The disqualification of company directors and its effect on entrepreneurship

The disqualification of directors or members of the management of a company, expressed as a prohibition for these persons to manage or take part in the management of the companies, is a highly significant Act of Company Law, which is implemented in many legislatures around the world. Utterly restrictive in its nature, it applies to the directors and members of the management team, and in some legislation systems even to the capital owners of the companies whose illegal actions initiate its application. The activation of this institution in precisely determined situations most often results in the prohibition of a particular person to manage a company for a definite period of time. These restrictive measures are effected with the purpose of establishing certain control in trading, while imposing limitations to a certain focus group. In its nature, these measures differ from those brought into effect in order to instigate entrepreneurship. For entrepreneurship in a given country to flourish would necessitate the realization of a liberalized regulation of the market. This paper focuses on the impact that this restrictive institution has in practice, and whether it is in fact achieving the objective(s) for which it was legally established. Particular attention is given to the adverse consequences that directors’ disqualification may bring on entrepreneurial freedom and innovation, and how this in turn could influence directly or indirectly economic growth or in weathering the recessional storm(s).peer-reviewe

Coxsackie and adenovirus receptor is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia.

OBJECTIVES: The aim of this study was to investigate the modulatory effect of the coxsackie and adenovirus receptor (CAR) on ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. BACKGROUND: A heritable component in the risk of ventricular fibrillation during myocardial infarction has been well established. A recent genome-wide association study of ventricular fibrillation during acute myocardial infarction led to the identification of a locus on chromosome 21q21 (rs2824292) in the vicinity of the CXADR gene. CXADR encodes the CAR, a cell adhesion molecule predominantly located at the intercalated disks of the cardiomyocyte. METHODS: The correlation between CAR transcript levels and rs2824292 genotype was investigated in human left ventricular samples. Electrophysiological studies and molecular analyses were performed using CAR haploinsufficient (CAR(+/-)) mice. RESULTS: In human left ventricular samples, the risk allele at the chr21q21 genome-wide association study locus was associated with lower CXADR messenger ribonucleic acid levels, suggesting that decreased cardiac levels of CAR predispose to ischemia-induced ventricular fibrillation. Hearts from CAR(+/-) mice displayed slowing of ventricular conduction in addition to an earlier onset of ventricular arrhythmias during the early phase of acute myocardial ischemia after ligation of the left anterior descending artery. Expression and distribution of connexin 43 were unaffected, but CAR(+/-) hearts displayed increased arrhythmia susceptibility on pharmacological electrical uncoupling. Patch-clamp analysis of isolated CAR(+/-) myocytes showed reduced sodium current magnitude specifically at the intercalated disk. Moreover, CAR coprecipitated with NaV1.5 in vitro, suggesting that CAR affects sodium channel function through a physical interaction with NaV1.5. CONCLUSIONS: CAR is a novel modifier of ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. Genetic determinants of arrhythmia susceptibility (such as CAR) may constitute future targets for risk stratification of potentially lethal ventricular arrhythmias in patients with coronary artery disease

Development of a framework for radiographer online clinical education (FORCE): the specifc strand of nuclear medicine within this european project

The overall aim of the FORCE project is to develop virtual web-based learning resources where Radiography undergraduates can engage in interactive, problem-based development of radiographic knowledge, ability and professional awareness. This European-funded project is internally divided in three diferent strands (Radiology Diagnostic Imaging, Radiotherapy and Nuclear Medicine). The aim of this presentation is to present the global project, mainly focusing developments, achievements and challenges within the Nuclear Medicine specifc strand.info:eu-repo/semantics/publishedVersio

A duality of generalized metric spaces

AbstractWe develop a duality theory for Lawvereʼs generalized metric spaces that extends the Lawson duality for continuous dcpos and open filter reflecting maps: we prove that the category of relatively cocomplete and continuous [0,∞]-categories considered with open filter reflecting maps is self-dual

Accuracy of self-reported physical activity in patients with anorexia nervosa: links with clinical features

BackgroundHigh levels of physical activity (PA) have long been described in patients with Anorexia Nervosa (AN). Despite the importance of measuring PA in this population, there are two important factors that remain unknown. First, it is not clear how accurate self-report measures of PA are among patients. Second, little is known about how clinical characteristics are associated with the accuracy of self-reported PA. Therefore, this study aimed to examine the accuracy of self-reported PA compared to an objective measure of PA in patients with AN. It also investigated whether levels of accuracy/inaccuracy were associated with compulsive exercise, motivation to change, and psychological distress.MethodData were analysed from 34 adult outpatients with AN. Patients wore an accelerometer device (ActiGraph) for 4 days and completed a retrospective self-report measure of exercise (Exercise Participation Screening Questionnaire). They also completed measures of compulsive exercise (Compulsive Exercise Test), motivation to change (The Anorexia Nervosa Stages of Change Questionnaire), and psychological distress (Kessler-10).ResultsOn the self-report measure, patients accurately reported their time spent in moderate and vigorous intensity PA, however, they significantly under-reported their light physical activity (compared to the accelerometer data). Accurate reporting of total PA was positively associated with higher levels of compulsive exercise. There was evidence to suggest that clinical features, such as motivation to change and psychological distress, may be associated with inaccurate reporting at some levels of PA intensity and not others.ConclusionsResults indicate that patients with AN are likely to under-report their light intensity PA. We also found preliminary evidence for how compulsive exercise, motivation to change, and distress are associated with self-reported PA accuracy. Clinical implications and directions for future research are considered

Exploring the Relationship Between Schizophrenia and Cardiovascular Disease:A Genetic Correlation and Multivariable Mendelian Randomization Study

Individuals with schizophrenia have a reduced life-expectancy compared to the general population, largely due to an increased risk of cardiovascular disease (CVD). Clinical and epidemiological studies have been unable to unravel the nature of this relationship. We obtained summary-data of genome-wide-association studies of schizophrenia (N = 130 644), heart failure (N = 977 323), coronary artery disease (N = 332 477), systolic and diastolic blood pressure (N = 757 601), heart rate variability (N = 46 952), QT interval (N = 103 331), early repolarization and dilated cardiomyopathy ECG patterns (N = 63 700). We computed genetic correlations and conducted bi-directional Mendelian randomization (MR) to assess causality. With multivariable MR, we investigated whether causal effects were mediated by smoking, body mass index, physical activity, lipid levels, or type 2 diabetes. Genetic correlations between schizophrenia and CVD were close to zero (−0.02–0.04). There was evidence that liability to schizophrenia causally increases heart failure risk. This effect remained consistent with multivariable MR. There was also evidence that liability to schizophrenia increases early repolarization pattern, largely mediated by BMI and lipids. Finally, there was evidence that liability to schizophrenia increases heart rate variability, a direction of effect contrasting clinical studies. There was weak evidence that higher systolic blood pressure increases schizophrenia risk. Our finding that liability to schizophrenia increases heart failure is consistent with the notion that schizophrenia involves a systemic dysregulation of the body with detrimental effects on the heart. To decrease cardiovascular mortality among individuals with schizophrenia, priority should lie with optimal treatment in early stages of psychosis

The cardiac sodium channel displays differential distribution in the conduction system and transmural heterogeneity in the murine ventricular myocardium

Cardiac sodium channels are responsible for conduction in the normal and diseased heart. We aimed to investigate regional and transmural distribution of sodium channel expression and function in the myocardium. Sodium channel Scn5a mRNA and Na(v)1.5 protein distribution was investigated in adult and embryonic mouse heart through immunohistochemistry and in situ hybridization. Functional sodium channel availability in subepicardial and subendocardial myocytes was assessed using patch-clamp technique. Adult and embryonic (ED14.5) mouse heart sections showed low expression of Na(v)1.5 in the HCN4-positive sinoatrial and atrioventricular nodes. In contrast, high expression levels of Na(v)1.5 were observed in the HCN4-positive and Cx43-negative AV or His bundle, bundle branches and Purkinje fibers. In both ventricles, a transmural gradient was observed, with a low Na(v)1.5 labeling intensity in the subepicardium as compared to the subendocardium. Similar Scn5a mRNA expression patterns were observed on in situ hybridization of embryonic and adult tissue. Maximal action potential upstroke velocity was significantly lower in subepicardial myocytes (mean +/- SEM 309 +/- 32 V/s; n = 14) compared to subendocardial myocytes (394 +/- 32 V/s; n = 11; P < 0.05), indicating decreased sodium channel availability in subepicardium compared to subendocardium. Scn5a and Na(v)1.5 show heterogeneous distribution patterns within the cardiac conduction system and across the ventricular wall. This differential distribution of the cardiac sodium channel may have profound consequences for conduction disease phenotypes and arrhythmogenesis in the setting of sodium channel diseas

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

The role of renin-angiotensin-aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

The phenotypic variability of hypertrophic cardiomyopathy (HCM) in patients with identical pathogenic mutations suggests additional modifiers. In view of the regulatory role in cardiac function, blood pressure, and electrolyte homeostasis, polymorphisms in the renin-angiotensin-aldosterone system (RAAS) are candidates for modifying phenotypic expression. In order to investigate whether RAAS polymorphisms modulate HCM phenotype, we selected a large cohort of carriers of one of the three functionally equivalent truncating mutations in the MYBPC3 gene. Family-based association analysis was performed to analyze the effects of five candidate RAAS polymorphisms (ACE, rs4646994; AGTR1, rs5186; CMA, rs1800875; AGT, rs699; CYP11B2, rs1799998) in 368 subjects carrying one of the three mutations in the MYBPC3 gene. Interventricular septum (IVS) thickness and Wigle score were assessed by 2D-echocardiography. SNPs in the RAAS system were analyzed separately and combined as a pro-left ventricular hypertrophy (LVH) score for effects on the HCM phenotype. Analyzing the five polymorphisms separately for effects on IVS thickness and Wigle score detected two modest associations. Carriers of the CC genotype in the AGT gene had less pronounced IVS thickness compared with CT and TT genotype carriers. The DD polymorphism in the ACE gene was associated with a high Wigle score (P=0.01). No association was detected between the pro-LVH score and IVS thickness or Wigle score. In conclusion, in contrast to previous studies, in our large study population of HCM patients with functionally equivalent mutations in the MYBPC3 gene we did not find major effects of genetic variation within the genes of the RAAS system on phenotypic expression of HCM