The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Maria Giovanna Marrosu - One of the best experts on this subject based on the ideXlab platform.
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fingolimod versus interferon beta glatiramer acetate after natalizumab suspension in multiple sclerosis
Brain, 2015Co-Authors: Pietro Iaffaldano, Angelo Ghezzi, Giuseppe Lucisano, Carlo Pozzilli, Vincenzo Brescia Morra, Enrico Millefiorini, Francesco Patti, Alessandra Lugaresi, G B Zimatore, Maria Giovanna MarrosuAbstract:The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in sepaRated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence Rate Ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence Rate Ratio = 2.33, P = 0.0288), patient's choice (incidence Rate Ratio = 2.18, P = 0.0064) and adverse events (incidence Rate Ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duRation longer than 3 months (incidence Rate Ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence Rate Ratio = 1.61, P < 0.0001; incidence Rate Ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence Rate Ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence Rate Ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence Rate Ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out duRations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard Ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting.
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fingolimod versus interferon beta glatiramer acetate after natalizumab suspension in multiple sclerosis
Brain, 2015Co-Authors: Pietro Iaffaldano, Angelo Ghezzi, Giuseppe Lucisano, Carlo Pozzilli, Enrico Millefiorini, Francesco Patti, Alessandra Lugaresi, G B Zimatore, Vincenzo Morra, Maria Giovanna MarrosuAbstract:The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in sepaRated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence Rate Ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence Rate Ratio = 2.33, P = 0.0288), patient’s choice (incidence Rate Ratio = 2.18, P = 0.0064) and adverse events (incidence Rate Ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duRation longer than 3 months (incidence Rate Ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence Rate Ratio = 1.61, P < 0.0001; incidence Rate Ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence Rate Ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence Rate Ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence Rate Ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate ( P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out duRations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard Ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting. * Abbreviations : BRACE : Betaferon®, Betaseron®, Rebif®, Avonex®, Copaxone® or Extavia® EDSS : Expanded Disability Status Scale IFNβ : interferon beta IRR : incidence Rate Ratio
Kousuke Hanada - One of the best experts on this subject based on the ideXlab platform.
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the nonsynonymous synonymous substitution Rate Ratio versus the radical conservative replacement Rate Ratio in the evolution of mammalian genes
Molecular Biology and Evolution, 2007Co-Authors: Kousuke Hanada, Shin-han ShiuAbstract:There are 2 ways to infer selection pressures in the evolution of protein-coding genes, the nonsynonymous and synonymous substitution Rate Ratio (K(A)/K(S)) and the radical and conservative amino acid replacement Rate Ratio (K(R)/K(C)). Because the K(R)/K(C) Ratio depends on the definition of radical and conservative changes in the classification of amino acids, we develop an amino acid classification that maximizes the correlation between K(A)/K(S) and K(R)/K(C). An analysis of 3,375 orthologous gene groups among 5 mammalian species shows that our classification gives a significantly higher correlation coefficient between the 2 Ratios than those of existing classifications. However, there are many orthologous gene groups with a low K(A)/K(S) but a high K(R)/K(C) Ratio. Examining the functions of these genes, we found an overrepresentation of functional categories related to development. To determine if the overrepresentation is stage specific, we examined the expression patterns of these genes at different developmental stages of the mouse. Interestingly, these genes are highly expressed in the early middle stage of development (blastocyst to amnion). It is commonly thought that developmental genes tend to be conservative in evolution, but some molecular changes in developmental stages should have contributed to morphological divergence in adult mammals. Therefore, we propose that the relaxed pressures indicated by the K(R)/K(C) Ratio but not by K(A)/K(S) in the early middle stage of development may be important for the morphological divergence of mammals at the adult stage, whereas purifying selection detected by K(A)/K(S) occurs in the early middle developmental stage.
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The Nonsynonymous/Synonymous Substitution Rate Ratio versus the Radical/Conservative Replacement Rate Ratio in the Evolution of Mammalian Genes
Molecular biology and evolution, 2007Co-Authors: Kousuke Hanada, Shin-han ShiuAbstract:There are 2 ways to infer selection pressures in the evolution of protein-coding genes, the nonsynonymous and synonymous substitution Rate Ratio (K(A)/K(S)) and the radical and conservative amino acid replacement Rate Ratio (K(R)/K(C)). Because the K(R)/K(C) Ratio depends on the definition of radical and conservative changes in the classification of amino acids, we develop an amino acid classification that maximizes the correlation between K(A)/K(S) and K(R)/K(C). An analysis of 3,375 orthologous gene groups among 5 mammalian species shows that our classification gives a significantly higher correlation coefficient between the 2 Ratios than those of existing classifications. However, there are many orthologous gene groups with a low K(A)/K(S) but a high K(R)/K(C) Ratio. Examining the functions of these genes, we found an overrepresentation of functional categories related to development. To determine if the overrepresentation is stage specific, we examined the expression patterns of these genes at different developmental stages of the mouse. Interestingly, these genes are highly expressed in the early middle stage of development (blastocyst to amnion). It is commonly thought that developmental genes tend to be conservative in evolution, but some molecular changes in developmental stages should have contributed to morphological divergence in adult mammals. Therefore, we propose that the relaxed pressures indicated by the K(R)/K(C) Ratio but not by K(A)/K(S) in the early middle stage of development may be important for the morphological divergence of mammals at the adult stage, whereas purifying selection detected by K(A)/K(S) occurs in the early middle developmental stage.
Shin-han Shiu - One of the best experts on this subject based on the ideXlab platform.
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the nonsynonymous synonymous substitution Rate Ratio versus the radical conservative replacement Rate Ratio in the evolution of mammalian genes
Molecular Biology and Evolution, 2007Co-Authors: Kousuke Hanada, Shin-han ShiuAbstract:There are 2 ways to infer selection pressures in the evolution of protein-coding genes, the nonsynonymous and synonymous substitution Rate Ratio (K(A)/K(S)) and the radical and conservative amino acid replacement Rate Ratio (K(R)/K(C)). Because the K(R)/K(C) Ratio depends on the definition of radical and conservative changes in the classification of amino acids, we develop an amino acid classification that maximizes the correlation between K(A)/K(S) and K(R)/K(C). An analysis of 3,375 orthologous gene groups among 5 mammalian species shows that our classification gives a significantly higher correlation coefficient between the 2 Ratios than those of existing classifications. However, there are many orthologous gene groups with a low K(A)/K(S) but a high K(R)/K(C) Ratio. Examining the functions of these genes, we found an overrepresentation of functional categories related to development. To determine if the overrepresentation is stage specific, we examined the expression patterns of these genes at different developmental stages of the mouse. Interestingly, these genes are highly expressed in the early middle stage of development (blastocyst to amnion). It is commonly thought that developmental genes tend to be conservative in evolution, but some molecular changes in developmental stages should have contributed to morphological divergence in adult mammals. Therefore, we propose that the relaxed pressures indicated by the K(R)/K(C) Ratio but not by K(A)/K(S) in the early middle stage of development may be important for the morphological divergence of mammals at the adult stage, whereas purifying selection detected by K(A)/K(S) occurs in the early middle developmental stage.
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The Nonsynonymous/Synonymous Substitution Rate Ratio versus the Radical/Conservative Replacement Rate Ratio in the Evolution of Mammalian Genes
Molecular biology and evolution, 2007Co-Authors: Kousuke Hanada, Shin-han ShiuAbstract:There are 2 ways to infer selection pressures in the evolution of protein-coding genes, the nonsynonymous and synonymous substitution Rate Ratio (K(A)/K(S)) and the radical and conservative amino acid replacement Rate Ratio (K(R)/K(C)). Because the K(R)/K(C) Ratio depends on the definition of radical and conservative changes in the classification of amino acids, we develop an amino acid classification that maximizes the correlation between K(A)/K(S) and K(R)/K(C). An analysis of 3,375 orthologous gene groups among 5 mammalian species shows that our classification gives a significantly higher correlation coefficient between the 2 Ratios than those of existing classifications. However, there are many orthologous gene groups with a low K(A)/K(S) but a high K(R)/K(C) Ratio. Examining the functions of these genes, we found an overrepresentation of functional categories related to development. To determine if the overrepresentation is stage specific, we examined the expression patterns of these genes at different developmental stages of the mouse. Interestingly, these genes are highly expressed in the early middle stage of development (blastocyst to amnion). It is commonly thought that developmental genes tend to be conservative in evolution, but some molecular changes in developmental stages should have contributed to morphological divergence in adult mammals. Therefore, we propose that the relaxed pressures indicated by the K(R)/K(C) Ratio but not by K(A)/K(S) in the early middle stage of development may be important for the morphological divergence of mammals at the adult stage, whereas purifying selection detected by K(A)/K(S) occurs in the early middle developmental stage.
Pietro Iaffaldano - One of the best experts on this subject based on the ideXlab platform.
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fingolimod versus interferon beta glatiramer acetate after natalizumab suspension in multiple sclerosis
Brain, 2015Co-Authors: Pietro Iaffaldano, Angelo Ghezzi, Giuseppe Lucisano, Carlo Pozzilli, Vincenzo Brescia Morra, Enrico Millefiorini, Francesco Patti, Alessandra Lugaresi, G B Zimatore, Maria Giovanna MarrosuAbstract:The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in sepaRated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence Rate Ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence Rate Ratio = 2.33, P = 0.0288), patient's choice (incidence Rate Ratio = 2.18, P = 0.0064) and adverse events (incidence Rate Ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duRation longer than 3 months (incidence Rate Ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence Rate Ratio = 1.61, P < 0.0001; incidence Rate Ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence Rate Ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence Rate Ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence Rate Ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out duRations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard Ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting.
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fingolimod versus interferon beta glatiramer acetate after natalizumab suspension in multiple sclerosis
Brain, 2015Co-Authors: Pietro Iaffaldano, Angelo Ghezzi, Giuseppe Lucisano, Carlo Pozzilli, Enrico Millefiorini, Francesco Patti, Alessandra Lugaresi, G B Zimatore, Vincenzo Morra, Maria Giovanna MarrosuAbstract:The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in sepaRated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence Rate Ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence Rate Ratio = 2.33, P = 0.0288), patient’s choice (incidence Rate Ratio = 2.18, P = 0.0064) and adverse events (incidence Rate Ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duRation longer than 3 months (incidence Rate Ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence Rate Ratio = 1.61, P < 0.0001; incidence Rate Ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence Rate Ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence Rate Ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence Rate Ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate ( P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out duRations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard Ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting. * Abbreviations : BRACE : Betaferon®, Betaseron®, Rebif®, Avonex®, Copaxone® or Extavia® EDSS : Expanded Disability Status Scale IFNβ : interferon beta IRR : incidence Rate Ratio
Seiji Shiroya - One of the best experts on this subject based on the ideXlab platform.
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Measurement and analysis of 241Am fission Rate Ratio relative to 235U fission Rate in thermal neutron systems using Kyoto University Critical Assembly
Journal of Nuclear Science and Technology, 2001Co-Authors: Hironobu Unesaki, Tomohiko Iwasaki, Takanori Kitada, Yoshitaka Ikeuchi, Seiji ShiroyaAbstract:Integral measurements of241 Am fission Rate Ratio relative to235 U fission Rate were performed at Kyoto University Critical Assembly. The fission Rates were measured using the back-to-back type double fission chamber at five thermal cores with different H/235 U Ratio so that the neutron spectra of the cores were systematically varied. The measured fission Rate Ratios, normalized to number of atoms, were 0. 0144 to 0. 0522, with a typical uncertainty of 2%. The measured data were compared with the calculated results using MVP based on JENDL-3.2, which gave the averaged calculated-to-experimental Ratio (C/E) of 0.88. Obtained results of C/E using 241Am fission cross sections from JENDL-3/2, ENDF/B-VI and JEF2.2 showed that the latter two gave larger C/E values than those by JENDL-3.2 by about 2% and 7 to 9%, respectively. It has been found that the large difference between JENDL-3.2 and JEF2.2 arises mainly from the significant cross section difference at the vicinity of resonance at 0.576 eV, whereas the d...
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measurement of 237np fission Rate Ratio relative to 235u fission Rate in cores with various thermal neutron spectrum at the kyoto university critical assembly
Journal of Nuclear Science and Technology, 2000Co-Authors: Hironobu Unesaki, Tomohiko Iwasaki, Takanori Kitada, Akio Kohashi, Daisuke Fujiwara, Mitsuo Kuroda, Takeshi Kato, Yoshitaka Ikeuchi, Seiji ShiroyaAbstract:Integral measurements of 237 Np fission Rate Ratio relative to 235 U fission Rate have been performed at Kyoto University Critical Assembly. The fission Rates have been measured using the back-to-back type double fission chamber at five thermal cores with different H/ 235 U Ratio so that the neutron spectra of the cores were systematically varied. The measured fission Rate Ratio per atom was 0.00439 to 0.0298, with a typical uncertainty of 2 to 3%. The measured data were compared with the calculated results using SRAC/TWOTRAN and MVP based on JENDL-3.2, which gave the averaged C/E values of 0.93 and 0.95, respectively. Obtained results of C/E using 237 Np cross sections from JENDL-3/2, ENDF/B-VI.5 and JEF2.2 show that the latter two gave smaller results than JENDL-3.2 by about 4%, which clearly reflects the discrepancy in the evaluated cross section among the libraries. This difference arises from both fast fission and resonance region. Although further improvement is recommended, 237 Np fission cross section in JENDL-3.2 is considered to be superior to those in the other libraries and can be adopted for use in design calculations for minor actinide transmutation system using thermal reactors with prediction precision of 237 Np fission Rate within 10%.
