A method for generating coherent spatially explicit maps of seasonal palaeoclimates from site-based reconstructions

We describe a method for reconstructing spatially explicit maps of seasonal palaeoclimate variables from site-based reconstructions. Using a 3D-Variational technique, the method finds the best statistically unbiased, and spatially continuous, estimate of the palaeoclimate anomalies through combining the site-based reconstructions and a prior estimate of the palaeoclimate state. By assuming a set of correlations in the error of the prior, the resulting climate is smoothed both from month to month and from grid cell to grid cell. The amount of smoothing can be controlled through the choice of two length-scale values. The method is applied to a set of reconstructions of the climate of the Last Glacial Maximum (ca. 21,000 years ago, yr BP) for southern Europe derived from pollen data with a prior derived from results from the third phase of the Palaeoclimate Intercomparison Project (PMIP3). We demonstrate how to choose suitable values for the smoothing length scales from the datasets used in the reconstruction

Kahler Geometry and Burgers' Vortices

We study the Navier-Stokes and Euler equations of incompressible hydrodynamics. Taking the divergence of the momentum equation leads, as usual, to a Poisson equation for the pressure: in this paper we study this equation in two spatial dimensions using Monge-Ampere structures. In two dimensional flows where the Laplacian of the pressure is positive, a Kahler geometry is described on the phase space of the fluid; in regions where the Laplacian of the pressure is negative, a product structure is described. These structures can be related to the ellipticity and hyperbolicity (respectively) of a Monge-Ampere equation. We then show how this structure can be extended to a class of canonical vortex structures in three dimensions

RIPK1-mediated immunogenic cell death promotes anti-tumour immunity against soft-tissue sarcoma.

Drugs that mobilise the immune system against cancer are dramatically improving care for many people. Dying cancer cells play an active role in inducing anti-tumour immunity but not every form of death can elicit an immune response. Moreover, resistance to apoptosis is a major problem in cancer treatment and disease control. While the term "immunogenic cell death" is not fully defined, activation of receptor-interacting serine/threonine-protein kinase 1 (RIPK1) can induce a type of death that mobilises the immune system against cancer. However, no clinical treatment protocols have yet been established that would harness the immunogenic potential of RIPK1. Here, we report the first pre-clinical application of an in vivo treatment protocol for soft-tissue sarcoma that directly engages RIPK1-mediated immunogenic cell death. We find that RIPK1-mediated cell death significantly improves local disease control, increases activation of CD8+ T cells as well as NK cells, and enhances the survival benefit of immune checkpoint blockade. Our findings warrant a clinical trial to assess the survival benefit of RIPK1-induced cell death in patients with advanced disease at limb extremities

Evidence-based intervention for preschool children with primary speech and language impairments: Child Talk - an exploratory mixed-methods study

BackgroundThe Child Talk study aimed to develop an evidence-based framework to support the decision-making of speech and language therapists (SLTs) as they design and plan interventions appropriate to the needs of individual children with primary speech and language impairments and their families. The need for early identification and effective intervention for these children continues to be a government policy priority because of the link between children’s early speech and language skills and their broader well-being and outcomes in later life. The first phase of Child Talk sought to map and describe current SLT practice for these children; identify and summarise the existing research evidence relating to practice; and investigate the perspectives of parents, early years practitioners, preschool children and ‘underserved’ communities on speech and language therapy. The second phase of Child Talk focused on the development of a toolkit – assessment tools, outcome measures and a data set – to support future service and economic evaluations of the framework.MethodsChild Talk adopted a mixed-methods design. Quantitative methods included surveys and investigated the prevalence and patterns of intervention usage; qualitative data collection methods included focus groups, interviews and reflection to investigate participants’ perspectives and understandings of interventions. Data analysis methods included descriptive and inferential statistics, thematic and content analysis and framework analysis. Participants were recruited nationally through six NHS sites, professional bodies, parent groups and advertising. Participants included SLTs (n = 677), parents (n = 84), preschool children (n = 24), early years practitioners (n = 31) and ‘underserved’ communities (n = 52).Key findingsSpeech and language therapy interventions were characterised in terms of nine themes, viewed as comprehensive and inclusive by practitioners. Relevant assessments, interventions and outcome domains were identified for the nine themes. Areas of tacit knowledge and underspecified processes contributed to variability in the detail of the framework. Systematic reviews identified 58 relevant and robust studies (from 55,271 papers retrieved from the initial literature search). The number of studies relevant to each theme varied from 1 to 33. Observational data on preschool children’s perspectives on speech and language therapy interventions revealed the dynamic nature of their interaction with different activities and people within therapy sessions. Parents’ experiences of speech and language therapy were generally positive although some reported that the rationale for therapy was not always clear. Parental perspectives in underserved communities suggested that, although parents were confident about how to support children’s language development, they were less informed about the nature of language impairments and the function of speech and language therapy. The availability of information regarding resources directed towards speech and language therapy services was poor. In particular, services lacked both a culture of collecting outcome data routinely and measures of professional input and costs associated with their activities.ConclusionA descriptive framework of SLT practice has been developed to support the discussions between therapists and families when making decisions regarding the selection of interventions and outcome measures. Further research is needed to address gaps in the intervention framework and evaluate its effectiveness and cost-effectiveness in improving outcomes for preschool children with primary speech and language impairments.Study registrationThis study is registered as PROSPERO CRD42013006369

Putting victims first? : a critique of Coalition anti-social behaviour policy

Anti-social behaviour (ASB) policy was not pursued by the Conservative–Liberal Democrat Coalition government with the same vigour as their New Labour predecessors. Where developments did take place a clear shift in emphasis was apparent, with the needs of ASB victims elevated to the forefront of policy. This article critically appraises two major developments that showcase the Coalition government’s attempts to overhaul ASB policy to ‘put victims first’, namely: the changes to call handling and case management processes, and the Community Trigger, which forces the authorities to review their responses to complaints of ASB in circumstances where victims feel they have been ignored. These particular policies aim to prioritise victims’ needs; however, it is argued the new victim-focus: is diluted by competing Coalition ASB agendas, demonstrates little connection between rhetoric and reality, provides limited redress for all victims and fails to coalesce with established attempts to tackle perpetrators of ASB

Constructions of vulnerability in comparative perspective: Scottish protection policies and the trouble with "adults at risk"

This paper places Scottish adult support and protection (ASP) policy in the context of debates about the nature of 'vulnerability' and its usefulness as a defining concept in law and social policy. It examines the construction of 'adults at risk' in ASP policy, using a comparison with the construction of children in Scottish child protection policy, on the one hand, and women in Scottish domestic abuse policy, on the other, to illuminate the nature of the vulnerability that ASP considers itself to be addressing. It then problematises this construction, drawing both on the social model of disability and on an ethic of care. It concludes that current ASP policy remains underpinned by unhelpful assumptions about disabled people, older people and people with mental or physical health problems. A more inclusive understanding of vulnerability would be more empowering to these people and others, in policies concerned with mistreatment and abuse