Identifying Barriers and Practical Solutions to Conducting Site-Based Research in North America: Exploring Acute Heart Failure Trials As a Case Study.

Although the prognosis of ambulatory heart failure (HF) has improved dramatically there have been few advances in the management of acute HF (AHF). Despite regional differences in patient characteristics, background therapy, and event rates, AHF clinical trial enrollment has transitioned from North America and Western Europe to Eastern Europe, South America, and Asia-Pacific where regulatory burden and cost of conducting research may be less prohibitive. It is unclear if the results of clinical trials conducted outside of North America are generalizable to US patient populations. This article uses AHF as a paradigm and identifies barriers and practical solutions to successfully conducting site-based research in North America.

Introduction: The apparel industry and North American economic integration

The economic and social consequences of international trade agreements have become a major area of inquiry in development studies in recent years. As evidenced by the energetic protests surrounding the Seattle meeting of the World Trade Organization (WTO) in December 1999 and the controversy about China's admission to the WTO, such agreements have also become a focus of political conflict in both the developed and developing countries. At issue are questions of job gains and job losses in different regions, prices paid by consumers, acceptable standards for wages and working conditions in transnational manufacturing industries, and the quality of the environment. All these concerns have arisen with regard to the North American Free Trade Agreement (NAFTA) and can be addressed through an examination of changes in the dynamics of the apparel industry in the post-NAFTA period.1 In this book, we examine the evolution of the apparel industry in North America in order to address some of these questions as they pertain to North America, with an eye toward the broader implications of our findings. We also consider the countries of the Caribbean Basin and Central America, whose textile and apparel goods are now allowed to enter the U.S. market on the same basis as those from Canada and Mexico (Odessey 2000). © 2009 by Temple University Press. All rights reserved.

NAFTA and uneven development in the North American apparel industry

The various contributions to this book have documented how NAFTA-inspired firm strategies are changing the geography of apparel production in North America. The authors show in myriad ways how companies at different positions along the apparel commodity chain are responding to the new institutional and regulatory environment that NAFTA creates. By making it easier for U.S. companies to take advantage of Mexico as a nearby low-cost site for export-oriented apparel production, NAFTA is deepening the regional division of labor within North America, and this process has consequences for firms and workers in each of the signatory countries. In the introduction to this book we alluded to the obvious implications of shifting investment and trade patterns in the North American apparel industry for employment in the different countries. In this concluding chapter we focus on Mexico in the NAFTA era, specifically the extent to which Mexico's role in the North American economy facilitates or inhibits its economic development. W e begin with a discussion of the contemporary debate about Mexico's development, which turns on the question of how to assess the implications of Mexico's rapid and pro-found process of economic reform. Second, we focus on the textile and apparel industries as sectors that have been significantly affected by changes in regulatory environments at both the global and regional levels. Third, we examine the evidence regarding Mexico's NAFTA-era export dynamism, and in particular we emphasize the importance of interfirm networks, both for making sense of Mexico's meteoric rise among apparel exporters and for evaluating the implications of this dynamism for development. Fourth, we turn to a consideration of the national political-economic environment that shapes developmental outcomes for all Mexicans. Although regional disparities within Mexico are profound, aspects of government policy, such as management of the national currency, and characteristics of the institutional environment, such as industrial relations, have nationwide effects, and critics of NAFTA charge that these factors are contributing to a process of economic and social polarization that is ever more evident (Morales 1999; Dussel Peters 2000). Finally, we suggest that the mixed consequences of Mexico's NAFTA-era growth can be taken as emblematic of the contradictions that the process of globalization poses for economic and social development. The anti-sweatshop campaign in North America is one example of transnational or crossborder movements that are emerging to address the negative consequences of this process. In bringing attention to the problem of sweatshop production in North America, activists are developing strategies that rely on a network logic that is not dissimilar to the approaches reflected in the various chapters of this book. © 2009 by Temple University Press. All rights reserved.

Morphologically cryptic biological species within the liverwort Frullania asagrayana.

UNLABELLED: PREMISE OF THE STUDY: The Frullania tamarisci complex includes eight Holarctic liverwort species. One of these, F. asagrayana, is distributed broadly throughout eastern North America from Canada to the Gulf Coast. Preliminary genetic data suggested that the species includes two groups of populations. This study was designed to test whether the two groups are reproductively isolated biological species. • METHODS: Eighty-eight samples from across the range of F. asagrayana, plus 73 samples from one population, were genotyped for 13 microsatellite loci. Sequences for two plastid loci and nrITS were obtained from 13 accessions. Genetic data were analyzed using coalescent models and Bayesian inference. • KEY RESULTS: Frullania asagrayana is sequence-invariant at the two plastid loci and ITS2, but two clear groups were resolved by microsatellites. The two groups are largely reproductively isolated, but there is a low level of gene flow from the southern to the northern group. No gene flow was detected in the other direction. A local population was heterogeneous but displayed strong genetic structure. • CONCLUSIONS: The genetic structure of F. asagrayana in eastern North America reflects morphologically cryptic differentiation between reproductively isolated groups of populations, near-panmixis within groups, and clonal propagation at local scales. Reproductive isolation between groups that are invariant at the level of nucleotide sequences shows that caution must be exercised in making taxonomic and evolutionary inferences from reciprocal monophyly (or lack thereof) between putative species.

Understanding GPU programming for statistical computation: Studies in massively parallel massive mixtures

This article describes advances in statistical computation for large-scale data analysis in structured Bayesian mixture models via graphics processing unit (GPU) programming. The developments are partly motivated by computational challenges arising in fitting models of increasing heterogeneity to increasingly large datasets. An example context concerns common biological studies using high-throughput technologies generating many, very large datasets and requiring increasingly high-dimensional mixture models with large numbers of mixture components.We outline important strategies and processes for GPU computation in Bayesian simulation and optimization approaches, give examples of the benefits of GPU implementations in terms of processing speed and scale-up in ability to analyze large datasets, and provide a detailed, tutorial-style exposition that will benefit readers interested in developing GPU-based approaches in other statistical models. Novel, GPU-oriented approaches to modifying existing algorithms software design can lead to vast speed-up and, critically, enable statistical analyses that presently will not be performed due to compute time limitations in traditional computational environments. Supplementalmaterials are provided with all source code, example data, and details that will enable readers to implement and explore the GPU approach in this mixture modeling context. © 2010 American Statistical Association, Institute of Mathematical Statistics, and Interface Foundation of North America.

A widespread chromosomal inversion polymorphism contributes to a major life-history transition, local adaptation, and reproductive isolation.

The role of chromosomal inversions in adaptation and speciation is controversial. Historically, inversions were thought to contribute to these processes either by directly causing hybrid sterility or by facilitating the maintenance of co-adapted gene complexes. Because inversions suppress recombination when heterozygous, a recently proposed local adaptation mechanism predicts that they will spread if they capture alleles at multiple loci involved in divergent adaptation to contrasting environments. Many empirical studies have found inversion polymorphisms linked to putatively adaptive phenotypes or distributed along environmental clines. However, direct involvement of an inversion in local adaptation and consequent ecological reproductive isolation has not to our knowledge been demonstrated in nature. In this study, we discovered that a chromosomal inversion polymorphism is geographically widespread, and we test the extent to which it contributes to adaptation and reproductive isolation under natural field conditions. Replicated crosses between the prezygotically reproductively isolated annual and perennial ecotypes of the yellow monkeyflower, Mimulus guttatus, revealed that alternative chromosomal inversion arrangements are associated with life-history divergence over thousands of kilometers across North America. The inversion polymorphism affected adaptive flowering time divergence and other morphological traits in all replicated crosses between four pairs of annual and perennial populations. To determine if the inversion contributes to adaptation and reproductive isolation in natural populations, we conducted a novel reciprocal transplant experiment involving outbred lines, where alternative arrangements of the inversion were reciprocally introgressed into the genetic backgrounds of each ecotype. Our results demonstrate for the first time in nature the contribution of an inversion to adaptation, an annual/perennial life-history shift, and multiple reproductive isolating barriers. These results are consistent with the local adaptation mechanism being responsible for the distribution of the two inversion arrangements across the geographic range of M. guttatus and that locally adaptive inversion effects contribute directly to reproductive isolation. Such a mechanism may be partially responsible for the observation that closely related species often differ by multiple chromosomal rearrangements.

The scale of population structure in Arabidopsis thaliana.

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales.

Electronically reconfigurable metal-on-silicon metamaterial

This work was supported by Toyota Motor Engineering and Manufacturing North America and partially supported by the Air Force Office of Scientific Research (Grant No. FA9550-09-1-0562).

Biogeographic analysis of the woody plants of the Southern Appalachians: Implications for the origins of a regional flora.

PREMISE OF THE STUDY: We investigated the origins of 252 Southern Appalachian woody species representing 158 clades to analyze larger patterns of biogeographic connectivity around the northern hemisphere. We tested biogeographic hypotheses regarding the timing of species disjunctions to eastern Asia and among areas of North America. METHODS: We delimited species into biogeographically informative clades, compiled sister-area data, and generated graphic representations of area connections across clades. We calculated taxon diversity within clades and plotted divergence times. KEY RESULTS: Of the total taxon diversity, 45% were distributed among 25 North American endemic clades. Sister taxa within eastern North America and eastern Asia were proportionally equal in frequency, accounting for over 50% of the sister-area connections. At increasing phylogenetic depth, connections to the Old World dominated. Divergence times for 65 clades with intercontinental disjunctions were continuous, whereas 11 intracontinental disjunctions to western North America and nine to eastern Mexico were temporally congruent. CONCLUSIONS: Over one third of the clades have likely undergone speciation within the region of eastern North America. The biogeographic pattern for the region is asymmetric, consisting of mostly mixed-aged, low-diversity clades connecting to the Old World, and a minority of New World clades. Divergence time data suggest that climate change in the Late Miocene to Early Pliocene generated disjunct patterns within North America. Continuous splitting times during the last 45 million years support the hypothesis that widespread distributions formed repeatedly during favorable periods, with serial cooling trends producing pseudocongruent area disjunctions between eastern North America and eastern Asia.

The East Asian Collection at Duke University: Dynamics of Change.

Traces the history of Duke's East Asian Studies program and associated library collections from the beginning of the twentieth century to the present. Describes the strengths of the Japanese, Chinese and Korean collections, materials in special collections and cooperation with the University of North Carolina.

NAFTA and the apparel commodity chain: Corporate strategies, interfirm networks, and industrial upgrading

The apparel industry is one of the oldest and largest export industries in the world, with global trade and production networks that connect firms and workers in countries at all levels of economic development. This chapter examines the impact of the North American Free Trade Agreement (NAFTA) as one of the most recent and significant developments to affect patterns of international trade and production in the apparel and textile industries. Tr ade policies are changing the institutional environment in which firms in this industry operate, and companies are responding to these changes with new strategies designed to increase their profitability and strengthen their control over the apparel commodity chain. Our hypothesis is that lead firms are establishing qualitatively different kinds of regional production networks in North America from those that existed prior to NAFTA, and that these networks have important consequences for industrial upgrading in the Mexican textile and apparel industries. Post-NAFTA crossborder production arrangements include full-package networks that link lead firms in the United States with apparel and textile manufacturers, contractors, and suppliers in Mexico. Full-package production is increasing the local value added provided by the apparel commodity chain in Mexico and creating new opportunities for Mexican firms and workers. The chapter is divided into four main sections. The first section uses trade and production data to analyze shifts in global apparel flows, highlighting the emergence and consolidation of a regional trade bloc in North America. The second section discusses the process of industrial upgrading in the apparel industry and introduces a distinction between assembly and full-package production networks. The third section includes case studies based on published industry sources and strategic interviews with several lead companies whose strategies are largely responsible for the shifting trade patterns and NAFTA-inspired cross-border production networks discussed in the previous section. The fourth section considers the implications of these changes for employment in the North American apparel industry. © 2009 by Temple University Press. All rights reserved.

Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes.

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.