Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011).

The detection of multi-resistant bacterial pathogens, particularly those to carbapenemases, in leukemic and stem cell transplant patients forces the use of old or non-conventional agents as the only remaining treatment options. These include colistin/polymyxin B, tigecycline, fosfomycin and various anti-gram-positive agents. Data on the use of these agents in leukemic patients are scanty, with only linezolid subjected to formal trials. The Expert Group of the 4(th) European Conference on Infections in Leukemia has developed guidelines for their use in these patient populations. Targeted therapy should be based on (i) in vitro susceptibility data, (ii) knowledge of the best treatment option against the particular species or phenotype of bacteria, (iii) pharmacokinetic/pharmacodynamic data, and (iv) careful assessment of the risk-benefit balance. For infections due to resistant Gram-negative bacteria, these agents should be preferably used in combination with other agents that remain active in vitro, because of suboptimal efficacy (e.g., tigecycline) and the risk of emergent resistance (e.g., fosfomycin). The paucity of new antibacterial drugs in the near future should lead us to limit the use of these drugs to situations where no alternative exists.

Gas exchanges in peach palms as a function of the spad chlorophyll meter readings

The close relationship between the chlorophyll-meters readings and the total chlorophyll and nitrogen contents in leaves, has allowed their evaluation both in annual and perennial species. Besides, some physiological events such as the CO2 assimilation have also been estimated by chlorophyll meters. This work was carried out aiming to evaluate the gas exchanges of peach palms as a function of the chlorophyll SPAD-Meter readings. Three year-old peach palms from Yurimaguas, Peru were studied in Ubatuba, SP, Brazil, spaced 2 x 1 m in area under a natural gradient of organic matter which allowed four plots to be considered, according to the peach palms leaves colors, from light yellow to dark green. The SPAD readings and the stomatal frequency of leaflets were evaluated. The photosynthetic photon flux density (PPFD, μmol m-2 s-1), the leaf temperature (Tleaf, ºC), the CO2 assimilation (A, μmol m-2 s-1), the stomatal conductance (g s, mol m-2 s-1), the transpiration (E, mmol m-2 s-1) and the intercellular CO2 concentration (Ci, μmol mol-1) were evaluated with a portable infrared gas analyzer (LCA-4, ADC BioScientific Ltd., Great Amwell, U.K.). A linear increase in the CO2 assimilation as a function of the SPAD readings (y = -0.34 + 0.19x, R² = 0.99), indicates that they can be a rapid and cheap complementary method to evaluate in peach palms some important physiological events, such as CO2 assimilation.

Antifungal activity of compounds targeting the Hsp90-calcineurin pathway against various mould species.

OBJECTIVES: Invasive mould infections are associated with a high mortality rate and the emergence of MDR moulds is of particular concern. Calcineurin and its chaperone, the heat shock protein 90 (Hsp90), represent an important pathway for fungal virulence that can be targeted at different levels. We investigated the antifungal activity of compounds directly or indirectly targeting the Hsp90-calcineurin axis against different mould species. METHODS: The in vitro antifungal activity of the anticalcineurin drug FK506 (tacrolimus), the Hsp90 inhibitor geldanamycin, the lysine deacetylase inhibitor trichostatin A and the Hsp70 inhibitor pifithrin-μ was assessed by the standard broth dilution method against 62 clinical isolates of Aspergillus spp. and non-Aspergillus moulds (Mucoromycotina, Fusarium spp., Scedosporium spp., Purpureocillium/Paecilomyces spp. and Scopulariopsis spp.) RESULTS: FK506 had variable antifungal activity against different Aspergillus spp. and was particularly active against Mucor spp. Geldanamycin had moderate antifungal activity against Fusarium spp. and Paecilomyces variotii. Importantly, trichostatin A had good activity against the triazole-resistant Aspergillus ustus and the amphotericin B-resistant Aspergillus terreus as well as the MDR Scedosporium prolificans. Moreover, trichostatin A exhibited synergistic interactions with caspofungin against A. ustus and with geldanamycin against Rhizopus spp. for which none of the other agents showed activity. Pifithrin-μ exhibited little antifungal activity. CONCLUSIONS: Targeting the Hsp90-calcineurin axis at different levels resulted in distinct patterns of susceptibility among different fungal species. Lysine deacetylase inhibition may represent a promising novel antifungal strategy against emerging resistant moulds.

Analysis of Earnings, Stock Prices and Bond Yields: The Fed Model Approach

Prediction of the stock market valuation is a common interest to all market participants. Theoretically sound market valuation can be achieved by discounting future earnings of equities to present. Competing valuation models seek to find variables that affect the equity market valuation in a way that the market valuation can be explained and also variables that could be used to predict market valuation. In this paper we test the contemporaneous relationship between stock prices, forward looking earnings and long-term government bond yields. We test this so-called Fed model in a long- and short-term time series analysis. In order to test the dynamics of the relationship, we use the cointegration framework. The data used in this study spans over four decades of various market conditions between 1964-2007, using data from United States. The empirical results of our analysis do not give support for the Fed model. We are able to show that the long-term government bonds do not play statistically significant role in this relationship. The effect of forward earnings yield on the stock market prices is significant and thus we suggest the use of standard valuation ratios when trying to predict the future paths of equity prices. Also, changes in the long-term government bond yields do not have significant short-term impact on stock prices.

Lateral gene exchanges shape the genomes of amoeba-resisting microorganisms.

Based on Darwin's concept of the tree of life, vertical inheritance was thought to be dominant, and mutations, deletions, and duplication were streaming the genomes of living organisms. In the current genomic era, increasing data indicated that both vertical and lateral gene inheritance interact in space and time to trigger genome evolution, particularly among microorganisms sharing a given ecological niche. As a paradigm to their diversity and their survival in a variety of cell types, intracellular microorganisms, and notably intracellular bacteria, were considered as less prone to lateral genetic exchanges. Such specialized microorganisms generally have a smaller gene repertoire because they do rely on their host's factors for some basic regulatory and metabolic functions. Here we review events of lateral gene transfer (LGT) that illustrate the genetic exchanges among intra-amoebal microorganisms or between the microorganism and its amoebal host. We tentatively investigate the functions of laterally transferred genes in the light of the interaction with their host as they should confer a selective advantage and success to the amoeba-resisting microorganisms (ARMs).

Determinants of the decision to appeal against motor bodily injury settlements awarded by Spanish trial courts

Automobile bodily injury disputes represent one of the main causes of litigation faced by Spanish Courts. In this paper a multinomial model is implemented to analyse which factors determine the decision to appeal against the verdicts of trial courts. Use of a dataset of motor insurance claims revealed differences between the determinants of a claimant’s decision to appeal and those of insurers. Among other results it is shown that discrepancies regarding the permanent disability sustained affect the insurer’s decision to appeal. In contrast, the claimant pays more attention to differences in the stated temporary disability. Conclusions are drawn regarding which factors could reduce the percentage of appealed cases.

Pricing anomalies in the Finnish stock market

The aim of this thesis is to examine whether the pricing anomalies exists in the Finnish stock markets by comparing the performance of quantile portfolios that are formed on the basis of either individual valuation ratios, composite value measures or combined value and momentum indicators. All the research papers included in the thesis show evidence of value anomalies in the Finnish stock markets. In the first paper, the sample of stocks over the 1991-2006 period is divided into quintile portfolios based on four individual valuation ratios (i.e., E/P, EBITDA/EV, B/P, and S/P) and three hybrids of them (i.e. composite value measures). The results show the superiority of composite value measures as selection criterion for value stocks, particularly when EBITDA/EV is employed as earnings multiple. The main focus of the second paper is on the impact of the holding period length on performance of value strategies. As an extension to the first paper, two more individual ratios (i.e. CF/P and D/P) are included in the comparative analysis. The sample of stocks over 1993- 2008 period is divided into tercile portfolios based on six individual valuation ratios and three hybrids of them. The use of either dividend yield criterion or one of three composite value measures being examined results in best value portfolio performance according to all performance metrics used. Parallel to the findings of many international studies, our results from performance comparisons indicate that for the sample data employed, the yearly reformation of portfolios is not necessarily optimal in order to maximally gain from the value premium. Instead, the value investor may extend his holding period up to 5 years without any decrease in long-term portfolio performance. The same holds also for the results of the third paper that examines the applicability of data envelopment analysis (DEA) method in discriminating the undervalued stocks from overvalued ones. The fourth paper examines the added value of combining price momentum with various value strategies. Taking account of the price momentum improves the performance of value portfolios in most cases. The performance improvement is greatest for value portfolios that are formed on the basis of the 3-composite value measure which consists of D/P, B/P and EBITDA/EV ratios. The risk-adjusted performance can be enhanced further by following 130/30 long-short strategy in which the long position of value winner stocks is leveraged by 30 percentages while simultaneously selling short glamour loser stocks by the same amount. Average return of the long-short position proved to be more than double stock market average coupled with the volatility decrease. The fifth paper offers a new approach to combine value and momentum indicators into a single portfolio-formation criterion using different variants of DEA models. The results throughout the 1994-2010 sample period shows that the top-tercile portfolios outperform both the market portfolio and the corresponding bottom-tercile portfolios. In addition, the middle-tercile portfolios also outperform the comparable bottom-tercile portfolios when DEA models are used as a basis for stock classification criteria. To my knowledge, such strong performance differences have not been reported in earlier peer-reviewed studies that have employed the comparable quantile approach of dividing stocks into portfolios. Consistently with the previous literature, the division of the full sample period into bullish and bearish periods reveals that the top-quantile DEA portfolios lose far less of their value during the bearish conditions than do the corresponding bottom portfolios. The sixth paper extends the sample period employed in the fourth paper by one year (i.e. 1993- 2009) covering also the first years of the recent financial crisis. It contributes to the fourth paper by examining the impact of the stock market conditions on the main results. Consistently with the fifth paper, value portfolios lose much less of their value during bearish conditions than do stocks on average. The inclusion of a momentum criterion somewhat adds value to an investor during bullish conditions, but this added value turns to negative during bearish conditions. During bear market periods some of the value loser portfolios perform even better than their value winner counterparts. Furthermore, the results show that the recent financial crisis has reduced the added value of using combinations of momentum and value indicators as portfolio formation criteria. However, since the stock markets have historically been bullish more often than bearish, the combination of the value and momentum criteria has paid off to the investor despite the fact that its added value during bearish periods is negative, on an average.

Effect of multidrug resistance modulators on the activity of ivermectin and moxidectin against selected strains of Haemonchus contortus infective larvae

Nematode parasites have shown resistance to the anthelmintics, ivermectin and moxidectin, and there is evidence that the over-expression of parasite P-glycoprotein (P-gp) may account, at least in part, for resistance to ivermectin. The objective of this study was to evaluate whether the multidrug resistance (MDR) modulators, verapamil, CL 347.099 (an analog of verapamil) and cyclosporin A, would enhance the efficacy of ivermectin and moxidectin against selected strains of Haemonchus contortus using an in vitro larval migration assay. The modulators had no effects on the number of migrating larvae when used alone. Ivermectin and moxidectin showed a significant (P<0.05) increase in its efficacy by 52.8 and 58.5% respectively, when used in association with verapamil against a moxidectin-selected strain. CL 347,099 also increased significantly (P<0.05) the ivermectin and moxidectin efficacy by 24.2 and 40.0% respectively, against an ivermectin-selected strain and by 40.0 and 75.6% respectively, against an moxidectin-selected strain. At the concentrations tested cyclosporin A showed a variable effect on increasing the efficacy of the anthelmintics against the susceptible and resistant strains.

Efficacy of the d-phenothrin/pyriproxyfen association against mites in naturally co-infested rabbits

The aim of the present study was to evaluate the efficacy of the d-phenothrin/pyriproxyfen association against Psoroptes ovis, Cheyletiella parasitivorax, and Leporacarus gibbus infestations in naturally co-infested rabbits. Twenty crossbreed (New Zealand White x California) rabbits concurrently infested by the three mite species were randomly divided in two groups. All rabbits presented with hyperemia, erythema and formation of crusts in the ear canals caused by P. ovis. Infestations by both C. parasitivorax and L. gibbus were considered asymptomatic in all animals.Ten animals were treated with a 4.4% d-phenothrin and 0.148% pyriproxyfen spray formulation until have their body surface uniformly sprayed, including external ear canals. The other ten rabbits remained untreated, serving as control group. Observations were done on days +7, +14, +21, +28, and +35 post-treatment. The d-phenothrin/pyriproxyfen association showed 100% efficacy against the three mite species and was responsible for the remission of psoroptic mange lesions on treated animals. No signs of intoxication were observed. The results indicate that d-phenothrin/pyriproxyfen spray formulation in a single application is an effective and clinically safe option for the control of different mite infestations in rabbits.

Stock Market reaction to the CSR announcements of American fast food companies

The purpose of this study is to examine whether Corporate Social Responsibility (CSR) announcements of the three biggest American fast food companies (McDonald’s, YUM! Brands and Wendy’s) have any effect on their stock returns as well as on the returns of the industry index (Dow Jones Restaurants and Bars). The time period under consideration starts on 1st of May 2001 and ends on 17th of October 2013. The stock market reaction is tested with an event study utilizing CAPM. The research employs the daily stock returns of the companies, the index and the benchmarks (NASDAQ and NYSE). The test of combined announcements did not reveal any significant effect on the index and McDonald’s. However the stock returns of Wendy’s and YUM! Brands reacted negatively. Moreover, the company level analyses showed that to their own CSR releases McDonald’s stock returns respond positively, YUM! Brands reacts negatively and Wendy’s does not have any reaction. Plus, it was found that the competitors of the announcing company tend to react negatively to all the events. Furthermore, the division of the events into sustainability categories showed statistically significant negative reaction from the Index, McDonald’s and YUM! Brands towards social announcements. At the same time only the index was positively affected by to the economic and environmental CSR news releases.

Regime-Switching in the Impact of Oil Price Shocks on Stock Market Volatility: Evidence from Oil-Importing and Oil-Exporting Countries

Research has highlighted the adequacy of Markov regime-switching model to address dynamic behavior in long term stock market movements. Employing a purposed Extended regime-switching GARCH(1,1) model, this thesis further investigates the regime dependent nonlinear relationship between changes in oil price and stock market volatility in Saudi Arabia, Norway and Singapore for the period of 2001-2014. Market selection is prioritized to national dependency on oil export or import, which also rationalizes the fitness of implied bivariate volatility model. Among two regimes identified by the mean model, high stock market return-low volatility regime reflects the stable economic growth periods. The other regime characterized by low stock market return-high volatility coincides with episodes of recession and downturn. Moreover, results of volatility model provide the evidence that shocks in stock markets are less persistent during the high volatility regime. While accelerated oil price rises the stock market volatility during recessions, it reduces the stock market risk during normal growth periods in Singapore. In contrast, oil price showed no significant notable impact on stock market volatility of target oil-exporting countries in either of the volatility regime. In light to these results, international investors and policy makers could benefit the risk management in relation to oil price fluctuation.

Glutathione and the redox control system trypanothione/trypanothione reductase are involved in the protection of Leishmania spp. against nitrosothiol-induced cytotoxicity

Glutathione is the major intracellular antioxidant thiol protecting mammalian cells against oxidative stress induced by oxygen- and nitrogen-derived reactive species. In trypanosomes and leishmanias, trypanothione plays a central role in parasite protection against mammalian host defence systems by recycling trypanothione disulphide by the enzyme trypanothione reductase. Although Kinetoplastida parasites lack glutathione reductase, they maintain significant levels of glutathione. The aim of this study was to use Leishmania donovani trypanothione reductase gene mutant clones and different Leishmania species to examine the role of these two individual thiol systems in the protection mechanism against S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a nitrogen-derived reactive species donor. We found that the resistance to SNAP of different species of Leishmania was inversely correlated with their glutathione concentration but not with their total low-molecular weight thiol content (about 0.18 nmol/10(7) parasites, regardless Leishmania species). The glutathione concentration in L. amazonensis, L. donovani, L. major, and L. braziliensis were 0.12, 0.10, 0.08, and 0.04 nmol/10(7) parasites, respectively. L. amazonensis, that have a higher level of glutathione, were less susceptible to SNAP (30 and 100 µM). The IC50 values of SNAP determined to L. amazonensis, L. donovani, L. major, and L. braziliensis were 207.8, 188.5, 160.9, and 83 µM, respectively. We also observed that L. donovani mutants carrying only one trypanothione reductase allele had a decreased capacity to survive (~40%) in the presence of SNAP (30-150 µM). In conclusion, the present data suggest that both antioxidant systems, glutathione and trypanothione/trypanothione reductase, participate in protection of Leishmania against the toxic effect of nitrogen-derived reactive species.

Antimicrobial activity of the essential oil from Lippia sidoides, carvacrol and thymol against oral pathogens

Dental caries and periodontal disease are associated with oral pathogens. Several plant derivatives have been evaluated with respect to their antimicrobial effects against such pathogenic microorganisms. Lippia sidoides Cham (Verbenaceae), popularly known as "Alecrim-pimenta" is a typical shrub commonly found in the Northeast of Brazil. Many plant species belonging to the genus Lippia yield very fragrant essential oils of potential economic value which are used by the industry for the commercial production of perfumes, creams, lotions, and deodorants. Since the leaves of L. sidoides are also extensively used in popular medicine for the treatment of skin wounds and cuts, the objective of the present study was to evaluate the composition and antimicrobial activity of L. sidoides essential oil. The essential oil was obtained by hydro-distillation and analyzed by GC-MS. Twelve compounds were characterized, having as major constituents thymol (56.7%) and carvacrol (16.7%). The antimicrobial activity of the oil and the major components was tested against cariogenic bacterial species of the genus Streptococcus as well as Candida albicans using the broth dilution and disk diffusion assays. The essential oil and its major components thymol and carvacrol exhibited potent antimicrobial activity against the organisms tested with minimum inhibitory concentrations ranging from 0.625 to 10.0 mg/mL. The most sensitive microorganisms were C. albicans and Streptococcus mutans. The essential oil of L. sidoides and its major components exert promising antimicrobial effects against oral pathogens and suggest its likely usefulness to combat oral microbial growth.

The Forecast Performance of Model-Free Implied Volatility: Evidence from DAX Index Options

Volatility has a central role in various theoretical and practical applications in financial markets. These include the applications related to portfolio theory, derivatives pricing and financial risk management. Both theoretical and practical applications require good estimates and forecasts for the asset return volatility. The goal of this study is to examine the forecast performance of one of the more recent volatility measures, model-free implied volatility. Model-free implied volatility is extracted from the prices in the option markets, and it aims to provide an unbiased estimate for the market’s expectation on the future level of volatility. Since it is extracted from the option prices, model-free implied volatility should contain all the relevant information that the market participants have. Moreover, model-free implied volatility requires less restrictive assumptions than the commonly used Black-Scholes implied volatility, which means that it should be less biased estimate for the market’s expectations. Therefore, it should also be a better forecast for the future volatility. The forecast performance of model-free implied volatility is evaluated by comparing it to the forecast performance of Black-Scholes implied volatility and GARCH(1,1) forecast. Weekly forecasts for six years period were calculated for the forecasted variable, German stock market index DAX. The data consisted of price observations for DAX index options. The forecast performance was measured using econometric methods, which aimed to capture the biasedness, accuracy and the information content of the forecasts. The results of the study suggest that the forecast performance of model-free implied volatility is superior to forecast performance of GARCH(1,1) forecast. However, the results also suggest that the forecast performance of model-free implied volatility is not as good as the forecast performance of Black-Scholes implied volatility, which is against the hypotheses based on theory. The results of this study are consistent with the majority of prior research on the subject.

Criminal liability of canadian corporations for international crimes

Ce mémoire porte sur la responsabilité pénale des entreprises canadiennes pour des crimes internationaux commis en partie ou entièrement à l’étranger. Dans la première partie, nous montrons que les premiers développements sur la reconnaissance de la responsabilité criminelle d’entités collectives devant les tribunaux militaires établis après la deuxième guerre mondiale n’ont pas été retenus par les tribunaux ad hoc des Nations Unies et par la Cour pénale internationale. En effet, la compétence personnelle de ces tribunaux permet uniquement de contraindre des personnes physiques pour des crimes internationaux. Dans la deuxième partie, nous offrons des exemples concrets illustrant que des entreprises canadiennes ont joué dans le passé et peuvent jouer un rôle criminel de soutien lors de guerres civiles et de conflits armés au cours desquels se commettent des crimes internationaux. Nous montrons que le droit pénal canadien permet d’attribuer une responsabilité criminelle à une organisation (compagnie ou groupe non incorporé) pour des crimes de droit commun commis au Canada, comme auteur réel ou comme complice. Nous soutenons qu’il est également possible de poursuivre des entreprises canadiennes devant les tribunaux canadiens pour des crimes internationaux commis à l’extérieur du Canada, en vertu de la Loi canadienne sur les crimes contre l’humanité et les crimes de guerre, du principe de la compétence universelle et des règles de droit commun. Bref, le Canada est doté d’instruments juridiques et judiciaires pour poursuivre des entreprises soupçonnées de crimes internationaux commis à l’étranger et peut ainsi mettre un terme à leur état indésirable d’impunité.