Effective service provision and partnerships in service providers for children and young people with special educational needs and disabilities: a mixed methods systematic review protocol

It is widely recognized that provision of services for children and young people (CYP) with Special Educational Needs and Disabilities (SEND) are enhanced when services such as healthcare, social care, and education collaborate and interact effectively, rather than separately. In the UK, while there have been significant changes to policy and provision which support and improve collaboration, professionals responsible for implementing these changes face multiple challenges, including a lack of specific implementation guidance and a logic model or framework to illustrate how effective multi-agency working could, or should, work. This systematic review aims to identify the ‘key ingredients’ for effective multi-agency working in services for CYP with SEND; and the most effective forms of partnership working in this setting. In addition, the review will highlight interventions that lead to improved service outcomes; and the conditions in the local area (organisational or geographical) that support and encourage success. This protocol has been written following the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols guidelines. Searches will be conducted on several health, care, education and applied social science databases from the year 2012 onwards. Citation chaining will be undertaken, as will broader grey literature searching to enrich the findings. Qualitative, quantitative, and mixed methods studies will be included, assessed independently and critically appraised or assessed for risk of bias using appropriate tools based on study design. Data will be extracted using a standardized, pre-piloted data extraction form. A convergent segregated approach to synthesis and integration will be used in which the quantitative and qualitative data will be synthesized independently, and then integrated using a joint display integration matrix. Results will be of interest to educators and health and social care professionals that provide services to those with SEND. These will also be used to develop policy recommendations for how UK healthcare, social care, and education services for CYP with SEND aged 0–25 can most effectively collaborate and improve service outcomes. The review will also identify any gaps in the literature to recommend areas for future research. Funding for this review was provided by the Department for Education.PROSPERO registration: CRD42022352194

Characterization of gene mutations and copy number changes in acute myeloid leukemia using a rapid target enrichment protocol

Prognostic stratification is critical for making therapeutic decisions and maximizing survival of patients with acute myeloid leukemia. Advances in the genomics of acute myeloid leukemia have identified several recurrent gene mutations whose prognostic impact is being deciphered. We used HaloPlex target enrichment and Illumina-based next generation sequencing to study 24 recurrently mutated genes in 42 samples of acute myeloid leukemia with a normal karyotype. Read depth varied between and within genes for the same sample, but was predictable and highly consistent across samples. Consequently, we were able to detect copy number changes, such as an interstitial deletion of BCOR, three MLL partial tandem duplications, and a novel KRAS amplification. With regards to coding mutations, we identified likely oncogenic variants in 41 of 42 samples. NPM1 mutations were the most frequent, followed by FLT3, DNMT3A and TET2. NPM1 and FLT3 indels were reported with good efficiency. We also showed that DNMT3A mutations can persist post-chemotherapy and in 2 cases studied at diagnosis and relapse, we were able to delineate the dynamics of tumor evolution and give insights into order of acquisition of variants. HaloPlex is a quick and reliable target enrichment method that can aid diagnosis and prognostic stratification of acute myeloid leukemia patients.This project was funded by the Wellcome Trust. NB is a fellow of the European Hematology Association and was supported by the Academy of Medical Sciences. EP is a European Hematology Association Advanced Research Fellow. GV is a Wellcome Trust Senior Fellow in Clinical Science. IV is funded by Spanish Ministerio de Economía y Competitividad subprograma Ramón y Cajal

What is the best way to evaluate social prescribing? A qualitative feasibility assessment for a national impact evaluation study in England

Objectives Despite significant investment in social prescribing in England over the last decade, we still do not know if it works, or how models of social prescribing fit within wider health and care policy and practice. This study explores current service delivery structures and assesses the feasibility of a national evaluation of the link worker model. Methods Semi-structured interviews were conducted between May and September 2020, with 25 key informants from across social prescribing services in England. Participants included link workers, voluntary, community and social enterprise staff, and those involved in policy and decision-making for social prescribing services. Interview and workshop transcripts were analysed thematically, adopting a framework approach. Results We found differences in how services are provided, including by individual link workers, and between organisations and regions. Standards, referral pathways, reporting, and monitoring structures differ or are lacking in voluntary services as compared to clinical services. People can self-refer to a link worker or be referred by a third party, but the lack of standardised processes generated confusion in both public and professional perceptions of the link worker model. We identified challenges in determining the appropriate outcomes and outcome measures needed to assess the impact of the link worker model. Conclusions The current varied service delivery structures in England poses major challenges for a national impact evaluation. Any future rigorous evaluation needs to be underpinned with national standardised outcomes and process measures which promote uniform data collection

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

The origin of water in the primitive Moon as revealed by the lunar highlands samples

The recent discoveries of hydrogen (H) bearing species on the lunar surface and in samples derived from the lunar interior have necessitated a paradigm shift in our understanding of the water inventory of the Moon, which was previously considered to be a ‘bone-dry’ planetary body. Most sample-based studies have focused on assessing the water contents of the younger mare basalts and pyroclastic glasses, which are partial-melting products of the lunar mantle. In contrast, little attention has been paid to the inventory and source(s) of water in the lunar highlands rocks which are some of the oldest and most pristine materials available for laboratory investigations, and that have the potential to reveal the original history of water in the Earth–Moon system. Here, we report in-situ measurements of hydroxyl (OH) content and H isotopic composition of the mineral apatite from four lunar highlands samples (two norites, a troctolite, and a granite clast) collected during the Apollo missions. Apart from troctolite in which the measured OH contents in apatite are close to our analytical detection limit and its H isotopic composition appears to be severely compromised by secondary processes, we have measured up to ~2200 ppm OH in the granite clast with a weighted average δD of ~-105±130‰, and up to ~3400 ppm OH in the two norites (77215 and 78235) with weighted average δD values of -281±49‰ and -27±98‰, respectively. The apatites in the granite clast and the norites are characterised by higher OH contents than have been reported so far for highlands samples, and have H isotopic compositions similar to those of terrestrial materials and some carbonaceous chondrites, providing one of the strongest pieces of evidence yet for a common origin for water in the Earth–Moon system. In addition, the presence of water, of terrestrial affinity, in some samples of the earliest-formed lunar crust suggests that either primordial terrestrial water survived the aftermath of the putative impact-origin of the Moon or water was added to the Earth–Moon system by a common source immediately after the accretion of the Moon

Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants

INTRODUCTION: There is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures. METHODS: We included 12,369 non-demented participants from eight population-based studies. Imputed genetic data and measured plasma Aβ1-40, Aβ1-42 levels and Aβ1-42/Aβ1-40 ratio were used to perform genome-wide association studies, and gene-based and pathway analyses. Significant variants and genes were followed up for their association with brain positron emission tomography Aβ deposition and AD risk. RESULTS: Single-variant analysis identified associations with apolipoprotein E (APOE) for Aβ1-42 and Aβ1-42/Aβ1-40 ratio, and BACE1 for Aβ1-40. Gene-based analysis of Aβ1-40 additionally identified associations for APP, PSEN2, CCK, and ZNF397. There was suggestive evidence for interaction between a BACE1 variant and APOE ε4 on brain Aβ deposition. DISCUSSION: Identification of variants near/in known major Aβ-processing genes strengthens the relevance of plasma-Aβ levels as an endophenotype of AD

Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH

Violence: a glossary

Violence has been explicitly identified as a significant public health problem. This glossary clarifies widely used definitions and concepts of violence within the public health field, building on those promoted through the 2002 World Report on Violence and Health. We provide definitions and concepts that can be usefully applied to identify points for public health intervention to prevent the social and health impacts of violence