To generate sufficient clinical-grade vector to support a phase I/II clinical trial of adeno-associated virus serotype 8 (AAV8)-mediated factor IX (FIX) gene transfer for hemophilia B, we have developed a large-scale, good manufacturing practice (GMP)-compatible method for vector production and purification. We used a 293T-based two-plasmid transient transfection system coupled with a three-column chromatography purification process to produce high-quality self-complementary AAV2/8 FIX clinical-grade vector. Two consecutive production campaigns using a total of 432 independent 10-stack culture chambers produced a total of *2Â10 15 vector genomes (VG) by dot-blot hybridization. Benzonase-treated microfluidized lysates generated from pellets of transfected cells were purified by group separation on Sepharose beads followed by anion-exchange chromatography. The virus-containing fractions were further processed by gel filtration and ultrafiltration, using a 100-kDa membrane. The vector was formulated in phosphate-buffered saline plus 0.25% human serum albumin. Spectrophotometric analysis suggested *20% full particles, with only low quantities of nonviral proteins were visible on silver-stained sodium dodecyl sulfate-polyacrylamide gels. A sensitive assay for the detection of replication-competent AAV was developed, which did reveal trace quantities of such contaminants in the final product. Additional studies have confirmed the long-term stability of the vector at À808C for at least 24 months and for at least 24 hr formulated in the clinical diluent and stored at room temperature within intravenous bags. This material has been approved for use in clinical trials in the United States and the United Kingdom.

Purpose -The purpose of this article is to demonstrate the importance of a strategic approach to collaborative innovation and the use of a value chain research methodology for identifying opportunities for co-innovation. Design/methodology/approach -Value chain analysis is used to map three flows in the Houston Farms value chain; material flow, information flow and relationships. Having diagnosed the current level of co-innovation we then identify improvement projects and opportunities for co-innovation to reduce cost and add value, for the benefit of the value chain as a whole. Findings -The application of the value chain analysis methodology to the Houston Farms value chain revealed the importance of strategy and robust processes in key areas for co-innovation -R&D and new product development. It also revealed that small businesses can enjoy a degree of success as a result of comparative advantage in certain areas but that sustainable competitive advantage cannot occur by chance -identifying the potential for coinnovation is an important first step in the right direction.Research limitations/implications -The value chain innovation roadmap represents a useful framework for exploring the current state and future capability for co-innovation in a value chain. The value chain analysis methodology is an effective diagnostic tool as it focuses on what happens at the interface between stakeholders and how this relates to what final consumers regard as value adding, rather than traditional financial and functional KPIs which make it difficult to explore the competitiveness of the value chain as a whole. Originality/value -The explicit and objective measurement of what consumers value is an important addition to the value chain analysis methodology and the co-innovation roadmap is an original attempt to illustrate the core drivers and capabilities for achieving co-innovation in a value chain. The insights from the case demonstrate the value of this approach to companies who are open to innovation and recognise the need to focus the use of scarce value-adding resources on specific value chains and the needs and wants of final consumers therein.

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Objectives This study examines predictors of the gender gap in life expectancy across a large cross‐national sample. Methods We employ random effects and fixed effects models of the gender difference (female–male) and gender ratio (female/male) in life expectancy during the 1980–2005 period. Results Women's status, traditional male hazards, and development/modernization processes tend to widen the gender gap in life expectancy. In addition, income inequality expands the gender gap, while female representation in parliament reduces it. We argue that these latter effects are a function of (1) the steeper socioeconomic gradient for men in predicting mortality and (2) the protection of economically vulnerable groups by female parliamentarians, which provides greater health returns to males. Conclusion Advances in gender equity along economic, political, and cultural lines appear to exert countervailing effects, both expanding and reducing the gender gap in mortality.

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While human rights treaties have become increasingly popular over the past quarter century, there has not been a corresponding improvement in human rights practices. This discrepancy implies that a country's formal pledge to uphold human rights principles is “loosely coupled” from its actual performance. In this study, I develop a model of loose coupling based on organizational research and apply it to the human rights sector of the world polity. Empirically, I identify a set of institutional states whose human rights practices fall short of their treaty commitments, as well as a set of technical states whose practices exceed their commitments. Analyzing an unbalanced data set with a maximum of 755 observations across 167 countries during the 1975 to 2000 period, I use random effects models to predict a state's location on the Human Rights Decoupling Index (HRDI). The findings illustrate the importance of several organizational concepts for predicting a state's HRDI score. In particular, the analyses reveal the countervailing effects of globalization. While economic globalization (i.e., trade and foreign investment) is associated with the technical (positive) end of the HRDI, cultural globalization (i.e., memberships in international organizations) is associated with the institutional (negative) end.

Dependency scholars emphasize the harmful effects of economic incorporation for nations residing in the periphery. Conversely, a network perspective of international relations suggests that the major problem peripheral countries face is isolation. Considered together, peripherality implies both resource and partner dependency. Applying dependency and network principles to the world economy and world polity, the author assembles a set of cross-national measures based on international trade relations and membership in international nongovernmental organizations (INGOs). Analyzing a sample of eighty-two developing countries during the 1980-2000 period, the author tests the effects of dependency and network integration on two measures of development: economic growth and tertiary school expansion. The author finds that dependent integration in trade and INGOs produces economic underdevelopment, while network integration in trade and INGOs positively affects economic growth and educational expansion. The findings broadly confirm dependency and network perspectives, demonstrating the developmental benefits that accrue to core/central actors relative to more dependent/peripheral economies.