David R. Meyer

Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer's disease

We performed an affected sib‐pair (ASP) linkage analysis to test for the effects of age at onset (AAO), rate of decline (ROD), and Apolipoprotein E (APOE) genotype on linkage to late‐onset Alzheimers disease (AD) in a sample comprising 428 sib‐pairs. We observed linkage of mean AAO to chromosome 21 in the whole sample (max LOD = 2.57). This came entirely from the NIMH sample (max LOD = 3.62), and was strongest in pairs with high mean AAO (>80). A similar effect was observed on chromosome 2q in the NIMH sample (max LOD = 2.73); this region was not typed in the IADC/UK sample. Suggestive evidence was observed in the combined sample of linkage of AAO difference to chromosome 19q (max LOD = 2.33) in the vicinity of APOE and 12p (max LOD = 2.22), with linkage strongest in sib‐pairs with similar AAO. Mean ROD showed suggestive evidence of linkage to chromosome 9q in the whole sample (max LOD = 2.29), with the effect strongest in the NIMH sample (max LOD = 3.58), and in pairs with high mean ROD. Additional suggestive evidence was also observed in the NIMH sample with AAO difference on chromosome 6p (max LOD = 2.44) and 15p (max LOD = 1.87), with linkage strongest in pairs with similar AAO, and in the UK sample with mean ROD on chromosome 1p (max LOD = 2.73, linkage strongest in pairs with high mean ROD). We also observed suggestive evidence of increased identical by descent (IBD) in APOE ε4 homozygotes on chromosome 1 (max LOD = 3.08) and chromosome 9 (max LOD = 3.34). The previously reported genome‐wide linkage of AD to chromosome 10 was not influenced by any of the covariates studied.

Emergence of the American manufacturing belt: an interpretation

Abstract This study proposes that the American manufacturing belt emerged during the antebellum years as a replicated set of regional industrial systems. A broad-based set of demands spurred the growth of regional manufactures, including the pivotal producer durables sector. Eastern regions industrialized first, and they were followed by frontier regions in the Midwest. The relative importance of regional market manufactures declined over time and multiregional/national market manufactures increased. Regional industrial systems became increasingly specialized; the result was higher levels of interregional trade in industrial specialties. The decline of regional market manufactures eroded the bases for the emergence of regional industrial systems by the 1860s. The westward spread of the manufacturing belt ended, and internal differentiation and structural change within the belt were characteristics of late nineteenth century industrialization. The South failed to join the manufacturing belt during the antebellum years because regional demands for manufactures were insufficient to support important regional industrial systems. It lacked the bases to participate significantly in late nineteenth century industrialization.

A Dynamic Model of the Integration of Frontier Urban Places into the United States System of Cities

A dynamic model of the system of cities in an areally expanding space-economy is proposed. In the model two processes govern the dynamics of the system of cities: control of exchange of stock and p...

Midwestern Industrialization and the American Manufacturing Belt in the Nineteenth Century

The Midwest made the transition from primary to secondary activity before 1880 by developing a large diversified industrial sector to serve burgeoning midwestern demand for manufactures. Because the Midwest had industrialized, its firms were able to compete with eastern producers in multiregional and national markets after 1880, when the transportation and communication systems were fully integrated. Supporting evidence is drawn from a national set of 327 urban-industrial counties, with a focus on the Midwest.

Trajectories of Industrial Districts: Impact of Strategic Intervention in Medical Districts

Abstract Actors employ strategic intervention to alter the trajectory of an industrial district because they are dissatisfied with an existing or expected trajectory. In this study we examine two medical industrial districts. In the Philadelphia biotechnology district, strategic intervention altered its trajectory; and in the Minneapolis biomedical technology district, the trajectory of the district has altered but no strategic intervention emerged to redirect the trajectory. The structure and functioning of social networks within each district had an impact on the strategic interventions. Philadelphia housed a larger array of powerful firms and institutions than Minneapolis, but no pharmaceutical giant dominated the spawning of spin-offs in Philadelphia comparable to the dominance of Medtronic in Minneapolis. Diverse medical facilities in Philadelphia diffuse technological information and contacts about starting firms, whereas the University of Minnesota Medical School and its research institutes create a centralized source of information and contacts. The venture-capital sector of Philadelphia draws on diverse pools of capital, with no dominant vested interest to defend sectors of biotechnology; however, in Minneapolis, a few financial actors and large firms direct that allocation of capital. Philadelphia contains numerous public-private partnerships; Minneapolis does not have that diversity. As increased FDA regulation and pressure from managed care firms create conditions that favor large firms, the Philadelphia region continues to support small firms, whereas the Minneapolis region is withdrawing support. Philadelphia’s wide-ranging social networks provide a more supportive framework for small firms than exists in Minneapolis, where the social networks have greater centralization and redundancy.

CHANGE IN THE WORLD SYSTEM OF METROPOLISES: THE ROLE OF BUSINESS INTERMEDIARIES

Business intermediaries engaged in the international exchange of capital and commodities (financiers, commodity brokers, wholesalers, corporate head offices) influence the formation of and change in the system of world metropolises through their reactions to competitioh: (1) altering transaction costs, (2) differentiation or dedifferentiation to control markets, and (3) appeal to force. Propositions about intermediary behavior are supported with evidence from the case study literature. These propositions form the basis for a synthesis of the changes in the system of world metropolises.

The world cities of Hong Kong and Singapore: Network hubs of global finance

The world cities of Hong Kong and Singapore, former creations of British colonialism, gained prominence as global financial centers primarily from decisions of firms headquartered in the core of Europe and North America to base their senior management in Hong Kong for Asia-Pacific and Singapore for Southeast Asia. This study uses qualitative interviews with financiers in both cities to examine how they use their networks to produce financial services from core-contending centers in a regional economy containing mostly core-contending, semiperipheral, and peripheral countries. The results reveal that Hong Kong’s and Singapore’s financiers and their firms gain competitive advantages in producing financial services from their network exploitation of their access to sophisticated information, knowledge, and expertise about Asia.

The Challenges of Research on the Global Network of Cities

The significant rise in global commodity trade, foreign direct investment, and global financial exchange during the 1980s was a key impetus to the contemporaneous sharp jump in attention of urban geographers and other social scientists to conceptualizing and empirically examining the global network of cities. Scholars accepted an assumption that the new international division of labor recast global relations, and this has not been questioned subsequently. Research during the 1980s focused on global corporations, corporate services, financial institutions, telecommunications, and transportation as actors or modes of linking global cities. This broad coverage framed subsequent research to the present, but the theory of the global network of cities did not advance much beyond the initial formulations. After 1990 some embellishments were made to the theory, and these were widely accepted. Although other theoretical proposals were made, none gained wide acceptance; nevertheless, scholars made some progress in clarifying the behavior of business actors. Researchers accumulated rich empirical evidence about the global network of cities, including extensive evidence on network relations. If scholars are to make greater progress in understanding the global network of cities, the theory needs deepening. A reexamination of the assumption that the new international division of labor has recast global relations might encourage greater emphasis on the principles of the intermediary behavior of the actors most responsible for global network relations.

Dynamics of the U.S. System of Cities, 1950 to 1980 The Impact of the Large Corporate Law Firm

Large law firms constitute integral components of the corporate complexes of cities. Analyses of data from 75 cities between 1950 and 1980 demonstrate that the increasing numbers, sizes, and branching of these corporate law firms correspond closely to the long-term processes of urban growth and change. The hierarchy of linked metropolises compose the key structure within which these firms operate. A governmental network headed by Washington, D.C., which also includes state capitals, overlaps it.

Impact of Human Capital on Joint-Venture Investment in Vietnam

Abstract Commitments of joint-venture investment in Vietnam expanded rapidly during 1988–93 as foreign firms eagerly took advantage of the economys opening. This investment concentrated heavily in the metropolitan core regions; nevertheless, investors remained sensitive to human capital considerations, controlling for income. They committed greater capital to provinces with higher levels of literacy, and poorer provinces outside the core also gained disproportionately. The nuanced locational choices for joint-venture investments suggest that Vietnamese partners provided sophisticated environmental scans to take advantage of high-quality labor, regardless of income level. Projected investments favor the South somewhat disproportionately, contributing to disparity in development.