Small business activity does not measure entrepreneurship

Entrepreneurship policy mainly aims to promote innovative Schumpeterian entrepreneurship. However, the rate of entrepreneurship is commonly proxied using quantity-based metrics, such as small business activity, the self-employment rate, or the number of startups. We argue that those metrics give rise to misleading inferences regarding high-impact Schumpeterian entrepreneurship. To unambiguously identify high-impact entrepreneurs we focus on self-made billionaires (in US dollars) who appear on Forbes Magazine’s list and who became wealthy by founding new firms. We identify 996 such billionaire entrepreneurs in 50 countries in 1996–2010, a systematic cross-country study of billionaire entrepreneurs. The rate of billionaire entrepreneurs correlates negatively with self-employment, small business ownership, and firm startup rates. Countries with higher income, higher trust, lower taxes, more venture capital investment, and lower regulatory burdens have higher billionaire entrepreneurship rates but less self-employment. Despite its limitations, the number of billionaire entrepreneurs appears to be a plausible cross-country measure of Schumpeterian entrepreneurship.Given the prominence of entrepreneurship, it may come as a surprise that there is no consensus on how it should be defined in empirical research. Sometimes entrepreneurship is used to refer to anyone operating a private business, regardless of size and activity. Driven by greater data availability, most empirical studies rely on definitions such as the self-employment rate, the number of startups, and small business activity (1). In other contexts, entrepreneurship refers to the subset of firms that are innovative and growth-driven (2, 3). This Schumpeterian definition of the entrepreneur as an innovator and as a driver of growth dominates in theoretical entrepreneurship research and in entrepreneurship policy (4, 5). Thus, when academics and business leaders were asked to define entrepreneurship, the most common choices were the creation and growth of new ventures and innovation. By contrast, the creation of a mom-and-pop business was not viewed as entrepreneurship (6).Leaving aside the semantic discussion of what exactly constitutes entrepreneurship, there is an important empirical issue of how well commonly used operationalizations capture the rate of Schumpeterian entrepreneurship. An implicit assumption appears to be that countries and industries with a large number of small firms and startups also tend to be those where most innovative high-growth firms emerge.However, an overwhelming majority of the self-employed are not entrepreneurial in the Schumpeterian sense, as they never bring a new innovation to the market and do not plan to grow their business. In the United States, the industries with the largest concentrations of self-employed men are construction, landscaping services, auto repair, restaurants, truck transportation, and farming. For women, the corresponding industries include private households (cooks and maids), child day care services, restaurants, and beauty salons. The majority of small businesses in the United States have no employees other than the owner. Nor do most small businesses eventually grow large. Most small businesses are best described as permanently small rather than nascent entrepreneurial firms.Shane (7) argues that necessity-driven and opportunity entrepreneurs should be treated separately, documenting a negative cross-country correlation between having many high- and low-expectation startups. Baumol (3) distinguishes between “innovative” and “replicative” entrepreneurs, where the former are the type of entrepreneurs studied by Schumpeter (2). Hurst and Pugsley (8) forcefully argue against using self-employment as synonymous with entrepreneurship. They estimate that only 10–20% of small businesses report any innovative activity at all and point out that when new startups were asked about growth ambitions, 75% of respondents stated that “I want a size I can manage myself or with a few key employees” (ref. 8, p. 96). Different types of business owners also differ in terms of personality traits (9).Both types of businesses are important for a well-functioning economy, but their workings are entirely different. Innovative and replicative businesses operate in different ways, but are not easily distinguishable in statistics, which means that special approaches must be designed for empirical analysis.One way through which scholars have attempted to distinguish the different classes of firms is by restricting attention to “high-impact entrepreneurs” (10, 11), which is to say those that grow rapidly. The difficulty of estimating the rate of high-impact entrepreneurship in a standardized way across countries has thus far prevented cross-country comparisons.We propose a measure of high-impact Schumpeterian entrepreneurship across countries using information from the Forbes Magazine worldwide list of billionaires during 2 decades. Our measure of high-impact entrepreneurship is based on the accumulation of wealth for founders of new business ventures. We compare this measure to quantity-based empirical proxies for entrepreneurship such as self-employment, small business ownership, and number of startups. Henceforth in the paper for the sake of brevity, “entrepreneurship” refers to billionaire entrepreneurship, the focus of this paper.For each billionaire, the source of wealth was investigated, allowing us to identify 996 self-made billionaires who became rich by founding new firms. Using these individuals to construct a per capita rate of high-impact entrepreneurship, we show that this measure is robustly and negatively correlated with self-employment rates, small business ownership rates, and the rate of startup activity.     

Salmonid alphavirus glycoprotein E2 requires low temperature and E1 for virion formation and induction of protective immunity

Salmonid alphavirus (SAV; also known as Salmon pancreas disease virus; family Togaviridae) causes pancreas disease and sleeping disease in Atlantic salmon and rainbow trout, respectively, and poses a major burden to the aquaculture industry. SAV infection in vivo is temperature-restricted and progeny virus is only produced at low temperatures (10–15 °C). Using engineered SAV replicons we show that viral RNA replication is not temperature-restricted suggesting that the viral structural proteins determine low-temperature dependency. The processing/trafficking of SAV glycoproteins E1 and E2 as a function of temperature was investigated via baculovirus vectors in Sf9 insect cells and by transfection of CHSE-214 fish cells with DNA constructs expressing E1 and E2. We identified SAV E2 as the temperature determinant by demonstrating that membrane trafficking and surface expression of E2 occurs only at low temperature and only in the presence of E1. Finally, a vaccination-challenge model in Atlantic salmon demonstrates the biological significance of our findings and shows that SAV replicon DNA vaccines encoding E2 elicit protective immunity only when E1 is co-expressed. This is the first study that identifies E2 as the critical determinant of SAV low-temperature dependent virion formation and defines the prerequisites for induction of a potent immune response in Atlantic salmon by DNA vaccination.     

Les complications respiratoires de la transfusion

Respiratory complications of blood transfusion have several possible causes. Transfusion-Associated Circulatory Overload (TACO) is often the first mentioned. Transfusion-Related Acute Lung Injury (TRALI), better defined since the consensus conference of Toronto in 2004, is rarely mentioned. French incidence is low. Non-hemolytic febrile reactions, allergies, infections and pulmonary embolism are also reported. The objective of this work was to determine the statistical importance of the different respiratory complications of blood transfusion. This work was conducted retrospectively on transfusion accidents in six health centers in Champagne-Ardenne, reported to Hemovigilance between 2000 and 2009 and having respiratory symptoms. The analysis of data was conducted by an expert committee. Eighty-three cases of respiratory complications are found (316,864 blood products). We have counted 26 TACO, 12 TRALI (only 6 cases were identified in the original investigation of Hemovigilance), 18 non-hemolytic febrile reactions, 16 cases of allergies, 5 transfusions transmitted bacterial infections and 2 pulmonary embolisms. Six new TRALI were diagnosed previously labeled TACO for 2 of them, allergy and infection in 2 other cases and diagnosis considered unknown for the last 2. Our study found an incidence of TRALI 2 times higher than that reported previously. Interpretation of the data by a multidisciplinary committee amended 20 % of diagnoses. This study shows the imperfections of our system for reporting accidents of blood transfusion when a single observer analyses the medical records.     

Interaction between nitric oxide and endogenous vasoconstrictors in control of renal blood flow

The level of renal blood flow (RBF) is controlled by opposing vasoconstrictor and vasodilator influences. In a recent investigation in normotensive dogs, we found that combined blockade of endothelin type A (ET(A)) receptors and angiotensin II formation induces marked increases in RBF that were much larger than the effects of blocking either system alone. The aim of the present study was to determine the contribution of nitric oxide (NO) to this vasodilator response. Experiments were made in 6 conscious, chronically instrumented dogs subjected to 5 different experimental treatments on separate days. Blockade of ET(A) receptors alone by the selective antagonist LU 135252 had only minor effects on RBF compared with time-control experiments. Additional blockade of angiotensin II formation by angiotensin-converting enzyme inhibition with trandolaprilat caused a substantial increase of RBF by approximately 50%. This vasodilation was entirely suppressed when NO formation was prevented by inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester HCl. However, when during NO synthase inhibition renal vascular NO concentrations were clamped at control levels by infusing the NO donor S-nitroso-N-acetyl-D, L-penicillamine, the vasodilator response to combined blockade of ET(A) receptors and angiotensin II formation was completely restored (DeltaRBF approximately 60%). These results indicate that the vasodilation after combined ET(A) receptor blockade and angiotensin-converting enzyme inhibition is not mediated by an increase in NO release but results from the unmasking of the tonic influence that is normally exerted by constitutively released NO. Accordingly, the tonic activity of endothelial NO synthase appears to be of major importance in the physiological regulation of renal vascular resistance by determining the vasomotor responses to endothelin and angiotensin II.     

Clostridium difficile toxins A and B directly stimulate human mast cells

Clostridium difficile toxins A and B (TcdA and TcdB) are the causative agents of antibiotic-associated pseudomembranous colitis. Mucosal mast cells play a crucial role in the inflammatory processes underlying this disease. We studied the direct effects of TcdA and TcdB on the human mast cell line HMC-1 with respect to degranulation, cytokine release, and the activation of proinflammatory signal pathways. TcdA and TcdB inactivate Rho GTPases, the master regulators of the actin cytoskeleton. The inactivation of Rho GTPases induced a reorganization of the actin cytoskeleton accompanied by morphological changes of cells. The TcdB-induced reorganization of the actin cytoskeleton in HMC-1 cells reduced the number of electron-dense mast cell-specific granules. Accordingly, TcdB induced the release of hexosaminidase, a marker for degranulation, in HMC-1 cells. The actin rearrangement was found to be responsible for degranulation since latrunculin B induced a comparable hexosaminidase release. In addition, TcdB as well as latrunculin B induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 and also resulted in a p38 MAPK-dependent increased formation of prostaglandins D(2) and E(2). The autocrine stimulation of HMC-1 cells by prostaglandins partially contributed to the degranulation. Interestingly, TcdB-treated HMC-1 cells, but not latrunculin B-treated HMC-1 cells, showed a strong p38 MAPK-dependent increase in interleukin-8 release. Differences in the mast cell responses to TcdB and latrunculin B are probably due to the presence of functionally inactive Rho GTPases in toxin-treated cells. Thus, the HMC-1 cell line is a promising model for studying the direct effects of C. difficile toxins on mast cells independently of the tissue context.     

New insights into the phenotypes of atopic dermatitis linked with allergies and asthma in children: An overview

Atopic dermatitis (AD) is a complex disease with multiple causes and complex mechanistic pathways according to age of onset, severity of the illness, ethnic modifiers, response to therapy and triggers. A group of difficult‐to‐manage patients characterized by early‐onset AD and severe lifelong disease associated with allergic asthma and/or food allergy (FA) has been identified. In this study, we focus on these severe phenotypes, analysing their links with other atopic comorbidities, and taking into account the results from recent cohort studies and meta‐analyses. The main hypothesis that is currently proposed to explain the onset of allergic diseases is an epithelial barrier defect. Thus, the atopic march could correspond to an epithelial dysfunction, self‐sustained by a secondary allergenic sensitization, explaining the transition from AD to allergic asthma. Furthermore, AD severity seems to be a risk factor for associated FA. Results from population‐based, birth and patient cohorts show that early‐onset and severe AD, male gender, parental history of asthma, and early and multiple sensitizations are risk factors leading to the atopic march and the development of asthma. The importance of environmental factors should be recognized in these high‐risk children and prevention programs adapted accordingly. Effective targeted therapies to restore both barrier function and to control inflammation are necessary; early emollient therapy is an important approach to prevent AD in high‐risk children. Clinicians should also keep in mind the specific risk of atopic comorbidities in case of filaggrin loss‐of‐function mutations and the rare phenotypes of orphan syndromes due to heritable mutations in skin barrier components.