and tissue structure is at the core of pathology diagnosis, but variations in staining can result in significantly different appearances of the tissue sample. While the human visual system is adept at compensating for stain variation, with the growth of digital imaging in pathology, the impact of this variation can be more profound. Despite the ubiquity of haematoxylin and eosin staining in clinical practice worldwide, objective quantification is not yet available. We propose a method for quantitative haematoxylin and eosin stain assessment to facilitate quality assurance of histopathology staining, enabling truly quantitative quality control and improved standardisation.MethodsThe stain quantification method comprises conventional microscope slides with a stain-responsive biopolymer film affixed to one side, called stain assessment slides. The stain assessment slides were characterised with haematoxylin and eosin, and implemented in one clinical laboratory to quantify variation levels.ResultsStain assessment slide stain uptake increased linearly with duration of haematoxylin and eosin staining (r = 0.99), and demonstrated linearly comparable staining to samples of human liver tissue (r values 0.98-0.99). Laboratory implementation of this technique quantified intra- and inter-instrument variation of staining instruments at one point in time and across a five-day period.ConclusionThe proposed method has been shown to reliably quantify stain uptake, providing an effective laboratory quality control method for stain variation. This is especially important for whole slide imaging and the future development of artificial intelligence in digital pathology., Funding Agencies|UK Research and Innovation

Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.

Introduction: Ethnic minorities (also called racialised groups) are more likely to experience severe mental illness (SMI). People with SMI are more likely to experience multimorbidity (MM), making psychosis among racialised groups more likely to lead to MM, poor outcomes, disability and premature mortality. Methods and analysis: This National Institute for Health and Care Research-funded study (151887) seeks to use innovative participatory methods including photovoice and biographical narrative interviews in urban and rural areas of England to assemble experience data. These data will be subjected to polytextual thematic analysis, and alongside pictures and captions, will inform an experienced-based co-design of interventions, the implementation of which will be evaluated. There will be an economic analysis and a process evaluation of the implementation. Ethics and dissemination: This programme of work has received ethical (IRAS 322421; Newcastle North Tyneside Research Ethics Committee 23/NE/0143) and sponsor approval. The findings will be disseminated in galleries showing the creative work, as lay and academic summaries and infographics; as practice briefings for practitioners, commissioners and policy makers; peer-reviewed publications. Trial registration number: https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/649c08111c037d0027b17d17

This study explores the metal enrichment signatures attributed to the first generation of stars (PopIII) in the Universe, focusing on the E-XQR-30 sample. We aim to identify traces of Pop III metal enrichment by analyzing neutral gas in the interstellar medium of primordial galaxies and their satellite clumps, detected in absorption. To chase the chemical signature of PopIII stars, we studied metal absorption systems in the E-XQR-30 sample, selected through the detection of the OI absorption line at 1302A. The OI line is a reliable tracer of HI and allowed us to overcome the challenges posed by the Lyman-$\alpha$ forest's increasing saturation at redshifts above $\sim5$ to identify Damped Lyman-$\alpha$ systems (DLA). We detected and analyzed 29 OI systems at $z\geq5.4$, differentiating between proximate DLAs (PDLA) and intervening DLAs. Voigt function fits were applied to obtain ionic column densities, and relative chemical abundances were determined for 28 systems. These were then compared with the predictions of theoretical models. Our findings expand the study of OI systems at $z\geq5.4$ fourfold. No systematic differences were observed in the average chemical abundances between PDLAs and intervening DLAs. The chemical abundances in our sample align with literature systems at $z>4.5$, suggesting a similar enrichment pattern for this class of absorption systems. A comparison between these DLA-analogues at $4.5

One of the surprising early findings with JWST has been the discovery of a strong "roll-over" or a softening of the absorption edge of Ly$\alpha$ in a large number of galaxies at ($z\gtrsim 6$), in addition to systematic offsets from photometric redshift estimates and fundamental galaxy scaling relations. This has been interpreted as damped Ly$\alpha$ absorption (DLA) wings from high column densities of neutral atomic hydrogen (HI), signifying major gas accretion events in the formation of these galaxies. To explore this new phenomenon systematically, we assemble the JWST/NIRSpec PRImordial gas Mass AssembLy (PRIMAL) legacy survey of 494 galaxies at $z=5.5-13.4$. We characterize this benchmark sample in full and spectroscopically derive the galaxy redshifts, metallicities, star-formation rates, and ultraviolet slopes. We define a new diagnostic, the Ly$\alpha$ damping parameter $D_{\rm Ly\alpha}$ to measure and quantify the Ly$\alpha$ emission strength, HI fraction in the IGM, or local HI column density for each source. The JWST-PRIMAL survey is based on the spectroscopic DAWN JWST Archive (DJA-Spec). All the software, reduced spectra, and spectroscopically derived quantities and catalogs are made publicly available in dedicated repositories. The fraction of strong galaxy DLAs are found to be in the range $65-95\%$ at $z>5.5$. The fraction of strong Ly$\alpha$ emitters (LAEs) is found to increase with decreasing redshift, in qualitative agreement with previous observational results, and are predominantly associated with low-metallicity and UV faint galaxies. By contrast, strong DLAs are observed in galaxies with a variety of intrinsic physical properties. Our results indicate that strong DLAs likely reflect a particular early assembly phase of reionization-era galaxies, at which point they are largely dominated by pristine HI gas accretion. [abridged], Comment: 20 pages, 18 figures, 3 tables. Submitted to A&A. Comments welcome! All data and catalogs are available through the DAWN JWST Archive (DJA): https://dawn-cph.github.io/dja/ and https://github.com/keheintz/jwst-primal

We present a new suite of late-end reionization simulations performed with ATON-HE, a revised version of the GPU-based radiative transfer code ATON that includes helium. The simulations are able to reproduce the Ly$\alpha$ flux distribution of the E-XQR-30 sample of QSO absorption spectra at $5 \lesssim z \lesssim 6.2$, and show that a large variety of reionization models are consistent with these data. We explore a range of variations in source models and in the early-stage evolution of reionization. Our fiducial reionization history has a midpoint of reionization at $z = 6.5$, but we also explore an `Early' reionization history with a midpoint at $z = 7.5$ and an `Extremely Early' reionization history with a midpoint at $z = 9.5$. Haloes massive enough to host observed Ly$\alpha$ emitters are highly biased. The fraction of such haloes embedded in ionized bubbles that are large enough to allow high Ly$\alpha$ transmission becomes close to unity much before the volume filling factor of ionized regions. For our fiducial reionization history this happens at $z = 8$, probably too late to be consistent with the detection by JWST of abundant Ly$\alpha$ emission out to $z = 11$. A reionization history in our `Early' model or perhaps even our `Extremely Early' model may be required, suggesting a Thomson scattering optical depth in tension with that reported by Planck, but consistent with recent suggestions of a significantly higher value., Comment: 25 pages, 15 figures

Intervening metal absorbers in quasar spectra at $z > 6$ can be used as probes to study the chemical enrichment of the Universe during the Epoch of Reionization (EoR). This work presents the comoving line densities ($dn/dX$) of low ionisation absorbers, namely, Mg II (2796\r{A}), C II (1334\r{A}) and O I (1302\r{A}) across $2 0.03$\r{A}. For the first time, we present the comoving line densities of 131 weak ($W < 0.3$\r{A}) intervening Mg II absorbers at $1.9 < z < 6.4$ which exhibit constant evolution with redshift similar to medium ($0.3 < W < 1.0$\r{A}) absorbers. However, the cosmic mass density of Mg II - dominated by strong Mg II systems - traces the evolution of global star formation history from redshift 1.9 to 5.5. E-XQR-30 also increases the absorption path length by a factor of 50% for C II and O I whose line densities show a rising trend towards $z > 5$, in agreement with previous works. In the context of a decline in metal enrichment of the Universe at $z > 5$, the overall evolution in the incidence rates of absorption systems can be explained by a weak - possibly soft fluctuating - UV background. Our results, thereby, provide evidence for a late reionization continuing to occur in metal-enriched and therefore, biased regions in the Universe., Comment: 20 pages, 21 figures

We study the effects due to mismatches in passbands, polarization angles, and temperature and polarization calibrations in the context of the upcoming cosmic microwave background experiment Simons Observatory (SO). Using the SO multi-frequency likelihood, we estimate the bias and the degradation of constraining power in cosmological and astrophysical foreground parameters assuming different levels of knowledge of the instrumental effects. We find that incorrect but reasonable assumptions on the values of all the systematics examined here can have important effects in cosmological analyses, hence requiring marginalization approaches at likelihood level. When doing so, we find that the most relevant effect is due to bandpass shifts. When marginalizing over them, the posteriors of parameters describing astrophysical microwave foregrounds (such as radio point sources or dust) get degraded, while cosmological parameters constraints are not significantly affected. Marginalization over polarization angles with up to 0.25$^\circ$ uncertainty causes an irrelevant bias $\lesssim 0.05 \sigma$ in all parameters. Marginalization over calibration factors in polarization broadens the constraints on the effective number of relativistic degrees of freedom $N_\mathrm{eff}$ by a factor 1.2, interpreted here as a proxy parameter for non standard model physics targeted by high-resolution CMB measurements., Comment: 61 pages (27 of which are appendices), 26 figures, 12 tables. (Replacement to update the acknowledgments)

The Crab Nebula, also known as Tau A, is a polarized astronomical source at millimeter wavelengths. It has been used as a stable light source for polarization angle calibration in millimeter-wave astronomy. However, it is known that its intensity and polarization vary as a function of time at a variety of wavelengths. Thus, it is of interest to verify the stability of the millimeter-wave polarization. If detected, polarization variability may be used to better understand the dynamics of Tau A, and for understanding the validity of Tau~A as a calibrator. One intriguing application of such observation is to use it for the search of axion-light particles (ALPs). Ultralight ALPs couple to photons through a Chern-Simons term, and induce a temporal oscillation in the polarization angle of linearly polarized sources. After assessing a number of systematic errors and testing for internal consistency, we evaluate the variability of the polarization angle of the Crab Nebula using 2015 and 2016 observations with the 150 GHz POLARBEAR instrument. We place a median 95% upper bound of polarization oscillation amplitude $A < 0.065^\circ$ over the oscillation frequencies from $0.75~\mathrm{year}^{-1}$ to $0.66~\mathrm{hour}^{-1}$. Assuming that no sources other than ALP are causing Tau A's polarization angle variation, that the ALP constitutes all the dark matter, and that the ALP field is a stochastic Gaussian field, this bound translates into a median 95% upper bound of ALP-photon coupling $g_{a\gamma\gamma} < 2.16\times10^{-12}\,\mathrm{GeV}^{-1}\times(m_a/10^{-21} \mathrm{eV})$ in the mass range from $9.9\times10^{-23} \mathrm{eV}$ to $7.7\times10^{-19} \mathrm{eV}$. This demonstrates that this type of analysis using bright polarized sources is as competitive as those using the polarization of cosmic microwave background in constraining ALPs., Comment: 24 pages, 19 figures, 5 tables. Submitted to PRD

The Simons Observatory (SO) experiment is a cosmic microwave background (CMB) experiment located in the Atacama Desert, Chile. The SO' s small aperture telescopes (SATs) consist of three telescopes designed for precise CMB polarimetry at large angular scales. Each SAT uses a cryogenic rotating half-wave plate (HWP) as a polarization modulator to mitigate atmospheric 1/f noise and other systematics. To realize efficient polarization modulation over the observation bands, we fabricated an achromatic HWP (AHWP) consisting of three sapphire plates with anti-reflection coatings. The AHWP is designed to have broadband modulation efficiency and transmittance. This paper reports on the design and the preliminary characterization of the AHWPs for SATs.

We present resolved images of IRAS 23077+6707 in $1.3\,\mathrm{mm}$/$225\,\mathrm{GHz}$ thermal dust and CO gas emission with the Submillimeter Array (SMA) and $grizy$ optical scattered light with the Panoramic Survey Telescope and Rapid Response System (Pan-STARRS). The Pan-STARRS data show a bipolar distribution of optically scattering dust that is characteristic for disks observed at high inclinations. Its radial extent in scattered light emission spans $\sim12''$, with two highly asymmetric filaments extending along the upper bounds of each nebula by $\sim9''$. The SMA data measure $1.3\,\mathrm{mm}$ continuum dust as well as $^{12}$CO, $^{13}$CO and C$^{18}$O $J$=2$-$1 line emission over $11''$-$16''$ extents, with the gas presenting the typical morphology of a disk in Keplerian rotation, in both position-velocity space and in each CO line spectra. IRAS 23077+6707 has no reported distance estimate, but if it is located in the Cepheus star-forming region ($180$-$800\,\mathrm{pc}$), it would have a radius spanning thousands of au. Taken together, we infer IRAS 23077+6707 to be a giant and gas-rich edge-on protoplanetary disk, which to our knowledge is the largest in extent so far discovered., Comment: submitted to ApJL, comments welcome

3C84 is a nearby radio source with a complex total intensity structure, showing linear polarisation and spectral patterns. A detailed investigation of the central engine region necessitates the use of VLBI above the hitherto available maximum frequency of 86GHz. Using ultrahigh resolution VLBI observations at the highest available frequency of 228GHz, we aim to directly detect compact structures and understand the physical conditions in the compact region of 3C84. We used EHT 228GHz observations and, given the limited (u,v)-coverage, applied geometric model fitting to the data. We also employed quasi-simultaneously observed, multi-frequency VLBI data for the source in order to carry out a comprehensive analysis of the core structure. We report the detection of a highly ordered, strong magnetic field around the central, SMBH of 3C84. The brightness temperature analysis suggests that the system is in equipartition. We determined a turnover frequency of $\nu_m=(113\pm4)$GHz, a corresponding synchrotron self-absorbed magnetic field of $B_{SSA}=(2.9\pm1.6)$G, and an equipartition magnetic field of $B_{eq}=(5.2\pm0.6)$G. Three components are resolved with the highest fractional polarisation detected for this object ($m_\textrm{net}=(17.0\pm3.9)$%). The positions of the components are compatible with those seen in low-frequency VLBI observations since 2017-2018. We report a steeply negative slope of the spectrum at 228GHz. We used these findings to test models of jet formation, propagation, and Faraday rotation in 3C84. The findings of our investigation into different flow geometries and black hole spins support an advection-dominated accretion flow in a magnetically arrested state around a rapidly rotating supermassive black hole as a model of the jet-launching system in the core of 3C84. However, systematic uncertainties due to the limited (u,v)-coverage, however, cannot be ignored., Comment: 15 pages, 6 figures, published in A&A

We present evidence of variable 1.3 millimeter emission from the 1-3 Myr, SpT G2-G5 class III YSO, HD~283572. HD~283572 was observed on 8 dates with the Submillimeter Array between 2021 December and 2023 May, a total on-source time of 10.2 hours, probing a range of timescales down to 5.2 seconds. Averaging all data obtained on 2022 Jan 17 shows a 4.4 mJy ($8.8\sigma$) point source detection with a negative spectral index ($\alpha{=}{-2.7}{\pm}1.2$), with peak emission rising to 13.8 mJy in one 3 minute span, and 25 mJy in one 29.7 second integration ($L_\nu=4.7\times10^{17}$ erg s$^{-1}$ Hz$^{-1}$). Combining our data for the other 7 dates shows no detection, with an rms noise of 0.24 mJy beam$^{-1}$. The stochastic millimeter enhancements on time frames of seconds--minutes--hours with negative spectral indices are most plausibly explained by synchrotron or gyro-synchrotron radiation from stellar activity. HD 283572's 1.3 mm light-curve has similarities with variable binaries, suggesting HD 283572's activity may have been triggered by interactions with an as-yet undetected companion. We additionally identify variability of HD 283572 at 10 cm, from VLASS data. This study highlights the challenges of interpreting faint mm emission from evolved YSOs that may host tenuous disks, and suggests that a more detailed temporal analysis of spatially unresolved data is generally warranted. The variability of class III stars may open up new ground for understanding the physics of flares in the context of terrestrial planet formation., Comment: Accepted for publication in ApJL. 12 pages, inc. 5 figures, 2 tables

Recent findings suggest that stigma and camouflaging contribute to mental health difficulties for autistic individuals, however, this evidence is largely based on UK samples. While studies have shown cross-cultural differences in levels of autism-related stigma, it is unclear whether camouflaging and mental health difficulties vary across cultures. Hence, the current study had two aims: (1) to determine whether significant relationships between autism acceptance, camouflaging, and mental health difficulties replicate in a cross-cultural sample of autistic adults, and (2) to compare these variables across cultures. To fulfil these aims, 306 autistic adults from eight countries (Australia, Belgium, Canada, Japan, New Zealand, South Africa, the United Kingdom, and the United States) completed a series of online questionnaires. We found that external acceptance and personal acceptance were associated with lower levels of depression but not camouflaging or stress. Higher camouflaging was associated with elevated levels of depression, anxiety, and stress. Significant differences were found across countries in external acceptance, personal acceptance, depression, anxiety, and stress, even after controlling for relevant covariates. Levels of camouflaging also differed across countries however this effect became non-significant after controlling for the covariates. These findings have significant implications, identifying priority regions for anti-stigma interventions, and highlighting countries where greater support for mental health difficulties is needed., SCOPUS: ar.j, info:eu-repo/semantics/published

We present the first multi-wavelength study of Mrk 501 including very-high-energy (VHE) gamma-ray observations simultaneous to X-ray polarization measurements from the Imaging X-ray Polarimetry Explorer (IXPE). We use radio-to-VHE data from a multi-wavelength campaign organized between 2022-03-01 and 2022-07-19. The observations were performed by MAGIC, Fermi-LAT, NuSTAR, Swift (XRT and UVOT), and several instruments covering the optical and radio bands. During the IXPE pointings, the VHE state is close to the average behavior with a 0.2-1 TeV flux of 20%-50% the emission of the Crab Nebula. Despite the average VHE activity, an extreme X-ray behavior is measured for the first two IXPE pointings in March 2022 with a synchrotron peak frequency >1 keV. For the third IXPE pointing in July 2022, the synchrotron peak shifts towards lower energies and the optical/X-ray polarization degrees drop. The X-ray polarization is systematically higher than at lower energies, suggesting an energy-stratification of the jet. While during the IXPE epochs the polarization angle in the X-ray, optical and radio bands align well, we find a clear discrepancy in the optical and radio polarization angles in the middle of the campaign. We model the broad-band spectra simultaneous to the IXPE pointings assuming a compact zone dominating in the X-rays and VHE, and an extended zone stretching further downstream the jet dominating the emission at lower energies. NuSTAR data allow us to precisely constrain the synchrotron peak and therefore the underlying electron distribution. The change between the different states observed in the three IXPE pointings can be explained by a change of magnetization and/or emission region size, which directly connects the shift of the synchrotron peak to lower energies with the drop in polarization degree., Comment: Accepted for publication in Astronomy & Astrophysics. 19 pages, 9 figures. Corresponding authors: Lea Heckmann, Axel Arbet Engels, David Paneque

The spectra of high-redshift ($z\gtrsim 6$) quasars contain valuable information on the progression of the Epoch of Reionization (EoR). At redshifts $z<6$, the observed Lyman-series forest shows that the intergalactic medium (IGM) is nearly ionized, while at $z>7$ the observed quasar damping wings indicate high neutral gas fractions. However, there remains a gap in neutral gas fraction constraints at $6\lesssim z \lesssim 7$ where the Lyman series forest becomes saturated but damping wings have yet to fully emerge. In this work, we use a sample of 18 quasar spectra at redshifts $6.0

Observations of linear polarization in the 2-8 keV energy range with the Imaging X-ray Polarimetry Explorer (IXPE) explore the magnetic field geometry and dynamics of the regions generating non-thermal radiation in relativistic jets of blazars. These jets, particularly in blazars whose spectral energy distribution peaks at X-ray energies, emit X-rays via synchrotron radiation from high-energy particles within the jet. IXPE observations of the X-ray selected BL Lac-type blazar 1ES 1959+650 in 2022 May 3-4 showed a significant linear polarization degree of $\Pi_\mathrm{x} = 8.0\% \pm 2.3\%$ at an electric-vector position angle $\psi_\mathrm{x} = 123^\circ \pm 8^\circ$. However, in 2022 June 9-12, only an upper limit of $\Pi_\mathrm{x} \leq 5.1\%$ could be derived (at the 99% confidence level). The degree of optical polarization at that time $\Pi_\mathrm{O} \sim 5\%$ is comparable to the X-ray measurement. We investigate possible scenarios for these findings, including temporal and geometrical depolarization effects. Unlike some other X-ray selected BL Lac objects, there is no significant chromatic dependence of the measured polarization in 1ES 1959+650, and its low X-ray polarization may be attributed to turbulence in the jet flow with dynamical timescales shorter than 1 day., Comment: 16 pages, 4 figures, accepted for publication in The Astrophysical Journal

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BACKGROUND: Seasonal malaria chemoprevention (SMC) is recommended by the World Health Organization for the sub-Sahel region in sub-Saharan Africa for preventing malaria in children 3 months old to younger than 5 years. Since 2016, the Malian National Malaria Control Program has deployed SMC countrywide during its high malaria transmission season at a rate of 4 monthly cycles annually. The standard SMC regimen includes sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ). Resistance against SP is suspected to be rising across West Africa; therefore, assessing the effectiveness of an alternative antimalarial drug for SMC is needed to provide a second-line regimen when it is ultimately needed. It is not well understood whether SMC effectively prevents malaria in children aged 5 years or older.OBJECTIVE: The primary goal of the study is to compare 2 SMC regimens (SP-AQ and dihydroartemisinin-piperaquine [DHA-PQ]) in preventing uncomplicated Plasmodium falciparum malaria in children 3 months to 9 years old. Secondly, we will assess the possible use of DHA-PQ as an alternative SMC drug in areas where resistance to SP or AQ may increase following intensive use.METHODS: The study design is a 3-arm cluster-randomized design comparing the SP-AQ and DHA-PQ arms in 2 age groups (younger than 5 years and 5-9 years) and a control group for children aged 5-9 years. Standard SMC (SP-AQ) for children younger than 5 years was provided to the control arm, while SMC with SP-AQ was delivered to children aged 3 months to 9 years (arm 2), and SMC with DHA-PQ will be implemented in study arm 3 for children up to 9 years of age. The study was performed in Mali's Koulikoro District, a rural area in southwest Mali with historically high malaria transmission rates. The study's primary outcome is P falciparum incidence for 2 SMC regimens in children up to 9 years of age. Should DHA-PQ provide an acceptable alternative to SP-AQ, a plausible second-line prevention option would be