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101.
Riad Kahoul Fran?ois Gueyffier Emmanuel Amsallem Margaret Haugh Ivanny Marchant Fran?ois-Henri Boissel Jean-Pierre Boissel 《Journal of the Royal Society Interface》2014,11(100)
Healthcare authorities make difficult decisions about how to spend limited budgets for interventions that guarantee the best cost-efficacy ratio. We propose a novel approach for treatment decision-making, OMES—in French: Objectif thérapeutique Modèle Effet Seuil (in English: Therapeutic Objective–Threshold–Effect Model; TOTEM). This approach takes into consideration results from clinical trials, adjusted for the patients'' characteristics in treatment decision-making. We compared OMES with the French clinical practice guidelines (CPGs) for the management of dyslipidemia with statin in a computer-generated realistic virtual population, representing the adult French population, in terms of the number of all-cause deaths avoided (number of avoided events: NAEs) under treatment and the individual absolute benefit. The total budget was fixed at the annual amount reimbursed by the French social security for statins. With the CPGs, the NAEs was 292 for an annual cost of 122.54 M€ compared with 443 with OMES. For a fixed NAEs, OMES reduced costs by 50% (60.53 M€ yr−1). The results demonstrate that OMES is at least as good as, and even better than, the standard CPGs when applied to the same population. Hence the OMES approach is a practical, useful alternative which will help to overcome the limitations of treatment decision-making based uniquely on CPGs. 相似文献
102.
Impact of oxygen transport properties on the kinetic modeling of polypropylene thermal oxidation. II. Effect of oxygen diffusivity 下载免费PDF全文
Alexandre François‐Heude Emmanuel Richaud Alain Guinault Eric Desnoux Xavier Colin 《应用聚合物科学杂志》2015,132(6)
The kinetic model, established in a previous article (François‐Heude et al., J. Appl. Polym. Sci., in press) to predict the homogeneous oxidation in iPP films typically thinner than 100 µm, is now extended to simulate the oxidation profiles in thicker plates by coupling the oxygen diffusion and its consumption by the chemical reactions. In this perspective, oxygen transport properties (namely oxygen solubility, diffusivity, and permeability) are measured by permeametry on a reference iPP. These values are compared with an exhaustive compilation of literature data to evaluate their variability among the whole iPP family, which one has been reasonably ascribed to initial differences in polymer morphology, but also to evaluate their consistency, especially their temperature dependence between 20 and 140°C. Failing to simulate oxidation profiles, the kinetic model is then used as an inverse resolution method for estimating more satisfactory values of oxygen transport properties. It is thus evidenced that the crystallinity changes induced by thermal oxidation largely explains the dramatic decrease in oxygen penetration toward the sample core just after the induction period. A strategy aimed for introducing the relationship between the polymer crystalline morphology and oxygen transport properties into the kinetic model is given in the graphical abstract, although the effect of polymer polarity remains to be established prior to this implementation. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41562. 相似文献
103.
Simoens François Meilhan Jérôme Nicolas Jean-Alain 《Journal of Infrared, Millimeter and Terahertz Waves》2015,36(10):961-985
Journal of Infrared, Millimeter, and Terahertz Waves - Sensitive and large-format terahertz focal plane arrays (FPAs) integrated in compact and hand-held cameras that deliver real-time terahertz... 相似文献
104.
Cyprien Wolff Nicolas Richart Jean‐François Molinari 《International journal for numerical methods in engineering》2015,101(12):933-949
Dynamic crack‐branching instabilities in a brittle material are studied numerically by using a non‐local damage model. PMMA is taken as our model brittle material. The simulated crack patterns, crack velocities, and dissipated energies compare favorably with experimental data gathered from the literature, as long as the critical strain for damage initiation as well as the parameters for a rate‐dependent damage law are carefully selected. Nonetheless, the transition from a straight crack propagation to the emergence of crack branches is very sensitive to the damage initiation threshold. The transition regime is thus a particularly interesting challenge for numerical approaches. We advocate using the present numerical study as a benchmark to test the robustness of alternative non‐local numerical approaches. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
105.
106.
Moïse Nola Mireille E. Nougang Olive V. Noah Ewoti Luciane M. Moungang François Krier Nour‐Eddine Chihib 《Water and Environment Journal》2013,27(3):328-337
This study was aimed at assessing the prevalence of pathogenic Escherichia coli strains, relative to the total count of E. coli, faecal coliforms and other heterotrophic mesophilic aerobic bacteria (HMAB) isolated in groundwater in the equatorial region of Cameroon (Central Africa). Bacteria were isolated using standard methods. Pathogenic E. coli strains were then identified using haemagglutination and antisera tests. The maximum abundance of HMAB, faecal coliforms and E. coli strains were 4.9 × 106, 5.6 × 103 and 1 × 103 colony‐forming units (CFU)/100 mL, respectively. The count of pathogenic E. coli strains reached 3 CFU/100 mL. The counts of commensal and pathogenic E. coli strains underwent temporal and spatial fluctuations. In 21% of sampling sites, the abundance of faecal coliforms was significantly correlated to that of E. coli (P < 0.05). However, the isolated bacterial count was not significantly correlated to that of the pathogenic E. coli strains (P > 0.05). The bacteria abundance dynamics may be impacted by many interacting factors. 相似文献
107.
Within Australian cities, social and economic inequalities manifest themselves spatially. Perceived neighbourhood disorder and neighbourhood reputation are relevant to considering the ways in which social and economic inequalities translate into place-based inequalities. This article explores the ways in which residents of two socio-economically contrasting urban areas describe and explain neighbourhood disorder and neighbourhood reputation. It draws upon qualitative data from 40 in-depth interviews, in addition to quantitative data from a postal survey. The qualitative findings highlighted how issues of neighbourhood disorder and reputation were intertwined. In both areas, participants sought to portray themselves and their neighbourhoods in positive ways, by attributing responsibility for neighbourhood disorder to people who were unlike themselves, and by highlighting places that were perceived to have worse reputations and higher levels of disorder. The findings are considered in light of Bourdieu's theory of capitals. This article indicates that both neighbourhood disorder and reputation are pathways through which social, economic and health inequities are maintained in urban areas. 相似文献
108.
BaTiO3 incorporation effect on the dielectric properties of polymer from aqueous emulsion: An enhanced dispersion technique 下载免费PDF全文
An economic and environment friendly process was adapted to synthesize new dielectric composite materials. Using ethylene vinyl acetate (EVA)/vinyl ester of versatic acid (VeoVa) terpolymer as an aqueous emulsion provides a homogenous dispersion of BaTiO3 (BT) particles, due to the high viscosity and polarity of the vinyl resin (VR). Composites films were obtained from these dispersions by water evaporation. The evolution of the dielectric properties as a function of the BaTiO3 content, was correctly fitted by a Maxwell‐Garnett model. This fitting of the experimental curve shows a good dispersion of filler in the vinyl resin and the particles separation by a layer of resin as expected for the preparation method used in this study. The VR/BT composites show good synergy between the dielectric properties of the different phases of the composites due to the formation of macrodipoles and to the strong interactions between polar EVA/VeoVa groups and the BaTiO3 particles surface. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44333. 相似文献
109.
Structure–Activity Relationships of JMV4463, a Vectorized Cathepsin D Inhibitor with Antiproliferative Properties: The Unique Role of the AMPA‐Based Vector 下载免费PDF全文
Dr. Lubomir L. Vezenkov Clément A. Sanchez Dr. Virginie Bellet Dr. Vincent Martin Dr. Marie Maynadier Dr. Nadir Bettache Prof. Vincent Lisowski Prof. Jean Martinez Dr. Marcel Garcia Dr. Muriel Amblard Dr. Jean‐François Hernandez 《ChemMedChem》2016,11(3):302-308
Cathepsin D (CathD) is overexpressed and secreted by several solid tumors and stimulates their growth, the mechanism of which is still not understood. In this context, the pepstatin bioconjugate JMV4463 [Ac‐arg‐O2Oc‐(Val)3‐Sta‐Ala‐Sta‐(AMPA)4‐NH2; O2Oc=8‐amino‐3,6‐dioxaoctanoyl, Sta=statine, AMPA=ortho‐aminomethylphenylacetyl], containing a new kind of cell‐penetrating vector, was previously shown to exhibit potent antiproliferative effects in vitro and to delay the onset of tumors in vivo. In this study, we performed a structure–activity relationship analysis to evaluate the significance of the inhibitor and vector moieties of JMV4463. By modifying both statine residues of pepstatin we found that the antiproliferative activity is correlated with CathD inhibition, supporting a major role of the catalytic activity of intracellular CathD in cancer cell proliferation. Replacing the vector composed of four AMPA units with other vectors was found to abolish cytotoxicity, although all of the conjugates enabled pepstatin transport into cells. In addition, the AMPA4 vector must be localized at the C terminus of the bioconjugate. The unexpected importance of the vector structure and position for cytotoxic action suggests that AMPA4 enables pepstatin to inhibit the proteolysis of critical CathD substrates involved in cell proliferation via a unique mechanism of action. 相似文献
110.
Discovery of Highly Potent Dual Orexin Receptor Antagonists via a Scaffold‐Hopping Approach 下载免费PDF全文
Dr. Bibia Heidmann Dr. John Gatfield Dr. Catherine Roch Dr. Alexander Treiber Dr. Simone Tortoioli Dr. Christine Brotschi Dr. Jodi T. Williams Dr. Martin H. Bolli Dr. Stefan Abele Dr. Thierry Sifferlen Dr. François Jenck Dr. Christoph Boss 《ChemMedChem》2016,11(19):2132-2146
Starting from suvorexant (trade name Belsomra), we successfully identified interesting templates leading to potent dual orexin receptor antagonists (DORAs) via a scaffold‐hopping approach. Structure–activity relationship optimization allowed us not only to improve the antagonistic potency on both orexin 1 and orexin 2 receptors (Ox1 and Ox2, respectively), but also to increase metabolic stability in human liver microsomes (HLM), decrease time‐dependent inhibition of cytochrome P450 (CYP) 3A4, and decrease P‐glycoprotein (Pgp)‐mediated efflux. Compound 80 c [{(1S,6R)‐3‐(6,7‐difluoroquinoxalin‐2‐yl)‐3,8‐diazabicyclo[4.2.0]octan‐8‐yl}(4‐methyl‐[1,1′‐biphenyl]‐2‐yl)methanone] is a potent and selective DORA that inhibits the stimulating effects of orexin peptides OXA and OXB at both Ox1 and Ox2. In calcium‐release assays, 80 c was found to exhibit an insurmountable antagonistic profile at both Ox1 and Ox2, while displaying a sleep‐promoting effect in rat and dog models, similar to that of the benchmark compound suvorexant. 相似文献