Impact of surrogate selection on risk assessment for total petroleum hydrocarbons

Environmental contamination involving total petroleum hydrocarbons (TPH) is being investigated and remediated at underground storage tanks, tank farms, pipelines, and refineries across the country. Human health and environmental risk play a significant role in decision making at these sites. However, risk assessment for sites contaminated with petroleum products typically is complicated by inadequate information about the composition of TPH present at the site and the physical and chemical properties and toxicity of the components. To address these data gaps, risk assessors can select surrogate compounds to represent the movement of TPH in the environment at the site and toxicity of TPH present at the site. This article illustrates the potential impact of choice of surrogates on risk estimates, which in turn affect remediation costs.     

Evaporative cooling feature selection for genotypic data involving interactions

MOTIVATION: The development of genome-wide capabilities for genotyping has led to the practical problem of identifying the minimum subset of genetic variants relevant to the classification of a phenotype. This challenge is especially difficult in the presence of attribute interactions, noise and small sample size. METHODS: Analogous to the physical mechanism of evaporation, we introduce an evaporative cooling (EC) feature selection algorithm that seeks to obtain a subset of attributes with the optimum information temperature (i.e. the least noise). EC uses an attribute quality measure analogous to thermodynamic free energy that combines Relief-F and mutual information to evaporate (i.e. remove) noise features, leaving behind a subset of attributes that contain DNA sequence variations associated with a given phenotype. RESULTS: EC is able to identify functional sequence variations that involve interactions (epistasis) between other sequence variations that influence their association with the phenotype. This ability is demonstrated on simulated genotypic data with attribute interactions and on real genotypic data from individuals who experienced adverse events following smallpox vaccination. The EC formalism allows us to combine information entropy, energy and temperature into a single information free energy attribute quality measure that balances interaction and main effects. AVAILABILITY: Open source software, written in Java, is freely available upon request.     

TAM selection of Drosophila somatic cell hybrids.

The selection of MDR3, an adenine-salvage-deficient variant of the Kc line, is described. It is resistant to methylpurine and to diaminopurine and is TAM (thymidine, adenine, methotrexate) sensitive. Two wild-type (TAM-resistant) cell lines, Schneider's line 3 (S3) and Dübendorfer's line 1 (D1), due to their different nutritional requirements, are unable to proliferate in medium ZH1% used for line MDR3. This allowed the selection of hybrids between MDR3 and either D1 or S3 in TAM cloning medium after treatment with polyethyleneglycol. Hybrids were identified by the isoenzyme pattern of NADP-dependent isocitrate dehydrogenase.     

X-chromosome inactivation and selection in somatic cells.

X-Chromosome inactivation leads to the formation of mosaic cell populations in the somatic cells of mammalian females. Cells have either a maternal or paternal X-chromosome active. If an individual is heterozygous for a cell autonomous X-linked trait, then a set of built-in cellular markers is provided for the investigation of various developmental phenomena, including selection. In the absence of somatic cell selection the tissues of an X-linked heterozygote should all be mosaic and should have a mosaic composition approaching 1:1. If somatic cell selection is occurring, it should be detectable by a significance shift from the random expected 1:1 mosaicism. The system is effective at detecting selection acting on X-linked loci and on newly arisen somatic autosomal variants, and several examples of somatic cell selection are described. However, it is concluded that somatic cell selection, as described above, is not a normal aspect of ontogeny.     

Prospects for incorporation of epigenetic biomarkers in human health and environmental risk assessment of chemicals

Epigenetic mechanisms have gained relevance in human health and environmental studies, due to their pivotal role in disease, gene × environment interactions and adaptation to environmental change and/or contamination. Epigenetic mechanisms are highly responsive to external stimuli and a wide range of chemicals has been shown to determine specific epigenetic patterns in several organisms. Furthermore, the mitotic/meiotic inheritance of such epigenetic marks as well as the resulting changes in gene expression and cell/organismal phenotypes has now been demonstrated. Therefore, epigenetic signatures are interesting candidates for linking environmental exposures to disease as well as informing on past exposures to stressors. Accordingly, epigenetic biomarkers could be useful tools in both prospective and retrospective risk assessment but epigenetic endpoints are currently not yet incorporated into risk assessments. Achieving a better understanding on this apparent impasse, as well as identifying routes to promote the application of epigenetic biomarkers within environmental risk assessment frameworks are the objectives of this review. We first compile evidence from human health studies supporting the use of epigenetic exposure‐associated changes as reliable biomarkers of exposure. Then, specifically focusing on environmental science, we examine the potential and challenges of developing epigenetic biomarkers for environmental fields, and discuss useful organisms and appropriate sequencing techniques to foster their development in this context. Finally, we discuss the practical incorporation of epigenetic biomarkers in the environmental risk assessment of chemicals, highlighting critical data gaps and making key recommendations for future research within a regulatory context.     

Accuracy of genotypic value predictions for marker-based selection in biparental plant populations

The availability of cheap and abundant molecular markers has led to plant-breeding methods that rely on the prediction of genotypic value from marker data, but published information is lacking on the accuracy of genotypic value predictions with empirical data in plants. Our objectives were to (1) determine the accuracy of genotypic value predictions from multiple linear regression (MLR) and genomewide selection via best linear unbiased prediction (BLUP) in biparental plant populations; (2) assess the accuracy of predictions for different numbers of markers (N _M) and progenies (N _P) used in estimation; and (3) determine if an empirical Bayes approach for modeling of the variances of individual markers and of epistatic effects leads to more accurate predictions in empirical data. We divided each of four maize (Zea mays L.) datasets, one Arabidopsis dataset, and two barley (Hordeum vulgare L.) datasets into an estimation set, where marker effects were calculated, and a test set, where genotypic values were predicted based on markers. Predictions were more accurate with BLUP than with MLR. Predictions became more accurate as N _P and N _M increased, until sufficient genome coverage was reached. Modeling marker variances with the empirical Bayes method sometimes led to slightly better predictions, but the accuracy with different variants of the empirical Bayes method was often inconsistent. In nearly all cases, the accuracy with BLUP was not significantly different from the highest accuracy across all methods. Accounting for epistasis in the empirical Bayes procedure led to poorer predictions. We concluded that among the methods considered, the quick and simple BLUP approach is the method of choice for predicting genotypic value in biparental plant populations.     

Quantitative risk assessment for developmental toxicity.

Pharmaceutical companies and governmental regulatory agencies are becoming increasingly aware of the need for improved statistical methods for developmental toxicity experiments. Although a number of statisticians have become interested in this area, activity has centered mostly on the development of methods to analyze binary outcomes, such as malformations among live pups, while accounting appropriately for the correlation induced by the litter effect. In contrast, the topic of quantitative risk assessment has received relatively little attention. This paper addresses the specific question of how to assess risk appropriately when exposure causes a variety of adverse effects, including resorption and fetal death, in addition to malformations. It will be seen that risk assessments based on a single developmental outcome, such as malformation, may be conservative. A method is proposed for estimating an exposure level at which the overall risk of any adverse effect is acceptably low. The method is based on a continuation ratio formulation of a multinomial distribution, with an additional scale parameter to account for overdispersion. Comparisons are made with binary models on prenatal death and malformation, as well as a binary model that makes no distinction between death and malformation, but simply classifies each fetus as normal or abnormal. Data from several developmental toxicity studies illustrate the results and findings.     

Prospects for improving reproductive performance through genetic selection

Prospects for improving female fertility in dairy cattle using genetic selection are reviewed. Today's high producing cows have shorter estrous cycles, fewer standing events, shorter duration of estrus, and more frequent multiple ovulations. Although high milk production is often implicated as the cause of impaired fertility, the impact of inadequate body condition appears to be greater, as the latter has a significant impact on probability of conception, rate of embryonic loss, and proportion of anestrous animals. Genetic improvement of female fertility can be achieved by indirect selection for longevity or body condition score, or by direct selection for traits such as daughter pregnancy rate. Most leading dairy countries have implemented genetic evaluation systems for female fertility in the past decade, but refinement of these systems to account for hormonal synchronization, differences in the voluntary waiting period, exposure to natural service bulls, and other confounding factors is warranted. Recent work has focused on the development of data collection and genetic evaluation systems that will allow selection of bulls that have daughters that are resistant to common health disorders, including mastitis, lameness, ketosis, displaced abomasum, and metritis. Such systems will allow selection of animals that can remain healthy and fertile while producing large quantities of milk.     

Temperature-dependent genotypic selection and embryonic survival of rainbow trout

The survival of rainbow trout (Salmo gairdneri) with different developmental rates and genotypes at eight polymorphic loci was compared in two experiments. The embryos were reared at temperatures colder (5 and 8°C) and warmer (12°C) than normally experienced by the strain (9.5°C). Embryo survival in five different hatching groups (representing the sequential order of hatching) was compared at 8 and 12°C. Embryos in the center of the hatching distribution (groups 2, 3, and 4) showed a greater survival to yolk sac resorption than those in the extremes (groups 1 and 5). These differences are significant in the embryos reared at 12°C in both experiments. Embryo survival from hatching to yolk sac resorption was poorer at 12 compared to 8°C. In the one experiment where it was examined, significantly fewer embryos hatched at 5 and 12 than at 8°C. Significant deviations from genotypic expectations (based upon parental allele frequencies) were detected in the progeny (23 of 34 cases). In contrast, few deviations from Hardy-Weinberg expectations were detected (5 of 34 cases) when progeny allele frequencies are used. Few significant differences in genotype frequencies were detected among the progeny reared at the different temperatures. This suggests that nonequal contributions of parental gametes rather than differential selection of genotypes account for the deviations from expectations in the progeny.This research was supported by National Science Foundation Grant BSR-8300039 awarded to Dr. Fred W. Allendorf. Moira M. Ferguson was supported by a postgraduate scholarship from the Natural Sciences and Engineering Research Council of Canada.     

Predation risk assessment by larval reef fishes during settlement-site selection

Predation rates of marine species are often highest during the transition from the pelagic to the benthic life stage. Consequently, the ability to assess predation risk when selecting a settlement site can be critical to survival. In this study, pairwise choice trials were used to determine whether larvae of three species of anemonefish (Amphiprion melanopus, A. percula and Premnas biaculeatus) are able to (1) assess the predation risk of potential anemone settlement sites through olfactory cues alone and (2) alter their settlement choices depending on the options available (host or non-host anemone). When predation risk was assessed with host and non-host anemone species independently, all species of anemonefish significantly chose the odor associated with the low-risk settlement option over the high-risk site. Most importantly, all species of anemonefish selected water with olfactory cues from their host anemone regardless of predation risk when paired against non-host anemone odor. These results demonstrate that larval reef fishes can use olfactory cues for complex risk assessment during settlement-site selection; however, locating the correct habitat is the most important factor when selecting a settlement site.     

Prospects for applying breeding for resistance to control scrapie in goats: The current situation in Italy

Genetic selection has been used to control transmissible spongiform encephalopathies (TSEs) in sheep populations based on the association between PRNP polymorphisms and resistance to scrapie. In goats even if a protective role has been suggested for several polymorphisms (I142M, H143R, N146D/S, R154H, R211Q, Q222K) by different European studies, a similar, univocal association has not been proved so far.The aim of this paper was to identify target polymorphisms in goats and their potential applicability in a selection plan in Italy. For this purpose, the existing genetic data on modulating resistance to classical and atypical scrapie in goats in this country will be used as starting point.Two Italian case–control studies concluded that the polymorphism at codon 222 (from glutamine to lysine Q/K) is important in influencing the susceptibility of goats to classical scrapie. Moreover, goats are susceptible to an unusual form of scrapie, named Nor98, and the H154 mutation was shown to be statistically associated with this disease in goats in an Italian case–control study. Currently, a strategy based on killing goats carrying the H154 mutation is being applied to manage atypical scrapie outbreaks in Italy.The current situation in Italy bodes well for the applicability of breeding plans based on the K222 mutation; data from independent studies on the role of K222 as a protective or even a resistance factor and its frequency in several Italian breeds are available. In the near future, as new data on K222 will be reported, testing the application of selective culling in classical scrapie goat outbreaks may become feasible.     

Prospects for a small molecule able to induce somatic growth through the growth hormone receptor

This article reviews the prospects for a small-molecule agonist of the growth hormone receptor in the light of current successes in identifying small agonist molecules for other homomeric class 1 cytokine receptors. A variety of mutagenic analyses on both hormone and receptor, studies with monoclonal antibody agonists of the GH receptor, and the use of a constitutively dimerized GH receptor chimera which displays constitutive activity lead us to believe that such a development is possible. However, it is likely that a precise alignment of the lower cytokine receptor homology domains will be necessary in order to facilitate cross-activation of cytoplasmic Janus kinases bound to Box 1.     

Lifestyle assessment: applying microcomputers in family practice.

A randomised trial of assessment by computer was conducted with 180 patients in a family practice clinic. Histories of alcohol, tobacco, and drug use were obtained by computer (n = 60), interview (n = 60), or self completed questionnaire (n = 60). The results of previous research suggest that some patients may provide more accurate information about "sensitive" problems to a computer. No significant differences, however, in levels of consumption or problems were reported for the three methods of assessment. Patients gave differential ratings about the method of assessment, with the computer rated as more interesting but also more mechanical, cold, and impersonal. Although the interview was initially preferred by most, patients who completed the assessment by computer showed a significant increase (13% to 43%) in their preference for the computer after the assessment. The results of our study indicate that patients'' acceptance of computers in family practice may be favourably influenced by direct experience with a microcomputer.     

Prospects for a small molecule able to induce somatic growth through the growth hormone receptor

Summary This article reviews the prospects for a small-molecule agonist of the growth hormone receptor in the light of current successes in identifying small agonist molecules for other homomeric class 1 cytokine receptors. A variety of mutagenic analyses on both hormone and receptor, studies with monoclonal antibody agonists of the GH receptor, and the use of a constitutively dimerized GH receptor chimera which displays constitutive activity lead us to believe that such a development is possible. However, it is likely that a precise alignment of the lower cytokine receptor homology domains will be necessary in order to facilitate cross-activation of cytoplasmic Janus kinases bound to Box 1.     

Fishery-induced selection for slow somatic growth in European eel

Both theoretical and experimental studies have shown that fishing mortality can induce adaptive responses in body growth rates of fishes in the opposite direction of natural selection. We compared body growth rates in European eel (Anguilla anguilla) from three Mediterranean stocks subject to different fishing pressure. Results are consistent with the hypotheses that i) fast-growing individuals are more likely to survive until sexual maturity than slow-growing ones under natural conditions (no fishing) and ii) fishing can select for slow-growing individuals by removing fast-growing ones. Although the possibility of human-induced evolution seems remote for a panmictic species like such as the European eel, further research is desirable to assess the implications of the intensive exploitation on this critically endangered fish.     

Co-dominant markers for the selection of somatic dihybrids and polyhybrids

Resistance to ouabain and puromycin are shown to represent very useful co-dominant characters for the selection of somatic hybrids between mammalian cells, after fusion with polyethylene glycol. We therefore used, with success, a number of Chinese hamster and mouse cell lines carrying these markers in association with thymidine kinase and hypoxanthine-guanine-phosphoribosyl transferase deficiency for selection of hybrids of triparental origin.     

Feature extraction and selection for objective gait analysis and fall risk assessment by accelerometry

Background  

Falls in the elderly is nowadays a major concern because of their consequences on elderly general health and moral states. Moreover, the aging of the population and the increasing life expectancy make the prediction of falls more and more important. The analysis presented in this article makes a first step in this direction providing a way to analyze gait and classify hospitalized elderly fallers and non-faller. This tool, based on an accelerometer network and signal processing, gives objective informations about the gait and does not need any special gait laboratory as optical analysis do. The tool is also simple to use by a non expert and can therefore be widely used on a large set of patients.     

The dynamics of predation risk assessment: responses of anuran larvae to chemical cues of predators

1. While the antipredator behaviour of prey has been well studied, little is known about the rules governing the predation risk assessment of prey. In this study, I measured the activity levels of predator-naive green frog (Rana clamitans) tadpoles during and after exposures to the chemical cue of predatory larval dragonflies (Anax spp.). I then used the lengths of the time lags from the end of the cue exposures until the tadpoles returned to a control level of activity as an index of the perceived risk of the tadpoles. 2. While tadpoles always responded upon exposure to the Anax chemical cue by strongly reducing their activity level, their perceived risk increased asymptotically over time during the initial period of the cue exposure. Tadpoles of all size classes perceived increasing risk in proportion to chemical cue concentration, but the length of time that tadpoles responded during cue exposure and the length of their post-exposure time lags decreased with increasing body mass. 3. The results suggest that the perceived risk of green frog tadpoles varies over time and does not correspond directly to their behavioural response (i.e. activity level). However, their perceived risk does appear to vary in accordance with the predation risk associated with the Anax chemical cue and the reliability of the information from the cue, and therefore may be predictable.     

Phenotypic and genotypic selection of microbiota surviving under dental restorations

The effects of sealing infected carious dentine below dental restorations on the phenotypic and genotypic diversity of the surviving microbiota was investigated. It was hypothesized that the microbiota would be subject to nutrient limitation or nutrient simplification, as it would no longer have access to dietary components or salivary secretion for growth. The available nutrients would be limited primarily to serum proteins passing from the pulp through the patent dentinal tubules to the infected dentine. Ten lesions were treated, and infected dentine was sealed below dental restorations for approximately 5 months. Duplicate standardized samples of infected dentine were taken at baseline and after the removal of the restorations. The baseline microbiota were composed primarily of Lactobacillus spp., Streptococcus mutans, Streptococcus parasanguinis, Actinomyces israelii, and Actinomyces gerencseriae. None of these taxa were isolated among the microbiota of the dentine samples taken after 5 months, which consisted of only Actinomyces naeslundii, Streptococcus oralis, Streptococcus intermedius, and Streptococcus mitis. The microbiota of the final sample exhibited a significantly (P < 0.001) increased ability to produce glycosidic enzymes (sialidase, beta-N-acetylglucosaminidase, and beta-galactosidase), which liberate sugars from glycoproteins. The genotypic diversity of S. oralis and A. naeslundii was significantly (P = 0.002 and P = 0.001, respectively) reduced in the final samples. There was significantly (P < 0.001) greater genotypic diversity within these taxa between the pairs of dentine samples taken at baseline than was found in the 5-month samples, indicating that the dentine was more homogenous than it was at baseline. We propose that during the interval between placement of the restorations and their removal, the available nutrient, primarily serum proteins, or the relative simplicity and homogeneity of the nutrient supply significantly affected the surviving microbiota. The surviving microbiota was less complex, based on compositional, phenotypic, and genotypic analyses, than that isolated from carious lesions which were also exposed to salivary secretions and pH perturbations.