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Risk assessment of "down-the-drain" chemicals: search for a suitable model.

Legal and regulatory authorities around the world generally require that risk assessments are undertaken for the licensing of new and existing substances that present high risk to the environment or the human health. This applies to 'down-the-drain' chemicals that are usually found in household products, such as detergents, that are mainly discharged into rivers via sewer systems. However, the data available for these chemicals is often limited due to cost constraints: in particular, concentration time series for works effluent are generally unavailable, even load data for specific works is often scarce. Although a wide range of models are available, there is a general lack of knowledge on their suitability to model the fate of down-the-drain chemicals at the catchment scale. Several models are presented in this review. The models selected are: the Mackay models, EUSES, Mike 11, QUAL2E, TOMCAT and GREAT-ER. Various applications of these models were investigated to investigate their strength and weaknesses. It appears that, where the availability of data is limited, multimedia fate models such as the Mackay models and EUSES may best be applied to estimate the global risk within each media. However, for site-specific risk assessment the GREAT-ER in-stream water quality model was considered to be more appropriate for modelling down-the-drain chemicals, because it accounts for both spatial and temporal variability, while its data requirements are lower than for models such as Mike 11 and QUAL2E.

Environment↗

Histological and lipid peroxidation changes after administration of 2-acetylaminofluorene in a rat liver injury model following selective periportal and pericentral damage.

Administration of 2-acetylaminofluorene (2-AAF) suppresses mature hepatocyte proliferation following selective periportal or pericentral damage induced by allyl-alcohol (AA) or carbon tetrachloride (CCl(4)) administration, respectively. The aim of the present study was to investigate the histological and the lipid peroxidation changes after 2-AAF administration following CCl(4) and AA treatment. The study comprised 108 male Wistar rats that were assigned in four groups: Group A: a placebo pellet was implanted in their neck and on 7th day single dosages of AA and CCl(4) were administrated. Group B: 28-day release 2-AAF pellets (7 0mg-2.5mg per day) were implanted on the neck and on 7th day received a single dose of CCl(4). Group C: 28-day release 2-AAF pellets (70-2.5mg per day) were implanted on the neck and on 7th day a single dose of AA and CCl(4) were administrated. Group D: Sham-operated. Rats of each group were sacrificed on the 9th, 11th, 13th and 21st day. Liver tissue was obtained for histological examination and blood was collected for lipid peroxidation evaluation by measuring malondialdehyde (MDA) and for liver enzymes. On the 9th and 21st day the histological score of liver necrosis was statistically higher on Groups B and C compared to Group A. Concentration of MDA in Group A was significantly higher than in Groups B and C on 9th and 11th days. Transaminase levels, however, were significantly higher in Group A on 9th day compare to the Groups B and C. In conclusion, it appears that oxidative stress was correlated with liver necrosis and with liver regeneration. Suppression of liver regeneration after 2-AAF administration leads to lower malondialdehyde concentrations.

2-Acetylaminofluorene↗

Comparison of selected retention models in reversed-phase liquid chromatography.

Retention models are usually compared by how well the model equation fits retention data for one solute taken over a range of mobile phase compositions. Even when retention data for multiple solutes are used, the quality of the fit is often judged by the statistical goodness-of-fit alone. This study compared four different RPLC retention models, encompassing three distinct mathematical forms. Each model was fit to the retention data of multiple solutes and the sets of best-fit parameters were examined in terms of the underlying physico-chemical assumptions of the models. Next, for the linear and quadratic models, some of the model parameters were calculated a priori and the rest of the model parameters were then obtained in subsequent fittings. The sets of best-fit parameters obtained in this manner were more consistent with the underlying assumptions of these models than were the sets of parameters obtained entirely through regressions to the experimental data. Thus, the extraction of parameters by fitting a model to the retention data of a single solute may result in unreliable values for those parameters, even in the case of a fit that would be considered good when judged by conventional statistical criteria. That is, although parameters extracted in such a fashion may be suitable for optimization or similar uses, they may not be suitable for determining the appropriateness of the underlying assumptions of retention models.

Chromatography, Liquid↗

Local resource competition and the evolution of male-biased sex ratios.

In many mammalian species, maturing males disperse from their natal groups, while females remain near their places of birth. If sources are limited locally, related females may be forced to compete with one another for access to resources, while mature males will compete primarily with unrelated individuals in non-natal groups. Clark (1978) suggested that under such circumstances the extent of competition among females could be reduced if females uniformly skewed the sex ratio of their offspring in favor of males. Skewed secondary sex ratios and investment patterns in galagos and red deer appear to be consistent with this hypothesis. Several authors have recently demonstrated that the evolution of skewed sex ratios may be influenced by population structure, and Wilson & Colwell (1981) have shown that male-biased sex ratios can evolve in structured haplodiploid populations. Here, I construct an intrademic group selection model to simulate the effects of density-dependent mortality upon diploid populations structured much as Clark describes: males disperse, females remain near their female relatives, and local resource competition limits the size of local groups. The results confirm that male-biased sex ratios can evolve in a diploid species, even when groups are large and the skew in sex ratio is substantial.

Alleles↗

Evolutionarily stable strategies of mutual help between relatives having unequal fertilities.

The evolutionarily stable strategy of mutual help between relatives having unequal fertilities is studied in a kin selection model, which also takes into account competition between kins and the possibility of reciprocation. It turns out that competition and reciprocation can establish ESSs which are completely different from those expected by Hamilton's basic theory.

Altruism↗

Modeling and forecasting monthly patient volume at a primary health care clinic using univariate time-series analysis.

Two univariate time-series analysis methods have been used to model and forecast the monthly patient volume at the family and community medicine primary health care clinic of King Faisal University, Al-Khobar, Saudi Arabia. Models were based on nine years of data and forecasts made for 2 years. The optimum ARIMA model selected is an autoregressive model of the fourth order operating on the data after differencing twice at the nonseasonal level and once at the seasonal level. It gives mean and maximum absolute percentage errors of 1.86 and 4.23%, respectively, over the forecasting interval. A much simpler method based on extrapolating the growth curve of the annual means of the patient volume using a polynomial fit gives the better figures of 0.55 and 1.17%, respectively. This is due to the fairly regular nature of the data and the lack of strong random components that require ARIMA processes for modeling.

Ambulatory Care↗

Serotonin produces an enhanced outward current recorded at rat dorsal lateral septal neurons from the Flinders Sensitive Line of rats, a genetically-selected animal model of depression.

Abnormalities in serotonin (5-HT), serotonin receptors, and serotonergic neurons have been reported in studies of brains from patients diagnosed clinically with depression. In this study, we examined a known cellular function of 5-HT(1A) receptor activation in dorsolateral septal nucleus (DLSN) neurons, namely, a concentration dependent 5-HT-induced outward current, and compared basic neuronal membrane properties and activities of DLSN neurons from two known genetic lines of rats. As compared to "control" rats (Flinders Resistant Line, FRL), DLSN neurons from Flinders Sensitive Line of rats (FSL) did not exhibit significant differences in resting membrane potential, membrane input resistance, or changes in typical spontaneous inhibitory or excitatory post-synaptic currents. FSL-rats exhibit a depressive phenotype and have been suggested to be rats with a genetic susceptibility to exhibit depressive behaviors. Exogenous application of 5-HT resulted in expected concentration-dependent outward currents; however, the amplitudes of these currents were enhanced significantly in 50% of DLSN neurons recorded from FSL rats compared to similar results recorded from FRL rats. Our results suggest that within a particular population of DLSN neurons from rats exhibiting a known phenotype of depression a post-synaptic 5-HT(1A) receptor is functionally hyper-responsive compared to controls.

Action Potentials↗

Pulmonary collectins selectively permeabilize model bacterial membranes containing rough lipopolysaccharide.

We have reported that Gram-negative organisms decorated with rough lipopolysaccharide (LPS) are particularly susceptible to the direct antimicrobial actions of the pulmonary collectins, surfactant proteins A (SP-A) and D (SP-D). In this study, we examined the lipid and LPS components required for the permeabilizing effects of the collectins on model bacterial membranes. Liposomes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), with or without rough Escherichia coli LPS (J5), smooth E. coli LPS (B5), or cholesterol, were loaded with self-quenching probes and exposed to native or oxidatively modified SP-A. Fluorescence that resulted from permeabilization of liposomes and diffusion of dyes was assessed by microscopy or fluorimetry. Human SP-A and melittin increased the permeability of J5 LPS/POPE liposomes, but not B5 LPS/POPE liposomes or control (POPE only) liposomes. At a human SP-A concentration of 100 microg/mL, the permeability of the J5 LPS/POPE membranes increased 4.4-fold (p < 0.02) compared to the control with no added SP-A. Rat SP-A and SP-D also permeabilized the J5-containing liposomes. Incorporation of cholesterol into J5 LPS/POPE liposomes at a POPE:cholesterol molar ratio of 1:0.15 blocked human SP-A or melittin-induced permeability (p < 0.05) compared to cholesterol-free liposomes. Exposure of human SP-A to surfactant lipid peroxidation blocked the permeabilizing activity of the protein. We conclude that SP-A permeabilizes phospholipid membranes in an LPS-dependent and rough LPS-specific manner, that the effect is neither SP-A- nor species-specific, and that oxidative damage to SP-A abolishes its membrane destabilizing properties. Incorporation of cholesterol into the membrane enhances resistance to permeabilization by SP-A, most likely by increasing the packing density and membrane rigidity.

Animals↗

Supervised self-organizing maps in drug discovery. 2. Improvements in descriptor selection and model validation.

The modeling of nonlinear descriptor-target relationships is a topic of considerable interest in drug discovery. We, herein, continue reporting the use of the self-organizing map-a nonlinear, topology-preserving pattern recognition technique that exhibits considerable promise in modeling and decoding these relationships. Since simulated annealing is an efficient tool for solving optimization problems, we combined the supervised self-organizing map with simulated annealing to build high-quality, highly predictive quantitative structure-activity/property relationship models. This technique was applied to six data sets representing a variety of biological endpoints. Since a high statistical correlation in the training set does not indicate a highly predictive model, the quality of all the models was confirmed by withholding a portion of each data set for external validation. Finally, we introduce new cross-validation and dynamic partitioning techniques to address model overfitting and assessment.

Algorithms↗

On the maximum spreading diameter of impacting droplets on well-prepared solid surfaces.

This paper presents a systematic study of liquid droplet impact on three polymer surfaces: poly(methyl methacrylate), poly(methyl methacrylate/n-butyl methacrylate), and poly(n-butyl methacrylate). Changing from one surface to the next represents an incremental variation in solid surface tensions of 5-6 mJ/m2. These surfaces were prepared through careful experimental procedures that were used for the determination of solid surface tensions from contact angles. Our data for the maximum spreading diameter of water and formamide impacting on these surfaces were compared with those predicted from literature models. Of the models selected, we modified the model of Pasandideh-Fard et al. [Phys. Fluids 1996, 8, 650] and the results yielded a least error of only 5.09 +/- 5.05% in the determination of the maximum spreading diameter. The improved model was also compared with literature data, and good agreement was found. Of course, any such comparisons would rely on accurate experimental impact dynamics data on carefully prepared surfaces.

Journal Article↗

"Hybrid" synapses formed by foreign innervation of parasympathetic neurons: a model for selectivity during competitive reinnervation.

Selectivity of synapse formation after nerve regeneration was tested in the parasympathetic cardiac ganglion of frogs (Rana pipiens). First, we tested the ability of somatic motor axons to establish synaptic connections with denervated ganglion cells by implanting the hypoglossus nerve into the vagotomized heart. After several weeks, stimulation of the implanted hypoglossus mediated a parasympathetic-like inhibition of the heart rate, and synaptic responses produced by hypoglossal stimulation were recorded intracellularly in ganglion cells. Light and electron microscopy indicated that implanted hypoglossal nerve terminals contacted parasympathetic ganglion cells only on their axons and not on the cell body (where most vagal synapses are found in control animals). Second, we tested whether regenerating vagal preganglionic axons would complete with foreign (hypoglossal) terminals for innervation of cardiac ganglion cells. We allowed the vagus nerve to regenerate in animals in which the implanted hypoglossus had established functional contacts with the cardiac ganglion. Vagal axons were able to reinnervate the heart and reestablish synaptic connections on the cell bodies of ganglion cells. Furthermore, functional transmission at the foriegn (hypoglossal) terminals disappeared concomitant with vagal reinnervation.

Animals↗

Complex dynamics of multilocus systems subjected to cyclical selection.

Earlier we have shown that oscillations with a long period ("supercycles") may arise in two-locus systems experiencing cyclical selection with a short period. However, this mode of complex limiting behavior appeared to be possible for narrow ranges of parameters. Here we demonstrate that a multilocus system subjected to stabilizing selection with cyclically moving optimum can generate ubiquitous complex limiting behavior including supercycles, T-cycles, and chaotic-like phenomena. This mode of multilocus dynamics far exceeds the potential attainable under ordinary selection models resulting in simple behavior. It may represent a novel evolutionary mechanism increasing genetic diversity over long-term time periods.

Biological Evolution↗

Interference from multi-dimensional objects during feature and conjunction discriminations.

Feature discrimination performance within an attended object and interference from irrelevant, multi-dimensional objects (distractors) were examined in a two-choice, response compatibility paradigm. Results showed that the amount of interference by multi-dimensional distractors was dependent on three factors: (1) the discriminability of the incompatible, task-relevant distractor features; (2) the number of incompatible, task-relevant distractor features; and (3) whether the task-relevant, incompatible features matched the task goals. The most interesting finding was that additive priming effects were found for multiple, task-relevant features that matched the task goals, whether these features were present in the attended object or in the ignored object. Models that assume that each task-relevant feature primes its corresponding decision/response asynchronously and that this priming is combined to meet a decision/response criterion (at least when attended) can account for distractor interference during conjunction discriminations. Implications of these findings for feature integration models, template models, and a response selection model are discussed.

Adult↗

Groundwater contamination downstream of a contaminant penetration site. II. Horizontal penetration of the contaminant plume.

Part I of this study (Rubin, H.; Buddemeier, R.W. Groundwater Contamination Downstream of a Contaminant Penetration Site Part 1: Extension-Expansion of the Contaminant Plume. J. of Environmental Science and Health Part A (in press).) addressed cases, in which a comparatively thin contaminated region represented by boundary layers (BLs) developed within the freshwater aquifer close to contaminant penetration site. However, at some distance downstream from the penetration site, the top of the contaminant plume reaches the top or bottom of the aquifer. This is the location of the "attachment point," which comprises the entrance cross section of the domain evaluated by the present part of the study. It is shown that downstream from the entrance cross section, a set of two BLs develop in the aquifer, termed inner and outer BLs. It is assumed that the evaluated domain, in which the contaminant distribution gradually becomes uniform, can be divided into two sections, designated: (a) the restructuring section, and (b) the establishment section. In the restructuring section, the vertical concentration gradient leads to expansion of the inner BL at the expense of the outer BL, and there is almost no transfer of contaminant mass between the two layers. In the establishment section, each of the BLs occupies half of the aquifer thickness, and the vertical concentration gradient leads to transfer of contaminant mass from the inner to the outer BL. By use of BL approximations, changes of salinity distribution in the aquifer are calculated and evaluated. The establishment section ends at the uniformity point, downstream from which the contaminant concentration profile is practically uniform. The length of the restructuring section, as well as that of the establishment section, is approximately proportional to the aquifer thickness squared, and is inversely proportional to the transverse dispersivity. The study provides a convenient set of definitions and terminology that are helpful in visualizing the gradual development of uniform contaminant concentration distribution in an aquifer subject to contaminant plume penetration. The method developed in this study can be applied to a variety of problems associated with groundwater quality, such as initial evaluation of field data, design of field data collection, the identification of appropriate boundary conditions for numerical models, selection of appropriate numerical modeling approaches, interpretation and evaluation of field monitoring results, etc.

Environmental Monitoring↗

Selecting animal models of human aging: inbred strains often exhibit less biological uniformity than F1 hybrids.

Most gerontological research is conducted using inbred strains of animals in an attempt to maximize phenotypic uniformity within experiments and thus increase the experimenter's statistical power to detect treatment effects. However, for a wide range of phenotypic traits, F1 hybrids between inbred strains are considerably less variable than the parental inbred strains themselves. Therefore, the use of F1 hybrids is preferable for many research applications. In this article, we discuss the sources of phenotypic variability and explain why F1 hybrids are often less variable than inbred strains; we review the empirical literature illustrating the large range of species and traits for which this is true; and finally we suggest how this finding suggests that F1 hybrids may often be superior animal models for studying the aging process and how to manipulate it.

Aging↗

Selecting a model to guide family assessment.

Theoretical models can help critical care nurses deliver planned and systematic care to families in a time-efficient manner. This article describes three family theoretical models: structural-functional, family systems, and family stress.

Family↗