Identity as a causal power : contextualising entrepreneurs' concerns

We propose a critical realist-informed conception of entrepreneurial identity – the personal power to create a new venture. Although most people have the power to become an entrepreneur, not everyone can, or is motivated to, realize that potential. Other countervailing powers – personal, material and social – can constrain, or discourage, action. Utilizing a stratified, emergent ontology, we contextualize entrepreneurial identity within three analytical orders – natural, practical and social. We distinguish personal identity, the set of concerns in the three orders that motivate action, from social identity, the roles we commit to in society. While entrepreneurial identity is a type of social identity, the underlying concerns that motivate commitment to an entrepreneurial role cannot be reduced to social interaction alone. The concept of internal conversation is used to theorize the connection of entrepreneurial motivation, context and behaviour. We draw on qualitative data from three UK-based disabled entrepreneurs to demonstrate the value of our framework

Using Genomic Sequencing for Classical Genetics in E. coli K12

We here develop computational methods to facilitate use of 454 whole genome shotgun sequencing to identify mutations in Escherichia coli K12. We had Roche sequence eight related strains derived as spontaneous mutants in a background without a whole genome sequence. They provided difference tables based on assembling each genome to reference strain E. coli MG1655 (NC_000913). Due to the evolutionary distance to MG1655, these contained a large number of both false negatives and positives. By manual analysis of the dataset, we detected all the known mutations (24 at nine locations) and identified and genetically confirmed new mutations necessary and sufficient for the phenotypes we had selected in four strains. We then had Roche assemble contigs de novo, which we further assembled to full-length pseudomolecules based on synteny with MG1655. This hybrid method facilitated detection of insertion mutations and allowed annotation from MG1655. After removing one genome with less than the optimal 20- to 30-fold sequence coverage, we identified 544 putative polymorphisms that included all of the known and selected mutations apart from insertions. Finally, we detected seven new mutations in a total of only 41 candidates by comparing single genomes to composite data for the remaining six and using a ranking system to penalize homopolymer sequencing and misassembly errors. An additional benefit of the analysis is a table of differences between MG1655 and a physiologically robust E. coli wild-type strain NCM3722. Both projects were greatly facilitated by use of comparative genomics tools in the CoGe software package (http://genomevolution.org/)

Construction of an odds model of coronary heart disease using published information: the Cardiovascular Health Improvement Model (CHIME)

Background: There is a need for a new cardiovascular disease model that includes a wider range of relevant risk factors, in particular lifestyle factors, to aid targeting of interventions and improve population models of the impact of cardiovascular disease and preventive strategies. The model needs to be applicable to a wider population including different ethnic groups, different countries and to those with and without cardiovascular disease. This paper describes the construction of the Cardiovascular Health Improvement Model that aims to meet these requirements. Method: An odds model is used. Information was taken from 2003 mortality statistics for England and Wales, the Health Survey for England 2003 and published data on relative risk in those with and without CVD and mean blood pressure values in hypertensives. The odds ratios used were taken from the INTERHEART study. Results: A worked example is given calculating the 10-year coronary heart disease risk for a 57 year-old non-diabetic male with no personal or family history of cardiovascular disease, who smokes 30 cigarettes a day and has a systolic blood pressure of 137 mmHg, a total cholesterol (TC) of 6.2 mmol/l, a high density lipoprotein (HDL) of 1.3 mol/l, and a body mass index of 21. He neither drinks regularly nor exercises. He can give no reliable information about his mental health or fruit and vegetable intake. His 10-year risk of CHD death is 2.47%. Conclusion: This paper demonstrates a method for developing a CHD risk model. Further improvements could be made to the model with additional information. The method is applicable to other causes of death

Effects of the Histone Deacetylase Inhibitor Valproic Acid on Human Pericytes In Vitro

Microvascular pericytes are of key importance in neoformation of blood vessels, in stabilization of newly formed vessels as well as maintenance of angiostasis in resting tissues. Furthermore, pericytes are capable of differentiating into pro-fibrotic collagen type I producing fibroblasts. The present study investigates the effects of the histone deacetylase (HDAC) inhibitor valproic acid (VPA) on pericyte proliferation, cell viability, migration and differentiation. The results show that HDAC inhibition through exposure of pericytes to VPA in vitro causes the inhibition of pericyte proliferation and migration with no effect on cell viability. Pericyte exposure to the potent HDAC inhibitor Trichostatin A caused similar effects on pericyte proliferation, migration and cell viability. HDAC inhibition also inhibited pericyte differentiation into collagen type I producing fibroblasts. Given the importance of pericytes in blood vessel biology a qPCR array focusing on the expression of mRNAs coding for proteins that regulate angiogenesis was performed. The results showed that HDAC inhibition promoted transcription of genes involved in vessel stabilization/maturation in human microvascular pericytes. The present in vitro study demonstrates that VPA influences several aspects of microvascular pericyte biology and suggests an alternative mechanism by which HDAC inhibition affects blood vessels. The results raise the possibility that HDAC inhibition inhibits angiogenesis partly through promoting a pericyte phenotype associated with stabilization/maturation of blood vessels

Brief psychological therapies for anxiety and depression in primary care: meta-analysis and meta-regression

Psychological therapies provided in primary care are usually briefer than in secondary care. There has been no recent comprehensive review comparing their effectiveness for common mental health problems. We aimed to compare the effectiveness of different types of brief psychological therapy administered within primary care across and between anxiety, depressive and mixed disorders

New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options

Joint trauma can lead to a spectrum of acute lesions, including osteochondral fractures, ligament or meniscus tears and damage to the articular cartilage. This is often associated with intraarticular bleeding and causes posttraumatic joint inflammation. Although the acute symptoms resolve and some of the lesions can be surgically repaired, joint injury triggers a chronic remodeling process in cartilage and other joint tissues that ultimately manifests as osteoarthritis in a majority of cases. The objective of the present review is to summarize information on pathogenetic mechanisms involved in the acute and chronic consequences of joint trauma and discuss potential pharmacological interventions. The focus of the review is on the early events that follow joint trauma since therapies for posttraumatic joint inflammation are not available and this represents a unique window of opportunity to limit chronic consequences