Re-Focusing - Building a Future for Entrepreneurial Education & Learning

The field of entrepreneurship has struggled with fundamental questions concerning the subject’s nature and purpose. To whom and to what means are educational and training agendas ultimately directed? Such questions have become of central importance to policy makers, practitioners and academics alike. There are suggestions that university business schools should engage more critically with the lived experiences of practising entrepreneurs through alternative pedagogical approaches and methods, seeking to account for and highlighting the social, political and moral aspects of entrepreneurial practice. In the UK, where funding in higher education has become increasingly dependent on student fees, there are renewed pressures to educate students for entrepreneurial practice as opposed to educating them about the nature and effects of entrepreneurship. Government and EU policies are calling on business schools to develop and enhance entrepreneurial growth and skill sets, to make their education and training programmes more proactive in providing innovative educational practices which help and facilitate life experiences and experiential learning. This paper makes the case for critical frameworks to be applied so that complex social processes become a source of learning for educators and entrepreneurs and so that innovative pedagogical approaches can be developed in terms both of context (curriculum design) and process (delivery methods)

A new nucleotide-excision-repair gene associated with the disorder trichothiodystrophy

The sun-sensitive, cancer-prone genetic disorder xeroderma pigmentosum (XP) is associated in most cases with a defect in the ability to carry out excision repair of UV damage. Seven genetically distinct complementation groups (i.e., A-G) have been identified. A large proportion of patients with the unrelated disorder trichothiodystrophy (TTD), which is characterized by hair-shaft abnormalities, as well as by physical and mental retardation, are also deficient in excision repair of UV damage. In most of these cases the repair deficiency is in the same complementation group as is XP group D. We report here on cells from a patient, TTD1BR, in which the repair defect complements all known XP groups (including XP-D). Furthermore, microinjection of various cloned human repair genes fails to correct the repair defect in this cell strain. The defect in TTD1BR cells is therefore in a new gene involved in excision repair in human cells. The finding of a second DNA repair gene that is associated with the clinical features of TTD argues strongly for an involvement of repair proteins in hair-shaft development.</p

A new nucleotide-excision-repair gene associated with the disorder trichothiodystrophy

The sun-sensitive, cancer-prone genetic disorder xeroderma pigmentosum (XP) is associated in most cases with a defect in the ability to carry out excision repair of UV damage. Seven genetically distinct complementation groups (i.e., A-G) have been identified. A large proportion of patients with the unrelated disorder trichothiodystrophy (TTD), which is characterized by hair-shaft abnormalities, as well as by physical and mental retardation, are also deficient in excision repair of UV damage. In most of these cases the repair deficiency is in the same complementation group as is XP group D. We report here on cells from a patient, TTD1BR, in which the repair defect complements all known XP groups (including XP-D). Furthermore, microinjection of various cloned human repair genes fails to correct the repair defect in this cell strain. The defect in TTD1BR cells is therefore in a new gene involved in excision repair in human cells. The finding of a second DNA repair gene that is associated with the clinical features of TTD argues strongly for an involvement of repair proteins in hair-shaft development.</p

Predictors of inappropriate hospital days in a department of internal medicine

Background This study aimed to identify predictors of inappropriate hospital days in a deparUnent of internal medicine, as a basis for quality improvement interventions. Methods The appropriateness of 5665 hospital days contributed by 500 patients admitted to the Department of Internal Medicine, Geneva University Hospitals, Switzerland, was assessed by means of the Appropriateness Evaluation Protocol. Predictor variables included patient's age and sex, manner of admission and discharge, and characteristics of hospital days (weekend, holiday, sequence). Results Overall, 15% of hospital admissions and 28% of hospital days were rated as inappropriate. In multivariate models, inappropriate hospital days were more frequent among patients whose admission was inappropriate (odds ratio [OR] = 5.3, 95% CI: 3.1-8.4) and among older patients (80-95 years: OR = 3.6. 95% CI: 1.7-7.0, versus <50 years). The likelihood of inappropriateness also increased with each subsequent hospital day, culminating on the day of discharge, regardless of the total length of stay. Conclusions This study identified both the admission and the discharge processes as important sources of inappropriate hospital use in a department of internal medicine. The oldest patients were also at high risk of remaining in the hospital inappropriately. Surprisingly, long hospital stays did not generate a higher proportion of inappropriate days than short hospital stays. This information proved useful in developing interventions to improve the hospitalization proces

Correction by the ercc2 gene of UV sensitivity and repair deficiency phenotype in a subset of trichothiodystrophy cells

Trichothiodystrophy (TTD) is a rare genetic disease with heterogeneous clinical features associated with specific deficiencies in nucleotide excision repair. Patients have brittle hair due to a reduced content of cysteine-rich matrix proteins. About 50% of the cases reported in the literature are photosensitive. In these patients an altered cellular response to UV, due to a specific deficiency in nucleotide excision repair, has been observed. The majority of repairdefective TTD patients have been assigned by complementation analysis to group D of xeroderma pigmentosum (XP). Recently, the human excision repair gene ERCC2 has been shown to correct the UV sensitivity of XP-D fibroblasts. In this work we describe the effect of ERCC2 on the DNA repair deficient phenotype of XP-D and on two repair-defective TTD cell strains (TTD1VI and TTD2VI) assigned by complementation analysis to group D of XP. ERCC2 cDNA, cloned into a mammalian expression vector, was introduced into TTD and XP fibroblasts via DNA-mediated transfection or microneedle injection. UV sensitivity and cellular DNA repair properties, including unscheduled DNA synthesis and reactivation of a UVirradiated plasmid containing the chloramphenicol acetyltransferase reporter gene (pRSVCat), were corrected to wild-type levels in both TTD and XP-D cells. These data show that a functional ERCC2 gene is sufficient to reestablish a wild-type DNA repair phenotype in TTD1VI and TTD2VI cells, confirming the genetic relationship between TTD and XP-D. Furthermore, our findings suggest that mutations at the ERCC2 locus are responsible for causing a similar phenotype in TTD and XP-D cells in response to UV irradiation, but produce quite different clinical symptorns.</p

Correction by the ercc2 gene of UV sensitivity and repair deficiency phenotype in a subset of trichothiodystrophy cells

Trichothiodystrophy (TTD) is a rare genetic disease with heterogeneous clinical features associated with specific deficiencies in nucleotide excision repair. Patients have brittle hair due to a reduced content of cysteine-rich matrix proteins. About 50% of the cases reported in the literature are photosensitive. In these patients an altered cellular response to UV, due to a specific deficiency in nucleotide excision repair, has been observed. The majority of repairdefective TTD patients have been assigned by complementation analysis to group D of xeroderma pigmentosum (XP). Recently, the human excision repair gene ERCC2 has been shown to correct the UV sensitivity of XP-D fibroblasts. In this work we describe the effect of ERCC2 on the DNA repair deficient phenotype of XP-D and on two repair-defective TTD cell strains (TTD1VI and TTD2VI) assigned by complementation analysis to group D of XP. ERCC2 cDNA, cloned into a mammalian expression vector, was introduced into TTD and XP fibroblasts via DNA-mediated transfection or microneedle injection. UV sensitivity and cellular DNA repair properties, including unscheduled DNA synthesis and reactivation of a UVirradiated plasmid containing the chloramphenicol acetyltransferase reporter gene (pRSVCat), were corrected to wild-type levels in both TTD and XP-D cells. These data show that a functional ERCC2 gene is sufficient to reestablish a wild-type DNA repair phenotype in TTD1VI and TTD2VI cells, confirming the genetic relationship between TTD and XP-D. Furthermore, our findings suggest that mutations at the ERCC2 locus are responsible for causing a similar phenotype in TTD and XP-D cells in response to UV irradiation, but produce quite different clinical symptorns.</p

Incidence, etiology and predictors of adverse outcomes in 43,315 patients presenting to the Emergency Department with syncope: An international meta-analysis.

BACKGROUND: Syncope remains challenging for Emergency Department (ED) physicians due to difficulties in assessing the risk of future adverse outcomes. The aim of this meta-analysis is to establish the incidence and etiology of adverse outcomes as well as the predictors, in patients presenting with syncope to the ED. METHODS: A systematic electronic literature review was performed looking for eligible studies published between 1990 and 2010. Studies reporting multivariate predictors of adverse outcomes in patients presenting with syncope to the ED were included and pooled, when appropriate, using a random-effect method. Adverse events were defined as 'incidence of death, or of hospitalization and interventional procedures because of arrhythmias, ischemic heart disease or valvular heart disease'. RESULTS: 11 studies were included. Pooled analysis showed 42% (CI 95%; 32-52) of patients were admitted to hospital. Risk of death was 4.4% (CI 95%; 3.1-5.1) and 1.1% (CI 95%; 0.7-1.5) had a cardiovascular etiology. One third of patients were discharged without a diagnosis, while the most frequent diagnosis was 'situational, orthostatic or vasavagal syncope' in 29% (CI 95%; 12-47). 10.4% (CI 95%; 7.8-16) was diagnosed with heart disease, the most frequent type being bradyarrhythmia, 4.8% (CI 95%; 2.2-6.4) and tachyarrhythmia 2.6% (CI 95%; 1.1-3.1). Palpitations preceding syncope, exertional syncope, a history consistent of heart failure or ischemic heart disease, and evidence of bleeding were the most powerful predictors of an adverse outcome. CONCLUSION: Syncope carries a high risk of death, mainly related to cardiovascular disease. This large study which has established the most powerful predictors of adverse outcomes, may enable care and resources to be better focused at high risk patients. Copyright \ua9 2011 Elsevier Ireland Ltd. All rights reserved

Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions

Doxorubicin (DOX) is an important tumor chemotherapeutic agent, acting mainly by genotoxic action. This work focus on cell processes that help cell survival, after DOX-induced DNA damage. in fact, cells deficient for XPA or DNA polymerase eta (pol eta, XPV) proteins (involved in distinct DNA repair pathways) are highly DOX-sensitive. Moreover, LY294002, an inhibitor of PIKK kinases, showed a synergistic killing effect in cells deficient in these proteins, with a strong induction of G2/M cell cycle arrest. Taken together, these results indicate that XPA and pol eta proteins participate in cell resistance to DOX-treatment, and kinase inhibitors can selectively enhance its killing effects, probably reducing the cell ability to recover from breaks induced in DNA. (C) 2011 Elsevier Ireland Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)USP-COFECUB (São Paulo, Brazil)Univ São Paulo, Dept Microbiol, Inst Biomed Sci, São Paulo, BrazilUniv Paris Sud, Inst Gustave Roussy, Ctr Natl Rech Sci, UMR8200, Villejuif, FranceFed Univ São Paulo UNIFESP, Dept Biol Sci, Diadema, SP, BrazilUniv Fed Rio Grande do Sul, Ctr Biotechnol, Dept Biophys, Porto Alegre, RS, BrazilFed Univ Hlth Sci Porto Alegre UFCSPA, Dept Basic Hlth Sci, Porto Alegre, RS, BrazilFed Univ São Paulo UNIFESP, Dept Biol Sci, Diadema, SP, BrazilWeb of Scienc

Infrapatellar fat pad gene expression and protein production in patients with and without osteoarthritis

Osteoarthritis (OA) is one of the most common joint disorders. Evidence suggests that the infrapatellar fat pad (IFP) is directly involved in OA pathology. However, a comparison between OA versus non-OA IFP is still missing. Thus, the aim of this study was to compare IFP molecular, adipocytes and extracellular matrix characteristics of patients affected by OA, and patients undergoing anterior cruciate ligament (ACL) reconstruction. We hypothesized that not only inflammation but also changes in adipocytes and extracellular matrix (ECM) composition might be involved in OA pathogenesis. Fifty-three patients were enrolled. IFP biopsies were obtained, evaluating: (a) lymphocytic infiltration and vascularization; (b) adipocytes area and number; (c) adipo-cytokines and extracellular matrix gene expression levels; (d) IL-6 and VEGF protein production; (e) collagen fibers distribution. OA IFP was more inflamed and vascularized compared to ACL IFP. OA IFP adipocytes were larger and numerically lower (1.3-fold) than ACL IFP adipocytes. An increase of gene expression of typical white adipose tissue genes was observed in OA compared to ACL IFP. Collagen-types distribution was different in the OA IFP group compared to controls, possibly explaining the change of the biomechanical characteristics found in OA IFP. Statistical linear models revealed that the adipocyte area correlated with BMI in the OA group. In conclusion, inflammation and fibrotic changes of OA IFP could represent novel therapeutic targets to counteract OA