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Accountability and hyperaccountability in child protection scandals
Get PDFThe number of child abuse–related deaths has decreased significantly in the United Kingdom over the past 50 years, but there remains public and political concern about the actual and perceived risk of child deaths, with resultant processes enacted to supervise child protection practice. Drawing upon an analysis of the ways in which the deaths of two children, Victoria Climbié and Peter Connelly, became child protection scandals in England, we examine the gap between notions of accountability as an ideal, and enacted accountability, as the embodiments of supervisory mechanisms. We consider how these two sides of accountability are produced in child protection practice via three mechanisms: the inspectorate, the child death review process, and the oversight of individual social workers by their employers and professional regulator. We explore how these mechanisms can lead to the unbalanced apportioning of blame in child protection scandals, whereby social workers and managers are held individually responsible for a child abuse–related death beyond any reasonable conception of answerability—what we refer to as hyperaccountability. Through exploring these issues, we seek to contribute to debates as to how child protection services can be robust, while proportionate, in how they seek to support families and protect vulnerable children
Imaging of human stem cell-derived dopamine grafts correlates with behavioural recovery and reveals microstructural brain changes
Get PDFCell therapy is a promising therapeutic intervention for Parkinson's disease (PD) and is currently undergoing safety and efficacy testing in clinical trials worldwide. The goals of this project were (1) to determine whether [18F]Fluorodopa or [18F]Fallypride imaging correlates robustly with functional recovery; and (2) to explore whether diffusion-weighted MR imaging (DWI) could detect graft-induced cytoarchitectural changes in the host brain. hfVM and hESC-derived dopamine precursor cells were transplanted into the 6-OHDA lesioned rat striatum. Tests of motor function and PET and MR imaging were conducted up to 6 months post-transplantation. Our data demonstrate that [18F]Fluorodopa imaging identified presynaptic DA synthesis from hfVM and hESC-derived dopaminergic grafts and [18F]Fallypride imaging confirmed occupancy and normalisation of D2/D3 receptor expression in the grafted hemisphere. In hfVM grafted rats, [18F]Fluorodopa binding correlated robustly with motor recovery on a range of drug-induced and drug-free behavioural tasks. In hESC-DA grafted rats, improvements in [18F]Fluorodopa PET imaging signals preceded recovery of naturalistic motor behaviours. DWI revealed widespread graft-mediated microstructural changes in the rodent brain, which did not identify graft placement, but instead may reflect remodelling of neuroglia. These data further our understanding of the impact of dopaminergic grafts on brain cytoarchitecture and the potential of these radioligands to predict graft efficacy may aid in the translation of therapeutics from preclinical to clinical settings
Implementation insights from the PEACE pathway across UK eating disorder services
Get PDFBackground/Objectives: Autistic individuals with eating disorders (ED) face socio-emotional, sensory, and communication difficulties that influence engagement and treatment outcomes. We examined how the PEACE Pathway—an autism-informed approach to ED treatment—addresses these challenges through tailored adaptations in clinical care. Methods: A qualitative multiple case studies design was employed, drawing data from clinical documentation, stakeholder feedback, and service evaluations. Results: We identified eight core domains essential for implementation: pathway knowledge, assessment and planning, psychological interventions, sensory management, nutritional care, lived-experience feedback, family/community engagement, and staff training. These domains informed the development of the PEACE Self-Assessment Checklist to support the wider adoption of the pathway. Conclusions: The PEACE Pathway offers a structured approach to adapting ED treatment for autistic individuals. The checklist provides practical guidance for implementing autism-friendly adaptions
Compound screening in human airway basal cells identifies Wnt pathway activators as potential pro-regenerative therapies
Get PDFRegeneration of the airway epithelium restores barrier function and mucociliary clearance following lung injury and infection. The mechanisms regulating the proliferation and differentiation of tissue-resident airway basal stem cells remain incompletely understood. To identify compounds that promote human airway basal cell proliferation, we performed phenotype-based compound screening of 1429 compounds (from the ENZO and Prestwick Chemical libraries) in 384-well format using primary cells transduced with lentiviral luciferase. A total of 17 pro-proliferative compounds were validated in independent donor cell cultures, including the antiretroviral therapy agent abacavir and several Wnt signalling pathway-activating compounds. The effects of compounds on proliferation were further explored in colony formation and 3D organoid assays. Structurally and functionally related compounds that more potently induced Wnt pathway activation were investigated. One such compound, 1-azakenpaullone, induced Wnt target gene activation and basal cell proliferation in mice. Our results demonstrate the pro-proliferative effect of small-molecule Wnt pathway activators on airway basal cells. These findings contribute to the rationale to develop novel approaches to modulate Wnt signalling during airway epithelial repair
Accessible, realistic genome simulation with selection using stdpopsim
Get PDFSelection is a fundamental evolutionary force that shapes patterns of genetic variation across species. However, simulations incorporating realistic selection along heterogeneous genomes in complex demographic histories are challenging, limiting our ability to benchmark statistical methods aimed at detecting selection and to explore theoretical predictions. stdpopsim is a community-maintained simulation library that already provides an extensive catalog of species-specific population genetic models. Here we present a major extension to the stdpopsim framework that enables simulation of various modes of selection, including background selection, selective sweeps, and arbitrary distributions of fitness effects (DFE) acting on annotated subsets of the genome (for instance, exons). This extension maintains stdpopsim's core principles of reproducibility and accessibility while adding support for species-specific genomic annotations and published DFE estimates. We demonstrate the utility of this framework by comparing methods for demographic inference, DFE estimation, and selective sweep detection across several species and scenarios. Our results demonstrate the robustness of demographic inference methods to selection on linked sites, reveal the sensitivity of DFE-inference methods to model assumptions, and show how genomic features, like recombination rate and functional sequence density, influence power to detect selective sweeps. This extension to stdpopsim provides a powerful new resource for the population genetics community to explore the interplay between selection and other evolutionary forces in a reproducible, user-friendly framework.</p
BA and object state changes:Unspecific morphosyntactic cues shape Mandarin discourse comprehension
Get PDFUnderstanding object state changes as consequences of transitive events is an important part of event cognition. How do people do this? Previous research shows that comprehenders use verb-based morphosyntactic cues that have specific meanings to generate expectations about the state of the upcoming objects in discourse processing. Can they also do so using non–verb-based and unspecific morphosyntactic cues, such as the preposition “BA” in the Mandarin “BA” structure? In four forced-choice image selection experiments, we found a robust “BA” effect in shaping Mandarin comprehenders’ discourse expectations about object state changes. Moreover, this effect was amplified by the presence of classifiers and modulated by contexts with varying levels of constraint on the upcoming objects. These findings provide important insights into discourse expectations based on a previously unstudied type of unspecific morphosyntactic cue (i.e., a preposition) and shed new light on language-mediated visual attention and event segmentation in discourse processing
Identifying and understanding how critical landscapes for carbon sequestration respond to development for low carbon energy production: insight to inform optimal land planning and management strategies
Get PDFWind farms can mitigate increasing CO2 emissions by fossil-fuel free energy generation. However, landscape disturbance during development must not have lasting impacts on C sequestration, an ecosystem service. To understand how a critical carbon landscape responds to wind farm development, we monitored for 10 years dissolved organic carbon (DOC) export in five catchments draining Europe's second largest onshore wind farm, Whitelee, UK. The DOC flux trend and seasonality were modelled using Generalised Additive and Mixed Models, novelly using first derivatives of trends to identify responses to wind farm development. Unlike a nearby, minimally-disturbed catchment, Whitelee catchment DOC fluxes increased over the decade, tracking successive phases of wind farm development, particularly forest felling to enable turbine location. Inter-catchment differences in the rate of DOC flux, where slowing suggests recovery (not always evident), reflect differing intensity (timing and spatial reach) of catchment disturbance. However, increased DOC flux approximated 3.5 % maximum of C likely sequestered and therefore soil C sequestration is unlikely to be compromised unless the soils are highly degraded and close to not being a C sink. For the greenest energy transition, responsible planning should minimise C losses, even when small, and in a critical landscape may require consideration of impact on other ecosystem services. For example, deterioration in quality of potable water supply occurred within the observation period. Ongoing provisioning of multiple ecosystem services from critical carbon landscapes requires planning. We demonstrate an example of such an approach for wind farm development considering in priority order carbon storage, forest products, potable water supply. Our findings are relevant to integrated landscape planning and management in temperate and high latitude/altitude peatlands globally that are subject to wind energy development and/or forest felling
Distinct Bone Metabolic Networks Identified in Phospho1-/- Mice Versus Wild Type Mice using [18F]FDG Total-Body PET
Get PDFIntroduction Total-body PET is a recent development in clinical imaging that produces large datasets involving multiple tissues, enabling the use of new analytical methods for multi-organ assessments, such as network analysis – a well-developed method in neuroimaging. The skeletal system provides a good model for applying network analysis to total-body PET, as bone serves many classical whole-body functions as well as being an endocrine regulator of metabolism. Previous reports have suggested an association between the expression of bone specific phosphatase, orphan 1 and disorders of altered energy metabolism such as obesity and diabetes. Here, we explore how lacking phosphatase, orphan 1 affects the skeletal metabolic networks of mice as a test approach for deploying network analysis in total-body PET. Methods We retrospectively analysed [18F]fluorodeoxyglucose total-body PET/CT images from six 13-week-old wild type mice, three 22-week-old wild type mice, and three 22-week-old Phospho1 −/− mice. Pearson correlation networks were created using the dynamic data from seven bone regions, with a Pearson threshold of r>0.6 (significant at p<0.005). Results The bone metabolic networks of 13-week-old wild type mice were found to robustly resist changes to the data from different PET measurements, increased noise, and shortened scan length. Key features were repeatedly observed, namely that all bones except the spine are highly inter-correlated, while the spine has minimal correlation to other bones. When networkanalysis was used to compare the three cohorts, the older wild type network had similar features to the young mouse, whereas the Phospho1−/− network had increased correlations across all bones. An all-cohort network separated the data into one part including only bones from the wild type mice (13 nodes) and one part only bones from the Phospho1 24 −/− mice (8 nodes, 95% separation purity). Within the wild type section, the same bone from each young and old mouse were correlated.Discussion We demonstrated network analysis is a promising method for studying whole-body PET, sensitive to dynamic details in the data without relying on assumptions or modelling. The proposed method could be applied to other total-body PET data – of healthy and diseased subjects, with different radiotracers, and more – to further elucidate tissue interactions at a systems level.<br/
Navigating negative emotions:The role of negativity bias in digital activism
Get PDFThis study investigates the influence of negativity bias in digital activism (e.g., #BlackLivesMatter, #AllLivesMatter, and Nike’s #TakeAKnee campaigns). Analyzing over 3.5 million tweets across a decade, the research highlights how predominantly negative emotions, such as anger and disgust, shape public perceptions in the context of social justice movements and brand involvement in social issues. The results from a robust methodological framework, using social media analytics and advanced sentiment analysis tools like VADER and the TTL transformer model, showed that negative emotions significantly impact the overall sentiment of African Americans and companies like Nike. Specifically, anger within the #BlackLivesMatter and #AllLivesMatter discourses negatively related to overall sentiment toward African Americans, while emotions such as sadness in the #TakeAKnee discussions positively related to overall sentiment toward Nike. Also, expressions of disgust within #AllLivesMatter and #TakeAKnee were associated with positive perceptions of African Americans. In contrast, positive emotions such as joy, and the neutral emotion of surprise showed no significant effects. These results underscore the dual impacts of negativity bias in digital activism, indicating the need for strategies to mitigate its effects and enhance the effectiveness of digital campaigns
Senescence, aging and disease throughout the gastrointestinal system
Get PDFSenescence is an irreversible cell cycle arrest -characterized by morphological alterations, genomic instability and secretome changes- that profoundly affects the tissue structure and function.Accumulating evidence indicates that senescence plays a relevant role in gastrointestinal pathologies: senescence contributes to salivary gland hypofunction, is instrumental in the development of oral sub-mucous fibrosis, drives age-dependent hepatic steatosis and regulates the clinical progression of steatotic liver disease. Senescence in the biliary tract develops in response to ischemic injury in biliary complications and is characteristic of biliary conditions such as biliary atresia, primary sclerosing cholangitis and primary biliary cirrhosis. Senescence also contributes to acute pancreatitis and plays a major role in the dysfunction of pancreatic beta cells. Moreover, senescence is a hallmark of a number of gastrointestinal conditions such as inflammatory bowel disease and colorectal cancer. These examples illustrate the widespread effect of cellular senescence in the gastrointestinal tract, not just as a consequence of the disease, but as a driver of pathology and a potential therapeutic target. In this review we describe the mechanisms, hallmarks and consequences of cellular senescence, as well as the therapeutic potential of senescence-targeting interventions. We aim to highlight the importance of understanding the molecular basis of senescence in gastroenterology, whilst connecting the worlds of research and clinical practice.<br/
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