Pharmacokinetic (PK)-based dosage individualization of imatinib: evaluation of efficiency and clinical usefulness

Background: Retrospective analyses suggest that personalized PK-based dosage might be useful for imatinib, as treatment response correlates with trough concentrations (Cmin) in cancer patients. Our objectives were to improve the interpretation of randomly measured concentrations and to confirm its efficiency before evaluating the clinical usefulness of systematic PK-based dosage in chronic myeloid leukemia patients. Methods and Results: A Bayesian method was validated for the prediction of individual Cmin on the basis of a single random observation, and was applied in a prospective multicenter randomized controlled clinical trial. 28 out of 56 patients were enrolled in the systematic dosage individualization arm and had 44 follow-up visits (their clinical follow-up is ongoing). PK-dose-adjustments were proposed in 39% having predicted Cmin significantly away from the target (1000 ng/ml). Recommendations were taken up by physicians in 57%, patients were considered non-compliant in 27%. Median Cmin at study inclusion was 754 ng/ml and differed significantly from the target (p=0.02, Wilcoxon test). On follow-up, Cmin was 984 ng/ml (p=0.82) in the compliant group. CV decreased from 46% to 27% (p=0.02, F-test). Conclusion: PK-based (Bayesian) dosage adjustment is able to bring individual drug exposure closer to a given therapeutic target. Its influence on therapeutic response remains to be evaluated.

The Design and efficiency of loyalty rewards

The goal of this paper is to reexamine the optimal design and efficiency of loyalty rewards in markets for final consumption goods. While the literature has emphasized the role of loyalty rewards as endogenous switching costs (which distort the efficient allocation of consumers), in this paper I analyze the ability of alternative designs to foster consumer participation and increase total surplus. First, the efficiency of loyalty rewards depend on their specific design. A commitment to the price of repeat purchases can involve substantial efficiency gains by reducing price-cost margins. However, discount policies imply higher future regular prices and are likely to reduce total surplus. Second, firms may prefer to set up inefficient rewards (discounts), especially in those circumstances where a commitment to the price of repeat purchases triggers Coasian dynamics.

Oil price shocks and labor market fluctuations

We examine the impact of real oil price shocks on labor market flows in the U.S. We first use smooth transition regression (STR) models to investigate to what extent oil prices can be considered as a driving force of labor market fluctuations. Then we develop and calibrate a modified version of Pissarides' (2000) model with energy costs, which we simulate in response to shocks mimicking the behavior of the actual oil price shocks. We find that (i) these shocks are an important driving force of job market flows; (ii) the job finding probability is the main transmission mechanism of such shocks; and (iii) they bring a new amplification mechanism for the volatility and should thus be seen as complementary of labor productivity shocks. Overall we conclude that shocks in oil prices cannot be neglected in explaining cyclical labor adjustments in the U.S.

Investor protection and income inequality: risk sharing vs risk taking

This paper studies the relationship between investor protection, entrepreneurial risk taking and income inequality. In the presence of market frictions, better protection makes investors more willing to take on entrepreneurial risk when lending to firms, thereby improving the degree of risk sharing between financiers and entrepreneurs. On the other hand, by increasing risk sharing, investor protection also induces more firms to undertake risky projects. By increasing entrepreneurial risk taking, it raises income dispersion. By reducing the risk faced by entrepreneurs, it reduces income volatility. As a result, investor protection raises income inequality to the extent that it fosters risk taking, while it reduces it for a given level of risk taking. Empirical evidence from a panel of forty-five countries spanning the period 1976-2000 supports the predictions of the model.

Stability and change in party preferences.

This article analyses stability and volatility of party preferences using data from the Swiss Household-Panel (SHP), which, for the first time, allow studying transitions and stability of voters over several years in Switzerland. Analyses cover the years 1999- 2007 and systematically distinguish changes between party blocks and changes within party blocks. The first part looks at different patterns of change, which show relatively high volatility. The second part tests several theories on causes of such changes applying a multinomial random-effects model. Results show that party preferences stabilise with their duration and with age and that the electoral cycle, political sophistication, socio-structural predispositions, the household-context as well as party size and the number of parties each explain part of electoral volatility. Different results for withinand between party-block changes underlie the importance of that differentiation.

Accounting conservatism and firm investment efficiency

Conservatism, through the timelier recognition of losses in the income statement, is expected to increase firm investment efficiency through three main channels: (1) by decreasing the adverse effect of information asymmetries between outside equity holders and managers, facilitating the monitoring of managerial investment decisions; (2) by increasing managerial incentives to abandon poorly performing projects earlier and to undertake fewer negative net present-value investments; and (3) by facilitating the access to external financing at lower cost. Using a large US sample for the period 1990-2007 we find a negative association between conservatism and measures of over- and under- investment, and a positive association between conservatism and future profitability. This is consistent with firms reporting more conservative numbers investing more efficiently and in more profitable projects. Our results add to a growing stream of literature suggesting that eliminating conservatism from accounting regulatory frameworks may lead to undesirable economic consequences.

Detection of Rotavirus in Sewage and Creek Water: Efficiency of the Concentration Method

Simian rotavirus SA-11, experimentally seeded, was recovered from raw domestic sewage by a two-step concentration procedure, using filtration through a positively charged microporous filter (Zeta Plus 60 S) followed by ultracentrifugation, effecting an 8,000-fold concentration. By this method, a mean recovery of 81% ± 7.5 of the SA-11 virus, was achieved

Origins and efficiency of the electric industry regulation in Spain, 1910-1936

The aim of this paper is to discover the origins of utility regulation in Spain, and to analyse, from a microeconomic perspective, its characteristics and the impact of regulation on consumers and utilities. Madrid and the Madrilenian utilities are taken as a case study. The electric industry in the period studied was a natural monopoly2. Each of the three phases of production, generation, transmission and distribution, had natural monopoly characteristics. Therefore, the most efficient form to generate, transmit and distribute electricity was the monopoly because one firm can produce a quantity at a lower cost than the sum of costs incurred by two or more firms. A problem arises because when a firm is the single provider it can charge prices above the marginal cost, at monopoly prices. When a monopolist reduces the quantity produced, price increases, causing the consumer to demand less than the economic efficiency level, incurring a loss of consumer surplus. The loss of the consumer surplus is not completely gained by the monopolist, causing a loss of social surplus, a deadweight loss. The main objective of regulation is going to be to reduce to a minimum the deadweight loss. Regulation is also needed because when the monopolist fixes prices at marginal cost equal marginal revenue there would be an incentive for firms to enter the market creating inefficiency. The Madrilenian industry has been chosen because of the availability of statistical information on costs and production. The complex industry structure and the atomised demand add interest to the analysis. This study will also provide some light on the tariff regulation of the period which has been poorly studied and will complement the literature on the US electric utilities regulation where a different type of regulation was implemented.

The effects of uncertainty about countries' compliance with the Stability and Growth Pact

The Stability and Growth Pact (SGP) was established to govern discretionary fiscal policy in the European Monetary Union. This article studies the effects created when there is uncertainty about the members’ commitment to respecting the established deficit limits in the SGP. We will show that, even if countries respect the SGP deficit ceiling, the presence of uncertainty about their compliance will bring about higher volatility in key economic variables, which could, in turn, affect unemployment and growth negatively. This finding shows that it is important to reduce uncertainty about the members’ commitment towards the SGP. Keywords: fiscal policy rules, monetary union, Stability and Growth Pact, uncertainty, commitment. JEL No.: E63, F55, H62, H87

Evaluation of subsidies programs to sell green cars: Impact on prices, quantities and efficiency

During the recent period of economic crisis, many countries have introduced scrappage schemes to boost the sale and production of vehicles, particularly of vehicles designed to pollute less. In this paper, we analyze the impact of a particular scheme in Spain (Plan2000E) on vehicle prices and sales figures as well as on the reduction of polluting emissions from vehicles on the road. We considered the introduction of this scheme an exogenous policy change and because we could distinguish a control group (non-subsidized vehicles) and a treatment group (subsidized vehicles), before and after the introduction of the Plan, we were able to carry out our analysis as a quasi-natural experiment. Our study reveals that manufacturers increased vehicle prices by the same amount they were granted through the Plan (1,000 €). In terms of sales, econometric estimations revealed an increase of almost 5% as a result of the implementation of the Plan. With regard to environmental efficiency, we compared the costs (inverted quantity of money) and the benefits of the program (reductions in polluting emissions and additional fiscal revenues) and found that the Plan would only be beneficial if it boosted demand by at least 30%.

Risk Factors for Human T Cell Lymphotropic Virus Type I among Injecting Drug Users in Northeast Brazil: Possibly Greater Efficiency of Male to Female Transmission

It was observed in the city of Salvador, State of Bahia, the highest seroprevalence of human T cell lymphotropic virus type 1 (HTLV-I) infection in Brazil as demonstrated by national wide blood bank surveys. In this paper, we report results of an investigation of drug use and sexual behavior associated with HTLV-I infection among male and female injecting drug users (IDUs) in Salvador. A cross sectional study was conducted in the Historical District of Salvador from 1994-1996 (Projeto Brasil-Salvador) and 216 asymptomatic IDUs were selected using the snowball contact technique. Blood samples were collected for serological assays. Sera were screened for human immunodeficiency virus (HIV-1/2) and HTLV-I/II antibodies by ELISA and confirmed by Western blot. The overall prevalence of HTLV-I/II was 35.2% (76/216). The seroprevalence of HTLV-I, HTLV-II and HIV-1 was for males 22%, 11.3% and 44.1% and for females 46.2%, 10.3% and 74.4% respectively. HTLV-I was identified in 72.4% of HTLV positive IDUs. Variables which were significantly associated with HTLV-I infection among males included needle sharing practices, duration of injecting drug use, HIV-1 seropositivity and syphilis. Among women, duration of injecting drug use and syphilis were strongly associated with HTLV-I infection. Multivariate analysis did not change the direction of these associations. Sexual intercourse might play a more important role in HTLV-I infection among women than in men.

Preliminary estimates and forecasts of the population prevalence of self reported of hypertension, of ischaemic heart disease and stroke in the Republic of Ireland from 2005 - 2015

Ireland and Northern Ireland’s Population Health Observatory (INIsPHO) recently published estimates of the population prevalence of diabetes in 2005 and forecasts to 2010 and 2015 for the island of Ireland, at the national and sub-national levels. These estimates are based the PBS Model developed by York and Humber Public Health Observatory (YHPHO), Brent NHS Trust and the School of Health and Related Research (ScHARR).The Department of Health and Children (DoHC) has requested additional estimates and forecasts for hypertension.This paper outlines the results from preliminary work from the initial steps towards a more systematic approach to monitoring the prevalence of other chronic diseases on the island.