A semiparametric response surface model for assessing drug interaction

Summary .   When multiple drugs are administered simultaneously, investigators are often interested in assessing whether the drug combinations are synergistic, additive, or antagonistic. Existing response surface models are not adequate to capture the complex patterns of drug interactions. We propose a two-component semiparametric response surface model with a parametric function to describe the additive effect of a combination dose and a nonparametric function to capture the departure from the additive effect. The nonparametric function is estimated using the technique developed in thin plate splines, and the pointwise bootstrap confidence interval for this function is constructed. The proposed semiparametric model offers an effective way of formulating the additive effect while allowing the flexibility of modeling a departure from additivity. Example and simulations are given to illustrate that the proposed model provides an excellent estimation for different patterns of interactions between two drugs.     

A novel method for the estimation of the relative importance of breeds in order to conserve the total genetic variance

The need for conservation of farm animal genetic resources is widely accepted. A key question is the choice of breeds to be conserved. For this purpose, a core set of breeds was introduced in that the total genetic variance of a hypothetical quantitative trait was maximised (MVT core set). For each breed the relative contribution to the core set was estimated and the breeds were ranked for conservation priority according to their relative contribution. The method was based on average kinships between and within breeds and these can be estimated using genetic marker data. The method was compared to a recently published core set method that maximises the variance of a hypothetical population that could be obtained by interbreeding the conserved breeds (MVO core set). The results show that the MVT (MVO) core set favours breeds with a high (low) within breed kinship that are not related to other breeds. Following this, the MVT core set method suggests conserving breeds that show a large difference in the respective population mean of a hypothetical quantitative trait. This maximises the speed of achieving selection response for this hypothetical selection direction. Additionally, bootstrap based methods for the estimation of the breed''s contribution to the core sets were introduced, substantially improving the accuracy of the contribution estimates.     

Comparison of cytotoxic activities betweenin vitro and field grown plants ofTyphonium flagelliforme (Lodd.) blume

Anin vitro cytotoxicity screening of theTyphonium flagelliforme extracts indicated high cytotoxicity effect on human lung carcinoma NCl-H23 cells and human mammary gland carcinoma T-47D cells, but the extracts were not active on human liver carcinoma HepG2 cells. NCl-H23 cells were more susceptible toT. flagelliforme extracts than T-47D cells. EDP₅₀ values of the hexane fractions of the mature plant and thein vitro plantlet ofT. flagelliforme on NCl-H23 cells were less than 2 μg/mL Extract from the mature plant was relatively more cytotoxic than the one fromin vitro plantlet except for the hexane fraction. The chloroform and butanol fraction of the mature plant had higher cytotoxicity effect than the fraction fromin vitro plantlet on NCl-H23 cells. All the 3 fractions (hexane, chloroform, and butanol) of the mature plant exhibited higher cytotoxicity effects on human mammary gland carcinoma T-47D cells than the 3 fractions ofin vitro plantlet. However, the human liver carcinoma cells were resistant toT. flagelliforme extracts except for higher concentration of hexane fractions of both the mature and thein vitro plants and the chloroform fraction of the mature plant. Micropropagated plantlets ofT. flagelliforme could hence be used as herbal materials for the treatment of human lung and breast cancers.     

Estimating plant responses to climate by direct gradient analysis and geographic distribution analysis

We characterised the climatic behaviour of 53 woody species in terms of the climatic factors that play the main role in controlling species distribution in the study area. Floristic and climatic data were obtained from 150 stands in sites under climatic control (i.e. eu-climatopes). The sampling strategy used allowed a reliable match between floristic and climatic observations. Different methods of frequency analysis and goodness-of-fit tests were used to identify associations between species occurrence and climatic characteristics. The species' responses were summarised by statistics describing ecological preferences and amplitudes, and species were grouped accordingly. A Gaussian response model was fitted to the abundance data along the main climatic gradients for selected species and response surfaces were derived by spatial analysis for a set of indicator species. Frequency analysis methods detected 42 indicator taxa for the Baudiere's Qe drought index, and lower numbers, 34 and 22, respectively, for the mean minimum coldest-month temperature and the daily temperature range in the coldest month. Goodness-of-fit tests revealed a lower number of ecological profiles with statistically significant deviations from equidistribution. We discuss the relative performance of the different methods and suggest that the combined use of statistical tests and frequency analyses may improve estimation of the environmental requirements of species. We also recommend using the species' responses to key environmental factors as reliable criteria in the definition of plant functional types. This revised version was published online in August 2006 with corrections to the Cover Date.     

What do the biodiversity experiments tell us about consequences of plant species loss in the real world?

Experiments where the diversity of species assemblage is manipulated are sometimes used to predict the consequences of species loss from real communities. However, their design corresponds to a random selection of the lost species. There are three main factors that limit species richness: harshness of the environment, competitive exclusion, and species pool limitation. Species loss is usually caused by increasing effects of these factors. In the first two cases, the species that are excluded are highly non-random subsets of the potential species set, and consequently, the predictions based on random selection of the lost species might be misleading. The data show that the least productive species are those being recently excluded from temperate grasslands and consequently, species loss is not connected with decline of productivity. The concurrent species loss in many communities, however, means also a reduction of the available diaspore pool on a landscape scale, and could result in increased species pool limitation in other communities.     

Landscape patterns of indicator plants for soil acidity in the Bavarian Alps

Aim Electronic distribution atlases and lists of ecological indicator values are becoming important tools in plant geography. In this contribution, we combine a geographical and an ecological data bank, and map out patterns of indicator value spectra (instead of single or average values) across a physiographically complex landscape. For our study, we select indicators of soil pH and carbonate content as key environmental factors that strongly affect overall plant diversity patterns in the temperate zone. Our goal is to relate the distribution and diversity of plant groups that are indicators of soil pH and carbonate content to environmental controls at the landscape‐scale, and thus contribute to a causal understanding of species pools. Location We studied the Bavarian Alps, which represent the German portion of the Northern Alps. Methods Based on the existing floristic survey, we calculated relative frequencies of nine classes of indicator plants for soil pH and carbonate content in grid cells. The resulting attribute matrix (cells by indicator class frequencies) was subjected to principal components analysis and to k‐means clustering. Results were compared and mapped out in the grid array of the whole region, resulting in continuous and discrete representations of species pool structure. We used a geographical information system to derive physiographical landscape properties from a geological map and a digital elevation model, and analysed their statistical relationship with the shapes of indicator spectra. Results and Main conclusions Averages of indicator values for soil pH and carbonate content follow the geological structure quite closely. Surprisingly, the diversity of indicator plant groups does not appear to be a function of geological or topographic heterogeneity. Rather, it seems to be related to areas of high elevation with uniform geology. The effect is a matter of additional acidophytes in high mountain areas and, in the high calcareous Alps, extreme calciphytes, while species with intermediate requirements are rarer than usual. For explanation, we suggest two facts: (1) a frequent lack of mature soils at high elevations and (2) particularities in soil genetic processes occurring under the harsh climatic conditions of high mountains.     

Public Health Perspectives on Dioxin Risks: Two Decades of Evaluations

The paper provides an overview of approaches to dioxin risk assessment employed by different agencies worldwide over the past 20 years. Our insights regarding understanding of the toxicity of dioxins have advanced tremendously in recent years; however, important data gaps still exist. More information on topics such as mechanism of interaction, effects at low levels of exposure, interspecies differences, and sensitive populations is needed. Some differences exist between USEPA's approach to dioxin assessment and that of other health organizations around the world. The authors conclude that USEPA's reassessment of dioxin and related compounds may place too much confidence in the ability to accurately predict cancer risks at low doses. Further, it is important to derive health-based guidance values for noncancer end points especially in accordance with emerging reports that reproductive and developmental end points are very sensitive to dioxins. A worldwide convergence on the health assessment value being around 1 to 4?pg/kg/day is noted.     

Urban biodiversity in local newspapers: a historical perspective

Due to rapid urbanization the conservation and values of urban wildlife are becoming increasingly important study objects. Unfortunately, the lack of historical data makes it difficult to assess the effects of long-term urban land-use changes and human attitudes on local biodiversity. In this paper we show that old newspapers may in some cases provide useful historical data on both urban wildlife and local attitudes towards it. In the city of Turku, southwest Finland, the leading newspaper published 316 observations or reports on local urban mammals, birds and reptiles in 1890–1920, and in addition to these a lot of information on contemporary attitudes towards urban wildlife. At least 12 species of noncaptive mammals, 32 species of birds, and three reptile species were documented in newspapers. The newspaper data seem fairly reliable, and provide valuable information on the development of urban biodiversity. In the study period animals visiting urban areas were often persecuted, in which both adults and children (mainly schoolboys) participated actively. Birds were persecuted less frequently than mammals or reptiles. Some bird species, especially 'song-birds', were actively supported by winter-feeding and by constructing nest-boxes. According to newspapers local people were interested in local biodiversity, especially on phenological events, and benefited from it by getting esthetic pleasure, pet animals, and information on seasonal changes.     

Normal serum biochemical and hematological parameters in Macaca fascicularis.

The effects of age, sex, pregnancy, were analyzed and data from fasted and fed animals were compared in a population of cynomolgus macaques. No significant sex effects were observed for biochemical values and no changes were found in male hematological parameters in relation to age. Most values of females during pregnancy were within normal ranges. Comparison between fed and fasted animals showed that several biochemical parameters (e.g., ALT, glucose, CPK, LDH) and several hematological parameters (e.g., monocytes, eosinophils, basophils, hemoglobin, MCV, MCHC, and MCH) were affected by food intake.