A model of the determinants of expenditure on children's personal social services

Every year the United Kingdom central government assesses the relative spending needs of English local authorities in respect of the services for which is it responsible. This is done by estimating a Standard Spending Assessment (SSA) for each service, which is intended to indicate the spending requirements of an authority if it were to adopt a standard level of services, given the circumstances in its area. In practice, statistical methods are used to develop SSAs for most services. This report describes the findings of a study designed to review the methods for setting SSAs for a single service: personal social services (PSS) for children, which in 1995/96 accounting for about £1.8 billion of expenditure (4.4% of total local government expenditure). The study was commissioned by the Department of Health and undertaken by a consortium which comprised The University of York, MORI and the National Children’s Bureau. The study was guided by a technical advisory group, comprising representatives from the local authority associations and the Department of Health. In seeking to limit the length of the report, the authors have necessarily omitted a great deal of the technical material produced in the course of the study. We understand that the Department of Health is willing to make this material and the data used in the study available to interested parties, subject to certain confidentiality restrictions. Existing methodology for constructing SSAs had been the subject of some criticism, both in general and specifically in respect of children’s PSS. This document reports the results of a study designed to apply a radically new statistical approach to estimating the SSA for children’s PSS. Previous methods were based on statistical analysis of local authority aggregate data. In contrast, this study is based on an analysis of PSS spending in 1,036 small areas (with populations of about 10,000) within 25 local authorities. A relatively new statistical method known as multilevel modelling, which was originally developed in the educational sector, was used for this purpose.children, SSA, social services

Heparan Sulfate-Editing Extracellular Sulfatases Enhance Vascular Endothelial Growth Factor Bioavailability for Ischemic Heart Repair

Korf-Klingebiel M, Reboll MR, Grote K, et al. Heparan Sulfate-Editing Extracellular Sulfatases Enhance Vascular Endothelial Growth Factor Bioavailability for Ischemic Heart Repair. Circulation research. 2019;125(9):787-801.RATIONALE: Mechanistic insight into the inflammatory response after acute myocardial infarction (MI) may inform new molecularly-targeted treatment strategies to prevent chronic heart failure.; OBJECTIVE: We identified the sulfatase SULF2 in an in silico secretome analysis in bone marrow cells from patients with acute MI and detected increased sulfatase activity in myocardial autopsy samples. SULF2 (Sulf2 in mice) and its isoform SULF1 (Sulf1) act as endo-sulfatases removing 6 O sulfate groups from heparan sulfate (HS) in the extracellular space, thus eliminating docking sites for HS binding proteins. We hypothesized that the Sulfs have a role in tissue repair after MI.; METHODS AND RESULTS: Both Sulfs were dynamically upregulated after coronary artery ligation in mice, attaining peak expression and activity levels during the first week after injury. Sulf2 was expressed by monocytes and macrophages, Sulf1 by endothelial cells and fibroblasts. Infarct border-zone capillarization was impaired, scar size increased, and cardiac dysfunction more pronounced in mice with a genetic deletion of either Sulf1 or Sulf2. Studies in bone marrow-chimeric Sulf-deficient mice and Sulf-deficient cardiac endothelial cells established that inflammatory cell-derived Sulf2 and endothelial cell-autonomous Sulf1 promote angiogenesis. Mechanistically, both Sulfs reduced HS sulfation in the infarcted myocardium, thereby diminishing vascular endothelial growth factor A (Vegfa) interaction with HS. Along this line, both Sulfs rendered infarcted mouse heart explants responsive to the angiogenic effects of HS-binding Vegfa164 but did not modulate the angiogenic effects of non-HS-binding Vegfa120. Treating wild-type mice systemically with the small molecule HS antagonist surfen (bis 2 methyl-4-amino-quinolyl-6-carbamide, 1 mg/kg/day) for 7 days after MI released Vegfa from HS, enhanced infarct border-zone capillarization, and exerted sustained beneficial effects on cardiac function and survival.; CONCLUSIONS: These findings establish HS-editing Sulfs as critical inducers of postinfarction angiogenesis and identify HS sulfation as a therapeutic target for ischemic tissue repair