Search

PURPOSE: Mental health comorbidities are commonplace among patients with cancer and have been associated with adverse health outcomes and elevated health care costs. Given the rapidly evolving cancer care landscape, an updated understanding of the prevalence and costs of mental health conditions among patients with cancer is needed. This study assessed the incremental costs of anxiety and depression among Medicare beneficiaries with cancer. METHODS: This retrospective cohort study used the SEER-Medicare database. Patients diagnosed with melanoma, breast, lung, prostate, or colorectal cancer between July 2013 and December 2017 were followed for at least 12 months and up to 36 months after cancer diagnosis. Patients were categorized on the basis of anxiety/depression (AD) diagnosis: (1) predating cancer, (2) onset after cancer, or (3) no AD. Multivariable regression was used to estimate differences in all-cause incremental costs (before v after cancer) between the three groups. RESULTS: Of 230,626 patients, 10% had AD before their cancer diagnosis and 22% were diagnosed after cancer. In the first year after cancer diagnosis, average monthly health care costs were $5,750 in US dollars (USD) for patients with newly onset, $5,208 (USD) for patients with preexisting, and $3,919 (USD) for patients without a diagnosis of AD. The incremental cost of cancer was the greatest among patients with newly onset AD—$1,458 (USD) per month greater than those with no AD. Similar patterns were observed across cancer types and stages. CONCLUSION: One in three Medicare beneficiaries with cancer in this study had a diagnosis of anxiety or depression. Newly onset AD is associated with an increase in health care costs of $17,496 (USD) per year. Screening and management of mental health conditions for patients with cancer should be part of coordinated oncology care.

BackgroundMultimorbidity is common in patients with breast cancer, thus increasing the complexity of cancer care and economic burden, worsening their prognosis and quality of life. The prevalence of multimorbidity and its influence on psychological distress among patients with breast cancer have not been well characterized.ObjectivesTo examine the prevalence of multimorbidity and its associations with anxiety and depression among newly diagnosed patients with breast cancer.MethodsWe conducted a retrospective observational cohort study using a large administrative claims database. Patients with breast cancer (ICD-10-CM: C50.x) were identified during the study period (1/1/2017-12/31/2020). The index date was defined as the diagnosis date of breast cancer. Demographics and comorbid conditions were assessed using data within 12 months prior to the index date. Multimorbidity was defined as the presence of ≥2 comorbid conditions. Anxiety and depression were examined using data within 12 months after the index date. Multivariable logistic regressions were performed to examine the associations between multimorbidity and anxiety and depression, adjusting for sociodemographic factors.ResultsOf the 6392 patients with newly diagnosed breast cancer, 86.9% had multimorbidity at the time of breast cancer diagnosis. The median number of comorbid conditions was 5. Overall, 27.7% experienced anxiety, and 21.9% experienced depression in the first year following breast cancer diagnosis. An increased number of comorbid conditions was associated with elevated prevalence of both anxiety and depression. After adjusting for possible confounding factors, number of comorbid conditions was significantly associated with risk of anxiety (adjusted odds ratio [95% confidence interval (CI)]: 1.17 [1.15-1.19]), and depression (1.24 [1.21-1.26]); all P < .0001.ConclusionsMultimorbidity was highly prevalent among patients with breast cancer and was strongly associated with increased risk of anxiety and depression in the first year following breast cancer diagnosis. The presence of multimorbidity, anxiety, and depression should be considered in the context of clinical decision making to optimize cancer care and improve mental health and quality of life.

Researchers have long searched for the underlying causes of growth. In developed countries, as they shifted from industrial to knowledge economies, researchers have recently stressed the following sources of growth embodied in its workforce: human capital (linked to education), entrepreneurship (variously measured), and the creative class (associated with worker occupations). This study first proposes new conceptual ways to portray the interrelationship of these knowledge-based attributes. Then simultaneously considers all of these factors in an empirical model using U.S. counties. We find that human capital as measured by educational attainment and the intensity of small and medium-sized firms are statistically associated with subsequent growth, while other factors such as the share of creative class workers or the share of advanced technology industries are insignificant. We conclude that economic development strategies are too focused on attracting large outside firms and attracting advanced technology firms and not enough attention is given to building a foundation of competitive small and medium-sized firms.

A sharp distinction between the virtual world and the real world continues but has become less tenable as technology has progressed. This review paper traces some early and recent views on this distinction, and highlights three: cyberscapes, cyberplaces, and code/space. Mobile applications, ubiquitous computing, and cloud data storage serve to blend the real and the virtual in a user-generated cyberspace. Within that space, knowledge production takes place in virtual spaces, as do less benign activities, such as surveillance and cybercrime. Policymakers must react to an increasingly complex environment of spaces in between real and virtual worlds.

The geography of the Internet is closely related to both the structures that link, at the highest level, world cities, and to the demand of large business customers that have always driven the demand for new telecommunications technology. This chapter reviews these themes and, with some evidence from the USA, concludes that, while some shifts are evident in the urban hierarchy, much stability remains. The Internet is a convergence or fusion of information types, information media, and information operators. The attraction of large-city markets results in several competitors, and network redundancy, in the Internet backbone on some city-pairs. The mesoscale is represented by the Points of Presence, which is typically a junction point of the high-bandwidth backbone network. Internet telephony continues to challenge traditional pricing models for long-distance and international service. As both technological change and market demand push further utilization of Internet-based business, geography and uneven local development are reaffirmed rather than eliminated.

This chapter is a brief review of some of the research themes of the past two decades on entrepreneurs, networks, and economic development. It begins with embeddedness and the heterogeneity of networks. Next, the chapter turns to a new concept that has emerged during the past decade: entrepreneurial ecosystems. Then, the author reviews the dynamics involved in entrepreneurship and regional development.

This chapter presents a study investigates the effect of solids retention time (SRT) on hydrolysis of diluted apple pomace. Apple pomace is the waste solids resulting from the production of apple juice or cider. The estimated disposal cost of the 1.5 million tons of pomace generated in the US each year exceeds $10 million. In addition to pomace, many processors discharge large quantities of wastewater generated during apple processing operations. Effluent limitation guidelines for the streams point source discharge generally require best conventional control technology. The most important factor having an impact on wastewater quality for juice manufacturers is quality of the raw fruit. For other products, the type of peeling operation employed, water use, and management attitude all have an important bearing on wastewater quality. Anaerobic digestion of apple wastes without nutrient or buffer addition results in a low cost alternative to disposal practices.

This chapter reviews the theoretical and empirical work on technological innovation and deals with the major stages of activity within technological change, including research and development, innovation, diffusion of innovations and technology transfer, and new firm formation in regional growth. It suggests avenues by which public policies can influence the process of technical change. The chapter emphasizes the diverse ways in which technology refashions regional economies and the critical role of entrepreneurship in the passage from innovation to regional economic change. S. J. Kline and N. Rosenberg elaborate on the linear model's shortcomings, stressing instead the diversity of activities that make up the innovation process, the variation across industry lines, and the apparent disorder-liness of the innovation process in reality. Product development is the last major stage in the linear model of innovation, and is that toward which the bulk of industrial research and development activity is oriented.

We follow Schumpeter in attributing to entrepreneurs the spark to bring new combinations to market by combining knowledge, perceived opportunity, and other resources to form new firms. A link between innovation and entrepreneurship was first seen in new firms exploiting new technologies in high-technology regions. This context set the tone for research, which we explore in this chapter. We identify four topics: entrepreneurship in high-tech contexts, spinoffs from university research, the local/regional ecosystem or innovation system, and flows of knowledge within social and professional networks. Underlying these four attributes of high-tech innovation are cultural outlooks and orientations. Without an understanding of how culture influences entrepreneurial and innovative activities, it is difficult to study their relationship with the cultural contexts in which they take place. Building on a nexus-based view of innovation and entrepreneurship, we argue that culture is best understood as a process through which actors interpret the world around them and which can either encourage or discourage entrepreneurial and innovative activity.

For many business leaders and policymakers, innovation and knowledge typify the characteristics of a knowledge economy and represent areas in which places compete. Rankings and comparisons among national and regional economies are now common. This chapter reviews the research on competitiveness, and demonstrates that knowledge, innovation and innovative capability are the core of economic competitiveness. The global innovation networks that enable creativity and innovation are formed in – and are attracted to – some places and not others. Although there are multiple dimensions of competitiveness, innovation is the fundamental dimension, comprised of local, global and virtual networks and systems of innovation.

In a globalising era, there have been many attempts to explain the processes of globalisation in urban studies. Beyond a global/world city hypothesis which mainly deals with macro-actors and top-down processes, this paper explores a grounded globalisation with the emergence of ethnic entrepreneurs who are rarely considered in global city research. We analyse business activities of Nigerian and Pakistani entrepreneurs within the district of Itaewon in Seoul, South Korea by examining two specific points: first, the division of ethnic entrepreneurs into two types: export-oriented and import-oriented, and second, the local-based transnational connections between home and host countries. We argue that the spontaneous transnational connections by ethnic entrepreneurs are an example of globalisation ‘from below’. In contrast to the homogenising Asian global cities, globalisation from below is crucial to understand the various forms of Asian global cities.

This paper provides an understanding of the regional determinants of research and development (R&D) institutions in India. R&D facilities locate across regions in response to factors such as: science and technology manpower availability, banking facilities, transport infrastructure, favorable real estate prices, state domestic product, patents, literacy, quality engineering colleges, higher education institutions, and investment via research and development expenditure. Further, R&D location brings regional change via industry location, employment and investment leading to regional economic development. The Indian government has pursued a balanced regional development strategy since the inception of planning in the 1950s. This strategy would need a dispersed location in geographical space. This policy changed to a market-oriented approach beginning in 1991. Various technology policy documents have emphasized upon ‘promotion of science and technology research’, ‘attainment of technological competence’, ‘enlarging investment in R&D’, and ‘synergize science, technology and innovation’. To examine the trends of R&D this paper addresses the following four questions: (1) what are the regional patterns of R&D distribution in India? (2) what are the sector patterns of R&D distribution in India? (3) What determines the regional distribution of patents? (4) What determines the regional distribution of R&D in India during the periods 1988–1989, 1998–1999 and 2009–2010? Multiple regression models are run to estimate the determinants of R&D in geographical space.

New technologies enable new urban patterns and new connections within and between cities. This paper reviews new and emerging technologies that are impacting cities internally and in their relations within larger networks. Policy and social attitudes also must change to incorporate and integrate new technologies. Forecasts and visions of urban futures are now more complicated by new technologies and by the global networks within which urban economies and urban dwellers operate.

Web 2.0 has yielded a wealth of publicly available data, largely through the popularization of social media and the proliferation of user-generated content (UGC). Thus, the data void in social science research is diminishing as these new data sources are exploited. The discipline of geography, in particular, stands to benefit considerably from geotagged UGC or volunteered geographic information (VGI). In this article, we utilize a form of UGC—restaurant reviews—to evaluate the geography of Web 2.0 in Franklin County, Ohio. We find that restaurant reviews are largely concentrated in relatively few areas of the city, indicating that the impacts of Web 2.0 have not touched down evenly within the central county of the Columbus metropolitan statistical area. We argue that an intraurban digital divide is still apparent and might even be exacerbated by Web 2.0.

We introduce the NOAO Fundamental Plane Survey (NFPS), a wide-field imaging/spectroscopic study of rich, low-redshift galaxy clusters. The survey targets X-ray-selected clusters at 0.010 < z < 0.067, distributed over the whole sky, with imaging and spectroscopic observations obtained for 93 clusters. This data set will be used in investigations of galaxy properties in the cluster environment and of large-scale velocity fields through the fundamental plane. In this paper, we present details of the cluster sample construction and the strategies employed to select early-type galaxy samples for spectroscopy. Details of the spectroscopic observations are reported. From observations of 5479 red galaxies, we present redshift measurements for 5388 objects and internal velocity dispersions for 4131. The velocity dispersions have a median estimated error ∼7%. The NFPS has ∼15% overlap with previously published velocity dispersion data sets. Comparisons to these external catalogs are presented and indicate typical external errors of ∼8%.

Urban rail networks are a critical component of successful cities able to compete at a global level in the twenty-first century. They enhance a city's economic efficiency, quality of life, and image through their traditional role as provider of local mobility between home, work, and leisure, as well as their new role in supporting global mobility between airports, business districts, and other critical economic nodes as a strategy to attract highly mobile high-human-capital individuals, investment, and tourists. Using a database of 140 urban rail transit systems at five intervals since 1970, we rank cities using an index that tracks each system's level of population exposure as well as its provision of airport access. We find that (1) higher ranked producer service cities provide better quality local and global mobility; (2) investment in urban rail has dramatically shifted to Asia and that continent's megacities are poised to become leaders in providing high levels of local and global mobility; and (3) s...

Malecki E. J. Regional social capital: why it matters, Regional Studies. Social capital refers to a culture of interaction among people, with productive economic outcomes. Social capital promotes regional learning both within a region and beyond, as it reinforces openness to the ideas of others. Regional cultures vary in the degree to which people – individually and within their organizations – trust and interact with one another, which is why regional outcomes vary. Innovation, learning and entrepreneurship – key processes of regional development – take place largely within and among people as members of companies and territorial organizations. Innovative milieus, industrial districts and knowledge economies are among the regions with extraordinary pools of social capital. Malecki E. J. 区域社会资本：有何相关性，区域研究。社会资本指一种人与人之间互动的文化，同时产生生产性经济结果。由于强化了人与人之间理念的互通，社会资本能够促进区域内外的区域性学习。不同个体之间及其组织间的信任与互动程度存在不同程度的差异, 这正是不同区域存在差异的原因。 作为区域发展中的核心过程，创新、学习以及公司多出现在公司以及领域性组织成员内部及相互之间。创新、产业区以及知识经济往往存在于拥有突出社会资本的区域。 社会资本 学习型区域 创新 学习 ...

Une tendance croissante aux États-Unis en matière de politique de développement rural consiste à créer des réseaux flexibles d’entreprises manufacturières, d’entreprises interreliées selon le modèle des districts industriels européens au Danemark et en Italie. Cet article étudie l’expérience de plusieurs réseaux en milieu rural et urbain aux États-Unis dans le but d’évaluer leur performance et leurs effets sur les entreprises qui en sont membres. Les entrevues en profondeur effectuées montrent que les réseaux sont plus utiles pour les nouvelles et les très petites entreprises (micro-entreprises). Comme institutions, les réseaux contribuent à la promotion des interactions interentreprises et à l’apprentissage collectif dans leur région. En plus, ils fournissent des services aux entreprises qui en sont membres.Il ressort que les réseaux enracinés dans leur région tendent à fournir plus à leurs membres que les réseaux moins intégrés. L’enracinement se manifeste par l’implication et le soutien financier (et matériel) des institutions locales et des résidents influents, en particulier la communauté d’entrepreneurs. Dans certaines régions où des réseaux n’étaient pas en opération, des entreprises ont été, en quelque sorte, en mesure de remplacer le réseau par un réseautage informationnel actif avec des entreprises situées en dehors de leur localité. Dans la plupart des régions, certaines politiques publiques de promotion semblent être nécessaires pour stimuler la formation de réseaux entre les entreprises locales., A growing trend in US rural (and urban) development policy is the formation of flexible manufacturing networks, interlinked firms patterned after European industrial districts in Denmark and Italy. This paper examines the experience of several such networks in the United States, in rural and in urban areas, in order to evaluate their performance and effects on member firms. Detailed interviews with firms in such networks indicate that networks are most useful for firms and very small firms (micro-enterprises). The networks as institutions promote inter-firm interaction and collective learning in their regions. In addition, the networks provide services to member firms. It appears that networks which become embedded in their region tend to provide more for their member firms than do less well-integrated networks.Embeddedness is indicated by the involvement and financial (and other) support or local institutions and of influential residents, especially community entrepreneurs. In only a few regions where no network operates, firms are able nearly to substitute for a network by means of active informal networking on their own with firms from outside the locality. In most regions, some public-policy « push » seems to be needed to foster networking among firms in the local area., Una nueva tendencia en las políticas de desarrollo rural y urbano en los Estados Unidos consiste en la formación de redes flexibles de conección entre manufactureros, modeladas de acuerdo a patrones establecidos en Dinamarca e Italia. Este artículo estudia las experiencias de varios de estos sistemas reticulares en los Estados Unidos, rural y urbano, con el propósito de evaluar su rendimiento y los efectos sobre las firmas que integran tales redes. Entrevistas detalladas con firmas en dichas redes indican que ellas son mas favorables para firmas nuevas y de peque o tama o (micro-empresas). Las redes promueven interaccciones entre las firmas incluidas y conocimientos colectivos acerca de las regiones donde ellas operan. Adicionalmente, las redes proveen servicios a las firmas asociadas.Parece ser que las redes que se han « insertado » en dichas regiones tienden a ofrecer mucho más para sus miembros que lo que ofrecen las redes menos integradas. La « Inserción » se revela en el grado de participación y apoyo financiero (o de otro orden) recibido por parte de instituciones locales y de residentes influyentes, especialmente empresarios de la comunidad. Sólo en regiones donde las redes no operan las firmas pueden sustituir dichas redes por medio de un sistema de integración propio en asociación con empresas de fuera de la localidad. En todas las regiones, se requieren ciertos impulsos creados por una política pública para promover la creación de inter-dependencias entre las firmas locales.

The oil-abundant, labour-deficient countries of the Persian Gulf are investing their wealth towards creating economic development beyond oil. At a minimum, these strategies are attempts to craft the basis for sustainable economic development in a global economy that is more dependent on human capital and creativity than on natural resource wealth. This paper examines the Gulf development experience in light of theories on the diversification of natural resource-based economies, the transition from pre- to post-industrial development, and the role of services as an economic base. The paper assesses the Gulf's current development efforts and post-oil, knowledge-based aspirations in terms of the region's competitiveness, knowledge accumulation, and labour market structure.

Malecki E. J. Global knowledge and creativity: new challenges for firms and regions, Regional Studies. As companies locate research and development in more places, they seek to tap knowledge in new, open ways, to respond to diverse customer demand and short product life cycles. The globalization of research and development has added costs as firms communicate across national, cultural, and linguistic boundaries, using both information and communication technology networks and face-to-face interaction. Intermediaries in knowledge transfer, such as knowledge brokers and gatekeepers, have become more important as new nodes join the global system of knowledge. As firms respond to the knowledge-based global economy, each region must construct a ‘knowledge monopoly’ to stand out in the global landscape of capabilities. Malecki E. J. La connaissance et la creativite mondiales: de nouveaux defis pour les entreprises et les regions, Regional Studies. Au fur et a mesure que la localisation des activites de recherch...

This paper reviews what we know about the spatial manifestations of knowledge. The knowledge production function addresses the easily measured portion of knowledge produced. Research on learning, particularly interactive and collective learning, in firms and in innovation systems, promises to unveil the human and organizational processes by which knowledge is created, stored, and transmitted to others. Our understanding of innovation and technological change depends on how well we tackle knowledge and its geography.

The concept of buzz is both new and heavily contested. One of the strongest debates about buzz is the possibility of ‘virtual buzz’ or buzz that takes place online. At the heart of this debate is the importance of real-time, face-to-face contact. To investigate virtual buzz we present a study of a network of weblogs, or blogs, which share a topical focus on the New York City theater scene. Using social network analysis we find that these blogs exhibit a dense network of interlinkages between each other, with no dominant blog controlling the discourse. We believe this to be indicative of a buzz-like environment. We conclude by discussing the advantages that the study of blogs has for the field of economic geography.

As more animated films are produced, new "worlds of production" have emerged. The animation production system is distinct from film production, relying on different technologies and labor skills. Its globalization, therefore, has taken place differently, although both are structured by the global production networks of the media conglomerates. We present a framework for understanding the animation industry, its international division of labor, and its diverse markets, enabled by pools of artistic labor, growing demand, and the diffusion of production skills. Copyright 2010 The Author 2009. Published by Oxford University Press on behalf of Associazione ICC. All rights reserved., Oxford University Press.

Submarine cables for telecommunications were an early catalyst of globalization and of transnational corporate production networks and they continue to facilitate global economic activity. This article describes increasing demand from Internet and mobile phones as well as new uses for cables, such as oil exploration and high-energy physics. We trace the history of submarine cables and their geography from their early days to the Internet era, and analyze a global data set of cables at four intervals since 1979. Although the traditional triad locations (Western Europe, North America, and East Asia) are among the best connected, new networks in new places—notably Asia—are poised to become key network nodes in the twenty-first century. Based on cable capacity, the future submarine cable network looks very different from the old, suggesting new economic geographies and new world cities for a new world economy.

The Internet is perhaps the defining technology of the emerging twenty-first century. This article examines the infrastructure that comprises the “network of networks” and the spatial patterns that...

Digital technology has permeated most sectors of the economy, a result of continuous improvement and convergence in computers and telecommunications, and the Internet revolution. Unprecedented tradability of digitized information and information-intensiveness of business are driving the collapsing of value chains’ organizational and spatial dimensions. We are witnessing a trend of vertical disintegration followed by complex re-arrangements that mix horizontal reintegration and spatial agglomeration with various patterns of dispersion. With the support of two empirical examples, this article endeavors to show that the territories of the digital economy are built under a permanent tension between these centripetal and centrifugal forces. Economic geography thinking should – in part – reject the traditional Christallerian hierarchy of scales, and consider instead the ability of contemporary business organizations and dynamics to squeeze out intermediary scales and places. The agglomeration theory, although still valid, is challenged by technological improvement and the evolution of the information society.

Competitive places have developed diverse, multidimensional ways to attract mobile workers as well as mobile investment. Creative workers are the core of the knowledge economy and account for the varieties in its geography. Benchmarks, including knowledge metrics, innovation indices, and report cards, are increasingly common and increasingly critical to the monitoring of key features of economies and societies whose factors of production and of success are highly mobile. Consequently policies have become more sophisticated, but policy makers need to grasp the nature of place competition and the critical roles of knowledge in the strategies of the most competitive places.

We place labor flows, involving both highly skilled professionals and unskilled workers, within the framework of research on world cities. These flows are central to understanding the growth of world cities, particularly those whose growth is not primarily a result of advanced producer services. The context of Arab Gulf cities allows us to understand urban growth in the region as an outcome of wealth accumulation that stimulates large flows of skilled westerners and of unskilled workers from poor regions in Asia. We conclude with an agenda for research on migration to world cities and the division of labor in those cities.

The field survey has been performed to study the epidemiology of calf coccidiosis in Poland. It was found that the Eimeria spp. coccidia occurred on 93.0 % of the investigated farms. But the highly pathogenic species (E. bovis and E. zuernii) were found on 88.4 % of the investigated farms. Those were also found more frequently in bigger farms (92.3%) compared to smaller ones (85.1%). However, the intensity of E. bovis as well as E. zuernii infection remained, in most cases, low – 75.4 and 79.8% or moderate – 21.3 and 18.5%, respectively. The intensity of those infections was, respectively, 3.1x and 1.9x higher in big farms. Conclusion: The Eimeria spp. are very common pathogens in cattle farms in Poland. The highly pathogenic Eimeria occurred more frequently in big rather than in small farms.

This article targets the role of intermediaries, such as refugee resettlement programs, in altering the geography of the foreign-born. It argues that, under such intermediaries, destination choice within the United States is largely determined not by economic mechanisms but instead by information-related factors such as friction of distance, migration chains, labor procurement, and resettlement intermediaries. Metropolitan statistical area (MSA) destinations are grouped into four profiles based on their mix of foreign-born. The result is sets of MSAs differentiated by the era of immigration, immigrant origins, geographic pattern, and place characteristics that draw migrants. To evaluate intermediary impacts, monies allocated to states by the Office of Refugee Resettlement, refugee resettlement by state, and refugee movements to MSAs are expressed as a Refugee Resettlement Index and linked to MSA profiles. We conclude that although refugees constitute only a portion of total immigration, their eff...

The NOTCH1 receptor is cleaved within its extracellular domain by furin during its maturation, yielding two subunits that are held together noncovalently by a juxtamembrane heterodimerization (HD) domain. Normal NOTCH1 signaling is initiated by the binding of ligand to the extracellular subunit, which renders the transmembrane subunit susceptible to two successive cleavages within and C terminal to the heterodimerization domain, catalyzed by metalloproteases and gamma-secretase, respectively. Because mutations in the heterodimerization domain of NOTCH1 occur frequently in human T-cell acute lymphoblastic leukemia (T-ALL), we assessed the effect of 16 putative tumor-associated mutations on Notch1 signaling and HD domain stability. We show here that 15 of the 16 mutations activate canonical NOTCH1 signaling. Increases in signaling occur in a ligand-independent fashion, require gamma-secretase activity, and correlate with an increased susceptibility to cleavage by metalloproteases. The activating mutations cause soluble NOTCH1 heterodimers to dissociate more readily, either under native conditions (n = 3) or in the presence of urea (n = 11). One mutation, an insertion of 14 residues immediately N terminal to the metalloprotease cleavage site, increases metalloprotease sensitivity more than all others, despite a negligible effect on heterodimer stability by comparison, suggesting that the insertion may expose the S2 site by repositioning it relative to protective NOTCH1 ectodomain residues. Together, these studies show that leukemia-associated HD domain mutations render NOTCH1 sensitive to ligand-independent proteolytic activation through two distinct mechanisms.

The US has been a world leader in innovation and knowledge activities since World War II. Because the US has become accustomed to a position of leadership, there is widespread insecurity—maybe even paranoia—regarding threats to its dominance in technology, beginning with Sputnik in 1956. This paper provides some details of US decline relative, in particular, to European countries over the past two decades, when both strengths and the weaknesses are evident in US innovation and technology. The US has moved from a position of dominance to a position of first among equals, in line with a more widely distributed pattern of science and technological capabilities.

Malecki E. J. (2004) Jockeying for position: what it means and why it matters to regional development policy when places compete, Regional Studies38, 1093-1112. The realization that places compete for investment has expanded in recent years to encompass competition among places for the attention of migrants, tourists and media glow as well as investment. The most competitive places have been multidimensional in their attractions and have made the transition to the knowledge-based economy. The latest priority is being placed on attracting mobile workers and mobile investment. Creative workers are the core of the knowledge economy and of its geographies such as 'intelligent places' and 'learning regions'. Knowledge metrics, innovation indices and report cards are increasingly common, each seemingly developed to sort the list of places in a different order. Lists or league tables of 'the best places' for business, to live, retire and visit are key features of economies and societies whose factors of success ...

A policy innovation that has achieved widespread diffusion across national and sub-national governments in industrialized countries is the promotion of networks among small manufacturers as a means of promoting competitiveness. However, research and evaluations of formal networks formed in response to policy initiatives tend not account for the informal networks that small manufacturers routinely use in gathering information and business resources. This study examines the use of informal networks by 50 small manufacturing firms in rural and urban regions of northern Florida. The analysis is inductive and designed to provide a point of comparison to the growing literature on formal small manufacturing networks. Unlike formal networks, the links that comprise informal networks tend to be geographically and socially mixed. Small firms use informal networks to gather information on a mix of issues. Urban and rural firms have similar patterns of network use on issues affecting product development and competitiveness. But they have different patters of network usage for issues associated with exporting and labor problems. Informal networks draw upon local and non-local information resources that do not require significant amounts of interpersonal contact across actors. Proximity is not a factor in the effective use of informal networks for information purposes. Rather the emphasis is upon locating "tried-and-true" solutions that solve the business needs. There is little evidence suggesting that the informal networks that these small manufacturers use are gravitating towards or seeking the development of formal networks. Thus, policy prescriptions identifying barriers to networking among small manufacturers are borne out in this study.

This paper examines the US portion of the global communications network known as the Internet. The stages in the Internet's evolution, telecommunications deregulation, and a rush by new competitors to new market opportunities associated with the Internet combined to prompt a flurry of investment in new fibre-optic networks. Frameworks to explain new networks built upon, and added to, existing telecommunications networks include network economies and the opportunity-rich paths located between the large markets on the east and west coasts of the country and a capital-driven set of new and old network suppliers. The paper then reviews the small but growing body of research on the geographic structure of the Internet. The empirical section of the paper focuses on analyses of the variation among urban areas both in bandwidth on interurban Internet backbone networks and in the number of web design firms in the USA. Bandwidth investment was attracted not only to cities with larger populations but also to cities ...