Strategic Responses to Parallel Trade

This paper examines how pharmaceutical firms have responded to changes in intellectual property rights and trade barriers that legalized "parallel imports" within the European Union. The threat of arbitrage by parallel traders reduces the ability of firms to price discriminate across countries. Due to regulations on price and antitrust law on rationing supply, pharmaceutical firms may rely on non-price responses. Such responses include differentiation of products across countries and selective "culling" of product lines to reduce arbitrage opportunities, as well as raising arbitrageurs' costs through choice of packaging. Using a dataset of drug prices and sales from 1993-2004 covering 30 countries, I find evidence that the behavior of pharmaceutical firms in the EU with respect to their product portfolios is consistent with attempts to reduce parallel trade. This may at least partially explain why parallel trade has not yet resulted in significant price convergence across EU countries. Accounting for non-price strategic responses may therefore be important in assessing the welfare effects of parallel imports.

Did U.S. Bank Supervisors Get Tougher During the Credit Crunch? Did They Get Easier During the Banking Boom? Did It Matter to Bank Lending?

We test three hypotheses regarding changes in supervisory toughness' and their effects on bank lending. The data provide modest support for all three hypotheses that there was an increase in toughness during the credit crunch period (1989-1992), that there was a decline in toughness during the boom period (1993-1998), and that changes in toughness, if they occurred, affected bank lending. However, all of the measured effects are small, with 1% or less of loans receiving harsher or easier classification, about 3% of banks receiving better or worse CAMEL ratings, and bank lending being changed by 1% or less of assets.

Public & Private Spillovers, Location and the Productivity of Pharmaceutical Research

While there is widespread agreement among economists and management scholars that knowledge spillovers exist and have important economic consequences, researchers know substantially less about the "micro mechanisms" of spillovers -- about the degree to which they are geographically localized, for example, or about the degree to which spillovers from public institutions are qualitatively different from those from privately owned firms (Jaffe, 1986; Krugman, 1991; Jaffe et al., 1993; Porter, 1990). In this paper we make use of the geographic distribution of the research activities of major global pharmaceutical firms to explore the extent to which knowledge spills over from proximate private and public institutions. Our data and empirical approach allow us to make advances on two dimensions. First, by focusing on spillovers in research productivity (as opposed to manufacturing productivity), we build closely on the theoretical literature on spillovers that suggests that knowledge externalities are likely to have the most immediate impact on the production of ideas (Romer, 1986; Aghion & Howitt, 1997). Second, our data allow us to distinguish spillovers from public research from spillovers from private, or competitively funded research, and to more deeply explore the role that institutions and geographic proximity play in driving knowledge spillovers.

Association between functional capacity and motivation to engage in physical activity before surgery

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Determining the adenoma detection rate and adenomas per colonoscopy by photography alone: proof-of-concept study

Background and study aims: The adenoma detection rate (ADR) and adenomas detected per colonoscopy (APC) are measures of the quality of mucosal inspection during colonoscopy. In a resect and discard policy, pathologic assessment for calculation of ADR and APC would not be available. The aim of this study was to determine whether ADR and APC calculation based on photography alone is adequate compared with the pathology-based gold standard. Patients and methods: A prospective, observational, proof-of-concept study was performed in an academic endoscopy unit. High definition photographs of consecutive polyps were taken, and pathology was estimated by the colonoscopist. Among 121 consecutive patients aged ≥ 50 years who underwent colonoscopy, 268 polyps were removed from 97 patients. Photographs of consecutive polyps were reviewed by a second endoscopist. Results: The resect and discard policy applied to lesions that were ≤ 5 mm in size. When only photographs of lesions that were ultimately proven to be adenomas were included, the reviewer assessed ADR and APC to be lower than that determined by pathology (absolute reductions of 6.6 % and 0.17, and relative reductions of 12.6 % and 13.1 % in ADR and APC, respectively). When all photographs were included for calculation of ADR and APC, the reviewer determined the ADR to be 3.3 % lower (absolute reduction) and the APC to be the same as the rates determined by pathology. Conclusions: In a simulated resect and discard strategy, a high-level detector can document adequate ADR and APC by photography alone

Tumor escape and progression of HER-2/neu negative breast cancer under immune pressure

<p>Abstract</p> <p>Background</p> <p>Emerging data from pre-clinical and clinical studies suggest that HER-2/neu-specific T cell responses could induce HER-2/neu antigen loss in the tumor cells. These data suggest that patients with HER-2/neu negative breast cancer might have had HER-2/neu positive premalignant lesions in the past that progressed to HER-2/neu negative breast cancer under HER-2/neu-specific immune pressure.</p> <p>Methods</p> <p>We conducted a pilot study in patients with HER-2/neu positive and HER-2/neu negative breast cancers as well as a patient with ductal carcinoma in situ (DCIS). HER-2/neu expression was determined by FISH. HER-2/neu-specific T cell responses were determined by using IFN-γ ELISA. Expression of IFN-γ Rα in the tumors was determined by immunohistochemistry analysis of paraffin-embedded tissues.</p> <p>Results</p> <p>We determined that majority of (10 of 12) patients with HER-2/neu negative breast cancer had HER-2/neu-specific IFN-γ producing T cell responses which was stronger than those in patients with HER-2/neu positive tumors. Such immune responses were associated with nuclear translocation of IFN-γ Rα in their tumor cells. Patient with DCIS also showed HER-2/neu-specific T cell responses.</p> <p>Conclusion</p> <p>These data suggest that conducting retrospective studies in patients with HER-2/neu negative breast cancers and prospective studies in patients with HER-2/neu positive DCIS can determine whether HER-2/neu negative invasive carcinomas arise from HER-2/neu positive DCIS under the immune pressure.</p

Cooperation Between Systemic and Mucosal Antibodies Induced by Virosomal Vaccines Targeting HIV-1 Env: Protection of Indian Rhesus Macaques Against Low-Dose Intravaginal SHIV Challenges.

A virosomal vaccine inducing systemic/mucosal anti-HIV-1 gp41 IgG/IgA had previously protected Chinese-origin rhesus macaques (RMs) against vaginal SHIVSF162P3 challenges. Here, we assessed its efficacy in Indian-origin RMs by intramuscular priming/intranasal boosting (n=12/group). Group K received virosome-P1-peptide alone (harboring the Membrane Proximal External Region), Group L combined virosome-rgp41 plus virosome-P1, and Group M placebo virosomes. Vaccination induced plasma binding but no neutralizing antibodies. Five weeks after boosting, all RMs were challenged intravaginally with low-dose SHIVSF162P3 until persistent systemic infection developed. After SHIV challenge #7, six controls were persistently infected versus only one Group L animal (vaccine efficacy 87%; P=0.0319); Group K was not protected. After a 50% SHIV dose increase starting with challenge #8, protection in Group L was lost. Plasmas/sera were analyzed for IgG phenotypes and effector functions; the former revealed that protection in Group L was significantly associated with increased binding to FcγR2/3(A/B) across several time-points, as were some IgG measurements. Vaginal washes contained low-level anti-gp41 IgGs and IgAs, representing a 1-to-5-fold excess over the SHIV inoculum's gp41 content, possibly explaining loss of protection after the increase in challenge-virus dose. Virosomal gp41-vaccine efficacy was confirmed during the initial seven SHIV challenges in Indian-origin RMs when the SHIV inoculum had at least 100-fold more HIV RNA than acutely infected men's semen. Vaccine protection by virosome-induced IgG and IgA parallels the cooperation between systemically administered IgG1 and mucosally applied dimeric IgA2 monoclonal antibodies that as single-agents provided no/low protection - but when combined, prevented mucosal SHIV transmission in all passively immunized RMs