Curcumin as Treatment for Bladder Cancer : A Preclinical Study of Cyclodextrin-Curcumin Complex and BCG as Intravesical Treatment in an Orthotopic Bladder Cancer Rat Model

Objective. To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. Methods. Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. Results. CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage. Conclusions. Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.Peer reviewe

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

American political affiliation, 2003–43: a cohort component projection

The recent rise and stability in American party identification has focused interest on the long-term dynamics of party bases. Liberal commentators cite immigration and youth as forces which will produce a natural Democratic advantage in the future while conservative writers highlight the importance of high Republican fertility in securing Republican growth. These concerns foreground the neglect of demography within political science. This paper addresses this omission by conducting the first ever cohort component projection of American partisan populations to 2043 based on survey and census data. A number of scenarios are modeled, but, on current trends, we predict that American partisanship will shift much less than the nation’s ethnic composition because the parties’ age structures are similar. Still, our projections find that the Democrats gain two to three percentage points from the Republicans by 2043, mainly through immigration, though Republican fertility may redress the balance in the very long term

Prehistory of Transit Searches

Nowadays the more powerful method to detect extrasolar planets is the transit method. We review the planet transits which were anticipated, searched, and the first ones which were observed all through history. Indeed transits of planets in front of their star were first investigated and studied in the solar system. The first observations of sunspots were sometimes mistaken for transits of unknown planets. The first scientific observation and study of a transit in the solar system was the observation of Mercury transit by Pierre Gassendi in 1631. Because observations of Venus transits could give a way to determine the distance Sun-Earth, transits of Venus were overwhelmingly observed. Some objects which actually do not exist were searched by their hypothetical transits on the Sun, as some examples a Venus satellite and an infra-mercurial planet. We evoke the possibly first use of the hypothesis of an exoplanet transit to explain some periodic variations of the luminosity of a star, namely the star Algol, during the eighteen century. Then we review the predictions of detection of exoplanets by their transits, those predictions being sometimes ancient, and made by astronomers as well as popular science writers. However, these very interesting predictions were never published in peer-reviewed journals specialized in astronomical discoveries and results. A possible transit of the planet beta Pic b was observed in 1981. Shall we see another transit expected for the same planet during 2018? Today, some studies of transits which are connected to hypothetical extraterrestrial civilisations are published in astronomical refereed journals. Some studies which would be classified not long ago as science fiction are now considered as scientific ones.Comment: Submiited to Handbook of Exoplanets (Springer

Photovoltaic power plants: a multicriteria approach to investment decisions and a case study in western Spain

his paper proposes a compromise programming (CP) model to help investors decide whether to construct photovoltaic power plants with government financial support. For this purpose, we simulate an agreement between the government, who pursues political prices (guaranteed prices) as low as possible, and the project sponsor who wants returns (stochastic cash flows) as high as possible. The sponsor s decision depends on the positive or negative result of this simulation, the resulting simulated price being compared to the effective guaranteed price established by the country legislation for photovoltaic energy. To undertake the simulation, the CP model articulates variables such as ranges of guaranteed prices, tech- nical characteristics of the plant, expected energy to be generated over the investment life, investment cost, cash flow probabilities, and others. To determine the CP metric, risk aver- sion is assumed. As an actual application, a case study on photovoltaic power investment in Extremadura, western Spain, is developed in detail.Garcia-Bernabeu, A.; Benito Benito, A.; Bravo Selles, M.; Pla Santamaría, D. (2015). Photovoltaic power plants: a multicriteria approach to investment decisions and a case study in western Spain. Annals of Operations Research. 1-12. doi:10.1007/s10479-015-1836-2S112Andrews, R. W., Pollard, A., & Pearce, J. M. (2012). Improved parametric empirical determination of module short circuit current for modelling and optimization of solar photovoltaic systems. Solar Energy, 86(9), 2240–2254.Anwar, Y., & Mulyadi, M. S. (2011). Income tax incentives on renewable energy industry: Case of geothermal industry in USA and Indonesia. African Journal of Business Management, 5(31), 12264–12270.Aouni, B., & Kettani, O. (2001). Goal programming model: A glorious history and a promising future. European Journal of Operational Research, 133(2), 225–231.Ballestero, E. (1997). 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I., & Toffel, M. W. (2009). How well do social ratings actually measure corporate social responsibility? Journal of Economics & Management Strategy, 18(1), 125–169.Copeland, T. E., & Weston, J. (1988). Financial theory and corporate policy. Reading, Massachusetts: Addison-Wesley.Gallagher, K. S. (2013). Why & how governments support renewable energy. Daedalus, 142(1), 59–77.García-Cascales, M. S., Lamata, M. T., & Sánchez-Lozano, J. M. (2012). Evaluation of photovoltaic cells in a multi-criteria decision making process. Annals of Operations Research, 199(1), 373–391.Gupta, S. (2012). Financing renewable energy. In F. L. Toth (Ed.), Energy for development (pp. 171–186). Springer.Karaarslan, A. (2012). Obtaining renewable energy from piezoelectric ceramics using Sheppard–Taylor converter. International Review of Electrical Engineering, 7(2), 3949–3956.Koellner, T., Weber, O., Fenchel, M., & Scholz, R. (2005). Principles for sustainability rating of investment funds. 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Feasibility analysis of solar photovoltaic commercial power generation in California. Engineering Management Journal, 24(4), 36–49.Yazdani-Chamzini, A., Fouladgar, M. M., Zavadskas, E. K., & Moini, S. H. H. (2013). Selecting the optimal renewable energy using multi criteria decision making. Journal of Business Economics and Management, 14(5), 957–978.Yu, P. (1985). Multiple criteria decision making: Concepts, techniques and extensions. New York: Springer.Zeleny, M. (1982). Multiple criteria decision making (Vol. 25). New York: McGraw-Hill.Zhao, R., Shi, G., Chen, H., Ren, A., & Finlow, D. (2011). Present status and prospects of photovoltaic market in China. Energy Policy, 39(4), 2204–2207

Applying valence framing to enhance the effect of information on transport-related carbon dioxide emissions

The provision of information about transport-related carbon dioxide (CO2) emissions to the traveler can be seen as an instrument to increase the likelihood of more sustainable choices being made by individuals. However, as transport-related CO2 emissions are largely seen as a 'social' cost rather than a 'private' cost to the individual, the behavioral engagement with and response to information on environmental effects of travel choices may be limited. It is argued that framing, studied in a range of contexts, can be used to enhance the evaluation of choice attributes and promote more sustainable choices. An experiment is reported that examines the effect of valence framing of amounts of CO2 emissions on the perceived differences between alternative amounts. Through the use of positive and negative terms, the information is framed to focus attention either on the potential of a travel mode to provide environmental benefit (positive frame) or on its potential to reduce environmental loss (negative frame). Survey participants' estimates of CO2 amounts were compared for positive and negative framing of the same information using an ordered logit model. The findings imply that negative framing is more effective than positive framing in highlighting differences between CO2 amounts of alternative travel modes and therefore is likely to influence travel-related choices. © 2012 Elsevier Ltd

Bacterial microevolution and the Pangenome

The comparison of multiple genome sequences sampled from a bacterial population reveals considerable diversity in both the core and the accessory parts of the pangenome. This diversity can be analysed in terms of microevolutionary events that took place since the genomes shared a common ancestor, especially deletion, duplication, and recombination. We review the basic modelling ingredients used implicitly or explicitly when performing such a pangenome analysis. In particular, we describe a basic neutral phylogenetic framework of bacterial pangenome microevolution, which is not incompatible with evaluating the role of natural selection. We survey the different ways in which pangenome data is summarised in order to be included in microevolutionary models, as well as the main methodological approaches that have been proposed to reconstruct pangenome microevolutionary history