Cost-effective experimental design to support modeling of concentration-response functions

Modeling concentration-response function became extremely popular in ecotoxicology during the last decade. Indeed, modeling allows determining the total response pattern of a given substance. However, reliable modeling is consuming in term of data, which is in contradiction with the current trend in ecotoxicology, which aims to reduce, for cost and ethical reasons, the number of data produced during an experiment. It is therefore crucial to determine experimental design in a cost-effective manner. In this paper, we propose to use the theory of locally D-optimal designs to determine the set of concentrations to be tested so that the parameters of the concentration-response function can be estimated with high precision. We illustrated this approach by determining the locally D-optimal designs to estimate the toxicity of the herbicide dinoseb on daphnids and algae. The results show that the number of concentrations to be tested is often equal to the number of parameters and often related to the their meaning, i.e. they are located close to the parameters. Furthermore, the results show that the locally D-optimal design often has the minimal number of support points and is not much sensitive to small changes in nominal values of the parameters. In order to reduce the experimental cost and the use of test organisms, especially in case of long-term studies, reliable nominal values may therefore be fixed based on prior knowledge and literature research instead of on preliminary experiments

Prediction of Infant Drug Exposure Through Breastfeeding: Population PK Modeling and Simulation of Fluoxetine Exposure.

The likelihood of significant exposure to drugs in infants through breast milk is poorly defined, given the difficulties of conducting pharmacokinetics (PK) studies. Using fluoxetine (FX) as an example, we conducted a proof-of-principle study applying population PK (popPK) modeling and simulation to estimate drug exposure in infants through breast milk. We simulated data for 1,000 mother-infant pairs, assuming conservatively that the FX clearance in an infant is 20% of the allometrically adjusted value in adults. The model-generated estimate of the milk-to-plasma ratio for FX (mean: 0.59) was consistent with those reported in other studies. The median infant-to-mother ratio of FX steady-state plasma concentrations predicted by the simulation was 8.5%. Although the disposition of the active metabolite, norfluoxetine, could not be modeled, popPK-informed simulation may be valid for other drugs, particularly those without active metabolites, thereby providing a practical alternative to conventional PK studies for exposure risk assessment in this population.

Transparency ratio in γ A -> η' A ' and the in-medium η ' width

The photoproduction of η′η′-mesons off different nuclei has been measured with the CBELSA/TAPS detector system for incident photon energies between 15002200 MeV. The transparency ratio has been deduced and compared to theoretical calculations describing the propagation of η′η′-mesons in nuclei. The comparison indicates a width of the η′η′-meson of the order of Γ=1525 MeVΓ=1525 MeV at ρ=ρ0ρ=ρ0 for an average momentum pη′=1050 MeV/cpη′=1050 MeV/c, at which the η′η′-meson is produced in the nuclear rest frame. The inelastic η′Nη′N cross section is estimated to be 310 mb. Parameterizing the photoproduction cross section of η′η′-mesons by σ(A)=σ0Aασ(A)=σ0Aα, a value of α=0.84±0.03α=0.84±0.03 has been deduced.

Comparison between artificial neural networks and maximum likelihood classification in digital soil mapping

Soil surveys are the main source of spatial information on soils and have a range of different applications, mainly in agriculture. The continuity of this activity has however been severely compromised, mainly due to a lack of governmental funding. The purpose of this study was to evaluate the feasibility of two different classifiers (artificial neural networks and a maximum likelihood algorithm) in the prediction of soil classes in the northwest of the state of Rio de Janeiro. Terrain attributes such as elevation, slope, aspect, plan curvature and compound topographic index (CTI) and indices of clay minerals, iron oxide and Normalized Difference Vegetation Index (NDVI), derived from Landsat 7 ETM+ sensor imagery, were used as discriminating variables. The two classifiers were trained and validated for each soil class using 300 and 150 samples respectively, representing the characteristics of these classes in terms of the discriminating variables. According to the statistical tests, the accuracy of the classifier based on artificial neural networks (ANNs) was greater than of the classic Maximum Likelihood Classifier (MLC). Comparing the results with 126 points of reference showed that the resulting ANN map (73.81 %) was superior to the MLC map (57.94 %). The main errors when using the two classifiers were caused by: a) the geological heterogeneity of the area coupled with problems related to the geological map; b) the depth of lithic contact and/or rock exposure, and c) problems with the environmental correlation model used due to the polygenetic nature of the soils. This study confirms that the use of terrain attributes together with remote sensing data by an ANN approach can be a tool to facilitate soil mapping in Brazil, primarily due to the availability of low-cost remote sensing data and the ease by which terrain attributes can be obtained.

Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study.

BACKGROUND: Poor tolerance and adverse drug reactions are main reasons for discontinuation of antiretroviral therapy (ART). Identifying predictors of ART discontinuation is a priority in HIV care. METHODS: A genetic association study in an observational cohort to evaluate the association of pharmacogenetic markers with time to treatment discontinuation during the first year of ART. Analysis included 577 treatment-naive individuals initiating tenofovir (n = 500) or abacavir (n = 77), with efavirenz (n = 272), lopinavir/ritonavir (n = 184), or atazanavir/ritonavir (n = 121). Genotyping included 23 genetic markers in 15 genes associated with toxicity or pharmacokinetics of the study medication. Rates of ART discontinuation between groups with and without genetic risk markers were assessed by survival analysis using Cox regression models. RESULTS: During the first year of ART, 190 individuals (33%) stopped 1 or more drugs. For efavirenz and atazanavir, individuals with genetic risk markers experienced higher discontinuation rates than individuals without (71.15% vs 28.10%, and 62.5% vs 14.6%, respectively). The efavirenz discontinuation hazard ratio (HR) was 3.14 (95% confidence interval (CI): 1.35-7.33, P = .008). The atazanavir discontinuation HR was 9.13 (95% CI: 3.38-24.69, P < .0001). CONCLUSIONS: Several pharmacogenetic markers identify individuals at risk for early treatment discontinuation. These markers should be considered for validation in the clinical setting.

Conviction Statistics as an Indicator of Crime Trends in Europe from 1990 to 2006

Convictions statistics were the first criminal statistics available in Europe during the nineteenth century. Their main weaknesses as crime measures and for comparative purposes were identified by Alphonse de Candolle in the 1830s. Currently, they are seldom used by comparative criminologists, although they provide a less valid but more reliable measure of crime and formal social control than police statistics. This article uses conviction statistics, compiled from the four editions of the European Sourcebook of Crime and Criminal Justice Statistics, to study the evolution of persons convicted in European countries from 1990 to 2006. Trends in persons convicted for six offences -intentional homicide, assault, rape, robbery, theft, and drug offences- and up to 26 European countries are analysed. These trends are established for the whole of Europe as well as for a cluster of Western European countries and a cluster of Central and Eastern European countries. The analyses show similarities between both regions of Europe at the beginning and at the end of the period under study. After a general increase of the rate of persons convicted in the early 1990s in the whole of Europe, trends followed different directions in Western and in Central and Eastern Europe. However, during the 2000s, it can be observed, throughout Europe, a certain stability of the rates of persons convicted for intentional homicides, accompanied by a general decrease of the rate of persons convicted for property offences, and an increase of the rate of those convicted for drug offences. The latter goes together with an increase of the rate of persons convicted for non lethal violent offences, which only reached some stability at the end of the time series. These trends show that there is no general crime drop in Europe. After a discussion of possible theoretical explanations, a multifactor model, inspired by opportunity-based theories, is proposed to explain the trends observed.

Divergent signal-to-noise ratio and stochastic resonance in monostable systems

We present a class of systems for which the signal-to-noise ratio always increases when increasing the noise and diverges at infinite noise level. This new phenomenon is a direct consequence of the existence of a scaling law for the signal-to-noise ratio and implies the appearance of stochastic resonance in some monostable systems. We outline applications of our results to a wide variety of systems pertaining to different scientific areas. Two particular examples are discussed in detail.

Socio-demographic and behavioural determinants of weight gain in the Swiss population.

BackgroundIn Switzerland, socio-demographic and behavioural factors are associated with obesity, but no study ever assessed their impact on weight gain using prospective data.MethodsData from 4,469 participants (53.0% women), aged 35 to 75 years at baseline and followed for 5.5 years. Weight gain was considered as a rate (kg/year) or as gaining ¿5 kg during the study period.ResultsRate of weight gain was lower among participants who were older (mean¿±¿standard deviation: 0.46¿±¿0.92, 0.33¿±¿0.88, 0.21¿±¿0.86 and 0.06¿±¿0.74 kg/year in participants aged [35-45[, [45-55[, [55¿65[and [65+ years, respectively, P<0.001); physically active (0.27¿±¿0.82 vs. 0.35¿±¿0.95 kg/year for sedentary, P¿<¿0.005) or living in a couple (0.29¿±¿0.84 vs. 0.35¿±¿0.96 kg/year for living single, P¿<¿0.05), and higher among current smokers (0.41¿±¿0.97, 0.26¿±¿0.84 and 0.29±0.85 kg/year for current, former and never smokers, respectively, p<0.001). These findings were further confirmed by multivariable analysis. Multivariable logistic regression showed that receiving social help, being a current smoker or obese increased the likelihood of gaining ¿5Kg: Odds ratio (OR) and 95% confidence interval (CI) 1.43 (1.16-1.77); 1.63 (1.35-1.95) and 1.95 (1.57-2.43), respectively, while living in couple or being physically active decreased the risk: 0.73 (0.62-0.86) and 0.72 (0.62-0.83), respectively. No association was found between weight gain and gender, being born in Switzerland or education.ConclusionsIn Switzerland, financial difficulties (indicated by receiving social help) and current smoking were associated with increases in body weight over a 5 years follow-up. Living in couple, being older or physically active were protective against weight gain.

Vital Statistics of Iowa, 2006

This publication is an historical recording of the most requested statistics on vital events and is a source of information that can be used in further analysis.

Vital Statistics of Iowa, 2007

This publication is an historical recording of the most requested statistics on vital events and is a source of information that can be used in further analysis.

Vital Statistics of Iowa, 2008

This publication is an historical recording of the most requested statistics on vital events and is a source of information that can be used in further analysis.

Vital Statistics of Iowa, 2009

This publication is an historical recording of the most requested statistics on vital events and is a source of information that can be used in further analysis.

Vital Statistics of Iowa, 2010

This publication is an historical recording of the most requested statistics on vital events and is a source of information that can be used in further analysis.