Biosimilars : lights and shadows in rheumatology

In the last 10 years, the growing approval and marketing of biological agents has significantly ameliorated the outcomes of rheumatoid arthritis and spondyloarthritis patients suffering from active and refractory disease despite conventional treatments. As patent protection of many biopharmaceuticals will expire in the next years, biosimilars could be proximally introduced. Such agents could be marked only when they will be proven, through in vitro and in vivo studies, to be similar enough to the original comparator in term of quality, efficacy and safety. As biosimilars are less expensive than corresponding originators, a wider use of these drugs may substantially cut off the expenditure of biopharmaceuticals. Nevertheless, ongoing debate exists in scientific community: the intrinsic complex and large structure of biologic molecules besides the natural variability in the manufacturing processes might lead to a slightly different product respect to the original one, so that relevant implications for efficacy and safety concerns might arise, especially in the long-term period. Immunogenicity and extended indications of biosimilars represent further matter of discussion, too. Thus, before their approval and marketing, specific guidelines and steps imposed by national and/or international regulatory agencies should be followed along with the respect of scientific societies position in each specific contest

Market Power and Collusion on Interconnection Phone Market in Tunisia : What Lessons from International Experiences

We try in this paper to characterize the state of mobile phone market in Tunisia. Our study is based on a survey of foreign experience (Europe) in detecting collusive behavior and a comparison of the critical threshold of collusion between operators in developing countries like Tunisia. The market power is estimated based on the work of Parker Roller (1997) and the assumption of "Balanced Calling Pattern". We use then the model of Friedman (1971) to compare the critical threshold of collusion. We show that the "conduct parameter" measuring the intensity of competition is not null during the period 1993-2011. Results show also that collusion is easier on the Tunisian market that on the Algerian, Jordanian, or Moroccan one

First FAMU observation of muon transfer from \u3bcp atoms to higher-Z elements

Abstract: The FAMU experiment aims to accurately measure the hyperfine splitting of the ground state of the muonic hydrogen atom. A measurement of the transfer rate of muons from hydrogen to heavier gases is necessary for this purpose. In June 2014, within a preliminary experiment, a pressurized gas-target was exposed to the pulsed low-energy muon beam at the RIKEN RAL muon facility (Rutherford Appleton Laboratory, U.K.). The main goal of the test was the characterization of both the noise induced by the pulsed beam and the X-ray detectors. The apparatus, to some extent rudimental, has served admirably to this task. Technical results have been published that prove the validity of the choices made and pave the way for the next steps. This paper presents the results of physical relevance of measurements of the muon transfer rate to carbon dioxide, oxygen, and argon from non-thermalized excited \u3bcp atoms. The analysis methodology and the approach to the systematics errors are useful for the subsequent study of the transfer rate as function of the kinetic energy of the \u3bcp currently under way

Conferred resistance to Botrytis cinerea in Lilium by overexpression of the RCH10 chitinase gene

The production of ornamentals is an important global industry, with Lilium being one of the six major bulb crops in the world. The international trade in ornamentals is in the order of £60-75 billion and is expected to increase worldwide by 2-4 % per annum. The continued success of the floriculture industry depends on the introduction of new species/cultivars with major alterations in key agronomic characteristics, such as resistance to pathogens. Fungal diseases are the cause of reduced yields and marketable quality of cultivated plants, including ornamental species. The fungal pathogen Botrytis causes extreme economic losses to a wide range of crop species, including ornamentals such as Lilium. Agrobacterium-mediated transformation was used to develop Lilium oriental cv. ‘Star Gazer’ plants that ectopically overexpress the Rice Chitinase 10 gene (RCH10), under control of the CaMV35S promoter. Levels of conferred resistance linked to chitinase expression were evaluated by infection with Botrytis cinerea; sporulation was reduced in an in vitro assay and the relative expression of the RCH10 gene was determined by quantitative Reverse-Transcriptase PCR. The extent of resistance to Botrytis, compared to that of the wild type plants, showed a direct correlation with the level of chitinase gene expression. Transgenic plants grown to flowering showed no detrimental phenotypic effects associated with transgene expression. This is the first report of Lilium plants with resistance to Botrytis cinerea generated by a transgenic approach

Search for the lepton flavour violating decay μ+→ e +γ with the full dataset of the MEG experiment: MEG Collaboration

none84siThe final results of the search for the lepton flavour violating decay mu(+) -> e(+)gamma based on the full dataset collected by the MEG experiment at the Paul Scherrer Institut in the period 2009-2013 and totalling 7.5x10(14) stopped muons on target are presented. Nosignificant excess of events is observed in the dataset with respect to the expected background and a new upper limit on the branching ratio of this decay of B(mu(+) -> e(+) gamma) < 4.2 x 10(-13) (90 % confidence level) is established, which represents the most stringent limit on the existence of this decay to date.Baldini, A.M.; Bao, Y.; Baracchini, E.; Bemporad, C.; Berg, F.; Biasotti, M.; Boca, G.; Cascella, M.; Cattaneo, P.W.; Cavoto, G.; Cei, F.; Cerri, C.; Chiarello, G.; Chiri, C.; Corvaglia, A.; de Bari, A.; De Gerone, M.; Doke, T.; D’Onofrio, A.; Dussoni, S.; Egger, J.; Fujii, Y.; Galli, L.; Gatti, F.; Grancagnolo, F.; Grassi, M.; Graziosi, A.; Grigoriev, D.N.; Haruyama, T.; Hildebrandt, M.; Hodge, Z.; Ieki, K.; Ignatov, F.; Iwamoto, T.; Kaneko, D.; Kang, T.I.; Kettle, P.-R.; Khazin, B.I.; Khomutov, N.; Korenchenko, A.; Kravchuk, N.; Lim, G.M.A.; Maki, A.; Mihara, S.; Molzon, W.; Mori, Toshinori; Morsani, F.; Mtchedilishvili, A.; Mzavia, D.; Nakaura, S.; Nardò, R.; Nicolò, D.; Nishiguchi, H.; Nishimura, M.; Ogawa, S.; Ootani, W.; Orito, S.; Panareo, M.; Papa, A.; Pazzi, R.; Pepino, A.; Piredda, G.; Pizzigoni, G.; Popov, A.; Raffaelli, F.; Renga, F.; Ripiccini, E.; Ritt, S.; Rossella, M.; Rutar, G.; Sawada, R.; Sergiampietri, F.; Signorelli, G.; Simonetta, M.; Tassielli, G.F.; Tenchini, F.; Uchiyama, Y.; Venturini, M.; Voena, C.; Yamamoto, A.; Yoshida, K.; You, Z.; Yudin, Yu. V.; Zanello, D.Baldini, A. M.; Bao, Y.; Baracchini, E.; Bemporad, C.; Berg, F.; Biasotti, M.; Boca, Gianluigi; Cascella, M.; Cattaneo, P. W.; Cavoto, G.; Cei, F.; Cerri, C.; Chiarello, G.; Chiri, C.; Corvaglia, A.; DE BARI, Antonio; De Gerone, M.; Doke, T.; D’Onofrio, A.; Dussoni, S.; Egger, J.; Fujii, Y.; Galli, L.; Gatti, F.; Grancagnolo, F.; Grassi, M.; Graziosi, A.; Grigoriev, D. N.; Haruyama, T.; Hildebrandt, M.; Hodge, Z.; Ieki, K.; Ignatov, F.; Iwamoto, T.; Kaneko, D.; Kang, T. I.; Kettle, P. R.; Khazin, B. I.; Khomutov, N.; Korenchenko, A.; Kravchuk, N.; Lim, G. M. A.; Maki, A.; Mihara, S.; Molzon, W.; Mori, Toshinori; Morsani, F.; Mtchedilishvili, A.; Mzavia, D.; Nakaura, S.; Nardo', Roberto; Nicolò, D.; Nishiguchi, H.; Nishimura, M.; Ogawa, S.; Ootani, W.; Orito, S.; Panareo, M.; Papa, A.; Pazzi, R.; Pepino, A.; Piredda, G.; Pizzigoni, G.; Popov, A.; Raffaelli, F.; Renga, F.; Ripiccini, E.; Ritt, S.; Rossella, M.; Rutar, G.; Sawada, R.; Sergiampietri, F.; Signorelli, G.; Simonetta, M.; Tassielli, G. F.; Tenchini, F.; Uchiyama, Y.; Venturini, M.; Voena, C.; Yamamoto, A.; Yoshida, K.; You, Z.; Yudin, Y. u. V.; Zanello, D

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Non-standard errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants