The relationship between Higher Education and labour market in Greece : the weakest link?

The high level of graduate unemployment, even though it is acknowledged as one of the most distinctive characteristics of the Greek labour market, it has not attracted enough attention in the academic literature. This paper utilizes micro-data from the Labour Force Survey in order to investigate how the employment situation of young (aged 35 and below) graduates varies across fields of study. The findings suggest that graduates of disciplines that have high levels of private sector employment, such as Polytechnics and Computer Science, are in general better off in the Greek labour market. On the other hand, graduates of disciplines that are traditionally related to the needs of the public sector, such as Sociology and Humanities, face poor employment prospects. The findings of this study highlight the need for drastic reforms of the Higher Education system

Detection and characterisation of bone destruction in murine rheumatoid arthritis using statistical shape models

Rheumatoid arthritis (RA) is an autoimmune disease in which chronic inflammation of the synovial joints can lead to destruction of cartilage and bone. Pre-clinical studies attempt to uncover the underlying causes by emulating the disease in genetically different mouse strains and characterising the nature and severity of bone shape changes as indicators of pathology. This paper presents a fully automated method for obtaining quantitative measurements of bone destruction from volumetric micro-CT images of a mouse hind paw. A statistical model of normal bone morphology derived from a training set of healthy examples serves as a template against which a given pathological sample is compared. Abnormalities in bone shapes are identified as deviations from the model statistics, characterised in terms of type (erosion / formation) and quantified in terms of severity (percentage affected bone area). The colour-coded magnitudes of the deviations superimposed on a three-dimensional rendering of the paw show at a glance the severity of malformations for the individual bones and joints. With quantitative data it is possible to derive population statistics characterising differences in bone malformations for different mouse strains and in different anatomical regions. The method was applied to data acquired from three different mouse strains. The derived quantitative indicators of bone destruction have shown agreement both with the subjective visual scores and with the previous biological findings. This suggests that pathological bone shape changes can be usefully and objectively identified as deviations from the model statistics

Partial inhibition of RNA polymerase I promotes animal health and longevity

Health and survival in old age can be improved by changes in gene expression. RNA polymerase (Pol) I is the essential, conserved enzyme whose task is to generate the pre-ribosomal RNA (rRNA). We find that reducing the levels of Pol I activity is sufficient to extend lifespan in the fruit fly. This effect can be recapitulated by partial, adult-restricted inhibition, with both enterocytes and stem cells of the adult midgut emerging as important cell types. In stem cells, Pol I appears to act in the same longevity pathway as Pol III, implicating rRNA synthesis in these cells as the key lifespan determinant. Importantly, reduction in Pol I activity delays broad, age-related impairment and pathology, improving the function of diverse organ systems. Hence, our study shows that Pol I activity in the adult drives systemic, age-related decline in animal health and anticipates mortality

Local and systemic glucocorticoid metabolism in inflammatory arthritis

Background: Isolated, primary synovial fibroblasts generate active glucocorticoids through expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This enzyme produces cortisol from inactive cortisone (and prednisolone from prednisone). Objective: To determine how intact synovial tissue metabolises glucocorticoids and to identify the local and systemic consequences of this activity by examination of glucocorticoid metabolism in patients with rheumatoid arthritis (RA). Methods: Synovial tissue was taken from patients with RA during joint replacement surgery. Glucocorticoid metabolism in explants was assessed by thin-layer chromatography and specific enzyme inhibitors. RT-PCR and immunohistochemistry were used to determine expression and distribution of 11β-HSD enzymes. Systemic glucocorticoid metabolism was examined in patients with RA using gas chromatography/mass spectrometry. Results: Synovial tissue synthesised cortisol from cortisone, confirming functional 11β-HSD1 expression. In patients with RA, enzyme activity correlated with donor erythrocyte sedimentation rate (ESR). Synovial tissues could also convert cortisol back to cortisone. Inhibitor studies and immunohistochemistry suggested this was owing to 11β-HSD2 expression in synovial macrophages, whereas 11β-HSD1 expression occurred primarily in fibroblasts. Synovial fluids exhibited lower cortisone levels than matched serum samples, indicating net local steroid activation. Urinary analyses indicated high 11β-HSD1 activity in untreated patients with RA compared with controls and a significant correlation between total body 11β-HSD1 activity and ESR. Conclusions: Synovial tissue metabolises glucocorticoids, the predominant effect being glucocorticoid activation, and this increases with inflammation. Endogenous glucocorticoid production in the joint is likely to have an impact on local inflammation and bone integrity

Targeting the rheumatoid arthritis synovial fibroblast via cyclin dependent kinase inhibition: An early phase trial

Introduction: Targeted biologic therapies demonstrate similar efficacies in rheumatoid arthritis despite distinct mechanisms of action. They also exhibit a ceiling effect, with 10% to 20% of patients achieving remission in clinical trials. None of these therapies target synovial fibroblasts, which drive and maintain synovitis. Seliciclib (R-roscovitine) is an orally available cyclin-dependent kinase inhibitor that suppresses fibroblast proliferation, and is efficacious in preclinical arthritis models. We aim to determine the toxicity and preliminary efficacy of seliciclib in combination with biologic therapies, to inform its potential as an adjunctive therapy in rheumatoid arthritis. Methods and analysis: TRAFIC is a non-commercial, multi-center, rolling phase Ib/IIa trial investigating the safety, tolerability, and efficacy of seliciclib in patients with moderate to severe rheumatoid arthritis receiving biologic therapies. All participants receive seliciclib with no control arm. The primary objective of part 1 (phase Ib) is to determine the maximum tolerated dose and safety of seliciclib over 4 weeks of dosing. Part 1 uses a restricted 1-stage Bayesian continual reassessment method based on a target dose-limiting toxicity probability of 35%. Part 2 (phase IIa) assesses the potential efficacy of seliciclib, and is designed as a single arm, single stage early phase trial based on a Fleming-A’Hern design using the maximum tolerated dose recommended from part 1. The primary response outcome after 12 weeks of therapy is a composite of clinical, histological and magnetic resonance imaging scores. Secondary outcomes include adverse events, pharmacodynamic and pharmacokinetic parameters, autoantibodies, and fatigue. Ethics and dissemination: The study has been reviewed and approved by the North East - Tyne & Wear South Research Ethics Committee (reference 14/NE/1075) and the Medicines and Healthcare Products Regulatory Agency (MHRA), United Kingdom. Results will be disseminated through publication in relevant peer-reviewed journals and presentation at national and international conferences. Trials Registration: ISRCTN, ISRCTN36667085. Registered on September 26, 2014; http://www.isrctn.com/ISRCTN36667085 Current protocol version: Protocol version 11.0 (March 21, 2019

Synergistic induction of local glucocorticoid generation by inflammatory cytokines and glucocorticoids: implications for inflammation associated bone loss

Objectives: Synovial fibroblasts and osteoblasts generate active glucocorticoids by means of the 11aβ-hydroxysteroid dehydrogenase type 1 (11aβ-HSD1) enzyme. This activity increases in response to proinflammatory cytokines or glucocorticoids. During inflammatory arthritis synovium and bone are exposed to both these factors. This study hypothesised that glucocorticoids magnify the effects of inflammatory cytokines on local glucocorticoid production in both synovium and bone. Methods: The effects of inflammatory cytokines (IL-1aβ/tumour necrosis factor alpha; TNFα) and glucocorticoids, alone or combined, were assessed on the expression and activity of 11β-HSD1 in primary synovial fibroblasts, primary human osteoblasts and MG-63 osteosarcoma cells. A range of other target genes and cell types were used to examine the specificity of effects. Functional consequences were assessed using IL-6 ELISA. Results: In synovial fibroblasts and osteoblasts, treatment with cytokines or glucocorticoids in isolation induced 11β-HSD1 expression and activity. However, in combination, 11β-HSD1 expression, activity and functional consequences were induced synergistically to a level not seen with isolated treatments. This effect was seen in normal skin fibroblasts but not foreskin fibroblasts or adipocytes and was only seen for the 11β-HSD1 gene. Synergistic induction had functional consequences on IL-6 production. Conclusions: Combined treatment with inflammatory cytokines and glucocorticoids synergistically induces 11aβ-HSD1 expression and activity in synovial fibroblasts and osteoblasts, providing a mechanism by which synovium and bone can interact to enhance anti-inflammatory responses by increasing localised glucocorticoid levels. However, the synergistic induction of 11β-HSD1 might also cause detrimental glucocorticoid accumulation in bone or surrounding tissues

Phenomenon of mathematical fluency.

This study explored the longitudinal relationship between motivation and acquisition of a second modern foreign language (MFL). Participants were 11 to 12 year-old pupils attending the first year of secondary school. They constituted a naïve population as formal MFL learning in the United Kingdom begins in secondary school. MFL achievement, assessed using national curriculum standards, and self-report measures of motivation were collected at four time points throughout the year. Previous motivation was found to be the only predictor of motivation at the end of the academic year. In the same way, previous achievement was the only predictor of final achievement. Results showed that the correlational relationship between motivation and achievement over time was stable, with modest effect size. Cross-lagged panel analysis was adopted in order to assess the causality of the observed relationship between motivation and achievement. However, no cross-lagged relationships were observed in this sample. Once accounting for the stability of the constructs and their cross-sectional (contemporaneous) relationship, no further variance was explained by cross-lagged relationships between motivation and achievement at different time points