Using knowledge brokering to produce community-generated evidence

Background: Devolution and integration of health and social care have placed increasing pressure on local statutory services, with a corresponding shift of health and social care to community organisations. The voluntary and charitable sector (VCS) is expected to make the case for increased funding by providing evidence of value and impact. Aims and objectives: This paper explores the challenges of compiling evidence on health outcomes which do not reflect the holistic nature of VCS support. We document how knowledge brokering can be used to enable the VCS to generate evidence. Key conclusions: Knowledge brokering (KB) may be an effective approach for developing community-generated evidence. Brokering is also needed to change perspectives on what counts as good evidence Key messages Health outcome measures are not seen to be appropriate by the voluntary sector for social prescribing services. A new evidence base is needed that reflects the social determinants of health. Knowledge brokering may be an effective approach for developing community-generated evidence. Brokering is also needed to change perspectives on what counts as good evidence

Simulation of Preterm Neonatal Brain Metabolism During Functional Neuronal Activation Using a Computational Model

We present a computational model of metabolism in the preterm neonatal brain. The model has the capacity to mimic haemodynamic and metabolic changes during functional activation and simulate functional near-infrared spectroscopy (fNIRS) data. As an initial test of the model's efficacy, we simulate data obtained from published studies investigating functional activity in preterm neonates. In addition we simulated recently collected data from preterm neonates during visual activation. The model is well able to predict the haemodynamic and metabolic changes from these observations. In particular, we found that changes in cerebral blood flow and blood pressure may account for the observed variability of the magnitude and sign of stimulus-evoked haemodynamic changes reported in preterm infants

Pharmacological Inhibition of polysialyltransferase ST8SiaII Modulates Tumour Cell Migration

YesPolysialic acid (polySia), an α-2,8-glycosidically linked polymer of sialic acid, is a developmentally regulated posttranslational modification predominantly found on NCAM (neuronal cell adhesion molecule). Whilst high levels are expressed during development, peripheral adult organs do not express polySia-NCAM. However, tumours of neural crest-origin re-express polySia-NCAM: its occurrence correlates with aggressive and invasive disease and poor clinical prognosis in different cancer types, notably including small cell lung cancer (SCLC), pancreatic cancer and neuroblastoma. In neuronal development, polySia-NCAM biosynthesis is catalysed by two polysialyltransferases, ST8SiaII and ST8SiaIV, but it is ST8SiaII that is the prominent enzyme in tumours. The aim of this study was to determine the effect of ST8SiaII inhibition by a small molecule on tumour cell migration, utilising cytidine monophosphate (CMP) as a tool compound. Using immunoblotting we showed that CMP reduced ST8iaII-mediated polysialylation of NCAM. Utilizing a novel HPLC-based assay to quantify polysialylation of a fluorescent acceptor (DMB-DP3), we demonstrated that CMP is a competitive inhibitor of ST8SiaII (Ki = 10 μM). Importantly, we have shown that CMP causes a concentration-dependent reduction in tumour cell-surface polySia expression, with an absence of toxicity. When ST8SiaII-expressing tumour cells (SH-SY5Y and C6-STX) were evaluated in 2D cell migration assays, ST8SiaII inhibition led to significant reductions in migration, while CMP had no effect on cells not expressing ST8SiaII (DLD-1 and C6-WT). The study demonstrates for the first time that a polysialyltransferase inhibitor can modulate migration in ST8SiaII-expressing tumour cells. We conclude that ST8SiaII can be considered a druggable target with the potential for interfering with a critical mechanism in tumour cell dissemination in metastatic cancers.Yorkshire Cancer Research; EPSRC; Association for International Cancer Research; Jordanian Government PhD scholarshi

Motor learning in developmental coordination disorder: behavioral and neuroimaging study

Developmental coordination disorder (DCD) is characterized by motor learning deficits that are poorly understood within whole-body activities context. Here we present results of one of the largest non-randomized interventional trials combining brain imaging and motion capture techniques to examine motor skill acquisition and its underpinning mechanisms in adolescents with and without DCD. A total of 86 adolescents with low fitness levels (including 48 with DCD) were trained on a novel stepping task for a duration of 7 weeks. Motor performance during the stepping task was assessed under single and dual-task conditions. Concurrent cortical activation in the prefrontal cortex (PFC) was measured using functional near-infrared spectroscopy (fNIRS). Additionally, structural and functional magnetic resonance imaging (MRI) was conducted during a similar stepping task at the beginning of the trial. The results indicate that adolescents with DCD performed similarly to their peers with lower levels of fitness in the novel stepping task and demonstrated the ability to learn and improve motor performance. Both groups showed significant improvements in both tasks and under single- and dual-task conditions at post-intervention and follow-up compared to baseline. While both groups initially made more errors in the Stroop task under dual-task conditions, at follow-up, a significant difference between single- and dual-task conditions was observed only in the DCD group. Notably, differences in prefrontal activation patterns between the groups emerged at different time points and task conditions. Adolescents with DCD exhibited distinct prefrontal activation responses during the learning and performance of a motor task, particularly when complexity was increased by concurrent cognitive tasks. Furthermore, a relationship was observed between MRI brain structure and function measures and initial performance in the novel stepping task. Overall, these findings suggest that strategies that address task and environmental complexities, while simultaneously enhancing brain activity through a range of tasks, offer opportunities to increase the participation of adolescents with low fitness in physical activity and sports

Multispecies Sustainability

The sustainability concept in its current form suffers from reductionism. The common interpretation of ‘meeting the needs of the present without compromising the ability of future generations to meet their own needs’ fails to explicitly recognize their interdependence with needs of current and future non-human generations. Here, we argue that the focus of sustainability on human well-being – a purely utilitarian view of nature as a resource for humanity – limits its conceptual and analytical power, as well as real-world sustainability transformation efforts. We propose a broadened concept of ‘multispecies sustainability’ by acknowledging interdependent needs of multiple species’ current and future generations. We develop the concept in three steps: (1) discussing normative aspects, fundamental principles underlying the con- cept, and potential visual models, (2) showcasing radically diverging futures emerging from a scenario thought experiment based on the axes sustainable-unsustainable and multispecies-anthropocentric, and (3) exploring how multispecies sustainability can be applied to research and policy-making through two case studies (a multispecies stakeholder framework and the Healthy Urban Microbiome Initiative)

Electron mobility and localization in dense He4 gas

The mobility was measured for gas densities 2< rho <40*1020 atoms cm-3, and for gas temperatures 4<T<300K. Refinements of former treatments of electron localization via the bubble model are presented which demonstrate a strong correlation between the mobility 'edge' and a localization criterion. Detailed agreement between theory and experiment is not realized, but the general features of the density and temperature dependence of the mobility are reproduced in a consistent manner.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48846/2/jbv6i5p908.pd

Particles-vortex interactions and flow visualization in He4

Recent experiments have demonstrated a remarkable progress in implementing and use of the Particle Image Velocimetry (PIV) and particle tracking techniques for the study of turbulence in He4. However, an interpretation of the experimental data in the superfluid phase requires understanding how the motion of tracer particles is affected by the two components, the viscous normal fluid and the inviscid superfluid. Of a particular importance is the problem of particle interactions with quantized vortex lines which may not only strongly affect the particle motion, but, under certain conditions, may even trap particles on quantized vortex cores. The article reviews recent theoretical, numerical, and experimental results in this rapidly developing area of research, putting critically together recent results, and solving apparent inconsistencies. Also discussed is a closely related technique of detection of quantized vortices negative ion bubbles in He4.Comment: To appear in the J Low Temperature Physic