Perspectives on innovation within medium-sized firms in Wales

The Welsh economy is heading towards a post-Brexit future with historically lower levels of productivity continuing to leave the country lagging behind the UK average (Huggins and Williams, 2011; Welsh Government, 2017). An understanding of how new models of innovation are constructed and developed are then particularly important for policy makers and academia in Wales. As noted by Baughan (2015), innovation accounts for 25-50% of labour productivity growth

Activities of organic farmers succeeding in reducing lameness in dairy cows

Sixty-seven organic producers were among 189 dairy farmers completing the “Healthy Feet Project” in the UK. This aimed to reduce lameness in dairy herds by implementing existing knowledge. Participants received input at two levels: monitoring alone, or monitoring with extra support through a single veterinary advisory visit, annual visits from a trained non-veterinary facilitator and materials and contacts to encourage change. On average lameness on organic farms reduced by 12 percentage points over the three year period. On the farms achieving the greatest reduction,the most common changes were improvements to tracks and cubicle comfort, and more frequent footbathing or foot trimming. Practices to improve foot cleanliness, such as more frequent removal of slurry, were less often adopted. Further progress might be achieved by improvements of foot hygiene. Several farms with low lameness that reduced prevalence further improved their handling facilities and treated cows more promptly

Investigating visual strategies during the recognition of static and dynamic facial affect in TBI and control cohorts

bjectives: Traumatic brain injury (TBI) often precipitates socio-emotional problems which impinge on social relationships. Although socio-emotional impairments are debilitating the mechanisms underpinning these are poorly understood. Social interactions are dynamic yet research frequently employs static assessments. We investigated eye scan patterns of TBI and controls viewing static/dynamic facial expressions. Design: Factorial analysis investigated correct response, reaction time, fixation duration/count to areas of interest (eyes, nose and mouth) across six emotions (anger, disgust, fear, happy, sadness and surprise). Methods: 17 TBI participants were recruited from the NHS and age/gender matched controls were recruited using stratified opportunity sampling. Images from the Amsterdam Dynamic Facial Expression Set (ADFES) were presented on a Tobii T120 Eye Tracker screen. Multivariate and correlational methods were used to analyse data. Static Results: Controls displayed greater fixation durations; counts to eyes were more accurate and quicker identifying emotions than TBI participants. The TBI group focused more on the nose compared to controls. Higher scores on the ADFES correlated with quicker responses across all emotions for all participants and positive relationships between empathy, emotion recognition and fixation patterns were revealed. Gaze-patterns for the six emotions differed slightly between the groups although fearful faces induced more/longer fixations and happy faces the least/shortest fixations. Dynamic Results: Controls were more accurate at identifying emotions than the TBI group but no group differences were found for gaze-patterns. Happy faces induced more/longer fixations and sad faces the least/shortest fixations. A positive correlation between correct scores on the ADFES and empathy scores across all emotions for all participants was established. Conclusions: Irregular gaze-patterns could underpin some socio-emotional problems after TBI, highlighting the potential for innovative rehabilitation approaches. Visual strategies underlying the recognition of static/dynamic emotions may differ. The key limitation was the small sample size which will hopefully be rectified in future wor

Don’t turn your back on the symptoms of psychosis : the results of a proof-of-principle, quasi-experimental intervention to reduce duration of untreated psychosis

Background No evidence based approach to reduce duration of untreated psychosis (DUP) has been effective in the UK. Existing interventions have many components and have been difficult to replicate. The majority of DUP in Birmingham, UK is accounted for by delays within mental health services (MHS) followed by help-seeking delay and, we hypothesise, these require explicit targeting. This study examined the feasibility and impact of an intervention to reduce DUP, targeting help-seeking and MHSs delays. Methods A dual-component intervention, comprising a direct care pathway, for 16-25 year olds, and a community psychosis awareness campaign, using our youth-friendly website as the central hub, was implemented, targeting the primary sources of care pathway delays experienced by those with long DUP. Evaluation, using a quasi-experimental, design compared DUP of cases in two areas of the city receiving early detection vs detection as usual, controlling for baseline DUP in each area. Results DUP in the intervention area was reduced from a median 71 days (mean 285) to 39 days (mean 104) following the intervention, with no change in the control area. Relative risk for the reduction in DUP was 0.74 (95 % CI 0.35 to 0.89; p = .004). Delays in MHSs and help-seeking were also reduced. Conclusions Our targeted approach appears to be successful in reducing DUP and could provide a generalizable methodology applicable in a variety of healthcare contexts with differing sources of delay. More research is needed, however, to establish whether our approach is truly effective

E-cadherin can limit the transforming properties of activating β-catenin mutations

Wnt pathway deregulation is a common characteristic of many cancers. But only Colorectal Cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of pancreas) have activating mutations in β-catenin (CTNNB1). We have compared the dynamics and the potency of β-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of β-catenin took much longer to achieve a Wnt deregulation and acquire a crypt-progenitor-cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of β-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of β-catenin mutation to differentially transform the SI versus the colon correlated with significantly higher expression of the β-catenin binding partner E-cadherin. This increased expression is associated with a higher number of E-cadherin:β-catenin complexes at the membrane. Reduction of E-cadherin synergised with an activating mutation of β-catenin so there was now a rapid CPC phenotype within the colon and SI. Thus there is a threshold of β-catenin that is required to drive transformation and E-cadherin can act as a buffer to prevent β-catenin accumulation

Lgr5 stem cells in epithelial self-renewal and cancer of the stmach

The 3rd International Symposium on Carcinogenic Spiral & International Symposium on Tumor Biology in Kanazawa, [DATE]: January 24(Thu)-25(Fri),2013, [Place]:Kanazawa Excel Hotel Tpkyu, Kanazawa, Japan, [Organizers]:Infection/Inflammation-Assisted Acceleration of the Carcinogenic Spiral and its Alteration through Vector Conversion of the Host Response to Tumors / Scientific Research on Innovative Areas, a MEXT Grant-in Aid Projec

Developing a typology of the roles public contributors undertake to establish legitimacy: A longitudinal case study of patient and public involvement in a health network

Objective To identify how public contributors established their legitimacy in the functioning of a patient and public involvement programme at a health network. Design A longitudinal case study with three embedded units (projects) involving public contributors. Interviews (n=24), observations (n=27) and documentary data collection occurred over 16 months. Setting The West of England Academic Health Science Network (WEAHSN), 1 of 15 regional AHSNs in England. Participants Interviews were conducted with public contributors (n=5) and professionals (n=19) who were staff from the WEAHSN, its member organisations and its partners. Results Public contributors established their legitimacy by using nine distinct roles: (1) lived experience, as a patient or carer; (2) occupational knowledge, offering job-related expertise; (3) occupational skills, offering aptitude developed through employment; (4) patient advocate, promoting the interests of patients; (5) keeper of the public purse, encouraging wise spending; (6) intuitive public, piloting materials suitable for the general public; (7) fresh-eyed reviewer, critiquing materials; (8) critical friend, critiquing progress and proposing new initiatives and (9) boundary spanner, urging professionals to work across organisations. Individual public contributors occupied many, but not all, of the roles. Conclusions Lived experience is only one of nine distinct public contributor roles. The WEAHSN provided a benign context for the study because in a health network public contributors are one of many parties seeking to establish legitimacy through finding valuable roles. The nine roles can be organised into a typology according to whether the basis for legitimacy lies in: the public contributor's knowledge, skills and experience; citizenship through the aspiration to achieve a broad public good; or being an outsider. The typology shows how public contributors can be involved in work where lived experience appears to lack relevance: strategic decision making; research unconnected to particular conditions; or acute service delivery

Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma

Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF MAPK pathway activation. Here, we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFb Smad signaling which is localised to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through BRafV600E or KRASG12D knockin) and TGFb signaling ablation (through Tgfbr1 deletion) in Lgr5+ve stem cells enables rapid cSCC development in the mouse. Mutation of TP53 (which is commonly mutated in sporadic cSCC) coupled with TGFbR1 deletion in Lgr5+ve cells also results in cSCC development. These findings indicate that Lgr5+ve stem cells can act as a cell of origin for cSCC and that RAS-RAF-MAPK pathway hyperactivation or TP53 mutation, coupled with loss of TGFb signaling, are driving events of skin tumorigenesis

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

A Comprehensive Model of the Spatio-Temporal Stem Cell and Tissue Organisation in the Intestinal Crypt

We introduce a novel dynamic model of stem cell and tissue organisation in murine intestinal crypts. Integrating the molecular, cellular and tissue level of description, this model links a broad spectrum of experimental observations encompassing spatially confined cell proliferation, directed cell migration, multiple cell lineage decisions and clonal competition