Consumption Externalities and Diffusion in Pharmaceutical Markets: Antiulcer Drugs

We examine the role of consumption externalities in the demand for pharmaceuticals at both the brand level and over a therapeutic class of drugs. These effects emerge when use of a drug by others affects its value, and/or conveys information abut efficacy and safety to patients and physicians. This can affect that rate of market diffusion for a new entrant, and can lead to herb behavior whereby a particular drug can dominate the market despite the availability of close substitutes. We use data for H2-antagonist antiulcer drugs to estimate a dynamic demand model and quantify these effects. The model has three components: an hedonic price equation that measures how the aggregate usage of a drug, as well as conventional attributes, affect brand valuation; equations relating equilibrium market shares to quality-adjusted prices and marketing levels; and diffusion equations describing the dynamic adjustment process. We find that consumption externalities influence both valuations and rates of diffusion, but that they operate at the brand and not the therapeutic class level.

The Diffusion of Scientific Knowledge across Time and Space

This chapter discusses the consequences of academic mobility and the extent to which the movement of high-achieving faculty members affects both scientific and commercialization activities at their old and new schools. It looks at articles published by, and patents granted to, the mobile scientist before they departed for the new school, comparing these to similar outputs by scientists who did not move. The heterogeneity that can distort simpler comparisons can be limited. The analysis suggests that the citations to a departing scientist's articles from the university where he or she departs are barely affected by the move. However, citations to the departing scientist's patents (whether made in articles or patents) decline sharply at the originating school. This suggests that the physical proximity of the researcher is important to ensuring knowledge flows to industry. Citations to the scientist's work at his or her new location increase dramatically once the move is complete. Barriers to scientific mobility may actually be socially detrimental, as they prevent the kind of knowledge gains from the mixing of ideas. Keywords: diffusion; scientific knowledge; professional transitions; academic mobility; physical proximity; researche

Public R&D Investments and Private-sector Patenting: Evidence from NIH Funding Rules

We quantify the impact of scientific grant funding at the National Institutes of Health (NIH) on patenting by pharmaceutical and biotechnology firms. Our article makes two contributions. First, we use newly constructed bibliometric data to develop a method for flexibly linking specific grant expenditures to private-sector innovations. Second, we take advantage of idiosyncratic rigidities in the rules governing NIH peer review to generate exogenous variation in funding across research areas. Our results show that NIH funding spurs the development of private-sector patents: a $10 million boost in NIH funding leads to a net increase of 2.7 patents. Though valuing patents is difficult, we report a range of estimates for the private value of these patents using different approaches.National Science Foundation (U.S.) (Award SBE-0738142)National Institutes of Health (U.S.) (Grant P01-AG039347

Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs)

BACKGROUND: Although patients with advanced or metastatic lung cancer have poor prognosis, admission to the ICU for management of life-threatening complications has increased over the years. Patients with newly diagnosed lung cancer appear as good candidates for ICU admission, but more robust information to assist decisions is lacking. The aim of our study was to evaluate the prognosis of newly diagnosed unresectable lung cancer patients. METHODS: A retrospective multicentric study analyzed the outcome of patients admitted to the ICU with a newly diagnosed lung cancer (diagnosis within the month) between 2010 and 2013. RESULTS: Out of the 100 patients, 30 had small cell lung cancer (SCLC) and 70 had non-small cell lung cancer. (Thirty patients had already been treated with oncologic treatments.) Mechanical ventilation (MV) was performed for 81 patients. Seventeen patients received emergency chemotherapy during their ICU stay. ICU, hospital, 3- and 6-month mortality were, respectively, 47, 60, 67 and 71%. Hospital mortality was 60% when invasive MV was used alone, 71% when MV and vasopressors were needed and 83% when MV, vasopressors and hemodialysis were required. In multivariate analysis, hospital mortality was associated with metastatic disease (OR 4.22 [1.4-12.4]; p = 0.008), need for invasive MV (OR 4.20 [1.11-16.2]; p = 0.030), while chemotherapy in ICU was associated with survival (OR 0.23, [0.07-0.81]; p = 0.020). CONCLUSION: This study shows that ICU management can be appropriate for selected newly diagnosed patients with advanced lung cancer, and chemotherapy might improve outcome for patients with SCLC admitted for cancer-related complications. Nevertheless, tumors' characteristics, numbers and types of organ dysfunction should be taken into account in the decisional process before admitting these patients in ICU.Peer reviewe

Beta-glucan reflects liver injury after preservation and transplantation in dogs.

Graft failure and extrahepatic organ complications, which frequently develop after transplantation, may be related to inflammatory mediators stimulated by endotoxin (ET). The role of endotoxemia after liver transplantation is controversial and may depend upon differences in the ET assay method used in the various contradicting studies. While the standard Limulus amebocyte lysate (LAL) is reactive for ET and beta-glucan, a novel turbidimetric assay method enables separate determinations of ET and beta-glucan. Beagle dogs undergoing orthotopic liver transplantation were divided into two groups. In Group I (n = 6) the grafts were transplanted immediately and in Group II (n = 6) grafts were preserved for 48 h in University of Wisconsin (UW) solution. Animals received cyclosporine immunosuppression and were followed for 14 days. Daily measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were performed. Samples for ET and beta-glucan measurement were collected serially and processed using the turbidimetric assay method. While no graft failure was seen in Group I, three of six Group II animals died from graft failure within 1 day after transplantation. Preservation and reperfusion injury was much more severe in the Group II grafts than in Group I grafts. While endotoxemia could not be detected, postoperative beta-glucan levels (undetectable pretransplant) were seen in both groups. Beta-glucan levels were much higher in Group II grafts than in Group I grafts, and correlated with the severity of liver damage. In conclusion, this study shows that beta-glucan, instead of ET, appears during the early posttransplant period. We believe that posttransplant elevation of beta-glucan is related to liver damage, especially endothelial damage by preservation and reperfusion

Exposition de la population française aux champs magnétiques 50 Hz : résultats partiels

Les champs magnétiques (CM) alternatifs de fréquence 50 Hz, liés à l'électricité en particulier, sont suspectés depuis une trentaine d'années d'être responsables de pathologies, notamment de leucémies chez l'enfant [1]. Les dernières expertises collectives (OMS 2007, SCENHIR 2009) ont conclu que la dernière grande interrogation en ce qui concerne les CM basse fréquence est l'association statistique observée dans plusieurs analyses conjointes entre l'augmentation du risque de leucémie de l'enfant et une exposition aux CM supérieure à 0,4 μT en valeur moyenne sur 24 h [2]. Actuellement, l'exposition de la population française à ces champs n'est connue que de manière très approximative. Une étude effectuée dans le département de la Côte d'Or sur des logements situés à proximité de lignes à haute et très haute tension a permis d'évaluer les expositions à l'intérieur de ces logements [3]. Mais, d'une part il s'agit d'un faible échantillon compte tenu de la diversité du parc de logements en France, d'autre part, il s'agit d'une exposition du logement et non des personnes. En effet, tout un chacun est exposé à de nombreuses sources de champ magnétique du simple fait qu'on ne reste pas chez soi 24 heures sur 24. Les transports, en particulier, représentent des sources d'exposition significatives, mais d'autres lieux de vie peuvent constituer des sources d'exposition, que ce soit le lieu de travail, le terrain de sport, le centre commercial ou l'école. Dans le cas où le CM supérieur 0,4 μT en moyenne représenterait un risque pour la santé, comment estimer la proportion de la population française à risque et identifier les sources favorisant l'exposition ? Pour répondre à cette question, la Direction Générale de la Santé a initié une étude sur l'exposition aux CM 50 Hz d'un échantillon représentatif de la population française. Une des problématiques de cette étude a été de réaliser cet échantillon et de collecter toutes les informations nécessaires. Pour réaliser cette étude, le recrutement des volontaires et les mesures du CM ont été effectués en trois campagnes. Nous présentons les résultats des deux premières campagnes

French population exposure to 50 Hz magnetic fields : intermediate results

International audienceFor the last thirty years, the electricity related 50 Hz magnetic fields (MF) have been suspected of being responsible for several pathologies, in particular childhood leukemia [1]. The most recent collective expertise (WHO 2007 and SCENHIR 2009) concluded that the last major interrogation with regard to low frequency MF is the statistical association observed in several joint analyses between the increase of risk of the childhood leukemia and a higher than 0.4 μT exposure to MF on average in a 24-hour period [2]. Currently, the exposure of the French population to these magnetic fields is only approximately known. A study carried out in residences located near high voltage power lines in the "département1 de la Côte d'Or" made it possible to assess the MF background level inside these residences [3]. However, these residences are a limited sample compared to the diversity of the housing developments in France and the study characterized the exposure of the houses and not of the resident people. We are all exposed to many sources of magnetic fields due the fact that we do not remain at home 24 hours a day. Transportation in particular, significantly contributes to the individual exposure. Other places or activities can also constitute sources of exposure such as the workplace, sport activity areas, shopping centers or schools. Should the MF in excess to 0.4 μT on average carry health risk, would the authorities be able to manage it, i.e. estimate the proportion of the French population at risk and identify and mitigate the main sources causing the exposure? To answer this question the Ministry of Health and Solidarities initiated a study on the exposure of a representative sample of the French population to 50 Hz MF. The major issues of this study were to select randomly a representative sample and to collect all of necessary data. Measurements were performed in three campaigns at winter time (October to April). The present paper gives the results of the two first campaigns

GSK3-mediated raptor phosphorylation supports amino acid-dependent Q2 mTORC1-directed signalling

The mammalian or mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a ubiquitously expressed multimeric protein kinase complex that integrates nutrient and growth factor signals for the co-ordinated regulation of cellular metabolism and cell growth. Herein, we demonstrate that suppressing the cellular activity of glycogen synthase kinase-3 (GSK3), by use of pharmacological inhibitors or shRNA-mediated gene silencing, results in substantial reduction in amino acid (AA)-regulated mTORC1-directed signalling, as assessed by phosphorylation of multiple downstream mTORC1 targets. We show that GSK3 regulates mTORC1 activity through its ability to phosphorylate the mTOR-associated scaffold protein raptor (regulatory-associated protein of mTOR) on Ser(859). We further demonstrate that either GSK3 inhibition or expression of a S859A mutated raptor leads to reduced interaction between mTOR and raptor and under these circumstances, irrespective of AA availability, there is a consequential loss in phosphorylation of mTOR substrates, such as p70S6K1 (ribosomal S6 kinase 1) and uncoordinated-51-like kinase (ULK1), which results in increased autophagic flux and reduced cellular proliferation

Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

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