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In 2004 an Institute of Medicine report warned of vaccine shortages, raising concerns about disease outbreaks. More than a decade later, we looked for progress in reducing vaccine shortages. We analyzed data on vaccine sales and shortages reported by practitioners and patients to the Food and Drug Administration and the American Society of Health-System Pharmacists in the period 2004-13. We found that the number of annual vaccine shortages peaked in 2007, when there were shortages of seven vaccines; there were only two shortages in 2013. There were no shortages of vaccines with a mean price per dose greater than $75 during the study period. Furthermore, we found that a 10 percent increase in price was associated with a nearly 1 percent decrease in the probability of a shortage. Government payers should carefully consider the benefits of averting shortages when evaluating prices for vaccines, including older vaccines whose prices have been subject to congressional price caps.

In this article, I study the relationship between valuable trademarks and a firm’s technology sourcing strategy. The Profiting from Innovation (PFI) and Transaction Cost Economics (TCE) perspectives have generated competing predictions regarding firms’ historical stock of valuable trademarks and their decision to pursue external technology sourcing. To conduct the empirical analysis, I use a sample of innovator firms in the manufacturing sectors from the Division of Innovative Labor survey, matched to the USPTO trademark data. Consistent with the TCE perspective, I find that firms with valuable trademarks are less likely to commercialize external inventions, and are likely to have lower innovation performance if they do so. I further show a boundary condition for PFI such that when firms are new entrants to an industry but already holding valuable trademarks, they are more likely to commercialize external innovations.

In this paper, I study the relationship between hiring and external technology sourcing. Hiring can either substitute for external technology sourcing by bringing new technologies/capabilities to a...

This study shows that firms are constantly hiring new inventors to conduct innovation, especially during technology changes. Talent acquisition is an important alternative to external sourcing of i...

The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1–2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for phenotype-driven priority screening and informs specific patient management.

In this paper, I study firms’ investment in innovation in response to exogenous shock in demand. Focusing on the manufacturing sectors from 2001 to 2011, I look at firms’ patenting activity and how that is correlated with US exportation to China, instrumented by the Chinese tariff. I use the cost spreading theory to explain the relationship between firms’ structure/diversification strategy and their response to increase in demand. Consistent with early studies, both size and scope confer an advantage in innovation when facing demand pull. Vertically integrated firms have a much higher response in innovation, mostly due to their ability to scale up dynamically and capture the market opportunity. This enables them to attain a larger output to spread the cost of innovation. Related diversified firms do not have such an advantage, and are not significantly different in their innovation investment from unrelated diversified firms.

Previous studies have investigated the correlation between firms’ trademarking activity and innovation. However, there is a lack of formal investigation on which firms file for trademarks and the s...

Contains fulltext : 88200.pdf (Publisher’s version ) (Closed access) Nephronophthisis-related ciliopathies (NPHP-RC) are recessive disorders that feature dysplasia or degeneration occurring preferentially in the kidney, retina and cerebellum. Here we combined homozygosity mapping with candidate gene analysis by performing 'ciliopathy candidate exome capture' followed by massively parallel sequencing. We identified 12 different truncating mutations of SDCCAG8 (serologically defined colon cancer antigen 8, also known as CCCAP) in 10 families affected by NPHP-RC. We show that SDCCAG8 is localized at both centrioles and interacts directly with OFD1 (oral-facial-digital syndrome 1), which is associated with NPHP-RC. Depletion of sdccag8 causes kidney cysts and a body axis defect in zebrafish and induces cell polarity defects in three-dimensional renal cell cultures. This work identifies loss of SDCCAG8 function as a cause of a retinal-renal ciliopathy and validates exome capture analysis for broadly heterogeneous single-gene disorders. 01 oktober 2010

BackgroundPolished rice is a staple food for over 50% of the world's population, but contains little bioavailable iron (Fe) to meet human needs. Thus, biofortifying the rice grain with novel promoters or enhancers of Fe utilization would be one of the most effective strategies to prevent the high prevalence of Fe deficiency and iron deficiency anemia in the developing world.Methodology/principal findingsWe transformed an elite rice line cultivated in Southern China with the rice nicotianamine synthase gene (OsNAS1) fused to a rice glutelin promoter. Endosperm overexpression of OsNAS1 resulted in a significant increase in nicotianamine (NA) concentrations in both unpolished and polished grain. Bioavailability of Fe from the high NA grain, as measured by ferritin synthesis in an in vitro Caco-2 cell model that simulates the human digestive system, was twice as much as that of the control line. When added at 1:1 molar ratio to ferrous Fe in the cell system, NA was twice as effective when compared to ascorbic acid (one of the most potent known enhancers of Fe bioavailability) in promoting more ferritin synthesis.ConclusionsOur data demonstrated that NA is a novel and effective promoter of iron utilization. Biofortifying polished rice with this compound has great potential in combating global human iron deficiency in people dependent on rice for their sustenance.

Clozapine is limitedly used due to its adverse effect including agranulocytosis and hepatotoxicity. However, the mechanism of clozapine toxicity is still not clear. The previous in vitro studies on microsomes proposed a possible mediation of cytochrome P450 (CYP) in producing reactive metabolites. In this paper, clozapine toxicity was, respectively, examined in two cultures of rat hepatocytes. Gel entrapment culture of hepatocytes with higher expression on CYP activities showed higher sensitivity to clozapine treatment than hepatocyte monolayer, indicating the possible involvement of CYP in hepatotoxicity of clozapine. Moreover, in each culture, CYP inhibitors were used to confirm the possible mediation of CYP enzymes. Pretreatment of hepatocytes with CYP 3A inhibitor (ketoconazole), CYP 2E1 inhibitor (diethyldithiocarbamate, DDC) and non-specific inhibitor (cimetidine) significantly reduced the toxicity of clozapine. But the pretreatment with CYP 1A2 inhibitor (fluvoxamine) had no such protective effect indicative of non-function of CYP 1A2 in clozapine toxicity. In addition, glycyrrhizic acid (GA), a scavenger of reactive oxygen species (ROS), also inhibited the adverse response to clozapine, suggesting the positive involvement of oxidant pressure. Thus, it could be concluded that clozapine-induced toxicity was mediated by CYP, particularly CYP 3A and CYP 2E1, and oxidant pressure.