Venture Investments in Israel - A Regional Perspective Dafna Schwartz and Raphael Bar-El Ben-Gurion University, School of Management, Israel

Venture Investments in Israel – a Regional Perspective This paper analyzes the geographic distribution of venture investments in start-ups in Israel, using data for the period of 1995-2004. The findings show that their location behavior differs from that of high-tech activities: they show a pattern of "dispersed concentration" (as compared with a pattern of "concentrated concentration" of high-tech activity), with high levels of concentration in focal places, but at a commuting distance from the main metropolis. This is explained by the fact that venture investors also play the role of entrepreneurs and managers. The comparison between different types of venture investors shows that local venture capital funds lead to the heaviest concentration in the metropolis, in comparison with foreign venture investors. This heavy concentration of venture investments implies increasing regional gaps, with a minimal participation of peripheral regions, even those that enjoy some high-tech activity.

Spatial urban restructuring for economic growth with distribution: The case of Ceara (Brazil)

One of the most important challenges of economic policy is the combination between economic growth and the reduction of inequality and poverty. The change of the regime in Brazil can be seen as a reaction to the failure of economic policy in this field. We focus on the case of one of Brazil's states in the Northeast, Ceara, that experienced a rapid macro economic growth in the last decade, but with no reduction of poverty and inequality. Established economic theory shows that economic growth generally implies a changing economic structure (relatively less agriculture, and more industry and later services), and a process of urbanization. Our hypothesis is that in addition to industrialization and urbanization, a component of spatial urban restructuring is necessary for the achievement of a more equalitarian economic growth. The persistence of inequalities and high levels of poverty in spite of the macro economic growth can be explained by the continuing high level of urban concentration, and the insufficient growth of urban centers outside the metropolis. We test this using data of economic growth in Ceara, compared with trends of urbanization and its concentration level, changing economic structures (distribution between agriculture, industry and services) in the regions outside the metropolis and levels of productivity. Results lead to the conclusion that economic policy measures should consider a spatial reallocation of public expenditures for physical and human infrastructures, leading to a spatial urban restructuring.

Targeted consultancy services as an instrument for the development of rural SMEs - a brazilian case

One of the problems that policy makers face in the process of development in many countries is the inequality between the periphery and the metropolis center. The periphery has difficulties making the structural adjustments needed to fit in the national growth, leading to growing unemployment rates, regional gaps and continuous migration to the big metropolis. One of the sectors that has a difficulty making the transition is the small business sector. Amongst the reasons is in-adequate skills and information of the business management and in some cases a lack of awareness to the importance of these fields in the potential growth to the business. In addition the government support systems for small businesses do not give an adequate response. Support programs for small businesses are mostly provided within the urban sector, and are not adapted to the needs of the rural sector. The outcome is that although there is a "potential" need among small businesses in the interior for business consultant's services and in-spite of there being a wide range system of support for small businesses at the national level, their access to such services is limited. As a consequence of the potential demand that doesn't come into expression in the existing structure and of a national supply of these services that does not meet the needs of this sector, the gaps between the rural area and the urban central area grows. Our hypothesis is that an effort to establish a link between the unexpressed demand and the inappropriate supply of services to small-scale businesses in the rural area may contribute to economic growth. We test this hypothesis by using a program that was launched in the state of Ceara, Brazil, that is set to aim at both the demand and supply, focusing on a specific population: non-agricultural businesses in the rural region. The program is intended in the first stage to create awareness in the business community to the potential for business development and to encourage their demand for such services. The program offers consultancy services suited to the special needs of businesses in the non-metropolitan region adopting a reach-out approach. The program is part of the San Jose Project directed by the Secretary of Rural Development of the State of Ceara, that is aimed to bring a reduction in poverty in rural poor areas. The first stage of the research is to identify the potential of demand for consulting services and identifying the main areas in which the consulting is needed. A questionnaire was applied to 224 entrepreneurs in three selected areas. The findings show that about all the entrepreneurs are interested in receiving the consulting services. 90% of them evaluated that they had a growth potential. The factors that they point out as main constraints are, in order: physical infrastructures (65%), marketing (60%), capital returns (52%) problems in management and labor force (37%) and administration problems (35%). The second stage of the research was focused on 140 entrepreneurs who responded to a few basic criteria and were entitled to receive basic consulting services, of up to 15 hours. At this stage the marketing turned up as a main problem, especially for businesses that are in a process of transition from local to national markets. The findings show also that the support system that provides the consultancy services needs to go through a process of adaptation. One important difficulty of the system is to switch from internal advisers to external ones who specialize in the field.

From metropolis to metropolis-based region: the case of Tel-Aviv

The decreasing importance of metropolitan areas in the distribution of population and economic activity within many nations of the developed world raises questions about the emergence of agglomeration diseconomies and about the changes in urban spatial structure. Here we explore the thesis that an emerging metropolitan area based region (MBR), comprising the metropolis and a surrounding territory, is gradually replacing the metropolis. Using data covering the last 22 years for the metropolis of Tel-Aviv (Israel) and its surrounding territory, various indicators are estimated. These include national and regional deconcentration (both measured in terms of population and employment), as well as centrality, dependence, attractiveness and integration (measured in terms of employment). The main results of the analysis include the following: the need to view metropolitan stagnation and deconcentration within the wider context of the MBR; employment deconcentration occurring at a slower rate than population deconcentration, leading to increasing levels of employment centrality within the MBR; the process of consolidation within the MBR and a strengthening of its economic role within the nation.

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

A Typology of Regional Cooperation Projects

Regional cooperation projects between countries in the Middle East are expected to provide benefits to all parties involved but their feasibility is subject to social, economic and political constraints. This article uses a database of planned projects in the last decade and tries to detect types of projects that are less sensitive to the constraints. A typology of projects shows the prevalence of two main groups. A first group of projects avoids constraints by focusing on relatively high micro-economic viability but with low intensity of cooperation: these are economic-business projects and some infrastructure projects that are based on mere coordination between countries and mostly implemented separately in a single country. A second group of projects are infrastructure and public services projects that involve a number of countries, and implementation through joint planning and management. We conclude that the response to the constraints for regional cooperation is found in the concentration in projects that do not require any intensive continuous contact between the populations, by choosing business projects that are implemented separately in each country, or public projects that are jointly implemented, but on the basis of cooperation between public officers, not necessarily the population.

Inter-regional labor market equilibrium: another pattern of spatial mismatch

D58, J23, J61, O18, R12,