Selection Effects in Entrepreneurship

My work is positioned within an emerging trend in entrepreneurial research which revises prior work by considering the impact of selection effects. Prior research on the individual-level determinants of start-up size, performance, and exit has ignored that individuals select into entrepreneurship and this might seriously bias our understanding of the post-entry process. I'm particularly well positioned to investigate the nature, the extent, and the consequences of these selection effects because I could access extraordinary data on the Swedish population, which allows me to incorporate information on individuals who were at risk but did not enter entrepreneurship. Yet, the overall contribution of my dissertation goes beyond flagging a selection problem and developing a method to cope with it. It comes up with reexamining and even questioning some of the most prominent theoretical explanations to fundamental issues in entrepreneurship, such as the notion of initial size, the liability of smallness, and the interplay between entrepreneurial performance and firm exit

Selection Effects in Entrepreneurship

My work is positioned within an emerging trend in entrepreneurial research which revises prior work by considering the impact of selection effects. Prior research on the individual-level determinants of start-up size, performance, and exit has ignored that individuals select into entrepreneurship and this might seriously bias our understanding of the post-entry process. I'm particularly well positioned to investigate the nature, the extent, and the consequences of these selection effects because I could access extraordinary data on the Swedish population, which allows me to incorporate information on individuals who were at risk but did not enter entrepreneurship. Yet, the overall contribution of my dissertation goes beyond flagging a selection problem and developing a method to cope with it. It comes up with reexamining and even questioning some of the most prominent theoretical explanations to fundamental issues in entrepreneurship, such as the notion of initial size, the liability of smallness, and the interplay between entrepreneurial performance and firm exit.My work is positioned within an emerging trend in entrepreneurial research which revises prior work by considering the impact of selection effects. Prior research on the individual-level determinants of start-up size, performance, and exit has ignored that individuals select into entrepreneurship and this might seriously bias our understanding of the post-entry process. I'm particularly well positioned to investigate the nature, the extent, and the consequences of these selection effects because I could access extraordinary data on the Swedish population, which allows me to incorporate information on individuals who were at risk but did not enter entrepreneurship. Yet, the overall contribution of my dissertation goes beyond flagging a selection problem and developing a method to cope with it. It comes up with reexamining and even questioning some of the most prominent theoretical explanations to fundamental issues in entrepreneurship, such as the notion of initial size, the liability of smallness, and the interplay between entrepreneurial performance and firm exit.LUISS PhD Thesi

Entrepreneurship and employment stability — Job matching, labour market value, and personal commitment

This paper challenges the conventional belief that entrepreneurship is an unstable career path. Using longitudinal matched employer–employee data from Denmark, the analysis reveals that a transition to entrepreneurship decreases individual's employment turnover tendency. Three explanations are identified and empirically explored: (i) job matching, (ii) labour market value, and (iii) personal commitment. Entrepreneurs appear to be more productive and thus better matched compared to wageworkers. However, they also appear to be locked in entrepreneurship because of their anticipated lower value in the labour market and because of their personal attachment to the venture. The counter-intuitive finding – entrepreneurship yields greater employment stability – only holds with respect to subsequent transitions to wagework and not for new venture founding. The results have implications for our understanding of entrepreneurial entry and labour market dynamics.</p

Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients

Background: Objective techniques to assess the amelioration of vision in patients with impaired visual function are needed to standardize efficacy assessment in gene therapy trials for ocular diseases. Pupillometry has been investigated in several diseases in order to provide objective information about the visual reflex pathway and has been adopted to quantify visual impairment in patients with Leber Congenital Amaurosis (LCA). In this paper, we describe detailed methods of pupillometric analysis and a case study on three Italian patients affected by Leber Congenital Amaurosis (LCA) involved in a gene therapy clinical trial at two follow-up time-points: 1 year and 3 years after therapy administration. Methods: Pupillary light reflexes (PLR) were measured in patients who had received a unilateral subretinal injection in a clinical gene therapy trial. Pupil images were recorded simultaneously in both eyes with a commercial pupillometer and related software. A program was generated with MATLAB software in order to enable enhanced pupil detection with revision of the acquired images (correcting aberrations due to the inability of these severely visually impaired patients to fixate), and computation of the pupillometric parameters for each stimulus. Pupil detection was performed through Hough Transform and a non-parametric paired statistical test was adopted for comparison. Results: The developed program provided correct pupil detection also for frames in which the pupil is not totally visible. Moreover, it provided an automatic computation of the pupillometric parameters for each stimulus and enabled semi-automatic revision of computerized detection, eliminating the need for the user to manually check frame by frame. With reference to the case study, the amplitude of pupillary constriction and the constriction velocity were increased in the right (treated eye) compared to the left (untreated) eye at both follow-up time-points, showing stability of the improved PLR in the treated eye. Conclusions: Our method streamlined the pupillometric analyses and allowed rapid statistical analysis of a range of parameters associated with PLR. The results confirm that pupillometry is a useful objective measure for the assessment of therapeutic effect of gene therapy in patients with LCA

RET: A Multi-Faceted Gene in Human Cancer

Receptor tyrosine kinases (RTK) are transmembrane (TM) proteins featuring an intracellular domain containing the tyrosine kinase (TK) enzyme. RTKs are often involved in cancer formation [13]. Notable examples are epidermal growth factor receptor (EGFR/ HER1) and anaplastic lymphoma kinase (ALK) in non-small cell lung carcinoma (NSCLC) [4], KIT in gastrointestinal stromal tumors (GIST) [5], FLT3 in acute myeloid leukemia (AML) [6], and HER2/ ERBB2/neu in breast cancer [7]. In some cases, cancer cells up-regulate expression of the RTK (as an example HER2 in breast cancer), its cognate growth factor or both, in other cases, structural alterations such as chromosomal rearrangements leading to the RTK recombination to heterologous genes (as an example EML4-ALK in lung adenocarcinoma) or point mutations (as EGFR, KIT or FLT3 mutations in NSCLC, GIST, or AML, respectively), lead to unchecked kinase and oncogenic activity [1-3]. This notion has stimulated the search for agents, such as monoclonal antibodies against the RTK extracellular domain (like trastuzumab for HER2 or cetuximab for EGFR) or ATP-competitive small molecule protein kinase inhibitors (PKIs) (like gefitinib and erlotinib for EGFR or crizotinib for ALK), to combat cancers driven by oncogenic RTKs [1-3]. The RET RTK was originally identified as an oncogene activated by a rearrangement occurred in vitro during transfection of NIH3T3 cells with human lymphoma DNA [8]. RET protein belongs to a cell-surface complex able to bind glial-derived neurotrophic factor (GDNF) ligands (GDNF, neurturin, artemin, and persephin) in conjunction with co-receptors of the GDNF receptor α family, designated GFRα 1-4 [9]. Binding to the ligand-co-receptor complex leads to RET dimerization and kinase activation. RET expression is tightly regulated during development and in the adulthood is limited to specific tissues, including neural crest-derived cells. RET is essential for the development of the enteric neurvous system and kidney, and germline loss-of-function mutations in RET cause Hirschsprung disease (aganglionic megacolon) and congenital anomalies of the kidney or lower urinary tract [10,11]. RET gene maps to chromosome 10q11.2. Fig. 1 shows that it is splitted in 21 coding exons. Exons 1-10 code for the extracellular region; exon 11 codes for the COOH-terminal part of the extracellular region, the TM domain, and the intracellular juxtamembrane domain. Finally, exons 12-21 code for the intracellular domain. An alternative splicing at exon 19 determine the synthesis of three RET protein isoforms with different C-terminal tails. In RET9 (1072 aa), exon 19 is unspliced; in RET51 (1114 aa), exon 19 is spliced to exon 20; in RET43 (1106 aa), exon 19 is spliced to to exon 21 [12-15]. RET9 and RET51 are the most abundant and well characterized isoforms (Fig. 1). RET protein features an extracellular portion (RET-EC) tha

Entrepreneurship and employment stability — Job matching, labour market value, and personal commitment

This paper challenges the conventional belief that entrepreneurship is an unstable career path. Using longitudinal matched employer–employee data from Denmark, the analysis reveals that a transition to entrepreneurship decreases individual's employment turnover tendency. Three explanations are identified and empirically explored: (i) job matching, (ii) labour market value, and (iii) personal commitment. Entrepreneurs appear to be more productive and thus better matched compared to wageworkers. However, they also appear to be locked in entrepreneurship because of their anticipated lower value in the labour market and because of their personal attachment to the venture. The counter-intuitive finding – entrepreneurship yields greater employment stability – only holds with respect to subsequent transitions to wagework and not for new venture founding. The results have implications for our understanding of entrepreneurial entry and labour market dynamics.</p

Analysis of Corneal Deformation in Paediatric Patients Affected by Maturity Onset Diabetes of the Young Type 2

Abstract Background: To evaluate corneal deformation in Maturity Onset Diabetes of the Young type 2 (MODY2), paediatric subjects were analysed using a Scheimpflug-based device. The purpose of this analysis was to find new biomarkers for MODY2 disease and to gain a better understanding of the pathogenesis of the disease. Methods: A total of 15 patients with genetic and metabolic diagnoses of MODY2 (mean age 12.8 ± 5.66 years) and 15 age-matched healthy subjects were included. The biochemical and anthropometric data of MODY2 patients were collected from clinical records, and a complete ophthalmic check with a Pentacam HR EM-3000 Specular Microscope and Corvis ST devices was performed in both groups. Results: Highest concavity (HC) deflection length, Applanation 1 (A1) deflection amplitude, and A1 deflection area showed significantly lower values in MODY2 patients compared to healthy subjects. A significant positive correlation was observed between Body Mass Index (BMI) and HC deflection area and between waist circumference (WC) and the following parameters: maximum deformation amplitude, HC deformation amplitude, and HC deflection area. The glycosylated hemoglobin level (HbA1c) showed a significant positive correlation with Applanation 2 time and HC time. Conclusions: The obtained results show, for the first time, differences regarding corneal distortion features in the MODY2 population compared with healthy eyes

Automatic Detection of Genetic Diseases in Pediatric Age Using Pupillometry

Inherited retinal diseases cause severe visual deficits in children. They are classified in outer and inner retina diseases, and often cause blindness in childhood. The diagnosis for this type of illness is challenging, given the wide range of clinical and genetic causes (with over 200 causative genes). It is routinely based on a complex pattern of clinical tests, including invasive ones, not always appropriate for infants or young children. A different approach is thus needed, that exploits Chromatic Pupillometry, a technique increasingly used to assess outer and inner retina functions. This paper presents a novel Clinical Decision Support System (CDSS), based on Machine Learning using Chromatic Pupillometry in order to support diagnosis of Inherited retinal diseases in pediatric subjects. An approach that combines hardware and software is proposed: a dedicated medical equipment (pupillometer) is used with a purposely designed custom machine learning decision support system. Two distinct Support Vector Machines (SVMs), one for each eye, classify the features extracted from the pupillometric data. The designed CDSS has been used for diagnosis of Retinitis Pigmentosa in pediatric subjects. The results, obtained by combining the two SVMs in an ensemble model, show satisfactory performance of the system, that achieved 0.846 accuracy, 0.937 sensitivity and 0.786 specificity. This is the first study that applies machine learning to pupillometric data in order to diagnose a genetic disease in pediatric age

The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins.

Abstract Thyroid cancer is frequently associated with the oncogenic conversion of the RET receptor tyrosine kinase. RET gene rearrangements, which lead to the generation of chimeric RET/papillary thyroid carcinoma (PTC) oncogenes, occur in PTC, whereas RET point mutations occur in familial multiple endocrine neoplasia type 2 (MEN2) and sporadic medullary thyroid carcinomas (MTC). We showed previously that the expression of the receptor-type protein tyrosine phosphatase J (PTPRJ) is suppressed in neoplastically transformed follicular thyroid cells. We now report that PTPRJ coimmunoprecipitates with wild-type RET and with the MEN2A-associated RET(C634R) oncoprotein but not with the RET/PTC1 and RET-MEN2B isoforms. Using mutated forms of PTPRJ and RET-MEN2A, we show that the integrity of the respective catalytic domains is required for the PTPRJ/RET-MEN2A interaction. PTPRJ expression induces dephosphorylation of the RET(C634R) and, probably via an indirect mechanism, RET/PTC1 oncoproteins on two key RET autophosphorylation sites (Tyr1062 and Tyr905). This results in a significant decrease of RET-induced Shc and extracellular signal-regulated kinase 1/2 phosphorylation levels. In line with this finding, adoptive PTPRJ expression reduced the oncogenic activity of RET(C634R) in an in vitro focus formation assay of NIH3T3 cells. As expected from the coimmunoprecipitation results, the RET(M918T) oncoprotein, which is associated to MEN2B and sporadic MTC, was resistant to the dephosphorylating activity of PTPRJ. Taken together, these findings identify RET as a novel substrate of PTPRJ and suggest that PTPRJ expression levels may affect tumor phenotype associated with RET/PTC1 and RET(C634R) mutants. On the other hand, resistance to PTPRJ may be part of the mechanism of RET oncogenic conversion secondary to the M918T mutation. (Cancer Res 2006; 66(12): 6280-7