The Estimation of GC Repeats in Promoter P1 of IGF-1 Gene and Their Influence on IGF-1 Plasma Levels in Stable Angina Patients

Increased plasma levels of insulin-like growth factor 1 (IGF-1) are observed in advanced arteriosclerosis, but the reasons for these elevated levels remain unknown. One possibility to explain them is variation in the sequences that control IGF-1 gene expression. The goal of this study was to determine the effect of molecular variants of the IGF-1 P1 promoter on IGF-1 serum levels and to determine the impact of IGF-1 levels on the severity of coronary atherosclerosis. Methods: Blood samples were collected from 101 consecutive patients undergoing routine angiography. Genomic DNA was isolated from the nucleated cells of the blood plasma as described (2). Based on the presence of conformational differences in the DNA strand and on the absence of single nucleotide polymorphisms, the DNA from 38 patients was further analyzed by the “allelic ladder” method to determine the number of repeated GC dinucleotides in the P1 promoter of the IGF-1 gene. In addition, we analyzed serum growth hormone levels in order to examine the effect on systemic IGF-1 synthesis. Results: Conformational differences in the P1 promoter of the IGF-1 gene were observed in 38 out of the 101 patients. Several genotypes, depending on the number of GC repeats, were observed (11/19,17/19,18/19,18/21,19/19,19/20,19/21). Interestingly, a family history of coronary artery disease was seen less often among individuals heterozygous for the GC repeats. A lower IGF-1 levels were seen in non-variant carriers (homozygous genotypes for 19 or 21 repeats of GC, or heterozygous genotype 19/21) when compared to the variant group (other heterozygous genotypes then 19/21) (181.6 ± 47.9 ng/mL vs. 227.7 ± 73.7, p = 0.026). A correlation between IGF-1, IGF-binding protein number 3, and growth hormone levels (p = ns) was not observed, and there were no significant differences in the growth hormone levels in the studied group of patients (p = ns)

Reconsidering "the love of art" : evaluating the potential of art museum outreach

Art museums have long been identified as bastions of social and cultural exclusion. This conclusion was best evidenced by the large-scale 1967 French study by Bourdieu and Darbel demonstrating the exclusionary nature of “The Love of Art.” However, in recent years there have been increasing efforts to reach out to a broader range of visitors beyond conventional audiences. The present study investigates the impacts of an outreach program at a UK art museum, which sought to engage socially excluded young mothers. This study employs ethnographic research methods on a longitudinal basis to develop qualitative insights about the program seeking to mitigate cultural exclusion. While the study’s findings uphold many longstanding critiques of art museums’ conventional approaches, the study also indicates that carefully designed outreach activities can overcome such limitations and enhance cultural engagement. Thus, art museums’ limited appeal is tied to problematic public engagement practices that can be changed

Are Elevated Levels of IGF-1 Caused by Coronary Arteriesoclerosis?: Molecular and Clinical Analysis

The importance of insulin-like growth factor-1 (IGF-1) in coronary artery disease (CAD) due to wide range of its biological effects and its therapeutic potential, has already been described. Our aim was to evaluate possible influence of IGF-1 serum level changes on coronary atherosclerosis. In case of existence of such association our further aim was to verify and explain this phenomenon by examination of promoter P1 of IGF-1gene and receptor gene for IGF-1. The study was performed in 101 consecutive patients undergo for routine coronary angiography. Quantitative and qualitative assessment of coronary atherosclerosis was performed respectively by estimation of the number of culprit lesions in coronary arteries and by Gensini score calculation. IGF-1, IGFBP3 and plasma lipoproteins were measured in all patients. In addition, we evaluated DNA from 101 patients, isolated from blood cells, which was amplified by using PCR with sophisticated primers for P1 promoter of IGF-1 gene and IGF-1 receptor gene, then analyzed utilizing SSCP technique and automatically sequenced. We observed significant increase of serum IGF-1 levels in patients with “3 vessel disease” and with high score in Gensini scale when compared to those without any narrowing lesions in coronary arteries and 0 Gensini score (in group with 3 vessel disease 215.0 ± 71.3 versuss 176.7 ± 34.2 ng/ml p = 0.04 and with high Gensini score 231.4 ± 59.3 versus 181.0 ± 37.8 ng/ml p = 0.01).We found different genotypes for five P1 promoter polymorphisms of IGF-1 gene (RS35767, RS5742612, RS228837, RS11829693, RS17879774). There were no significant associations between the observed single nucleotide polymorphism (SNP) and coronary atherosclerosis nor with levels of circulating IGF-1. We found no structural polymorphism in receptor gene for IGF-1 nor in its extracellular domain(exon 2–4) nor in internal domain (exon 16–21). The effect of increased IGF-1 serum level in our study was probably independent from structural polymorphism in promoter P1 for IGF-1 or in receptor gene for IGF-1

More than sense of place? Exploring the emotional dimension of rural tourism experiences

It is widely suggested that participation in rural tourism is underpinned by a sense of rural place or “rurality”. However, although nature and the countryside have long been recognised as a source of spiritual or emotional fulfilment, few have explored the extent to which tourism, itself often claimed to be a sacred experience, offers an emotional/spiritual dimension in the rural context. This paper addresses that literature gap. Using in-depth interviews with rural tourists in the English Lake District, it explores the extent to which, within respondents’ individual understanding of spirituality, a relationship exists between sense of place and deeper, emotional experiences and, especially, whether participation in rural tourism may induce spiritual or emotional responses. The research revealed that all respondents felt a strong attachment to the Lake District; similarly, and irrespective of their openness to spirituality, engaging in rural tourism activities resulted in highly emotive experiences for all respondents, the description/interpretation of such experiences being determined by individual “beliefs”. However, sense of place was not a prerequisite to emotional or spiritual experiences. Being in and engaging with the landscape � effectively becoming part of it � especially through physical activity is fundamental to emotional responses

Exclusionary employment in Britain’s broken labour market

There is growing evidence of the problematic nature of the UK’s ‘flexible labour market’ with rising levels of in-work poverty and insecurity. Yet successive Governments have stressed that paid work is the route to inclusion, focussing attention on the divide between employed and unemployed. Past efforts to measure social exclusion have tended to make the same distinction. The aim of this paper is to apply Levitas et al’s (2007) framework to assess levels of exclusionary employment, i.e. exclusion arising directly from an individual’s labour market situation. Using data from the Poverty and Social Exclusion UK survey, results show that one in three adults in paid work is in poverty, or in insecure or poor quality employment. One third of this group have not seen any progression in their labour market situation in the last five years. The policy focus needs to shift from ‘Broken Britain’ to Britain’s broken labour market

An investigation of the construct validity of the ICECAP-A capability measure

Abstract Purpose To investigate the construct validity of the ICECAP-A capability wellbeing measure. Methods A face-to-face interview-administered survey was conducted with 418 members of the UK general population, randomly sampled from the Postcode Address File. Pre-specified hypotheses were developed about the expected associations between individuals’ ICECAP-A responses and their socio-economic circumstances, health and freedom. The hypotheses were investigated using statistical tests of association. Results The ICECAP-A responses and scores reflected differences across different health and socioeconomic groups as anticipated, but did not distinguish individuals by the level of local deprivation. Mean ICECAP-A scores reflected individuals’ perceived freedom slightly more closely than did measures of health and happiness. Conclusion This study suggests that the ICECAP-A measure can identify expected differences in capability wellbeing in a general population sample. Further work could establish whether self-reported capabilities exhibit desirable validity and acceptability in sub-groups of the population such as patients, social care recipients and informal carers

RadioActive101-Learning through radio, learning for life: an international approach to the inclusion and non-formal learning of socially excluded young people

This article describes an original international approach to inclusion and non-formal learning of socially excluded young people, through participatory internet radio - RadioActive101. First, we critically discuss the social and digital exclusion of young people. We then describe our approach - that includes partic-ipatory action research methods that are influenced by the work of Dewey and Freire, and operate as a process of complex intervention. This supports the inclusive co-production of radio content in ways that support non-formal learning in two EU contexts – the UK and Portugal. We then summarise and compare a qualitative investigation of RadioActive101. This showed positive results, with important similarities and differences between the two contexts. Participants reported that RadioActive101 was motivating and contributed to the development of contemporary skills, and also stimulated improvements in psychosocial dimensions such as confidence (self-efficacy) and self-esteem. This investigation informed the development of an original recog-nition system for non-formal learning that maps EU Key Competences for Lifelong Learning to radio practic-es and activities that are recognised through electronic badges. Our final reflections emphasise that in order to support the non-formal learning of socially excluded young people we must foreground our attention to foster-ing psychosocial dimensions alongside developing contemporary competences

Local treatment of cancellous bone grafts with BMP-7 and zoledronate increases both the bone formation rate and bone density: A bone chamber study in rats

Background and purpose The remodeling of morselized bone grafts in revision surgery can be enhanced by an anabolic substance such as a bone morphogenetic protein (BMP). On the other hand, BMPs boost catabolism and might cause a premature resorption, both of the graft and of the new-formed bone. Bisphosphonates inactivate osteoclasts and can be used to control the resorption. We studied a combination of both drugs as a local admix to a cancellous allograft. Methods Cancellous bone allografts were harvested and freeze-dried. Either saline, BMP-7, the bisphosphonate zoledronate, or a combination of BMP-7 and zoledronate were added in solution. The grafts were placed in bone conduction chambers and implanted in the proximal tibia of 34 rats. The grafts were harvested after 6 weeks and evaluated by histomorphometry. Results Bone volume/total volume (BV/TV) was 50% in the grafts treated with the combination of BMP-7 and zoledronate and 16% in the saline controls (p < 0.001). In the zoledronate group BV/TV was 56%, and in the BMP group it was 14%. The ingrowth distance of new bone into the graft was 3.5 mm for the combination of BMP-7 and zoledronate and 2.6 mm in the saline control (p = 0.002). The net amount of retained remodeled bone was more than 4 times higher when BMP-7 and zoledronate were combined than in the controls. Interpretation An anabolic drug like BMP-7 can be combined with an anti-catabolic bisphosphonate as local bone graft adjunct, and the combination increases the amount of remaining bone after remodeling is complete

Mitigation of Moral Hazard and Adverse Selection in Venture Capital Financing: The Influence of the Country’s Institutional Setting

A venture capitalist (VC) needs to trade off benefits and costs when attempting to mitigate agency problems in their investor-investee relationship. We argue that signals of ventures complement the VC’s capacity to screen and conduct a due diligence during the pre-investment phase, but its attractiveness may diminish in institutional settings supporting greater transparency. Similarly, whereas a VC may opt for contractual covenants to curb potential opportunism by ventures in the post-investment phase, this may only be effective in settings supportive of shareholder rights enforcement. Using an international sample of VC contracts, our study finds broad support for these conjectures. It delineates theoretical and practical implications for how investors can best deploy their capital in different institutional settings whilst nurturing their relationships with entrepreneurs