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Sample records for risk characterization glycoalkaloids

  1. Probabilistic modelling of exposure doses and implications for health risk characterization: glycoalkaloids from potatoes.

    PubMed

    Ruprich, J; Rehurkova, I; Boon, P E; Svensson, K; Moussavian, S; Van der Voet, H; Bosgra, S; Van Klaveren, J D; Busk, L

    2009-12-01

    Potatoes are a source of glycoalkaloids (GAs) represented primarily by alpha-solanine and alpha-chaconine (about 95%). Content of GAs in tubers is usually 10-100 mg/kg and maximum levels do not exceed 200 mg/kg. GAs can be hazardous for human health. Poisoning involve gastrointestinal ailments and neurological symptoms. A single intake of >1-3 mg/kg b.w. is considered a critical effect dose (CED). Probabilistic modelling of acute and chronic (usual) exposure to GAs was performed in the Czech Republic, Sweden and The Netherlands. National databases on individual consumption of foods, data on concentration of GAs in tubers (439 Czech and Swedish results) and processing factors were used for modelling. Results concluded that potatoes currently available at the European market may lead to acute intakes >1 mg GAs/kg b.w./day for upper tail of the intake distribution (0.01% of population) in all three countries. 50 mg GAs/kg raw unpeeled tubers ensures that at least 99.99% of the population does not exceed the CED. Estimated chronic (usual) intake in participating countries was 0.25, 0.29 and 0.56 mg/kg b.w./day (97.5% upper confidence limit). It remains unclear if the incidence of GAs poisoning is underreported or if assumptions are the worst case for extremely sensitive persons.

  2. A human dietary risk assessment associated with glycoalkaloid responses of potato to Colorado potato beetle defoliation.

    PubMed

    Dinkins, Courtney L Pariera; Peterson, Robert K D

    2008-08-01

    A quantitative human dietary risk assessment was conducted using the glycoalkaloid concentrations measured from tubers of plants defoliated by Colorado potato beetles and undefoliated (control). There was a significantly greater production of glycoalkaloids for defoliated plants compared to control plants for both skin and inner tissue of tubers. The dietary risk posed to different human subgroups associated with the consumption of potatoes was estimated for the 50th, 95th, and 99.9th percentile US national consumption values. Exposures were compared to a toxic threshold of 1.0mg/kg body weight. Defoliation by Colorado potato beetles increased dietary risk by approximately 48%. Glycoalkaloid concentrations within the inner tissue of tubers, including undefoliated controls, exceeded the toxic threshold for all human subgroups at less than the 99.9th percentile of exposure, but not the 95th percentile.

  3. Characterization and Transcriptional Profile of Genes Involved in Glycoalkaloid Biosynthesis in New Varieties of Solanum tuberosum L.

    PubMed

    Mariot, Roberta Fogliatto; de Oliveira, Luisa Abruzzi; Voorhuijzen, Marleen M; Staats, Martijn; Hutten, Ronald C B; van Dijk, Jeroen P; Kok, Esther J; Frazzon, Jeverson

    2016-02-03

    Before commercial release, new potato (Solanum tuberosum) varieties must be evaluated for content of toxic compounds such as glycoalkaloids (GAs), which are potent poisons. GA biosynthesis proceeds via the cholesterol pathway to α-chaconine and α-solanine. The goal of this study was to evaluate the relationship between total glycoalkaloid (TGA) content and the expression of GAME, SGT1, and SGT3 genes in potato tubers. TGA content was measured by HPLC-MS, and reverse transcription quantitative polymerase chain reactions were performed to determine the relative expression of GAME, SGT1, and SGT3 genes. We searched for cis-elements of the transcription start site using the PlantPAN database. There was a relationship between TGA content and the relative expression of GAME, SGT1, and SGT3 genes in potato tubers. Putative promoter regions showed the presence of several cis-elements related to biotic and abiotic stresses and light. These findings provide an important step toward understanding TGA regulation and variation in potato tubers.

  4. [Teratogenic effect of potato glycoalkaloids].

    PubMed

    Wang, X G

    1993-02-01

    Potato glycoalkaloids were extracted from potato sprout and then analyzed to determine their purity by using TLC and HPLC methods and compare with pure alpha-Solanine and alpha-Chaconine of Sigma. The result indicated that the purity of potato glycoalkaloids is 78. 31%, which contains 73.64% alpha-Solanine and 4.67% alpha-Chaconine. The LD50 of mice was 44.721 +/- 5.860 4 mg/kg. In order to determine the toxicity and teratogenicity of potato glycoalkaloids, the effect of potato glycoalkaloids on Kunming pregnant mice were studied. The results showed that: (1) potato glycoalkaloids have teratogenic effects on embryos of mice. It could induce neural tube defects (NTDs), and may be an important teratogen of NTDs. (2) potato glycoalkaloids have embryo toxicity. It could cause the death of embryos and result in absorbed and dead fetuses. (3) potato glycoalkaloids could evidently affect the development of embryos and lead to intrauterine growth retardation (IUGR). An interesting phenomena which just like the clinical manifestation of miscarriage in human being was noticed. If potato glycoalkaloids were given to the pregnant mice on the 5th or 6th day of gestation intraabdominally, vaginal bleeding and abortion would occur, and this has not been reported yet. The animal model of NTDs in this experiments supported our hypothesis that sprouted potato could be a teratogen of NTDs.

  5. Glycoalkaloids and calystegine alkaloids in potatoes

    USDA-ARS?s Scientific Manuscript database

    Potatoes contain two classes of alkaloids: the glycoalkaloids and the calystegines. The presence of glycoalkaloids in potatoes and their toxicity has been known for more than a century and much has been written about them. Discovery of the nortropane calystegine alkaloids is more recent, and the k...

  6. Risk Characterization Handbook

    EPA Pesticide Factsheets

    This Handbook has two parts. The first is the Risk Characterization guidance itself. The second part comprises the Appendices which contain the Risk Characterization Policy, the risk characterization case studies and references.

  7. Fate of toxic potato glycoalkaloids in a potato field.

    PubMed

    Jensen, Pia H; Strobel, Bjarne W; Hansen, Hans Christian B; Jacobsen, Ole Stig

    2009-04-08

    The toxic glycoalkaloids, alpha-solanine and alpha-chaconine, are present in all parts of the potato plant and are possibly transferred to the terrestrial environment. The amounts of glycoalkaloids in plant, soil, and groundwater were followed in a potato field to investigate their distribution and fate during the season. The amount of glycoalkaloids in the plants was up to 25 kg/ha during maturity and decreased to below 0.63 kg/ha during plant senescence. The glycoalkaloids were detected in the upper soil (up to 0.6 kg/ha); this amount accounted only for a minor fraction of the amount present in the plants. Maximum glycoalkaloid concentration of 2.8 mg/kg dry weight soil was detected in September. Dissipation during winter appeared to be slow because glycoalkaloids were still present in the soil in March. No traces of glycoalkaloids were detected in the groundwater (detection limit 0.2 microg/L). From these results, the leaching potential of the glycoalkaloids is evaluated to be small.

  8. Molluscicidal steroid glycoalkaloids possessing stereoisomeric spirosolane structures.

    PubMed

    Alzérreca, A; Hart, G

    1982-07-01

    Both the steroidal glycoalkaloid mixture obtained from Solanum mammosum fruits (solasonine 1 and solamargine 2) and the stereoisomeric glycosidic alkaloid tomatine 3 are toxic at 10 and 25 ppm to Lymnaea cubensis and Biomphalaria glabratus, respectively. Their aglycones solasodine 4 and tomatidine 5 obtained by hydrolysis of the glycosides showed no toxicity to either mollusk under the test conditions used. Preliminary structure-activity correlations indicate that the molluscicidal properties depend on the type of aglycones and on the glycoside bond. A common molecular structure in molluscicidal spirosolane and spirostane glycosides is recognized.

  9. Effects of glycoalkaloids from Solanum plants on cucumber root growth.

    PubMed

    Sun, Fang; Li, Shengyu; He, Dajun; Cao, Gang; Ni, Xiuzhen; Tai, Guihua; Zhou, Yifa; Wang, Deli

    2010-09-01

    The phytotoxic effect of four glycoalkaloids and two 6-O-sulfated glycoalkaloid derivatives were evaluated by testing their inhibition of cucumber root growth. The bioassays were performed using both compounds singly and in equimolar mixtures, respectively. Cucumber root growth was reduced by chaconine (C), solanine (S), solamargine (SM) and solasonine (SS) with IC(50) values of 260 (C), 380 (S), 530 (SM), and 610 microM (SS). The inhibitory effect was concentration-dependent. 6-O-sulfated chaconine and 6-O-sulfated solamargine had no inhibitory effects, which indicated that the carbohydrate moieties play an important role in inhibiting cucumber root growth. The equimolar mixtures of paired glycoalkaloids, both chaconine/solanine and solamargine/solasonine, produced synergistic effects on inhibition of cucumber root growth. By contrast, mixtures of unpaired glycoalkaloids from different plants had no obviously synergistic effects. The growth inhibited plant roots lacked hairs, which implied that inhibition was perhaps at the level of root hair growth.

  10. Risk characterization: principles and practice.

    PubMed

    Williams, Pamela R D; Paustenbach, Dennis J

    2002-01-01

    In the field of risk assessment, characterizing the nature and magnitude of human health or environmental risks is arguably the most important step in the analytical process. In this step, data on the dose-response relationship of an agent are integrated with estimates of the degree of exposure in a population to characterize the likelihood and severity of risk. Although the purpose of risk characterizations is to make sense of the available data and describe what they mean to a broad audience, this step is often given insufficient attention in health risk evaluations. Too often, characterizations fail to interpret or summarize risk information in a meaningful way, or they present single numerical estimates of risk without an adequate discussion of the uncertainties inherent in key exposure parameters or the dose-response assessment, model assumptions, or analytical limitations. Consequently, many users of risk information have misinterpreted the findings of a risk assessment or have false impressions about the degree of accuracy (or the confidence of the scientist) in reported risk estimates. In this article we collected and integrated the published literature on conducting and reporting risk characterizations to provide a broad, yet comprehensive, analysis of the risk characterization process as practiced in the United States and some other countries. Specifically, the following eight topics are addressed: (1) objective of risk characterization, (2) guidance documents on risk characterization, (3) key components of risk characterizations, (4) toxicity criteria for evaluating health risks, (5) descriptors used to characterize health risks, (6) methods for quantifying human health risks, (7) key uncertainties in risk characterizations, and (8) the risk decision-making process. A brief discussion is also provided on international aspects of risk characterization. A number of examples are presented that illustrate key concepts, and citations are provided for

  11. A multiresidual method for the simultaneous determination of the main glycoalkaloids and flavonoids in fresh and processed tomato (Solanum lycopersicum L.) by LC-DAD-MS/MS.

    PubMed

    Dall'Asta, Chiara; Falavigna, Claudia; Galaverna, Gianni; Sforza, Stefano; Dossena, Arnaldo; Marchelli, Rosangela

    2009-11-01

    A new multiresidual LC-DAD-MS/MS method for the simultaneous detection of the major flavonoids and glycoalkaloids occurring in tomatoes has been developed and applied to the characterization of seven varieties of raw tomatoes grown in Italy and to their processed products. The new method allowed to determine rapidly the concentration of these secondary metabolites in a single analysis, showing that their content can be quite variable among the different varieties considered. On the contrary, a great depletion in glycoalkaloids and flavonoids is observed after processing, probably due to the harsh thermal treatment, which prevents the recognition of the varieties in the processed products.

  12. Glycoalkaloid responses of potato to Colorado potato beetle defoliation.

    PubMed

    Pariera Dinkins, Courtney L; Peterson, Robert K D; Gibson, James E; Hu, Qing; Weaver, David K

    2008-08-01

    Two experiments were conducted to measure the glycoalkaloid concentrations of potato tubers in response to Colorado potato beetle and manual defoliation. For plants defoliated by Colorado potato beetles, there was a significantly greater production of glycoalkaloids than in control plants and manually defoliated plants for both skin and inner tissue of tubers in experiment 1. In experiment 1, there was a 58.1% and 48.3% increase in glycoalkaloids in skin and inner tissue of tubers, respectively, from plants defoliated at high levels by Colorado potato beetles compared to control plants. In experiment 2, although a significant difference in glycoalkaloid concentration was not observed among the treatments, the skin and inner tissue of tubers from plants defoliated at high levels by Colorado potato beetles increased glycoalkaloid concentration by 23.4% and 14.5%, respectively, compared to tubers from control plants. In experiment 1, the concentration of tuber extract required to reduce Chinese hamster ovary (CHO) cellular proliferation by 50% was 10-fold less for the skin versus the inner tissue, indicating that skin tissue was more toxic under the in vitro conditions of this assay.

  13. Steroidal glycoalkaloid profiling and structures of glycoalkaloids in wild tomato fruit.

    PubMed

    Iijima, Yoko; Watanabe, Bunta; Sasaki, Ryosuke; Takenaka, Makiko; Ono, Hiroshi; Sakurai, Nozomu; Umemoto, Naoyuki; Suzuki, Hideyuki; Shibata, Daisuke; Aoki, Koh

    2013-11-01

    Steroidal glycoalkaloids (SGAs) constitute one of the main groups of secondary metabolites in tomato fruit. However, the detailed composition of SGAs other than α-tomatine, dehydrotomatine and esculeoside A, remains unclear. Comparative SGA profiling was performed in eight tomato accessions, including wild tomato species by HPLC-Fourier transform ion cyclotron resonance mass spectrometry (HPLC-FTICR/MS). On the basis of molecular formulae obtained from accurate m/z and fragmentation patterns by multistage MS/ MS (MS(n)), 123 glycoalkaloids in total were screened. Detailed MS(n) analysis showed that the observed structural diversity was derived from various chemical modifications, such as glycosylation, acetylation, hydroxylation and isomerization. Total SGA content in each tomato accession was in the range of 121-1986 nmol/gfr.wt. Furthermore, the compositional variety of SGA structures was distinctive in some tomato accessions. While most tomato accessions were basically categorized as α-tomatine-rich or esculeoside A-rich group, other specific SGAs also accumulated at high levels in wild tomato. Here, five such SGAs were isolated and their structures were determined by NMR spectroscopic analysis, indicating three of them were presumably synthesized during α-tomatine metabolism.

  14. Glycoalkaloid and calystegine levels in table potato cultivars subjected to wounding, light, and heat treatments.

    PubMed

    Petersson, Erik V; Arif, Usman; Schulzova, Vera; Krtková, Veronika; Hajšlová, Jana; Meijer, Johan; Andersson, Hans Christer; Jonsson, Lisbeth; Sitbon, Folke

    2013-06-19

    Potato tubers naturally contain a number of defense substances, some of which are of major concern for food safety. Among these substances are the glycoalkaloids and calystegines. We have here analyzed levels of glycoalkaloids (α-chaconine and α-solanine) and calystegines (A₃, B₂, and B₄) in potato tubers subjected to mechanical wounding, light exposure, or elevated temperature: stress treatments that are known or anticipated to induce glycoalkaloid levels. Basal glycoalkaloid levels in tubers varied between potato cultivars. Wounding and light exposure, but not heat, increased tuber glycoalkaloid levels, and the relative response differed among the cultivars. Also, calystegine levels varied between cultivars, with calystegine B4 showing the most marked variation. However, the total calystegine level was not affected by wounding or light exposure. The results demonstrate a strong variation among potato cultivars with regard to postharvest glycoalkaloid increases, and they suggest that the biosynthesis of glycoalkaloids and calystegines occurs independently of each other.

  15. Degradation of the potato glycoalkaloid alpha-solanine in three agricultural soils.

    PubMed

    Jensen, Pia H; Pedersen, Rasmus B; Svensmark, Bo; Strobel, Bjarne W; Jacobsen, Ole Stig; Hansen, Hans Christian B

    2009-08-01

    The toxic glycoalkaloids produced by the potato plant (Solanum tuberosum L.) have previously been found in upper soil from a potato field during several months. Further insight into the fate of the glycoalkaloids is needed, as only little information about their degradation in soil is available. Degradation of the glycoalkaloid, alpha-solanine, has been followed for 42d in three agricultural soils with common texture and carbon contents. A similar degradation pattern was found in all soils, and the kinetics was well described by a sum of two first-order equations. Overall, degradation rates for the initial first reaction were in the range 0.22-1.64d(-1). Estimated half-lives were in the range 1.8-4.1d for the three top soils at 15 degrees C; the fastest degradation was observed in the sandy soil. The major proportion of alpha-solanine in the sandy soil was degraded by the fast process, while the proportion was lower for the two other soils. Fast degradation appeared to be related to the presence of low amount of sorbents. Additionally, degradation was followed at 5 degrees C in A- and C-horizon soil from the sandy location, and for both horizons the half-lives were of similar length (4.7-8.7d). For the slow process, degradation rates were in the range 0.000-0.123d(-1), and residuals were still present in all soils and all temperatures at the end of the experiment (d 42). Overall, fast degradation was found in both top- and subsoil even at low temperatures, and the risk for alpha-solanine leaching to the groundwater appears to be low.

  16. Modifying glycoalkaloid content in transgenic potato – Metabolome impacts

    USDA-ARS?s Scientific Manuscript database

    Metabolite profiling has been used to assess the potential for unintended composition changes in potato (Solanum tuberosum L. cv. Desirée) tubers, which have been genetically modified (GM) to reduce glycoalkaloid content via the independent down-regulation of three genes SGT1, SGT2 and SGT3 known t...

  17. Potato glycoalkaloids and metabolites: roles in the plant and in the diet.

    PubMed

    Friedman, Mendel

    2006-11-15

    Potatoes, members of the Solanaceae plant family, serve as major, inexpensive low-fat food sources providing energy (starch), high-quality protein, fiber, and vitamins. Potatoes also produce biologically active secondary metabolites, which may have both adverse and beneficial effects in the diet. These include glycoalkaloids, calystegine alkaloids, protease inhibitors, lectins, phenolic compounds, and chlorophyll. Because glycoalkaloids are reported to be involved in host-plant resistance and to have a variety of adverse as well as beneficial effects in cells, animals, and humans, a need exists to develop a clearer understanding of their roles both in the plant and in the diet. To contribute to this effort, this integrated review presents data on the (a) history of glycoalkaloids; (b) glycoalkaloid content in different parts of the potato plant, in processed potato products, and in wild, transgenic, and organic potatoes; (c) biosynthesis, inheritance, plant molecular biology, and glycoalkaloid-plant phytopathogen relationships; (d) dietary significance with special focus on the chemistry, analysis, and nutritional quality of low-glycoalkaloid potato protein; (e) pharmacology and toxicology of the potato glycoalkaloids comprising alpha-chaconine and alpha-solanine and their hydrolysis products (metabolites); (f) anticarcinogenic and other beneficial effects; and (g) possible dietary consequences of concurrent consumption of glycoalkaloids and other biologically active compounds present in fresh and processed potatoes. An enhanced understanding of the multiple and overlapping aspects of glycoalkaloids in the plant and in the diet will benefit producers and consumers of potatoes.

  18. [Survey of glycoalkaloids content in the various potatoes].

    PubMed

    Shimoi, Toshiko; Ushiyama, Hirofumi; Kan, Kimiko; Saito, Kazuo; Kamata, Kunihiro; Hirokado, Masako

    2007-06-01

    The content of potato glycoalkaloid (PGA) was investigated in 27 cultivars of raw potatoes and 31 potatoes in commercial foods with peel. The investigation of the 27 cultivars of potatoes showed different contents of glycoalkaloids. "May queen" and "Sherry" showed high contents of PGA (180 mg/kg and 320 mg/kg, respectively) among the raw potatoes of middle size (ca. 100 g). On the other hand, "Inca red" showed the lowest content of 21 mg/kg. Higher contents of PGA were found in smaller potatoes in this study. The content of PGA varied in the range of 48-350 mg/kg in the potatoes in commercial foods with peel.

  19. Glycoalkaloid and calystegine contents of eight potato cultivars.

    PubMed

    Friedman, Mendel; Roitman, James N; Kozukue, Nobuyuki

    2003-05-07

    Diverse procedures have been reported for the separation and analysis by HPLC of the two major glycoalkaloids present in potatoes, alpha-chaconine and alpha-solanine. To further improve the usefulness of the HPLC method, studies were carried out on the influence of several salient parameters on the analysis of the two potato glycoalkaloids. Effects on retention (elution, separation) times of the (a) composition and pH of the mobile phase (acetonitrile and phosphate buffer), (b) concentration of the phosphate buffer, (c) capacity values of column packing of four commercial HPLC amino columns, (d) column temperature were studied. Except for pH, all of the variables significantly influenced the retention times. The results make it possible to select analysis conditions that produce well-separated as well as symmetrical peaks of the two glycoalkaloids. This improved HPLC method (limit of detection of approximately 150 ng) was evaluated with extracts from the cortex of one whole potato variety (May Queen) grown in Japan and the freeze-dried peel and flesh from the following eight cultivars grown in the United States: Atlantic, Dark Red Norland, Ranger Russet, Red Lasoda, Russet Burbank, Russet Norkota, Shepody, and Snowden. In addition, the same samples were analyzed by GC-MS for the presence of two water-soluble nortropane alkaloids, calystegine A(3) and calystegine B(2), reported to be potent glycosidase inhibitors. The following ranges for the eight varieties of total glycoalkaloid and calystegine levels were observed: dry flesh, 5-592 and 6-316 mg/kg; dry peel, 84-2226 and 218-2581 mg/kg; dry whole potatoes, 40-883 and 34-326 mg/kg; wet flesh, 1-148 and 1-68 mg/kg; wet peel, 12-429 and 35-467 mg/kg; wet whole potatoes, 7-187 and 5-68 mg/kg. The possible significance of the results to plant and food sciences is discussed.

  20. Modifying glycoalkaloid content in transgenic potato--Metabolome impacts.

    PubMed

    Shepherd, Louise Vida Traill; Hackett, Christine Anne; Alexander, Colin James; McNicol, James William; Sungurtas, Julia Anne; Stewart, Derek; McCue, Kent Frank; Belknap, William Richardson; Davies, Howard Vivian

    2015-11-15

    Metabolite profiling has been used to assess the potential for unintended composition changes in potato (Solanum tuberosum L. cv. Desirée) tubers, which have been genetically modified (GM) to reduce glycoalkaloid content, via the independent down-regulation of three genes SGT1, SGT2 and SGT3 known to be involved in glycoalkaloid biosynthesis. Differences between the three groups of antisense lines and control lines were assessed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography (GC)-MS, and data analysed using principal component analysis and analysis of variance. Compared with the wild-type (WT) control, LC-MS revealed not only the expected changes in specific glycoalkaloid levels in the GM lines, but also significant changes in several other metabolites, some of which were explicable in terms of known pathways. Analysis of polar and non-polar metabolites by GC-MS revealed other significant (unintended) differences between SGT lines and the WT, but also between the WT control and other control lines used.

  1. Characterizing perception of ecological risk.

    PubMed

    McDaniels, T; Axelrod, L J; Slovic, P

    1995-10-01

    Relatively little attention has been paid to the role of human perception and judgment in ecological risk management. This paper attempts to characterize perceived ecological risk, using the psychometric paradigm developed in the domain of human health risk perception. The research began by eliciting a set of scale characteristics and risk items (e.g., technologies, actions, events, beliefs) from focus group participants. Participants in the main study were 68 university students who completed a survey instrument that elicited ratings for each of 65 items on 30 characteristic scales and one scale regarding general risk to natural environments. The results are presented in terms of mean responses over individuals for each scale and item combination. Factor analyses show that five factors characterize the judgment data. These have been termed: impact on species, human benefits, impact on humans, avoidability, and knowledge of impacts. The factor results correspond with initial expectations and provide a plausible characterization of judgments regarding ecological risk. Some comparisons of mean responses for selected individual items are also presented.

  2. Comparison of high- and low-energy collision-induced dissociation tandem mass spectrometry in the analysis of glycoalkaloids and their aglycons.

    PubMed

    Claeys, M; Van den Heuvel, H; Chen, S; Derrick, P J; Mellon, F A; Price, K R

    1996-02-01

    Four aglycons (tomatidine, demissidine, solanidine, and solasodine) and three glycoalkaloids (α-tomatine, α-chaconine, and α-solanine) have been analyzed by positive ion liquid secondary ion high-energy and low-energy collision-induced dissociation (CID) tandem mass Spectrometry, performed on a four-sector (EBEB) and a hybrid (EBQQ) instrument, respectively. Both high- and low-energy collision-induced dissociation mass spectra of [M+H](+) ions of these compounds provided structural information that aided the characterization of the different aglycons and of the carbohydrate sequence and linkage sites in the glycoalkaloids. Low-energy CID favors charge-driven fragmentation of the aglycon rings, whilst high-energy CID spectra are more complex and contain additional ions that appear to result from charge-remote fragmentations, multiple cleavages, or complex charge-driven rearrangements. With respect to the structural characterization of the carbohydrate part, low-energy CID fragmentations of sugar residues in the glycoalkaloids generate Y n (+) ions and some low intensity Z n (+) ions; the high-energy spectra also exhibit strong (1,5)X n (+) ions, formed by multiple cleavage of the sugar ring, and significant Z n (+) ions.

  3. The inactivation of herpes simplex virus by some Solanaceae glycoalkaloids.

    PubMed

    Thorne, H V; Clarke, G F; Skuce, R

    1985-12-01

    The infectivity of herpes simplex virus Type I in tissue culture was inhibited by prior incubation with aqueous suspensions of glycoalkaloids in order of activity alpha-chaconine greater than alpha-tomatine greater than alpha-solasonine but not by the corresponding aglycones, solanidine, tomatidine and solasodine. However, inhibition was not only dependent on the presence of a sugar moiety since the glycone alpha-solanine was inactive under the conditions used. The glycones, but not the aglycones, showed cytopathic effects on cellular membranes of Vero cells and erythrocytes; therefore, it is suggested that inactivation of virus results from insertion of the glycones into the viral envelope.

  4. Polyphenol and glycoalkaloid contents in potato cultivars grown in Luxembourg.

    PubMed

    Deusser, Hannah; Guignard, Cédric; Hoffmann, Lucien; Evers, Danièle

    2012-12-15

    The polyphenol (phenolic acids, flavanols and flavonols) and glycoalkaloid (α-chaconine and α-solanine) contents of potato tubers grown in Luxembourg were analyzed by UPLC-DAD and HPLC-MS/MS separately in peel (approx. 2mm), outer (approx. 1cm) and inner flesh. Polyphenol contents decreased from the peel via the outer to the inner flesh and differed among the cultivars. The cultivars Vitelotte and Luminella had the highest polyphenol contents (5202 and 572 μg/g dry weight (DW) in the outer flesh), whereas Charlotte and Bintje had the lowest contents (19.5 and 48.0 μg/g DW). Chlorogenic acid and its isomers (neo- and cryptochlorogenic acid) were the major polyphenols. Glycoalkaloid contents were highest in the peel and lowest in the inner flesh, values in the flesh were below guideline limits in all cultivars. In conclusion, potatoes contribute to the daily intake of polyphenols and their consumption, thereby, may have positive effects on health.

  5. CHARACTERIZATION OF RISKS POSED BY COMBUSTOR EMISSIONS

    EPA Science Inventory

    Risk characterization is the final step of the risk assessment process as practiced in the U.S. EPA. In risk characterization, the major scientific evidence and "bottom-line" results from the other components of the risk assessment process, hazard identification, dose-response as...

  6. CHARACTERIZATION OF RISKS POSED BY COMBUSTOR EMISSIONS

    EPA Science Inventory

    Risk characterization is the final step of the risk assessment process as practiced in the U.S. EPA. In risk characterization, the major scientific evidence and "bottom-line" results from the other components of the risk assessment process, hazard identification, dose-response as...

  7. The chemistry and anticarcinogenic mechanisms of glycoalkaloids produced by eggplants, potatoes, and tomatoes

    USDA-ARS?s Scientific Manuscript database

    Inhibition of cancer can occur via apoptosis, a genetically directed process of cell self-destruction that involves numerous biomarkers and signaling pathways. Glycoalkaloids are nitrogen-containing secondary plant metabolites found in numerous Solanaceous plants including eggplants, potatoes, and ...

  8. Degradation of the potato glycoalkaloids--alpha-solanine and alpha-chaconine in groundwater.

    PubMed

    Jensen, Pia H; Jacobsen, Ole S; Henriksen, Trine; Strobel, Bjarne W; Hansen, Hans Christian B

    2009-06-01

    The potato glycoalkaloids alpha-chaconine and alpha-solanine are produced in high amounts in potato plants from where release to soil takes place. Degradation of the compounds in groundwater was investigated, as their fate in the terrestrial environment is unknown. Abiotic and microbial degradation were followed in groundwater sampled from below a potato field and spiked with the glycoalkaloids (115 nmol/l). Degradation was primarily microbial and the glycoalkaloids were degraded within 21-42 days. The metabolites beta(1)-solanine, gamma-solanine, and solanidine were formed from alpha-solanine, while beta-chaconine, gamma-chaconine and solanidine were detected from alpha-chaconine. Thus, indigenous groundwater microorganisms are capable of degrading the glycoalkaloids.

  9. pH-Zone-refining centrifugal partition chromatography for preparative isolation and purification of steroidal glycoalkaloids from Solanum xanthocarpum.

    PubMed

    Maurya, Anupam; Gupta, Shalini; Negi, Suroochi; Srivastava, Santosh Kumar

    2009-09-01

    pH-Zone-refining centrifugal-partition chromatography (CPC) was successfully applied in the separation of complex polar steroidal glycoalkaloids of close Rf values, directly from a crude extract of Solanum xanthocarpum. The experiment was performed with a two phase solvent system composed of ethyl acetate/butanol/water (1:4:5 by volume) where triethylamine (5 mM) was added to the upper organic mobile phase as an eluter and TFA (10 mM) to the aqueous stationary phase as a retainer. Separation of 1 g of crude extract over CPC resulted in two distinct pH-zones. The fractions collected in pH-zone i afforded 72 mg of solasonine while the fractions collected in pH-zone ii were slightly impure, hence were purified over medium pressure LC, which afforded 30 mg of solasonine and further 15 mg of solamargine (SM). The steroidal glycoalkaloids, SM and solasonine were isolated in 93.3 and 91.6% purity, respectively. The isolated alkaloids were characterized on the basis of their (1)H, (13)C-NMR, and ESI-MS data.

  10. Differential gene expression in intestinal epithelial cells induced by single and mixtures of potato glycoalkaloids.

    PubMed

    Mandimika, Tafadzwa; Baykus, Hakan; Vissers, Yvonne; Jeurink, Prescilla; Poortman, Jenneke; Garza, Cutberto; Kuiper, Harry; Peijnenburg, Ad

    2007-11-28

    Alpha-chaconine and alpha-solanine are naturally occurring toxins. They account for 95% of the total glycoalkaloids in potatoes ( Solanum tuberosum L.). At high levels, these glycoalkaloids may be toxic to humans, mainly by disrupting cell membranes of the gastrointestinal tract. Gene-profiling experiments were performed, whereby Caco-2 cells were exposed to equivalent concentrations (10 microM) of pure alpha-chaconine or alpha-solanine or glycoalkaloid mixtures of varying alpha-chaconine/alpha-solanine ratios for 6 h. In addition, lactate dehydrogenase, cell cycle, and apoptosis analyses experiments were also conducted to further elucidate the effects of glycoalkaloids. The main aims of the study were to determine the transcriptional effects of these glycoalkaloid treatments on Caco-2 cells and to investigate DNA microarray utility in conjunction with conventional toxicology in screening for potential toxicities and their severity. Gene expression and pathway analyses identified changes related to cholesterol biosynthesis, growth signaling, lipid and amino acid metabolism, mitogen-activated protein kinase (MAPK) and NF-kappaB cascades, cell cycle, and cell death/apoptosis. To varying extents, DNA microarrays discriminated the severity of the effect among the different glycoalkaloid treatments.

  11. Effects of the extract and glycoalkaloids of Solanum lycocarpum St. Hill on Giardia lamblia trophozoites

    PubMed Central

    Martins, Gilmarcio Z.; Moreira, Raquel R. D.; Planeta, Cleopatra S.; Almeida, Adélia E.; Bastos, Jairo K.; Salgueiro, Lígia; Cavaleiro, Carlos; do Céu Sousa, Maria

    2015-01-01

    Background: Solanum lycocarpum has great importance for food and medicinal traditional use. Recently, it was also evidenced that extracts of S. lycocarpum St. Hill (Solanaceae) and its glycoalkaloids, solamargine (Sg) and solasonine (Sn), are active against flagellated protozoa. Objective: The aim was to assess the effects of the extract of S. lycocarpum and its glycoalkaloids, Sn, and Sg, on Giardia lamblia trophozoites. Materials and Methods: A crude extract (96%ethanol) (EB) of fruits of S. lycocarpum was prepared and fractionated by partition with 40%ethanol and n-hexane: Ethyl acetate. Glycoalkaloids, Sn, and Sg were recognized in the ethanol fraction (EF) and further isolated by column chromatography. EB, EF, the isolated Sn and Sg and a mixture (1:1) of both glycoalkaloids were tested on cultures of G. lamblia trophozoites and macrophages. Results: EB, EF and glycoalkaloids of S. lycocarpum showed activity against Giardia (95.0 < Inhibitory concentration 50 [IC50] ≤120.3 μg/mL). The mixture of glycoalkaloids (1:1) was more active (IC50 = 13.23 μg/mL) than each one individually, suggesting a synergic effect. Moreover, the mixture is nontoxic to macrophage cells. Conclusion: Results are optimistic concerning the anti-Giardia potential of the mixture Sn + Sg. Further studies, in vitro and in vivo, will be required to consolidate the usefulness of the mixture of Sn + Sg in view of a new therapeutic strategy for giardiasis. PMID:26109762

  12. Effects of steroidal glycoalkaloids from potatoes (Solanum tuberosum) on in vitro bovine embryo development.

    PubMed

    Wang, S; Panter, K E; Gaffield, W; Evans, R C; Bunch, T D

    2005-02-01

    alpha-Solanine and alpha-chaconine are two naturally occurring steroidal glycoalkaloids in potatoes (Solanum tuberosum), and solanidine-N-oxide is a corresponding steroidal aglycone. The objective of this research was to screen potential cyto-toxicity of these potato glycoalkaloids using bovine oocyte maturation, in vitro fertilization techniques and subsequent embryonic development as the in vitro model. A randomized complete block design with four in vitro oocyte maturation (IVM) treatments (Experiment 1) and four in vitro embryo culture (IVC) treatments (Experiment 2) was used. In Experiment 1, bovine oocytes (n=2506) were matured in vitro in medium supplemented with 6 microM of alpha-solanine, alpha-chaconine, solanidine-N-oxide or IVM medium only. The in vitro matured oocytes were then subject to routine IVF and IVC procedures. Results indicated that exposure of bovine oocytes to the steroidal glycoalkaloids during in vitro maturation inhibited subsequent pre-implantation embryo development. Potency of the embryo-toxicity varied between these steroidal glycoalkaloids. In Experiment 2, IVM/IVF derived bovine embryos (n=2370) were cultured in vitro in medium supplemented with 6 microM of alpha-solanine, alpha-chaconine, solanidine-N-oxide or IVC medium only. The results showed that the pre-implantation embryo development is inhibited by exposure to these glycoalkaloids. This effect is significant during the later pre-implantation embryo development period as indicated by fewer numbers of expanded and hatched blastocysts produced in the media containing these alkaloids. Therefore, we conclude that in vitro exposure of oocytes and fertilized ova to the steroidal glycoalkaloids from potatoes inhibits pre-implantation embryo development. Furthermore, we suggest that ingestion of Solanum species containing toxic amounts of glycoalkaloids may have negative effects on pre-implantation embryonic survival.

  13. Anticarcinogenic effects of glycoalkaloids from potatoes against human cervical, liver, lymphoma, and stomach cancer cells.

    PubMed

    Friedman, Mendel; Lee, Kap-Rang; Kim, Hyun-Jeong; Lee, In-Seon; Kozukue, Nobuyuke

    2005-07-27

    Methods were devised for the isolation of large amounts of pure alpha-chaconine and alpha-solanine from Dejima potatoes and for the extraction and analysis of total glycoalkaloids from five fresh potato varieties (Dejima, Jowon, Sumi, Toya, and Vora Valley). These compounds were then evaluated in experiments using a tetrazolium microculture (MTT) assay to assess the anticarcinogenic effects of (a) the isolated pure glycoalkaloids separately, (b) artificial mixtures of the two glycoalkaloids, and (c) the total glycoalkaloids isolated from each of the five potato varieties. All samples tested reduced the numbers of the following human cell lines: cervical (HeLa), liver (HepG2), lymphoma (U937), stomach (AGS and KATO III) cancer cells and normal liver (Chang) cells. The results show that (a) the effects of the glycoalkaloids were concentration dependent in the range of 0.1-10 mug/mL (0.117-11.7 nmol/mL); (b) alpha-chaconine was more active than was alpha-solanine; (c) some mixtures exhibited synergistic effects, whereas other produced additive ones; (d) the different cancer cells varied in their susceptibilities to destruction; and (e) the destruction of normal liver cells was generally lower than that of cancer liver cells. The decreases in cell populations were also observed visually by reversed-phase microscopy. The results complement related observations on the anticarcinogenic potential of food ingredients.

  14. Potato glycoalkaloids and adverse effects in humans: an ascending dose study.

    PubMed

    Mensinga, Tjeert T; Sips, Adrienne J A M; Rompelberg, Cathy J M; van Twillert, Klaas; Meulenbelt, Jan; van den Top, Hester J; van Egmond, Hans P

    2005-02-01

    Glycoalkaloids in potatoes may induce gastro-intestinal and systemic effects, by cell membrane disruption and acetylcholinesterase inhibition, respectively. The present single dose study was designed to evaluate the toxicity and pharmacokinetics of orally administered potato glycoalkaloids (alpha-chaconine and alpha-solanine). It is the first published human volunteer study were pharmacokinetic data were obtained for more than 24 h post-dose. Subjects (2-3 per treatment) received one of the following six treatments: (1-3) solutions with total glycoalkaloid (TGA) doses of 0.30, 0.50 or 0.70 mg/kg body weight (BW), or (4-6) mashed potatoes with TGA doses of 0.95, 1.10 or 1.25 mg/kg BW. The mashed potatoes had a TGA concentration of nearly 200 mg/kg fresh weight (the presently recognised upper limit of safety). None of these treatments induced acute systemic effects. One subject who received the highest dose of TGA (1.25 mg/kg BW) became nauseous and started vomiting about 4 h post-dose, possibly due to local glycoalkaloid toxicity (although the dosis is lower than generally reported in the literature to cause gastro-intestinal disturbances). Most relevant, the clearance of glycoalkaloids usually takes more than 24 h, which implicates that the toxicants may accumulate in case of daily consumption.

  15. Cardioactive properties of Solanaceae plant extracts and pure glycoalkaloids on Zophobas atratus.

    PubMed

    Ventrella, Emanuela; Marciniak, Paweł; Adamski, Zbigniew; Rosiński, Grzegorz; Chowański, Szymon; Falabella, Patrizia; Scrano, Laura; Bufo, Sabino A

    2015-04-01

    Glycoalkaloids, the biologically active secondary metabolites produced by Solanaceae plants, are natural defenses against animals, insects and fungi. In this paper, the effects of glycoalkaloids present in extracts of Solanaceae plants (potato, tomato and black nightshade) or pure commercial glycoalkaloids on the coleopteran Zophobas atratus F. were evaluated by in vitro and in vivo bioassays using heart experimental models. Each tested extract induced a dose-dependent cardioinhibitory effect. The perfusion of Zophobas atratus semi-isolated heart using the highest potato and tomato extract concentration (1 mmol/L) caused irreversible cardiac arrests, while extract from black nightshade produced fast but reversible arrests. Pure commercial glycoalkaloids caused similar but less evident effects compared with extracts. Our results showed that the bioactivity of tested compounds depended on their structure and suggested the existence of synergistic interactions when combinations of the main glycoalkaloids of potato and black nightshade were used for trials. Surprisingly, injection of tomato and potato extracts in 1-day-old pupae of Zophobas atratus induced reversible positive chronotropic effects and decreased the duration of the both phases (anterograde and retrograde) of the heart contractile activity. Furthermore, these extracts affected the amplitude of the heart contractions. © 2014 Institute of Zoology, Chinese Academy of Sciences.

  16. Synergism between the potato glycoalkaloids alpha-chaconine and alpha-solanine in inhibition of snail feeding.

    PubMed

    Smith, D B; Roddick, J G; Jones, J L

    2001-05-01

    Snails (Helix aspersa L.) were fed filter paper treated with the potato glycoalkaloids, alpha-solanine and alpha-chaconine, singly or together. In pure form, both glycoalkaloids deterred feeding, with chaconine being the more active compound. In combination, authentic solanine and chaconine interacted synergistically in their inhibition of feeding. The antifeedant activities of methanolic extracts of tuber peel of the potato varieties Majestic and Sharpe's Express presented via filter paper discs did not differ significantly from those of authentic glycoalkaloid solutions of comparable concentration and ratio. In contrast, feeding inhibition by diluted tuber peel extracts of the variety Homeguard was greater than that elicited by comparable authentic glycoalkaloid solutions suggesting additional inhibitory compound(s) in the peel of this variety. Comparison of data from peel extracts of all three potato varieties and authentic glycoalkaloids indicated that the level of feeding inhibition by the extracts was, at least in part, a consequence of a synergism between solanine and chaconine.

  17. Determination of potato glycoalkaloids using high-pressure liquid chromatography-electrospray ionisation/mass spectrometry.

    PubMed

    Matsuda, Fumio; Morino, Keiko; Miyazawa, Haruna; Miyashita, Masahiro; Miyagawa, Hisashi

    2004-01-01

    A method for quantifying two toxic glycoalkaloids, alpha-solanine and alpha-chaconine, in potato (Solanum tuberosum) tuber tissue was developed using HPLC-electrospray ionisation (ESI)/MS. Potato samples were extracted with 5% aqueous acetic acid, and the extracts were subjected directly to HPLC-ESI/MS after filtration. By determining the intensities of the protonated molecules of alpha-solanine (m/z 868) and alpha-chaconine (m/z 852) using selected ion monitoring (positive ion mode), a sensitive assay was attained with detection limits of 38 and 14 ppb for the two glycoalkaloids, respectively. The high sensitivity and selectivity of MS detection effectively reduced the time of analysis thus enabling a high throughput assay of glycoalkaloids in potato tubers.

  18. Glycoalkaloids in potato tubers grown under controlled environments

    NASA Technical Reports Server (NTRS)

    Nitithamyong, A.; Vonelbe, J. H.; Wheeler, R. M.; Tibbitts, T. W.

    1999-01-01

    Tuber content of alpha-solanine, alpha-chaconine, and total glycoalkaloids (TGA) was determined for the potato cultivars, Norland, Russet Burbank, and Denali grown under different environmental conditions in growth chambers. The lowest TGA concentrations (0.30 to 0.35 mg g-1 dry tissue) were found in the cv. Norland with 400 micromoles m-2 s-1 photosynthetic photon flux (PPF), 12 h day length, 16 C temperature, and 350 micromoles mol-1 carbon dioxide. The ratio of alpha-chaconine to alpha-solanine was close to 60:40 under all growing conditions, except that it was 50:50 under the low temperature of 12 C. Cultivars responded similarly to environmental conditions although TGA was about 20% greater in cv. Russet Burbank and about 30% greater in Denali compared to Norland. The largest changes in TGA occurred with changes in temperature. In comparison to 16 C, TGA were 40% greater at 12 C, 80% greater at 20 C, and 125% greater at 24 C (0.70 mg g-1 dry weight). The TGA concentration increased from 10 to 25% with an increase in light from 400 to 800 micromoles m-2 s-1 PPF for all three cultivars. TGA increased 20% with extension of the day length from 12 to 24 hr and also increased 20% when carbon dioxide was increased from 350 to 1000 micromoles mol-1. TGA concentrations were not influenced by changes in relative humidity from 50 to 80%. TGA concentrations decreased only slightly in harvests made from 9 to 21 weeks after planting. Variations in TGA among the different growing conditions and cultivars were below 20 mg/100 g fresh weight (approximately 1.0 mg g-1 dry weight) recognized as the upper concentration for food safety. However the results suggest that TGA should be considered when potatoes are grown at temperatures above 20 C.

  19. Hepatic ornithine decarboxylase induction by potato glycoalkaloids in rats.

    PubMed

    Caldwell, K A; Grosjean, O K; Henika, P R; Friedman, M

    1991-08-01

    The induction of hepatic ornithine decarboxylase (ODC) activity in rat livers by the potato glycoalkaloids alpha-solanine, alpha-chaconine, and their aglycone solanidine, has been studied. Ip administration of alpha-solanine at 7.5, 15 and 30 mg/kg body weight produced markedly elevated enzyme activity at 4 hr after treatment, with a linear dose response. The increase was four-fold at the lowest dose administered to 12-fold at the highest. ODC activity was measured at 1, 2, 3, 4, 5, 6, 8, and 24hr after alpha-solanine was given. A statistically significant increase in enzyme activity was evident at 3 hr after treatment; maximal activity occurred at 5 hr and was approximately 12 times greater than the dimethylsulphoxide (DMSO) control level. Elevated activities persisted for several hours, decreasing to about one-third of the maximal level at 8 hr. The relative effects of alpha-solanine, alpha-chaconine and solanidine on ODC activities were studied at 4 hr using an equimolar dose of 17 mM/kg body weight. ODC activity induced by alpha-chaconine was higher than that induced by alpha-solanine; the latter activity was two-thirds that of the former. The aglycone solanidine did not induce any increase in activity compared with the DMSO control. ODC activity with dexamethasone, a glucocorticoid, at 4 mg/kg body weight, followed a pattern similar to that of alpha-solanine. However, maximal activity occurred slightly earlier at 4 hr after treatment. The results show that the extent of induced ODC activity depends on the structure of the potato alkaloid.

  20. Glycoalkaloids in potato tubers grown under controlled environments.

    PubMed

    Nitithamyong, A; Vonelbe, J H; Wheeler, R M; Tibbitts, T W

    1999-01-01

    Tuber content of alpha-solanine, alpha-chaconine, and total glycoalkaloids (TGA) was determined for the potato cultivars, Norland, Russet Burbank, and Denali grown under different environmental conditions in growth chambers. The lowest TGA concentrations (0.30 to 0.35 mg g-1 dry tissue) were found in the cv. Norland with 400 micromoles m-2 s-1 photosynthetic photon flux (PPF), 12 h day length, 16 C temperature, and 350 micromoles mol-1 carbon dioxide. The ratio of alpha-chaconine to alpha-solanine was close to 60:40 under all growing conditions, except that it was 50:50 under the low temperature of 12 C. Cultivars responded similarly to environmental conditions although TGA was about 20% greater in cv. Russet Burbank and about 30% greater in Denali compared to Norland. The largest changes in TGA occurred with changes in temperature. In comparison to 16 C, TGA were 40% greater at 12 C, 80% greater at 20 C, and 125% greater at 24 C (0.70 mg g-1 dry weight). The TGA concentration increased from 10 to 25% with an increase in light from 400 to 800 micromoles m-2 s-1 PPF for all three cultivars. TGA increased 20% with extension of the day length from 12 to 24 hr and also increased 20% when carbon dioxide was increased from 350 to 1000 micromoles mol-1. TGA concentrations were not influenced by changes in relative humidity from 50 to 80%. TGA concentrations decreased only slightly in harvests made from 9 to 21 weeks after planting. Variations in TGA among the different growing conditions and cultivars were below 20 mg/100 g fresh weight (approximately 1.0 mg g-1 dry weight) recognized as the upper concentration for food safety. However the results suggest that TGA should be considered when potatoes are grown at temperatures above 20 C.

  1. Probabilistic Exposure Analysis for Chemical Risk Characterization

    PubMed Central

    Bogen, Kenneth T.; Cullen, Alison C.; Frey, H. Christopher; Price, Paul S.

    2009-01-01

    This paper summarizes the state of the science of probabilistic exposure assessment (PEA) as applied to chemical risk characterization. Current probabilistic risk analysis methods applied to PEA are reviewed. PEA within the context of risk-based decision making is discussed, including probabilistic treatment of related uncertainty, interindividual heterogeneity, and other sources of variability. Key examples of recent experience gained in assessing human exposures to chemicals in the environment, and other applications to chemical risk characterization and assessment, are presented. It is concluded that, although improvements continue to be made, existing methods suffice for effective application of PEA to support quantitative analyses of the risk of chemically induced toxicity that play an increasing role in key decision-making objectives involving health protection, triage, civil justice, and criminal justice. Different types of information required to apply PEA to these different decision contexts are identified, and specific PEA methods are highlighted that are best suited to exposure assessment in these separate contexts. PMID:19223660

  2. Glycoalkaloid content in pet food by UPLC-tandem mass spectrometry.

    PubMed

    Sheridan, Robert S; Kemnah, Jennifer L

    2010-11-01

    The glycoalkaloid content of pet food containing potatoes is investigated using a liquid-liquid solvent extraction followed by analysis by ultra-high pressure liquid chromatography tandem mass spectrometry (UPLC-MS-MS). Pet food samples are homogenized and extracted with a solution of 50:50 (v/v) acetonitrile-deionized water containing 5% acetic acid. Following vortexing and centrifugation, 3 mL of the supernatant is filtered and diluted in deionized water. The extract is injected onto a reverse phase C18 UPLC column with an initial mobile phase composed of 0.15% acetic acid in water (A) and 0.15% acetic acid in methanol (B) in a ratio of 70:30, respectively. The mobile phase reaches a final concentration of 15% A and 85% B over 10 min, at which point it is returned to the initial conditions. α-Solanine is measured by monitoring transitions m/z = 868.50 → 398.40 and 868.50 → 722.50, while α-chaconine is measure by monitoring transitions m/z = 852.60 → 97.80 and 852.60 → 706.50. Each analyte is measured and combined to determine total glycoalkaloid content (TGA). The results of the analysis of 52 pet food samples indicate both glycoalkaloids are present in all samples and two pet foods were found to contain > 100 μg/g total glycoalkaloid.

  3. Effect of genotype and environment on the glycoalkaloid content of rare, heritage, and commercial potato varieties.

    PubMed

    Valcarcel, Jesus; Reilly, Kim; Gaffney, Michael; O'Brien, Nora

    2014-05-01

    Potatoes accumulate toxic steroidal compounds that could be harmful for humans if consumed in high quantities and must be controlled. In this study, we were interested in assessing the levels and variation of glycoalkaloid content in 60 varieties of potato planted in 2 trial sites over 2 y. Total glycoalkaloid levels ranged from 4 to 957 mg/kg of dry weight in the flesh and from 150 to 8133 mg/kg in the skin, with the latter accumulating generally more α-chaconine than α-solanine. Contents in the flesh were below the safe limit for all varieties, but were generally above in the skin. Maximum values in each site and year of cultivation were found for varieties "Beauty of Hebron," "May Queen," and "Arran Pilot" in the skin and "Beauty of Hebron," "International Kidney," and "Congo" in the flesh. Year of cultivation had a significant effect on total glycoalkaloid content (P < 0.0001), with interactions between variety and site of cultivation and variety and year of cultivation also significant (P < 0.0001), implying that environmental effects seem to act differentially and could induce high levels in genetically predisposed varieties. This paper reports the levels of toxic glycoalkaloids in 60 varieties of potato. Dietary intake and safety of consumers is discussed and varieties used by the potato processing industry are assessed in terms of safety and potential use of waste peel as raw material. © 2014 Institute of Food Technologists®

  4. Induction of the cholesterol biosynthesis pathway in differentiated Caco-2 cells by the potato glycoalkaloid alpha-chaconine.

    PubMed

    Mandimika, Tafadzwa; Baykus, Hakan; Poortman, Jenneke; Garza, Cutberto; Kuiper, Harry; Peijnenburg, Ad

    2007-10-01

    Glycoalkaloids are naturally occurring toxins in potatoes, which at high levels may induce toxic effects in humans, mainly on the gastrointestinal tract by cell membrane disruption. In order to better understand the molecular mechanisms underlying glycoalkaloid toxicity, we examined the effects of alpha-chaconine on gene expression in the Caco-2 intestinal epithelial cell line using DNA microarrays. Caco-2 cells were exposed for 6h to 10 microM alpha-chaconine in three independent experiments (randomized block design). The most prominent finding from our gene expression and pathway analyses was the upregulation of expression of several genes involved in cholesterol biosynthesis. This to some extent is in line with the literature-described mechanism of cell membrane disruption by glycoalkaloids. In addition, various growth factor signaling pathways were found to be significantly upregulated. This study is useful in understanding the mechanism(s) of alpha-chaconine toxicity, which may be extended to other potato glycoalkaloids more generally.

  5. Anti-protozoal effects of the tomato tetrasaccharide glycoalkaloid tomatine and the aglycone tomatidine on mucosal trichomonads

    USDA-ARS?s Scientific Manuscript database

    The present study investigated the inhibitory effects of the commercial tetrasaccharide tomato glycoalkaloid tomatine and the aglycone tomatidine on three mucosal pathogenic protozoa that are reported to infect humans, cattle, and cats, respectively: Trichomonas vaginalis Strain G3, Tritrichomonas f...

  6. Inheritance of morphological characters and glycoalkaloids in potatoes of somatic hybrids between dihaploid Solanum acauleand tetraploid Solanum tuberosum.

    PubMed

    Kozukue, N; Misoo, S; Yamada, T; Kamijima, O; Friedman, M

    1999-10-01

    Steroidal glycoalkaloids occur in potatoes and are reported to impart resistance to phytopathogens including bacteria, fungi, and insects. Because glycoalkaloids can be passed to progenies during breeding programs designed to develop improved potatoes, it is of importance to determine the quality of desired characteristics and the composition of glycoalkaloids of new somatic hybrids. The objective of this study was to determine the appearance, size, and shape (morphological characters) as well as the glycoalkaloid content of potato tubers of somatic hybrids between tetraploid Solanum tuberosum cv. Dejima (2n = 4x = 48 chromosomes) and the dihaploid clone ATDH-1 (2n = 2x = 24 chromosomes) induced by anther culture from Solanum acuale-T (acl-T, 2n = 4x = 48 chromosomes). Tuber size and shape in somatic hybrids were in accord with those of cv. Dejima, whereas the tuber skin color resembled that of ATDH-1. Thin-layer chromatography, high-performance liquid chromatography, and gas-liquid chromatography/mass spectrometry studies showed that the two steroidal glycoalkaloids (alpha-chaconine and alpha-solanine) were present in the tubers of S. tuberosum, whereas acl-T and ATDH-1 tubers were found to contain alpha-tomatine and demissine. The concentrations of total glycoalkaloids in both acl-T and ATDH-1 was >100 mg/100 g of fresh weight tuber cortex, much higher than in S. tuberosum. All somatic hybrids, except one clone, contained four glycoalkaloids (alpha-chaconine, alpha-solanine, alpha-tomatine, and demissine) derived from the fusion parents. The lack of alpha-tomatine in the remaining clone may be due to somaclonal variation. The results show that character expression is influenced by ploidy level and that total glycoalkaloid levels in most somatic hybrids were intermediate between those of the fusion parents. The possible significance of these findings for plant breeding and food safety is discussed.

  7. Preparative separation of glycoalkaloids α-solanine and α-chaconine by centrifugal partition chromatography.

    PubMed

    Attoumbré, Jacques; Lesur, David; Giordanengo, Philippe; Baltora-Rosset, Sylvie

    2012-11-01

    The main glycoalkaloids of a commercial potato cultivar, α-chaconine and α-solanine, were extracted from sprouts of Solanum tuberosum cv. Pompadour by a mixture of MeOH/H(2)O/CH(3)COOH (400/100/50, v/v/v). In these conditions, 2.8±0.62g of crude extract were obtained from 50g of fresh sprouts and the total glycoalkaloid content was determined by analytical HPLC at 216.5mg/100g. α-Chaconine and α-solanine were separated in a preparative scale using centrifugal partition chromatography (CPC). In a solvent system composed of a mixture of ethyl acetate/butanol/water (15/35/50, v/v/v), α-chaconine (54mg) and α-solanine (15mg) were successfully isolated from the crude extract in one step of purification. The purity of isolated compounds was determined to be higher than 92% by HPLC analysis.

  8. Reversed-phase liquid chromatographic separation and simultaneous profiling of steroidal glycoalkaloids and their aglycones.

    PubMed

    Kuronen, P; Väänänen, T; Pehu, E

    1999-11-19

    Improved and simplified reversed-phase liquid chromatographic conditions for the separation and simultaneous profiling of both steroidal glycoalkaloids and their aglycones, having solanidane- or spirosolane-type structures, are described. The most reproducible retention behavior for these ionizable compounds on C18 columns was achieved under isocratic and gradient elution conditions using acetonitrile in combination with triethylammonium phosphate buffer at pH 3.0, when basic functional groups of solutes and silanol groups on the silica are fully protonated minimizing ionic interactions. Gradient elution was the only feasible approach for the simultaneous separation of steroidal glycoalkaloids and their aglycones. A Zorbax SB C18 column, specially designed for low-pH separations, showed good performance in critical separations. The impurities of the commercial tomatine and tomatidine standards were studied and confirmed using mass spectrometric, liquid chromatographic and thin-layer chromatographic methods.

  9. [Study of the interaction of main potato glycoalkaloids in inhibition of immobilized butyryl cholinesterase].

    PubMed

    Arkhypova, V M; Dziadevych, S V; Jaffrezic-Renault, N; Martelet, C; Soldatkin, O P

    2006-01-01

    The interaction of main potato glycoalkaloids alpha-solanine and alpha-chaconine in inhibition of horse serum butyryl cholinesterases immobilized on the pH-sensitive field-effect transistors has been investigated. The method of isobol diagram of Loewe and Muishnek has been used for interpretation of results. It has been shown the alpha-chaconine inhibits the immobilized bytyryl cholinesterases more strongly than alpha-solanine, and their mixture has the addition effect.

  10. Lanosterol synthase-like is involved with differential accumulation of steroidal glycoalkaloids in potato.

    PubMed

    Kumar, Akhilesh; Fogelman, Edna; Weissberg, Mira; Tanami, Zachariah; Veilleux, Richard E; Ginzberg, Idit

    2017-08-21

    Phytosterol homeostasis may be maintained in leaves through diversion of intermediates into glycoalkaloid biosynthesis, whereas in tuber flesh, excess intermediates are catalyzed by tuber-specific StLAS - like , resulting in low tuber glycoalkaloids. Lanosterol synthase (LAS) and cycloartenol synthase (CAS) are phylogenetically related enzymes. Cycloartenol is the accepted precursor leading to cholesterol and phytosterols, and in potato, to steroidal glycoalkaloid (SGA) biosynthesis. LAS was also shown to synthesize some plant sterols, albeit at trace amounts, questioning its role in sterol homeostasis. Presently, a potato LAS-related gene (StLAS-like) was identified and its activity verified in a yeast complementation assay. A transgenic approach with targeted gene expression and metabolic profiling of sterols and SGAs was used. Analyses of StLAS-like transcript levels and StLAS-like-promoter::GUS reporter assays indicated specific expression in tuber flesh tissue. Overexpression of Arabidopsis AtLAS in leaves where the endogenic StLAS-like is not expressed, resulted with increased SGA level and reduced phytosterol level, while in the tuber flesh SGA level was reduced. StLAS-like expression only in tuber flesh may explain the differential accumulation of SGAs in commercial cultivars-low in tubers, high in leaves. In leaves, to maintain phytosterol homeostasis, an excess of intermediates may be diverted into SGA biosynthesis, whereas in tuber flesh these intermediates are catalyzed by tuber-specific StLAS-like instead, resulting in low levels of SGA.

  11. Glycoalkaloid development during greening of fresh market potatoes (Solanum tuberosum L.).

    PubMed

    Grunenfelder, Laura A; Knowles, Lisa O; Hiller, Larry K; Knowles, N Richard

    2006-08-09

    Chlorophyll and glycoalkaloid synthesis in potato (Solanum tuberosum L.) tubers occur in direct response to light. The two processes are concurrent, but independent. Color photographic indices to subjectively grade fresh market potatoes for the extent of greening were developed under lighting conditions consistent with those of retail markets. Total glycoalkaloid (TGA) and chlorophyll accumulation for four cultivars were determined over the respective greening scales, thus calibrating the scales for TGA content. On average, TGA concentrations in complete longitudinal sections of tubers (flesh samples) were highest in Dark Red Norland followed by Russet Norkotah, Yukon Gold, and White Rose. TGA concentrations of flesh samples of White Rose and Yukon Gold tubers were somewhat variable and did not increase in direct proportion to greening level and chlorophyll content, particularly at higher levels of greening. TGA concentrations in Dark Red Norland and Russet Norkotah tubers were highly correlated (P < or = 0.001) with greening level and chlorophyll concentrations. When averaged over greening levels, skin samples contained 3.4- to 6.8-fold higher concentrations of TGAs than flesh samples, depending on the cultivar. The TGA concentration in periderm samples ranged from 37 to 160 mg/100 g of dry wt. Regardless of greening level, concentrations of TGAs in the flesh samples (including attached periderm) remained within limits presumed safe for human consumption. Discrimination of greened tubers on the basis of perceived glycoalkaloid toxicity is likely unfounded for the cultivars and greening levels studied.

  12. Technical Overview of Ecological Risk Assessment - Analysis Phase: Exposure Characterization

    EPA Pesticide Factsheets

    Exposure Characterization is the second major component of the analysis phase of a risk assessment. For a pesticide risk assessment, the exposure characterization describes the potential or actual contact of a pesticide with a plant, animal, or media.

  13. Glycoalkaloid, phenolic, and flavonoid content and antioxidative activities of conventional (nonorganic) and organic potato peel powders from commercial Gold, Red, and Russet Potatoes

    USDA-ARS?s Scientific Manuscript database

    The content of glycoalkaloids a-chaconine and a-solanine, individual and total phenolics compounds, and total flavonoids for three peels prepared from conventional and three from organic commercial potatoes as well antioxidant activities using three different methods were evaluated. Glycoalkaloids ...

  14. Composition of phenolic compounds and glycoalkaloids alpha-solanine and alpha-chaconine during commercial potato processing.

    PubMed

    Mäder, Jens; Rawel, Harshadrai; Kroh, Lothar W

    2009-07-22

    The influence of a commercial production process for dehydrated potato flakes on the content of free phenolic compounds, total phenolics, and glycoalkaloids in potatoes during the subsequent processing steps was determined. Processing byproducts, such as potato peel (steam peeling), mashed potato residues, and side streams (blanching and cooking waters), have also been investigated. A high-performance liquid chromatography (HPLC) method was developed to separate and quantify caffeic acid, gallic acid, ferulic acid, p-coumaric acid, p-hydoxybenzoic acid, protocatechuic acid, vanillic acid, catechin, and three isomers of caffeoylquinic acid: chlorogenic, neochlorogenic and cryptochlorogenic acid. Determination of the glycoalkaloids alpha-solanine and alpha-chaconine was performed by using a high-performance thin-layer chromatography (HPTLC) method. The deliverables reveal that processing potatoes to potato flakes remarkably diminishes the content of the analyzed compounds, mainly due to peeling and leaching. The influence of thermal exposure is less significant. About 43% of the initial phenolic acids and 10% of the glycoalkaloids remain after processing. The results of the total phenolic content assay by Folin-Ciocalteu reagent are proportional to the content of phenolic compounds determined by HPLC. Steam peeling has a higher influence on glycoalkaloid losses compared to that on phenolics. The highest amounts of phenolic compounds and glycoalkaloids were found in peeling byproduct. During processing, the amount of chlorogenic acid decreased, whereas the concentration of neochlorogenic acid increased due to isomerization. The impact of the results on potato processing technology is discussed.

  15. The folic acid analogue methotrexate protects frog embryo cell membranes against damage by the potato glycoalkaloid alpha-chaconine.

    PubMed

    McWilliams, M L; Blankemeyer, J T; Friedman, M

    2000-10-01

    As part of an effort to improve the safety of plant foods, a need exists to more clearly delineate the mechanisms of toxicities of glycoalkaloids, which may be present in Solanum plant species such as potatoes, tomatoes and eggplants. Alpha-chaconine is a major glycoalkaloid present in potatoes. To assess the possible influence of structure of pteridine derivatives on toxicity of potato glycoalkaloids, a previous study that demonstrated the protective effects of folic acid against the Solanum glycoalkaloid alpha-chaconine-induced toxicity on Xenopus laevis frog embryo cell membranes was extended to two folate analogues--a synthetic compound widely used as a therapeutic agent methotrexate, and naturally occurring L-monapterin. Adverse effects on embryos were evaluated by observing changes in membrane potentials with an electrochromic dye, di-4-ANEPPS, as a fluorescent probe for the integrity of the membranes. Methotrexate decreased alpha-chaconine-induced polarization, as did folic acid. This decrease may result from an alteration of membrane conformations that prevents the binding of the glycoalkaloid to the membrane receptor sites, and/or from effects on folic acid metabolism. In contrast, L-monapterin did not significantly reduce the alpha-chaconine-induced toxicity. The possible significance of these results to food safety is discussed.

  16. Antifungal activity of secondary plant metabolites from potatoes (Solanum tuberosum L.): Glycoalkaloids and phenolic acids show synergistic effects.

    PubMed

    Sánchez-Maldonado, A F; Schieber, A; Gänzle, M G

    2016-04-01

    To study the antifungal effects of the potato secondary metabolites α-solanine, α-chaconine, solanidine and caffeic acid, alone or combined. Resistance to glycoalkaloids varied among the fungal species tested, as derived from minimum inhibitory concentrations assays. Synergistic antifungal activity between glycoalkaloids and phenolic compounds was found. Changes in the fluidity of fungal membranes caused by potato secondary plant metabolites were determined by calculation of the generalized polarization values. The results partially explained the synergistic effect between caffeic acid and α-chaconine and supported findings on membrane disruption mechanisms from previous studies on artificial membranes. LC/MS analysis was used to determine variability and relative amounts of sterols in the different fungal species. Results suggested that the sterol pattern of fungi is related to their resistance to potato glycoalkaloids and to their taxonomy. Fungal resistance to α-chaconine and possibly other glycoalkaloids is species dependent. α-Chaconine and caffeic acid show synergistic antifungal activity. The taxonomic classification and the sterol pattern play a role in fungal resistance to glycoalkaloids. Results improve the understanding of the antifungal mode of action of potato secondary metabolites, which is essential for their potential utilization as antifungal agents in nonfood systems. © 2016 The Society for Applied Microbiology.

  17. Implementing the Deputy Administrator's Risk Characterization Memorandum, May 26, 1992

    EPA Pesticide Factsheets

    The purpose of this memorandum is to implement in the Superfund program the reccomendations of the Deputy Administrator in his memorandum of February 26, 1992, 'Guidance on risk characterization for risk managers and risk assessors.'

  18. Potato glycoalkaloids in soil-optimising liquid chromatography-time-of-flight mass spectrometry for quantitative studies.

    PubMed

    Jensen, Pia H; Juhler, René K; Nielsen, Nikoline J; Hansen, Thomas H; Strobel, Bjarne W; Jacobsen, Ole S; Nielsen, John; Hansen, Hans Christian B

    2008-02-22

    Potato glycoalkaloids are produced in high amounts in potato fields during the growth season and losses to soil potentially impact shallow groundwater and via tiles to fresh water ecosystems. A quantitative liquid chromatography-electrospray ionization time-of-flight mass spectrometry (LC-ESI-TOF-MS) method for determination and quantification of potato glycoalkaloids and their metabolites in aqueous soil extracts was developed. The LC-ESI-TOF-MS method had linearities up to 2000microg/L for alpha-solanine and alpha-chaconine and up to 760microg/L for solanidine. No matrix effect was observed, and the detection limits found were in the range 2.2-4.7microg/L. The method enabled quantification of the potato glycoalkaloids in environmental samples.

  19. The challenge of risk characterization: current practice and future directions.

    PubMed Central

    Gray, G M; Cohen, J T; Graham, J D

    1993-01-01

    Risk characterization is perhaps the most important part of risk assessment. As currently practiced, risk characterizations do not convey the degree of uncertainty in a risk estimate to risk managers, Congress, the press, and the public. Here, we use a framework put forth by an ad hoc study group of industry and government scientists and academics to critique the risk characterizations contained in two risks assessments of gasoline vapor. After discussing the strengths and weaknesses of each assessment's risk characterization, we detail an alternative approach that conveys estimates in the form of a probability distribution. The distributional approach can make use of all relevant scientific data and knowledge, including alternative data sets and all plausible mechanistic theories of carcinogenesis. As a result, this approach facilitates better public health decisions than current risk characterization procedures. We discuss methodological issues, as well as strengths and weaknesses of the distributional approach. PMID:8020444

  20. Chemistry and anticarcinogenic mechanisms of glycoalkaloids produced by eggplants, potatoes, and tomatoes.

    PubMed

    Friedman, Mendel

    2015-04-08

    Inhibition of cancer can occur via apoptosis, a genetically directed process of cell self-destruction that involves numerous biomarkers and signaling pathways. Glycoalkaloids are nitrogen-containing secondary plant metabolites found in numerous Solanaceous plants including eggplants, potatoes, and tomatoes. Exposure of cancer cells to glycoalkaloids produced by eggplants (α-solamargine and α-solasonine), potatoes (α-chaconine and α-solanine), and tomatoes (α-tomatine) or their hydrolysis products (mono-, di-, and trisaccharide derivatives and the aglycones solasodine, solanidine, and tomatidine) inhibits the growth of the cells in culture (in vitro) as well as tumor growth in vivo. This overview comprehensively surveys and consolidates worldwide efforts to define the following aspects of these natural compounds: (a) their prevalence in the three foods; (b) their chemistry and structure-activity relationships; (c) the reported factors (biomarkers, signaling pathways) associated with apoptosis of bone, breast, cervical, colon, gastric, glioblastoma, leukemia, liver, lung, lymphoma, melanoma, pancreas, prostate, and squamous cell carcinoma cell lines in vitro and the in vivo inhibition of tumor formation and growth in fish and mice and in human skin cancers; and (d) future research needs. The described results may make it possible to better relate the structures of the active compounds to their health-promoting function, individually, in combination, and in food, and allow the consumer to select glycoalkaloid-containing food with the optimal content of nontoxic beneficial compounds. The described findings are expected to be a valuable record and resource for further investigation of the health benefits of food-related natural compounds.

  1. Toxic effect of the glycoalkaloids solanine and tomatine on cultured neonatal rat heart cells.

    PubMed

    Bergers, W W; Alink, G M

    1980-06-01

    The toxic effects of the glycoalkaloids, alpha-solanine and tomatine, were studied in beating heart cell cultures from 1--2-day-old rats. After addition of alpha-solanine (80 microgram/ml) and tomatine (40 microgram/ml) to the culture medium, the cells ceased beating within a few minutes. At a concentration of 40 microgram/ml alpha-solanine and 20 microgram/ml tomatine, both compounds caused a pronounced increase of the contraction frequency, lasting for at least 2h. K-strophantin, a reference heart glycoside, caused arrhythmic beating at 20 microgram/ml and complete cessation of contractions at 160 microgram/ml.

  2. Impact of light-exposure on the metabolite balance of transgenic potato tubers with modified glycoalkaloid biosynthesis

    USDA-ARS?s Scientific Manuscript database

    Metabolite profiling has been used to assess the impact of light exposure on the composition of potato (Solanum tuberosum L. cv. Desirée) tubers genetically modified (GM) to reduce glycoalkaloid (specifically a-solanine) content via the down-regulation of the SGT1 gene. Using a combination of liq...

  3. Bioassay-guided fractionation of extracts from Easter lily (Lilium longiflorum) flowers reveals unprecedented structural variability of steroidal glycoalkaloids.

    PubMed

    Uhlig, Silvio; Hussain, Fozia; Wisløff, Helene

    2014-12-15

    Several Lilium species are nephrotoxic in cats (Felis silvestris catus), among them Easter lilies (Lilium longiflorum). Although clinical trials have been carried out, the causative toxic phytochemicals have not yet been identified. We thus aimed to determine the toxic constituents of Easter lily flowers applying a bioassay-guided approach based on a feline kidney cell line model. The bioassay-guided fractionation traced the observed cytotoxicity to a complex mixture of compounds that were tentatively identified as steroidal glycoalkaloids of the solasodine-type, based on multiple-fragmentation ion trap and high-resolution mass spectrometry. The glycoalkaloids in the active fraction possessed trisaccharide chains, and at least 16 different congeners could be separated using liquid chromatography-mass spectrometry. The two principal compounds were solasodine trisaccharides containing two hexose and one deoxy-hexose unit. In the remaining 14 analogues, one or two of the hydroxyl groups of the second hexose from the aglycone were acetylated. In addition, some of the analogues appeared to be carbonate esters. Esterification of steroidal glycoalkaloids in plants has only been reported once and was in accordance with higher antifungal activity of the acetylated versus the parent congener. Our pilot study shows that esterification of steroidal glycoalkaloids in Lilium species might be common resulting in an array of different analogues with largely unexplored structural variability and bioactivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Elucidation of the mass fragmentation pathways of potato glycoalkaloids and aglycons using Orbitrap mass spectrometry.

    PubMed

    Cahill, Michael G; Caprioli, Giovanni; Vittori, Sauro; James, Kevin J

    2010-09-01

    The mass fragmentation of potato glycoalkaloids, α-solanine and α-chaconine, and the aglycons, demissidine and solasodine were studied using the Orbitrap Fourier transform (FT) mass spectrometer. Using the linear ion trap (LIT) mass spectrometry, multistage collisional-induced dissociation (CID) experiments (MS(n)) on the [M + H](+) precursor ions were performed to aid the elucidation of the mass fragmentation pathways. In addition, higher energy collisional-induced dissociation (HCD) mass spectra were generated for these toxins at a high resolution setting [100,000 FWHM (full width at half maximum)] using the Orbitrap. This hybrid mass spectrometry instrumentation was exploited to produce MS(3) spectra by selecting MS(2) product ions, generated using LIT MS, and fragmentation using HCD. The accurate mass data in the MS(3) spectra aided the confirmation of proposed product ion formulae. The precursor and product ions from glycoalkaloids lost up to four sugars from different regions during MS(n) experiments. Mass fragmentation of the six-ring aglycons were similar, generating major product ions that resulted from cleavages at the B-rings and E-rings.

  5. Capillary electrophoresis of tropane alkaloids and glycoalkaloids occurring in Solanaceae plants.

    PubMed

    Cataldi, Tommaso R I; Bianco, Giuliana

    2008-01-01

    This chapter examines the role of capillary electrophoresis (CE) in the separation of tropane alkaloids, glycoalkaloids, and closely related compounds that have either pharmaceutical value or toxicological effects on humans. The latest significant developments in CE analysis have been selected and critically discussed. When the conventional CE mode was found unable to provide an acceptable selectivity towards the analytes, the addition of either an organic solvent, a chiral selector, or a surfactant to the running buffers was exploited. Likewise, nonaqueous CE (NACE) was also employed to increase solute solubilities and for a better compatibility of this media with mass spectrometry. It turns out that, upon selecting the most appropriate experimental conditions, the CE separation of tropane alkaloids and steroidal glycoalkaloids of Solanaceae plants was successfully accomplished. All major steps involved in the separation and detection of these secondary metabolites in complex samples are described and the relevant aspects of each application are examined with emphasis on the main aspects entailed a typical assay. More applications have yet to be developed in order to encourage more labs to exploit the tremendous potential of capillary electrophoresis.

  6. Solanaceous steroidal glycoalkaloids and poisoning by Solanum torvum, the normally edible susumber berry.

    PubMed

    Smith, Silas W; Giesbrecht, Esther; Thompson, Margaret; Nelson, Lewis S; Hoffman, Robert S

    2008-11-01

    Ingestion of immature, environmentally stressed, or cultivar-specific Solanum species (particularly the potato) has been previously associated with gastrointestinal and neurological symptoms caused by solanaceous steroidal glycoalkaloids (SGAs). We report on two geographically, temporally disparate outbreaks of poisoning by susumber berries (Solanum torvum- Solanaceae) and on detection of alkaloids not present in non-toxic berries. Five family members in New York City participated in a traditional evening meal containing Jamaican susumber berries. All those consuming berries were symptomatic the following morning with varying degrees of gastrointestinal distress, dizziness, slurred speech, cranial nerve deficits, and ataxia. The most seriously afflicted patient developed hypertension, confusion, proximal upper extremity weakness, and hypercapnic respiratory failure requiring prolonged mechanical ventilation. A separate cohort of six patients in Toronto ate unripe Jamaican susumber berries. They presented 14h post-ingestion with varying degrees of diarrhea, weakness, facial paralysis, slurred speech, ataxia, early hypertension, and proximal weakness. Two patients had ventilatory decompensation; one required intubation. Poisonous berries appeared indistinguishable from non-toxic varieties. We isolated solasonine, larger amounts of solamargine, and other steroidal glycoalkaloids in the toxic berry strains. S. torvum poisoning can produce significant neurological and gastrointestinal effects which appear to be mediated by SGAs present in the berries.

  7. Glycoalkaloid profile in potato haploids derived from solanum tuberosum-S. bulbocastanum somatic hybrids.

    PubMed

    Carputo, Domenico; Savarese, Salvatore; Andolfi, Anna; Aversano, Riccardo; Cimmino, Alessio; Frusciante, Luigi; Evidente, Antonio

    2010-08-01

    Cultivated and wild potato species synthesize a wide variety of steroidal glycoalkaloids (GA) that may affect either human health or biotic stress resistance. Therefore, GA composition must be a major criterion in the evaluation of breeding products when species genomes are merged and/or manipulated. This work reports the results of GA analysis performed on unique haploid (2n=2x=24) plants obtained from tetraploid (2n=4x=48) Solanum bulbocastanum-S. tuberosum hybrids through in vitro anther culture. Glycoalkaloids were extracted from tubers and analyzed by HPLC. Haploids generally showed the occurrence of parental GA. However, in several cases loss of parental GA and gain of new GA lacking in the parents was observed. It may be hypothesized that new GA profiles of our haploids is the result of either genetic recombination or combinatorial biochemistry events. To highlight differences between haploids and parents, soluble proteins and antioxidant activities were also determined. Both were always higher in haploids compared to their parents. The nature of the newly formed GAs will be further investigated, because they may represent new metabolites that can be used against pest and diseases, or are useful for human health.

  8. Antiprotozoal Effects of the Tomato Tetrasaccharide Glycoalkaloid Tomatine and the Aglycone Tomatidine on Mucosal Trichomonads.

    PubMed

    Liu, Jenny; Kanetake, Sierra; Wu, Yun-Hsuan; Tam, Christina; Cheng, Luisa W; Land, Kirkwood M; Friedman, Mendel

    2016-11-23

    The present study investigated the inhibitory effects of the commercial tetrasaccharide tomato glycoalkaloid tomatine and the aglycone tomatidine on three mucosal pathogenic protozoa that are reported to infect humans, cattle, and cats, respectively: Trichomonas vaginalis strain G3, Tritrichomonas foetus strain D1, and Tritrichomonas foetus strain C1. A preliminary screen showed that tomatine at 100 μM concentration completely inhibited the growth of all three trichomonads. In contrast, the inhibition of all three pathogens by tomatidine was much lower, suggesting the involvement of the lycotetraose carbohydrate side chain in the mechanism of inhibition. Midpoints of concentration-response sigmoid plots of tomatine on the three strains correspond to IC50 values, the concentration that inhibits 50% of growth of the pathogenic protozoa. The concentration data were used to calculate the IC50 values for G3, D1, and C1 of 7.9, 1.9, and 2.2 μM, respectively. The results show an approximately 4-fold variation from the lowest to the highest value (lowest activity). Although the inhibition by tomatine was not as effective as that of the medicinal drug metronidazole, the relatively low IC50 values for both T. vaginalis and T. foetus indicated tomatine as a possible natural alternative therapeutic for trichomoniasis in humans and food-producing (cattle and pigs) and domestic (cats) animals. Because tomatine has the potential to serve as a new antiprotozoan functional (medical) food, the distribution of this glycoalkaloid in tomatoes and suggestions for further research are discussed.

  9. GLYCOALKALOID METABOLISM1 is required for steroidal alkaloid glycosylation and prevention of phytotoxicity in tomato.

    PubMed

    Itkin, Maxim; Rogachev, Ilana; Alkan, Noam; Rosenberg, Tally; Malitsky, Sergey; Masini, Laura; Meir, Sagit; Iijima, Yoko; Aoki, Koh; de Vos, Ric; Prusky, Dov; Burdman, Saul; Beekwilder, Jules; Aharoni, Asaph

    2011-12-01

    Steroidal alkaloids (SAs) are triterpene-derived specialized metabolites found in members of the Solanaceae family that provide plants with a chemical barrier against a broad range of pathogens. Their biosynthesis involves the action of glycosyltransferases to form steroidal glycoalkaloids (SGAs). To elucidate the metabolism of SGAs in the Solanaceae family, we examined the tomato (Solanum lycopersicum) GLYCOALKALOID METABOLISM1 (GAME1) gene. Our findings imply that GAME1 is a galactosyltransferase, largely performing glycosylation of the aglycone tomatidine, resulting in SGA production in green tissues. Downregulation of GAME1 resulted in an almost 50% reduction in α-tomatine levels (the major SGA in tomato) and a large increase in its precursors (i.e., tomatidenol and tomatidine). Surprisingly, GAME1-silenced plants displayed growth retardation and severe morphological phenotypes that we suggest occur as a result of altered membrane sterol levels caused by the accumulation of the aglycone tomatidine. Together, these findings highlight the role of GAME1 in the glycosylation of SAs and in reducing the toxicity of SA metabolites to the plant cell.

  10. Glycoalkaloid levels in potato tubers and leaves after intermittent plant exposure to ozone

    SciTech Connect

    Speroni, J.J.; Pell, E.J.; Weissberger, W.C.

    1981-01-01

    Irish potato vines of Norland and Kennebec cultivars were exposed to 387 ..mu..g/m/sup 3/ ozone for 3 hr once every wk throughout their growth. Tubers of Norland and Kennebec were harvested at 120 and 140 days, respectively, from exposed and non-exposed plants. The experiment was conducted in 1977 and again in 1978. Ozone induced severe foliar injury to Norland and slight injury to leaves of Kennebec. Tubers from ozone treated plants displayed a significant reduction (0.35 mg TTGA/100 g fresh weight tuber tissue) in tuber total glycoalkaloids (TTGA) when expressed on a fresh weight basis. However, since differences were not detected for TTGA on a dry-weight basis, the fresh-weight TTGA differences may only reflect variations in moisture content. In a separate experiment, both Norland and Kennebec were exposed to 488 ..mu..g/m/sup 3/ ozone for 3 hr when the plants were 18 days old. When leaves were harvested three days later, no significant differeces were detected between leaf total glycoalkaloid (LTGA) levels of treated and nontreated plants. 26 references, 2 tables.

  11. RISK-INFORMED SAFETY MARGIN CHARACTERIZATION

    SciTech Connect

    Nam Dinh; Ronaldo Szilard

    2009-07-01

    The concept of safety margins has served as a fundamental principle in the design and operation of commercial nuclear power plants (NPPs). Defined as the minimum distance between a system’s “loading” and its “capacity”, plant design and operation is predicated on ensuring an adequate safety margin for safety-significant parameters (e.g., fuel cladding temperature, containment pressure, etc.) is provided over the spectrum of anticipated plant operating, transient and accident conditions. To meet the anticipated challenges associated with extending the operational lifetimes of the current fleet of operating NPPs, the United States Department of Energy (USDOE), the Idaho National Laboratory (INL) and the Electric Power Research Institute (EPRI) have developed a collaboration to conduct coordinated research to identify and address the technological challenges and opportunities that likely would affect the safe and economic operation of the existing NPP fleet over the postulated long-term time horizons. In this paper we describe a framework for developing and implementing a Risk-Informed Safety Margin Characterization (RISMC) approach to evaluate and manage changes in plant safety margins over long time horizons.

  12. Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells.

    PubMed

    Lee, Kap-Rang; Kozukue, Nobuyuki; Han, Jae-Sook; Park, Joon-Hong; Chang, Eun-Young; Baek, Eun-Jung; Chang, Jong-Sun; Friedman, Mendel

    2004-05-19

    As part of an effort to improve plant-derived foods such as potatoes, eggplants, and tomatoes, the antiproliferative activities against human colon (HT29) and liver (HepG2) cancer cells of a series of structurally related individual compounds were examined using a microculture tetrazolium (MTT) assay. The objective was to assess the roles of the carbohydrate side chain and aglycon part of Solanum glycosides in influencing inhibitory activities of these compounds. Evaluations were carried out with four concentrations each (0.1, 1, 10, and 100 microg/mL) of the the potato trisaccharide glycoalkaloids alpha-chaconine and alpha-solanine; the disaccharides beta(1)-chaconine, beta(2)-chaconine, and beta(2)-solanine; the monosaccharide gamma-chaconine and their common aglycon solanidine; the tetrasaccharide potato glycoalkaloid dehydrocommersonine; the potato aglycon demissidine; the tetrasaccharide tomato glycoalkaloid alpha-tomatine, the trisaccharide beta(1)-tomatine, the disaccharide gamma-tomatine, the monosaccharide delta-tomatine, and their common aglycon tomatidine; the eggplant glycoalkaloids solamargine and solasonine and their common aglycon solasodine; and the nonsteroidal alkaloid jervine. All compounds were active in the assay, with the glycoalkaloids being the most active and the hydrolysis products less so. The effectiveness against the liver cells was greater than against the colon cells. Potencies of alpha-tomatine and alpha-chaconine at a concentration of 1 microg/mL against the liver carcinoma cells were higher than those observed with the anticancer drugs doxorubicin and camptothecin. Because alpha-chaconine, alpha-solanine, and alpha-tomatine also inhibited normal human liver HeLa (Chang) cells, safety considerations should guide the use of these compounds as preventative or therapeutic treatments against carcinomas.

  13. Reduction of Cholesterol and Glycoalkaloid Levels in Transgenic Potato Plants by Overexpression of a Type 1 Sterol Methyltransferase cDNA1

    PubMed Central

    Arnqvist, Lisa; Dutta, Paresh C.; Jonsson, Lisbeth; Sitbon, Folke

    2003-01-01

    Transgenic potato (Solanum tuberosum cv Désirée) plants overexpressing a soybean (Glycine max) type 1 sterol methyltransferase (GmSMT1) cDNA were generated and used to study sterol biosynthesis in relation to the production of toxic glycoalkaloids. Transgenic plants displayed an increased total sterol level in both leaves and tubers, mainly due to increased levels of the 24-ethyl sterols isofucosterol and sitosterol. The higher total sterol level was due to increases in both free and esterified sterols. However, the level of free cholesterol, a nonalkylated sterol, was decreased. Associated with this was a decreased glycoalkaloid level in leaves and tubers, down to 41% and 63% of wild-type levels, respectively. The results show that glycoalkaloid biosynthesis can be down-regulated in transgenic potato plants by reducing the content of free nonalkylated sterols, and they support the view of cholesterol as a precursor in glycoalkaloid biosynthesis. PMID:12692338

  14. Transcript profiling of two potato cultivars during glycoalkaloid-inducing treatments shows differential expression of genes in sterol and glycoalkaloid metabolism

    PubMed Central

    Nahar, Nurun; Westerberg, Erik; Arif, Usman; Huchelmann, Alexandre; Olarte Guasca, Alexandra; Beste, Lisa; Dalman, Kerstin; Dutta, Paresh C.; Jonsson, Lisbeth; Sitbon, Folke

    2017-01-01

    Steroidal glycoalkaloids (SGA) are sterol-derived neurotoxic defence substances present in several members of the Solanaceae. In the potato (Solanum tuberosum), high SGA levels may render tubers harmful for consumption. Tuber SGA levels depend on genetic factors, and can increase as a response to certain stresses and environmental conditions. To identify genes underlying the cultivar variation in tuber SGA levels, we investigated two potato cultivars differing in their SGA accumulation during wounding or light exposure; two known SGA-inducing treatments. Using microarray analysis coupled to sterol and SGA quantifications, we identified a small number of differentially expressed genes that were associated with increased SGA levels. Two of these genes, encoding distinct types of sterol Δ24-reductases, were by sense/antisense expression in transgenic potato plants shown to have differing roles in sterol and SGA metabolism. The results show that an increased SGA level in potato tubers during both wounding and light exposure is mediated by coordinated expression of a set of key genes in isoprenoid and steroid metabolism, and suggest that differences in this expression underlie cultivar variations in SGA levels. These results may find use within potato breeding and quality assessment. PMID:28256633

  15. Risk Assessment: Perchloroethylene Dry Cleaners Refined Human Health Risk Characterization

    EPA Pesticide Factsheets

    This November 2005 memo and appendices describe the methods by which EPA conducted its refined risk assessment of the Major Source and Area Source facilities within the perchloroethylene (perc) dry cleaners source category.

  16. Electrochemical Determination of Glycoalkaloids Using a Carbon Nanotubes-Phenylboronic Acid Modified Glassy Carbon Electrode

    PubMed Central

    Wang, Huiying; Liu, Mingyue; Hu, Xinxi; Li, Mei; Xiong, Xingyao

    2013-01-01

    A versatile strategy for electrochemical determination of glycoalkaloids (GAs) was developed by using a carbon nanotubes-phenylboronic acid (CNTs-PBA) modified glassy carbon electrode. PBA reacts with α-solanine and α-chaconine to form a cyclic ester, which could be utilized to detect GAs. This method allowed GA detection from 1 μM to 28 μM and the detection limit was 0.3 μM. Affinity interaction of GAs and immobilized PBA caused an essential change of the peak current. The CNT-PBA modified electrodes were sensitive for detection of GAs, and the peak current values were in quite good agreement with those measured by the sensors. PMID:24287539

  17. The Steroidal Glycoalkaloids from Solanaceae: Toxic Effect, Antitumour Activity and Mechanism of Action.

    PubMed

    Sucha, Lenka; Tomsik, Pavel

    2016-03-01

    Steroidal glycoalkaloids present in Solanaceae are toxic compounds biosynthesised for the protection of the plants. However, many health benefits of these compounds have been reported so far. One of their promising targets might be cancer, as demonstrated in a large number of studies. However, the main mechanism of action seems to be unclear. It could include the induction of apoptosis or trigger a necrosis with a subsequent inflammatory response. The relatively high systemic toxicity of steroidal compounds is another effect that must be taken into account in anticancer research. The main aim of this work was to summarise the recent progress in the investigation of the mechanisms of their antitumour action and to discuss their potential.

  18. Isolation, identification and quantification of unsaturated fatty acids, amides, phenolic compounds and glycoalkaloids from potato peel.

    PubMed

    Wu, Zhi-Gang; Xu, Hai-Yan; Ma, Qiong; Cao, Ye; Ma, Jian-Nan; Ma, Chao-Mei

    2012-12-15

    Eleven compounds were isolated from potato peels and identified. Their structures were determined by interpretation of UV, MS, 1D, and 2D NMR spectral data and by comparison with reported data. The main components of the potato peels were found to be chlorogenic acid and other phenolic compounds, accompanied by 2 glycoalkaloids, 3 low-molecular-weight amide compounds, and 2 unsaturated fatty acids, including an omega-3 fatty acid. The potato peels showed more potent radical scavenging activity than the flesh. The quantification of the 11 components indicated that the potato peels contained a higher amount of phenolic compounds than the flesh. These results suggest that peel waste from the industry of potato chips and fries may be a source of useful compounds for human health. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Electrochemical determination of glycoalkaloids using a carbon nanotubes-phenylboronic acid modified glassy carbon electrode.

    PubMed

    Wang, Huiying; Liu, Mingyue; Hu, Xinxi; Li, Mei; Xiong, Xingyao

    2013-11-27

    A versatile strategy for electrochemical determination of glycoalkaloids (GAs) was developed by using a carbon nanotubes-phenylboronic acid (CNTs-PBA) modified glassy carbon electrode. PBA reacts with α-solanine and α-chaconine to form a cyclic ester, which could be utilized to detect GAs. This method allowed GA detection from 1 μM to 28 μM and the detection limit was 0.3 μM. Affinity interaction of GAs and immobilized PBA caused an essential change of the peak current. The CNT-PBA modified electrodes were sensitive for detection of GAs, and the peak current values were in quite good agreement with those measured by the sensors.

  20. Isolation and chemoenzymatic treatment of glycoalkaloids from green, sprouting and rotting Solanum tuberosum potatoes for solanidine recovery.

    PubMed

    Koffi, Grokoré Yvonne; Remaud-Simeon, Magali; Due, Ahipo Edmond; Combes, Didier

    2017-04-01

    The estimation of glycoalkaloids in the flesh of different types of decayed potatoes was evaluated. The results showed that turned green and also sprouting or rotting potato flesh contain high amounts of toxic solanine and chaconine, exceeding by 2-5-fold the recommended limit, and ranging from 2578±86mg/kg to 5063±230mg/kg of dry weight potato flesh. For safety consideration, these decayed potatoes should be systematically set aside. To avoid a net economic loss and encourage the removal of this hazardous food, a recycling process was investigated to generate added-value compounds from the toxic glycoalkaloids. A simple chemo-enzymatic protocol comprising a partial acidic hydrolysis followed by an enzymatic treatment with the β-glycosidase from Periplaneta americana allowed the efficient conversion of α-chaconine to solanidine.

  1. Two Cytochrome P450 Monooxygenases Catalyze Early Hydroxylation Steps in the Potato Steroid Glycoalkaloid Biosynthetic Pathway1[OPEN

    PubMed Central

    Nakayasu, Masaru; Ohyama, Kiyoshi; Saito, Kazuki

    2016-01-01

    α-Solanine and α-chaconine, steroidal glycoalkaloids (SGAs) found in potato (Solanum tuberosum), are among the best-known secondary metabolites in food crops. At low concentrations in potato tubers, SGAs are distasteful; however, at high concentrations, SGAs are harmful to humans and animals. Here, we show that POTATO GLYCOALKALOID BIOSYNTHESIS1 (PGA1) and PGA2, two genes that encode cytochrome P450 monooxygenases (CYP72A208 and CYP72A188), are involved in the SGA biosynthetic pathway, respectively. The knockdown plants of either PGA1 or PGA2 contained very little SGA, yet vegetative growth and tuber production were not affected. Analyzing metabolites that accumulated in the plants and produced by in vitro enzyme assays revealed that PGA1 and PGA2 catalyzed the 26- and 22-hydroxylation steps, respectively, in the SGA biosynthetic pathway. The PGA-knockdown plants had two unique phenotypic characteristics: The plants were sterile and tubers of these knockdown plants did not sprout during storage. Functional analyses of PGA1 and PGA2 have provided clues for controlling both potato glycoalkaloid biosynthesis and tuber sprouting, two traits that can significantly impact potato breeding and the industry. PMID:27307258

  2. A Validated Reverse Phase HPLC Analytical Method for Quantitation of Glycoalkaloids in Solanum lycocarpum and Its Extracts

    PubMed Central

    Tiossi, Renata Fabiane Jorge; Miranda, Mariza Abreu; de Sousa, João Paulo Barreto; Praça, Fabíola Silva Garcia; Bentley, Maria Vitória Lopes Badra; McChesney, James Dewey; Bastos, Jairo Kenupp

    2012-01-01

    Solanum lycocarpum (Solanaceae) is native to the Brazilian Cerrado. Fruits of this species contain the glycoalkaloids solasonine (SN) and solamargine (SM), which display antiparasitic and anticancer properties. A method has been developed for the extraction and HPLC-UV analysis of the SN and SM in different parts of S. lycocarpum, mainly comprising ripe and unripe fruits, leaf, and stem. This analytical method was validated and gave good detection response with linearity over a dynamic range of 0.77–1000.00 μg mL−1 and recovery in the range of 80.92–91.71%, allowing a reliable quantitation of the target compounds. Unripe fruits displayed higher concentrations of glycoalkaloids (1.04% ± 0.01 of SN and 0.69% ± 0.00 of SM) than the ripe fruits (0.83% ± 0.02 of SN and 0.60% ± 0.01 of SM). Quantitation of glycoalkaloids in the alkaloidic extract gave 45.09% ± 1.14 of SN and 44.37% ± 0.60 of SM, respectively. PMID:22567576

  3. Synergistic interaction of glycoalkaloids alpha-chaconine and alpha-solanine on developmental toxicity in Xenopus embryos.

    PubMed

    Rayburn, J R; Friedman, M; Bantle, J A

    1995-12-01

    The embryo toxicities of two major potato glycoalkaloids, alpha-chaconine and alpha-solanine, were examined individually and in mixtures using the frog embryo teratogenesis assay-Xenopus. Calculations of toxic units (TUs) were used to assess possible antagonism, synergism or response addition of several mixtures ranging from approximately 3:1 to 1:20 TUs of alpha-chaconine to alpha-solanine. Some combinations exhibited strong synergism in the following measures of developmental toxicity: (a) 96-hr LC50, defined as the median concentration causing 50% embryo lethality; (b) 96-hr EC50 (malformation), defined as the concentration causing 50% malformation of the surviving embryos; and (c) teratogenic index which is equal to LC50/EC50 (malformation). The results indicated that each of the mixtures caused synergistic mortality or malformation. Furthermore, these studies suggested that the synergism observed for a specific mixture cannot be used to predict possible synergism of other mixtures with different ratios of the two glycoalkaloids; toxicities observed for individual glycoalkaloids may not be able to predict toxicities of mixtures; and specific combinations found in different potato varieties need to be tested to assess the safety of a particular cultivar.

  4. Anti-inflammatory properties of potato glycoalkaloids in stimulated Jurkat and Raw 264.7 mouse macrophages.

    PubMed

    Kenny, Olivia M; McCarthy, Catherine M; Brunton, Nigel P; Hossain, Mohammad B; Rai, Dilip K; Collins, Stuart G; Jones, Peter W; Maguire, Anita R; O'Brien, Nora M

    2013-04-19

    The potato glycoalkaloids, α-chaconine, α-solanine and solanidine, along with potato peel extracts were investigated for potential anti-inflammatory effects in vitro. Their potential to reduce two biomarkers of inflammation, cytokine and nitric oxide (NO) productions, were assessed in the stimulated Jurkat and macrophage models, respectively. Cytokine and nitric oxide productions were stimulated in Jurkat and Raw 264.7 macrophages with Concanavalin A (Con A; 25 μg/ml) and lipopolysaccaride (LPS; 1 μg/ml), respectively. Selective concentrations of glycoalkaloids and potato peel extracts were added simultaneously with Con A or LPS for 24h to investigate their potential to reduce inflammatory activity. α-Chaconine and solanidine significantly reduced interleukin-2 (IL-2) and interleukin-8 (IL-8) productions in Con A-induced Jurkat cells. The potato peel extracts did not influence cytokine production. In LPS-stimulated Raw macrophages, α-solanine, solanidine and two potato peel extracts significantly reduced induced NO production. Our findings suggest that sub-cytotoxic concentrations of potato glycoalkaloids and potato peel extracts possess anti-inflammatory effects in vitro and with further investigation may be useful in the prevention of anti-inflammatory diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. High-performance liquid chromatographic determination of the glycoalkaloids alpha-solanine and alpha-chaconine in 12 commercial varieties of Mexican potato.

    PubMed

    Sotelo, A; Serrano, B

    2000-06-01

    The glycoalkaloid content in 12 commercial varieties of Mexican potatoes was measured by HPLC in both the peel and the flesh of the potato. The principal glycoalkaloids alpha-solanine and alpha-chaconine were present in higher concentration in the peel than in the flesh of all varieties. The main alkaloid in the peel of the potatoes was alpha-chaconine and comprised about 65-71% of the total glycoalkaloids. The high concentration of alpha-chaconine in peel, which is more toxic than alpha-solanine, gives more protection to the tuber against predators. The total alkaloids in the peel of Alpha, Juanita, Michoacan, Norteña, Rosita, and Tollocan varieties were higher than the limit recommended for food safety. However, the peel represents less than 10% of the total tuber in most of the varieties. The total alkaloids contained in the peel of Atzimba, Lopez, Marciana, Montsama, Murca, and Puebla was lower than the limits recommended for food safety. The glycoalkaloid content in the boiled peeled potatoes was less than 9 mg/100 g but in Alpha, Montsama, and Puebla varieties, both glycoalkaloids were absent. According to the results, the consumption of the 12 commercial varieties of Mexican potatoes does not represent any danger to human health.

  6. Physical characterization of MMVF for risk assessment.

    PubMed

    Schneider, T

    1995-10-01

    Size and other physical properties of MMVF play a central role in risk assessment. They can be affected by, for example, conditions during manufacturing, and preparation prior to administration to experimental animals or cells. It is suggested that a necessary requirement for stating that an experiment has been repeated should be documented evidence that: (i) the administered fibres are alike when analysed with not less than a minimum number of well-established methods on single fibre and on bulk sample level; and (ii) doses must be equal, and the fibre concentrations and sizes at the primary target tissue must be documented. Assessment of fibre toxicity and assessment of potential for exposure are equally important in the risk assessment process. The physics of fibrous dust release is described and methods for a priori assessment of exposure are classified into three levels depending on the analytical effort involved: (1) direct analysis of the fibrous bulk material; (2) bench-scale test; and (3) full-scale tests of prefabricated insulation material in a test room during standardized insulation work. For the first method, two approaches are investigated. One relates the size-dependent measures (the mass of fibres with D < 3 microns, the total length of fibres with D < 3 microns and the total number of WHO fibres per unit mass of fibres) and the other considers fractions (the fraction of total fibre length with D < 3 microns, the fraction of WHO fibre number, and the fraction of fibre number with D < 3 microns). The values of the size-dependent measures that are quoted span 2-4 orders of magnitude for the ranges of nominal diameter and GSD(D) considered, and show strong and similar dependence on GSD(D). The second group of measures, based on fractions only range up to 2 orders of magnitude and are almost independent on GSD(D) for nominal diameters ranging 2-4 microns. The combined effect on exposure of bulk fibre size, and of addition of oil and binder, should be

  7. A risk-driven approach for subsurface site characterization

    NASA Astrophysics Data System (ADS)

    de Barros, F. P. J.; Rubin, Y.

    2008-01-01

    We present a probabilistic framework to addressing adverse human health effects due to groundwater contamination. One of the main challenges in health risk assessment is in relating it to subsurface data acquisition and to improvement in our understanding of human physiological responses to contamination. In this paper we propose to investigate this problem through an approach that integrates flow, transport and human health risk models with hydrogeological characterization. A human health risk cumulative distribution function is analytically developed to account for both uncertainty and variability in hydrogeological as well as human physiological parameters. With our proposed approach, we investigate under which conditions the reduction of uncertainties from flow physics, human physiology and exposure related parameters might contribute to a better understanding of human health risk assessment. Results indicate that the human health risk cumulative distribution function becomes less sensitive to uncertainty in physiological parameters at lower risk values associated with longer traveltimes. We also present a graphical tool that allows to investigate the relative impact of hydrogeological and physiological parameters in human health risk. A metric α that relates hydrogeological uncertainty to physiological uncertainty was developed to help decision makers set priorities in data acquisition. Other results show that the worth of hydrogeological characterization in human health risk depends on the time the contaminant plume takes to cross the control plane and on the exposure duration of the population to certain chemicals.

  8. The effect of some Solanum steroidal alkaloids and glycoalkaloids on larvae of the red flour beetle, Tribolium castaneum, and the tobacco hornworm, Manduca sexta.

    PubMed

    Weissenberg, M; Levy, A; Svoboda, J A; Ishaaya, I

    1998-01-01

    Evaluation of the inhibitory effect of a series of secondary plant compounds including steroidal alkaloids and glycoalkaloids on larvae of the red flour beetle, Tribolium castaneum, was investigated. Larval growth was inhibited on artificial diets containing 1 mumol g-1 diet of the glycoalkaloids solamargine, solasonine and tomatine, whereas the corresponding aglycones solasodine and tomatidine, and also tomatidenol, were inactive. The inhibitory effect of solamargine and tomatine, but not of solasonine, was completely abolished by addition of 1 mumol g-1 diet cholesterol and/or sitosterol. Nonetheless, synthetic cholesteryl tomatide displayed significant activity at 2 mumol g-1 diet. Parallel studies with the tobacco hornworm, Manduca sexta, showed marked inhibitory activity of tomatine at a dietary concentration of 1 mumol g-1, whereas the other compounds did not affect sterol metabolism or larval development. An appraisal of the factors influencing the mode of action of the active steroidal glycoalkaloids is attempted.

  9. Potato steroidal glycoalkaloid levels and the expression of key isoprenoid metabolic genes.

    PubMed

    Krits, Pinchas; Fogelman, Edna; Ginzberg, Idit

    2007-12-01

    The potato steroidal glycoalkaloids (SGA) are toxic secondary metabolites, and their total content in tubers should not exceed 20 mg/100 g fresh weight. The two major SGA in cultivated potato (Solanum tuberosum) are alpha-chaconine and alpha-solanine. SGA biosynthetic genes and the genetic factors that control their expression have not yet been determined. In the present study, potato genotypes exhibiting different levels of SGA content showed an association between high SGA levels in their leaves and tubers and high expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase 1 (hmg1) and squalene synthase 1 (pss1), genes of the mevalonic/isoprenoid pathway. Transcripts of other key enzymes of branches of the isoprenoid pathway, vetispiradiene/sesquiterpene synthase (pvs1) and sterol C24-methyltransferase type1 (smt1), were undetectable or exhibited stable expression regardless of SGA content, respectively, suggesting facilitated precursor flow to the SGA biosynthetic branch. The transcript ratio of solanidine glucosyltransferase (sgt2) to solanidine galactosyltransferase (sgt1) was correlated to the documented chaconine-to-solanine ratio in the tested genotypes. Significantly higher expression of hmg1, pss1, smt1, sgt1 and sgt2 was monitored in the tuber phelloderm than in the parenchyma of the tuber's flesh, targeting the former as the main SGA-producing tissue in the tuber, in agreement with the known high SGA content in the layers directly under the tuber skin.

  10. Glycoalkaloids as biomarkers for recognition of cultivated, wild, and somatic hybrids of potato.

    PubMed

    Savarese, Salvatore; Andolfi, Anna; Cimmino, Alessio; Carputo, Domenico; Frusciante, Luigi; Evidente, Antonio

    2009-04-01

    Cultivated and wild potato species synthesize a wide variety of steroidal glycoalkaloids (GAs). During breeding programs, species genomes are often put together through either sexual or somatic hybridization. Therefore, the determination of the GA composition of hybrids is very important in that it may affect either human consumption, or resistance to pathogen and pests. Here, we report the results of GA analysis performed on wild Solanum bulbocastanum, haploids of cultivated potato S. tuberosum and their interspecific somatic hybrids. GAs were extracted from tubers and analyzed by HPLC. HPLC Profile of S. tuberosum haploids showed, as expected, the presence of alpha-solanine and alpha-chaconine. The profile of S. bulbocastanum extract showed lack of alpha-solanine and alpha-chaconine, and the presence of four GAs. The GA pattern of the somatic hybrids was the sum of their parents' profile. This represents a noteworthy tool for their unequivocal recognition. Interestingly, two hybrids produced not only GAs of both parents but also new compounds to be further investigated. This provided evidence that somatic hybridization induced the synthesis of new metabolites. The nature of the probable unidentified GAs associated to S. bulbocastanum and its somatic hybrids was ascertained by chemical degradation and spectroscopic analysis of their aglycones and sugar moieties. Our results suggest their close relation with GAs of both wild and cultivated potato species.

  11. Colorado potato beetle toxins revisited: evidence the beetle does not sequester host plant glycoalkaloids.

    PubMed

    Armer, Christine A

    2004-04-01

    The Colorado potato beetle feeds only on glycoalkaloid-laden solanaceous plants, appears to be toxic to predators, and has aposematic coloration, suggesting the beetle may sequester alkaloids from its host plants. This study tested 4th instars and adults, as well as isolated hemolymph and excrement, to determine if the beetles sequester, metabolize, or excrete alkaloids ingested from their host plants. HPLC analysis showed: that neither the larvae nor the adults sequestered either solanine or chaconine from potato foliage; that any alkaloids in the beetles were at concentrations well below 1 ppm; and that alkaloids were found in the excrement of larvae at approximately the same concentrations as in foliage. Analysis of alkaloids in the remains of fed-upon leaflet halves plus excreta during 24 hr feeding by 4th instars, as compared to alkaloids in the uneaten halves of the leaflets, showed that equal amounts of alkaloids were excreted as were ingested. The aposematic coloration probably warns of a previously-identified toxic dipeptide instead of a plant-derived alkaloid, as the Colorado potato beetle appears to excrete, rather than sequester or metabolize, the alkaloids from its host plants.

  12. Detection of glycoalkaloids using disposable biosensors based on genetically modified enzymes.

    PubMed

    Espinoza, Michelle Arredondo; Istamboulie, Georges; Chira, Ana; Noguer, Thierry; Stoytcheva, Margarita; Marty, Jean-Louis

    2014-07-15

    In this work we present a rapid, selective, and highly sensitive detection of α-solanine and α-chaconine using cholinesterase-based sensors. The high sensitivity of the devices is brought by the use of a genetically modified acetylcholinesterase (AChE), combined with a one-step detection method based on the measurement of inhibition slope. The selectivity was obtained by using butyrylcholinesterase (BChE), an enzyme able to detect these two toxins with differential inhibition kinetics. The enzymes were immobilized via entrapment in PVA-AWP polymer directly on the working electrode surface. The analysis of the resulting inhibition slope was performed employing linear regression function included in Matlab. The high toxicity of α-chaconine compared to α-solanine due to a better affinity to the active site was proved. The inhibition of glycoalkaloids (GAs) mixture was performed over AChE enzyme wild-type AChE and BChE biosensors resulting in the detection of synergism effect. The developed method allows the detection of (GAs) at 50 ppb in potato matrix.

  13. Determination of solanidine- and tomatidine-type glycoalkaloid aglycons by gas Chromatography/Mass spectrometry.

    PubMed

    Laurila, J; Laakso, I; Väänänen, T; Kuronen, P; Huopalahti, R; Pehu, E

    1999-07-01

    A combined derivatization method for gas chromatographic/mass spectrometric (GC/MS) analysis of steroidal glycoalkaloid (SGA) aglycons was developed using both trimethylsilylation and pentafluoropropionylation. In comparison with underivatized or only silylated aglycons, the new technique produces more specific and abundant fragmentation for compounds with a tomatidine-type structure. For example, the difference between solasodine and tomatidine, the former containing a double bond at position 5,6 in the steroidal skeleton, can be observed by their base peak fragments at m/z 417 (C(24)H(41)O(2)Si(2)) and m/z 419 (C(24)H(43)O(2)Si(2)). The method is well suited for the simultaneous determination of both solanidane- and spirosolane-type SGA aglycons from Solanum species and hybrids. The reproducibility of the method, including SGA extraction, hydrolysis, derivatization, and quantitative GC/MS analysis, was <6% (CV) for the principal aglycons determined from a hybrid between a wild potato species, Solanum brevidens Phil., and a cultivated potato, S. tuberosum L. A single ion monitoring technique using specific fragments m/z 419 and 417 could be applied for the determination of minor stereoisomers, which are often overlapped by large amounts of tomatidine.

  14. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster.

    PubMed

    Langkilde, Søren; Mandimika, Tafadzwa; Schrøder, Malene; Meyer, Otto; Slob, Wout; Peijnenburg, Ad; Poulsen, Morten

    2009-06-01

    Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanumtuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha-solanine to alpha-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. The aim of the present study was to investigate whether an altered ratio of alpha-solanine and alpha-chaconine would reduce the toxicity of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios resulted in distended and fluid filled small intestines and stomach. Animals receiving the ratio with the reduced content of alpha-solanine were less affected compared to those receiving the other ratio. Gene expression profiling experiments were conducted using RNA from epithelial scrapings from the small intestines of the hamsters administered the highest doses of the glycoalkaloid treatments. In general, more differential gene expression was observed in the epithelial scrapings of the hamsters fed the ratio of 1:3.7. Mostly, pathways involved in lipid and energy metabolism were affected by the ratio of 1:3.7.

  15. Determination of glycoalkaloids and relative aglycones by nonaqueous capillary electrophoresis coupled with electrospray ionization-ion trap mass spectrometry.

    PubMed

    Bianco, Giuliana; Schmitt-Kopplin, Philippe; De Benedetto, Giuseppe; Kettrup, Antonius; Cataldi, Tommaso R I

    2002-09-01

    Glycoalkaloids are naturally occurring nitrogen-containing compounds present in many species of the family Solanaceae, including cultivated and wild potatoes (Solanum spp.), tomatoes (Lycopersicon spp.), etc. These compounds have pharmacological and toxicological effects on humans due to their significant anticholinesterase activity and disruption of cell membranes. Herein is reported the development of a capillary electrophoresis (CE) method using nonaqueous (NA) separation solutions in combination with ion trap mass spectrometry (MS and MS/MS) detection for the identification and quantification of glycoalkaloids and their relative aglycones. A mixture 90:10 v/v of MeCN-MeOH containing 50 mM ammonium acetate and 1.2 M acetic acid (applied voltage of 25.5 kV) was selected as a good compromise for the separation and detection of these compounds. The electrospray MS measurements were carried out in the positive ionization mode using a coaxial sheath liquid, methanol-water (1:1) with 1% of acetic acid at a flow rate of 2.5 microL/min. Under optimized experimental conditions, the predominant ion was the protonated molecular ion ([M+H](+)) of solanidine (m/z = 398), tomatidine (m/z = 416), chaconine (m/z = 852), solanine (m/z = 868), and tomatine (m/z = 1034). MS/MS experiments were carried out systematically by changing the relative collisional energy and monitoring the intensities of the fragment ions that were not high enough to allow better quantification than with the mother ions. The method was used for analyzing glycoalkaloids in potato extracts.

  16. Conversion of Exogenous Cholesterol into Glycoalkaloids in Potato Shoots, Using Two Methods for Sterol Solubilisation

    PubMed Central

    Petersson, Erik V.; Nahar, Nurun; Dahlin, Paul; Broberg, Anders; Tröger, Rikard; Dutta, Paresh C.; Jonsson, Lisbeth; Sitbon, Folke

    2013-01-01

    Steroidal glycoalkaloids (SGA) are toxic secondary metabolites naturally occurring in the potato, as well as in certain other Solanaceous plant species, such as tomato, eggplant and pepper. To investigate the steroidal origin of SGA biosynthesis, cut potato shoots were fed cholesterol labelled with deuterium (D) in the sterol ring structure (D5- or D6-labelled), or side chain (D7-labelled), and analysed after three or five weeks. The labelled cholesterol and presence of D-labelled SGA were analysed by GC-MS and LC-MS/MS, respectively. When feeding D-labelled cholesterol solubilised in Tween-80, labelled cholesterol in free form became present in both leaves and stems, although the major part was recovered as steryl esters. Minor amounts of D-labelled SGA (α-solanine and α-chaconine) were identified in cholesterol-treated shoots, but not in blank controls, or in shoots fed D6-27-hydroxycholesterol. Solubilising the labelled cholesterol in methyl-β-cyclodextrin instead of Tween-80 increased the levels of labelled SGA up to 100-fold, and about 1 mole% of the labelled cholesterol was recovered as labelled SGA in potato leaves. Both side chain and ring structure D labels were retained in SGA, showing that the entire cholesterol molecule is converted to SGA. However, feeding side chain D7-labelled cholesterol resulted in D5-labelled SGA, indicating that two hydrogen atoms were released during formation of the SGA nitrogen-containing ring system. Feeding with D7-sitosterol did not produce any labelled SGA, indicating that cholesterol is a specific SGA precursor. In conclusion, we have demonstrated a superior performance of methyl-β-cyclodextrin for delivery of cholesterol in plant tissue feeding experiments, and given firm evidence for cholesterol as a specific sterol precursor of SGA in potato. PMID:24349406

  17. Effect of selenate supplementation on glycoalkaloid content of potato (Solanum tuberosum L.).

    PubMed

    Turakainen, Marja; Väänänen, Tiina; Anttila, Katja; Ollilainen, Velimatti; Hartikainen, Helinä; Seppänen, Mervi

    2004-11-17

    Potatoes (Solanum tuberosum L.) supplemented with increasing amounts of sodium selenate were analyzed for glycoalkaloid (GA) content. GAs were extracted with 5% acetic acid from freeze-dried tubers of two potato cultivars, Satu and Sini, harvested 10 weeks after planting as immature. The GAs alpha-solanine and alpha-chaconine were quantified by reverse-phase high-performance liquid chromatography (RP-HPLC) with diode array detection. Two independent experiments were performed. In the first experiment, the total GA concentration +/- standard error of the tubers ranged between 105 +/- 9 and 124 +/- 10 mg kg(-1) fresh weight in Satu and between 194 +/- 26 and 228 +/- 10 mg kg(-1) fresh weight in Sini. The ratio of alpha-solanine to alpha-chaconine was 0.2 in Satu and 0.5-0.6 in Sini. In the second experiment, the total GA concentration +/- standard error was 75 +/- 4 to 96 +/- 11 mg kg(-1) fresh weight, and the ratio of alpha-solanine to alpha-chaconine was 0.3-0.4 in Satu. A high sodium selenate supplementation (0.9 mg of Se kg(-1) quartz sand) slightly decreased the GA content in Satu, but this decrease was not statistically significant. Furthermore, at this addition level the Se concentration increased to a very high level of 20 microg g(-1) dry weight, which cannot be recommended for human consumption. In both experiments, the Se concentration in tubers increased with increasing sodium selenate application levels. Our results show that acceptable application levels of selenate did not have an effect on the GA concentration in immature potato tubers.

  18. Glycoalkaloids of wild and cultivated Solanum: effects on specialist and generalist insect herbivores.

    PubMed

    Altesor, Paula; García, Álvaro; Font, Elizabeth; Rodríguez-Haralambides, Alejandra; Vilaró, Francisco; Oesterheld, Martín; Soler, Roxina; González, Andrés

    2014-06-01

    Plant domestication by selective breeding may reduce plant chemical defense in favor of growth. However, few studies have simultaneously studied the defensive chemistry of cultivated plants and their wild congeners in connection to herbivore susceptibility. We compared the constitutive glycoalkaloids (GAs) of cultivated potato, Solanum tuberosum, and a wild congener, S. commersonii, by liquid chromatography coupled to mass spectrometry. We also determined the major herbivores present on the two species in field plots, and tested their preference for the plants and their isolated GAs in two-choice bioassays. Solanum commersonii had a different GA profile and higher concentrations than S. tuberosum. In the field, S. tuberosum was mostly attacked by the generalist aphids Myzus persicae and Macrosiphum euphorbiae, and by the specialist flea beetle Epitrix argentinensis. In contrast, the most common herbivore on S. commersonii was the specialist sawfly Tequus sp. Defoliation levels were higher on the wild species, probably due to the chewing feeding behavior of Tequus sp. As seen in the field, M. persicae and E. argentinensis preferred leaf disks of the cultivated plant, while Tequus sp. preferred those of the wild one. Congruently, GAs from S. commersonii were avoided by M. persicae and preferred by Tequus sp. The potato aphid performed well on both species and was not deterred by S. commersonii GAs. These observations suggest that different GA profiles explain the feeding preferences of the different herbivores, and that domestication has altered the defensive capacity of S. tuberosum. However, the wild relative is still subject to severe defoliation by a specialist herbivore that may cue on the GAs.

  19. Promise assessment: A corollary to risk assessment for characterizing benefits

    SciTech Connect

    Sholtis, J.A. Jr. )

    1993-01-10

    Decisions involving the use of hazardous technologies are often made based on risk-benefit considerations. This is the case for U.S. space mission use of nuclear power and propulsion systems, where launch decisions are made within the office of the President. A great deal of time and effort is spent characterizing the risk for each nuclear-powered space mission. However, this is not so for benefits, even though they are no less important. To correct this situation, a new technical term--promise--is defined, and a new methodology--promise assessment--is proposed. This paper introduces and advances this concept, addresses its future application, as a tool, can be developed sufficiently and applied to methodically identify and characterized benefits. Further, it can introduce a degree of balance when judgments concerning the use of hazardous technologies are involved.

  20. A major QTL and an SSR marker associated with glycoalkaloid content in potato tubers from Solanum tuberosum x S. sparsipilum located on chromosome I.

    PubMed

    Sørensen, Kirsten Kørup; Kirk, Hanne Grethe; Olsson, Kerstin; Labouriau, Rodrigo; Christiansen, Jørgen

    2008-06-01

    New potato (Solanum tuberosum) varieties are required to contain low levels of the toxic glycoalkaloids and a potential approach to obtain this is through marker-assisted selection (MAS). Before applying MAS it is necessary to map quantitative trait loci (QTLs) for glycoalkaloid content in potato tubers and identify markers that link tightly to this trait. In this study, tubers of a dihaploid BC(1) population, originating from a cross between 90-HAF-01 (S. tuberosum(1)) and 90-HAG-15 (S. tuberosum(2) x S. sparsipilum), were evaluated for content of alpha-solanine and alpha-chaconine (total glycoalkaloid, TGA) after field trials. In addition, tubers were assayed for TGA content after exposure to light. A detailed analysis of segregation patterns indicated that a major QTL is responsible for the TGA content in tubers of this potato population. One highly significant QTL was mapped to chromosome I of the HAG and the HAF parent. Quantitative trait loci for glycoalkaloid production in foliage of different Solanum species have previously been mapped to this chromosome. In the present research, QTLs for alpha-solanine and alpha-chaconine content were mapped to the same location as for TGA content. Similar results were observed for tubers exposed to light. The simple sequence repeat marker STM5136 was closely linked to the identified QTL.

  1. Phenolic and Glycoalkaloid Levels of S. Jamesii Accessions and their Anti-Proliferative Effect on Human Prostate and Colon Cancer Cells In Vitro

    USDA-ARS?s Scientific Manuscript database

    Some tuber-bearing wild potato species are higher in antioxidant activity (AOA), phenolics (TP) and glycoalkaloids (TGA >200 mg/kg) than the potato of commerce. Hence, use of wild species as parental material in breeding for high AOA and TP might result in progenies with high TGA, if the traits are ...

  2. Impact of light-exposure on the metabolite balance of transgenic potato tubers with modified glycoalkaloid biosynthesis.

    PubMed

    Shepherd, Louise Vida Traill; Hackett, Christine Anne; Alexander, Colin James; McNicol, James William; Sungurtas, Julia Anne; McRae, Diane; McCue, Kent Frank; Belknap, William Richardson; Davies, Howard Vivian

    2016-06-01

    Metabolite profiling (liquid chromatography-mass spectrometry (LC-MS) and gas chromatography (GC-MS)) was used to assess the impact of light on the composition of transgenic potato (Solanum tuberosum L. cv. Desirée) with reduced glycoalkaloid content via the down-regulation of the SGT1 gene. Transgenic tubers exhibited an almost complete knock-out of α-solanine production and light had little impact on its accumulation. Levels of α-chaconine increased significantly in the peel of both the control and transgenic lines when exposed to light, particularly in the transgenic line. Major differences in metabolite profiles existed between outer and inner tuber tissues, and between light and dark-treated tubers. Many of the light-induced changes are explicable in terms of pathways known to be affected by stress responses. The impact of transgenesis on profiles was much less than that of tissue type or light and most differences were explicable in terms of the modification to the glycoalkaloid pathway.

  3. GLYCOALKALOID METABOLISM1 Is Required for Steroidal Alkaloid Glycosylation and Prevention of Phytotoxicity in Tomato[W

    PubMed Central

    Itkin, Maxim; Rogachev, Ilana; Alkan, Noam; Rosenberg, Tally; Malitsky, Sergey; Masini, Laura; Meir, Sagit; Iijima, Yoko; Aoki, Koh; de Vos, Ric; Prusky, Dov; Burdman, Saul; Beekwilder, Jules; Aharoni, Asaph

    2011-01-01

    Steroidal alkaloids (SAs) are triterpene-derived specialized metabolites found in members of the Solanaceae family that provide plants with a chemical barrier against a broad range of pathogens. Their biosynthesis involves the action of glycosyltransferases to form steroidal glycoalkaloids (SGAs). To elucidate the metabolism of SGAs in the Solanaceae family, we examined the tomato (Solanum lycopersicum) GLYCOALKALOID METABOLISM1 (GAME1) gene. Our findings imply that GAME1 is a galactosyltransferase, largely performing glycosylation of the aglycone tomatidine, resulting in SGA production in green tissues. Downregulation of GAME1 resulted in an almost 50% reduction in α-tomatine levels (the major SGA in tomato) and a large increase in its precursors (i.e., tomatidenol and tomatidine). Surprisingly, GAME1-silenced plants displayed growth retardation and severe morphological phenotypes that we suggest occur as a result of altered membrane sterol levels caused by the accumulation of the aglycone tomatidine. Together, these findings highlight the role of GAME1 in the glycosylation of SAs and in reducing the toxicity of SA metabolites to the plant cell. PMID:22180624

  4. Developing Hydrogeological Site Characterization Strategies based on Human Health Risk

    NASA Astrophysics Data System (ADS)

    de Barros, F.; Rubin, Y.; Maxwell, R. M.

    2013-12-01

    In order to provide better sustainable groundwater quality management and minimize the impact of contamination in humans, improved understanding and quantification of the interaction between hydrogeological models, geological site information and human health are needed. Considering the joint influence of these components in the overall human health risk assessment and the corresponding sources of uncertainty aid decision makers to better allocate resources in data acquisition campaigns. This is important to (1) achieve remediation goals in a cost-effective manner, (2) protect human health and (3) keep water supplies clean in order to keep with quality standards. Such task is challenging since a full characterization of the subsurface is unfeasible due to financial and technological constraints. In addition, human exposure and physiological response to contamination are subject to uncertainty and variability. Normally, sampling strategies are developed with the goal of reducing uncertainty, but less often they are developed in the context of their impacts on the overall system uncertainty. Therefore, quantifying the impact from each of these components (hydrogeological, behavioral and physiological) in final human health risk prediction can provide guidance for decision makers to best allocate resources towards minimal prediction uncertainty. In this presentation, a multi-component human health risk-based framework is presented which allows decision makers to set priorities through an information entropy-based visualization tool. Results highlight the role of characteristic length-scales characterizing flow and transport in determining data needs within an integrated hydrogeological-health framework. Conditions where uncertainty reduction in human health risk predictions may benefit from better understanding of the health component, as opposed to a more detailed hydrogeological characterization, are also discussed. Finally, results illustrate how different dose

  5. Flood Risk Characterization for the Eastern United States

    NASA Astrophysics Data System (ADS)

    Villarini, G.; Smith, J. A.; Ntelekos, A. A.

    2009-04-01

    Tropical cyclones landfalling in the eastern United States pose a major risk for insured property and can lead to extensive damage through storm surge flooding, inland flooding or extreme windspeeds. Current hurricane cat-models do not include calculations of inland flooding from the outer rainfall bands of tropical cyclones but the issue is becoming increasingly important for commercial insurance risk assessment. The results of this study could be used to feed into the next generation of hurricane cat-models and assist in the calculation of damages from inland hurricane flood damage. Annual maximum peak discharge records from more than 400 stations in the eastern United States with at least 75 years of record to examine the role of landfalling tropical cyclones in controlling the upper tail of inland flood risk for the eastern United States. In addition to examining tropical cyclone inland flood risk at specific locations, the spatial extent of extreme flooding from lanfalling tropical cyclones is analyzed. Analyses of temporal trends and abrupt changes in the mean and variance of annual flood peaks are performed. Change-point analysis is performed using the non-parametric Pettitt test. Two non-parametric (Mann-Kendall and Spearman) tests and one parametric (Pearson) test are applied to detect the presence of temporal trends. Flood risk characterization centers on assessments of the spatial variation in "upper tail" properties of annual flood peak distributions. The modeling framework for flood frequency analysis is provided by the Generalized Additive Models for Location Scale and Shape (GAMLSS).

  6. Risk Informed Margins Management as part of Risk Informed Safety Margin Characterization

    SciTech Connect

    Curtis Smith

    2014-06-01

    The ability to better characterize and quantify safety margin is important to improved decision making about Light Water Reactor (LWR) design, operation, and plant life extension. A systematic approach to characterization of safety margins and the subsequent margin management options represents a vital input to the licensee and regulatory analysis and decision making that will be involved. In addition, as research and development in the LWR Sustainability (LWRS) Program and other collaborative efforts yield new data, sensors, and improved scientific understanding of physical processes that govern the aging and degradation of plant SSCs needs and opportunities to better optimize plant safety and performance will become known. To support decision making related to economics, readability, and safety, the Risk Informed Safety Margin Characterization (RISMC) Pathway provides methods and tools that enable mitigation options known as risk informed margins management (RIMM) strategies.

  7. Characterization of drinking water treatment for virus risk assessment.

    PubMed

    Teunis, P F M; Rutjes, S A; Westrell, T; de Roda Husman, A M

    2009-02-01

    Removal or inactivation of viruses in drinking water treatment processes can be quantified by measuring the concentrations of viruses or virus indicators in water before and after treatment. Virus reduction is then calculated from the ratio of these concentrations. Most often only the average reduction is reported. That is not sufficient when treatment efficiency must be characterized in quantitative risk assessment. We present three simple models allowing statistical analysis of series of counts before and after treatment: distribution of the ratio of concentrations, and distribution of the probability of passage for unpaired and paired water samples. Performance of these models is demonstrated for several processes (long and short term storage, coagulation/filtration, coagulation/sedimentation, slow sand filtration, membrane filtration, and ozone disinfection) using microbial indicator data from full-scale treatment processes. All three models allow estimation of the variation in (log) reduction as well as its uncertainty; the results can be easily used in risk assessment. Although they have different characteristics and are present in vastly different concentrations, different viruses and/or bacteriophages appear to show similar reductions in a particular treatment process, allowing generalization of the reduction for each process type across virus groups. The processes characterized in this paper may be used as reference for waterborne virus risk assessment, to check against location specific data, and in case no such data are available, to use as defaults.

  8. Glycoalkaloids (α-chaconine and α-solanine) contents of selected Pakistani potato cultivars and their dietary intake assessment.

    PubMed

    Aziz, Abdul; Randhawa, Muhammad Atif; Butt, Masood Sadiq; Asghar, Ali; Yasin, Muhammad; Shibamoto, Takayuki

    2012-03-01

    Glycoalkaloids (α-solanine and α-chaconine) are naturally occurring toxic compounds in potato tuber (Solanum tuberosum L.) that cause acute intoxication in humans after their consumption. Present research was conducted to evaluate α-chaconine, α-solanine, and total glycoalkaloids (TGAs) contents in the peel and flesh portions by high-performance liquid chromatography method in selected Pakistani potato cultivars. The α-solanine content varies 45.98 ± 1.63 to 2742.60 ± 92.97 mg/100 g of dry weight (DW) in peel and from 4.01 ± 0.14 to 2466.56 ± 87.21 mg/100 g of DW in flesh. Similarly, α-chaconine content varied from 4.42 ± 0.16 to 6818.40 ± 211.07 mg/100 g of DW in potato peel and from 3.94 ± 0.14 to 475.33 ± 16.81 mg/100 g DW in flesh portion. The TGA concentration varied from 177.20 ± 6.26 to 5449.90 ± 192.68 mg/100 g of DW in peel and from 3.08 ± 0.11 to 14.69 ± 0.52 mg/100 g of DW in flesh portion of all the potato cultivars tested. All the potato cultivars contained lower concentration of TGA than the limits recommended as safe, except 2 cultivars, that is FD8-3 (2539.18 ± 89.77 mg/100 g of DW) and Cardinal (506.16 ± 17.90 mg/kg). The dietary intake assessment of potato cultivars revealed that Cardinal, FD 35-36, FD 8-3, and FD 3-9 contained higher amount of TGA in whole potato, although FD 8-3 only possessed higher content of TGA (154.93 ± 7.75) in its flesh portion rendering it unfit for human consumption. Practical Application:  This paper was based on the research conducted on toxic compounds present in all possible potato cultivars in Pakistan. Actually, we quantify the toxic compounds (glycoalkaloids) of potato cultivars through HPLC and their dietary assessment. This paper revealed safety assessment and their application in food industries especially potato processing.

  9. Pathogen and Pest Responses Are Altered Due to RNAi-Mediated Knockdown of GLYCOALKALOID METABOLISM 4 in Solanum tuberosum.

    PubMed

    Paudel, Jamuna Risal; Davidson, Charlotte; Song, Jun; Maxim, Itkin; Aharoni, Asaph; Tai, Helen H

    2017-09-06

    Steroidal glycoalkaloids (SGAs) are major secondary metabolites constitutively produced in cultivated potato Solanum tuberosum, and α-solanine and α-chaconine are the most abundant SGAs. SGAs are toxic to humans at high levels but their role in plant protection against pests and pathogens is yet to be established. In this study, levels of SGAs in potato were reduced by RNA interference (RNAi)-mediated silencing of GLYCOALKALOID METABOLISM 4 (GAME4)-a gene encoding cytochrome P450, involved in an oxidation step in the conversion of cholesterol to SGA aglycones. Two GAME4 RNAi lines, T8 and T9, were used to investigate the effects of manipulation of the SGA biosynthetic pathway in potato. Growth and development of an insect pest, Colorado potato beetle (CPB), were affected in these lines. While no effect on CPB leaf consumption or weight gain was observed, early instar larval death and accelerated development of the insect was found while feeding on leaves of GAME4 RNAi lines. Modulation of SGA biosynthetic pathway in GAME4 RNAi plants was associated with a larger alteration to the metabolite profile, including increased levels of one or both the steroidal saponins or phytoecdysteroids, which could affect insect mortality as well as development time. Colonization by Verticillium dahliae on GAME4 RNAi plants was also tested. There were increased pathogen levels in the T8 GAME4 RNAi line but not in the T9. Metabolite differences between T8 and T9 were found and may have contributed to differences in V. dahliae infection. Drought responses created by osmotic stress were not affected by modulation of SGA biosynthetic pathway in potato.

  10. Risk-Informed Safety Margin Characterization Methods Development Work

    SciTech Connect

    Smith, Curtis L; Ma, Zhegang; Riley, Tom; Mandelli, Diego; Nielsen, Joseph W; Alfonsi, Andrea; Rabiti, Cristian

    2014-09-01

    This report summarizes the research activity developed during the Fiscal year 2014 within the Risk Informed Safety Margin and Characterization (RISMC) pathway within the Light Water Reactor Sustainability (LWRS) campaign. This research activity is complementary to the one presented in the INL/EXT-??? report which shows advances Probabilistic Risk Assessment Analysis using RAVEN and RELAP-7 in conjunction to novel flooding simulation tools. Here we present several analyses that prove the values of the RISMC approach in order to assess risk associated to nuclear power plants (NPPs). We focus on simulation based PRA which, in contrast to classical PRA, heavily employs system simulator codes. Firstly we compare, these two types of analyses, classical and RISMC, for a Boiling water reactor (BWR) station black out (SBO) initiating event. Secondly we present an extended BWR SBO analysis using RAVEN and RELAP-5 which address the comments and suggestions received about he original analysis presented in INL/EXT-???. This time we focus more on the stochastic analysis such probability of core damage and on the determination of the most risk-relevant factors. We also show some preliminary results regarding the comparison between RELAP5-3D and the new code RELAP-7 for a simplified Pressurized Water Reactors system. Lastly we present some conceptual ideas regarding the possibility to extended the RISMC capabilities from an off-line tool (i.e., as PRA analysis tool) to an online-tool. In this new configuration, RISMC capabilities can be used to assist and inform reactor operator during real accident scenarios.

  11. Characterization of Evidence for Human System Risk Assessment

    NASA Technical Reports Server (NTRS)

    Steinberg, S. L.; Van Baalen, M.; Rossi, M.; Riccio, G.; Romero, E.; Francisco, D.

    2016-01-01

    Understanding the kinds of evidence available and using the best evidence to answer a question is critical to evidenced-based decision-making, and it requires synthesis of evidence from a variety of sources. Categorization of human system risks in spaceflight, in particular, focuses on how well the integration and interpretation of all available evidence informs the risk statement that describes the relationship between spaceflight hazards and an outcome of interest. A mature understanding and categorization of these risks requires: 1) sufficient characterization of risk, 2) sufficient knowledge to determine an acceptable level of risk (i.e., a standard), 3) development of mitigations to meet the acceptable level of risk, and 4) identification of factors affecting generalizability of the evidence to different design reference missions. In the medical research community, evidence is often ranked by increasing confidence in findings gleaned from observational and experimental research (e.g., "levels of evidence"). However, an approach based solely on aspects of experimental design is problematic in assessing human system risks for spaceflight. For spaceflight, the unique challenges and opportunities include: (1) The independent variables in most evidence are the hazards of spaceflight, such as space radiation or low gravity, which cannot be entirely duplicated in terrestrial (Earth-based) analogs, (2) Evidence is drawn from multiple sources including medical and mission operations, Lifetime Surveillance of Astronaut Health (LSAH), spaceflight research (LSDA), and relevant environmental & terrestrial databases, (3) Risk metrics based primarily on LSAH data are typically derived from available prevalence or incidence data, which may limit rigorous interpretation, (4) The timeframe for obtaining adequate spaceflight sample size (n) is very long, given the small population, (5) Randomized controlled trials are unattainable in spaceflight, (6) Collection of personal and

  12. Quantitative risk assessment of Listeria monocytogenes in French cold-smoked salmon: II. Risk characterization.

    PubMed

    Pouillot, Régis; Goulet, Véronique; Delignette-Muller, Marie Laure; Mahé, Aurélie; Cornu, Marie

    2009-06-01

    A model for the assessment of exposure to Listeria monocytogenes from cold-smoked salmon consumption in France was presented in the first of this pair of articles (Pouillot et al., 2007, Risk Analysis, 27:683-700). In the present study, the exposure model output was combined with an internationally accepted hazard characterization model, adapted to the French situation, to assess the risk of invasive listeriosis from cold-smoked salmon consumption in France in a second-order Monte Carlo simulation framework. The annual number of cases of invasive listeriosis due to cold-smoked salmon consumption in France is estimated to be 307, with a very large credible interval ([10; 12,453]), reflecting data uncertainty. This uncertainty is mainly associated with the dose-response model. Despite the significant uncertainty associated with the predictions, this model provides a scientific base for risk managers and food business operators to manage the risk linked to cold-smoked salmon contaminated with L. monocytogenes. Under the modeling assumptions, risk would be efficiently reduced through a decrease in the prevalence of L. monocytogenes or better control of the last steps of the cold chain (shorter and/or colder storage during the consumer step), whereas reduction of the initial contamination levels of the contaminated products and improvement in the first steps of the cold chain do not seem to be promising strategies. An attempt to apply the recent risk-based concept of FSO (food safety objective) on this example underlines the ambiguity in practical implementation of the risk management metrics and the need for further elaboration on these concepts.

  13. Human health risk characterization of petroleum coke calcining facility emissions.

    PubMed

    Singh, Davinderjit; Johnson, Giffe T; Harbison, Raymond D

    2015-12-01

    Calcining processes including handling and storage of raw petroleum coke may result in Particulate Matter (PM) and gaseous emissions. Concerns have been raised over the potential association between particulate and aerosol pollution and adverse respiratory health effects including decrements in lung function. This risk characterization evaluated the exposure concentrations of ambient air pollutants including PM10 and gaseous pollutants from a petroleum coke calciner facility. The ambient air pollutant levels were collected through monitors installed at multiple locations in the vicinity of the facility. The measured and modeled particulate levels in ambient air from the calciner facility were compared to standards protective of public health. The results indicated that exposure levels were, on occasions at sites farther from the facility, higher than the public health limit of 150 μg/m(3) 24-h average for PM10. However, the carbon fraction demonstrated that the contribution from the calciner facility was de minimis. Exposure levels of the modeled SO2, CO, NOx and PM10 concentrations were also below public health air quality standards. These results demonstrate that emissions from calcining processes involving petroleum coke, at facilities that are well controlled, are below regulatory standards and are not expected to produce a public health risk.

  14. Exploring public databases to characterize urban flood risks in Amsterdam

    NASA Astrophysics Data System (ADS)

    Gaitan, Santiago; ten Veldhuis, Marie-claire; van de Giesen, Nick

    2015-04-01

    Cities worldwide are challenged by increasing urban flood risks. Precise and realistic measures are required to decide upon investment to reduce their impacts. Obvious flooding factors affecting flood risk include sewer systems performance and urban topography. However, currently implemented sewer and topographic models do not provide realistic predictions of local flooding occurrence during heavy rain events. Assessing other factors such as spatially distributed rainfall and socioeconomic characteristics may help to explain probability and impacts of urban flooding. Several public databases were analyzed: complaints about flooding made by citizens, rainfall depths (15 min and 100 Ha spatio-temporal resolution), grids describing number of inhabitants, income, and housing price (1Ha and 25Ha resolution); and buildings age. Data analysis was done using Python and GIS programming, and included spatial indexing of data, cluster analysis, and multivariate regression on the complaints. Complaints were used as a proxy to characterize flooding impacts. The cluster analysis, run for all the variables except the complaints, grouped part of the grid-cells of central Amsterdam into a highly differentiated group, covering 10% of the analyzed area, and accounting for 25% of registered complaints. The configuration of the analyzed variables in central Amsterdam coincides with a high complaint count. Remaining complaints were evenly dispersed along other groups. An adjusted R2 of 0.38 in the multivariate regression suggests that explaining power can improve if additional variables are considered. While rainfall intensity explained 4% of the incidence of complaints, population density and building age significantly explained around 20% each. Data mining of public databases proved to be a valuable tool to identify factors explaining variability in occurrence of urban pluvial flooding, though additional variables must be considered to fully explain flood risk variability.

  15. Characterizing and Reaching High-Risk Drinkers Using Audience Segmentation

    PubMed Central

    Moss, Howard B.; Kirby, Susan D.; Donodeo, Fred

    2010-01-01

    Background Market or audience segmentation is widely used in social marketing efforts to help planners identify segments of a population to target for tailored program interventions. Market-based segments are typically defined by behaviors, attitudes, knowledge, opinions, or lifestyles. They are more helpful to health communication and marketing planning than epidemiologically-defined groups because market-based segments are similar in respect to how they behave or might react to marketing and communication efforts. However, market segmentation has rarely been used in alcohol research. As an illustration of its utility, we employed commercial data that describes the sociodemographic characteristics of high-risk drinkers as an audience segment; where they tend to live, lifestyles, interests, consumer behaviors, alcohol consumption behaviors, other health-related behaviors, and cultural values. Such information can be extremely valuable in targeting and planning public health campaigns, targeted mailings, prevention interventions and research efforts. Methods We describe the results of a segmentation analysis of those individuals who self-report consuming five or more drinks per drinking episode at least twice in the last 30-days. The study used the proprietary PRIZM™ audience segmentation database merged with Center for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS) database. The top ten of the 66 PRIZM™ audience segments for this risky drinking pattern are described. For five of these segments we provide additional in-depth details about consumer behavior and the estimates of the market areas where these risky drinkers reside. Results The top ten audience segments (PRIZM clusters) most likely to engage in high-risk drinking are described. The cluster with the highest concentration of binge drinking behavior is referred to as the “Cyber Millenials.” This cluster is characterized as “the nation's tech-savvy singles

  16. Characterizing and reaching high-risk drinkers using audience segmentation.

    PubMed

    Moss, Howard B; Kirby, Susan D; Donodeo, Fred

    2009-08-01

    Market or audience segmentation is widely used in social marketing efforts to help planners identify segments of a population to target for tailored program interventions. Market-based segments are typically defined by behaviors, attitudes, knowledge, opinions, or lifestyles. They are more helpful to health communication and marketing planning than epidemiologically defined groups because market-based segments are similar in respect to how they behave or might react to marketing and communication efforts. However, market segmentation has rarely been used in alcohol research. As an illustration of its utility, we employed commercial data that describes the sociodemographic characteristics of high-risk drinkers as an audience segment, including where they tend to live, lifestyles, interests, consumer behaviors, alcohol consumption behaviors, other health-related behaviors, and cultural values. Such information can be extremely valuable in targeting and planning public health campaigns, targeted mailings, prevention interventions, and research efforts. We described the results of a segmentation analysis of those individuals who self-reported to consume 5 or more drinks per drinking episode at least twice in the last 30 days. The study used the proprietary PRIZM (Claritas, Inc., San Diego, CA) audience segmentation database merged with the Center for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS) database. The top 10 of the 66 PRIZM audience segments for this risky drinking pattern are described. For five of these segments we provided additional in-depth details about consumer behavior and the estimates of the market areas where these risky drinkers resided. The top 10 audience segments (PRIZM clusters) most likely to engage in high-risk drinking are described. The cluster with the highest concentration of binge-drinking behavior is referred to as the "Cyber Millenials." This cluster is characterized as "the nation's tech

  17. Assessing Risks to Populations at Superfund and Rcra Sites: Characterizing Effects on Populations (Final)

    EPA Science Inventory

    The Ecological Risk Assessment Support Center (ERASC) announced the release of the final document titled, Assessing Risks to Populations at Superfund and RCRA Sites: Characterizing Effects on Populations.

  18. Assessing Risks to Populations at Superfund and Rcra Sites: Characterizing Effects on Populations (Final)

    EPA Science Inventory

    The Ecological Risk Assessment Support Center (ERASC) announced the release of the final document titled, Assessing Risks to Populations at Superfund and RCRA Sites: Characterizing Effects on Populations.

  19. Comparative assessment of absolute cardiovascular disease risk characterization from non-laboratory-based risk assessment in South African populations

    PubMed Central

    2013-01-01

    Background All rigorous primary cardiovascular disease (CVD) prevention guidelines recommend absolute CVD risk scores to identify high- and low-risk patients, but laboratory testing can be impractical in low- and middle-income countries. The purpose of this study was to compare the ranking performance of a simple, non-laboratory-based risk score to laboratory-based scores in various South African populations. Methods We calculated and compared 10-year CVD (or coronary heart disease (CHD)) risk for 14,772 adults from thirteen cross-sectional South African populations (data collected from 1987 to 2009). Risk characterization performance for the non-laboratory-based score was assessed by comparing rankings of risk with six laboratory-based scores (three versions of Framingham risk, SCORE for high- and low-risk countries, and CUORE) using Spearman rank correlation and percent of population equivalently characterized as ‘high’ or ‘low’ risk. Total 10-year non-laboratory-based risk of CVD death was also calculated for a representative cross-section from the 1998 South African Demographic Health Survey (DHS, n = 9,379) to estimate the national burden of CVD mortality risk. Results Spearman correlation coefficients for the non-laboratory-based score with the laboratory-based scores ranged from 0.88 to 0.986. Using conventional thresholds for CVD risk (10% to 20% 10-year CVD risk), 90% to 92% of men and 94% to 97% of women were equivalently characterized as ‘high’ or ‘low’ risk using the non-laboratory-based and Framingham (2008) CVD risk score. These results were robust across the six risk scores evaluated and the thirteen cross-sectional datasets, with few exceptions (lower agreement between the non-laboratory-based and Framingham (1991) CHD risk scores). Approximately 18% of adults in the DHS population were characterized as ‘high CVD risk’ (10-year CVD death risk >20%) using the non-laboratory-based score. Conclusions We found a high level of

  20. Characterizing risk factors for pediatric lamp oil product exposures

    PubMed Central

    SHEIKH, S.; CHANG, A.; KIESZAK, S.; LAW, R.; BENNETT, H. K. W.; ERNST, E.; BOND, G. R.; SPILLER, H. A.; SCHURZ-ROGERS, H.; CHU, A.; BRONSTEIN, A. C.; SCHIER, J. G.

    2015-01-01

    Poisonings from lamp oil ingestion continue to occur worldwide among the pediatric population despite preventive measures such as restricted sale of colored and scented lamp oils. This suggests that optimal prevention practices for unintentional pediatric exposures to lamp oil have yet to be identified and/or properly implemented. Objective To characterize demographic, health data, and potential risk factors associated with reported exposures to lamp oil by callers to poison centers (PCs) in the US and discuss their public health implications. Study design . This was a two part study in which the first part included characterizing all exposures to a lamp oil product reported to the National Poison Data System (NPDS) with regard to demographics, exposure, health, and outcome data from 1/1/2000 to 12/31/2010. Regional penetrance was calculated using NPDS data by grouping states into four regions and dividing the number of exposure calls by pediatric population per region (from the 2000 US census). Temporal analyses were performed on NPDS data by comparing number of exposures by season and around the July 4th holiday. Poisson regression was used to model the count of exposures for these analyses. In the second part of this project, in order to identify risk factors we conducted a telephone-based survey to the parents of children from five PCs in five different states. The 10 most recent lamp oil product exposure calls for each poison center were systematically selected for inclusion. Calls in which a parent or guardian witnessed a pediatric lamp oil product ingestion were eligible for inclusion. Data on demographics, exposure information, behavioral traits, and health were collected. A descriptive analysis was performed and Fisher’s exact test was used to evaluate associations between variables. All analyses were conducted using SAS v9.3. Results Among NPDS data, 2 years was the most common patient age reported and states in the Midwestern region had the highest

  1. Medication Desensitization: Characterization of Outcomes and Risk Factors for Reactions.

    PubMed

    Murray, Taryn S; Rice, Todd W; Wheeler, Arthur P; Phillips, Elizabeth J; Dworski, Ryszard T; Stollings, Joanna L

    2016-03-01

    Although its mechanisms are poorly understood, desensitization has been used to induce a temporary state of immune unresponsiveness in patients who have IgE-, non-IgE-, or pharmacologically mediated reactions when a drug has no alternatives. The purpose of this study was to characterize the outcomes and identify risk factors for reactions during drug desensitization. A retrospective review of electronic medical records of adult patients undergoing drug desensitization from January 1, 2011, to December 31, 2013, was conducted in 2 intensive care units at a tertiary medical center. We used multivariate analysis to determine if specified risk factors were associated with reacting during the desensitization. Reactions were classified according to the pretest probability prior to desensitization, and then, reactions during desensitization were classified based on the occurrence of cutaneous reactions as follows: successful with no reaction, mild reaction, moderate reaction, or failed. Failure could result from any systemic allergic or cutaneous reaction resulting in procedure termination. The desensitizations were also assessed to determine if the patient required de-escalation secondary to a reaction. A total of 88 desensitizations were performed in 69 patients. Desensitization was completed with no cutaneous reaction in 85% of patients. No baseline characteristic, medication class (P = 0.46), or indication for desensitization (P = 0.59) was associated with having a reaction. Reported histories of urticaria (P < 0.0001) and labored breathing (P = 0.003) during prior exposure were significant in identifying patients who might have a reaction during desensitization. However, neither history of urticaria nor labored breathing was independently associated with having a reaction in multivariate analysis (OR = 0.979, 95% CI = 0.325-2.952, P = 0.970, and OR = 1.626, 95% CI = 0.536-4.931, P = 0.739, respectively). Drug desensitization is safe for patients who have no

  2. Influence of incorporated wild Solanum genomes on potato properties in terms of starch nanostructure and glycoalkaloid content.

    PubMed

    Väänänen, Tiina; Ikonen, Teemu; Rokka, Veli-Matti; Kuronen, Pirjo; Serimaa, Ritva; Ollilainen, Velimatti

    2005-06-29

    Interspecific somatic hybrids produced by protoplast fusion between two wild Solanum species (S. acaule, acl; S. brevidens, brd) and cultivated potato Solanum tuberosum (tbr) were analyzed in terms of the starch nanometer-range structure and glycoalkaloid (GA) contents. The crystallinity of starch granules, the average size of starch crystallites, and the lamellar distances were obtained from tuber samples using wide-angle and small-angle X-ray scattering methods. These measurements showed that incorporation of wild genomes from either nontuberous (brd) or tuberous (acl) Solanum species caused no significant modifications of the nanostructure of potato starch. In contrast, the GA profiles of the hybrids, which were analyzed by LC-ESI-MS in both tuber and foliage samples, differed considerably from those of cultivated potato. Regardless of the low total tuber GA concentrations (approximately 9 mg/100 g of fresh weight), the somatic hybrids contained GAs not detected in the parental species. A high proportion of spirotype GAs consisting of 5,6-dihydrogenated aglycons, for example, alpha-tomatine and tomatidine bound with solatriose, and chacotriose were found in the hybrids. In conclusion, the foliage of interspecific hybrids contained a higher variation in the structures of GAs than did the tubers.

  3. Ecological risk characterization based on exposure to contaminants through the Rocky Mountain Arsenal aquatic food chains

    SciTech Connect

    Toll, J.E.; Cothern, K.A.; Pavlou, S.; Tate, D.J.; Armstrong, J.P.

    1994-12-31

    This paper describes ecological risk characterization methods and results for characterizing potential risk from exposure to bioaccumulative contaminants of concern (aldrin, dieldrin, endrin, DDT, DDE, and mercury) through the lake food chains at Rocky Mountain Arsenal (RMA). Aquatic risks were estimated for the bald eagle, great blue heron, shorebird, and water bird using a prey-tissue-concentration-based food web model. Methods for estimating missing tissue concentration data were developed on a case-by-case basis and will be described. A sediment-based food web model was also considered and the reasons for its rejection will be described. Generalizable insights from the aquatic ecological risk characterization will be discussed.

  4. Characterizing Contamination and Assessing Exposure, Risk and Resilience

    EPA Pesticide Factsheets

    EPA supports its responders' ability to characterize site contamination by developing sampling protocols, sample preparation methods, and analytical methods for chemicals, biotoxins, microbial pathogens, and radiological agents.

  5. Sequence Diversity in Coding Regions of Candidate Genes in the Glycoalkaloid Biosynthetic Pathway of Wild Potato Species

    PubMed Central

    Manrique-Carpintero, Norma C.; Tokuhisa, James G.; Ginzberg, Idit; Holliday, Jason A.; Veilleux, Richard E.

    2013-01-01

    Natural variation in five candidate genes of the steroidal glycoalkaloid (SGA) metabolic pathway and whole-genome single nucleotide polymorphism (SNP) genotyping were studied in six wild [Solanum chacoense (chc 80-1), S. commersonii, S. demissum, S. sparsipilum, S. spegazzinii, S. stoloniferum] and cultivated S. tuberosum Group Phureja (phu DH) potato species with contrasting levels of SGAs. Amplicons were sequenced for five candidate genes: 3-hydroxy-3-methylglutaryl coenzyme A reductase 1 and 2 (HMG1, HMG2) and 2.3-squalene epoxidase (SQE) of primary metabolism, and solanidine galactosyltransferase (SGT1), and glucosyltransferase (SGT2) of secondary metabolism. SNPs (n = 337) producing 354 variations were detected within 3.7 kb of sequenced DNA. More polymorphisms were found in introns than exons and in genes of secondary compared to primary metabolism. Although no significant deviation from neutrality was found, dN/dS ratios < 1 and negative values of Tajima’s D test suggested purifying selection and genetic hitchhiking in the gene fragments. In addition, patterns of dN/dS ratios across the SGA pathway suggested constraint by natural selection. Comparison of nucleotide diversity estimates and dN/dS ratios showed stronger selective constraints for genes of primary rather than secondary metabolism. SNPs (n = 24) with an exclusive genotype for either phu DH (low SGA) or chc 80-1 (high SGA) were identified for HMG2, SQE, SGT1 and SGT2. The SolCAP 8303 Illumina Potato SNP chip genotyping revealed eight informative SNPs on six pseudochromosomes, with homozygous and heterozygous genotypes that discriminated high, intermediate and low levels of SGA accumulation. These results can be used to evaluate SGA accumulation in segregating or association mapping populations. PMID:23853090

  6. Quantitative, Qualitative and Geospatial Methods to Characterize HIV Risk Environments.

    PubMed

    Conners, Erin E; West, Brooke S; Roth, Alexis M; Meckel-Parker, Kristen G; Kwan, Mei-Po; Magis-Rodriguez, Carlos; Staines-Orozco, Hugo; Clapp, John D; Brouwer, Kimberly C

    2016-01-01

    Increasingly, 'place', including physical and geographical characteristics as well as social meanings, is recognized as an important factor driving individual and community health risks. This is especially true among marginalized populations in low and middle income countries (LMIC), whose environments may also be more difficult to study using traditional methods. In the NIH-funded longitudinal study Mapa de Salud, we employed a novel approach to exploring the risk environment of female sex workers (FSWs) in two Mexico/U.S. border cities, Tijuana and Ciudad Juárez. In this paper we describe the development, implementation, and feasibility of a mix of quantitative and qualitative tools used to capture the HIV risk environments of FSWs in an LMIC setting. The methods were: 1) Participatory mapping; 2) Quantitative interviews; 3) Sex work venue field observation; 4) Time-location-activity diaries; 5) In-depth interviews about daily activity spaces. We found that the mixed-methodology outlined was both feasible to implement and acceptable to participants. These methods can generate geospatial data to assess the role of the environment on drug and sexual risk behaviors among high risk populations. Additionally, the adaptation of existing methods for marginalized populations in resource constrained contexts provides new opportunities for informing public health interventions.

  7. Characterizing vaccine-associated risks using cubic smoothing splines.

    PubMed

    Brookhart, M Alan; Walker, Alexander M; Lu, Yun; Polakowski, Laura; Li, Jie; Paeglow, Corrie; Puenpatom, Tosmai; Izurieta, Hector; Daniel, Gregory W

    2012-11-15

    Estimating risks associated with the use of childhood vaccines is challenging. The authors propose a new approach for studying short-term vaccine-related risks. The method uses a cubic smoothing spline to flexibly estimate the daily risk of an event after vaccination. The predicted incidence rates from the spline regression are then compared with the expected rates under a log-linear trend that excludes the days surrounding vaccination. The 2 models are then used to estimate the excess cumulative incidence attributable to the vaccination during the 42-day period after vaccination. Confidence intervals are obtained using a model-based bootstrap procedure. The method is applied to a study of known effects (positive controls) and expected noneffects (negative controls) of the measles, mumps, and rubella and measles, mumps, rubella, and varicella vaccines among children who are 1 year of age. The splines revealed well-resolved spikes in fever, rash, and adenopathy diagnoses, with the maximum incidence occurring between 9 and 11 days after vaccination. For the negative control outcomes, the spline model yielded a predicted incidence more consistent with the modeled day-specific risks, although there was evidence of increased risk of diagnoses of congenital malformations after vaccination, possibly because of a "provider visit effect." The proposed approach may be useful for vaccine safety surveillance.

  8. Quantitative, Qualitative and Geospatial Methods to Characterize HIV Risk Environments

    PubMed Central

    Conners, Erin E.; West, Brooke S.; Roth, Alexis M.; Meckel-Parker, Kristen G.; Kwan, Mei-Po; Magis-Rodriguez, Carlos; Staines-Orozco, Hugo; Clapp, John D.; Brouwer, Kimberly C.

    2016-01-01

    Increasingly, ‘place’, including physical and geographical characteristics as well as social meanings, is recognized as an important factor driving individual and community health risks. This is especially true among marginalized populations in low and middle income countries (LMIC), whose environments may also be more difficult to study using traditional methods. In the NIH-funded longitudinal study Mapa de Salud, we employed a novel approach to exploring the risk environment of female sex workers (FSWs) in two Mexico/U.S. border cities, Tijuana and Ciudad Juárez. In this paper we describe the development, implementation, and feasibility of a mix of quantitative and qualitative tools used to capture the HIV risk environments of FSWs in an LMIC setting. The methods were: 1) Participatory mapping; 2) Quantitative interviews; 3) Sex work venue field observation; 4) Time-location-activity diaries; 5) In-depth interviews about daily activity spaces. We found that the mixed-methodology outlined was both feasible to implement and acceptable to participants. These methods can generate geospatial data to assess the role of the environment on drug and sexual risk behaviors among high risk populations. Additionally, the adaptation of existing methods for marginalized populations in resource constrained contexts provides new opportunities for informing public health interventions. PMID:27191846

  9. Evaluation of glycoalkaloids in tubers of genetically modified virus Y-resistant potato plants (var. Désirée) by non-aqueous capillary electrophoresis coupled with electrospray ionization mass spectrometry (NACE-ESI-MS).

    PubMed

    Bianco, Giuliana; Schmitt-Kopplin, Philippe; Crescenzi, Aniello; Comes, Soccorsa; Kettrup, Antonius; Cataldi, Tommaso R I

    2003-03-01

    The glycoalkaloid content of transgenic potatoes was evaluated by an optimised method based on non-aqueous capillary electrophoresis coupled on-line with electrospray ionization-mass spectrometry (NACE-ESI-MS). The potato material consisted of tubers from a conventional cv. Désirée and from three lines of modified plants resistant, intermediate and susceptible to infection by potato virus Y (PVY). The main glycoalkaloids were confirmed to be alpha-solanine and alpha-chaconine with parent ion masses m/z 852 and 868, respectively. In addition, an unknown minor peak at m/z 850.6 was found both in conventional (control) and susceptible line potato tubers. Such a compound exhibited an MS(2) spectrum with fragments ions at 704 and 396 m/z derived by loss of two ions, i.e. m/z 146 and 307, most likely corresponding to a rhamnose unit and a [glucose-(rhamnose)(2)] moiety, respectively. Up to 30-80-fold higher concentrations of total glycoalkaloids were found in the peel compared to flesh samples of all tubers examined. TGA content was nearly doubled in peel samples of resistant compared to control lines, and these levels were lower than the limit recommended for food safety, i.e. 20-60 mg of TGA per 100 g fresh weight. Moreover, it was established that tubers produced by virus-resistant clones are substantially equivalent in glycoalkaloid contents to those produced by conventional potato varieties.

  10. Glycoalkaloid aglycone accumulations associated with infection by Clavibacter michiganensis ssp. sepedonicus in potato species Solanum acaule and Solanum tuberosum and their interspecific somatic hybrids.

    PubMed

    Rokka, V-M; Laurila, J; Tauriainen, A; Laakso, I; Larkka, J; Metzler, M; Pietilä, L

    2005-03-01

    Solanum acaule Bitt., a wild potato species, is closely related to cultivated potato (Solanum. tuberosum L.). Incorporation of desirable traits from allotetraploid [2n=4x=48, 2 endosperm balance number (EBN)] S. acaule (acl) into autotetraploid (2n=4x=48, 4EBN) S. tuberosum (tbr) is difficult due to incongruity boundaries. In this study, three hybrid combinations, each with a specific genome constitution, were produced through protoplast fusion: (1) hexaploid 2x acl (+) 4x tbr, (2) tetraploid 2x acl (+) 2x tbr, and (3) hexaploid 4x acl (+) 2x tbr hybrids. In terms of glycoalkaloid aglycones, the hybrids produced demissidine, tomatidine and solanidine, similarly to the S. acaule parental species, but S. tuberosum synthesised only solanidine. Inoculations with Clavibacter michiganensis ssp. sepedonicus (Cms), which is the causal agent of bacterial ring rot in potato, yielded significantly lower total glycoalkaloid aglycone accumulation both in S. acaule plants and in interspecific hybrids in comparison with the corresponding mock-inoculated plants. However, in S. tuberosum the aglycone levels were either higher or unchanged as a result of infection by Cms. To incorporate the desirable traits of the interspecific somatic hybrids into 4EBN S. tuberosum, sexual backcrosses were carried out. The hexaploid 4x acl (+) 2x tbr hybrids with the hypothetical 4EBN showed the greatest capacity to undergo backcrosses with S. tuberosum.

  11. AN APPROACH FOR CHARACTERIZING TROPOSPHERIC OZONE RISK TO FOREST

    EPA Science Inventory

    The risk tropospheric ozone poses to forests in the United States is dependent on the variation in ozone exposure across the distribution of the forests in question and the various environmental and climate factors predominant in the region. All these factors have a spatial natur...

  12. AN APPROACH FOR CHARACTERIZING TROPOSPHERIC OZONE RISK TO FOREST

    EPA Science Inventory

    The risk tropospheric ozone poses to forests in the United States is dependent on the variation in ozone exposure across the distribution of the forests in question and the various environmental and climate factors predominant in the region. All these factors have a spatial natur...

  13. Profile sampling to characterize particulate lead risks in potable water.

    PubMed

    Clark, Brandi; Masters, Sheldon; Edwards, Marc

    2014-06-17

    Traditional lead (Pb) profiling, or collecting sequential liters of water that flow from a consumer tap after a stagnation event, has recently received widespread use in understanding sources of Pb in drinking water and risks to consumer health, but has limitations in quantifying particulate Pb risks. A new profiling protocol was developed in which a series of traditional profiles are collected from the same tap at escalating flow rates. The results revealed marked differences in risks of Pb exposure from one consumer home to another as a function of flow rate, with homes grouped into four risk categories with differing flushing requirements and public education to protect consumers. On average, Pb concentrations detected in water at high flow without stagnation were at least three to four times higher than in first draw samples collected at low flow with stagnation, demonstrating a new "worst case" lead release scenario, contrary to the original regulatory assumption that stagnant, first draw samples contain the highest lead concentrations. Testing also revealed that in some cases water samples with visible particulates had much higher Pb than samples without visible particulates, and tests of different sample handling protocols confirmed that some EPA-allowed methods would not quantify as much as 99.9% of the Pb actually present (avg. 27% of Pb not quantified).

  14. A Risk Management Framework to Characterize Black Swan Risks: A Case Study of Lightning Effects on Insensitive High Explosives

    NASA Astrophysics Data System (ADS)

    Sanders, Gary A.

    Effective and efficient risk management processes include the use of high fidelity modeling and simulation during the concept exploration phase as part of the technology and risk assessment activities, with testing and evaluation tasks occurring in later design development phases. However, some safety requirements and design architectures may be dominated by the low probability/high consequence "Black Swan" vulnerabilities that require very early testing to characterize and efficiently mitigate. Failure to address these unique risks has led to catastrophic systems failures including the space shuttle Challenger, Deepwater Horizon, Fukushima nuclear reactor, and Katrina dike failures. Discovering and addressing these risks later in the design and development process can be very costly or even lead to project cancellation. This paper examines the need for risk management process adoption of early hazard phenomenology testing to inform the technical risk assessment, requirements definition and conceptual design. A case study of the lightning design vulnerability of the insensitive high explosives being used in construction, mining, demolition, and defense industries will be presented to examine the impact of this vulnerability testing during the concept exploration phase of the design effort. While these insensitive high explosives are far less sensitive to accidental initiation by fire, impact, friction or even electrical stimuli, their full range of sensitivities have not been characterized and ensuring safe engineering design and operations during events such as lightning storms requires vulnerability testing during the risk assessment phase.

  15. EVALUATION OF RISKS AND WASTE CHARACTERIZATION REQUIREMENTS FOR THE TRANSURANIC WASTE EMPLACED IN WIPP DURING 1999

    SciTech Connect

    Channell, J.K.; Walker, B.A.

    2000-05-01

    Specifically this report: 1. Compares requirements of the WAP that are pertinent from a technical viewpoint with the WIPP pre-Permit waste characterization program, 2. Presents the results of a risk analysis of the currently emplaced wastes. Expected and bounding risks from routine operations and possible accidents are evaluated; and 3. Provides conclusions and recommendations.

  16. FASTER SCIENCE FOR BETTER DECISIONS: CHARACTERIZING ENVIRONMENTAL CONTAMINANT RISK FROM HIGH THROUGHPUT DATA

    EPA Science Inventory

    Tens of thousands of chemicals and other man-made contaminants exist in our environment, but only a fraction of these have been characterized for their potential risk to humans and there is widespread interest in closing this data gap in order to better manage contaminant risk. C...

  17. Improving Risk Characterizations Based on Time to Response

    DTIC Science & Technology

    1986-05-01

    response as a function of exposure . The type of modeling has generally been of the form where the frequency of response is modeled as a function of dose ...67 REFERENCES Armitage, P. (1982). The assessment of low- dose carcinogenicity. Biometrics 38 ( Supplement on Current Topics in Biostatistics and...important aspects of quantitative cancer risk assessment is to model the frequency of a carcinogenic response as a function of exposure . Most of the

  18. Risk characterization of detergent surfactants in the Netherlands

    SciTech Connect

    Feijtel, T.; Plassche, E. van de

    1995-12-31

    The Dutch Soap Association (NVZ) and the Dutch Environmental Ministry (VROM) developed in 1991 an aquatic hazard priority list of all detergent ingredients. The agreed priority list consisted of linear alkylbenzene sulfonate (LAS), alcohol ethoxylates (AE), alcohol ethoxylated sulfates (AES), and soap. A stepwise or tiered risk assessment approach was adopted as the recommended approach to evaluate the risk of these surfactants. This implies that depending on the risk (or PEC/PNEC) ratio, the sequential test program or assessment would proceed further, to ensure adequate protection of the ecosystem. The agreed calculation scheme for the aquatic compartment is based on the comparison of the 90th percentile of Predicted Environmental Concentrations (PEC) in the Netherlands -- at 1,000 meter below the sewage outfall -- to the Predicted No Effect Concentration (PNEC) for ecosystems. The 90th percentile surfactant concentrations at 1,000 meter below the sewage outfall can be calculated using information or data on (1) release, (2) in-sewer removal, (3) treatment efficiency, (4) dilution and (5) instream-removal and/or measured in representative sites in The Netherlands. In addition, all toxicological data was critically reviewed by company experts and experts of RIVM and VROM to present a rationale for a sound database for the derivation of a Predicted No Effect Concentration (PNEC). It was concluded that the risk of LAS, AE and AES and soap for the aquatic environment is low. Also taking the estimated uncertainty into account, the predicted environmental concentrations are always considerably lower that the predicted no effect concentrations.

  19. Treatment of Passive Component Reliability in Risk-Informed Safety Margin Characterization FY 2010 Report

    SciTech Connect

    Robert W Youngblood

    2010-09-01

    The Risk-Informed Safety Margin Characterization (RISMC) pathway is a set of activities defined under the U.S. Department of Energy (DOE) Light Water Reactor Sustainability Program. The overarching objective of RISMC is to support plant life-extension decision-making by providing a state-of-knowledge characterization of safety margins in key systems, structures, and components (SSCs). A technical challenge at the core of this effort is to establish the conceptual and technical feasibility of analyzing safety margin in a risk-informed way, which, unlike conventionally defined deterministic margin analysis, is founded on probabilistic characterizations of SSC performance.

  20. Characterizing occupational risk perception: the case of biological, ergonomic and organizational hazards in Spanish healthcare workers.

    PubMed

    Portell, Mariona; Gil, Rosa M; Losilla, Josep M; Vives, Jaume

    2014-01-01

    Understanding how risk is perceived by workers is necessary for effective risk communication and risk management. This study adapts key elements of the psychometric perspective to characterize occupational risk perception at a worker level. A total of 313 Spanish healthcare workers evaluated relevant hazards in their workplaces related to biological, ergonomic and organizational factors. A questionnaire elicited workers' ratings of 3 occupational hazards on 9 risk attributes along with perceived risk. Factor and regression analyses reveal regularities in how different risks are perceived, while, at the same time, the procedure helps to summarize specificities in the perception of each hazard. The main regularity is the weight of feeling of dread/severity in order to characterize the risk perceived (β ranges from .22 to .41; p < .001). Data also suggest an underestimation of expert knowledge in relation to the personal knowledge of risk. Thus, participants consider their knowledge of the risk related to biological, ergonomic, and organizational hazards to be higher than the knowledge attributed to the occupational experts (mean differences 95% CIs [.10, .30], [.54, .94], and [0.52, 1.05]). We demonstrate the application of a feasible and systematic procedure to capture how workers perceive hazards in their immediate work environment.

  1. Acute toxicity of high doses of the glycoalkaloids, alpha-solanine and alpha-chaconine, in the Syrian Golden hamster.

    PubMed

    Langkilde, Søren; Schrøder, Malene; Stewart, Derek; Meyer, Otto; Conner, Sean; Davies, Howard; Poulsen, Morten

    2008-09-24

    Sprouted, stressed, or spoiled potato tubers have reportedly led to human acute intoxication, coma, and death when consumed in high amounts. These effects have been attributed to glycoalkaloids (GAs), primarily alpha-solanine and alpha-chaconine, naturally present in all potatoes. The level of GAs in potato tubers has previously been shown to increase substantially as a result of improper handling and postharvest storage. A short-term study was performed to investigate the dose-response profile of alpha-solanine and alpha-chaconine alone or in combination, administered daily by oral gavage to Syrian Golden hamsters. Daily doses of 100 mg of alpha-solanine [kg body weight (BW)] (-1) induced death in two of four hamsters within 4 days, when administered by gavage to female Syrian hamsters. Doses of 100 mg of alpha-chaconine alone or alpha-solanine and alpha-chaconine combined in a ratio of 1:2.5, in doses of 75 or 100 mg (kg BW) (-1), induced death in one of four hamsters within the same period. Animals dosed with alpha-solanine alone or in combination with alpha-chaconine suffered from fluid-filled and dilated small intestines. The GA administration had no effect on acetyl cholinesterase (AChE) or butyryl cholinesterase (BuChE) activity in plasma or brain. Liquid chromatography-mass spectrometry-based metabolomics showed that there was a specific accumulation of alpha-chaconine in the liver tissues. In addition, metabolomics gave direct evidence of glycolytic metabolism of the GA with the beta 1, beta 2, and gamma-GAs detected in the urine and, to a lesser extent, the feces. Doses from 75 mg (kg BW) (-1) of alpha-chaconine, alpha-solanine, or the two compounds combined were potentially lethal within 4-5 days in the Syrian Golden hamster. However, the cause of death in these studies could not be established. No synergistic effects of alpha-solanine combined with alpha-chaconine were evident.

  2. Neuropathic pain after breast cancer treatment: characterization and risk factors.

    PubMed

    Pereira, Susana; Fontes, Filipa; Sonin, Teresa; Dias, Teresa; Fragoso, Maria; Castro-Lopes, José; Lunet, Nuno

    2017-08-07

    Neuropathic pain (NP) may be an important contributor to the morbidity burden of breast cancer. We aimed to quantify the incidence of NP in the first year after diagnosis of breast cancer, and to identify its main determinants. We performed a prospective cohort study including 506 patients with incident breast cancer, recruited at the Portuguese Institute of Oncology of Porto, and followed for one year; patients with incident NP were additionally evaluated when this condition was diagnosed and after six months, to identify chronic NP. During the first year, 156 patients were diagnosed with NP [30.8%, 95% confidence interval (95%CI): 27.0-35.0]. Anxiety [relative risk (RR)=1.50; 95%CI: 1.06-2.13], arm symptoms (RR=1.44; 95%CI: 1.02-2.05), cancer stage III/IV (RR=2.47; 95%CI: 1.66-3.66), breast-conserving surgery with axillary lymph node dissection (ALND) (RR=3.13; 95%CI: 1.51-6.48), mastectomy with ALND (RR=2.52; 95%CI: 1.25-5.11) and damaging of the intercostobrachial nerve (RR=2.05; 95%CI:1.25-3.37) were predictors of a higher risk of NP. A total of 97 patients (62.2%, 95%CI: 54.4-69.4) diagnosed with NP remained symptomatic after six months. NP and chronic NP were frequent in this population, being associated with anxiety and arm symptoms prior to breast cancer treatments, as well as type of surgical management. These results highlight the need for monitoring the occurrence of this neurological side effect of treatments and to develop strategies for reducing the morbidity burden of breast cancer. Copyright © 2017. Published by Elsevier Inc.

  3. Uncertainty characterization approaches for risk assessment of DBPs in drinking water: a review.

    PubMed

    Chowdhury, Shakhawat; Champagne, Pascale; McLellan, P James

    2009-04-01

    The management of risk from disinfection by-products (DBPs) in drinking water has become a critical issue over the last three decades. The areas of concern for risk management studies include (i) human health risk from DBPs, (ii) disinfection performance, (iii) technical feasibility (maintenance, management and operation) of treatment and disinfection approaches, and (iv) cost. Human health risk assessment is typically considered to be the most important phase of the risk-based decision-making or risk management studies. The factors associated with health risk assessment and other attributes are generally prone to considerable uncertainty. Probabilistic and non-probabilistic approaches have both been employed to characterize uncertainties associated with risk assessment. The probabilistic approaches include sampling-based methods (typically Monte Carlo simulation and stratified sampling) and asymptotic (approximate) reliability analysis (first- and second-order reliability methods). Non-probabilistic approaches include interval analysis, fuzzy set theory and possibility theory. However, it is generally accepted that no single method is suitable for the entire spectrum of problems encountered in uncertainty analyses for risk assessment. Each method has its own set of advantages and limitations. In this paper, the feasibility and limitations of different uncertainty analysis approaches are outlined for risk management studies of drinking water supply systems. The findings assist in the selection of suitable approaches for uncertainty analysis in risk management studies associated with DBPs and human health risk.

  4. Reference manual for toxicity and exposure assessment and risk characterization. CERCLA Baseline Risk Assessment

    SciTech Connect

    1995-03-01

    The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA, 1980) (CERCLA or Superfund) was enacted to provide a program for identifying and responding to releases of hazardous substances into the environment. The Superfund Amendments and Reauthorization Act (SARA, 1986) was enacted to strengthen CERCLA by requiring that site clean-ups be permanent, and that they use treatments that significantly reduce the volume, toxicity, or mobility of hazardous pollutants. The National Oil and Hazardous Substances Pollution Contingency Plan (NCP) (USEPA, 1985; USEPA, 1990) implements the CERCLA statute, presenting a process for (1) identifying and prioritizing sites requiring remediation and (2) assessing the extent of remedial action required at each site. The process includes performing two studies: a Remedial Investigation (RI) to evaluate the nature, extent, and expected consequences of site contamination, and a Feasibility Study (FS) to select an appropriate remedial alternative adequate to reduce such risks to acceptable levels. An integral part of the RI is the evaluation of human health risks posed by hazardous substance releases. This risk evaluation serves a number of purposes within the overall context of the RI/FS process, the most essential of which is to provide an understanding of ``baseline`` risks posed by a given site. Baseline risks are those risks that would exist if no remediation or institutional controls are applied at a site. This document was written to (1) guide risk assessors through the process of interpreting EPA BRA policy and (2) help risk assessors to discuss EPA policy with regulators, decision makers, and stakeholders as it relates to conditions at a particular DOE site.

  5. Characterizing Wildfire Regimes and Risk in the USA

    NASA Astrophysics Data System (ADS)

    Malamud, B. D.; Millington, J. D.; Perry, G. L.

    2004-12-01

    Over the last decade, high profile wildfires have resulted in numerous fatalities and loss of infrastructure. Wildfires also have a significant impact on climate and ecosystems, with recent authors emphasizing the need for regional-level examinations of wildfire-regime dynamics and change, and the factors driving them. With implications for hazard management, climate studies, and ecosystem research, there is therefore significant interest in appropriate analysis of historical wildfire databases. Insightful studies using wildfire database statistics exist, but are often hampered by the low spatial and/or temporal resolution of their datasets. In this paper, we use a high-resolution dataset consisting of 88,855 USFS wildfires over the time period 1970--2000, and consider wildfire occurrence across the conterminous USA as a function of ecoregion (land units classified by climate, vegetation, and topography), ignition source (anthropogenic vs. lightning), and decade (1970--1979, 1980--1989, 1990--1999). We find that for the conterminous USA (a) wildfires exhibit robust frequency-area power-law behavior in 17 different ecoregions, (b) normalized power-law exponents may be used to compare the scaling of wildfire burned areas between regions, (c) power-law exponents change systematically from east to west, (d) wildfires in 75% of the conterminous USA (particularly the east) have higher power-law exponents for anthropogenic vs. lightning ignition sources, and (e) recurrence intervals for wildfires of a given burned area or larger for each ecoregion can be assessed, allowing for the classification of wildfire regimes for probabilistic hazard estimation in the same vein as is now used for earthquakes. By examining wildfire statistics in a spatially and temporally explicit manner, we are able to present resultant wildfire regime summary statistics and conclusions, along with a probabilistic hazard assessment of wildfire risk at the ecoregion division level across the

  6. Liquid chromatographic determination of the glycoalkaloids alpha-solanine and alpha-chaconine in potato tubers: NMKL Interlaboratory Study. Nordic Committee on Food Analysis.

    PubMed

    Hellenäs, K E; Branzell, C

    1997-01-01

    Twelve laboratories participated in a collaborative study to evaluate precision parameters of a liquid chromatographic method for analysis of the glycoalkaloids alpha-solanine and alpha-chaconine in potato tubers. Samples consisted of frozen potato tuber homogenates distributed as 3 blind duplicates and 3 split-level pairs. The analytical method included aqueous extraction, workup on disposable solid-phase extraction cartridges, and reversed-phase chromatography with photometric detection at 202 nm. Results for alpha-solanine and alpha-chaconine were received from 10 and 9 laboratories, respectively. Relative standard deviations for reproducibility for alpha-solanine and alpha-chaconine were similar, ranging from 8 to 13% in the applied concentration range of 12 to 260 mg/kg fresh weight.

  7. Environmental auditing: An approach for characterizing tropospheric ozone risk to forests

    SciTech Connect

    Hogsett, W.E.; Weber, J.E.; Tingey, D.; Herstrom, A.; Lee, E.H.; Laurence, J.A.

    1997-01-01

    The risk tropospheric ozone poses to forests in the United States dependents on the variation in ozone exposure across the forests and the various environmental and climate factors predominant in the region. All these factors have a spatial nature; an approach to characterization of ozone risk is presented that places ozone exposure-response functions for species as seedlings and model-simulated tree and stand responses in a spatial context using a geographical information systems (GIS). The GIS is used to aggregate factors considered important in a risk characterization: (1) estimated ozone exposures over forested regions, (2) measures of ozone effects on species` and stand growth, and (3) spatially distributed environmental, genetic, and exposure influences on species` response to ozone. The GIS-based risk characterization provides an estimation the extent and magnitude of the potential ozone impact on forests. A preliminary risk characterization demonstrating this considered only the eastern United States and only the limited empirical data quantifying the effect of ozone exposures on forest tree species as seedlings. The area-weighted response of the annual seedling biomass loss formed the basis for a sensitivity ranking: sensitive-aspen and black cherry (14%-33% biomass loss over 50% of their distribution); moderately sensitive-tulip popular, loblolly pine, eastern white pine, and sugar maple (5%-13% biomass loss); insensitive-Virginia pine and red maple (0%-1% loss). Future GIS-based risk characterizations will include process-based model simulations of the three- to 5-year growth response of individual species as large trees. The interactive nature of GIS provides a tool to explore consequences of the range of climate conditions across a species` distribution, forest management practices, changing ozone precursors, regulatory control strategies, and other factors influencing the spatial distribution of ozone over time. 43 refs., 11 figs., 3 tabs.

  8. A biological approach to characterizing exposure to metalworking fluids and risk of prostate cancer (United States).

    PubMed

    Agalliu, Ilir; Eisen, Ellen A; Kriebel, David; Quinn, Margaret M; Wegman, David H

    2005-05-01

    Prostate cancer is hormone-related and chemicals that interfere with hormones may contribute to carcinogenesis. In a cohort of autoworkers we characterized exposure to metalworking fluids (MWF) into age windows with homogenous biological risk for prostate cancer, and examined exposure-response relationships using semi-parametric modeling. Incident cases (n=872) were identified via Michigan cancer registry from 1985 through 2000. Controls were selected using incidence-density sampling, 5:1 ratio. Using a hormonal-based model, exposure was accumulated in three windows: (1) late puberty, (2) adulthood, and (3) middle age. We used penalized splines to model risk as a smooth function of exposure, and controlled for race and calendar year of diagnosis in a Cox model. Risk of prostate cancer linearly increased with exposure to straight MWF in the first window, with a relative risk of 2.4 per 10 mg/m(3)-years. Autoworkers exposed to MWF at a young age also had an increased risk associated with MWF exposure incurred later in life. For soluble MWF there was a slightly increased risk in the third window. Exposure characterization based on a hormonal model identified heightened risk with early age of exposure to straight MWF. Results also support a long latency period for exposure related prostate cancer.

  9. CHARACTERIZATION OF DATA VARIABILITY AND UNCERTAINTY: HEALTH EFFECTS ASSESSMENTS IN THE INTEGRATED RISK INFORMATION SYSTEM (IRIS)

    EPA Science Inventory

    In response to a Congressional directive contained in HR 106-379 regarding EPA's appropriations for FY2000, EPA has undertaken an evaluation of the characterization of data variability and uncertainty in its Integrated Risk Information System (IRIS) health effects information dat...

  10. CHARACTERIZATION OF DATA VARIABILITY AND UNCERTAINTY: HEALTH EFFECTS ASSESSMENTS IN THE INTEGRATED RISK INFORMATION SYSTEM (IRIS)

    EPA Science Inventory

    In response to a Congressional directive contained in HR 106-379 regarding EPA's appropriations for FY2000, EPA has undertaken an evaluation of the characterization of data variability and uncertainty in its Integrated Risk Information System (IRIS) health effects information dat...

  11. Complex mixtures of air pollutants: characterizing the cancer risk of polycyclic organic matter.

    PubMed Central

    Lewtas, J

    1993-01-01

    Complex mixtures of polycyclic organic matter (POM) are used to illustrate the scientific problems and issues associated with characterizing the comparative risk of related complex mixtures. The complexity of mixtures in which the active components are not well characterized present special challenges, which include identifying the critical components of mixtures, their sources, and the appropriate biomarker(s) of exposure and dose; developing the appropriate experimental models for dose-response assessment; species extrapolation; and developing a scientific basis for predicting from one mixture to another. Strategies for addressing these issues include bioassay-directed chemical characterization of bioactive components of complex mixtures, apportionment methods to determine the source of biological activity and risk, DNA adduct methods to determine tissue exposure and target dose of mixtures, and comparative approaches to determining the relative similarity, potency, and risk of complex mixtures. Epidemiological data are available for humans exposed to POM from coke ovens, coal roofing tar, coal smoke, aluminum smelters, and cigarette smoke. These emissions are characterized and compared to POM from automotive emissions (diesel and gasoline), woodstove emissions, residential oil furnace emissions, and ambient air particles. The tumor potency and estimated cancer risks for these POM mixtures ranges over nearly three orders of magnitude. PMID:8354169

  12. Landscape characterization of peridomestic risk for Lyme disease using satellite imagery

    NASA Technical Reports Server (NTRS)

    Dister, S. W.; Fish, D.; Bros, S. M.; Frank, D. H.; Wood, B. L.

    1997-01-01

    Remotely sensed characterizations of landscape composition were evaluated for Lyme disease exposure risk on 337 residential properties in two communities of suburban Westchester County, New York. Properties were categorized as no, low, or high risk based on seasonally adjusted densities of Ixodes scapularis nymphs, determined by drag sampling during June and July 1990. Spectral indices based on Landsat Thematic Mapper data provided relative measures of vegetation structure and moisture (wetness), as well as vegetation abundance (greenness). A geographic information system (GIS) was used to spatially quantify and relate the remotely sensed landscape variables to risk category. A comparison of the two communities showed that Chappaqua, which had more high-risk properties (P < 0.001), was significantly greener and wetter than Armonk (P < 0.001). Furthermore, within Chappaqua, high-risk properties were significantly greener and wetter than lower-risk properties in this community (P < 0.01). The high-risk properties appeared to contain a greater proportion of broadleaf trees, while lower-risk properties were interpreted as having a greater proportion of nonvegetative cover and/or open lawn. The ability to distinguish these fine scale differences among communities and individual properties illustrates the efficiency of a remote sensing/GIS-based approach for identifying peridomestic risk of Lyme disease over large geographic areas.

  13. Landscape characterization of peridomestic risk for Lyme disease using satellite imagery

    NASA Technical Reports Server (NTRS)

    Dister, S. W.; Fish, D.; Bros, S. M.; Frank, D. H.; Wood, B. L.

    1997-01-01

    Remotely sensed characterizations of landscape composition were evaluated for Lyme disease exposure risk on 337 residential properties in two communities of suburban Westchester County, New York. Properties were categorized as no, low, or high risk based on seasonally adjusted densities of Ixodes scapularis nymphs, determined by drag sampling during June and July 1990. Spectral indices based on Landsat Thematic Mapper data provided relative measures of vegetation structure and moisture (wetness), as well as vegetation abundance (greenness). A geographic information system (GIS) was used to spatially quantify and relate the remotely sensed landscape variables to risk category. A comparison of the two communities showed that Chappaqua, which had more high-risk properties (P < 0.001), was significantly greener and wetter than Armonk (P < 0.001). Furthermore, within Chappaqua, high-risk properties were significantly greener and wetter than lower-risk properties in this community (P < 0.01). The high-risk properties appeared to contain a greater proportion of broadleaf trees, while lower-risk properties were interpreted as having a greater proportion of nonvegetative cover and/or open lawn. The ability to distinguish these fine scale differences among communities and individual properties illustrates the efficiency of a remote sensing/GIS-based approach for identifying peridomestic risk of Lyme disease over large geographic areas.

  14. Impact of ground motion characterization on conservatism and variability in seismic risk estimates

    SciTech Connect

    Sewell, R.T.; Toro, G.R.; McGuire, R.K.

    1996-07-01

    This study evaluates the impact, on estimates of seismic risk and its uncertainty, of alternative methods in treatment and characterization of earthquake ground motions. The objective of this study is to delineate specific procedures and characterizations that may lead to less biased and more precise seismic risk results. This report focuses on sources of conservatism and variability in risk that may be introduced through the analytical processes and ground-motion descriptions which are commonly implemented at the interface of seismic hazard and fragility assessments. In particular, implication of the common practice of using a single, composite spectral shape to characterize motions of different magnitudes is investigated. Also, the impact of parameterization of ground motion on fragility and hazard assessments is shown. Examination of these results demonstrates the following. (1) There exists significant conservatism in the review spectra (usually, spectra characteristic of western U.S. earthquakes) that have been used in conducting past seismic risk assessments and seismic margin assessments for eastern U.S. nuclear power plants. (2) There is a strong dependence of seismic fragility on earthquake magnitude when PGA is used as the ground-motion characterization. When, however, magnitude-dependent spectra are anchored to a common measure of elastic spectral acceleration averaged over the appropriate frequency range, seismic fragility shows no important nor consistent dependence on either magnitude or strong-motion duration. Use of inelastic spectral acceleration (at the proper frequency) as the ground spectrum anchor demonstrates a very similar result. This study concludes that a single, composite-magnitude spectrum can generally be used to characterize ground motion for fragility assessment without introducing significant bias or uncertainty in seismic risk estimates.

  15. Stepwise quantitative risk assessment as a tool for characterization of microbiological food safety.

    PubMed

    van Gerwen, S J; te Giffel, M C; van't Riet, K; Beumer, R R; Zwietering, M H

    2000-06-01

    This paper describes a system for the microbiological quantitative risk assessment for food products and their production processes. The system applies a stepwise risk assessment, allowing the main problems to be addressed before focusing on less important problems. First, risks are assessed broadly, using order of magnitude estimates. Characteristic numbers are used to quantitatively characterize microbial behaviour during the production process. These numbers help to highlight the major risk-determining phenomena, and to find negligible aspects. Second, the risk-determining phenomena are studied in more detail. Both general and/or specific models can be used for this and varying situations can be simulated to quantitatively describe the risk-determining phenomena. Third, even more detailed studies can be performed where necessary, for instance by using stochastic variables. The system for quantitative risk assessment has been implemented as a decision supporting expert system called SIEFE: Stepwise and Interactive Evaluation of Food safety by an Expert System. SIEFE performs bacterial risk assessments in a structured manner, using various information sources. Because all steps are transparent, every step can easily be scrutinized. In the current study the effectiveness of SIEFE is shown for a cheese spread. With this product, quantitative data concerning the major risk-determining factors were not completely available to carry out a full detailed assessment. However, this did not necessarily hamper adequate risk estimation. Using ranges of values instead helped identifying the quantitatively most important parameters and the magnitude of their impact. This example shows that SIEFE provides quantitative insights into production processes and their risk-determining factors to both risk assessors and decision makers, and highlights critical gaps in knowledge.

  16. Probabilistic environmental risk characterization of pharmaceuticals in sewage treatment plant discharges.

    PubMed

    Christensen, Anne Munch; Markussen, Bo; Baun, Anders; Halling-Sørensen, Bent

    2009-10-01

    The occurrence of pharmaceuticals in different water bodies and the findings of effects on aquatic organisms in ecotoxicity tests have raised concerns about environmental risks of pharmaceuticals in receiving waters. Due to the fact that the amount of ecotoxicological studies has increased significantly during the last decade, probabilistic approaches for risk characterization of these compounds may be feasible. This approach was evaluated by applying it to 22 human-used pharmaceuticals covering both pharmaceuticals with a high volume and high ecotoxicity, using ecotoxicological effect data from laboratory studies and comparing these to monitoring data on the effluents from sewage treatment plants in Europe and pharmaceutical sales quantities. We found that for 19 of the 22 selected pharmaceuticals the existing data were sufficient for probabilistic risk characterizations. The subsequently modeled ratios between monitored concentrations and low-effect concentrations were mostly above a factor of 100. Compared to the current paradigm for EU environmental risk assessment where a safety factor of 10 or 100 might have been used it seems that for the modeled compounds there's a low environmental risk. However, similarly calculated ratios for five pharmaceuticals (propranolol, ibuprofen, furosemide, ofloxacin, and ciprofloxacin) were below 100, while ibuprofen and ciprofloxacin are considered to be of high concern due to lack of ecotoxicity studies. This paper shows that by applying probabilistic approaches, existing data can be used to execute a comprehensive study on probability of impacts, thereby contributing to a more comprehensive environmental risk assessment of pharmaceuticals.

  17. Defining, characterizing, and establishing "safe enough" risk thresholds for human space flight

    NASA Astrophysics Data System (ADS)

    Ocampo, Robert Paul

    No spacecraft will ever be perfectly safe. Consequently, engineers must strive to design, develop, and operate spacecraft that are safe enough. This thesis presents a conceptual framework for defining and characterizing "safe" and distinguishing "safe enough" from "not safe enough." Space Shuttle and Soyuz safety records are presented in the context of this framework, and compared to the safety records of various modes of transportation (automotive, rail, boating, general aviation, commercial aviation) and adventure sport activities (skydiving, mountaineering, SCUBA diving). From these comparisons, a heuristic method for predicting space flight risk is derived. This method, which is built upon the inverse correlation between risk and usage, can coarsely predict risk in the absence of detailed spacecraft data. Based on these predictions, spacecraft risk can either be accepted as "safe enough" or rejected as "not safe enough."

  18. Characterization of vascular disease risk in postmenopausal women and its association with cognitive performance.

    PubMed

    Dowling, N Maritza; Gleason, Carey E; Manson, Joann E; Hodis, Howard N; Miller, Virginia M; Brinton, Eliot A; Neal-Perry, Genevieve; Santoro, M Nanette; Cedars, Marcelle; Lobo, Rogerio; Merriam, George R; Wharton, Whitney; Naftolin, Frederick; Taylor, Hugh; Harman, S Mitchell; Asthana, Sanjay

    2013-01-01

    While global measures of cardiovascular (CV) risk are used to guide prevention and treatment decisions, these estimates fail to account for the considerable interindividual variability in pre-clinical risk status. This study investigated heterogeneity in CV risk factor profiles and its association with demographic, genetic, and cognitive variables. A latent profile analysis was applied to data from 727 recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Women were cognitively healthy, within three years of their last menstrual period, and free of current or past CV disease. Education level, apolipoprotein E ε4 allele (APOE4), ethnicity, and age were modeled as predictors of latent class membership. The association between class membership, characterizing CV risk profiles, and performance on five cognitive factors was examined. A supervised random forest algorithm with a 10-fold cross-validation estimator was used to test accuracy of CV risk classification. The best-fitting model generated two distinct phenotypic classes of CV risk 62% of women were "low-risk" and 38% "high-risk". Women classified as low-risk outperformed high-risk women on language and mental flexibility tasks (p = 0.008) and a global measure of cognition (p = 0.029). Women with a college degree or above were more likely to be in the low-risk class (OR = 1.595, p = 0.044). Older age and a Hispanic ethnicity increased the probability of being at high-risk (OR = 1.140, p = 0.002; OR = 2.622, p = 0.012; respectively). The prevalence rate of APOE-ε4 was higher in the high-risk class compared with rates in the low-risk class. Among recently menopausal women, significant heterogeneity in CV risk is associated with education level, age, ethnicity, and genetic indicators. The model-based latent classes were also associated with cognitive function. These differences may point to phenotypes for CV disease risk. Evaluating the

  19. Pre-site characterization risk analysis for commercial-scale carbon sequestration.

    PubMed

    Dai, Zhenxue; Stauffer, Philip H; Carey, J William; Middleton, Richard S; Lu, Zhiming; Jacobs, John F; Hnottavange-Telleen, Ken; Spangler, Lee H

    2014-04-01

    This study develops a probability framework to evaluate subsurface risks associated with commercial-scale carbon sequestration in the Kevin Dome, Montana. Limited knowledge of the spatial distribution of physical attributes of the storage reservoir and the confining rocks in the area requires using regional data to estimate project risks during the pre-site characterization analysis. A set of integrated Monte Carlo simulations are used to assess four risk proxies: the CO2 injectivity, area of review (AoR), migration rate into confining rocks, and a monitoring strategy prior to detailed site characterization. Results show a reasonable likelihood of reaching the project goal of injecting 1 Mt in 4 years with a single injection well (>58%), increasing to >70% if the project is allowed to run for 5 years. The mean radius of the AoR, based on a 0.1 MPa pressure change, is around 4.8 km. No leakage of CO2 through the confining units is seen in any simulations. The computed CO2 detection probability suggests that the monitoring wells should be located at less than 1.2 km away from the injection well so that CO2 is likely to be detected within the time frame of the project. The scientific results of this study will be used to inform the detailed site characterization process and to provide more insight for understanding operational and technical risks before injecting CO2.

  20. Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans

    PubMed Central

    Chen, Fang; Chen, Gary K.; Millikan, Robert C.; John, Esther M.; Ambrosone, Christine B.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J.; Ziegler, Regina G.; Deming, Sandra L.; Bandera, Elisa V.; Nyante, Sarah; Palmer, Julie R.; Rebbeck, Timothy R.; Ingles, Sue A.; Press, Michael F.; Rodriguez-Gil, Jorge L.; Chanock, Stephen J.; Le Marchand, Loïc; Kolonel, Laurence N.; Henderson, Brian E.; Stram, Daniel O.; Haiman, Christopher A.

    2011-01-01

    Genome-wide association studies (GWAS) have revealed 19 common genetic variants that are associated with breast cancer risk. Testing of the index signals found through GWAS and fine-mapping of each locus in diverse populations will be necessary for characterizing the role of these risk regions in contributing to inherited susceptibility. In this large study of breast cancer in African-American women (3016 cases and 2745 controls), we tested the 19 known risk variants identified by GWAS and replicated associations (P < 0.05) with only 4 variants. Through fine-mapping, we identified markers in four regions that better capture the association with breast cancer risk in African Americans as defined by the index signal (2q35, 5q11, 10q26 and 19p13). We also identified statistically significant associations with markers in four separate regions (8q24, 10q22, 11q13 and 16q12) that are independent of the index signals and may represent putative novel risk variants. In aggregate, the more informative markers found in the study enhance the association of these risk regions with breast cancer in African Americans [per allele odds ratio (OR) = 1.18, P = 2.8 × 10−24 versus OR = 1.04, P = 6.1 × 10−5]. In this detailed analysis of the known breast cancer risk loci, we have validated and improved upon markers of risk that better characterize their association with breast cancer in women of African ancestry. PMID:21852243

  1. Using the Lorenz Curve to Characterize Risk Predictiveness and Etiologic Heterogeneity.

    PubMed

    Mauguen, Audrey; Begg, Colin B

    2016-07-01

    The Lorenz curve is a graphical tool that is used widely in econometrics. It represents the spread of a probability distribution, and its traditional use has been to characterize population distributions of wealth or income, or more specifically, inequalities in wealth or income. However, its utility in public health research has not been broadly established. The purpose of this article is to explain its special usefulness for characterizing the population distribution of disease risks, and in particular for identifying the precise disease burden that can be predicted to occur in segments of the population that are known to have especially high (or low) risks, a feature that is important for evaluating the yield of screening or other disease prevention initiatives. We demonstrate that, although the Lorenz curve represents the distribution of predicted risks in a population at risk for the disease, in fact it can be estimated from a case-control study conducted in the population without the need for information on absolute risks. We explore two different estimation strategies and compare their statistical properties using simulations. The Lorenz curve is a statistical tool that deserves wider use in public health research.

  2. Self-Awareness of Falls Risk Among Elderly Patients: Characterizing Awareness Deficits and Exploring Associated Factors.

    PubMed

    Mihaljcic, Tijana; Haines, Terry P; Ponsford, Jennie L; Stolwyk, Renerus J

    2015-12-01

    To characterize self-awareness in older adults undergoing inpatient rehabilitation and explore factors associated with reduced awareness of falls risk. Prospective, cross-sectional design. Older adult inpatient rehabilitation setting. Rehabilitation inpatients (N=91; mean age, 77.97±8.04y) and their treating physiotherapist. None. Three aspects of self-awareness (intellectual, emergent, anticipatory) were measured using the Self-Awareness of Falls Risk Measure. Demographic, medical, and cognitive (Mini-Mental State Examination) information were collected. Current ability was measured using the FIM and timed Up and Go test. Of the patients in the sample, 31% to 63% underestimated falls risk and 3% to 10% overestimated falls risk depending on the aspect of awareness measured. Different aspects of reduced self-awareness were correlated with being a man, higher educational attainment, neurologic history, lower cognitive ability, and lower functional ability. Regression analysis indicated that sex (β=-.33, P=.004), education (β=-.30, P=.006), and neurologic history (β=-.22, P=.038) were independently associated with overall self-awareness. The results suggest that a proportion of older adults undergoing inpatient rehabilitation underestimate personal falls risk. Further research is required to investigate the contributors to and effects of reduced self-awareness of falls risk. Greater understanding of these factors will facilitate the development of strategies to increase awareness of falls risk and increase engagement in falls prevention. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  3. Characterization of Vascular Disease Risk in Postmenopausal Women and Its Association with Cognitive Performance

    PubMed Central

    Dowling, N. Maritza; Gleason, Carey E.; Manson, JoAnn E.; Hodis, Howard N.; Miller, Virginia M.; Brinton, Eliot A.; Neal-Perry, Genevieve; Santoro, M. Nanette; Cedars, Marcelle; Lobo, Rogerio; Merriam, George R.; Wharton, Whitney; Naftolin, Frederick; Taylor, Hugh; Harman, S. Mitchell; Asthana, Sanjay

    2013-01-01

    Objectives While global measures of cardiovascular (CV) risk are used to guide prevention and treatment decisions, these estimates fail to account for the considerable interindividual variability in pre-clinical risk status. This study investigated heterogeneity in CV risk factor profiles and its association with demographic, genetic, and cognitive variables. Methods A latent profile analysis was applied to data from 727 recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Women were cognitively healthy, within three years of their last menstrual period, and free of current or past CV disease. Education level, apolipoprotein E ε4 allele (APOE4), ethnicity, and age were modeled as predictors of latent class membership. The association between class membership, characterizing CV risk profiles, and performance on five cognitive factors was examined. A supervised random forest algorithm with a 10-fold cross-validation estimator was used to test accuracy of CV risk classification. Results The best-fitting model generated two distinct phenotypic classes of CV risk 62% of women were “low-risk” and 38% “high-risk”. Women classified as low-risk outperformed high-risk women on language and mental flexibility tasks (p = 0.008) and a global measure of cognition (p = 0.029). Women with a college degree or above were more likely to be in the low-risk class (OR = 1.595, p = 0.044). Older age and a Hispanic ethnicity increased the probability of being at high-risk (OR = 1.140, p = 0.002; OR = 2.622, p = 0.012; respectively). The prevalence rate of APOE-ε4 was higher in the high-risk class compared with rates in the low-risk class. Conclusion Among recently menopausal women, significant heterogeneity in CV risk is associated with education level, age, ethnicity, and genetic indicators. The model-based latent classes were also associated with cognitive function. These differences may point to

  4. Characterization and risk of exposure to elements from artisanal gold mining operations in the Bolivian Andes.

    PubMed

    Pavilonis, Brian; Grassman, Jean; Johnson, Glen; Diaz, Yilmael; Caravanos, Jack

    2017-04-01

    Artisanal and small-scale gold mining (ASGM) offers low-skilled workers an opportunity to elevate themselves out of poverty. However, this industry operates with little to no pollution controls and the cost to the environment and human health can be large. The objectives of this study were to measure levels of arsenic (As), manganese (Mn), cobalt (Co), lead (Pb), and mercury (Hg) in the environment and characterize health risks to miners and residents in an area with active ASGM operations. An exposure assessment was conducted at two different mining sites and a nearby village in the Bolivian Anders. The resulting measurements were then used to quantify cancerous and noncancerous health risks to children and adults working at and living near ASGM areas. Soil concentrations of As were well above background levels and showed great variations between the village and mining area. Mercury vapor levels at the two mining sites were approximately 30 times larger than the EPA reference concentration. The risk of developing non-cancerous health effects were primarily due to exposure to As and Hg. The probability of individuals developing cancer was considerably increased with adult miners having a probability of 1.3 out of 100. Cancer potential was driven by exposure to As, with de minimus cancer risk from all other elements. Based on the environmental characterization of elements in soils and Hg vapors, the risk of developing cancerous and non-cancerous health outcomes were above a level of concern based on EPA risk assessment guidance. Personal protective equipment was not worn by workers and Hg amalgam is commonly heated in workers' homes. Better education of the risks of ASGM is needed as well as simple controls to reduce exposure. Published by Elsevier Inc.

  5. Characterizing coronary heart disease risk in chronic schizophrenia: high prevalence of the metabolic syndrome.

    PubMed

    Cohn, Tony; Prud'homme, Denis; Streiner, David; Kameh, Homa; Remington, Gary

    2004-11-01

    To determine the prevalence and characteristics of coronary heart disease (CHD) risk factors in patients with chronic schizophrenia or schizoaffective disorder. We compared individual CHD risk factors and Framingham risk predictions in a group of 240 patients with a large national sample (Canadian Heart Health Survey) matched for age and sex. In addition, we compared rates of the metabolic syndrome (syndrome X) with recently published rates in the US adult population. Compared with the reference population, Framingham 10-year risk of myocardial infarction was greater in the male patients (t3091 = 4.35, P < 0.001) but not in the female patients. Prevalence rates of the metabolic syndrome in the patients (42.6% of men and 48.5% of women) were approximately 2 times published rates in the US adult population. Further, the syndrome appears to occur at a younger age than in the general population. These long-term patients have increased CHD risks best captured by the metabolic syndrome conceptualization coupled with a high rate of cigarette smoking. This characterization is consistent with increased cardiovascular morbidity and decreased life expectancy in both men and women. We underscore the importance of both screening for and treating potentially reversible CHD risk factors in schizophrenia patients.

  6. A risk characterization of safety research areas for Integral Fast Reactor program planning

    SciTech Connect

    Mueller, C.J.; Cahalan, J.E.; Hill, D.J.; Kramer, J.M.; Marchaterre, J.F.; Pedersen, D.R.; Sevy, R.H.; Tilbrook, R.W.; Wei, T.Y.; Wright, A.E.

    1988-01-01

    This paper characterizes the areas of Integral Fast Reactor (IFR) safety research in terms of their importance in addressing the risk of core disruption sequences for innovative designs. Such sequences have traditionally been determined to constitute the primary risk to public health and safety. All core disruption sequences are folded into four fault categories: classic unprotected (unscrammed) events; loss of decay heat; local fault propagation; and failure of critical reactor structures. Event trees are used to describe these sequences and the areas in the IFR Safety and related Base Technology research programs are discussed with respect to their relevance in addressing the key issues in preventing or delimiting core disruptive sequences. Thus a measure of potential for risk reduction is obtained for guidance in establishing research priorites.

  7. Cumulative Risk Assessment in the Lorraine Region: A Framework to Characterize Environmental Health Inequalities.

    PubMed

    Caudeville, Julien; Ioannidou, Despoina; Boulvert, Emmanuelle; Bonnard, Roseline

    2017-03-10

    The study explores spatial data processing methods and the associated impact on the characterization and quantification of a combined health risk indicator at a regional scale and at fine resolution. To illustrate the methodology of combining multiple publicly available data sources, we present a case study of the Lorraine region (France), where regional stakeholders were involved in the global procedures for data collection and organization. Different indicators are developed by combining technical approaches for assessing and characterizing human health exposure to chemical substances (in soil, air and water) and noise risk factors. The results permit identification of pollutant sources, determinants of exposure, and potential hotspot areas. A test of the model's assumptions to changes in sub-indicator spatial distribution showed the impact of data transformation on identifying more impacted areas. Cumulative risk assessment permits the combination of quantitative and qualitative evaluation of health risks by including stakeholders in the decision process, helping to define a subjective conceptual analysis framework or assumptions when uncertainties or knowledge gaps operate.

  8. Cumulative Risk Assessment in the Lorraine Region: A Framework to Characterize Environmental Health Inequalities

    PubMed Central

    Caudeville, Julien; Ioannidou, Despoina; Boulvert, Emmanuelle; Bonnard, Roseline

    2017-01-01

    The study explores spatial data processing methods and the associated impact on the characterization and quantification of a combined health risk indicator at a regional scale and at fine resolution. To illustrate the methodology of combining multiple publicly available data sources, we present a case study of the Lorraine region (France), where regional stakeholders were involved in the global procedures for data collection and organization. Different indicators are developed by combining technical approaches for assessing and characterizing human health exposure to chemical substances (in soil, air and water) and noise risk factors. The results permit identification of pollutant sources, determinants of exposure, and potential hotspot areas. A test of the model’s assumptions to changes in sub-indicator spatial distribution showed the impact of data transformation on identifying more impacted areas. Cumulative risk assessment permits the combination of quantitative and qualitative evaluation of health risks by including stakeholders in the decision process, helping to define a subjective conceptual analysis framework or assumptions when uncertainties or knowledge gaps operate. PMID:28287441

  9. RISK CHARACTERIZATION OF MATERNAL AND NEONATAL TETANUS IN VIEW OF TETANUS VACCINATION CAMPAIGNS IN PAKISTAN.

    PubMed

    Khan, Ejaz A; Khan, Rownak; Iqbal, Muhammad Tariq; Hasan, Quamrul; Farrukh, Saadia; Rana, Muhammad Safdar; Khan, Wasiq Mehmood

    2015-01-01

    Pakistan is one of the remaining 24 countries which have not yet achieved Maternal and Neonatal Tetanus Elimination (MNTE), The country adopted high-risk approach for 56 out of 119 districts with country-wide Tetanus Toxoid (TT) provision in Routine Immunization (RI) during early 2000-2003. The TT's mass campaigns could only cover 13% of high risk districts for 2009- 2011, and mostly for the Punjab province. To achieve MNT elimination, the country needs risk mapping for cost-effective intervention. We used both the quantitative and qualitative methods to conduct risk characterization. All the three available data sets (Reported EPI coverage data, PDHS 2012-13, and PSLM 2010-11) were assessed. A mix of core and surrogate indicators-for risk categorization was used through ranking and scoring the aggregated data and considering the past tetanus campaigns' coverage. Tetanus Toxoid (TT2+)-coverage of pregnant women and delivery in health facility, both received more weightage in scoring. We based the higher and lower cuts off points for each indicator on data ranges. The districts with higher scores, i.e., 10.5 and above were ranked good followed by medium (5.5-10.4) and low performing (less than 5.5). Consultations with the national and provincial field officers were utilized to understand the local context. In Pakistan, there are 139 districts out of which, 60 are the high risk districts for tetanus. Highest percentage is for Baluchistan (83%) followed by Sindh (52%), and Khyber Pakhtunkhwa (40%). Most of the Punjab is at medium risk (55%), followed by KP (52%), and Sindh (39%). Pakistan is at medium to high risk of MNT with a great variation at the sub-national level. Campaigns aiming to these districts may bring the country closer to MNT elimination target.

  10. Characterizing the genetic risk for Type 2 diabetes in a Malaysian multi-ethnic cohort.

    PubMed

    Abdullah, N; Abdul Murad, N A; Attia, J; Oldmeadow, C; Mohd Haniff, E A; Syafruddin, S E; Abd Jalal, N; Ismail, N; Ishak, M; Jamal, R; Scott, R J; Holliday, E G

    2015-10-01

    To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project. We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups. After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance. This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  11. Characterization of candidate genes in inflammatory bowel disease–associated risk loci

    PubMed Central

    Peloquin, Joanna M.; Sartor, R. Balfour; Newberry, Rodney D.; McGovern, Dermot P.; Yajnik, Vijay; Lira, Sergio A.

    2016-01-01

    GWAS have linked SNPs to risk of inflammatory bowel disease (IBD), but a systematic characterization of disease-associated genes has been lacking. Prior studies utilized microarrays that did not capture many genes encoded within risk loci or defined expression quantitative trait loci (eQTLs) using peripheral blood, which is not the target tissue in IBD. To address these gaps, we sought to characterize the expression of IBD-associated risk genes in disease-relevant tissues and in the setting of active IBD. Terminal ileal (TI) and colonic mucosal tissues were obtained from patients with Crohn’s disease or ulcerative colitis and from healthy controls. We developed a NanoString code set to profile 678 genes within IBD risk loci. A subset of patients and controls were genotyped for IBD-associated risk SNPs. Analyses included differential expression and variance analysis, weighted gene coexpression network analysis, and eQTL analysis. We identified 116 genes that discriminate between healthy TI and colon samples and uncovered patterns in variance of gene expression that highlight heterogeneity of disease. We identified 107 coexpressed gene pairs for which transcriptional regulation is either conserved or reversed in an inflammation-independent or -dependent manner. We demonstrate that on average approximately 60% of disease-associated genes are differentially expressed in inflamed tissue. Last, we identified eQTLs with either genotype-only effects on expression or an interaction effect between genotype and inflammation. Our data reinforce tissue specificity of expression in disease-associated candidate genes, highlight genes and gene pairs that are regulated in disease-relevant tissue and inflammation, and provide a foundation to advance the understanding of IBD pathogenesis. PMID:27668286

  12. Sterol Side Chain Reductase 2 Is a Key Enzyme in the Biosynthesis of Cholesterol, the Common Precursor of Toxic Steroidal Glycoalkaloids in Potato[W][OPEN

    PubMed Central

    Sawai, Satoru; Ohyama, Kiyoshi; Yasumoto, Shuhei; Seki, Hikaru; Sakuma, Tetsushi; Yamamoto, Takashi; Takebayashi, Yumiko; Kojima, Mikiko; Sakakibara, Hitoshi; Aoki, Toshio; Muranaka, Toshiya; Saito, Kazuki; Umemoto, Naoyuki

    2014-01-01

    Potatoes (Solanum tuberosum) contain α-solanine and α-chaconine, two well-known toxic steroidal glycoalkaloids (SGAs). Sprouts and green tubers accumulate especially high levels of SGAs. Although SGAs were proposed to be biosynthesized from cholesterol, the biosynthetic pathway for plant cholesterol is poorly understood. Here, we identify sterol side chain reductase 2 (SSR2) from potato as a key enzyme in the biosynthesis of cholesterol and related SGAs. Using in vitro enzyme activity assays, we determined that potato SSR2 (St SSR2) reduces desmosterol and cycloartenol to cholesterol and cycloartanol, respectively. These reduction steps are branch points in the biosynthetic pathways between C-24 alkylsterols and cholesterol in potato. Similar enzymatic results were also obtained from tomato SSR2. St SSR2-silenced potatoes or St SSR2-disrupted potato generated by targeted genome editing had significantly lower levels of cholesterol and SGAs without affecting plant growth. Our results suggest that St SSR2 is a promising target gene for breeding potatoes with low SGA levels. PMID:25217510

  13. Alpha-chaconine, a potato glycoalkaloid, induces apoptosis of HT-29 human colon cancer cells through caspase-3 activation and inhibition of ERK 1/2 phosphorylation.

    PubMed

    Yang, Seun-Ah; Paek, Seung-Hwan; Kozukue, Nobuyuki; Lee, Kap-Rang; Kim, Jung-Ae

    2006-06-01

    Although alpha-chaconine, one of the two major potato trisaccharide glycoalkaloids, have shown cytotoxic effects on human cancer cells, the exact mechanism of this action of alpha-chaconine is not completely understood. In this study, we found that alpha-chaconine induced apoptosis of HT-29 cells in a time- and concentration-dependent manner by using flow cytometric analysis. We also found that caspase-3 activity and the active form of caspase-3 were increased 12 h after alpha-chaconine treatment. Caspase inhibitors, N-Ac-DEVD-CHO and Z-VAD-fmk, prevented alpha-chaconine-induced apoptosis, whereas alpha-chaconine-induced apoptosis was potentiated by PD98059, an extracellular signal-regulated kinase (ERK) inhibitor. However, pretreatment of the cells with LY294002 and SB203580, inhibitors of PI3K and p38, respectively, BAPTA-AM, an intracellular Ca(2+) chelator, and antioxidants such as N-acetylcysteine (NAC) and Trolox had no effect on the alpha-chaconine-induced cell death. In addition, phosphorylation of ERK was reduced by the treatment with alpha-chaconine. Moreover, alpha-chaconine-induced caspase-3 activity was further increased by the pretreatment with PD98059. Thus, the results indicate that alpha-chaconine induces apoptosis of HT-29 cells through inhibition of ERK and, in turn, activation of caspase-3.

  14. Development of a liquid chromatography-tandem mass spectrometric method for the simultaneous determination of tropane alkaloids and glycoalkaloids in crops.

    PubMed

    Jandrić, Z; Rathor, M N; Švarc-Gajić, J; Maestroni, B M; Sasanya, J J; Djurica, R; Cannavan, A

    2011-09-01

    A new, rapid and sensitive multiresidue method is reported for the simultaneous determination of tropane alkaloids (tropine, atropine, scopolamine, homatropine, anisodamine) and glycoalkaloids (α-solanine, α-chaconine) in grains and seeds (wheat, rye, maize, soybean, linseed). Dispersive solid phase extraction (DSPE) was performed with 0.5% formic acid in acetonitrile/water and a mixture of magnesium sulphate, sodium chloride and sodium citrate. For a fast and effective clean-up procedure for oily matrices such as soybean and linseed, matrix solid phase dispersion (MSPD) C(18) material was used to remove co-extracted non-polar components. No clean-up was necessary for less oily matrices following extraction. The analytes were separated by isocratic HPLC on a Chirobiotic V column and detected using a triple quadrupole mass spectrometer with electrospray ionization (ESI). All analytes were monitored in the positive ion mode. The method performance is presented in terms of linearity in the range 5-80 ng/g (r(2)=0.998), specifity, selectivity, accuracy (recoveries from 61-111%), precision (CV<5%) and ruggedness. The limits of quantitation (LOQ) were in the range 2.2-4.9 ng/g. © 2011 Taylor & Francis

  15. Application of single-stage Orbitrap mass spectrometry and differential analysis software to nontargeted analysis of contaminants in dog food: detection, identification, and quantification of glycoalkaloids.

    PubMed

    Lohne, Jack J; Turnipseed, Sherri B; Andersen, Wendy C; Storey, Joseph; Madson, Mark R

    2015-05-20

    The objective of this study was to perform a preliminary investigation of the nontargeted search and quantitative capabilities of a single-stage Exactive High-Resolution Mass Spectrometer (HRMS). To do this, the instrument and its associated software performed a non-targeted search for deleterious substances in a dog food sample suspected of causing gastrointestinal problems in dogs. A single-stage Orbitrap/high-performance liquid chromatography method and differential expression analysis software (Sieve) was used to detect and identify, and subsequently quantify, nontargeted compounds occurring only in the suspect dog food sample. When combined with an online database (ChemSpider), a preliminary identification of one of the nontargeted compounds was determined to be potato glycoalkaloids. The diagnostic product ion ratios and quantitative data accuracy generated by the single-stage Orbitrap MS were shown to be similar to results obtained using a triple quadrupole LC-MS/MS. Additionally, the ability of the single-stage Orbitrap instrument to provide precursor and product ion accurate masses and isotope patterns was also investigated.

  16. Assessing Freshwater Ecosystem Service Risk over Ecological, Socioeconomic, and Cultural Gradients: Problem Space Characterization and Methodology

    NASA Astrophysics Data System (ADS)

    Harmon, T. C.; Villamizar, S. R.; Conde, D.; Rusak, J.; Reid, B.; Astorga, A.; Perillo, G. M.; Piccolo, M. C.; Zilio, M.; London, S.; Velez, M.; Hoyos, N.; Escobar, J.

    2014-12-01

    Freshwater ecosystems and the services they provide are under increasing anthropogenic pressure at local (e.g., irrigation diversions, wastewater discharge) and global scales (e.g., climate change, global trading). The impact depends on an ecosystem's sensitivity, which is determined by its geophysical and ecological settings, and the population and activities in its surrounding watershed. Given the importance of ecosystem services, it is critical that we improve our ability to identify and understand changes in aquatic ecosystems, and translate them to risk of service loss. Furthermore, to inspire changes in human behavior, it is equally critical that we learn to communicate risk, and pose risk mitigation strategies, in a manner acceptable to a broad spectrum of stakeholders. Quantifying the nature and timing of the risk is difficult because (1) we often fail to understand the connection between anthropogenic pressures and the timing and extent of ecosystem changes; and (2) the concept of risk is inherently coupled to human perception, which generally differs with cultural and socio-economic conditions. In this study, we endeavor to assess aquatic ecosystem risks across an international array of six study sites. The challenge is to construct a methodology capable of capturing the marked biogeographical, socioeconomic, and cultural differences among the sites, which include: (1) Muskoka River watershed in humid continental Ontario, Canada; (2) Lower San Joaquin River, an impounded snow-fed river in semi-arid Central California; (3) Ciénaga Grande de Santa Marta, a tropical coastal lagoon in Colombia; (4) Senguer River basin in the semi-arid part of Argentina; (5) Laguna de Rocha watershed in humid subtropical Uruguay; and (6) Palomas Lake complex in oceanic Chilean Patagonia. Results will include a characterization of the experimental gradient over the six sites, an overview of the risk assessment methodology, and preliminary findings for several of the sites.

  17. Characterization and solubility measurements of uranium-contaminated soils to support risk assessment

    SciTech Connect

    Elless, M.P.; Armstrong, A.Q.; Lee, S.Y.

    1997-05-01

    Remediation of uranium-contaminated soils is considered a high priority by the US Department of Energy because these soils, if left untreated, represent a hazard to the environment and human health. Because the risk to human health is a function of the solubility of uranium in the soils, the objectives of this work are to measure the uranium solubility of two contaminated soils, before and after remedial treatment, and determine the health risk associated with these soils. Two carbonate-rich, uranium-contaminated soils from the US Department of Energy Fernald Environmental Management Project facility near Cincinnati, Ohio, as well as two nearby background soils were characterized and their uranium solubility measured in a 75-d solubility experiment using acid rain, groundwater, lung serum, and stomach acid simulants. Results show that the soluble uranium levels of each soil by each simulant are greatly influenced by their contamination source term. Risk calculations and biokinetic modeling based on the solubility data show that the risks from the soil ingestion and groundwater ingestion pathways are the predominant contributors to the total carcinogenic risk, whereas the risk from the soil inhalation pathway is the smallest contributor to this risk. However, kidney toxicity was the greater health concern of the Fernald Environmental Management Project soils, primarily from undiluted ingestion of the groundwater solution following contact with the contaminated soils. Sensitivity analyses indicate that uranium solubility is a key parameter in defining kidney toxicity; therefore, without proper consideration of the solubility of radionuclides/metals in untreated and treated soils, important factors may be overlooked which may result in soil cleanup goals or limits which are not protective of human health and the environment.

  18. CHARACTERIZATION OF ORGANIC EMISSIONS FROM HAZARDOUS WASTE INCINERATION PROCESSES UNDER THE NEW EPA DRAFT RISK BURN GUIDANCE: MEASUREMENT ISSUES

    EPA Science Inventory

    The paper discusses measurement issues relating to the characterization of organic emissions from hazardous waste incineration processes under EPA's new risk burn guidance. The recently published draft quidance recommends that hazardous waste combustion facilities complete a mass...

  19. CHARACTERIZATION OF ORGANIC EMISSIONS FROM HAZARDOUS WASTE INCINERATION PROCESSES UNDER THE NEW EPA DRAFT RISK BURN GUIDANCE: MEASUREMENT ISSUES

    EPA Science Inventory

    The paper discusses measurement issues relating to the characterization of organic emissions from hazardous waste incineration processes under EPA's new risk burn guidance. The recently published draft quidance recommends that hazardous waste combustion facilities complete a mass...

  20. Yucca Mountain transportation routes: Preliminary characterization and risk analysis; Volume 1, Research report

    SciTech Connect

    Souleyrette, R.R. II; Sathisan, S.K.; di Bartolo, R.

    1991-05-31

    In this study, rail and highway routes which may be used for shipments of high-level nuclear waste to a proposed repository at Yucca Mountain, Nevada are characterized. This characterization facilitates three types of impact analysis: comparative study, limited worst-case assessment, and more sophisticated probabilistic risk assessment techniques. Data for relative and absolute impact measures are provided to support comparisons of routes based on selected characteristics. A worst-case scenario assessment is included to determine potentially critical and most likely places for accidents or incidents to occur. The assessment facilitated by the data in this study is limited because impact measures are restricted to the identification of potential areas or persons affected. No attempt is made to quantify the magnitude of these impacts. Most likely locations for accidents to occur are determined relative to other locations within the scope of this study. Independent factors and historical trends used to identify these likely locations are only proxies for accident probability.

  1. Characterization of risk factors for DNA damage among paddy farm worker exposed to mixtures of organophosphates.

    PubMed

    How, Vivien; Hashim, Zailina; Ismail, Patimah; Omar, Dzolkhifli; Said, Salmiah Md; Tamrin, Shamsul Bahri Mohd

    2015-01-01

    This is a cross-sectional study conducted among paddy farmers to characterize potential risk factors that influence levels of DNA damage from exposure to mixtures of organophosphates. Comet assay was used to determine the level of DNA damage by measuring the comet tail length from the exfoliated buccal mucosa. The result suggests that farmers who chronically exposure to a mixture of organophosphates has at least 2-fold significant increase of DNA damage as compared with control group. Factor analysis and linear regression both suggest that DNA damage reported by farmers may influence individual, occupational, and residential factors and are reported as significant predictor factors, whereas this effect is mainly caused by individual factors among the control group. The findings of the present study suggest that either farmer or control group bear certain extent of genotoxic burden contributed by different risk factors.

  2. Characterization of ecological risks at the Milltown Reservoir-Clark Fork River Sediments Superfund Site, Montana

    USGS Publications Warehouse

    Pascoe, Gary A.; Blanchet, Richard J.; Linder, Greg L.; Palawski, Don; Brumbaugh, William G.; Canfield, Tim J.; Kemble, Nile E.; Ingersoll, Chris G.; Farag, Aïda M.; DalSoglio, Julie A.

    1994-01-01

    A comprehensive field and laboratory approach to the ecological risk assessment for the Milltown Reservoir-Clark Fork River Sediments Site, a Superfund site in the Rocky Mountains of Montana, has been described in the preceding reports of this series. The risk assessment addresses concerns over the ecological impacts of upstream releases of mining wastes to fisheries of the upper Clark Fork River (CFR) and the benthic and terrestrial habitats further downstream in Milltown Reservoir. The risk characterization component of the process integrated results from a triad of information sources: (a) chemistry studies of environmental media to identify and quantify exposures of terrestrial and aquatic organisms to site-related contaminants; (b) ecological or population studies of terrestrial vegetation, birds, benthic communities, and fish; and (c) in situ and laboratory toxicity studies with terrestrial and aquatic invertebrates and plants, small mammals, amphibians, and fish exposed to contaminated surface water, sediments, wetland soils, and food sources. Trophic transfer studies were performed on waterfowl, mammals, and predatory birds using field measurement data on metals concentrations in environmental media and lower trophic food sources. Studies with sediment exposures were incorporated into the Sediment Quality Triad approach to evaluate risks to benthic ecology. Overall results of the wetland and terrestrial studies suggested that acute adverse biological effects were largely absent from the wetland; however, adverse effects to reproductive, growth, and physiological end points of various terrestrial and aquatic species were related to metals exposures in more highly contaminated depositional areas. Feeding studies with contaminated diet collected from the upper CFR indicated that trout are at high risk from elevated metals concentrations in surface water, sediment, and aquatic invertebrates. Integration of chemical analyses with toxicological and ecological

  3. Integrated exposure and risk characterization of bisphenol-A in Europe.

    PubMed

    Sarigiannis, Dimosthenis A; Karakitsios, Spyros P; Handakas, Evangelos; Simou, Konstantina; Solomou, Ermioni; Gotti, Alberto

    2016-12-01

    The current study aims at a comprehensive risk characterization of bisphenol A (BPA) supported by an integrated exposure modelling framework that comprises far field and near field exposure modelling coupled to a dynamic lifetime PBTK model. Exposure analysis was done on European data of BPA food residues and human biomonitoring (HBM). The latter were further assimilated through an advanced exposure reconstruction modelling framework to estimate the corresponding external and internal systemic dose of BPA and its metabolites. Special attention was paid on the assessment of exposure to BPA during critical developmental stages such as gestation by modelling the mother-fetus toxicokinetic interaction. Our findings showed that current exposure levels in Europe are below the temporary Tolerable Daily Intake (t-TDI) of 4 μg/kg_bw/d proposed by the European Food Safety Authority. Taking into account age-dependent bioavailability differences, internal exposure of premature neonates hosted in intensive care units was reckoned close to the biologically effective dose (BED) resulting from translating the EFSA temporary total daily intake (t-TDI) into equivalent internal dose. Use of the ToxCast21 Biological Pathway Altering Dose (BPAD) as an alternative internal exposure reference value, resulted in increased margins of safety compared to the conventional exposure/risk characterization scheme.

  4. Characterizing exposure to physical risk factors among reforestation hand planters in the Southeastern United States.

    PubMed

    Granzow, Robert F; Schall, Mark C; Smidt, Mathew F; Chen, Howard; Fethke, Nathan B; Huangfu, Rong

    2018-01-01

    Low back and neck/shoulder pain are commonly reported among reforestation hand planters. While some studies have documented the intensive cardiovascular demands of hand planting, limited information is available regarding exposures to physical risk factors associated with the development of musculoskeletal disorders (MSDs) among hand planters. This study used surface electromyography (EMG) and inertial measurement units (IMUs) to characterize the muscle activation patterns, upper arm and trunk postures, movement velocities, and physical activity (PA) of fourteen Southeastern reforestation hand planters over one work shift. Results indicated that hand planters are exposed to physical risk factors such as extreme trunk postures (32.5% of time spent in ≥45° trunk flexion) and high effort muscle exertions (e.g., mean root-mean-square right upper trapezius amplitude of 54.1% reference voluntary exertion) that may place them at increased risk for developing MSDs. The findings indicate a need for continued field-based research among hand planters to identify and/or develop maximally effective interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Characterization of heavy-metal-contaminated sediment by using unsupervised multivariate techniques and health risk assessment.

    PubMed

    Wang, Yeuh-Bin; Liu, Chen-Wuing; Wang, Sheng-Wei

    2015-03-01

    This study characterized the sediment quality of the severely contaminated Erjen River in Taiwan by using multivariate analysis methods-including factor analysis (FA), self-organizing maps (SOMs), and positive matrix factorization (PMF)-and health risk assessment. The SOMs classified the dataset with similar heavy-metal-contaminated sediment into five groups. FA extracted three major factors-traditional electroplating and metal-surface processing factor, nontraditional heavy-metal-industry factor, and natural geological factor-which accounted for 80.8% of the variance. The SOMs and FA revealed the heavy-metal-contaminated-sediment hotspots in the middle and upper reaches of the major tributary in the dry season. The hazardous index value for health risk via ingestion was 0.302. PMF further qualified the source apportionment, indicating that traditional electroplating and metal-surface-processing industries comprised 47% of the health risk posed by heavy-metal-contaminated sediment. Contaminants discharged from traditional electroplating and metal-surface-processing industries in the middle and upper reaches of the major tributary must be eliminated first to improve the sediment quality in Erjen River. The proposed assessment framework for heavy-metal-contaminated sediment can be applied to contaminated-sediment river sites in other regions.

  6. Stochastic modeling of solute transport in aquifers: From heterogeneity characterization to risk analysis

    NASA Astrophysics Data System (ADS)

    Fiori, A.; Bellin, A.; Cvetkovic, V.; de Barros, F. P. J.; Dagan, G.

    2015-08-01

    The article presents a few recent developments advanced by the authors in a few key areas of stochastic modeling of solute transport in heterogeneous aquifers. First, a brief review of the Lagrangian approach to modeling plumes longitudinal mass distribution and temporal (the breakthrough curve) mass arrival, is presented. Subsequently, transport in highly heterogeneous aquifers is analyzed by using a recently developed predictive model. It relates the non-Gaussian BTC to the permeability univariate pdf and integral scale, with application to the MADE field observations. Next, the approach is extended to transport of reactive solute, combinnig the effects of the random velocity field and multirate mass transfer on the BTC, with application to mass attenuation. The following topic is modeling of the local concentration field as affected by mixing and dilution due to pore scale dispersion. The results are applied to the analysis of concentration measurements at the Cape Cod field experiment. The last section incorporates the results of the preceding ones in health risk assessment by analyzing the impact of concentration prediction on risk uncertainty. It is illustrated by assessing the effect of identification of macrodispersivity from field characterization and transport modeling, upon the probability of health risk.

  7. Induction of potato steroidal glycoalkaloid biosynthetic pathway by overexpression of cDNA encoding primary metabolism HMG-CoA reductase and squalene synthase.

    PubMed

    Ginzberg, Idit; Thippeswamy, Muddarangappa; Fogelman, Edna; Demirel, Ufuk; Mweetwa, Alice M; Tokuhisa, James; Veilleux, Richard E

    2012-06-01

    Potato steroidal glycoalkaloids (SGAs) are toxic secondary metabolites whose total content in tubers must be regulated. SGAs are biosynthesized by the sterol branch of the mevalonic acid/isoprenoid pathway. In a previous study, we showed a correlation between SGA levels and the abundance of transcript coding for HMG-CoA reductase 1 (HMG1) and squalene synthase 1 (SQS1) in potato tissues and potato genotypes varying in SGA content. Here, Solanum tuberosum cv. Desirée (low SGA producer) was transformed with a gene construct containing the coding region of either HMG1 or SQS1 of Solanum chacoense Bitt. clone 8380-1, a high SGA producer. SGA levels in transgenic HMG-plants were either greater than (in eight of 14 plants) or no different from untransformed controls, whereas only four of 12 SQS-transgenics had greater SGA levels than control, as determined by HPLC. Quantitative real-time PCR was used to estimate relative steady-state transcript levels of isoprenoid-, steroid-, and SGA-related genes in leaves of the transgenic plants compared to nontransgenic controls. HMG-transgenic plants exhibited increased transcript accumulation of SQS1, sterol C24-methyltransferase type1 (SMT1), and solanidine glycosyltransferase 2 (SGT2), whereas SQS-transgenic plants, had consistently lower transcript levels of HMG1 and variable SMT1 and SGT2 transcript abundance among different transgenics. HMG-transgenic plants exhibited changes in transcript accumulation for some sterol biosynthetic genes as well. Taken together, the data suggest coordinated regulation of isoprenoid metabolism and SGA secondary metabolism.

  8. Biomonitoring as a tool in the human health risk characterization of dermal exposure.

    PubMed

    Boogaard, P J

    2008-04-01

    Dermal exposure is an important factor in risk characterization. In occupational settings it becomes relatively more important because of the continuous reduction in inhalation exposure. In the public health arena, dermal exposure may also form a significant contribution to the total exposure. Dermal exposure, however, is difficult to assess directly because it is determined by a host of factors, which are difficult to quantify. As a consequence, dermal exposure is often estimated by application of models for external exposure. In combination with modeled or measured data for percutaneous penetration, these provide an estimate for the internal exposure that is directly related to the systemic effects. The advantages and drawbacks of EASE (Estimation and Assessment of Substance Exposure) and RISKOFDERM (Risk Assessment of Occupational Dermal Exposure), two models for external exposure that are mentioned in the Technical Guidance Document for the European Union risk assessments performed under the Existing Substances Regulation (EEC/793/93), are discussed. Although new chemicals regulation (REACh, 1907/2006/EC) is now in place in the European Union, the principles applied under the previous legislation do not change and the same models will continue to be used. The results obtained with these models for styrene, 2-butoxyethanol, and 1-methoxy-2-propanol in specific exposure scenarios are compared with an alternative method that uses biomonitoring data to assess dermal exposure. Actual external exposure measurements combined with measured or modeled percutaneous penetration data give acceptable results in risk assessment of dermal exposure, but modeled data of external dermal exposure should only be used if no other data are available. However, if available, biomonitoring should be considered the method of choice to assess (dermal) exposure.

  9. Characterization and risk estimate of cancer in patients with primary Sjögren syndrome.

    PubMed

    Brito-Zerón, Pilar; Kostov, Belchin; Fraile, Guadalupe; Caravia-Durán, Daniel; Maure, Brenda; Rascón, Francisco-Javier; Zamora, Mónica; Casanovas, Arnau; Lopez-Dupla, Miguel; Ripoll, Mar; Pinilla, Blanca; Fonseca, Eva; Akasbi, Miriam; de la Red, Gloria; Duarte-Millán, Miguel-Angel; Fanlo, Patricia; Guisado-Vasco, Pablo; Pérez-Alvarez, Roberto; Chamorro, Antonio J; Morcillo, César; Jiménez-Heredia, Iratxe; Sánchez-Berná, Isabel; López-Guillermo, Armando; Ramos-Casals, Manuel

    2017-04-17

    The purpose of this study is to characterize the risk of cancer in a large cohort of patients with primary Sjögren syndrome (SjS). We had analyzed the development of cancer in 1300 consecutive patients fulfilling the 2002 SjS classification criteria. The baseline clinical and immunological characteristics and systemic activity (ESSDAI scores) were assessed at diagnosis as predictors of cancer using Cox proportional hazards regression analysis adjusted for age at diagnosis and gender. The sex-and age-specific standardized incidence ratios (SIR) of cancer were estimated from 2012 Spanish mortality data. After a mean follow-up of 91 months, 127 (9.8%) patients developed 133 cancers. The most frequent type of cancer was B-cell lymphoma (including 27 MALT and 19 non-MALT B-cell lymphomas). Systemic activity at diagnosis of primary SjS correlated with the risk of hematological neoplasia and cryoglobulins with a high risk of either B-cell or non-B-cell lymphoma subtypes. Patients with cytopenias had a high risk of non-MALT B-cell and non-B-cell cancer, while those with low C3 levels had a high risk of MALT lymphomas and those with monoclonal gammopathy and low C4 levels had a high risk of non-MALT lymphomas. The estimated SIR for solid cancer was 1.13 and 11.02 for hematological cancer. SIRs for specific cancers were 36.17 for multiple myeloma and immunoproliferative diseases, 19.41 for Hodgkin lymphoma, 6.04 for other non-Hodgkin lymphomas, 5.17 for thyroid cancer, 4.81 for cancers of the lip and oral cavity, and 2.53 for stomach cancer. One third of cancers developed by patients with primary SjS are B-cell lymphomas. The prognostic factors identified at SjS diagnosis differed according to the subtype of B-cell lymphoma developed. Primary SjS is also associated with the development of some non-hematological cancers (thyroid, oral cavity, and stomach).

  10. Characterizing the Epidemiological Transition in Mexico: National and Subnational Burden of Diseases, Injuries, and Risk Factors

    PubMed Central

    Stevens, Gretchen; Dias, Rodrigo H; Thomas, Kevin J. A; Rivera, Juan A; Carvalho, Natalie; Barquera, Simón; Hill, Kenneth; Ezzati, Majid

    2008-01-01

    Background Rates of diseases and injuries and the effects of their risk factors can have substantial subnational heterogeneity, especially in middle-income countries like Mexico. Subnational analysis of the burden of diseases, injuries, and risk factors can improve characterization of the epidemiological transition and identify policy priorities. Methods and Findings We estimated deaths and loss of healthy life years (measured in disability-adjusted life years [DALYs]) in 2004 from a comprehensive list of diseases and injuries, and 16 major risk factors, by sex and age for Mexico and its states. Data sources included the vital statistics, national censuses, health examination surveys, and published epidemiological studies. Mortality statistics were adjusted for underreporting, misreporting of age at death, and for misclassification and incomparability of cause-of-death assignment. Nationally, noncommunicable diseases caused 75% of total deaths and 68% of total DALYs, with another 14% of deaths and 18% of DALYs caused by undernutrition and communicable, maternal, and perinatal diseases. The leading causes of death were ischemic heart disease, diabetes mellitus, cerebrovascular disease, liver cirrhosis, and road traffic injuries. High body mass index, high blood glucose, and alcohol use were the leading risk factors for disease burden, causing 5.1%, 5.0%, and 7.3% of total burden of disease, respectively. Mexico City had the lowest mortality rates (4.2 per 1,000) and the Southern region the highest (5.0 per 1,000); under-five mortality in the Southern region was nearly twice that of Mexico City. In the Southern region undernutrition and communicable, maternal, and perinatal diseases caused 23% of DALYs; in Chiapas, they caused 29% of DALYs. At the same time, the absolute rates of noncommunicable disease and injury burdens were highest in the Southern region (105 DALYs per 1,000 population versus 97 nationally for noncommunicable diseases; 22 versus 19 for injuries

  11. Quantifying Safety Margin Using the Risk-Informed Safety Margin Characterization (RISMC)

    SciTech Connect

    Grabaskas, David; Bucknor, Matthew; Brunett, Acacia; Nakayama, Marvin

    2015-04-26

    The Risk-Informed Safety Margin Characterization (RISMC), developed by Idaho National Laboratory as part of the Light-Water Reactor Sustainability Project, utilizes a probabilistic safety margin comparison between a load and capacity distribution, rather than a deterministic comparison between two values, as is usually done in best-estimate plus uncertainty analyses. The goal is to determine the failure probability, or in other words, the probability of the system load equaling or exceeding the system capacity. While this method has been used in pilot studies, there has been little work conducted investigating the statistical significance of the resulting failure probability. In particular, it is difficult to determine how many simulations are necessary to properly characterize the failure probability. This work uses classical (frequentist) statistics and confidence intervals to examine the impact in statistical accuracy when the number of simulations is varied. Two methods are proposed to establish confidence intervals related to the failure probability established using a RISMC analysis. The confidence interval provides information about the statistical accuracy of the method utilized to explore the uncertainty space, and offers a quantitative method to gauge the increase in statistical accuracy due to performing additional simulations.

  12. Molecular Characterization and Risk Factors of Giardia duodenalis among School Children from La Habana, Cuba

    PubMed Central

    Jerez Puebla, Luis Enrique; Núñez, Fidel A.; Martínez Silva, Isabel; Rojas Rivero, Lázara; Martínez González, Marta; Méndez Sutil, Yuliet; Ayllón Valdés, Lucía; Atencio Millán, Iraís; Müller, Norbert

    2015-01-01

    Giardia duodenalis is considered the most common protozoan infecting humans worldwide. Molecular characterization of G. duodenalis isolates has revealed the existence of eight groups (assemblages A to H) which differ in their host distribution. A cross-sectional study was conducted in 639 children from La Habana between January and December 2013. Two assemblage-specific PCRs were carried out for the molecular characterization. The overall prevalence of Giardia infection was 11.9%. DNA from 63 of 76 (82.9%) samples was successfully amplified by PCR-tpi, while 58 from 76 (76.3%) were detected by PCRE1-HF. Similar results by both PCRs were obtained in 54 from 76 samples (71%). According to these analyses, assemblage B and mixed assemblages A + B account for most of the Giardia infections in the cohort of children tested. Our current study identified assemblage B as predominant genotype in children infected with Giardia. Univariate analysis indicated that omission of washing hands before eating and keeping dogs at home were significant risk factors for a Giardia infection. In the future, novel molecular tools for a better discrimination of assemblages at the subassemblages level are needed to verify possible correlations between Giardia genotypes and symptomatology of giardiasis. PMID:26693345

  13. Characterizing Stressors and Modifiable Health Risk Factors Among Homeless Smokers: An Exploratory Pilot Study.

    PubMed

    Kendzor, Darla E; Reitzel, Lorraine R; Businelle, Michael S

    2015-10-01

    This pilot study was conducted to explore the associations between stressors related to homelessness and modifiable health risk factors (poor diet, insufficient physical activity, and overweight/obesity) and to provide direction for future research. Participants (N = 57) were homeless adults enrolled in a smoking cessation program. Analyses were conducted to characterize the sample as well as the relations between relevant stressors (discrimination, chronic stress, and fear and mistrust) and health risk factors. Inadequate daily consumption of fruits, vegetables, and fiber was common. High-fat diet and insufficient physical activity were also prevalent, and the majority of participants were overweight/obese. Participants commonly endorsed discrimination, fear of victimization, mistrust of others, and several other stressors. Greater endorsement of stressors was associated with a high-fat diet. Results suggest that lifestyle interventions and policy changes may be warranted in homeless shelters to attenuate the potential effects of stressors on high-fat dietary consumption among smokers. © 2015 Society for Public Health Education.

  14. Characterization of biological aerosol exposure risks from automobile air conditioning system.

    PubMed

    Li, Jing; Li, Mingzhen; Shen, Fangxia; Zou, Zhuanglei; Yao, Maosheng; Wu, Chang-yu

    2013-09-17

    Although use of automobile air conditioning (AC) was shown to reduce in-vehicle particle levels, the characterization of its microbial aerosol exposure risks is lacking. Here, both AC and engine filter dust samples were collected from 30 automobiles in four different geographical locations in China. Biological contents (bacteria, fungi, and endotoxin) were studied using culturing, high-throughput gene sequence, and Limulus amebocyte lysate (LAL) methods. In-vehicle viable bioaerosol concentrations were directly monitored using an ultraviolet aerodynamic particle sizer (UVAPS) before and after use of AC for 5, 10, and 15 min. Regardless of locations, the vehicle AC filter dusts were found to be laden with high levels of bacteria (up to 26,150 CFU/mg), fungi (up to 1287 CFU/mg), and endotoxin (up to 5527 EU/mg). More than 400 unique bacterial species, including human opportunistic pathogens, were detected in the filter dusts. In addition, allergenic fungal species were also found abundant. Surprisingly, unexpected fluorescent peaks around 2.5 μm were observed during the first 5 min use of AC, which was attributed to the reaerosolization of those filter-borne microbial agents. The information obtained here can assist in minimizing or preventing the respiratory allergy or infection risk from the use of automobile AC system.

  15. Characterization and Preoperative Risk Analysis of Leiomyosarcomas at a High-Volume Tertiary Care Center.

    PubMed

    Peters, Ann; Sadecky, Amanda M; Winger, Daniel G; Guido, Richard S; Lee, Ted T M; Mansuria, Suketu M; Donnellan, Nicole M

    2017-07-01

    Uterine morcellation in minimally invasive surgery has recently come under scrutiny because of inadvertent dissemination of malignant tissue, including leiomyosarcomas commonly mistaken for fibroids. Identification of preoperative risk factors is crucial to ensure that oncologic care is delivered when suspicion for malignancy is high, while offering minimally invasive hysterectomies to the remaining patients. The aim of this study was to characterize risk factors for uterine leiomyosarcomas by reviewing preoperative, intraoperative, and postoperative data with an emphasis on the presence of concurrent fibroids. A retrospective case-control study of women undergoing hysterectomy with pathologic diagnosis of uterine leiomyosarcoma at a tertiary care center between January 2005 and April 2014. Thirty-one women were identified with leiomyosarcoma and matched to 124 controls. Cases with leiomyosarcoma were more likely to have undergone menopause and to present with larger uteri (19- vs 9-week sized), with the most common presenting complaint being a pelvic mass (35.5% vs 8.9%). Controls were ten times more likely to have undergone a tubal ligation (30.6% vs 3.2%). Endometrial sampling detected malignancy preoperatively in only 50% of cases. Leiomyosarcomas were more commonly present when pelvic masses were identified in addition to fibroids on preoperative imaging. Most leiomyosarcoma cases (77.4%) were performed by oncologists via an abdominal approach (83.9%), with only 2 of 31 leiomyosarcomas being morcellated. Comparative analysis of preoperative imaging and postoperative pathology showed that in patients with leiomyosarcoma, fibroids were misdiagnosed 58.1% of the time, and leiomyosarcomas arose directly from fibroids in only 6.5% of cases. Leiomyosarcoma risk factors include older age/postmenopausal status, enlarged uteri of greater than 10 weeks, and lack of previous tubal ligation. Preoperative testing failed to definitively identify leiomyosarcomas, although

  16. Scientific reporting is suboptimal for aspects that characterize genetic risk prediction studies: a review of published articles based on the Genetic RIsk Prediction Studies statement.

    PubMed

    Iglesias, Adriana I; Mihaescu, Raluca; Ioannidis, John P A; Khoury, Muin J; Little, Julian; van Duijn, Cornelia M; Janssens, A Cecile J W

    2014-05-01

    Our main objective was to raise awareness of the areas that need improvements in the reporting of genetic risk prediction articles for future publications, based on the Genetic RIsk Prediction Studies (GRIPS) statement. We evaluated studies that developed or validated a prediction model based on multiple DNA variants, using empirical data, and were published in 2010. A data extraction form based on the 25 items of the GRIPS statement was created and piloted. Forty-two studies met our inclusion criteria. Overall, more than half of the evaluated items (34 of 62) were reported in at least 85% of included articles. Seventy-seven percentage of the articles were identified as genetic risk prediction studies through title assessment, but only 31% used the keywords recommended by GRIPS in the title or abstract. Seventy-four percentage mentioned which allele was the risk variant. Overall, only 10% of the articles reported all essential items needed to perform external validation of the risk model. Completeness of reporting in genetic risk prediction studies is adequate for general elements of study design but is suboptimal for several aspects that characterize genetic risk prediction studies such as description of the model construction. Improvements in the transparency of reporting of these aspects would facilitate the identification, replication, and application of genetic risk prediction models. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: characterization and risk factors

    PubMed Central

    2014-01-01

    Background Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa. The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined. To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients. Methods A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year. High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients. P. aeruginosa isolates were genotyped by PFGE. Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis. Results P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%). Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization. In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation. Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75). In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients. Conclusions The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics. Over 10% of these patients fulfilled criteria for

  18. Health risk characterization of maximum legal exposures for persistent organic pollutant (POP) pesticides in residential soil: An analysis.

    PubMed

    Li, Zijian

    2017-10-02

    Regulations for pesticides in soil are important for controlling human health risk; humans can be exposed to pesticides by ingesting soil, inhaling soil dust, and through dermal contact. Previous studies focused on analyses of numerical standard values for pesticides and evaluated the same pesticide using different standards among different jurisdictions. To understand the health consequences associated with pesticide soil standard values, lifetime theoretical maximum contribution and risk characterization factors were used in this study to quantify the severity of damage using disability-adjusted life years (DALYs) under the maximum "legal" exposure to persistent organic pollutant (POP) pesticides that are commonly regulated by the Stockholm Convention. Results show that computed soil characterization factors for some pesticides present lognormal distributions, and some of them have DALY values higher than 1000.0 per million population (e.g., the DALY for dichlorodiphenyltrichloroethane [DDT] is 14,065 in the Netherlands, which exceeds the tolerable risk of uncertainty upper bound of 1380.0 DALYs). Health risk characterization factors computed from national jurisdictions illustrate that values can vary over eight orders of magnitude. Further, the computed characterization factors can vary over four orders of magnitude within the same national jurisdiction. These data indicate that there is little agreement regarding pesticide soil regulatory guidance values (RGVs) among worldwide national jurisdictions or even RGV standard values within the same jurisdiction. Among these POP pesticides, lindane has the lowest median (0.16 DALYs) and geometric mean (0.28 DALYs) risk characterization factors, indicating that worldwide national jurisdictions provide relatively conservative soil RGVs for lindane. In addition, we found that some European nations and members of the former Union of Soviet Socialist Republics share the same pesticide RGVs and data clusters for the

  19. Characterization of the human kinetic adjustment factor for the health risk assessment of environmental contaminants.

    PubMed

    Valcke, Mathieu; Krishnan, Kannan

    2014-03-01

    A default uncertainty factor of 3.16 (√10) is applied to account for interindividual variability in toxicokinetics when performing non-cancer risk assessments. Using relevant human data for specific chemicals, as WHO/IPCS suggests, it is possible to evaluate, and replace when appropriate, this default factor by quantifying chemical-specific adjustment factors for interindividual variability in toxicokinetics (also referred to as the human kinetic adjustment factor, HKAF). The HKAF has been determined based on the distributions of pharmacokinetic parameters (e.g., half-life, area under the curve, maximum blood concentration) in relevant populations. This article focuses on the current state of knowledge of the use of physiologically based algorithms and models in characterizing the HKAF for environmental contaminants. The recent modeling efforts on the computation of HKAF as a function of the characteristics of the population, chemical and its mode of action (dose metrics), as well as exposure scenario of relevance to the assessment are reviewed here. The results of these studies, taken together, suggest the HKAF varies as a function of the sensitive subpopulation and dose metrics of interest, exposure conditions considered (route, duration, and intensity), metabolic pathways involved and theoretical model underlying its computation. The HKAF seldom exceeded the default value of 3.16, except in very young children (i.e., <≈ 3 months) and when the parent compound is the toxic moiety. Overall, from a public health perspective, the current state of knowledge generally suggest that the default uncertainty factor is sufficient to account for human variability in non-cancer risk assessments of environmental contaminants. Copyright © 2013 John Wiley & Sons, Ltd.

  20. Characterizing trabecular bone structure for assessing vertebral fracture risk on volumetric quantitative computed tomography

    NASA Astrophysics Data System (ADS)

    Nagarajan, Mahesh B.; Checefsky, Walter A.; Abidin, Anas Z.; Tsai, Halley; Wang, Xixi; Hobbs, Susan K.; Bauer, Jan S.; Baum, Thomas; Wismüller, Axel

    2015-03-01

    While the proximal femur is preferred for measuring bone mineral density (BMD) in fracture risk estimation, the introduction of volumetric quantitative computed tomography has revealed stronger associations between BMD and spinal fracture status. In this study, we propose to capture properties of trabecular bone structure in spinal vertebrae with advanced second-order statistical features for purposes of fracture risk assessment. For this purpose, axial multi-detector CT (MDCT) images were acquired from 28 spinal vertebrae specimens using a whole-body 256-row CT scanner with a dedicated calibration phantom. A semi-automated method was used to annotate the trabecular compartment in the central vertebral slice with a circular region of interest (ROI) to exclude cortical bone; pixels within were converted to values indicative of BMD. Six second-order statistical features derived from gray-level co-occurrence matrices (GLCM) and the mean BMD within the ROI were then extracted and used in conjunction with a generalized radial basis functions (GRBF) neural network to predict the failure load of the specimens; true failure load was measured through biomechanical testing. Prediction performance was evaluated with a root-mean-square error (RMSE) metric. The best prediction performance was observed with GLCM feature `correlation' (RMSE = 1.02 ± 0.18), which significantly outperformed all other GLCM features (p < 0.01). GLCM feature correlation also significantly outperformed MDCTmeasured mean BMD (RMSE = 1.11 ± 0.17) (p< 10-4). These results suggest that biomechanical strength prediction in spinal vertebrae can be significantly improved through characterization of trabecular bone structure with GLCM-derived texture features.

  1. Characterization of backyard poultry production systems and disease risk in the central zone of Chile.

    PubMed

    Hamilton-West, C; Rojas, H; Pinto, J; Orozco, J; Hervé-Claude, L P; Urcelay, S

    2012-08-01

    Backyard poultry production systems (BPS) are an important and widespread form of poultry production. There is a common perception that biosecurity standards in BPS are generally poor and BPS are usually associated with animal diseases and zoonoses. In this study BPS were identified in the vicinity of six wetlands, having these a higher risk of presenting and introducing avian diseases such as HPAI and Newcastle disease, as defined by the national veterinary services, in to Chile's main poultry production area. BPS were characterized through a field questionnaire and the main areas covered by the survey were BPS structure, biosecurity and value chain. The BPS identified in this study share most characteristics on biosecurity, poultry management and product commercialization, but it was possible to identify a certain degree of variation within and among the study sites. BPS in Chile are similar to those in other regions, with a relatively small flock size (average 37 birds), a low level of biosecurity measures and lack of poultry disease management. Management findings include that most farmers used mixed/partial confinement, with low or no biosecurity and disease control measures in place. Eggs were the main output and were used mainly for home consumption or sale at local markets. Sick birds' treatment with drugs approved for other species or for human use could represent a risk to human health, owing to the possible presence of drug residues in poultry products. Despite the different structures of the poultry sector worldwide, BPS can play a major role in disease maintenance and spread because its management conditions characteristics and the lack of animal health services adapted to these production systems. This should be an alert message to the veterinary authorities to improve coverage of veterinary assistance and surveillance activities in backyard poultry production. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Characterization of germline copy number variation in high-risk African American families with prostate cancer.

    PubMed

    Ledet, Elisa M; Hu, Xiaofeng; Sartor, Oliver; Rayford, Walter; Li, Marilyn; Mandal, Diptasri

    2013-05-01

    Prostate cancer is a complex multi-allelic disease and the most common malignancy in men. The incidence of prostate cancer in African American men is more than twice as high as that of any other race. Despite the high prevalence of prostate cancer amongst African American men, this population has been under represented in genetic studies of prostate cancer. Although genomic copy number variations (CNVs) have been detected in prostate tumors, this is the first study describing germline CNVs in African American hereditary prostate cancer families. Ten high-risk African American families with three or more affected individuals and with an early age of onset were recruited. From these families, 37 individuals, including 23 affected males, and 14 unaffected males, were selected for CNV analysis. Array comparative genomic hybridization was used to characterize germline CNVs unique to African American men with hereditary prostate cancer. Through common aberration analysis in affected family members; novel CNVs were identified at chromosomes 1p36.13 and 16q23.3. Differential analysis comparing affected and unaffected family members identified 9.4 kb duplication on chromosome 14q32.33 which segregate with prostate cancer patients in these high-risk families. The duplication at 14q32.33 encompasses IGHG3 gene which has been shown to have both significant gains in copy number as well as overexpression in prostate tumors in African Americans. These CNVs may represent a component of genetic predisposition which contributes to the high prevalence and mortality of prostate cancer in African American men. Copyright © 2012 Wiley Periodicals, Inc.

  3. Brain network characterization of high-risk preterm-born school-age children

    PubMed Central

    Fischi-Gomez, Elda; Muñoz-Moreno, Emma; Vasung, Lana; Griffa, Alessandra; Borradori-Tolsa, Cristina; Monnier, Maryline; Lazeyras, François; Thiran, Jean-Philippe; Hüppi, Petra S.

    2016-01-01

    Higher risk for long-term cognitive and behavioral impairments is one of the hallmarks of extreme prematurity (EP) and pregnancy-associated fetal adverse conditions such as intrauterine growth restriction (IUGR). While neurodevelopmental delay and abnormal brain function occur in the absence of overt brain lesions, these conditions have been recently associated with changes in microstructural brain development. Recent imaging studies indicate changes in brain connectivity, in particular involving the white matter fibers belonging to the cortico-basal ganglia-thalamic loop. Furthermore, EP and IUGR have been related to altered brain network architecture in childhood, with reduced network global capacity, global efficiency and average nodal strength. In this study, we used a connectome analysis to characterize the structural brain networks of these children, with a special focus on their topological organization. On one hand, we confirm the reduced averaged network node degree and strength due to EP and IUGR. On the other, the decomposition of the brain networks in an optimal set of clusters remained substantially different among groups, talking in favor of a different network community structure. However, and despite the different community structure, the brain networks of these high-risk school-age children maintained the typical small-world, rich-club and modularity characteristics in all cases. Thus, our results suggest that brain reorganizes after EP and IUGR, prioritizing a tight modular structure, to maintain the small-world, rich-club and modularity characteristics. By themselves, both extreme prematurity and IUGR bear a similar risk for neurocognitive and behavioral impairment, and the here defined modular network alterations confirm similar structural changes both by IUGR and EP at school age compared to control. Interestingly, the combination of both conditions (IUGR + EP) does not result in a worse outcome. In such cases, the alteration in network

  4. Case Characterization, Clinical Features and Risk Factors in Drug-Induced Liver Injury

    PubMed Central

    Ortega-Alonso, Aida; Stephens, Camilla; Lucena, M. Isabel; Andrade, Raúl J.

    2016-01-01

    Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) presents with a range of both phenotypes and severity, from acute hepatitis indistinguishable of viral hepatitis to autoimmune syndromes, steatosis or rare chronic vascular syndromes, and from asymptomatic liver test abnormalities to acute liver failure. DILI pathogenesis is complex, depending on the interaction of drug physicochemical properties and host factors. The awareness of risk factors for DILI is arising from the analysis of large databases of DILI cases included in Registries and Consortia networks around the world. These networks are also enabling in-depth phenotyping with the identification of predictors for severe outcome, including acute liver failure and mortality/liver transplantation. Genome wide association studies taking advantage of these large cohorts have identified several alleles from the major histocompatibility complex system indicating a fundamental role of the adaptive immune system in DILI pathogenesis. Correct case definition and characterization is crucial for appropriate phenotyping, which in turn will strengthen sample collection for genotypic and future biomarkers studies. PMID:27187363

  5. Case Characterization, Clinical Features and Risk Factors in Drug-Induced Liver Injury.

    PubMed

    Ortega-Alonso, Aida; Stephens, Camilla; Lucena, M Isabel; Andrade, Raúl J

    2016-05-12

    Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) presents with a range of both phenotypes and severity, from acute hepatitis indistinguishable of viral hepatitis to autoimmune syndromes, steatosis or rare chronic vascular syndromes, and from asymptomatic liver test abnormalities to acute liver failure. DILI pathogenesis is complex, depending on the interaction of drug physicochemical properties and host factors. The awareness of risk factors for DILI is arising from the analysis of large databases of DILI cases included in Registries and Consortia networks around the world. These networks are also enabling in-depth phenotyping with the identification of predictors for severe outcome, including acute liver failure and mortality/liver transplantation. Genome wide association studies taking advantage of these large cohorts have identified several alleles from the major histocompatibility complex system indicating a fundamental role of the adaptive immune system in DILI pathogenesis. Correct case definition and characterization is crucial for appropriate phenotyping, which in turn will strengthen sample collection for genotypic and future biomarkers studies.

  6. Extreme Learning Machine Framework for Risk Stratification of Fatty Liver Disease Using Ultrasound Tissue Characterization.

    PubMed

    Kuppili, Venkatanareshbabu; Biswas, Mainak; Sreekumar, Aswini; Suri, Harman S; Saba, Luca; Edla, Damodar Reddy; Marinhoe, Rui Tato; Sanches, J Miguel; Suri, Jasjit S

    2017-08-23

    Fatty Liver Disease (FLD) is caused by the deposition of fat in liver cells and leads to deadly diseases such as liver cancer. Several FLD detection and characterization systems using machine learning (ML) based on Support Vector Machines (SVM) have been applied. These ML systems utilize large number of ultrasonic grayscale features, pooling strategy for selecting the best features and several combinations of training/testing. As result, they are computationally intensive, slow and do not guarantee high performance due to mismatch between grayscale features and classifier type. This study proposes a reliable and fast Extreme Learning Machine (ELM)-based tissue characterization system (a class of Symtosis) for risk stratification of ultrasound liver images. ELM is used to train single layer feed forward neural network (SLFFNN). The input-to-hidden layer weights are randomly generated reducing computational cost. The only weights to be trained are hidden-to-output layer which is done in a single pass (without any iteration) making ELM faster than conventional ML methods. Adapting four types of K-fold cross-validation (K = 2, 3, 5 and 10) protocols on three kinds of data sizes: S0-original, S4-four splits, S8-sixty four splits (a total of 12 cases) and 46 types of grayscale features, we stratify the FLD US images using ELM and benchmark against SVM. Using the US liver database of 63 patients (27 normal/36 abnormal), our results demonstrate superior performance of ELM compared to SVM, for all cross-validation protocols (K2, K3, K5 and K10) and all types of US data sets (S0, S4, and S8) in terms of sensitivity, specificity, accuracy and area under the curve (AUC). Using the K10 cross-validation protocol on S8 data set, ELM showed an accuracy of 96.75% compared to 89.01% for SVM, and correspondingly, the AUC: 0.97 and 0.91, respectively. Further experiments also showed the mean reliability of 99% for ELM classifier, along with the mean speed improvement of 40% using

  7. Integrating Safety Assessment Methods using the Risk Informed Safety Margins Characterization (RISMC) Approach

    SciTech Connect

    Curtis Smith; Diego Mandelli

    2013-03-01

    Safety is central to the design, licensing, operation, and economics of nuclear power plants (NPPs). As the current light water reactor (LWR) NPPs age beyond 60 years, there are possibilities for increased frequency of systems, structures, and components (SSC) degradations or failures that initiate safety significant events, reduce existing accident mitigation capabilities, or create new failure modes. Plant designers commonly “over-design” portions of NPPs and provide robustness in the form of redundant and diverse engineered safety features to ensure that, even in the case of well-beyond design basis scenarios, public health and safety will be protected with a very high degree of assurance. This form of defense-in-depth is a reasoned response to uncertainties and is often referred to generically as “safety margin.” Historically, specific safety margin provisions have been formulated primarily based on engineering judgment backed by a set of conservative engineering calculations. The ability to better characterize and quantify safety margin is important to improved decision making about LWR design, operation, and plant life extension. A systematic approach to characterization of safety margins and the subsequent margin management options represents a vital input to the licensee and regulatory analysis and decision making that will be involved. In addition, as research and development (R&D) in the LWR Sustainability (LWRS) Program and other collaborative efforts yield new data, sensors, and improved scientific understanding of physical processes that govern the aging and degradation of plant SSCs needs and opportunities to better optimize plant safety and performance will become known. To support decision making related to economics, readability, and safety, the RISMC Pathway provides methods and tools that enable mitigation options known as margins management strategies. The purpose of the RISMC Pathway R&D is to support plant decisions for risk

  8. Integrating mechanistic and polymorphism data to characterize human genetic susceptibility for environmental chemical risk assessment in the 21st century

    SciTech Connect

    Mortensen, Holly M.; Euling, Susan Y.

    2013-09-15

    Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be applied to account for the lack of information about susceptibility. Defining genetic susceptibility in response to environmental chemicals across human populations is an area of interest in the NAS' new paradigm of toxicity pathway-based risk assessment. Data from high-throughput/high content (HT/HC), including -omics (e.g., genomics, transcriptomics, proteomics, metabolomics) technologies, have been integral to the identification and characterization of drug target and disease loci, and have been successfully utilized to inform the mechanism of action for numerous environmental chemicals. Large-scale population genotyping studies may help to characterize levels of variability across human populations at identified target loci implicated in response to environmental chemicals. By combining mechanistic data for a given environmental chemical with next generation sequencing data that provides human population variation information, one can begin to characterize differential susceptibility due to genetic variability to environmental chemicals within and across genetically heterogeneous human populations. The integration of such data sources will be informative to human health risk assessment.

  9. Modification of the health-promoting value of potato tubers field grown under drought stress: emphasis on dietary antioxidant and glycoalkaloid contents in five native andean cultivars (Solanum tuberosum L.).

    PubMed

    Andre, Christelle M; Schafleitner, Roland; Guignard, Cédric; Oufir, Mouhssin; Aliaga, Carlos Alberto Alvarado; Nomberto, Giannina; Hoffmann, Lucien; Hausman, Jean-François; Evers, Danièle; Larondelle, Yvan

    2009-01-28

    The effects of drought stress on dietary antioxidant and glycoalkaloid contents in potato tubers were investigated using a selection of five native Andean cultivars. Both freshly harvested and 4 month-stored tubers were analyzed. Responses to drought stress were highly cultivar-specific. The antioxidant contents of the yellow tuber-bearing cultivars (Sipancachi and SS-2613) were weakly affected by the drought treatment, whereas the pigmented cultivars demonstrated highly cultivar-dependent variations. A drastic reduction of anthocyanins and other polyphenols was revealed in the red- (Sullu) and purple-fleshed (Guincho Negra) cultivars, whereas an increase was shown in the purple-skinned and yellow-fleshed cultivar (Huata Colorada). The hydrophilic antioxidant capacity (evaluated by Folin-Ciocalteu and H-oxygen radical absorbance capacity assays) was highly correlated with the polyphenol content and followed, therefore, the same behavior upon drought. Carotenoid contents, including beta-carotene, as well as vitamin E, tended to increase or remain stable following drought exposure, except for the cultivar Sullu, in which the level of these lipophilic antioxidants was decreased. Vitamin C contents were not affected by drought with the exception of Guincho Negra, in which the level was increased. These variations of health-promoting compounds were associated with increased or stable levels of the toxic glycoalkaloids, alpha-solanine and alpha-chaconine. Storage at 10 degrees C for 4 months tended to decrease the concentrations of all dietary antioxidants, except those of vitamin E. This storage also reduced the drought-induced variations observed in freshly harvested tubers. These results were discussed in terms of their implications for human diet and health as well as in plant stress defense mechanisms.

  10. Preliminary characterization of risks in the nuclear waste management system based on information in the literature

    SciTech Connect

    Daling, P.M.; Rhoads, R.E.; Van Luick, A.E.; Fecht, B.A.; Nilson, S.A.; Sevigny, N.L.; Armstrong, G.R.; Hill, D.H.; Rowe, M.; Stern, E.

    1992-01-01

    This document presents preliminary information on the radiological and nonradiological risks in the nuclear waste management system. The objective of the study was to (1) review the literature containing information on risks in the nuclear waste management system and (2) use this information to develop preliminary estimates of the potential magnitude of these risks. Information was collected on a broad range of risk categories to assist the US Department of Energy (DOE) in communicating information about the risks in the waste management systems. The study examined all of the portions of the nuclear waste management system currently expected to be developed by the DOE. The scope of this document includes the potential repository, the integral MRS facility, and the transportation system that supports the potential repository and the MRS facility. Relevant literature was reviewed for several potential repository sites and geologic media. A wide range of ``risk categories`` are addressed in this report: (1) public and occupational risks from accidents that could release radiological materials, (2) public and occupational radiation exposure resulting from routine operations, (3) public and occupational risks from accidents involving hazards other than radioactive materials, and (4) public and occupational risks from exposure to nonradioactive hazardous materials during routine operations. The report is intended to provide a broad spectrum of risk-related information about the waste management system. This information is intended to be helpful for planning future studies.

  11. Methodology for characterizing high-risk orbital debris in the geosynchronous orbit regime

    NASA Astrophysics Data System (ADS)

    Anderson, Paul V.; Schaub, Hanspeter

    2016-01-01

    Forecasting of localized debris congestion in the geostationary (GEO) ring is performed to formulate and investigate methodology for identifying the debris objects that pose the highest risk to operational satellites in this ring. Proximity and speed relative to GEO during near-miss events detected under a torus intersection metric are translated into a combined risk factor that is accumulated during propagation. This accumulated risk is then used to identify the objects that have the highest risk contributions, either globally or in the vicinity of one of the two gravitational wells at 75°E and 105°W. Results show that nearly 60% of the total risk surrounding the Western well is attributed to 10 derelicts alone, which has critical implications for active debris removal (ADR) target selection for attenuating risk levels in this ring.

  12. [Integration of demographic factors in the characterization of risk areas for sleeping sickness in Côte d'Ivoire].

    PubMed

    Fournet, F; Kone, A; Meda, A H; Traore, S; Hervouet, J P

    2001-01-01

    The purpose of this study was to classify the risk for transmission of African human trypanosomiasis (sleeping sickness) according to population and settlement densities in four different areas of Zoukougbeu, Cote d'Ivoire, where the exact location of cases reported since 1990 is known. Epidemiological risk indexes were calculated from entomological data obtained from three surveys and analyzed with respect to presence of patients and occupancy rate in each area. Results indicated that there was a risk of transmission near the village of Bahigbeu II where the population density is between 30 and 40 inhabitants per km2 and settlement density is 4 per km2. There was also a risk in less inhabited areas such as Ouatigbeu where the population density is less than 30 inhabitants per km2 and dwelling density less than 4 per km2. In fact, cases are regularly reported in Ouatigbeu but never in Bahigbeu II. Based on these findings, we conclude that, while land occupancy can be considered as a risk factor for sleeping sickness, other factors such as human mobility must be taken into account to characterize risk areas and predict outbreaks.

  13. Depleted uranium risk assessment for Jefferson Proving Ground using data from environmental monitoring and site characterization. Final report

    SciTech Connect

    Ebinger, M.H.; Hansen, W.R.

    1996-10-01

    This report documents the third risk assessment completed for the depleted uranium (DU) munitions testing range at Jefferson Proving Ground (JPG), Indiana, for the U.S. Army Test and Evaluation command. Jefferson Proving Ground was closed in 1995 under the Base Realignment and Closure Act and the testing mission was moved to Yuma Proving Ground. As part of the closure of JPG, assessments of potential adverse health effects to humans and the ecosystem were conducted. This report integrates recent information obtained from site characterization surveys at JPG with environmental monitoring data collected from 1983 through 1994 during DU testing. Three exposure scenarios were evaluated for potential adverse effects to human health: an occasional use scenario and two farming scenarios. Human exposure was minimal from occasional use, but significant risk were predicted from the farming scenarios when contaminated groundwater was used by site occupants. The human health risk assessments do not consider the significant risk posed by accidents with unexploded ordnance. Exposures of white-tailed deer to DU were also estimated in this study, and exposure rates result in no significant increase in either toxicological or radiological risks. The results of this study indicate that remediation of the DU impact area would not substantially reduce already low risks to humans and the ecosystem, and that managed access to JPG is a reasonable model for future land use options.

  14. The Development of Dynamic Human Reliability Analysis Simulations for Inclusion in Risk Informed Safety Margin Characterization Frameworks

    SciTech Connect

    Jeffrey C. Joe; Diego Mandelli; Ronald L. Boring; Curtis L. Smith; Rachel B. Shirley

    2015-07-01

    The United States Department of Energy is sponsoring the Light Water Reactor Sustainability program, which has the overall objective of supporting the near-term and the extended operation of commercial nuclear power plants. One key research and development (R&D) area in this program is the Risk-Informed Safety Margin Characterization pathway, which combines probabilistic risk simulation with thermohydraulic simulation codes to define and manage safety margins. The R&D efforts to date, however, have not included robust simulations of human operators, and how the reliability of human performance or lack thereof (i.e., human errors) can affect risk-margins and plant performance. This paper describes current and planned research efforts to address the absence of robust human reliability simulations and thereby increase the fidelity of simulated accident scenarios.

  15. Risk-based ecological soil quality criteria for the characterization of contaminated soils. Combination of chemical and biological tools.

    PubMed

    Fernández, María Dolores; Vega, María Milagrosa; Tarazona, José Vicente

    2006-08-01

    This paper describes the development of soil quality criteria for the characterization of soils focused on the potential risk to the ecosystem. The approach combines both Generic Soil Quality standards (GSQs) for individual chemicals and direct ecotoxicity assays on soil samples taken from the site. Criteria establish three main risk levels with their corresponding trigger values. The trigger values to determine high risk or "polluted" soils are exclusively based on direct toxicity assessments. The trigger values for the other categories are established by a combination of the application of GSQs and the results of bioassays. Low-risk is assumed when no toxicity is observed and GSQs based on precautionary ecotoxicity thresholds are not exceeded; high-risk must be considered if acute toxicity above the proposed trigger value is observed in soil or leachate samples. In between these levels, the risk cannot be elucidated and a site-specific assessment is required. The GSQs take into account the current or future land use, thus defining three categories: industrial soils, urban/residential soils and natural/agricultural/forest soils, each of them with different ecological requirements. The GSQ values are established following an inverse risk assessment methodology, integrating ecotoxicity and exposure models and setting the soil levels associated to pre-established criteria for the assumption of low risk. The proposed methodology covers all relevant ecological receptors and processes, soil organisms, potential contamination of ground and surface waters, and exposure of terrestrial vertebrates due to bioaccumulation and biomagnification. Exposure routes and protection criteria are defined in each protection goal. The relevance of each receptor and route is established according to the land use.

  16. Characterization of the chronic risk and hazard of hazardous air pollutants in the United States using ambient monitoring data.

    PubMed

    McCarthy, Michael C; O'Brien, Theresa E; Charrier, Jessica G; Hafner, Hilary R

    2009-05-01

    Ambient measurements of hazardous air pollutants (air toxics) have been used to validate model-predicted concentrations of air toxics but have not been used to perform risk screening at the national level. We used ambient concentrations of routinely measured air toxics to determine the relative importance of individual air toxics for chronic cancer and noncancer exposures. We compiled 3-year averages for ambient measurement of air toxics collected at monitoring locations in the United States from 2003 through 2005. We then used national distributions of risk-weighted concentrations to identify the air toxics of most concern. Concentrations of benzene, carbon tetrachloride, arsenic, 1,3-butadiene, and acetaldehyde were above the 10(-6) cancer risk level at most sites nationally with a high degree of confidence. Concentrations of tetrachloroethylene, ethylene oxide, acrylonitrile, and 1,4-dichlorobenzene were also often greater than the 10(-6) cancer risk level, but we have less confidence in the estimated risk associated with these pollutants. Formaldehyde and chromium VI concentrations were either above or below the 10(-6) cancer risk level, depending on the choice of agency-recommended 10(-6) level. The method detection limits of eight additional pollutants were too high to rule out that concentrations were above the 10(-6) cancer risk level. Concentrations of 52 compounds compared with chronic noncancer benchmarks indicated that only acrolein concentrations were greater than the noncancer reference concentration at most monitoring sites. Most pollutants with national site-level averages greater than health benchmarks were also pollutants of concern identified in modeled national-scale risk assessments. Current monitoring networks need more sensitive ambient measurement techniques to better characterize the air toxics problem in the United States.

  17. Characterization of the Chronic Risk and Hazard of Hazardous Air Pollutants in the United States Using Ambient Monitoring Data

    PubMed Central

    McCarthy, Michael C.; O’Brien, Theresa E.; Charrier, Jessica G.; Hafner, Hilary R.

    2009-01-01

    Background Ambient measurements of hazardous air pollutants (air toxics) have been used to validate model-predicted concentrations of air toxics but have not been used to perform risk screening at the national level. Objectives We used ambient concentrations of routinely measured air toxics to determine the relative importance of individual air toxics for chronic cancer and noncancer exposures. Methods We compiled 3-year averages for ambient measurement of air toxics collected at monitoring locations in the United States from 2003 through 2005. We then used national distributions of risk-weighted concentrations to identify the air toxics of most concern. Results Concentrations of benzene, carbon tetrachloride, arsenic, 1,3-butadiene, and acetaldehyde were above the 10−6 cancer risk level at most sites nationally with a high degree of confidence. Concentrations of tetrachloroethylene, ethylene oxide, acrylonitrile, and 1,4-dichlorobenzene were also often greater than the 10−6 cancer risk level, but we have less confidence in the estimated risk associated with these pollutants. Formaldehyde and chromium VI concentrations were either above or below the 10−6 cancer risk level, depending on the choice of agency-recommended 10−6 level. The method detection limits of eight additional pollutants were too high to rule out that concentrations were above the 10−6 cancer risk level. Concentrations of 52 compounds compared with chronic noncancer benchmarks indicated that only acrolein concentrations were greater than the noncancer reference concentration at most monitoring sites. Conclusions Most pollutants with national site-level averages greater than health benchmarks were also pollutants of concern identified in modeled national-scale risk assessments. Current monitoring networks need more sensitive ambient measurement techniques to better characterize the air toxics problem in the United States. PMID:19479023

  18. Characterizing ecological risk for polycyclic aromatic hydrocarbons in water from Lake Taihu, China.

    PubMed

    Guo, Guanghui; Wu, Fengchang; He, Hongping; Zhang, Ruiqing; Feng, Chenglian; Li, Huixian; Chang, Ming

    2012-11-01

    Lake Taihu provides vital ecological services for humans in China; it receives a great deal of attention regarding its ecological and environmental conditions. In this study, the ecological risks of eight individual polycyclic aromatic hydrocarbons (PAHs) in water were assessed using probabilistic distributions of the hazard quotient based on Monte Carlo simulation. The results show that the 95th percentile of the hazard quotients ranged from 0.00074 to 2.831, and the ecological risk of Flua was highest, followed by, in descending order of risk, B[a]P > Pyr > Ant > Phe > Flu > Ace > Chr. The probabilities of hazard quotients exceeding a decision criteria of 0.3 were 18.09%, 6.51%, 3.76%, and 2.85% for Flua, B[a]P, Pyr, and Ant, respectively, indicating their potential ecological risks to aquatic organisms. The spatial distribution of hazard quotients for these four individual PAHs with potential ecological risk were obtained using Geographic Information System (GIS), and similar spatial distribution patterns were also observed in the lake. The highest ecological risks of these four individual PAHs to aquatic organisms were found in Meiliang Bay, followed by Gonghu Bay and Xukou Bay. The uncertainty within the ecological risk assessment was also discussed.

  19. The Effects of Revealed Information on Catastrophe Loss Projection Models' Characterization of Risk: Damage Vulnerability Evidence from Florida.

    PubMed

    Karl, J Bradley; Medders, Lorilee A; Maroney, Patrick F

    2016-06-01

    We examine whether the risk characterization estimated by catastrophic loss projection models is sensitive to the revelation of new information regarding risk type. We use commercial loss projection models from two widely employed modeling firms to estimate the expected hurricane losses of Florida Atlantic University's building stock, both including and excluding secondary information regarding hurricane mitigation features that influence damage vulnerability. We then compare the results of the models without and with this revealed information and find that the revelation of additional, secondary information influences modeled losses for the windstorm-exposed university building stock, primarily evidenced by meaningful percent differences in the loss exceedance output indicated after secondary modifiers are incorporated in the analysis. Secondary risk characteristics for the data set studied appear to have substantially greater impact on probable maximum loss estimates than on average annual loss estimates. While it may be intuitively expected for catastrophe models to indicate that secondary risk characteristics hold value for reducing modeled losses, the finding that the primary value of secondary risk characteristics is in reduction of losses in the "tail" (low probability, high severity) events is less intuitive, and therefore especially interesting. Further, we address the benefit-cost tradeoffs that commercial entities must consider when deciding whether to undergo the data collection necessary to include secondary information in modeling. Although we assert the long-term benefit-cost tradeoff is positive for virtually every entity, we acknowledge short-term disincentives to such an effort.

  20. Characterizing Genetic Risk at Known Prostate Cancer Susceptibility Loci in African Americans

    PubMed Central

    Haiman, Christopher A.; Chen, Gary K.; Blot, William J.; Strom, Sara S.; Berndt, Sonja I.; Kittles, Rick A.; Rybicki, Benjamin A.; Isaacs, William B.; Ingles, Sue A.; Stanford, Janet L.; Diver, W. Ryan; Witte, John S.; Chanock, Stephen J.; Kolb, Suzanne; Signorello, Lisa B.; Yamamura, Yuko; Neslund-Dudas, Christine; Thun, Michael J.; Murphy, Adam; Casey, Graham; Sheng, Xin; Wan, Peggy; Pooler, Loreall C.; Monroe, Kristine R.; Waters, Kevin M.; Le Marchand, Loic; Kolonel, Laurence N.; Stram, Daniel O.; Henderson, Brian E.

    2011-01-01

    GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10−4) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry. PMID:21637779

  1. Risk

    PubMed Central

    Cole, Stephen R.; Hudgens, Michael G.; Brookhart, M. Alan; Westreich, Daniel

    2015-01-01

    The epidemiologist primarily studies transitions between states of health and disease. The purpose of the present article is to define a foundational parameter for such studies, namely risk. We begin simply and build to the setting in which there is more than 1 event type (i.e., competing risks or competing events), as well as more than 1 treatment or exposure level of interest. In the presence of competing events, the risks are a set of counterfactual cumulative incidence functions for each treatment. These risks can be depicted visually and summarized numerically. We use an example from the study of human immunodeficiency virus to illustrate concepts. PMID:25660080

  2. Children's exposure to harmful elements in toys and low-cost jewelry: characterizing risks and developing a comprehensive approach.

    PubMed

    Guney, Mert; Zagury, Gerald J

    2014-04-30

    Contamination problem in jewelry and toys and children's exposure possibility have been previously demonstrated. For this study, risk from oral exposure has been characterized for highly contaminated metallic toys and jewelry ((MJ), n=16) considering three scenarios. Total and bioaccessible concentrations of Cd, Cu, Ni, and Pb were high in selected MJ. First scenario (ingestion of parts or pieces) caused unacceptable risk for eight items for Cd, Ni, and/or Pb (hazard index (HI)>1, up to 75, 5.8, and 43, respectively). HI for ingestion of scraped-off material scenario was always <1. Finally, saliva mobilization scenario caused HI>1 in three samples (two for Cd, one for Ni). Risk characterization identified different potentially hazardous items compared to United States, Canadian, and European Union approaches. A comprehensive approach was also developed to deal with complexity and drawbacks caused by various toy/jewelry definitions, test methods, exposure scenarios, and elements considered in different regulatory approaches. It includes bioaccessible limits for eight priority elements (As, Cd, Cr, Cu, Hg, Ni, Pb, and Sb). Research is recommended on metals bioaccessibility determination in toys/jewelry, in vitro bioaccessibility test development, estimation of material ingestion rates and frequency, presence of hexavalent Cr and organic Sn, and assessment of prolonged exposure to MJ. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Molecular Characterization of High-Risk Human Papillomavirus in Women in Bobo-Dioulasso, Burkina Faso.

    PubMed

    Traore, Ina Marie Angèle; Zohoncon, Théodora Mahoukèdè; Dembele, Adama; Djigma, Florencia W; Obiri-Yeboah, Dorcas; Traore, Germain; Bambara, Moussa; Ouedraogo, Charlemagne; Traore, Yves; Simpore, Jacques

    2016-01-01

    High-risk human papillomavirus (HPV) is found in over 99% of cervical cancers. The aim of this study was to determine the prevalence of HPV in a population of women in Bobo-Dioulasso and to identify the high-risk types present in these women. From May to June, 2015, 181 women who came for consultation at the Souro Sanou University Hospital of Bobo-Dioulasso have been included in this study. Uterine endocervical swabs have been taken in these women. DNA obtained by extraction from the samples thus collected was used to determine the prevalence of high-risk human papillomavirus genotypes through real-time PCR. The age of the women ranged from 20 to 56 years with a mean of 35.3 ± 8.1 years. The prevalence of infection by high-risk HPV types was 25.4% (46/181). The most common high-risk HPV genotypes were HPV 39 (18.5%), HPV 52 (16.7%), HPV 18 (14.8%), and HPV 35 (13.0%). HPV 16 which is included in the HPV vaccines was not found in the population studied. This type of study which is the first one in Bobo-Dioulasso has showed a high prevalence of genotypes HPV 39, HPV 52, and HPV 35 which are not yet covered by a vaccine.

  4. Molecular Characterization of High-Risk Human Papillomavirus in Women in Bobo-Dioulasso, Burkina Faso

    PubMed Central

    Traore, Ina Marie Angèle; Dembele, Adama; Obiri-Yeboah, Dorcas; Traore, Germain; Bambara, Moussa; Ouedraogo, Charlemagne; Traore, Yves

    2016-01-01

    High-risk human papillomavirus (HPV) is found in over 99% of cervical cancers. The aim of this study was to determine the prevalence of HPV in a population of women in Bobo-Dioulasso and to identify the high-risk types present in these women. From May to June, 2015, 181 women who came for consultation at the Souro Sanou University Hospital of Bobo-Dioulasso have been included in this study. Uterine endocervical swabs have been taken in these women. DNA obtained by extraction from the samples thus collected was used to determine the prevalence of high-risk human papillomavirus genotypes through real-time PCR. The age of the women ranged from 20 to 56 years with a mean of 35.3 ± 8.1 years. The prevalence of infection by high-risk HPV types was 25.4% (46/181). The most common high-risk HPV genotypes were HPV 39 (18.5%), HPV 52 (16.7%), HPV 18 (14.8%), and HPV 35 (13.0%). HPV 16 which is included in the HPV vaccines was not found in the population studied. This type of study which is the first one in Bobo-Dioulasso has showed a high prevalence of genotypes HPV 39, HPV 52, and HPV 35 which are not yet covered by a vaccine. PMID:27525275

  5. Characterization of municipal solid waste temporary storage sites: risks posed to surrounding areas as a consequence of fire incidents.

    PubMed

    Ibrahim, Muhammad Asim; Göransson, Görgen; Kaczala, Fabio; Hogland, William; Marques, Marcia

    2013-11-01

    In this study temporary storage sites of municipal solid waste were characterized based on their potential social, health and environmental impacts as a consequence of spontaneous fires, by employing Boolean as well as weighted-linear-combination approaches in connection with various fuzzy set functions of population density around the storage sites. Sweden was used as the case study and data from 105 storage sites were analysed; of these, 38 were identified to be posing high risk for downwind residing population. Furthermore, during the past 10years, the fire frequency and the average population residing within a radius of 1, 2, and 3km were found to be comparatively higher for storage sites owned by private companies than for those owned by municipalities. The study provided first-cut information of poorly sited temporary storage sites and can help in formalizing the comprehensive risk analysis in the future.

  6. U-shaped dose-response curves: implications for risk characterization of essential elements and other chemicals.

    PubMed

    Douron, Michael

    2010-01-01

    The existing risk assessment and management model is a general framework that can incorporate the assessment of numerous types of chemicals, such as essential elements. The general nature of the framework, however, often precludes precise statements of risk and only gives assurances of accuracy by way of a judicious use of conservative assumptions. A mode-of-action framework may provide approaches that are both more precise and accurate, and that may be used for characterizing both risk and benefit of essential elements, but such a framework needs to address the differing severity of adverse effects. Current dose-response data gaps often hinder the evaluation of the risk and benefit of several essential elements; however, new modeling methods, such as categorical regression, need to be further explored. Finally, the essentiality of certain elements provides evidence that two thresholds likely exist in an individual for adverse effect, one at low doses for undernutrition, and another at high doses for toxicity, for the element of concern. This evidence may aid in the estimation of such thresholds in populations.

  7. Plant characterization of Roundup Ready 2 Yield ® soybean, MON 89788, for use in ecological risk assessment.

    PubMed

    Horak, Michael J; Rosenbaum, Eric W; Kendrick, Daniel L; Sammons, Bernard; Phillips, Samuel L; Nickson, Thomas E; Dobert, Raymond C; Perez, Tim

    2015-04-01

    During the development of a genetically modified (GM) crop product, extensive phenotypic and agronomic data are collected to characterize the plant in comparison to a conventional control with a similar genetic background. The data are evaluated for potential differences resulting from the genetic modification process or the GM trait, and the differences--if any--are subsequently considered in the context of contributing to the pest potential of the GM crop. Ultimately, these study results and those of other studies are used in an ecological risk assessment of the GM crop. In the studies reported here, seed germination, vegetative and reproductive growth, and pollen morphology of Roundup Ready 2 Yield(®) soybean, MON 89788, were compared to those of A3244, a conventional control soybean variety with the same genetic background. Any statistically significant differences were considered in the context of the genetic variation known to occur in soybean and were evaluated as indicators of an effect of the genetic modification process and assessed for impact on plant pest (weed) characteristics and adverse ecological impact (ecological risk). The results of these studies revealed no effects attributable to the genetic modification process or to the GM trait in the plant that would result in increased pest potential or adverse ecological impact of MON 89788 compared with A3244. These results and the associated risk assessments obtained from diverse geographic and environmental conditions in the United States and Argentina can be used by regulators in other countries to inform various assessments of ecological risk.

  8. Changes in free amino acid, phenolic, chlorophyll, carotenoid, and glycoalkaloid contents in tomatoes during 11 stages of growth and inhibition of cervical and lung human cancer cells by green tomato extracts.

    PubMed

    Choi, Suk-Hyun; Lee, Sang-Hwa; Kim, Hyun-Jeong; Lee, In-Seon; Kozukue, Nobuyuki; Levin, Carol E; Friedman, Mendel

    2010-07-14

    Tomato ( Solanum lycopersicum ) plants synthesize nutrients, pigments, and secondary metabolites that benefit nutrition and human health. The concentrations of these compounds are strongly influenced by the maturity of the tomato fruit on the vine. Widely consumed Korean tomatoes of the variety Doturakworld were analyzed for changes in the content of free amino acids, phenolic compounds, chlorophylls, carotenoids, and glycoalkaloids at 11 stages (S1-S11) of ripeness. The results show that (a) the total content (in mg/100 g of FW) of the free amino acids and other nitrogen-containing compounds in the extracts ranged from about 41 to 85 in the green tomato extracts S1-S7 and then increased to 251 (S9) in the red extracts, followed by a decrease to 124 in S11 red extracts; (b) the total initial concentration and composition of up to 12 phenolic compounds of approximately 2000 microg/100 g of FW varied throughout the ripening process, with the quantity decreasing and the number of individual compounds increasing in the red tomato; (c) chlorophyll a and b content of tomatoes harvested during S1 was 5.73 mg/100 g of fresh pericarp and then decreased continuously to 1.14 mg/100 g for S11; (d) the concentration (in mg/100 g of FW) of lycopene in the S8 red extract of 0.32 increased to 1.27 in S11; and (e) tomatoes harvested during S1 contained 48.2 mg of dehydrotomatine/100 g of FW, and this value continually decreased to 1.5 in S7, with no detectable levels in S8-S11. The corresponding alpha-tomatine content decreased from S1 (361) to S8 (13.8). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell assay IC(50) values showed that Hel299 lung cells, A549 lung cancer cells, and HeLa cervical carcinoma cells were highly susceptible to inactivation by glycoalkaloid-rich green tomato extracts. Chang normal liver cells and U937 lymphoma cells were less susceptible. The possible significance of the results for plant physiology and the diet is discussed.

  9. Risk

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel

    2016-01-01

    Speaking up, i.e. expressing ones concerns, is a critical piece of effective communication. Yet, we see many situations in which crew members have concerns and still remain silent. Why would that be the case? And how can we assess the risks of speaking up vs. the risks of keeping silent? And once we do make up our minds to speak up, how should we go about it? Our workshop aims to answer these questions, and to provide us all with practical tools for effective risk assessment and effective speaking-up strategies..

  10. Characterizing Stressors and Modifiable Health Risk Factors among Homeless Smokers: An Exploratory Pilot Study

    ERIC Educational Resources Information Center

    Kendzor, Darla E.; Reitzel, Lorraine R.; Businelle, Michael S.

    2015-01-01

    This pilot study was conducted to explore the associations between stressors related to homelessness and modifiable health risk factors (poor diet, insufficient physical activity, and overweight/obesity) and to provide direction for future research. Participants (N = 57) were homeless adults enrolled in a smoking cessation program. Analyses were…

  11. Characterizing Stressors and Modifiable Health Risk Factors among Homeless Smokers: An Exploratory Pilot Study

    ERIC Educational Resources Information Center

    Kendzor, Darla E.; Reitzel, Lorraine R.; Businelle, Michael S.

    2015-01-01

    This pilot study was conducted to explore the associations between stressors related to homelessness and modifiable health risk factors (poor diet, insufficient physical activity, and overweight/obesity) and to provide direction for future research. Participants (N = 57) were homeless adults enrolled in a smoking cessation program. Analyses were…

  12. Pathology of wildfire risk: A characterization of social and ecological dimensions

    Treesearch

    A. Paige Fischer; Thomas A Spies; Toddi A Steelman; Cassandra Moseley; Bart R Johnson; John D Bailey; Alan A Ager; Patrick Bourgeron; Susan Charnley; Brandon M Collins; Jeffrey D Kline; Jessica E Leahy; Jeremy S Littell; James DA Millington; Max Nielsen-Pincus; Christine S Olsen; Travis B Paveglio; Christopher I Roos; Michelle M Steen-Adams; Forrest R Stevens; Jelena Vukomanovic; Eric M White; David M. J. S. Bowman

    2016-01-01

    Despite dramatic increases in suppression spending, the risk of life and property loss associated with wildfire has continued to rise in recent decades. Economic losses from wildfires have doubled in the United States and suppression expenses have tripled between 2002 and 2012 compared to the decade prior. Loss of property to wildfire has outpaced efforts to reduce...

  13. Characterizing the Risk Factors Associated With Venous Thromboembolism in Pediatric Patients After Central Venous Line Placement

    PubMed Central

    Eades, Shannan; Turiy, Yuliya

    2015-01-01

    OBJECTIVES: With the apparent increase in venous thromboembolism noted in the pediatric population, it is important to define which children are at risk for clots and to determine optimal preventative therapy. The purpose of this study was to determine the risk factors for venous thromboembolism in pediatric patients with central venous line placement. METHODS: This was an observational, retrospective, case-control study. Control subjects were patients aged 0 to 18 years who had a central venous line placed. Case subjects had a central line and a radiographically confirmed diagnosis of venous thromboembolism. RESULTS: A total of 150 patients were included in the study. Presence of multiple comorbidities, particularly the presence of a congenital heart defect (34.7% case vs. 14.7% control; p < 0.005), was found to put pediatric patients at increased risk for thrombosis. Additionally, the administration of parenteral nutrition through the central line (34.7% case vs. 18.7% control; p = 0.03) and location of the line increased the risk for clot formation. CONCLUSIONS: With increased awareness of central venous line–related thromboembolism, measures should be taken to reduce the number and duration of central line placements, and further studies addressing the need for thromboprophylaxis should be conducted. PMID:26472949

  14. Site characterization to support risk assessment of contaminated ground-water- some case studies

    EPA Science Inventory

    In the USA, “risk assessment" generally refers to an evaluation of the impact of a known concentration of a hazardous material in ground water on human health or environmental quality. This presentation is different. It deals with the impact of a spill or release of hazardous m...

  15. Site characterization to support risk assessment of contaminated ground-water- some case studies

    EPA Science Inventory

    In the USA, “risk assessment" generally refers to an evaluation of the impact of a known concentration of a hazardous material in ground water on human health or environmental quality. This presentation is different. It deals with the impact of a spill or release of hazardous m...

  16. Light Water Reactor Sustainability Program Risk Informed Safety Margin Characterization (RISMC) Advanced Test Reactor Demonstration Case Study

    SciTech Connect

    Curtis Smith; David Schwieder; Cherie Phelan; Anh Bui; Paul Bayless

    2012-08-01

    Safety is central to the design, licensing, operation, and economics of Nuclear Power Plants (NPPs). Consequently, the ability to better characterize and quantify safety margin holds the key to improved decision making about LWR design, operation, and plant life extension. A systematic approach to characterization of safety margins and the subsequent margins management options represents a vital input to the licensee and regulatory analysis and decision making that will be involved. The purpose of the RISMC Pathway R&D is to support plant decisions for risk-informed margins management with the aim to improve economics, reliability, and sustain safety of current NPPs. Goals of the RISMC Pathway are twofold: (1) Develop and demonstrate a risk-assessment method coupled to safety margin quantification that can be used by NPP decision makers as part of their margin recovery strategies. (2) Create an advanced “RISMC toolkit” that enables more accurate representation of NPP safety margin. This report describes the RISMC methodology demonstration where the Advanced Test Reactor (ATR) was used as a test-bed for purposes of determining safety margins. As part of the demonstration, we describe how both the thermal-hydraulics and probabilistic safety calculations are integrated and used to quantify margin management strategies.

  17. Polybrominated diphenyl ethers (PBDEs) concentration in soil from San Luis Potosi, Mexico: levels and ecological and human health risk characterization.

    PubMed

    Pérez-Vázquez, Francisco J; Orta-García, Sandra T; Ochoa-Martínez, Ángeles C; Pruneda-Álvarez, Lucia G; Ruiz-Vera, Tania; Jiménez-Avalos, Jorge Armando; González-Palomo, Ana K; Pérez-Maldonado, Iván N

    2016-01-01

    The aim of this study was to assess the levels of polybrominated diphenyl ethers (PBDEs) in soils from the city of San Luis Potosi in Mexico and perform an ecological and human health risk characterization. In order to confirm the presence of PBDEs, outdoor surface soil samples were collected and the concentrations of PBDEs in urban, industrial, agricultural, and brick kiln industry areas were determined. The mean total PBDEs levels obtained in the study sites were 25.0 ± 39.5 μg/kg (geometric mean ± standard deviation) in the brick kiln industry zone; 34.5 ± 36.0 μg/kg in the urban zone; 8.00 ± 7.10 μg/kg in the industrial zone and 16.6 ± 15.3 μg/kg in the agricultural zone. The ecological and human health risk characterization showed relatively low-hazard quotient values. However, the moderately high PBDEs levels found in soils highlight the necessity to establish a systematic monitoring process for PBDEs in environmental and biological samples.

  18. Prototype Near-Field/GIS Model for Sequestered-CO2 Risk Characterization and Management

    SciTech Connect

    Bogen, K T; Homann, S G; Gouveia, F J; Neher, L A

    2006-02-10

    Detecting unmapped abandoned wells thus remains a major carbon sequestration (CS) technology gap. Many (>10{sup 5}) abandoned wells are thought to lie in potential sequestration sites. For such wells, risk analysis to date has focused on aggregate long-term future impacts of seepage at rates < or << {approx}1 g m{sup 2} d{sup -1} on storage goals as sequestered plumes encroach upon wells with assumed distributions of seal ineffectiveness (Oldenburg and Unger, 2003; Saripali et al. 2003; Celia, 2005). However, unmapped abandoned wells include an unknown number without any effective seal at all, venting through which may dominate CO{sub 2}-loss scenarios. A model of such a well is Crystal Geyser (CG), a prospective oil well abandoned in the 1930s with no barrier installed after it encountered a natural CO{sub 2} reservoir rather than oil (Baer and Rigby, 1978; Rinehart, 1980). CG demonstrates how an unimpeded conduit to the surface now regularly vents from 10{sup 3} to >10{sup 4} kg of CO{sub 2} gas to the terrestrial surface (Figure 1). Unique field data recently gathered from Crystal Geyser (CG) in Utah (Gouveia et al. 2005) confirm that, although resulting surface CO{sub 2} concentrations resulting from CG-like eruptions would likely be safe in general, they could accumulate to pose lethal hazards under relatively rare meteorological and topographic (MT) conditions. This source of foreseeable risk needs to be managed if carbon sequestration is to be publicly accepted. To address this concern, we used CG field data to estimate the source term for a prototype model that identifies zones at relatively highly elevated risk for sequestered-CO{sub 2} casualties. Such a model could be applied both to design and comply with future regulatory requirements to survey high-risk zones in each proposed sequestration site for improperly sealed wells.

  19. Characterization and Optimal Management of High-Risk Pancreatic Anastomoses During Pancreatoduodenectomy.

    PubMed

    Ecker, Brett L; McMillan, Matthew T; Asbun, Horacio J; Ball, Chad G; Bassi, Claudio; Beane, Joal D; Behrman, Stephen W; Berger, Adam C; Dickson, Euan J; Bloomston, Mark; Callery, Mark P; Christein, John D; Dixon, Elijah; Drebin, Jeffrey A; Castillo, Carlos Fernandez-Del; Fisher, William E; Fong, Zhi Ven; Haverick, Ericka; Hollis, Robert H; House, Michael G; Hughes, Steven J; Jamieson, Nigel B; Javed, Ammar A; Kent, Tara S; Kowalsky, Stacy J; Kunstman, John W; Malleo, Giuseppe; Poruk, Katherine E; Salem, Ronald R; Schmidt, Carl R; Soares, Kevin; Stauffer, John A; Valero, Vicente; Velu, Lavanniya K P; Watkins, Amarra A; Wolfgang, Christopher L; Zureikat, Amer H; Vollmer, Charles M

    2017-06-07

    The aim of this study was to identify the optimal fistula mitigation strategy following pancreaticoduodenectomy. The utility of technical strategies to prevent clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) may vary by the circumstances of the anastomosis. The Fistula Risk Score (FRS) identifies a distinct high-risk cohort (FRS 7 to 10) that demonstrates substantially worse clinical outcomes. The value of various fistula mitigation strategies in these particular high-stakes cases has not been previously explored. This multinational study included 5323 PDs performed by 62 surgeons at 17 institutions. Mitigation strategies, including both technique related (ie, pancreatogastrostomy reconstruction; dunking; tissue patches) and the use of adjuvant strategies (ie, intraperitoneal drains; anastomotic stents; prophylactic octreotide; tissue sealants), were evaluated using multivariable regression analysis and propensity score matching. A total of 522 (9.8%) PDs met high-risk FRS criteria, with an observed CR-POPF rate of 29.1%. Pancreatogastrostomy, prophylactic octreotide, and omission of externalized stents were each associated with an increased rate of CR-POPF (all P < 0.001). In a multivariable model accounting for patient, surgeon, and institutional characteristics, the use of external stents [odds ratio (OR) 0.45, 95% confidence interval (95% CI) 0.25-0.81] and the omission of prophylactic octreotide (OR 0.49, 95% CI 0.30-0.78) were independently associated with decreased CR-POPF occurrence. In the propensity score matched cohort, an "optimal" mitigation strategy (ie, externalized stent and no prophylactic octreotide) was associated with a reduced rate of CR-POPF (13.2% vs 33.5%, P < 0.001). The scenarios identified by the high-risk FRS zone represent challenging anastomoses associated with markedly elevated rates of fistula. Externalized stents and omission of prophylactic octreotide, in the setting of

  20. Risk Characterization for Future Training Scenarios at the Massachusetts Military Reservation (MMR), Final Results

    DTIC Science & Technology

    2005-08-01

    irritation to the respiratory system. The non- carcinogenic and carcinogenic risks were estimated according to the route of exposure , i.e., dermal... exposure and effect through the air inhalation pathway/route. However, lack of input toxicological data for most of the 219 chemicals limited the...impacts. More realistic emission durations could be used and would reduce conservatism. The assumption of no degradation overestimated exposure

  1. Characterization and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in urban atmospheric Particulate of Tehran, Iran.

    PubMed

    Hoseini, Mohammad; Yunesian, Masud; Nabizadeh, Ramin; Yaghmaeian, Kamyar; Ahmadkhaniha, Reza; Rastkari, Noushin; Parmy, Saeid; Faridi, Sasan; Rafiee, Ata; Naddafi, Kazem

    2016-01-01

    In this study, atmospheric concentrations of particulate-bound polycyclic aromatic hydrocarbons (PAHs) in Tehran megacity were determined to investigate the concentration, distribution, and sources of PAHs in PM10. The health risk from exposure to airborne BaPeq through inhalation pathway was also assessed. Toxic equivalency factors (TEFs) approach was used for quantitative risk estimate, and incremental lifetime cancer risk (ILCR) was calculated. PM10 samples were collected at ten sampling locations during the summer 2013 and winter 2014 by using two independent methods of field sampling. The PM10 concentration in winter (89.55 ± 15.56 μg m(-3)) was 1.19 times higher than that in summer (75.42 ± 14.93 μg m(-3)). Sixteen PAHs were measured with the total average concentrations of PAHs ranged from 56.98 ± 15.91 to 110.35 ± 57.31 ng m(-3) in summer and from 125.87 ± 79.02 to 171.25 ± 73.94 ng m(-3) in winter which were much higher than concentrations measured in most similar studies conducted around the world. Molecular diagnostic ratios were used to identify PAH emission sources. The results indicated that gasoline-driven vehicles are the major sources of PAHs in the study area. Risk analysis showed that the mean and 90 % probability estimated inhalation ILCRs were 7.85 × 10(-6) and 16.78 × 10(-6), respectively. Results of a sensitivity analysis indicated that BaP concentration and cancer slope factor (CSF) contributed most to effect on ILCR mean.

  2. Modeling of Near-Surface Leakage and Seepage of CO2 for Risk Characterization

    SciTech Connect

    Oldenburg, Curtis M.; Unger, Andre A.J.

    2004-02-18

    The injection of carbon dioxide (CO2) into deep geologic carbon sequestration sites entails risk that CO2 will leak away from the primary storage formation and migrate upwards to the unsaturated zone from which it can seep out of the ground. We have developed a coupled modeling framework called T2CA for simulating CO2 leakage and seepage in the subsurface and in the atmospheric surface layer. The results of model simulations can be used to calculate the two key health, safety, and environmental (HSE) risk drivers, namely CO2 seepage flux and nearsurface CO2 concentrations. Sensitivity studies for a subsurface system with a thick unsaturated zone show limited leakage attenuation resulting in correspondingly large CO2 concentrations in the shallow subsurface. Large CO2 concentrations in the shallow subsurface present a risk to plant and tree roots, and to humans and other animals in subsurface structures such as basements or utility vaults. Whereas CO2 concentrations in the subsurface can be high, surfacelayer winds reduce CO2 concentrations to low levels for the fluxes investigated. We recommend more verification and case studies be carried out with T2CA, along with the development of extensions to handle additional scenarios such as calm conditions, topographic effects, and catastrophic surface-layer discharge events.

  3. Lead bioaccessibility in food web intermediates and the influence on ecological risk characterization.

    PubMed

    Kaufman, Claire A; Bennett, Joseph R; Koch, Iris; Reimer, Kenneth J

    2007-08-15

    Models simulating gastric conditions of mammalian (eastern cottontail, Sylvilagus floridanus; short-tailed shrew, Blarina brevicauda) and avian (American robin, Turdus migratorius) receptors were used to investigate the proportion of lead (Pb) mobilized into the digestive juices (the bioaccessible fraction) from soil, earthworms, and vegetation collected at a rifle and pistol (RP) range in eastern Ontario, Canada. Pb concentrations averaged 5044 mg kg(-1) in RP range surface soils, 727 mg kg(-1) in earthworm tissue, and 2945 mg kg(-1) in unwashed vegetation. For mammalian gastric models, the bioaccessible fraction of Pb in soils was 66 +/- 22%, in earthworm tissue was 77 +/- 14%, and in unwashed vegetation was 50 +/- 37%. For the avian gastric model, the bioaccessible fraction of Pb in soil was 53 +/- 43% and in earthworm tissue was 73 +/- 13%. The incorporation of soil and food web intermediate bioaccessibility data into standard risk calculations resulted in predicted risk being reduced for all receptors. The inclusion of bioaccessibility during ecological risk assessment affords a more realistic estimate of contaminant exposure, and is a valuable tool for use in contaminated sites management.

  4. Replacement of HEPA Filters at the LANL CMR Facility: Risks Reduced by Comprehensive Waste Characterization

    SciTech Connect

    Corpion, J.; Barr, A.; Martinez, P.; Bader, M.

    2002-02-28

    In March 2001, the Los Alamos National Laboratory (LANL) completed the replacement of 720 radioactively contaminated HEPA filters for $5.7M. This project was completed five months ahead of schedule and $6.0M under budget with no worker injuries or contaminations. Numerous health and safety, environmental, and waste disposal problems were overcome, including having to perform work in a radioactively contaminated work environment, that was also contaminated with perchlorates (potential explosive). High waste disposal costs were also an issue. A project risk analysis and government cost estimate determined that the cost of performing the work would be $11.8M. To reduce risk, a $1.2M comprehensive condition assessment was performed to determine the degree of toxic and radioactive contamination trapped on the HEPA filters; and to determine whether explosive concentrations of perchlorates were present. Workers from LANL and personnel from Waldheim International of Knoxville, TN collected hundreds of samples wearing personnel protective gear against radioactive, toxic, and explosive hazards. LANL also funded research at the New Mexico Institute of Mining and Technology to determine the explosivity of perchlorates. The data acquired from the condition assessment showed that toxic metals, toxic organic compounds, and explosive concentrations of perchlorates were absent. The data also showed that the extent of actinide metal contamination was less than expected, reducing the potential of transuranic waste generation by 50%. Consequently, $4.2M in cost savings and $1.8M in risk reduction were realized by increased worker productivity and waste segregation.

  5. Replacement of HEPA Filters at the LANL CMR Facility : risk reduced by comprehensive waste characterization

    SciTech Connect

    Corpion, J. C.

    2002-01-01

    In March 2001, the Los Alamos National Laboratory (LANL) completed the replacement of 720 radioactively contaminated HEPA filters for $5.7M. This project was completed five months ahead of schedule and $6.0M under budget with no worker injuries or contaminations. Numerous health and safety, environmental, and waste disposal problems were overcome, including having to perform work in a radioactively contaminated work environment, that was also contaminated with perchlorates (potential explosive). High waste disposal costs were also an issue. A project risk analysis and government cost estimate determined that the cost of performing the work would be $11.8M. To reduce risk, a $1.2M comprehensive condition assessment was performed to determine the degree of toxic and radioactive contamination trapped on the HEPA filters; and to determine whether explosive concentrations of perchlorates were present. Workers from LANL and personnel from Waldheim International of Knoxville, TN collected hundreds of samples wearing personnel protective gear against radioactive, toxic, and explosive hazards. LANL also funded research at the New Mexico Institute of Mining and Technology to determine the explosivity of perchlorates. The data acquired from the condition assessment showed that toxic metals, toxic organic compounds, and explosive concentrations of perchlorates were absent. The data also showed that the extent of actinide metal contamination was less than expected, reducing the potential of transuranic waste generation by 50%. Consequently, $4.2M in cost savings and $1.8M in risk reduction were realized by increased worker productivity and waste segregation.

  6. Characterization of the nuclear localization signal of high risk HPV16 E2 protein

    SciTech Connect

    Klucevsek, Kristin; Wertz, Mary; Lucchi, John; Leszczynski, Anna; Moroianu, Junona . E-mail: moroianu@bc.edu

    2007-03-30

    The E2 protein of high risk human papillomavirus type 16 (HPV16) contains an amino-terminal (N) domain, a hinge (H) region and a carboxyl-terminal (C) DNA-binding domain. Using enhanced green fluorescent protein (EGFP) fusions with full length E2 and E2 domains in transfection assays in HeLa cells, we found that the C domain is responsible for the nuclear localization of E2 in vivo, whereas the N and H domains do not contain additional nuclear localization signals (NLSs). Deletion analysis of EGFP-E2 and EGFP-cE2 determined that the C domain contains an {alpha} helix cNLS that overlaps with the DNA-binding region. Mutational analysis revealed that the arginine and lysine residues in this cNLS are essential for nuclear localization of HPV16 E2. Interestingly, these basic amino acid residues are well conserved among the E2 proteins of BPV-1 and some high risk HPV types but not in the low risk HPV types, suggesting that there are differences between the NLSs and corresponding nuclear import pathways between these E2 proteins.

  7. Characterization of pharmaceutically active compounds in Dongting Lake, China: Occurrence, chiral profiling and environmental risk.

    PubMed

    Ma, Ruixue; Wang, Bin; Lu, Shaoyong; Zhang, Yizhe; Yin, Lina; Huang, Jun; Deng, Shubo; Wang, Yujue; Yu, Gang

    2016-07-01

    Twenty commonly used pharmaceuticals including eight chiral drugs were investigated in Dongting Lake, China. The contamination level was relatively low on a global scale. Twelve pharmaceuticals were identified. The most abundant compound was caffeine followed by diclofenac, DEET, mefenamic acid, fluoxetine, ibuprofen and carbamazepine with mean concentrations from 2.0 to 80.8ngL(-1). Concentrations between East and West Dongting Lake showed spatial difference, with the West Dongting Lake less polluted. The relatively high ratio of caffeine versus carbamazepine (over 50) may indicate there was possible direct discharge of domestic wastewater into the lake. This is the first study presenting a survey allowing for comprehensive analysis of multiclass achiral and chiral pharmaceuticals including beta-blockers, antidepressants and anti-inflammatory drugs in freshwater lake. The enantiomeric compositions presented racemic to weakly enantioselective, with the highest enantiomeric fraction (EF) of 0.63 for fluoxetine. Meanwhile, venlafaxine was identified and evaluated the environment risk in surface water in China for the first time. The results of risk assessment suggested that fluoxetine, venlafaxine and diclofenac acid might pose a significant risk to aquatic organisms in Dongting Lake. The resulting data will be useful to enrich the research of emerging pollutants in freshwater lake and stereochemistry for environment investigations. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Oxidative stress as a risk factor for osteoporosis in elderly Mexicans as characterized by antioxidant enzymes

    PubMed Central

    Sánchez-Rodríguez, Martha A; Ruiz-Ramos, Mirna; Correa-Muñoz, Elsa; Mendoza-Núñez, Víctor Manuel

    2007-01-01

    Background Oxidative stress (OxS) has recently been linked with osteoporosis; however, we do not know the influence of OxS as an independent risk factor for this disease. Methods We conducted a case-control study in 94 subjects ≥60 years of age, 50 healthy and 44 with osteoporosis. We measured total antioxidant status, plasma lipid peroxides, antioxidant activity of superoxide dismutase and glutathione peroxidase (GPx), and calculated the SOD/GPx ratio. Bone mineral density was obtained at the peripheral DXA in calcaneus using a portable Norland Apollo Densitometer®. Osteoporosis was considered when subjects had a BMD of 2.5 standard deviations or more below the mean value for young adults. Results GPx antioxidant activity was significantly lower in the group of subjects with osteoporosis in comparison with the group of healthy subjects (p < 0.01); in addition, the SOD/GPx ratio was significantly higher in the group of individuals with osteoporosis (p < 0.05). In logistic regression analysis, we found OxS to be an independent risk factor for osteoporosis (odds ratio [OR] = 2.79; 95% confidence interval [95% CI] = 1.08–7.23; p = 0.034). Conclusion Our findings suggest that OxS is an independent risk factor for osteoporosis linked to increase of SOD/GPx ratio. PMID:18088440

  9. Characterizing non-monosexual women at risk for poor mental health outcomes: A mixed methods study.

    PubMed

    Ross, Lori E; Manley, Melissa H; Goldberg, Abbie E; Januwalla, Alia; Williams, Keisha; Flanders, Corey E

    2017-09-14

    Non-monosexual women - those who report attraction to or sexual relationships with individuals of more than one gender - have elevated risk for poor mental health outcomes. We aimed to examine which elements of non-monosexual experience are associated with this elevated risk. We conducted a sequential exploratory mixed methods analysis of qualitative interview and survey data from 39 non-monosexual women recruited consecutively through prenatal care providers. Qualitative analyses identified distinguishing features, and quantitative analyses tested associations between these features and mental health symptoms. Nine qualitative themes were identified to describe distinguishing features of non-monosexual women. Of these, current and past five years partner gender, lack of LGBTQ community connection, and low centrality of sexual minority identity were associated with anxiety symptoms. Latent class analysis revealed significantly higher levels of anxiety symptoms among non-monosexual women partnered with men relative to those partnered with women. Sexual minority women who partner with men may be particularly at risk for poor mental health. Considering this group's invisibility in public health research and practice, interventions are needed to address this disparity.

  10. [Epidemiology and characterization of high-risk genotypes of human Papillomavirus in a population of sexually active adolescents in Ouagadougou].

    PubMed

    Ouédraogo, C M R; Rahimy, R M L; Zohoncon, T M; Djigma, F W; Yonli, A T; Ouermi, D; Sanni, A; Lankoande, J; Simpore, J

    2015-10-01

    This cross-sectional study was to determine the prevalence and characterization of high-risk HPV genotypes circulating among adolescents in Ouagadougou. From September to December 2013, 200 adolescents recruited from a youth counseling center have voluntarily accepted a swab of the endocervical canal. The identification of the genotypes of the human Papillomavirus (HPV) was performed by real-time polymerase chain reaction technique. The mean age of adolescents was 18.7±0.7 years and 83/200 adolescents were positive for at least one high-risk genotype HPV a prevalence of 41.5%. Twelve genotypes corresponding to 136 infections were characterized: HPV 52 (22.8%), HPV 59 (14.0%), HPV 39 (13.2%), HPV 35 (10.3%), HPV 51 (10.3%), HPV 56 (8.8%), HPV 16 (5.2%), HPV 18 (5.2%), HPV 58 (4.4%), HPV 31 (3.6%), HPV 45 (1.5%), HPV 33 (0.7%). Multiple infections (2-5 virus) statistically associated with age (p=0.0318) was detected in 42.2% of infected females. If the number of sexual partners was statistically associated with the porting of HPV (OR=2.18; 95% CI=1.17 to 4.09), early sexual intercourse and the recent change of sexual partner were not (p>0,05) CONCLUSION: The prevalence of carriage of HPV in this study is high, as described in young people at the start of sexual activity. Identified genotypes are different from those targeted by prophylactic vaccines currently available. A larger study to map genotypes of high-risk HPV circulating in West Africa is necessary for a suitable vaccine. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. Neural correlates of risk taking in violent criminal offenders characterized by emotional hypo- and hyper-reactivity.

    PubMed

    Prehn, Kristin; Schlagenhauf, Florian; Schulze, Lars; Berger, Christoph; Vohs, Knut; Fleischer, Monika; Hauenstein, Karlheinz; Keiper, Peter; Domes, Gregor; Herpertz, Sabine C

    2013-01-01

    Recent approaches suggest that emotional reactivity can be used to differentiate between subgroups of individuals who are at risk for showing elevated levels of aggression and violence. In this study, we examined how emotion governs decision making within two subgroups of antisocial criminal offenders with either emotional hypo- or hyper-reactivity compared with healthy, noncriminal controls. Offenders were recruited from high-security forensic treatment facilities and penal institutions and underwent functional magnetic resonance imaging during a financial decision-making task. In this task, participants were required to choose between low-risk (bonds) and high-risk alternatives (stocks). Bonds were always the safe choice; stocks could win or lose, with a varying degree of uncertainty. We found that emotionally hypo-reactive offenders differed most from healthy controls by showing diminished neural activation in the rostral anterior cingulate cortex in response to uncertainty as well as decreased activity in the prefrontal cortex when trying to regulate their behavior accordingly (i.e., when consistently choosing "safe alternatives"). Hence, the data indicate that emotionally hypo-reactive offenders (with psychopathic traits) constitute a special subgroup within antisocial offenders characterized in particular by a limited capacity to emotionally represent uncertainty and to anticipate punishment.

  12. Equipment characterization to mitigate risks during transfers of cell culture manufacturing processes.

    PubMed

    Sieblist, Christian; Jenzsch, Marco; Pohlscheidt, Michael

    2016-08-01

    The production of monoclonal antibodies by mammalian cell culture in bioreactors up to 25,000 L is state of the art technology in the biotech industry. During the lifecycle of a product, several scale up activities and technology transfers are typically executed to enable the supply chain strategy of a global pharmaceutical company. Given the sensitivity of mammalian cells to physicochemical culture conditions, process and equipment knowledge are critical to avoid impacts on timelines, product quantity and quality. Especially, the fluid dynamics of large scale bioreactors versus small scale models need to be described, and similarity demonstrated, in light of the Quality by Design approach promoted by the FDA. This approach comprises an associated design space which is established during process characterization and validation in bench scale bioreactors. Therefore the establishment of predictive models and simulation tools for major operating conditions of stirred vessels (mixing, mass transfer, and shear force.), based on fundamental engineering principles, have experienced a renaissance in the recent years. This work illustrates the systematic characterization of a large variety of bioreactor designs deployed in a global manufacturing network ranging from small bench scale equipment to large scale production equipment (25,000 L). Several traditional methods to determine power input, mixing, mass transfer and shear force have been used to create a data base and identify differences for various impeller types and configurations in operating ranges typically applied in cell culture processes at manufacturing scale. In addition, extrapolation of different empirical models, e.g. Cooke et al. (Paper presented at the proceedings of the 2nd international conference of bioreactor fluid dynamics, Cranfield, UK, 1988), have been assessed for their validity in these operational ranges. Results for selected designs are shown and serve as examples of structured

  13. Characterization and health risk assessment of VOCs in occupational environments in Buenos Aires, Argentina

    NASA Astrophysics Data System (ADS)

    Colman Lerner, J. E.; Sanchez, E. Y.; Sambeth, J. E.; Porta, A. A.

    2012-08-01

    To detect volatile organic compounds (VOCs) in indoor air in small enterprises in La Plata city and surrounding areas, sampling was conducted using passive diffusion monitors (3M-3500) and analysis of the samples were performed byCG-FID. Analytic methodology was optimized for 23 VOCs (n-alkanes, cycloalkanes, aromatic and chlorinated compounds, ketones and terpenes compounds) by determining the recovery factor and detection limit for each analyte. Different recovery values were obtained by desorbing with a mixture of dichloromethane: methanol (50:50), with a standard deviation lower than 5%. Enterprise analyzed included chemical analysis laboratories, sewing workrooms, electromechanical repair and car painting centers, take away food shops, and a photocopy center. The highest levels of VOCs were found to be in electromechanical repair and car painting centers (hexane, BTEX, CHCl3, CCl4) followed by chemical analysis laboratories and sewing workrooms. Cancer and noncancer risks were assessed using conventional approaches (HQ and LCR, US EPA) using the benzene, trichloroethylene, chloroform for cancer risk, and toluene, xylene and n-hexane, for noncancer risks as markers. The results showed different LCR for benzene and trichloroethylene between the different indoor environments analyzed (electromechanical repair and car painting center ≫ others) and chloroform (laboratory > others), but comparing with the results obtained by other research, are in similar order of magnitude for equivalents activities. Similar finding were founded for HQ. Comparing these results with the worker protection legislation the electromechanical repair and car painting center and chemical analysis laboratories are close to the limits advised by OSHA and ACGIH. These facts show the importance of the use of abatement technologies for the complete reduction of VOCs levels, to mitigate their impact in the worker's health and their venting to the atmosphere.

  14. Wind Characterization for the Assessment of Collision Risk During Flight Level Changes

    NASA Technical Reports Server (NTRS)

    Carreno, Victor; Chartrand, Ryan

    2009-01-01

    A model of vertical wind gradient is presented based on National Oceanic and Atmospheric Administration (NOAA) wind data. The objective is to have an accurate representation of wind to be used in Collision Risk Models (CRM) of aircraft procedures. Depending on how an aircraft procedure is defined, wind and the different characteristics of the wind will have a more severe or less severe impact on distances between aircraft. For the In-Trail Procedure, the non-linearity of the vertical wind gradient has the greatest impact on longitudinal distance. The analysis in this paper extracts standard deviation, mean, maximum, and linearity characteristics from the NOAA data.

  15. Trace Elemental Characterization of Chalk Dust and Their Associated Health Risk Assessment.

    PubMed

    Maruthi, Y A; Ramprasad, S; Lakshmana Das, N

    2017-02-01

    It is evident that chalk produces dust on use, i.e., particulate matter, which will alter the air quality of classrooms and can cause health hazards in teachers. The possible causes for health effects of chalk dust on teachers are still unclear. Hence, the aim of this study is to estimate the concentration of trace elements (Al, Cr, Mn, Fe, Co, Ni, Si, Pb) in chalk dust collected from classrooms by using ICP-MS. Both suspended and settled chalk dust was collected from selected classrooms. Suspended chalk dust was collected with PM2.5 filter paper using fine dust sampler, and settled chalk dust was collected by placing petriplates at a distance of 3 m from the board for a duration period of 30 min. Scanning electron microscopy images of chalk dust were taken up. Potential health risk analysis was also assessed. Results showed that Al, Fe, and Mn are in higher concentration (>1000 μg kg(-1)) in both settled and suspended chalk dust. Cr, Mn, Fe, Co, and Ni were beyond the minimal risk levels in both settled and suspended chalk dust. There are no minimal risk levels for the elements Al, Si, and Pb. The concentration of trace elements in suspended chalk dust was higher than that in settled chalk dust. The SEM images of PM2.5 filter papers (suspended chalk dust) showed that all pores of the sampled filter papers are clogged with chalk dust. The few SEM images of the settled chalk dust showed fibrous shape which is associated with good-quality chalk whereas others showed circular and more aggregated nature of chalk dust from low-quality chalk from which the dust production will be very high. As observed from the result that the trace elements concentration was high in the suspended chalk dust, the fact can be correlated with the SEM images which have shown high density of absorbed chalk dust. With reference to human health risk, dermal exposure was the main route of exposure followed by inhalation and ingestion. Al (aluminum), Fe (iron), Si (silicon), and Mn

  16. Risk factors associated with endometriosis: importance of study population for characterizing disease in the ENDO Study

    PubMed Central

    Peterson, C. Matthew; Johnstone, Erica B.; Hammoud, Ahmad O.; Stanford, Joseph B.; Varner, Michael W.; Kennedy, Anne; Chen, Zhen; Sun, Liping; Fujimoto, Victor Y.; Hediger, Mary L.; Buck Louis, Germaine M.

    2014-01-01

    OBJECTIVE We sought to identify risk factors for endometriosis and their consistency across study populations in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study. STUDY DESIGN In this prospective matched, exposure cohort design, 495 women aged 18–44 years undergoing pelvic surgery (exposed to surgery, operative cohort) were compared to an age- and residence-matched population cohort of 131 women (unexposed to surgery, populationcohort). Endometriosis was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging in the operative and population cohorts, respectively. Logistic regression estimated the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each cohort. RESULTS The incidence of visualized endometriosis was 40% in the operative cohort (11.8% stage 3–4 by revised criteria from the American Society for Reproductive Medicine), and 11% stage 3–4 in the population cohort by magnetic resonance imaging. An infertility history increased the odds of an endometriosis diagnosis in both the operative (AOR, 2.43; 95% CI, 1.57–3.76) and population (AOR, 7.91; 95% CI, 1.69–37.2) cohorts. In the operative cohort only, dysmenorrhea (AOR, 2.46; 95% CI, 1.28–4.72) and pelvic pain (AOR, 3.67; 95% CI, 2.44–5.50) increased the odds of diagnosis, while gravidity (AOR, 0.49; 95% CI, 0.32–0.75), parity (AOR, 0.42; 95% CI, 0.28–0.64), and body mass index (AOR, 0.95; 95% CI, 0.93–0.98) decreased the odds of diagnosis. In all sensitivity analyses for different diagnostic subgroups, infertility history remained a strong risk factor. CONCLUSION An infertility history was a consistent risk factor for endometriosis in both the operative and population cohorts of the ENDO Study. Additionally, identified risk factors for endometriosis vary based upon cohort selection and diagnostic accuracy. Finally, endometriosis in the population may be more common than recognized. PMID:23454253

  17. Characterization and risk assessment of polychlorinated biphenyls in city park soils of Xi'an, China.

    PubMed

    Lu, Hongxuan; Liu, Weiguo

    2015-03-01

    Polychlorinated biphenyl (PCB) concentrations in surface soil samples (0-10 cm) from 23 city parks (8 urban and 15 suburban) from Xi'an, China were presented. The average concentration of Σ7 PCBs among all the sites was 1.68 ng g(-1) dry weight. High detection frequency (100 %) of PCB 28 and PCB 52 suggested wide occurrence of PCB contaminations in Xi'an. Among these PCBs, PCB 28, 52 and 153 were the most dominant compounds (14.9 %, 39.3 % and 9.5 % of the Σ7 PCBs on average, respectively). "Urban fractionation effect" was found in Xi'An. In other words, PCB concentrations were higher in the urban city park soils than those in suburban park soils. The PCB contamination in Xi'an city park soils were at a low level based on the Dutch guideline. However, dioxin-like PCB congeners were detected from 12 parks, which indicated further investigation was urgently required in future. Furthermore, total PCB concentrations were used to evaluate the cancer risk via ingestion, dermal and inhalation and the results showed that the total cancer risk was at the very low level in this area.

  18. Characterization and ecological risk assessment of nanoparticulate CeO2 as a diesel fuel catalyst.

    PubMed

    Batley, Graeme E; Halliburton, Brendan; Kirby, Jason K; Doolette, Casey L; Navarro, Divina; McLaughlin, Mike J; Veitch, Colin

    2013-08-01

    Nanoparticulate cerium dioxide (nano-CeO2 ), when combusted as an additive to diesel fuel, was transformed from 6 nm to 14 nm sizes into particles near 43 nm, with no obvious change in the unit cell dimensions or crystalline form. Cerium sulfate, if formed during combustion, was below detection limits. Ceria nanoparticles were agglomerated within the soot matrix, with a mean aerodynamic diameter near 100 nm. The dissolution of cerium from the dried ceria catalyst in synthetic soft water was extremely small (<0.0006% or <0.2 µg Ce/L), with particles being highly agglomerated (<450 nm). Agglomeration was reduced in the presence of humic acid. In the combusted samples, soot was dominant, and the solubility of cerium in soft water showed an almost 100-fold increase in the <1 nm fraction compared to that before combustion. It appeared that the nano-CeO2 remained agglomerated within the soot matrix and would not be present as dispersed nanoparticles in aquatic or soil environments. Despite the increased dissolution, the solubility was not sufficient for the combusted ceria to represent a risk in aquatic ecosystems. The predicted environmental concentrations were still orders of magnitude below the predicted no effects concentration of near 1 mg/L. In the soil environment, any cerium released from soot materials would interact with natural colloids, decreasing cerium concentrations in soil solutions and further minimizing the potential risk to soil organisms.

  19. Emissions of particulate-bound elements from stationary diesel engine: Characterization and risk assessment

    NASA Astrophysics Data System (ADS)

    Betha, Raghu; Balasubramanian, Rajasekhar

    2011-09-01

    There has been an increasing concern about the emissions of airborne particulate matter (PM) from diesel engines because of their close association with adverse health and environmental impacts. Among the alternative fuels being considered, biodiesel made by the transesterification of waste cooking oil has received wide attention in recent years because of its low cost and the added advantage of reducing waste oil disposal. This study was conducted to make a comparative evaluation of the particulate-bound elements emitted from ultra low sulphur diesel (ULSD) and waste cooking oil-derived biodiesel (B100) and a blend of both the fuels (B50). It was observed that the PM mass concentrations were reduced by about 36% when B100 was used. Crustal elements such as Mg, K and Al were found to be in higher concentrations compared to other elements emitted from both B100 and ULSD. Zn, Cr, Cu, Fe, Ni, Mg, Ba, K were found to be higher in the biodiesel exhaust while Co, Pb, Mn, Cd, Sr, and As were found to be higher in the ULSD exhaust. To evaluate the potential health risk due to inhalation of PM emitted from diesel engines running on ULSD and B100, health risk estimates based on exposure and dose-response assessments of particulate-bound elements were calculated assuming exposure for 24 h. The findings indicate that the exposure to PM of the B100 exhaust is relatively more hazardous and may pose adverse health effects compared to ULSD.

  20. Characterizing the landscape dynamics of an invasive plant and risk of invasion using remote sensing.

    PubMed

    Bradley, Bethany A; Mustard, John F

    2006-06-01

    Improved understanding of the spatial dynamics of invasive plant species may lead to more effective land management and reduced future invasion. Here, we identified the spatial extents of nonnative cheatgrass (Bromus tectorum) in the north central Great Basin using remotely sensed data from Landsat MSS, TM, and ETM+. We compared cheatgrass extents in 1973 and 2001 to six spatially explicit landscape variables: elevation, aspect, hydrographic channels, cultivation, roads, and power lines. In 2001, Cheatgrass was 10% more likely to be found in elevation ranges from 1400 to 1700 m (although the data suggest a preferential invasion into lower elevations by 2001), 6% more likely on west and northwest facing slopes, and 3% more likely within hydrographic channels. Over this time period, cheatgrass expansion was also closely linked to proximity to land use. In 2001, cheatgrass was 20% more likely to be found within 3 km of cultivation, 13% more likely to be found within 700 m of a road, and 15% more likely to be found within 1 km of a power line. Finally, in 2001 cheatgrass was 26% more likely to be present within 150 m of areas occupied by cheatgrass in 1973. Using these relationships, we created a risk map of future cheatgrass invasion that may aid land management. These results highlight the importance of including land use variables and the extents of current plant invasion in predictions of future risk.

  1. Value of Donor-Specific Anti-HLA Antibody Monitoring and Characterization for Risk Stratification of Kidney Allograft Loss.

    PubMed

    Viglietti, Denis; Loupy, Alexandre; Vernerey, Dewi; Bentlejewski, Carol; Gosset, Clément; Aubert, Olivier; Duong van Huyen, Jean-Paul; Jouven, Xavier; Legendre, Christophe; Glotz, Denis; Zeevi, Adriana; Lefaucheur, Carmen

    2017-02-01

    The diagnosis system for allograft loss lacks accurate individual risk stratification on the basis of donor-specific anti-HLA antibody (anti-HLA DSA) characterization. We investigated whether systematic monitoring of DSA with extensive characterization increases performance in predicting kidney allograft loss. This prospective study included 851 kidney recipients transplanted between 2008 and 2010 who were systematically screened for DSA at transplant, 1 and 2 years post-transplant, and the time of post-transplant clinical events. We assessed DSA characteristics and performed systematic allograft biopsies at the time of post-transplant serum evaluation. At transplant, 110 (12.9%) patients had DSAs; post-transplant screening identified 186 (21.9%) DSA-positive patients. Post-transplant DSA monitoring improved the prediction of allograft loss when added to a model that included traditional determinants of allograft loss (increase in c statistic from 0.67; 95% confidence interval [95% CI], 0.62 to 0.73 to 0.72; 95% CI, 0.67 to 0.77). Addition of DSA IgG3 positivity or C1q binding capacity increased discrimination performance of the traditional model at transplant and post-transplant. Compared with DSA mean fluorescence intensity, DSA IgG3 positivity and C1q binding capacity adequately reclassified patients at lower or higher risk for allograft loss at transplant (category-free net reclassification index, 1.30; 95% CI, 0.94 to 1.67; P<0.001 and 0.93; 95% CI, 0.49 to 1.36; P<0.001, respectively) and post-transplant (category-free net reclassification index, 1.33; 95% CI, 1.03 to 1.62; P<0.001 and 0.95; 95% CI, 0.62 to 1.28; P<0.001, respectively). Thus, pre- and post-transplant DSA monitoring and characterization may improve individual risk stratification for kidney allograft loss. Copyright © 2017 by the American Society of Nephrology.

  2. Characterization of the vaginal microbiota among sexual risk behavior groups of women with bacterial vaginosis.

    PubMed

    Muzny, Christina A; Sunesara, Imran R; Kumar, Ranjit; Mena, Leandro A; Griswold, Michael E; Martin, David H; Lefkowitz, Elliot J; Schwebke, Jane R; Swiatlo, Edwin

    2013-01-01

    The pathogenesis of bacterial vaginosis (BV) remains elusive. BV may be more common among women who have sex with women (WSW). The objective of this study was to use 454 pyrosequencing to investigate the vaginal microbiome of WSW, women who have sex with women and men (WSWM), and women who have sex with men (WSM) with BV to determine if there are differences in organism composition between groups that may inform new hypotheses regarding the pathogenesis of BV. Vaginal swab specimens from eligible women with BV at the Mississippi State Department of Health STD Clinic were used. After DNA extraction, 454 pyrosequencing of PCR-amplified 16S rRNA gene sequences was performed. Sequence data was classified using the Ribosomal Database Program classifer. Complete linkage clustering analysis was performed to compare bacterial community composition among samples. Differences in operational taxonomic units with an abundance of ≥ 2% between risk behavior groups were determined. Alpha and beta diversity were measured using Shannon's Index implemented in QIIME and Unifrac analysis, respectively. 33 WSW, 35 WSWM, and 44 WSM were included. The vaginal bacterial communities of all women clustered into four taxonomic groups with the dominant taxonomic group in each being Lactobacillus, Lachnospiraceae, Prevotella, and Sneathia. Regarding differences in organism composition between risk behavior groups, the abundance of Atopobium (relative ratio (RR)=0.24; 95%CI 0.11-0.54) and Parvimonas (RR=0.33; 95%CI 0.11-0.93) were significantly lower in WSW than WSM, the abundance of Prevotella was significantly higher in WSW than WSWM (RR=1.77; 95%CI 1.10-2.86), and the abundance of Atopobium (RR=0.41; 95%CI 0.18-0.88) was significantly lower in WSWM than WSM. Overall, WSM had the highest diversity of bacterial taxa. The microbiology of BV among women in different risk behavior groups is heterogeneous. WSM in this study had the highest diversity of bacterial taxa. Additional studies are

  3. Characterization of the Vaginal Microbiota among Sexual Risk Behavior Groups of Women with Bacterial Vaginosis

    PubMed Central

    Muzny, Christina A.; Sunesara, Imran R.; Kumar, Ranjit; Mena, Leandro A.; Griswold, Michael E.; Martin, David H.; Lefkowitz, Elliot J.; Schwebke, Jane R.

    2013-01-01

    Background The pathogenesis of bacterial vaginosis (BV) remains elusive. BV may be more common among women who have sex with women (WSW). The objective of this study was to use 454 pyrosequencing to investigate the vaginal microbiome of WSW, women who have sex with women and men (WSWM), and women who have sex with men (WSM) with BV to determine if there are differences in organism composition between groups that may inform new hypotheses regarding the pathogenesis of BV. Methods Vaginal swab specimens from eligible women with BV at the Mississippi State Department of Health STD Clinic were used. After DNA extraction, 454 pyrosequencing of PCR-amplified 16S rRNA gene sequences was performed. Sequence data was classified using the Ribosomal Database Program classifer. Complete linkage clustering analysis was performed to compare bacterial community composition among samples. Differences in operational taxonomic units with an abundance of ≥2% between risk behavior groups were determined. Alpha and beta diversity were measured using Shannon’s Index implemented in QIIME and Unifrac analysis, respectively. Results 33 WSW, 35 WSWM, and 44 WSM were included. The vaginal bacterial communities of all women clustered into four taxonomic groups with the dominant taxonomic group in each being Lactobacillus, Lachnospiraceae, Prevotella, and Sneathia. Regarding differences in organism composition between risk behavior groups, the abundance of Atopobium (relative ratio (RR)=0.24; 95%CI 0.11-0.54) and Parvimonas (RR=0.33; 95%CI 0.11-0.93) were significantly lower in WSW than WSM, the abundance of Prevotella was significantly higher in WSW than WSWM (RR=1.77; 95%CI 1.10-2.86), and the abundance of Atopobium (RR=0.41; 95%CI 0.18-0.88) was significantly lower in WSWM than WSM. Overall, WSM had the highest diversity of bacterial taxa. Conclusion The microbiology of BV among women in different risk behavior groups is heterogeneous. WSM in this study had the highest diversity of

  4. Characterizing the impacts of water resources infrastructure, humans, and hydrologic nonstationarity on changes in flood risk across the Himalaya region

    NASA Astrophysics Data System (ADS)

    Tullos, D. D.

    2014-12-01

    As flood control infrastructure reaches its design life, and climate change, population growth, and urban migration increase flood risk, the historical paradigm of store-then-release floodwaters behind rigid infrastructure is of decreasing physical and socioeconomic value. Instead, a new paradigm of sustainable flood management is emerging, which can be framed in the context of three elements that can contribute to and/or mitigate flood risk: 1) water resources infrastructure, 2) policies and socioeconomics, and 3) changing climates and land use. In this presentation, I present the results of analysis on the role of these three elements in contributing to flood risk of the Sutlej River (India) and the Koshi River (Nepal) basins for six historical flood events. The Himalaya region was selected based on the a) increasing intensity of monsoonal rains, b) increasing prevalence of glacial lake outburst floods, c) water resources management that achieves short-term development goals but lacks long-term sustainability, and d) other socio-economic, environmental, and geopolitical factors. I develop and apply a flood risk management framework that is based on metrics for characterizing the losses associated with the three elements contributing to major floods in the Himalaya region. Derived from a variety of data sources, results highlight how, across different hydrogeologic settings and various flood magnitudes, the largest influences on high flood losses are associated with inflexible water resources infrastructure and inappropriate development and flood management policies. Particularly for the most destructive events, which are generally associated with landslides and other natural hazards in this region, the effectiveness of some types of traditional and inflexible flood management infrastructure, including large dams and levees, is limited. As opposed to the probability of a particular flood event, findings illustrate the importance of the damages side of the flood

  5. Development of a drone equipped with optimized sensors for nuclear and radiological risk characterization

    SciTech Connect

    Boudergui, K.; Carrel, F.; Domenech, T.; Guenard, N.; Poli, J. P.; Ravet, A.; Schoepff, V.; Woo, R.

    2011-07-01

    The MOBISIC project, funded by the Systematic Paris-Region cluster, is being developed in the context of local crisis (attack bombing in urban environment, in confined space such as an underground train tunnel etc.) or specific event securing (soccer world cup, political meeting etc.). It consists in conceiving, developing and experimenting a mobile, modular ('plug and play') and multi-sensors securing system. In this project, CEA LIST has suggested different solutions for nuclear risks detection and identification. It results in embedding a CZT sensor and a gamma camera in an indoor drone. This article first presents the different modifications carried out on the UAV and different sensors, and focuses then on the experimental performances. (authors)

  6. Improved Sampling Algorithms in the Risk-Informed Safety Margin Characterization Toolkit

    SciTech Connect

    Mandelli, Diego; Smith, Curtis Lee; Alfonsi, Andrea; Rabiti, Cristian; Cogliati, Joshua Joseph

    2015-09-01

    The RISMC approach is developing advanced set of methodologies and algorithms in order to perform Probabilistic Risk Analyses (PRAs). In contrast to classical PRA methods, which are based on Event-Tree and Fault-Tree methods, the RISMC approach largely employs system simulator codes applied to stochastic analysis tools. The basic idea is to randomly perturb (by employing sampling algorithms) timing and sequencing of events and internal parameters of the system codes (i.e., uncertain parameters) in order to estimate stochastic parameters such as core damage probability. This approach applied to complex systems such as nuclear power plants requires to perform a series of computationally expensive simulation runs given a large set of uncertain parameters. These types of analysis are affected by two issues. Firstly, the space of the possible solutions (a.k.a., the issue space or the response surface) can be sampled only very sparsely, and this precludes the ability to fully analyze the impact of uncertainties on the system dynamics. Secondly, large amounts of data are generated and tools to generate knowledge from such data sets are not yet available. This report focuses on the first issue and in particular employs novel methods that optimize the information generated by the sampling process by sampling unexplored and risk-significant regions of the issue space: adaptive (smart) sampling algorithms. They infer system response from surrogate models constructed from existing samples and predict the most relevant location of the next sample. It is therefore possible to understand features of the issue space with a small number of carefully selected samples. In this report, we will present how it is possible to perform adaptive sampling using the RISMC toolkit and highlight the advantages compared to more classical sampling approaches such Monte-Carlo. We will employ RAVEN to perform such statistical analyses using both analytical cases but also another RISMC code: RELAP-7.

  7. Characterization of Eyjafjallajökull volcanic ash particles and a protocol for rapid risk assessment

    PubMed Central

    Gislason, S. R.; Hassenkam, T.; Nedel, S.; Bovet, N.; Eiriksdottir, E. S.; Alfredsson, H. A.; Hem, C. P.; Balogh, Z. I.; Dideriksen, K.; Oskarsson, N.; Sigfusson, B.; Larsen, G.; Stipp, S. L. S.

    2011-01-01

    On April 14, 2010, when meltwaters from the Eyjafjallajökull glacier mixed with hot magma, an explosive eruption sent unusually fine-grained ash into the jet stream. It quickly dispersed over Europe. Previous airplane encounters with ash resulted in sandblasted windows and particles melted inside jet engines, causing them to fail. Therefore, air traffic was grounded for several days. Concerns also arose about health risks from fallout, because ash can transport acids as well as toxic compounds, such as fluoride, aluminum, and arsenic. Studies on ash are usually made on material collected far from the source, where it could have mixed with other atmospheric particles, or after exposure to water as rain or fog, which would alter surface composition. For this study, a unique set of dry ash samples was collected immediately after the explosive event and compared with fresh ash from a later, more typical eruption. Using nanotechniques, custom-designed for studying natural materials, we explored the physical and chemical nature of the ash to determine if fears about health and safety were justified and we developed a protocol that will serve for assessing risks during a future event. On single particles, we identified the composition of nanometer scale salt coatings and measured the mass of adsorbed salts with picogram resolution. The particles of explosive ash that reached Europe in the jet stream were especially sharp and abrasive over their entire size range, from submillimeter to tens of nanometers. Edges remained sharp even after a couple of weeks of abrasion in stirred water suspensions. PMID:21518890

  8. Marine ω-3 Polyunsaturated Fatty Acid Intake and Risk of Colorectal Cancer Characterized by Tumor-Infiltrating T Cells.

    PubMed

    Song, Mingyang; Nishihara, Reiko; Cao, Yin; Chun, Eunyoung; Qian, Zhi Rong; Mima, Kosuke; Inamura, Kentaro; Masugi, Yohei; Nowak, Jonathan A; Nosho, Katsuhiko; Wu, Kana; Wang, Molin; Giovannucci, Edward; Garrett, Wendy S; Fuchs, Charles S; Ogino, Shuji; Chan, Andrew T

    2016-09-01

    Marine ω-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid, possess potent immunomodulatory activity and may protect against cancer development. However, evidence relating marine ω-3 PUFAs to colorectal cancer (CRC) risk remains inconclusive. To test the hypothesis that marine ω-3 PUFA intake may be associated with lower risk of CRC subsets characterized by immune infiltrate. This prospective cohort study was conducted among participants in the Nurses' Health Study (1984-2010) and Health Professionals Follow-up Study (1986-2010). Intake of marine ω-3 PUFAs. Incidence of CRC characterized by CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+ T-cell densities in tumor tissue, measured by immunohistochemical and computer-assisted image analysis. Among 173 229 predominantly white participants, 125 172 with 2 895 704 person-years of follow-up provided data about marine ω-3 PUFA intake every 4 years through a validated food frequency questionnaire and followed up for incident CRC evaluation. Of 2504 CRC cases, we documented 614 (252 men, 362 women) from which we could assess T-cell infiltration in the tumor microenvironment. The inverse association of marine ω-3 PUFAs intake with CRC risk differed according to FOXP3+ T-cell infiltration: compared with intake of less than 0.15 g/d of marine ω-3 PUFAs, intake of at least 0.35 g/d was associated with a multivariable hazard ratio (HR) of 0.57 (95% CI, 0.40-0.81; P < .001 for trend) for FOXP3+ T-cell-high tumors. In contrast, the HR for FOXP3+ T-cell-low tumors was 1.14 (95% CI, 0.8-1.60) (P = .77 for trend; P = .01 for heterogeneity). No statistically significant differential association was found for high-density tumors (compared with low-density tumors) according to CD3+, CD8+, or CD45RO+ cell density (P ≥ .34 for heterogeneity for all comparisons). In functional assays, the suppressive activity of regulatory T cells was

  9. UTILIZATION OF RISK-BASED METHODOLOGY AND NON-DESTRUCTIVE ASSAY TECHNOLOGIES TO CHARACTERIZE AND DISPOSITION LEGACY LOW-LEVEL RADIOACTIVE WASTE

    SciTech Connect

    Wolf, J

    2004-12-03

    A scaled risk and technology based disposition path was developed to characterize and certify Lawrence Livermore National Laboratory (LLNL) legacy waste (LW) for disposal at Envirocare of Utah and the Nevada Test Site (NTS). A combination of LLNL and commercially provided non-destructive assay (NDA) techniques were utilized to characterize waste and facilitate the safe, efficient and cost-effective characterization and disposition of 490 cubic meters of LW in Fiscal Year (FY) 2004. The approach and technologies described in this paper are adaptable to most waste characterization programs and will be utilized to meet future project milestones.

  10. Characterizing the risk assessment of heavy metals and sampling uncertainty analysis in paddy field by geostatistics and GIS.

    PubMed

    Liu, Xingmei; Wu, Jianjun; Xu, Jianming

    2006-05-01

    For many practical problems in environmental management, information about soil heavy metals, relative to threshold values that may be of practical importance is needed at unsampled sites. The Hangzhou-Jiaxing-Huzhou (HJH) Plain has always been one of the most important rice production areas in Zhejiang province, China, and the soil heavy metal concentration is directly related to the crop quality and ultimately the health of people. Four hundred and fifty soil samples were selected in topsoil in HJH Plain to characterize the spatial variability of Cu, Zn, Pb, Cr and Cd. Ordinary kriging and lognormal kriging were carried out to map the spatial patterns of heavy metals and disjunctive kriging was used to quantify the probability of heavy metal concentrations higher than their guide value. Cokriging method was used to minimize the sampling density for Cu, Zn and Cr. The results of this study could give insight into risk assessment of environmental pollution and decision-making for agriculture.

  11. Prevalence, risk factors of infection and molecular characterization of trichomonads in puppies from French breeding kennels.

    PubMed

    Grellet, Aurélien; Brunopolack; Feugier, Alexandre; Boucraut-Baralon, Corine; Grandjean, Dominique; Vandewynckel, Laurine; Cian, Amandine; Meloni, Dionigia; Viscogliosi, Eric

    2013-11-08

    The trichomonad species Tritrichomonas fetus and Pentatrichomonas hominis were recently identified in the feces of dogs with diarrhea. However the prevalence and pathogenicity of these parasites in the canine population still remained poorly resolved. Therefore the aim of the present study was (1) to determine the prevalence of trichomonads infecting puppies living in French breeding kennels, (2) to confirm the predominance of P. hominis in dogs, (3) to investigate the genetic diversity of P. hominis isolates identified in the French canine population and (4) to evaluate the risk factors for infection by P. hominis and the influence of the parasite on feces consistency. A total of 215 both diarrheic and non-diarrheic puppies from 25 French breeding kennels were included in this epidemiological survey. Fecal samples from each puppy were examined for 6 gastrointestinal pathogens: parvovirus type 2 (CPV2), coronavirus, Toxocara canis, Cystoisospora ohioensis-complex, Cystoisospora canis, and Giardia intestinalis. A part of each collected stool was also tested for the presence of motile trichomonads by microscopy after culturing. The prevalence of trichomonad infection was 15.8% (34/215) among puppies and 20% (5/25) among breeding kennels. DNA from 26 of the 34 positive samples was successfully amplified using a trichomonad-specific primer pair. Analysis of the sequences of PCR products indicated that P. hominis was the only trichomonad infecting the canine population. All the puppies infected with P. hominis belonged to large breed dogs. Moreover, puppies from large breeding kennels, excreting a high level of G. intestinalis and/or excreting a high level of C. canis oocysts showed a higher probability of being positive for P. hominis infection. Univariate analysis also revealed an increased risk for P. hominis infection in puppies with abnormal feces. However, in a multivariate analysis, CPV2 was the only gastrointestinal pathogen associated with abnormal feces. Since

  12. Combined (18)F-Fluciclovine PET/MRI shows potential for detection and characterization of high-risk prostate cancer.

    PubMed

    Elschot, Mattijs; Selnæs, Kirsten M; Sandsmark, Elise; Krüger-Stokke, Brage; Størkersen, Øystein; Giskeødegård, Guro F; Tessem, May-Britt; Moestue, Siver A; Bertilsson, Helena; Bathen, Tone F

    2017-10-06

    The objective of this study is to investigate if quantitative imaging features derived from combined (18)F-Fluciclovine Positron Emission Tomograpy (PET) / multiparametric Magnetic Resonance Imaging (MRI) show potential for detection and characterization of primary prostate cancer. Methods: Twenty-eight (28) patients diagnosed with high-risk prostate cancer underwent simultaneous (18)F-Fluciclovine PET/MRI before radical prostatectomy. Volumes-of-interest (VOIs) of prostate tumors, benign prostatic hyperplasia (BPH) nodules, prostatitis, and healthy tissue were delineated on T2-weighted images using histology as a reference. Tumor VOIs were marked as high-grade (≥ Gleason Grade group 3) or not. MRI and PET features were extracted on the voxel and VOI-level. Partial least-squared discriminant analysis (PLS-DA) with double leave-one-patient-out cross validation was performed to classify tumor from benign tissue (BPH, prostatitis, healthy tissue) and high-grade tumor from other tissue (low-grade tumor, benign tissue). The performances of PET, MRI, and combined PET/MRI features were compared using the area under the receiver operating characteristic curve (AUC). Results: Voxel and VOI features were extracted from 40 tumor (26 high-grade), 36 BPH, 6 prostatitis, and 37 healthy tissue VOIs. PET/MRI performed better than MRI and PET for classification of tumor vs benign tissue (voxel: AUC 87%, 81%, and 83%; VOI: AUC 96%, 93%, and 93%, respectively) and high-grade tumor vs other tissue (voxel: AUC 85%, 79%, and 81%; VOI: AUC 93%, 93%, and 91%, respectively). T2-weighted MRI, diffusion-weighted MRI and PET features were most important for classification. Conclusion: Combined (18)F-Fluciclovine PET/multiparametric MRI shows potential for improving detection and characterization of high-risk prostate cancer, in comparison to MRI and PET alone. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  13. Workflow Integrating Fracture Permeability Characterization and Multiphase Flow Modeling for CO2 Storage and Risk Assessments in Fractured Reservoirs

    NASA Astrophysics Data System (ADS)

    Jin, G.; Pashin, J. C.

    2014-12-01

    Ensuring safe and permanent storage of sequestered CO2in naturally fractured geological media is vital for the success of geologic storage projects. Critical needs exist to develop advanced techniques to characterize and model fluid transport in naturally fractured reservoirs and seals. We have developed a scale-independent 3-D stochastic fracture permeability characterization workflow that employs multiple discrete fracture network (DFN) realizations. The workflow deploys a multidirectional flux-based upwind weighting scheme that is capable of modeling multiphase flow in highly heterogeneous fractured media. The techniques employed herein show great promise for increasing the accuracy of capacity determinations and the prediction of pressure footprints associated with injected CO2 plumes. The proposed workflow has been conducted in a simulation study of flow transport and risk assessment of CO2 injection into a deep fractured saline formation using geological parameters from Knox Group carbonate and Red Mountain shale rocks in central Alabama. A 3-D fracture permeability map was generated from multiple realizations of DFN models. A multiphase flow model composed of supercritical CO2 and saline water was applied to simulate CO2 plume evolution during and after injection. Injection simulation reveals significant permeability anisotropy that favors development of northeast-elongate CO2 plumes. The spreading front of the CO2 plume shows strong viscous fingering effects. Post-injection simulation indicates significant lateral spreading of CO2 near the top of the fractured formations because of the buoyancy of injectate in rock matrix and strata-bound vertical fractures. Risk assessment shows that although pressure drops faster in the fractured formations than in those lacking fractures, lateral movement of CO2 along natural fractures necessitates that the injectate be confined by widespread seals with high integrity.

  14. Towards improved characterization of high-risk releases using heterogeneous indoor sensor systems

    SciTech Connect

    Sreedharan, Priya; Sohn, Michael D.; Nazaroff, William W.; J. Gadgil, Ashok

    2010-06-30

    The sudden release of toxic contaminants that reach indoor spaces can be hazardous to building occupants. For an acutely toxic contaminant, the speed of the emergency response strongly influences the consequences to occupants. The design of a real time sensor system is made challenging both by the urgency and complex nature of the event, and by the imperfect sensors and models available to describe it. In this research, we use Bayesian modeling to combine information from multiple types of sensors to improve the characterization of a release. We discuss conceptual and algorithmic considerations for selecting and fusing information from disparate sensors. To explore system performance, we use both real tracer gas data from experiments in a three story building, along with synthetic data, including information from door position sensors. The added information from door position sensors is found to be useful for many scenarios, but not always. We discuss the physical conditions and design factors that affect these results, such as the influence of the door positions on contaminant transport. We highlight potential benefits of multisensor data fusion, challenges in realizing those benefits, and opportunities for further improvement.

  15. Methods to identify and characterize developmental neurotoxicity for human health risk assessment. I: behavioral effects.

    PubMed Central

    Cory-Slechta, D A; Crofton, K M; Foran, J A; Ross, J F; Sheets, L P; Weiss, B; Mileson, B

    2001-01-01

    Alterations in nervous system function after exposure to a developmental neurotoxicant may be identified and characterized using neurobehavioral methods. A number of methods can evaluate alterations in sensory, motor, and cognitive functions in laboratory animals exposed to toxicants during nervous system development. Fundamental issues underlying proper use and interpretation of these methods include a) consideration of the scientific goal in experimental design, b) selection of an appropriate animal model, c) expertise of the investigator, d) adequate statistical analysis, and e) proper data interpretation. Strengths and weaknesses of the assessment methods include sensitivity, selectivity, practicality, and variability. Research could improve current behavioral methods by providing a better understanding of the relationship between alterations in motor function and changes in the underlying structure of these systems. Research is also needed to develop simple and sensitive assays for use in screening assessments of sensory and cognitive function. Assessment methods are being developed to examine other nervous system functions, including social behavior, autonomic processes, and biologic rhythms. Social behaviors are modified by many classes of developmental neurotoxicants and hormonally active compounds that may act either through neuroendocrine mechanisms or by directly influencing brain morphology or neurochemistry. Autonomic and thermoregulatory functions have been the province of physiologists and neurobiologists rather than toxicologists, but this may change as developmental neurotoxicology progresses and toxicologists apply techniques developed by other disciplines to examine changes in function after toxicant exposure. PMID:11250808

  16. Characterizing Golden Eagle risk to lead and anticoagulant rodenticide exposure: A review

    USGS Publications Warehouse

    Herring, Garth; Eagles-Smith, Collin A.; Buck, Jeremy A.

    2017-01-01

    Contaminant exposure is among the many threats to Golden Eagle (Aquila chrysaetos) populations throughout North America, particularly lead poisoning and anticoagulant rodenticides (AR). These threats may act in concert with others (e.g., lead poisoning and trauma associated with striking objects) to exacerbate risk. Golden Eagles are skilled hunters but also exploit scavenging opportunities, making them particularly susceptible to contaminant exposure from ingesting tissues of poisoned or shot animals. Lead poisoning has long been recognized as an important source of mortality for Golden Eagles throughout North America. More recently, ARs have been associated with both sublethal and lethal effects in raptor species worldwide. In this review, we examine the current state of knowledge for lead and AR exposure in Golden Eagles, drawing from the broader raptor contaminant ecology literature. We examine lead and AR sources within Golden Eagle habitats, exposure routes and toxicity, effects on individuals and populations, synergistic effects, and data and information needs. Continued research addressing data needs and information gaps will help with Golden Eagle conservation planning.

  17. Characterization and Potential Environmental Risks of Leachate from Shredded Rubber Mulches

    PubMed Central

    Kanematsu, Masakazu; Hayashi, Ai; Denison, Michael S.; Young, Thomas M.

    2009-01-01

    In order to determine whether shredded rubber mulches (RM) posed water quality risks when used in stormwater best management practices (BMPs) such as bioretention basins, batch leaching tests were conducted to identify and quantify constituents in leachates from RM such as metal ions, nutrients, total organic carbon (TOC), and aryl hydrocarbon receptor (AhR) activity (determined by the chemically activated luciferase gene expression (CALUX) bioassay) at varied temperature and initial pH values. The results indicate that aqueous extracts of RM contain high concentrations of zinc (Zn) compared with wood mulches (WM), and its concentration increased at lower pH and higher temperature. Although methanol extracts of RM displayed high AhR activity, none of the aqueous extracts of RM had significant activity. Hence, while unknown constituents that have significant AhR activity are present in RM, they appear to be not measurably extracted by water under environmental conditions relevant for stormwater (5 < pH < 9, 10 < T < 40°C). Our results suggests that organic constituents in water extracts of RM which have AhR activity may not be of significant concern while leaching of Zn from RM appears to be a potentially larger water quality issue for RM. PMID:19450864

  18. Characterization and potential environmental risks of leachate from shredded rubber mulches.

    PubMed

    Kanematsu, Masakazu; Hayashi, Ai; Denison, Michael S; Young, Thomas M

    2009-08-01

    In order to determine whether shredded rubber mulches (RM) pose water quality risks when used in stormwater best management practices (BMPs) such as bioretention basins, batch leaching tests were conducted to identify and quantify constituents in leachates from RM such as metal ions, nutrients, total organic carbon (TOC), and aryl hydrocarbon receptor (AhR) activity (determined by the chemically activated luciferase gene expression (CALUX) bioassay) at varied temperature and initial pH values. The results indicate that aqueous extracts of RM contain high concentrations of zinc (Zn) compared with wood mulches (WM), and its concentration increased at lower pH and higher temperature. Although methanol extracts of RM displayed high AhR activity, none of the aqueous extracts of RM had significant activity. Hence, while unknown constituents that have significant AhR activity are present in RM, they appear to be not measurably extracted by water under environmental conditions relevant for stormwater (5

  19. In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa.

    PubMed

    Mutyal, Nikhil N; Radosevich, Andrew J; Bajaj, Shailesh; Konda, Vani; Siddiqui, Uzma D; Waxman, Irving; Goldberg, Michael J; Rogers, Jeremy D; Gould, Bradley; Eshein, Adam; Upadhye, Sudeep; Koons, Ann; Gonzalez-Haba Ruiz, Mariano; Roy, Hemant K; Backman, Vadim

    2015-07-01

    To reduce pancreatic cancer mortality, a paradigm shift in cancer screening is needed. Our group pioneered the use of low-coherence enhanced backscattering (LEBS) spectroscopy to predict the presence of pancreatic cancer by interrogating the duodenal mucosa. A previous ex vivo study (n = 203) demonstrated excellent diagnostic potential: sensitivity, 95%; specificity, 71%; and accuracy, 85%. The objective of the current case-control study was to evaluate this approach in vivo. We developed a novel endoscope-compatible fiber-optic probe to measure LEBS in the periampullary duodenum of 41 patients undergoing upper endoscopy. This approach enables minimally invasive detection of the ultrastructural consequences of pancreatic field carcinogenesis. The LEBS parameters and optical properties were significantly altered in patients harboring adenocarcinomas (including early-stage) throughout the pancreas relative to healthy controls. Test performance characteristics were excellent with sensitivity = 78%, specificity = 85%, and accuracy = 81%. Moreover, the LEBS prediction rule was not confounded by patients' demographics. We demonstrate the feasibility of in vivo measurement of histologically normal duodenal mucosa to predict the presence of adenocarcinoma throughout the pancreas. This represents the next step in establishing duodenal LEBS analysis as a prescreening technique that identifies clinically asymptomatic patients who are at elevated risk of PC.

  20. Redox subpopulations and the risk of cancer progression: a new method for characterizing redox heterogeneity

    NASA Astrophysics Data System (ADS)

    Xu, He N.; Li, Lin Z.

    2016-02-01

    It has been shown that a malignant tumor is akin to a complex organ comprising of various cell populations including tumor cells that are genetically, metabolically and functionally different. Our redox imaging data have demonstrated intra-tumor redox heterogeneity in all mouse xenografts derived from human melanomas, breast, prostate, and colon cancers. Based on the signals of NADH and oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD)) and their ratio, i.e., the redox ratio, which is an indicator of mitochondrial metabolic status, we have discovered several distinct redox subpopulations in xenografts of breast tumors potentially recapitulating functional/metabolic heterogeneity within the tumor. Furthermore, xenografts of breast tumors with higher metastatic potential tend to have a redox subpopulation whose redox ratio is significantly different from that of tumors with lower metastatic potential and usually have a bi-modal distribution of the redox ratio. The redox subpopulations from human breast cancer samples can also be very complex with multiple subpopulations as determined by fitting the redox ratio histograms with multi- Gaussian functions. In this report, we present a new method for identifying the redox subpopulations within individual breast tumor xenografts and human breast tissues, which may be used to differentiate between breast cancer and normal tissue and among breast cancer with different risks of progression.

  1. Data Analysis Approaches for the Risk-Informed Safety Margins Characterization Toolkit

    SciTech Connect

    Mandelli, Diego; Alfonsi, Andrea; Maljovec, Daniel P.; Parisi, Carlo; Cogliati, Joshua J.; Talbot, Paul W.; Smith, Curtis L.; Rabiti, Cristian; Picoco, Claudia

    2016-09-01

    In the past decades, several numerical simulation codes have been employed to simulate accident dynamics (e.g., RELAP5-3D, RELAP-7, MELCOR, MAAP). In order to evaluate the impact of uncertainties into accident dynamics, several stochastic methodologies have been coupled with these codes. These stochastic methods range from classical Monte-Carlo and Latin Hypercube sampling to stochastic polynomial methods. Similar approaches have been introduced into the risk and safety community where stochastic methods (such as RAVEN, ADAPT, MCDET, ADS) have been coupled with safety analysis codes in order to evaluate the safety impact of timing and sequencing of events. These approaches are usually called Dynamic PRA or simulation-based PRA methods. These uncertainties and safety methods usually generate a large number of simulation runs (database storage may be on the order of gigabytes or higher). The scope of this paper is to present a broad overview of methods and algorithms that can be used to analyze and extract information from large data sets containing time dependent data. In this context, “extracting information” means constructing input-output correlations, finding commonalities, and identifying outliers. Some of the algorithms presented here have been developed or are under development within the RAVEN statistical framework.

  2. Assessing vertebral fracture risk on volumetric quantitative computed tomography by geometric characterization of trabecular bone structure

    NASA Astrophysics Data System (ADS)

    Checefsky, Walter A.; Abidin, Anas Z.; Nagarajan, Mahesh B.; Bauer, Jan S.; Baum, Thomas; Wismüller, Axel

    2016-03-01

    The current clinical standard for measuring Bone Mineral Density (BMD) is dual X-ray absorptiometry, however more recently BMD derived from volumetric quantitative computed tomography has been shown to demonstrate a high association with spinal fracture susceptibility. In this study, we propose a method of fracture risk assessment using structural properties of trabecular bone in spinal vertebrae. Experimental data was acquired via axial multi-detector CT (MDCT) from 12 spinal vertebrae specimens using a whole-body 256-row CT scanner with a dedicated calibration phantom. Common image processing methods were used to annotate the trabecular compartment in the vertebral slices creating a circular region of interest (ROI) that excluded cortical bone for each slice. The pixels inside the ROI were converted to values indicative of BMD. High dimensional geometrical features were derived using the scaling index method (SIM) at different radii and scaling factors (SF). The mean BMD values within the ROI were then extracted and used in conjunction with a support vector machine to predict the failure load of the specimens. Prediction performance was measured using the root-mean-square error (RMSE) metric and determined that SIM combined with mean BMD features (RMSE = 0.82 +/- 0.37) outperformed MDCT-measured mean BMD (RMSE = 1.11 +/- 0.33) (p < 10-4). These results demonstrate that biomechanical strength prediction in vertebrae can be significantly improved through the use of SIM-derived texture features from trabecular bone.

  3. Coronary heart disease risk equivalence in diabetes and arterial diseases characterized by endothelial function and endothelial progenitor cell.

    PubMed

    Liao, Yun-fei; Feng, Yong; Chen, Lu-Lu; Zeng, Tian-shu; Yu, Fan; Hu, Li-jun

    2014-01-01

    patients (P<0.05). The results of this study supported the equivalents hypothesis and revealed that "CHD risk equivalents" were characterized by the consistent physiological changes of blood vessels in angiogenesis, repairing ability and endothelial function. © 2014.

  4. Commercial squids: characterization, assessment of potential health benefits/risks and discrimination based on mineral, lipid and vitamin E concentrations.

    PubMed

    Torrinha, A; Gomes, F; Oliveira, M; Cruz, R; Mendes, E; Delerue-Matos, C; Casal, S; Morais, S

    2014-05-01

    The most consumed squid species worldwide were characterized regarding their concentrations of minerals, fatty acids, cholesterol and vitamin E. Interspecific comparisons were assessed among species and geographical origin. The health benefits derived from squid consumption were assessed based on daily minerals intake and on nutritional lipid quality indexes. Squids contribute significantly to daily intake of several macro (Na, K, Mg and P) and micronutrients (Cu, Zn and Ni). Despite their low fat concentration, they are rich in long-chain omega-3 fatty acids, particularly docosahexaenoic (DHA) and eicosapentanoic (EPA) acids, with highly favorable ω-3/ω-6 ratios (from 5.7 to 17.7), reducing the significance of their high cholesterol concentration (140-549 mg/100g ww). Assessment of potential health risks based on minerals intake, non-carcinogenic and carcinogenic risks indicated that Loligo gahi (from Atlantic Ocean), Loligo opalescens (from Pacific Ocean) and Loligo duvaucelii (from Indic Ocean) should be eaten with moderation due to the high concentrations of Cu and/or Cd. Canonical discriminant analysis identified the major fatty acids (C14:0, C18:0, C18:1, C18:3ω-3, C20:4ω-6 and C22:5ω-6), P, K, Cu and vitamin E as chemical discriminators for the selected species. These elements and compounds exhibited the potential to prove authenticity of the commercially relevant squid species.

  5. The characterization and risk assessment of the `Red Forest` radioactive waste burial site at Chernobyl Nuclear Power Plant

    SciTech Connect

    Bungai, D.A.; Skalskij, A.S.; Dzhepo, S.P.; Waters, R.D.

    1996-06-01

    The `Red Forest` radioactive waste burials created during emergency clean-up activities at Chernobyl Nuclear Power Plant represent a serious source of radioactive contamination of the local ground water system with 9OSr concentration in ground water exceeding the drinking water standard by 3-4 orders of magnitude. In this paper we present results of our hydrogeological and radiological `Red Forest` site characterization studies, which allow us to estimate 9OSr subsurface migration parameters. We use then these parameters to assess long terrain radionuclide transport to groundwater and surface water, and to analyze associated health risks. Our analyses indicate that 9OSr transport via ground water pathway from `Red Forest` burials to the adjacent Pripyat River is relatively insignificant due to slow release of 9OSr from the waste burials (less than 1% of inventory per year) and due to long enough ground water residence time in the subsurface, which allows substantial decay of the radioactive contaminant. Tins result and our previous analyses indicate, that though conditions of radioactive waste storage in burials do not satisfy Ukrainian regulation on radiation protection, health risks caused by radionuclide migration to ground water from `Red Forest` burials do not justify application of expensive countermeasures.

  6. Risk-Informed Safety Margin Characterization (RISMC): Integrated Treatment of Aleatory and Epistemic Uncertainty in Safety Analysis

    SciTech Connect

    R. W. Youngblood

    2010-10-01

    The concept of “margin” has a long history in nuclear licensing and in the codification of good engineering practices. However, some traditional applications of “margin” have been carried out for surrogate scenarios (such as design basis scenarios), without regard to the actual frequencies of those scenarios, and have been carried out with in a systematically conservative fashion. This means that the effectiveness of the application of the margin concept is determined in part by the original choice of surrogates, and is limited in any case by the degree of conservatism imposed on the evaluation. In the RISMC project, which is part of the Department of Energy’s “Light Water Reactor Sustainability Program” (LWRSP), we are developing a risk-informed characterization of safety margin. Beginning with the traditional discussion of “margin” in terms of a “load” (a physical challenge to system or component function) and a “capacity” (the capability of that system or component to accommodate the challenge), we are developing the capability to characterize probabilistic load and capacity spectra, reflecting both aleatory and epistemic uncertainty in system response. For example, the probabilistic load spectrum will reflect the frequency of challenges of a particular severity. Such a characterization is required if decision-making is to be informed optimally. However, in order to enable the quantification of probabilistic load spectra, existing analysis capability needs to be extended. Accordingly, the INL is working on a next-generation safety analysis capability whose design will allow for much more efficient parameter uncertainty analysis, and will enable a much better integration of reliability-related and phenomenology-related aspects of margin.

  7. Characterization of agricultural drought risk by a two-dimensional copula

    NASA Astrophysics Data System (ADS)

    Vergni, Lorenzo; Todisco, Francesca; Mannocchi, Francesco

    2015-04-01

    In this work, the joint probability distribution of two agricultural drought characteristics (Relative Severity, RS, and Onset, O) has been modeled by a two-dimensional copula. The application is illustrated with reference to a single-station case study (Perugia, Central Italy) and to the crop sunflower, widely grown in Central Italy, usually under rainfed conditions. The 86-year time series of daily precipitation and maximum and minimum temperature from the Perugia station (Central Italy) were used to simulate the soil water dynamics in the root-zone of sunflower. For each year, single seasonal values of RS and O have been quantified by applying the theory of runs to the soil water volume dynamics, with a threshold equal to the crop critical point. RS derives from the summation of the severities (i.e. total water stress) of the drought runs occurred during the growing season. The attribute 'relative' is here used because the severity value is corrected taking into account both the available water capacity of the soil and the growing season length. Thus, RS is a non-dimensional value ranging between 0 (no water stress) and 1 (maximum theoretical water stress for a given growing season length). The characteristic O describes the water stress temporal position (with respect to the growing season length) and it derives from a weighted average of the times of occurrence of the different drought runs (run severities being the weights). O is a non-dimensional value that expresses the temporal position of water stress as percentage of residual growing season, and it ranges between 0 (drought location at harvest) and 1 (drought location at seeding). The information provided by this characteristic can be considered particularly useful in agricultural drought risk management, because, as it is known, the drought impact on crop yield (being equal the severity) can vary substantially with the sensitivity of the growth stages affected by water stress conditions. The analysis

  8. Characterizing the spatial distribution of multiple pollutants and populations at risk in Atlanta, Georgia.

    PubMed

    Pearce, John L; Waller, Lance A; Sarnat, Stefanie E; Chang, Howard H; Klein, Mitch; Mulholland, James A; Tolbert, Paige E

    2016-08-01

    Exposure metrics that identify spatial contrasts in multipollutant air quality are needed to better understand multipollutant geographies and health effects from air pollution. Our aim is to improve understanding of: (1) long-term spatial distributions of multiple pollutants; and (2) demographic characteristics of populations residing within areas of differing air quality. We obtained average concentrations for ten air pollutants (p=10) across a 12 km grid (n=253) covering Atlanta, Georgia for 2002-2008. We apply a self-organizing map (SOM) to our data to derive multipollutant patterns observed across our grid and classify locations under their most similar pattern (i.e, multipollutant spatial type (MST)). Finally, we geographically map classifications to delineate regions of similar multipollutant characteristics and characterize associated demographics. We found six MSTs well describe our data, with profiles highlighting a range of combinations, from locations experiencing generally clean air to locations experiencing conditions that were relatively dirty. Mapping MSTs highlighted that downtown areas were dominated by primary pollution and that suburban areas experienced relatively higher levels of secondary pollution. Demographics show the largest proportion of the overall population resided in downtown locations experiencing higher levels of primary pollution. Moreover, higher proportions of nonwhites and children in poverty reside in these areas when compared to suburban populations that resided in areas exhibiting relatively lower pollution. Our approach reveals the nature and spatial distribution of differential pollutant combinations across urban environments and provides helpful insights for identifying spatial exposure and demographic contrasts for future health studies. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Risk characterization of methyl tertiary butyl ether (MTBE) in tap water.

    PubMed

    Stern, B R; Tardiff, R G

    1997-12-01

    Methyl tertiary butyl ether (MTBE) can enter surface water and groundwater through wet atmospheric deposition or as a result of fuel leaks and spills. About 30% of the U.S. population lives in areas where MTBE is in regular use. Ninety-five percent of this population is unlikely to be exposed to MTBE in tap water at concentrations exceeding 2 ppb, and most will be exposed to concentrations that are much lower and may be zero. About 5% of this population may be exposed to higher levels of MTBE in tap water, resulting from fuel tank leaks and spills into surface or groundwater used for potable water supplies. This paper describes the concentration ranges found and anticipated in surface and groundwater, and estimates the distribution of doses experienced by humans using water containing MTBE to drink, prepare food, and shower/bathe. The toxic properties (including potency) of MTBE when ingested, inhaled, and in contact with the skin are summarized. Using a range of human toxic potency values derived from animal studies, margins of exposure (MOE) associated with alternative chronic exposure scenarios are estimated to range from 1700 to 140,000. Maximum concentrations of MTBE in tap water anticipated not to cause adverse health effects are determined to range from 700 to 14,000 ppb. The results of this analysis demonstrate that no health risks are likely to be associated with chronic and subchronic human exposures to MTBE in tap water. Although some individuals may be exposed to very high concentrations of MTBE in tap water immediately following a localized spill, these exposures are likely to be brief in duration due to large-scale dilution and rapid volatilization of MTBE, the institution of emergency response and remediation measures to minimize human exposures, and the low taste and odor thresholds of MTBE which ensure that its presence in tap water is readily detected at concentrations well below the threshold for human injury.

  10. Using NASA Remotely Sensed Data to Help Characterize Environmental Risk Factors for National Public Health Applications

    NASA Technical Reports Server (NTRS)

    Al-Hamdan, Mohammad; Crosson, William; Economou, Sigrid; Estes, Maurice, Jr.; Estes, Sue; Hemmings, Sarah; Kent, Shia; Quattrochi, Dale; Wade, Gina; McClure, Leslie

    2011-01-01

    NASA Marshall Space Flight Center is collaborating with the University of Alabama at Birmingham (UAB) School of Public Health and the Centers for Disease Control and Prevention (CDC) National Center for Public Health Informatics to address issues of environmental health and enhance public health decision making by utilizing NASA remotely sensed data and products. The objectives of this study are to develop high-quality spatial data sets of environmental variables, link these with public health data from a national cohort study, and deliver the linked data sets and associated analyses to local, state and federal end-user groups. Three daily environmental data sets will be developed for the conterminous U.S. on different spatial resolutions for the period 2003-2008: (1) spatial surfaces of estimated fine particulate matter (PM2.5) exposures on a 10-km grid utilizing the US Environmental Protection Agency (EPA) ground observations and NASA's MODerate-resolution Imaging Spectroradiometer (MODIS) data; (2) a 1-km grid of Land Surface Temperature (LST) using MODIS data; and (3) a 12-km grid of daily Solar Insolation (SI) using the North American Land Data Assimilation System (NLDAS) forcing data. These environmental data sets will be linked with public health data from the UAB REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study to determine whether exposures to these environmental risk factors are related to cognitive decline and other health outcomes. These environmental datasets and public health linkage analyses will be disseminated to end-users for decision making through the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) system.

  11. Genomic characterization of high-risk non-muscle invasive bladder cancer

    PubMed Central

    Pai, Sachin G.; Oberlin, Daniel T.; Rademaker, Alfred; Fedorchak, Kyle; Balasubramanian, Sohail; Elvin, Julia; Beaubier, Nike; Giles, Francis J.

    2016-01-01

    The genetic mechanisms associated with progression of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) have not been described. We conducted selective next-generation sequencing (NGS) of HR-NMIBC and compared the genomic profiles of cancers that responded to intravesical therapy and those that progressed to muscle-invasive or advanced disease. DNA was extracted from paraffin-embedded sections from 25 HR-NMIBCs (22 with T1HG; 3 with TaHG with or without carcinoma in situ). Ten patients with HR-NMIBC developed progression (pT2+ or N+) (“progressors”). Fifteen patients had no progression (“non-progressors”). Tissue from 11 patients with metastatic bladder cancer (BC) were analyzed for comparison. We found no difference in frequency of mutations of TP53, PIK3CA, or KMT2D between the primary tumors of progressors compared to non-progressors and metastatic tumors. An increased frequency of deletions of CDKN2A/B was identified in tumors at progression (37%) compared to non-progressors (6%) (p = 0.10). We found a significant decrease in total mutational burden (TMB) that has been associated with immunotherapy response comparing non-progressors, progressors and metastatic tumors at 15, 10.1 and 5.1 mutations/MB respectively (p = 0.02). This association suggests more advanced tumors have decreased neoantigen burden and may explain the mechanism of BCG response in non-progressors. We found no novel genetic drivers in progressors and HR-NMIBC had many genetic features similar to metastatic BC. Loss of CDKN2A/B may occur late during invasion of BC and may represent an important step in progression. Further research is necessary to evaluate TMB and loss of CDKN2A/B locus as a biomarker for progression of NMIBC. PMID:27750214

  12. Reduced Order Model Implementation in the Risk-Informed Safety Margin Characterization Toolkit

    SciTech Connect

    Mandelli, Diego; Smith, Curtis L.; Alfonsi, Andrea; Rabiti, Cristian; Cogliati, Joshua J.; Talbot, Paul W.; Rinaldi, Ivan; Maljovec, Dan; Wang, Bei; Pascucci, Valerio; Zhao, Haihua

    2015-09-01

    The RISMC project aims to develop new advanced simulation-based tools to perform Probabilistic Risk Analysis (PRA) for the existing fleet of U.S. nuclear power plants (NPPs). These tools numerically model not only the thermo-hydraulic behavior of the reactor primary and secondary systems but also external events temporal evolution and components/system ageing. Thus, this is not only a multi-physics problem but also a multi-scale problem (both spatial, µm-mm-m, and temporal, ms-s-minutes-years). As part of the RISMC PRA approach, a large amount of computationally expensive simulation runs are required. An important aspect is that even though computational power is regularly growing, the overall computational cost of a RISMC analysis may be not viable for certain cases. A solution that is being evaluated is the use of reduce order modeling techniques. During the FY2015, we investigated and applied reduced order modeling techniques to decrease the RICM analysis computational cost by decreasing the number of simulations runs to perform and employ surrogate models instead of the actual simulation codes. This report focuses on the use of reduced order modeling techniques that can be applied to any RISMC analysis to generate, analyze and visualize data. In particular, we focus on surrogate models that approximate the simulation results but in a much faster time (µs instead of hours/days). We apply reduced order and surrogate modeling techniques to several RISMC types of analyses using RAVEN and RELAP-7 and show the advantages that can be gained.

  13. Risk characterization data manual for Category D inactive liquid low-level waste tank systems at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1997-04-01

    This manual reports the results of a risk characterization of Category D inactive liquid low-level radioactive waste (LLLW) at the Oak Ridge National Laboratory (ORNL). The risk characterization is required by the Federal Facility Agreement between the Department of Energy-Oak Ridge Operations Office, the Environmental Protection Agency-Region IV, and the Tennessee Department of Environment and Conservation. The intent of the risk characterization is to determine relative priorities for assessment and remediation. When the scores for all tanks had been weighted and summed, the tanks were ranked in descending order on the basis of their total scores. The highest possible score for a tank is 30. The descending order represents the recommended priorities for evaluation: the higher the score, the higher the priority for evaluation.

  14. CHARACTERIZING THE SPATIAL DISTRIBUTION OF MULTIPLE POLLUTANTS AND POPULATIONS AT RISK IN ATLANTA, GEORGIA

    PubMed Central

    Pearce, John L.; Waller, Lance A.; Sarnat, Stefanie E.; Chang, Howard H.; Klein, Mitch; Mulholland, James A.; Tolbert, Paige E.

    2016-01-01

    Background Development of exposure metrics that identify contrasts in multipollutant air quality across space are needed to better understand multipollutant geographies and health effects from air pollution. Objective Our aim is to improve understanding of: 1) long-term spatial distributions of multiple pollutants across urban environments; and 2) demographic characteristics of populations residing within areas that experience differing long-term air quality in order to assist in the development of future epidemiologic studies. Methods Data available for this study included seven years of spatiotemporally resolved concentrations for ten ambient air pollutants across the Atlanta metropolitan area. To analyze, we first distinguish the long-term behavior of air pollution at each grid location (n=253) by calculating study period means for each pollutant (n=10). Then, we apply the self-organizing map (SOM) technique to derive patterns in the multipollutant combinations observed among grid cells, i.e., multipollutant spatial types (MSTs), project results onto an ‘organized map’, and classify each grid cell under its most similar MST. Finally, we geographically map grid cell classifications to delineate regions of similar multipollutant characteristics and characterize associated population demographics using geographic information systems. Results We found six MSTs well describe the nature of multipollutant combinations experienced at locations in our study area. MST profiles highlighted a range of combinations, from locations experiencing generally clean air quality (all pollutants low) to locations experiencing conditions that were relatively dirty (high long-term concentrations of several pollutants). Mapping the spatial distribution of MSTs revealed strong within-class contiguity and highlighted that downtown areas were dominated by primary pollution and that suburban areas experienced relatively higher levels of secondary pollution. Demographics show that the

  15. Responses of Lyngbya wollei to algaecide exposures and a risk characterization associated with their use.

    PubMed

    Calomeni, Alyssa J; Iwinski, Kyla J; Kinley, Ciera M; McQueen, Andrew; Rodgers, John H

    2015-06-01

    To make informed decisions regarding management of noxious algal growths, water resource managers require information on responses of target and non-target species to algaecide exposures. Periodic treatments of Phycomycin®-SCP (sodium carbonate peroxyhydrate) followed by Algimycin®-PWF (gluconate and citrate chelated copper) to control Lyngbya wollei growths for ten years provided an opportunity for a risk evaluation of treated coves in Lay Lake, AL. Abiotic sediment characteristics (acid soluble copper concentrations, acid volatile sulfides, percent organic matter and cation exchange capacity) and survival of Hyalella azteca and Chironomus dilutus were measured in sediment samples from treated and untreated coves to assess the bioavailability of potential copper-residuals. In laboratory studies to seek a more effective approach for managing the growth of Lyngbya, six algaecide treatments consisting of combinations of copper-based algaecides (Cutrine®-Ultra, Clearigate® and Algimycin®- PWF), a hydrogen peroxide based algaecide (Phycomycin®-SCP) and an adjuvant (Cide-Kick II) were assessed for efficacy in controlling L. wollei sampled from Lay Lake. The most efficient algaecide treatment was determined based on post-treatment algal wet weight and visual observations of responses to exposures. To estimate the margin of safety for non-target organisms, Pimephales promelas was exposed to the most efficacious treatment and a treatment of Phycomycin®-SCP followed by Algimycin®-PWF. Results from sediment experiments demonstrated that there were no measureable copper residuals and no adverse effects on H. azteca and C. dilutus from sediments following ten years of copper-based algaecide treatments. Based on the laboratory results, a treatment of Phycomycin®-SCP at 10.1 mg H2O2/L followed by Cide-Kick II at 0.2 mg/L and Algimycin®- PWF at 0.26 mg Cu/L could control the growth of Lyngbya wollei from Lay Lake, AL and enhance the margin of safety for non

  16. Using NASA Remotely Sensed Data to Help Characterize Environmental Risk Factors for National Public Health Applications

    NASA Astrophysics Data System (ADS)

    Al-Hamdan, M. Z.; Crosson, W. L.; Economou, S.; Estes, M., Jr.; Estes, S. M.; Hemmings, S. N.; Kent, S.; Loop, M.; Puckett, M.; Quattrochi, D. A.; Wade, G.; McClure, L.

    2012-12-01

    The overall goal of this study is to address issues of environmental health and enhance public health decision making by using NASA remotely sensed data and products. This study is a collaboration between NASA Marshall Space Flight Center, Universities Space Research Association (USRA), the University of Alabama at Birmingham (UAB) School of Public Health and the Centers for Disease Control and Prevention (CDC) Office of Surveillance, Epidemiology and Laboratory Services. The objectives of this study are to develop high-quality spatial data sets of environmental variables, link these with public health data from a national cohort study, and deliver the environmental data sets and associated public health analyses to local, state and federal end-user groups. Three daily environmental data sets were developed for the conterminous U.S. on different spatial resolutions for the period 2003-2008: (1) spatial surfaces of estimated fine particulate matter (PM2.5) on a 10-km grid using US Environmental Protection Agency (EPA) ground observations and NASA's MODerate-resolution Imaging Spectroradiometer (MODIS) data; (2) a 1-km grid of MODIS Land Surface Temperature (LST); and (3) a 12-km grid of daily incoming solar radiation and maximum and minimum air temperature using the North American Land Data Assimilation System (NLDAS) data. These environmental datasets were linked with public health data from the UAB REasons for Geographic and Racial Differences in Stroke (REGARDS) national cohort study to determine whether exposures to these environmental risk factors are related to cognitive decline, stroke and other health outcomes. These environmental national datasets will also be made available to public health professionals, researchers and the general public via the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) system, where they can be aggregated to the county-level, state-level, or regional-level as per users' need and downloaded in tabular, graphical

  17. Using NASA Remotely Sensed Data to Help Characterize Environmental Risk Factors for National Public Health Applications

    NASA Technical Reports Server (NTRS)

    Al-Hamdan, Mohammad; Crosson, William; Economou, Sigrid; Estes,Maurice, Jr.; Estes, Sue; Hemmings, Sarah; Kent, Shia; Puckett, Mark; Quattrochi, Dale; Wade, Gina; McClure, Leslie

    2012-01-01

    The overall goal of this study is to address issues of environmental health and enhance public health decision making by using NASA remotely sensed data and products. This study is a collaboration between NASA Marshall Space Flight Center, Universities Space Research Association (USRA), the University of Alabama at Birmingham (UAB) School of Public Health and the Centers for Disease Control and Prevention (CDC) Office of Surveillance, Epidemiology and Laboratory Services. The objectives of this study are to develop high-quality spatial data sets of environmental variables, link these with public health data from a national cohort study, and deliver the environmental data sets and associated public health analyses to local, state and federal end ]user groups. Three daily environmental data sets were developed for the conterminous U.S. on different spatial resolutions for the period 2003-2008: (1) spatial surfaces of estimated fine particulate matter (PM2.5) on a 10-km grid using US Environmental Protection Agency (EPA) ground observations and NASA's MODerate-resolution Imaging Spectroradiometer (MODIS) data; (2) a 1-km grid of MODIS Land Surface Temperature (LST); and (3) a 12-km grid of daily incoming solar radiation and maximum and minimum air temperature using the North American Land Data Assimilation System (NLDAS) data. These environmental datasets were linked with public health data from the UAB REasons for Geographic and Racial Differences in Stroke (REGARDS) national cohort study to determine whether exposures to these environmental risk factors are related to cognitive decline, stroke and other health outcomes. These environmental national datasets will also be made available to public health professionals, researchers and the general public via the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) system, where they can be aggregated to the county-level, state-level, or regional-level as per users f need and downloaded in tabular, graphical

  18. Characterization of selected organo-nitrogen herbicides in South Florida canals: exposure and risk assessments.

    PubMed

    Wilson, P Chris; Boman, Brian J

    2011-12-15

    Much uncertainty exists regarding the discharge characteristics of terrestrial-use herbicides into aquatic systems. This study evaluated the temporal distribution and concentrations of five commonly used herbicides (atrazine, bromacil, metolachlor, norflurazon, and simazine) in a typical South Florida watershed. Surface water samples were collected weekly over a 3-yr period from four canals and Ten Mile Creek. These systems received drainage water from a variety of land-uses, including residential, pastures, and citrus production. Herbicides were extracted and analyzed by GC-MS/SIM. Atrazine was most frequently detected (87% of samples) in the canal serving the residentially developed sub-basin, with median and maximum concentrations of 0.43 and 6.67 μg L(-1), respectively. Norflurazon was most frequently detected (90-95% of samples) in the systems serving agricultural production areas, with median and maximum concentrations ranging from 0.37-0.63 μg L(-1) and 1.98-6.97 μg L(-1), respectively. Bromacil was detected in 14-36% of samples with median and maximum concentrations ranging from 0.50-0.67 μg L(-1) and 2.31-4.96 μg L(-1), respectively. Metolachlor was detected in 1.8-10% of the samples, with median and maximum concentrations ranging from 0.16-0.2 μgL(-1) and 0.17-1.55 μg L(-1), respectively. Simazine was detected in 10-35% of the samples, with median and maximum concentrations ranging from 0.18-0.28 μg L(-1) and 0.37-1.35 μg L(-1), respectively. Bromacil+norflurazon was the most commonly detected (240 samples of 1060 total) binary combination of herbicides; whereas bromacil+norflurazon+simazine was the most frequently detected tertiary combination (58 samples). While detectable concentrations were present for significant periods of time, risks of acute toxicity were relatively low; affecting <1% of the potentially affected fraction (PAF) of plant species based on 90th centile exposure concentrations and 10th centile effects concentrations from

  19. Characterization of incident stroke signs and symptoms: findings from the atherosclerosis risk in communities study.

    PubMed

    Rathore, Saif S; Hinn, Albert R; Cooper, Lawton S; Tyroler, Herman A; Rosamond, Wayne D

    2002-11-01

    Although patterns of stroke occurrence and mortality have been well studied, few epidemiological data are available regarding the clinical characteristics of stroke events. We evaluated hospitalized stroke events reported in the Atherosclerosis Risk in Communities (ARIC) Study to describe the clinical characteristics of incident stroke. Confirmed stroke cases (n=474) were evaluated for stroke symptoms (headache, vertigo, gait disturbance, convulsions) and stroke signs (hemianopia, diplopia, speech deficits, paresis, paresthesia/sensory deficits) and their univariate associations with race, sex, and stroke subtype. Over 9.2 years of follow-up, 402 (85%) ischemic and 72 (15%) hemorrhagic strokes occurred. Frequency of stroke symptoms (95% CIs) were as follows: headache (27.4%; 23.4% to 31.4%), gait disturbance (10.8%; 7.9% to 13.6%), convulsions (4.4%; 2.6% to 6.3%), and vertigo (2.1%; 0.8% to 3.4%). Speech deficits occurred in 24.0% (20.2% to 27.9%), hemianopia in 14.6% (11.4% to 17.7%), and diplopia in 5.5% (3.4% to 7.5%) of cases. Most cases involved paresis (81.6%; 78.1% to 85.1%), while fewer cases experienced sensory deficits (44.5%; 40.0% to 49.0%). Blacks were more likely than whites to experience paresis (85.4% versus 78.2%; P=0.044). Men were more likely than women to experience a gait disturbance (14.4% versus 6.7%; P=0.007). Persons with hemorrhagic strokes had a higher proportion of headaches (55.6% versus 22.4%; P=0.001) and convulsions (11.1% versus 3.2%; P=0.003) than those with ischemic events, while speech and sensory deficits were more common in ischemic strokes (26.1% versus 12.5%, P=0.013, and 49.0% versus 19.4%, P=0.001, respectively). We present epidemiological data concerning the clinical characteristics of incident stroke in a population-based cohort. Although minor differences by race, sex, and stroke subtype were observed, data from additional follow-up are required to confirm observed variations.

  20. Health Risk Assessment for Uranium in Groundwater - An Integrated Case Study Based on Hydrogeological Characterization and Dose Calculation

    NASA Astrophysics Data System (ADS)

    Franklin, M. R.; Veiga, L. H.; Py, D. A., Jr.; Fernandes, H. M.

    2010-12-01

    The uranium mining and milling facilities of Caetité (URA) is the only active uranium production center in Brazil. Operations take place at a very sensitive semi-arid region in the country where water resources are very scarce. Therefore, any contamination of the existing water bodies may trigger critical consequences to local communities because their sustainability is closely related to the availability of the groundwater resources. Due to the existence of several uranium anomalies in the region, groundwater can present radionuclide concentrations above the world average. The radiological risk associated to the ingestion of these waters have been questioned by members of the local communities, NGO’s and even regulatory bodies that suspected that the observed levels of radionuclide concentrations (specially Unat) could be related to the uranium mining and milling operations. Regardless the origin of these concentrations the fear that undesired health effects were taking place (e.g. increase in cancer incidence) remain despite the fact that no evidence - based on epidemiological studies - is available. This paper intends to present the connections between the local hydrogeology and the radiological characterization of groundwater in the neighboring areas of the uranium production center to understand the implications to the human health risk due to the ingestion of groundwater. The risk assessment was performed, taking into account the radiological and the toxicological risks. Samples from 12 wells have been collected and determinations of Unat, Thnat, 226Ra, 228Ra and 210Pb were performed. The radiation-related risks were estimated for adults and children by the calculation of the annual effective doses. The potential non-carcinogenic effects due to the ingestion of uranium were evaluated by the estimation of the hazard index (HI). Monte Carlo simulations were used to calculate the uncertainty associated with these estimates, i.e. the 95% confidence interval

  1. A dietary pattern characterized by high intake of vegetables, fruits, and vegetable oils is associated with reduced risk of preeclampsia in nulliparous pregnant Norwegian women.

    PubMed

    Brantsaeter, Anne Lise; Haugen, Margaretha; Samuelsen, Sven Ove; Torjusen, Hanne; Trogstad, Lill; Alexander, Jan; Magnus, Per; Meltzer, Helle Margrete

    2009-06-01

    Several dietary substances have been hypothesized to influence the risk of preeclampsia. Our aim in this study was to estimate the association between dietary patterns during pregnancy and the risk of preeclampsia in 23,423 nulliparous pregnant women taking part in the Norwegian Mother and Child Cohort Study (MoBa). Women participating in MoBa answered questionnaires at gestational wk 15 (a general health questionnaire) and 17-22 (a FFQ). The pregnancy outcomes were obtained from the Medical Birth Registry of Norway. Exploratory factor analysis was used to assess the associations among food variables. Principal component factor analysis identified 4 primary dietary patterns that were labeled: vegetable, processed food, potato and fish, and cakes and sweets. Relative risks of preeclampsia were estimated as odds ratios (OR) and confounder control was performed with multiple logistic regression. Women with high scores on a pattern characterized by vegetables, plant foods, and vegetable oils were at decreased risk [relative risk (OR) for tertile 3 vs. tertile 1: 0.72; 95% CI: 0.62, 0.85]. Women with high scores on a pattern characterized by processed meat, salty snacks, and sweet drinks were at increased risk [OR for tertile 3 vs. tertile 1: 1.21; 95% CI: 1.03, 1.42]. These findings suggest that a dietary pattern characterized by high intake of vegetables, plant foods, and vegetable oils decreases the risk of preeclampsia, whereas a dietary pattern characterized by high consumption of processed meat, sweet drinks, and salty snacks increases the risk.

  2. A Dietary Pattern Characterized by High Intake of Vegetables, Fruits, and Vegetable Oils Is Associated with Reduced Risk of Preeclampsia in Nulliparous Pregnant Norwegian Women1–3

    PubMed Central

    Brantsæter, Anne Lise; Haugen, Margaretha; Samuelsen, Sven Ove; Torjusen, Hanne; Trogstad, Lill; Alexander, Jan; Magnus, Per; Meltzer, Helle Margrete

    2009-01-01

    Several dietary substances have been hypothesized to influence the risk of preeclampsia. Our aim in this study was to estimate the association between dietary patterns during pregnancy and the risk of preeclampsia in 23,423 nulliparous pregnant women taking part in the Norwegian Mother and Child Cohort Study (MoBa). Women participating in MoBa answered questionnaires at gestational wk 15 (a general health questionnaire) and 17–22 (a FFQ). The pregnancy outcomes were obtained from the Medical Birth Registry of Norway. Exploratory factor analysis was used to assess the associations among food variables. Principal component factor analysis identified 4 primary dietary patterns that were labeled: vegetable, processed food, potato and fish, and cakes and sweets. Relative risks of preeclampsia were estimated as odds ratios (OR) and confounder control was performed with multiple logistic regression. Women with high scores on a pattern characterized by vegetables, plant foods, and vegetable oils were at decreased risk [relative risk (OR) for tertile 3 vs. tertile 1: 0.72; 95% CI: 0.62, 0.85]. Women with high scores on a pattern characterized by processed meat, salty snacks, and sweet drinks were at increased risk [OR for tertile 3 vs. tertile 1: 1.21; 95% CI: 1.03, 1.42]. These findings suggest that a dietary pattern characterized by high intake of vegetables, plant foods, and vegetable oils decreases the risk of preeclampsia, whereas a dietary pattern characterized by high consumption of processed meat, sweet drinks, and salty snacks increases the risk. PMID:19369368

  3. Health risk characterization of chlorpyrifos using epidemiological dose-response data and probabilistic techniques: a case study with rice farmers in Vietnam.

    PubMed

    Phung, Dung Tri; Connell, Des; Yu, Qiming; Chu, Cordia

    2013-09-01

    Various methods for risk characterization have been developed using probabilistic approaches. Data on Vietnamese farmers are available for the comparison of outcomes for risk characterization using different probabilistic methods. This article addresses the health risk characterization of chlorpyrifos using epidemiological dose-response data and probabilistic techniques obtained from a case study with rice farmers in Vietnam. Urine samples were collected from farmers and analyzed for trichloropyridinol (TCP), which was converted into absorbed daily dose of chlorpyrifos. Adverse health response doses due to chlorpyrifos exposure were collected from epidemiological studies to develop dose-adverse health response relationships. The health risk of chlorpyrifos was quantified using hazard quotient (HQ), Monte Carlo simulation (MCS), and overall risk probability (ORP) methods. With baseline (prior to pesticide spraying) and lifetime exposure levels (over a lifetime of pesticide spraying events), the HQ ranged from 0.06 to 7.1. The MCS method indicated less than 0.05% of the population would be affected while the ORP method indicated that less than 1.5% of the population would be adversely affected. With postapplication exposure levels, the HQ ranged from 1 to 32.5. The risk calculated by the MCS method was that 29% of the population would be affected, and the risk calculated by ORP method was 33%. The MCS and ORP methods have advantages in risk characterization due to use of the full distribution of data exposure as well as dose response, whereas HQ methods only used the exposure data distribution. These evaluations indicated that single-event spraying is likely to have adverse effects on Vietnamese rice farmers.

  4. Characterization and assessment of potential environmental risk of tailings stored in seven impoundments in the Aries river basin, Western Romania

    PubMed Central

    2013-01-01

    Background The objective of this study was to examine the potential environmental risk of tailings resulted after precious and base metal ores processing, stored in seven impoundments located in the Aries river basin, Romania. The tailings were characterized by mineralogical and elemental composition, contamination indices, acid rock drainage generation potential and water leachability of hazardous/priority hazardous metals and ions. Multivariate statistical methods were used for data interpretation. Results Tailings were found to be highly contaminated with several hazardous/priority hazardous metals (As, Cu, Cd, Pb), and pose potential contamination risk for soil, sediments, surface and groundwater. Two out of the seven studied impoundments does not satisfy the criteria required for inert wastes, shows acid rock drainage potential and thus can contaminate the surface and groundwater. Three impoundments were found to be highly contaminated with As, Pb and Cd, two with As and other two with Cu. The tailings impoundments were grouped based on the enrichment factor, geoaccumulation index, contamination factor and contamination degree of 7 hazardous/priority hazardous metals (As, Cd, Cr, Cu, Ni, Pb, Zn) considered typical for the studied tailings. Principal component analysis showed that 47% of the elemental variability was attributable to alkaline silicate rocks, 31% to acidic S-containing minerals, 12% to carbonate minerals and 5% to biogenic elements. Leachability of metals and ions was ascribed in proportion of 61% to silicates, 11% to acidic minerals and 6% to the organic matter. A variability of 18% was attributed to leachability of biogenic elements (Na, K, Cl-, NO3-) with no potential environmental risk. Pattern recognition by agglomerative hierarchical clustering emphasized the grouping of impoundments in agreement with their contamination degree and acid rock drainage generation potential. Conclusions Tailings stored in the studied impoundments were found to

  5. Characterizing the intersection of Co-occurring risk factors for illicit drug abuse and dependence in a U.S. nationally representative sample.

    PubMed

    Kurti, Allison N; Keith, Diana R; Noble, Alyssa; Priest, Jeff S; Sprague, Brian; Higgins, Stephen T

    2016-11-01

    Few studies have attempted to characterize how co-occurring risk factors for substance use disorders intersect. A recent study examined this question regarding cigarette smoking and demonstrated that co-occurring risk factors generally act independently. The present study examines whether that same pattern of independent intersection of risk factors extends to illicit drug abuse/dependence using a U.S. nationally representative sample (National Survey on Drug Use and Health, 2011-2013). Logistic regression and classification and regression tree (CART) modeling were used to examine risk of past-year drug abuse/dependence associated with a well-established set of risk factors for substance use (age, gender, race/ethnicity, education, poverty, smoking status, alcohol abuse/dependence, mental illness). Each of these risk factors was associated with significant increases in the odds of drug abuse/dependence in univariate logistic regressions. Each remained significant in a multivariate model examining all eight risk factors simultaneously. CART modeling of these 8 risk factors identified subpopulation risk profiles wherein drug abuse/dependence prevalence varied from <1% to >80% corresponding to differing combinations of risk factors present. Alcohol abuse/dependence and cigarette smoking had the strongest associations with drug abuse/dependence risk. These results demonstrate that co-occurring risk factors for illicit drug/abuse dependence generally intersect in the same independent manner as risk factors for cigarette smoking, underscoring further fundamental commonalities across these different types of substance use disorders. These results also underscore the fundamental importance of differences in the presence of co-occurring risk factors when considering the often strikingly different prevalence rates of illicit drug abuse/dependence in U.S. population subgroups.

  6. Characterization and risk factors of vancomycin-resistant Enterococci (VRE) among animal-affiliated workers in Malaysia.

    PubMed

    Getachew, Y; Hassan, L; Zakaria, Z; Zaid, C Z M; Yardi, A; Shukor, R A; Marawin, L T; Embong, F; Aziz, S A

    2012-11-01

    This study determined the risk factors and characteristics of vancomycin-resistant Enterococci (VRE) among individuals working with animals in Malaysia. Targeted cross-sectional studies accompanied with laboratory analysis for the identification and characterization of resistance and virulence genes and with genotype of VRE were performed. VRE were detected in 9·4% (95% CI: 6·46-13·12) of the sampled populations. Enterococcus faecium, Enterococcus faecalis and Enterococcus gallinarum were isolated, and vanA was detected in 70% of the isolates. Enterococcus faecalis with vanB was obtained from one foreign poultry worker. At least one virulence gene was detected in >50% of Ent. faecium and Ent. faecalis isolates. The esp and gelE genes were common among Ent. faecium (58·3%) and Ent. faecalis (78%), respectively. The VRE species showed diverse RAPD profiles with some clustering of strains based on the individual's background. However, the risk factors found to be significantly associated with the prevalence of VRE were age (OR: 5·39, 95% CI: 1·98-14·61) and previous hospitalization (OR: 4·06, 95% CI: 1·33-12·35). VRE species isolated from individuals in this study have high level of vancomycin resistance, were genetically diverse and possessed the virulence traits. Age of individuals and history of hospitalization rather than occupational background determined VRE colonization. This study provides comprehensive findings on the epidemiological and molecular features of VRE among healthy individuals working with animals. © 2012 The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

  7. Characterization of risk factors for adjuvant radiotherapy-associated pain in a tri-racial/ethnic breast cancer population.

    PubMed

    Lee, Eunkyung; Takita, Cristiane; Wright, Jean L; Reis, Isildinha M; Zhao, Wei; Nelson, Omar L; Hu, Jennifer J

    2016-05-01

    Pain related to cancer or treatment is a critical quality of life issue for breast cancer survivors. In a prospective study of 375 patients with breast cancer (enrolled during 2008-2014), we characterized the risk factors for adjuvant radiotherapy (RT)-associated pain. Pain score was assessed at pre-RT and post-RT as the mean of 4 pain severity items (ie, pain at its worst, least, average, and now) from the Brief Pain Inventory with 11-point numeric rating scale (0-10). Pain scores of 4 to 10 were considered clinically relevant pain. The study consists of 58 non-Hispanic whites (15%), 78 black or African Americans (AA; 21%), and 239 Hispanic whites (HW; 64%). Overall, the prevalence of pre-RT, post-RT, and RT-associated clinically relevant pain was 16%, 31% and 20%, respectively. In univariate analysis, AA and HW had significantly higher pre-RT and post-RT pain than non-Hispanic whites. In multivariable logistic regression analysis, pre-RT pain was significantly associated with HW and obesity; post-RT pain was significantly associated with AA, HW, younger age, ≥2 comorbid conditions, above-median hotspot volume receiving >105% prescribed dose, and pre-RT pain score ≥4. Radiotherapy-associated pain was significantly associated with AA (odds ratio [OR] = 3.27; 95% confidence interval [CI] = 1.09-9.82), younger age (OR = 2.44, 95% CI = 1.24-4.79), and 2 or ≥3 comorbid conditions (OR = 3.06, 95% CI = 1.32-7.08; OR = 4.61, 95% CI = 1.49-14.25, respectively). These risk factors may help to guide RT decision-making process, such as hypofractionated RT schedule. Furthermore, effective pain management strategies are needed to improve quality of life in patients with breast cancer with clinically relevant pain.

  8. A Risk-Based Characterization of Sediment Contamination by Legacy and Emergent Contaminants of Concern in Coastal British Columbia, Canada.

    PubMed

    Morales-Caselles, Carmen; Desforges, Jean-Pierre W; Dangerfield, Neil; Ross, Peter S

    2017-08-01

    Sediments have long been used to help describe pollution sources, contaminated sites, trends over time, and habitat quality for marine life. We collected surficial sediments from 12 sites at an average seawater depth of 25 m in three near-urban areas of the Salish Sea (British Columbia, Canada) to investigate habitat quality for marine life, including heavily contaminated killer whales. Samples were analyzed using high-resolution instrumentation for a wide variety of congeners of polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs), hexabromocyclododecane (HBCDD), polybrominated biphenyls, polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans, organochlorine pesticides, and polychlorinated naphthalenes (PCNs). The top six contaminant classes detected in sediments were ∑PCB > ∑PBDE > ∑PCDD/F > DDT > ∑HBCDD > ∑PCN. Near-urban harbor sediments had up to three orders of magnitude higher concentrations of contaminants than more remote sites. With limited tools available to characterize biological risks associated with complex mixtures in the real world, we applied several available approaches to prioritize the pollutant found in our study: (1) sediment quality guidelines from the Canadian Council of Ministers of the Environment where available; (2) US NOAA effects range low and other international guidelines; (3) total TEQ for dioxin-like PCBs for the protection of mammals; and (4) the calculation of risk quotients. Our findings provide an indication of the state of contamination of coastal environments in British Columbia and guidance for chemical regulations and priority setting, as well as management actions including best-practices, dredging, disposal at sea, and source control. In this regard, the legacy PCB and the emergent PBDEs should command continued priority monitoring.

  9. Characterization of thigh and shank segment angular velocity during jump landing tasks commonly used to evaluate risk for ACL injury.

    PubMed

    Dowling, Ariel V; Favre, Julien; Andriacchi, Thomas P

    2012-09-01

    The dynamic movements associated with anterior cruciate ligament (ACL) injury during jump landing suggest that limb segment angular velocity can provide important information for understanding the conditions that lead to an injury. Angular velocity measures could provide a quick and simple method of assessing injury risk without the constraints of a laboratory. The objective of this study was to assess the inter-subject variations and the sensitivity of the thigh and shank segment angular velocity in order to determine if these measures could be used to characterize jump landing mechanisms. Additionally, this study tested the correlation between angular velocity and the knee abduction moment. Thirty-six healthy participants (18 male) performed drop jumps with bilateral and unilateral landing. Thigh and shank angular velocities were measured by a wearable inertial-based system, and external knee moments were measured using a marker-based system. Discrete parameters were extracted from the data and compared between systems. For both jumping tasks, the angular velocity curves were well defined movement patterns with high inter-subject similarity in the sagittal plane and moderate to good similarity in the coronal and transverse planes. The angular velocity parameters were also able to detect differences between the two jumping tasks that were consistent across subjects. Furthermore, the coronal angular velocities were significantly correlated with the knee abduction moment (R of 0.28-0.51), which is a strong indicator of ACL injury risk. This study suggested that the thigh and shank angular velocities, which describe the angular dynamics of the movement, should be considered in future studies about ACL injury mechanisms.

  10. Caresoil: A multidisciplinar Project to characterize, remediate, monitor and evaluate the risk of contaminated soils in Madrid (Spain)

    NASA Astrophysics Data System (ADS)

    Muñoz-Martín, Alfonso; Antón, Loreto; Granja, Jose Luis; Villarroya, Fermín; Montero, Esperanza; Rodríguez, Vanesa

    2016-04-01

    Soil contamination can come from diffuse sources (air deposition, agriculture, etc.) or local sources, these last being related to anthropogenic activities that are potentially soil contaminating activities. According to data from the EU, in Spain, and particularly for the Autonomous Community of Madrid, it can be considered that heavy metals, toxic organic compounds (including Non Aqueous Phases Liquids, NAPLs) and combinations of both are the main problem of point sources of soil contamination in our community. The five aspects that will be applied in Caresoil Program (S2013/MAE-2739) in the analysis and remediation of a local soil contamination are: 1) the location of the source of contamination and characterization of soil and aquifer concerned, 2) evaluation of the dispersion of the plume, 3) application of effective remediation techniques, 4) monitoring the evolution of the contaminated soil and 5) risk analysis throughout this process. These aspects involve advanced technologies (hydrogeology, geophysics, geochemistry,...) that require new developing of knowledge, being necessary the contribution of several researching groups specialized in the fields previously cited, as they are those integrating CARESOIL Program. Actually two cases concerning hydrocarbon spills, as representative examples of soil local contamination in Madrid area, are being studied. The first is being remediated and we are monitoring this process to evaluate its effectiveness. In the second location we are defining the extent of contamination in soil and aquifer to define the most effective remediation technique.

  11. Estimating exposure and dose to characterize health risks: the role of human tissue monitoring in exposure assessment.

    PubMed Central

    Sexton, K; Callahan, M A; Bryan, E F

    1995-01-01

    Exposure assessment is an integral part of health risk characterization. Exposure assessments typically address three critical aspects of exposure: the number of people exposed to the environmental toxicant, at specific concentrations, for the time period of interest; the resulting dose; and the relative contribution of important sources and pathways to exposure/dose. Because historically both "point-of-contact" measurements and information about dose and related pharmacokinetic processes have been lacking, exposure assessments have had to rely on construction of "scenarios" to estimate exposure and dose. This could change, however, as advances in development of biologic markers of exposure and dose make it possible to measure and interpret toxicant concentrations in accessible human tissues. The increasing availability of "biomarkers," coupled with improvements in pharmacokinetic understanding, present opportunities to estimate ("reconstruct") exposure from measurements of dose and knowledge of intake and uptake parameters. Human tissue monitoring, however, is not a substitute for more traditional methods of measuring exposure, but rather a complementary approach. A combination of exposure measurements and dose measurements provides the most credible scientific basis for exposure assessment. PMID:7635107

  12. Characterization of the transport signals that mediate the nucleocytoplasmic traffic of low risk HPV11 E7

    SciTech Connect

    McKee, Courtney H.; Onder, Zeynep; Ashok, Aditya; Cardoso, Rebeca; Moroianu, Junona

    2013-08-15

    We previously discovered that nuclear import of low risk HPV11 E7 is mediated by its zinc-binding domain via a pathway that is independent of karyopherins/importins (Piccioli et al., 2010. Virology 407, 100–109). In this study we mapped and characterized a leucine-rich nuclear export signal (NES), {sub 76}IRQLQDLLL{sub 84}, within the zinc-binding domain that mediates the nuclear export of HPV11 E7 in a CRM1-dependent manner. We also identified a mostly hydrophobic patch {sub 65}VRLVV{sub 69} within the zinc-binding domain that mediates nuclear import of HPV11 E7 via hydrophobic interactions with the FG-repeats domain of Nup62. Substitutions of hydrophobic residues to alanine within the {sub 65}VRLVV{sub 69} sequence disrupt the nuclear localization of 11E7, whereas the R66A mutation has no effect. Overall the data support a model of nuclear entry of HPV11 E7 protein via hydrophobic interactions with FG nucleoporins at the nuclear pore complex. - Highlights: • HPV11 E7 has a leucine-rich nuclear export signal that mediates its nuclear export via CRM1. • HPV11 E7 interacts via its unique cNLS with the FG domain of Nup62. • Identification of a hydrophobic patch essential for nuclear localization of HPV11 E7.

  13. RISK CHARACTERIZATION OF DIOXINS

    EPA Science Inventory

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; "Dioxin") is the most toxic member of a family of structurally related compounds which are ubiquitous environmental pollutants. The most potent of these, the polyhalogenated dibenzo-p-dioxins and furans, were never produced int...

  14. RISK CHARACTERIZATION OF DIOXINS

    EPA Science Inventory

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; "Dioxin") is the most toxic member of a family of structurally related compounds which are ubiquitous environmental pollutants. The most potent of these, the polyhalogenated dibenzo-p-dioxins and furans, were never produced int...

  15. Risk characterization data manual for Category D inactive liquid low-level waste tank systems at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    Not Available

    1993-09-01

    This manual reports the results of a risk characterization of Category D inactive liquid low-level radioactive waste (LLLW) underground storage tanks (Uses) at the Oak Ridge National Laboratory (ORNL). The risk characterization is required by the Federal Facility Agreement between the Department of Energy-Oak Ridge Operations Office, the Environmental Protection Agency-Region IV, and the Tennessee Department of Environment and Conservation. The intent of the risk characterization is to determine relative priorities for assessment and remediation. A total of 55 FFA Category D inactive LLLW tanks are discussed in this manual. Of the 39 tanks at ORNL that have been accepted into the Environmental Restoration (ER) Program, all have been sampled for preliminary characterization, except for 5 tanks that were found to be empty plus I that was found not to exist. The remaining 16 tanks are in the Waste Management (WM) Program. Twelve were sampled for preliminary characterization, and four were found empty. Each sampled tank was scored on a scale of I to 5 on the basis of three criteria: (1) leak characteristics, (2) location, and (3) toxicological characteristics of residual sludges and liquids. Each criterion was assigned a weighing factor based on perceived importance. The criterion score multiplied by the weighting factor equaled the tank`s total score for that criterion. The three weighted criterion scores for each tank were then summed for a total score for that tank. When the scores for all tanks had been weighted and summed, the tanks were ranked in descending order on the basis of their total scores. The highest possible score for a tank is 30. The descending rank order represents the recommended priorities for evaluation: the higher the score, the higher the priority for evaluation. Of the 54 tanks sampled in the risk characterization, 23 tanks scored 16 or higher, 11 scored between 10 and 15, 5 scored between 4 and 9, and 15 scored 3 or less.

  16. Glycoalkaloid Levels in Solanum Microdontum and S. Jamesii Accessions: A Consideration in Parental Selection When Breeding for High Antioxidant Activity in Potato

    USDA-ARS?s Scientific Manuscript database

    Antioxidants are useful in reducing risk of several diseases associated with free radicals. While potatoes are not as high in antioxidants as fruits, the fact that large quantities of potatoes are consumed (~130 lbs per capita) suggests that any increase in tuber antioxidants would greatly benefit h...

  17. Assessing the joint impact of DNAPL source-zone behavior and degradation products on the probabilistic characterization of human health risk

    NASA Astrophysics Data System (ADS)

    Henri, Christopher V.; Fernàndez-Garcia, Daniel; de Barros, Felipe P. J.

    2016-02-01

    The release of industrial contaminants into the subsurface has led to a rapid degradation of groundwater resources. Contamination caused by Dense Non-Aqueous Phase Liquids (DNAPLs) is particularly severe owing to their limited solubility, slow dissolution and in many cases high toxicity. A greater insight into how the DNAPL source zone behavior and the contaminant release towards the aquifer impact human health risk is crucial for an appropriate risk management. Risk analysis is further complicated by the uncertainty in aquifer properties and contaminant conditions. This study focuses on the impact of the DNAPL release mode on the human health risk propagation along the aquifer under uncertain conditions. Contaminant concentrations released from the source zone are described using a screening approach with a set of parameters representing several scenarios of DNAPL architecture. The uncertainty in the hydraulic properties is systematically accounted for by high-resolution Monte Carlo simulations. We simulate the release and the transport of the chlorinated solvent perchloroethylene and its carcinogenic degradation products in randomly heterogeneous porous media. The human health risk posed by the chemical mixture of these contaminants is characterized by the low-order statistics and the probability density function of common risk metrics. We show that the zone of high risk (hot spot) is independent of the DNAPL mass release mode, and that the risk amplitude is mostly controlled by heterogeneities and by the source zone architecture. The risk is lower and less uncertain when the source zone is formed mostly by ganglia than by pools. We also illustrate how the source zone efficiency (intensity of the water flux crossing the source zone) affects the risk posed by an exposure to the chemical mixture. Results display that high source zone efficiencies are counter-intuitively beneficial, decreasing the risk because of a reduction in the time available for the production

  18. Risk-Informed Safety Margin Characterization Case Study: Selection of Electrical Equipment to Be Subjected to Environmental Qualification

    SciTech Connect

    D. P. Blanchard; R. W. Youngblood

    2014-06-01

    The Risk-Informed Safety Margin Characterization (RISMC) pathway of the DOE’s Light Water Reactor Sustainability (LWRS) program focuses on advancing the state of the art in safety analysis and risk assessment to support decision-making on nuclear power plant operation well beyond the originally designed lifetime of the plants (i.e., beyond 60 years). Among the issues being addressed in RISMC is the significance of SSC aging and how confident we are about our understanding of its impact on the margin between the loads SSCs are expected to see during normal operation and accident conditions, and the SSC capacities (their ability to resist those loads) as the SSCs age. In this paper, a summary is provided of a case study that examines SSC aging from an environmental qualification (EQ) perspective. The case study illustrates how the state of knowledge regarding SSC margin can be characterized given the overall integrated plant design, and was developed to demonstrate a method for deciding on which cables to focus, which cables are not so important from an environmental qualification margin standpoint, and what plant design features or operating characteristics determine the role that environmental qualification plays in establishing a safety case on which decisions regarding margin can be made. The selection of cables for which demonstration of margin with respect to aging and environmental challenges uses a technique known as Prevention Analysis. Prevention Analysis is a Boolean method for optimal selection of SSCs (that is, those combinations of SSCs both necessary and sufficient to meet a predetermined selection criterion) in a manner that allows demonstration that plant-level safety can be demonstrated by the collection of selected SSCs alone. Choosing the set of SSCs that is necessary and sufficient to satisfy the safety objectives, and demonstrating that the safety objectives can be met effectively, determines where resources are best allocated to assure SSC

  19. Overview of the Capstone depleted uranium study of aerosols from impact with armored vehicles: test setup and aerosol generation, characterization, and application in assessing dose and risk.

    PubMed

    Parkhurst, Mary Ann; Guilmette, Raymond A

    2009-03-01

    The Capstone Depleted Uranium (DU) Aerosol Characterization and Risk Assessment Study was conducted to generate data about DU aerosols generated during the perforation of armored combat vehicles with large-caliber DU penetrators, and to apply the data in assessments of human health risks to personnel exposed to these aerosols, primarily through inhalation, during the 1991 Gulf War or in future military operations. The Capstone study consisted of two components: 1) generating, sampling, and characterizing DU aerosols by firing at and perforating combat vehicles, and 2) applying the source-term quantities and characteristics of the aerosols to the evaluation of doses and risks. This paper reviews the background of the study including the bases for the study, previous reviews of DU particles and health assessments from DU used by the U.S. military, the objectives of the study components, the participants and oversight teams, and the types of exposures it was intended to evaluate. It then discusses exposure scenarios used in the dose and risk assessment and provides an overview of how the field tests and dose and risk assessments were conducted.

  20. Overview of the Capstone Depleted Uranium Study of Aerosols from Impact with Armored Vehicles: Test Setup and Aerosol Generation, Characterization, and Application in Assessing Dose and Risk

    SciTech Connect

    Parkhurst, MaryAnn; Guilmette, Raymond A.

    2009-03-01

    The Capstone Depleted Uranium (DU) Aerosol Characterization and Risk Assessment Study was conducted to generate data about DU aerosols generated during the perforation of armored combat vehicles with large-caliber DU penetrators, and to apply the data in assessments of human health risks to personnel exposed to these aerosols, primarily through inhalation, during the 1991 Gulf War or in future military operations. The Capstone study consisted of two components: 1) generating, sampling and characterizing DU aerosols by firing at and perforating combat vehicles and 2) applying the source-term quantities and characteristics of the aerosols to the evaluation of doses and risks. This paper reviews the background of the study including the bases for the study, previous reviews of DU particles and health assessments from DU used by the U.S. military, the objectives of the study components, the participants and oversight teams, and the types of exposures it was intended to evaluate. It then discusses exposure scenarios used in the dose and risk assessment and provides an overview of how the field tests and dose and risk assessments were conducted.

  1. PI3K/AKT, JNK, and ERK pathways are not crucial for the induction of cholesterol biosynthesis gene transcription in intestinal epithelial cells following treatment with the potato glycoalkaloid alpha-chaconine.

    PubMed

    Mandimika, Tafadzwa; Baykus, Hakan; Poortman, Jenneke; Garza, Cutberto; Kuiper, Harry; Peijnenburg, Ad

    2008-09-24

    We previously reported that exposure of the intestinal epithelial Caco-2 cell line to noncytotoxic concentrations of potato glycoalkaloids resulted in increased expression of cholesterol biosynthesis genes. Genes involved in mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (AKT) pathways and their downstream effectors such as Jun, c-Myc, and Fos also were induced. MAPK and PI3K/AKT pathways have been described to regulate the activity of sterol regulatory element binding transcription factors (SREBPs) and consequently the expression of cholesterol biosynthesis genes. In this study, to understand the mechanism of induction of cholesterol biosynthesis upon alpha-chaconine treatment, its effect on SREBP-2 protein levels was investigated. We also examined whether MAPK and PI3K/AKT pathways are required for the observed induction of these genes following exposure of cells to alpha-chaconine. Differentiated Caco-2 cells were pretreated with LY294002 (PI3K inhibitor), PD98059 (MEK1 inhibitor), or SP600125 (JNK inhibitor) or a combination of all inhibitors for 24 h prior to coincubation with 10 microM alpha-chaconine for 6 h. Significant increases in precursor and mature protein levels of SREBP-2 were observed after alpha-chaconine exposure. We also observed that alpha-chaconine treatment resulted in significant phosphorylation of AKT, extracellular signal related protein kinase (ERK), and c-jun N terminal protein kinase (JNK) but not that of p38. In general, the kinase inhibitor experiments revealed that phosphorylation of kinases of PI3K/AKT, ERK, and JNK pathways was not crucial for the induction of expression of cholesterol biosynthesis genes, with the exception of SC5DL. The transcription of this later gene was reduced when all three pathways were inhibited. On the basis of these results, it can be postulated that other mechanisms, which may be independent of the MAPK and PI3K/AKT pathways

  2. Analytical characterization of movements of the spinal column and risk assessment due to repeated movements of the upper limbs of building painters.

    PubMed

    Antonucci, Andrea; Forcella, Laura; Bonfiglioli, Roberta; Boscolo, Paolo; Violante, Francesco Saverio

    2016-09-01

    Manual activities of construction workers may induce musculoskeletal disorders. This study on a group of painters aimed to analytically characterize movements of the spinal column by both lumbar motion monitor and television cameras and to determine, using the Occupational Repetitive Actions (OCRA) Index method, the risk exerted by repeated movements of the upper limbs. The main results are: painting with a roller generally exposes workers to a lesser risk for upper limbs than painting with a brush; a roller-stick fixed at the wrong length can lead to stretching of the back at lumbar and cervical levels; to remain within the range of 'acceptable risk' (OCRA Index evaluation), a worker should not paint a vertical wall for over 3 h if using a roller and 2.5 h if painting with a brush; and, on average, a painter who paints for 5 h in a day lifts the bucket about 120,140 times.

  3. Procedures for addressing uncertainty and variability in exposure to characterize potential health risk from trichloroethylene contaminated groundwater at Beale Air Force Base in California

    SciTech Connect

    Bogen, K T; Daniels, J I; Hall, L C

    1999-09-01

    This study was designed to accomplish two objectives. The first was to provide to the US Air Force and the regulatory community quantitative procedures that they might want to consider using for addressing uncertainty and variability in exposure to better characterize potential health risk. Such methods could be used at sites where populations may now or in the future be faced with using groundwater contaminated with low concentrations of the chemical trichloroethylene (TCE). The second was to illustrate and explain the application of these procedures with respect to available data for TCE in ground water beneath an inactive landfill site that is undergoing remediation at Beale Air Force Base in California. The results from this illustration provide more detail than the more traditional conservative deterministic, screening-level calculations of risk, also computed for purposes of comparison. Application of the procedures described in this report can lead to more reasonable and equitable risk-acceptability criteria for potentially exposed populations at specific sites.

  4. Occurrence of pharmaceutically active compounds in surface waters of the Henares-Jarama-Tajo River system (Madrid, Spain) and a potential risk characterization.

    PubMed

    Fernández, C; González-Doncel, M; Pro, J; Carbonell, G; Tarazona, J V

    2010-01-01

    The Henares-Jarama-Tajo river system is the largest drainage basin in the Province of Madrid, Spain. This area is characterized by the presence of intensive urban and industrial activities influenced by a continental Mediterranean climate with rainfalls presenting substantial fluctuations along the different seasons. This research aimed to monitor seasonal variations in concentrations of 22 pharmaceutically active compounds (PhACs) in this river system and to establish the potential risk of sublethal effects on aquatic organisms. A total of 10 sampling sites were selected along the river system with samples collected in each of the four seasons during a year-round schedule. Most of the PhACs detected were present in sampling sites downstream in the vicinity of the most populated cities (i.e. Madrid, Guadalajara and Alcalá de Henares). Only two PhACs, fluoxetine and paraxantine, were detected in all sites regardless of the season, and showed median (+/- interquartile range) concentrations of 21.4 (+/-31.2) ng L(-1) and 8.5 (+/-5.3) ng L(-1), respectively. Other PhACs were detected with a frequency >80% and included, caffeine, diphenylhydantoin, hydrochlorotiazide, ibuprofen, ketoprofen, diclofenac, sulfamethoxazole, atenolol, naproxen, carbamazepine and propanolol. Seasonal variations were observed with the highest concentrations in December and the lowest in September. By combining measured environmental concentrations with toxicity data (either publicly available or obtained experimentally in our laboratory), and by calculating an Maximum Risk Index (MaxRI) that each combination of PhACs should have for non exceeding the risk threshold, a high potential for long-term risk (MaxRI<10) was estimated for most of the sampling sites and sampling dates. This research allowed the characterization of the potential risk for each of the PhACs to exert sublethal effects on aquatic organisms using acute screening methods, justifying the need for chronic data in order to

  5. Integrating mechanistic and polymorphism data to characterize human genetic susceptibility for environmental chemical risk assessment in the 21st century

    EPA Science Inventory

    Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be ap...

  6. Integrating mechanistic and polymorphism data to characterize human genetic susceptibility for environmental chemical risk assessment in the 21st century

    EPA Science Inventory

    Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be ap...

  7. Condom use, frequency of sex, and number of partners: multidimensional characterization of adolescent sexual risk-taking.

    PubMed

    Beadnell, Blair; Morrison, Diane M; Wilsdon, Anthony; Wells, Elizabeth A; Murowchick, Elise; Hoppe, Marilyn; Gillmore, Mary Rogers; Nahom, Deborah

    2005-08-01

    Sexual health research often relies on single risk indicators. However multi-variable composites may better capture the underlying construct of risk-taking. Latent Profile Analysis identified subgroups based on condom use consistency, partner numbers, and sex frequency among 605 adolescents. Three profiles were identified for each of grades 8 to 10 (Condom Users, Few Partners, and Risk-Takers) and 4 in grades 11 and 12 (Condom Users, One Partner Two Partners, and Risk-Takers). Inconsistent condom use groups reported more non-condom (and often less effective) birth control use and STD and pregnancy histories. Females had greater representation in the Few Partners, One Partners, and Two Partners groups, which also contained increasing proportions of participants in each subsequent year. Males had greater representation in the Risk-Takers group. A profile approach to measurement has methodological advantages, can add to substantive knowledge, and can inform content, timing, and targets of sexual health interventions.

  8. Inferring the potential risks of H7N9 infection by spatiotemporally characterizing bird migration and poultry distribution in eastern China

    PubMed Central

    2013-01-01

    Background In view of the rapid geographic spread and the increasing number of confirmed cases of novel influenza A(H7N9) virus infections in eastern China, we developed a diffusion model to spatiotemporally characterize the impacts of bird migration and poultry distribution on the geographic spread of H7N9 infection. Methods Three types of infection risks were estimated for 12 weeks, from February 4 to April 28, 2013, including (i) the risk caused by bird migration, (ii) the risk caused by poultry distribution, and (iii) the integrated risk caused by both bird migration and poultry distribution. To achieve this, we first developed a method for estimating the likelihood of bird migration based on available environmental and meteorological data. Then, we adopted a computational mobility model to estimate poultry distribution based on annual poultry production and consumption of each province/municipality. Finally, the spatiotemporal risk maps were created based on the integrated impacts of both bird migration and poultry distribution. Results In the study of risk estimation caused by bird migration, the likelihood matrix was estimated based on the 7-day temperature, from February 4 to April 28, 2013. It was found the estimated migrant birds mainly appear in the southeastern provinces of Zhejiang, Shanghai and Jiangsu during Weeks 1 to 4, and Week 6, followed by appearing in central eastern provinces of Shandong, Hebei, Beijing, and Tianjin during Weeks 7 to 9, and finally in northeastern provinces of Liaoning, Jilin, and Heilongjiang during Weeks 10 to 12. In the study of risk caused by poultry distribution, poultry distribution matrix was created to show the probability of poultry distribution. In spite of the fact that the majority of the initial infections were reported in Shanghai and Jiangsu, the relative risk of H7N9 infection estimated based on the poultry distribution model predicted that Jiangsu may have a slightly higher likelihood of H7N9 infection than

  9. RIPARIAN CHARACTERIZATION USING SUB-PIXEL ANALYSIS OF LANDSAT TM IMAGERY FOR USE IN ECOLOGICAL RISK ASSESSMENT

    EPA Science Inventory

    Landuse/land cover and riparian corridor characterization for 7 major watersheds in western Ohio was accomplished using sub-pixel analysis and traditional classification techniques. Areas
    representing forest, woodland, shrub, and herbaceous vegetation were delineated using a ...

  10. Contribution for tier 1 of the ecological risk assessment of Cunha Baixa uranium mine (Central Portugal): I soil chemical characterization.

    PubMed

    Pereira, R; Antunes, S C; Marques, S M; Gonçalves, F

    2008-02-15

    Within the tier 1 of a site specific risk assessment, the pseudo-total concentrations (extracted with aqua regia) and the potential mobile fractions of metals were determined to perform a preliminary evaluation of risks posed by contaminated soils from an abandoned uranium mine (Mangualde, Central Portugal). Considering the mobile fractions of metals, extracted with artificial rain water, aluminium and uranium were the most concerning elements, since their concentrations were above soil quality criteria values (SQGVs) established for both elements. However, according to the evaluation based on potential mobile fractions of elements, rather than on pseudo-total metal concentrations the risks were limited to sites within the exploitation area, where contamination derives mainly from past in-situ leaching activities of pore ore as well as from the deposition of sludge from the effluent pond. The exclusion of other sites under evaluation, from the risk assessment process, requires additional data provided by soil screening ecotoxicological assays.

  11. Characterization and source apportionment of health risks from ambient PM10 in Hong Kong over 2000-2011

    NASA Astrophysics Data System (ADS)

    Li, Zhiyuan; Yuan, Zibing; Li, Ying; Lau, Alexis K. H.; Louie, Peter K. K.

    2015-12-01

    Atmospheric particulate matter (PM) pollution is a major public health concern in Hong Kong. In this study, the spatiotemporal variations of health risks from ambient PM10 from seven air quality monitoring stations between 2000 and 2011 were analyzed. Positive matrix factorization (PMF) was adopted to identify major source categories of ambient PM10 and quantify their contributions. Afterwards, a point-estimated risk model was used to identify the inhalation cancer and non-cancer risks of PM10 sources. The long-term trends of the health risks from classified local and non-local sources were explored. Furthermore, the reason for the increase of health risks during high PM10 days was discussed. Results show that vehicle exhaust source was the dominant inhalation cancer risk (ICR) contributor (72%), whereas trace metals and vehicle exhaust sources contributed approximately 27% and 21% of PM10 inhalation non-cancer risk (INCR), respectively. The identified local sources accounted for approximately 80% of the ICR in Hong Kong, while contribution percentages of the non-local and local sources for INCR are comparable. The clear increase of ICR at high PM days was mainly attributed to the increase of contributions from coal combustion/biomass burning and secondary sulfate, while the increase of INCR at high PM days was attributed to the increase of contributions from the sources coal combustion/biomass burning, secondary nitrate, and trace metals. This study highlights the importance of health risk-based source apportionment in air quality management with protecting human health as the ultimate target.

  12. Characterizing the Benefits of Seismic Isolation for Nuclear Structures: A Framework for Risk-Based Decision Making

    SciTech Connect

    Bolisetti, Chandrakanth; Yu, Chingching; Coleman, Justin; Whittaker, Andrew; Kosbab, Ben

    2016-11-01

    This report provides a framework for assessing the benefits of seismic isolation and exercises the framework on a Generic Department of Energy Nuclear Facility (GDNF). These benefits are (1) reduction in the risk of unacceptable seismic performance and a dramatic reduction in the probability of unacceptable performance at beyond-design basis shaking, and (2) a reduction in capital cost at sites with moderate to high seismic hazard. The framework includes probabilistic risk assessment and estimates of overnight capital cost for the GDNF.

  13. Definition and GIS-based characterization of an integral risk index applied to a chemical/petrochemical area.

    PubMed

    Nadal, Martí; Kumar, Vikas; Schuhmacher, Marta; Domingo, José L

    2006-08-01

    A risk map of the chemical/petrochemical industrial area of Tarragona (Catalonia, Spain) was designed following a two-stage procedure. The first step was the creation of a ranking system (Hazard Index) for a number of different inorganic and organic pollutants: heavy metals, polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polychlorinated aromatic hydrocarbons (PAHs) by applying self-organizing maps (SOM) to persistence, bioaccumulation and toxicity properties of the chemicals. PCBs seemed to be the most hazardous compounds, while the light PAHs showed the minimum values. Subsequently, an Integral Risk Index was developed taking into account the Hazard Index and the concentrations of all pollutants in soil samples collected in the assessed area of Tarragona. Finally, a risk map was elaborated by representing the spatial distribution of the Integral Risk Index with a geographic information system (GIS). The results of the present study seem to indicate that the development of an integral risk map might be useful to help in making-decision processes concerning environmental pollutants.

  14. Expression of p-AKT characterizes adenoid cystic carcinomas of head and neck with a higher risk for tumor relapses

    PubMed Central

    Völker, Hans-Ullrich; Scheich, Matthias; Berndt, Annette; Haubitz, Imme; Metzger, Alexandra; Müller-Hermelink, Hans-Konrad; Kämmerer, Ulrike; Schmidt, Melanie

    2009-01-01

    Background Adenoid cystic carcinomas are rare tumors with an indolent clinical course, but frequent local relapses. The identification of tumors with a higher relapse risk seems to be interesting. Hence we investigated parameters of glucose metabolism, which were found associated with poor prognosis in other malignancies. Methods Specimen of 29 patients were investigated immunohistochemically with antibodies against p-AKT, TKTL-1 (transketolase-like 1), M2PK (M2 pyruvate kinase), and GLUT-1. Proliferation was investigated by staining with Ki67. The tumors were located at the major or minor salivary glands. Only the typical cribriform subtype was investigated. The initial tumor stage was pT1 or pT2. Results Expression of p-AKT was significantly (P = 0.036) associated with a higher relapse risk in multivariate analysis. Low expression of M2PK was non-significantly (P = 0.065) predictive for a higher risk. TKTL-1 and GLUT-1 were expressed in the majority of cases, albeit not associated with relapse risk. Conclusion Adenoid cystic carcinomas positive for p-AKT show a higher relapse risk. However, other parameters of glucose metabolism investigated here or proliferation (Ki67) were not predictive in this entity. Our findings demonstrate a possible background for therapeutic approaches targeting the inhibition of PI3K/AKT pathway. PMID:19545368

  15. Characterization of risk/exposure to climate extremes for the Brazilian Northeast—case study: Rio Grande do Norte

    NASA Astrophysics Data System (ADS)

    Silva, Bruce Kelly N.; Lucio, Paulo Sergio

    2015-10-01

    Climate change would increase the risk of floods or droughts. So far, only a few studies have projected changes in extremes on a regional or local scale. None of these studies relied on multiple climate proxies. Only some studies have started to estimate the exposure to flooding or drought as a proxy of risk; so, here, we present an exercise in risk analysis. Studies of climate change and its impacts rarely yield consensus on the distribution of exposure, vulnerability or possible outcomes. In addition, Northeast Brazil (NEB) is known for its temporal and spatial variability of rainfall and several studies have investigated this variability in order to understand damaging episodes such as droughts and floods. In NEB, the phenomenon of drought is a complex issue because millions of people are affected, and so, it is an important object of study in various fields of knowledge. One way of trying to argue about this phenomenon is through the concept of vulnerability. In this preliminary study, one will determine the risk or exposure factor to drought, which is one component of vulnerability, mainly concerning agricultural activities. The drought risk/exposure indicator was constructed based on three indices: the standardized precipitation index (SPI), the precipitation concentration period (PCP) and the precipitation concentration degree (PCD). The exposure indices showed an increase in high values from 1979 to 2008. On the contrary, the period from 1967 to 1996 showed that the risk factor in some micro-regions had low indices in a larger number; one can note that the dynamics of the factor is in an evolution between high and extremes.

  16. Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study.

    PubMed

    Lerman, Joseph B; Joshi, Aditya A; Chaturvedi, Abhishek; Aberra, Tsion M; Dey, Amit K; Rodante, Justin A; Salahuddin, Taufiq; Chung, Jonathan H; Rana, Anshuma; Teague, Heather L; Wu, Jashin J; Playford, Martin P; Lockshin, Benjamin A; Chen, Marcus Y; Sandfort, Veit; Bluemke, David A; Mehta, Nehal N

    2017-07-18

    Psoriasis, a chronic inflammatory disease associated with an accelerated risk of myocardial infarction, provides an ideal human model to study inflammatory atherogenesis in vivo. We hypothesized that the increased cardiovascular risk observed in psoriasis would be partially attributable to an elevated subclinical coronary artery disease burden composed of noncalcified plaques with high-risk features. However, inadequate efforts have been made to directly measure coronary artery disease in this vulnerable population. As such, we sought to compare total coronary plaque burden and noncalcified coronary plaque burden (NCB) and high-risk plaque (HRP) prevalence between patients with psoriasis (n=105), patients with hyperlipidemia eligible for statin therapy under National Cholesterol Education Program-Adult Treatment Panel III guidelines (n=100) who were ≈10 years older, and healthy volunteers without psoriasis (n=25). Patients underwent coronary computed-tomography angiography for total coronary plaque burden and NCB quantification and HRP identification, defined as low attenuation (<30 hounsfield units), positive remodeling (>1.10), and spotty calcification. A consecutive sample of the first 50 patients with psoriasis was scanned again 1 year after therapy. Despite being younger and at lower traditional risk than patients with hyperlipidemia, patients with psoriasis had increased NCB (mean±SD: 1.18±0.33 versus 1.11±0.32, P=0.02) and similar HRP prevalence (P=0.58). Furthermore, compared to healthy volunteers, patients with psoriasis had increased total coronary plaque burden (1.22±0.31 versus 1.04±0.22, P=0.001), NCB (1.18±0.33 versus 1.03±0.21, P=0.004), and HRP prevalence beyond traditional risk (odds ratio, 6.0; 95% confidence interval, 1.1-31.7; P=0.03). Last, among patients with psoriasis followed for 1 year, improvement in psoriasis severity was associated with improvement in total coronary plaque burden (β=0.45, 0.23-0.67; P<0.001) and NCB (β=0.53, 0

  17. Procedures for addressing uncertainty and variability in exposure to characterize potential health risk from trichloroethylene contaminated ground water at Beale Air Force Base in California

    SciTech Connect

    Daniels, J I; Bogen, K T; Hall, L C

    1999-10-05

    Conservative deterministic, screening-level calculations of exposure and risk commonly are used in quantitative assessments of potential human-health consequences from contaminants in environmental media. However, these calculations generally are based on multiple upper-bound point estimates of input parameters, particularly for exposure attributes, and can therefore produce results for decision makers that actually overstate the need for costly remediation. Alternatively, a more informative and quantitative characterization of health risk can be obtained by quantifying uncertainty and variability in exposure. This process is illustrated in this report for a hypothetical population at a specific site at Beale Air Force Base in California, where there is trichloroethylene (TCE) contaminated ground water and a potential for future residential use. When uncertainty and variability in exposure were addressed jointly for this case, the 95th-percentile upper-bound value of individual excess lifetime cancer risk was a factor approaching 10 lower than the most conservative deterministic estimate. Additionally, the probability of more than zero additional cases of cancer can be estimated, and in this case it is less than 0.5 for a hypothetical future residential population of up to 26,900 individuals present for any 7.6-y interval of a 70-y time period. Clearly, the results from application of this probabilistic approach can provide reasonable and equitable risk-acceptability criteria for a contaminated site.

  18. Variations of emission characterization of PAHs emitted from different utility boilers of coal-fired power plants and risk assessment related to atmospheric PAHs.

    PubMed

    Wang, Ruwei; Liu, Guijian; Zhang, Jiamei

    2015-12-15

    Coal-fired power plants (CFPPs) represent important source of atmospheric PAHs, however, their emission characterization are still largely unknown. In this work, the concentration, distribution and gas-particle partitioning of PM10- and gas-phase PAHs in flue gas emitted from different coal-fired utility boilers were investigated. Moreover, concentration and distribution in airborne PAHs from different functional areas of power plants were studied. People's inhalatory and dermal exposures to airborne PAHs at these sites were estimated and their resultant lung cancer and skin cancer risks were assessed. Results indicated that the boiler capacity and operation conditions have significant effect on PAH concentrations in both PM10 and gas phases due to the variation of combustion efficiency, whereas they take neglected effect on PAH distributions. The wet flue gas desulphurization (WFGD) takes significant effect on the scavenging of PAH in both PM10 and gas phases, higher scavenging efficiency were found for less volatile PAHs. PAH partitioning is dominated by absorption into organic matter and accompanied by adsorption onto PM10 surface. In addition, different partitioning mechanism is observed for individual PAHs, which is assumed arising from their chemical affinity and vapor pressure. Risk assessment indicates that both inhalation and dermal contact greatly contribute to the cancer risk for CFPP workers and nearby residents. People working in workshop are exposed to greater inhalation and dermal exposure risk than people living in nearby vicinity and working office.

  19. Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry

    PubMed Central

    Paula, André E.; Pereira, Rui; Andrade, Carlos E.; Felicio, Paula S.; Souza, Cristiano P.; Mendes, Deise R.P.; Volc, Sahlua; Berardinelli, Gustavo N.; Grasel, Rebeca S.; Sabato, Cristina S.; Viana, Danilo V.; Machado, José Carlos; Costa, José Luis; Mauad, Edmundo C.; Scapulatempo-Neto, Cristovam; Arun, Banu; Reis, Rui M.; Palmero, Edenir I.

    2016-01-01

    Background There are very few data about the mutational profile of families at-risk for hereditary breast and ovarian cancer (HBOC) from Latin America (LA) and especially from Brazil, the largest and most populated country in LA. Results Of the 349 probands analyzed, 21.5% were BRCA1/BRCA2 mutated, 65.3% at BRCA1 and 34.7% at BRCA2 gene. The mutation c.5266dupC (former 5382insC) was the most frequent alteration, representing 36.7% of the BRCA1 mutations and 24.0% of all mutations identified. Together with the BRCA1 c.3331_3334delCAAG mutation, these mutations constitutes about 35% of the identified mutations and more than 50% of the BRCA1 pathogenic mutations. Interestingly, six new mutations were identified. Additionally, 39 out of the 44 pathogenic mutations identified were not previously reported in the Brazilian population. Besides, 36 different variants of unknown significance (VUS) were identified. Regarding ancestry, average ancestry proportions were 70.6% European, 14.5% African, 8.0% Native American and 6.8% East Asian. Materials and methods This study characterized 349 Brazilian families at-risk for HBOC regarding their germline BRCA1/BRCA2 status and genetic ancestry. Conclusions This is the largest report of BRCA1/BRCA2 assessment in an at-risk HBOC Brazilian population. We identified 21.5% of patients harboring BRCA1/BRCA2 mutations and characterized the genetic ancestry of a sample group at-risk for hereditary breast cancer showing once again how admixed is the Brazilian population. No association was found between genetic ancestry and mutational status. The knowledge of the mutational profile in a population can contribute to the definition of more cost-effective strategies for the identification of HBOC families. PMID:27741520

  20. Contamination of public transports by Staphylococcus aureus and its carriage by biomedical students: point-prevalence, related risk factors and molecular characterization of methicillin-resistant strains.

    PubMed

    Mendes, Â; Martins da Costa, P; Rego, D; Beça, N; Alves, C; Moreira, T; Conceição, T; Aires-de-Sousa, M

    2015-08-01

    To analyse the contamination of public transports by Staphylococcus aureus and assess its carriage by biomedical students, focussing on the point-prevalence, related risk factors and molecular characterization of methicillin-resistant strains. Cross-sectional survey. Methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) isolated from handrails of buses (n = 112) and trains (n = 79) circulating in Porto and from nasal swabs of local university students (n = 475) were quantified, characterized by molecular typing methods and related to possible risk factors. The MRSA prevalence in buses (16.1%) was not significantly different from trains (8.9%). There was also no identifiable association between the counts of MSSA and MRSA in buses and trains and the number of travellers in each sampling day, specific routes (including those passing by main hospitals) or other risk factors. Of the students, 37.1% carried S. aureus, and having a part-time job or smoking were found to be risk factors for carriage. EMRSA-15 (ST22-SCCmecIVh) was the prevalent MRSA clonal lineage, found not only in the buses (n = 14) and trains (n = 2) but also in the single MRSA-carrier among the students. The characteristics of the community-associated Southwest Pacific MRSA clone were found in a single ST30-IVa isolate, which may suggest a recent SCCmec acquisition by an MSSA background in the community. The spread of EMRSA-15, a common hospital-associated lineage, among different public transports and as a nasal coloniser is of concern and warrants adequate public health control measures. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  1. Prospect theory and body mass: characterizing psychological parameters for weight-related risk attitudes and weight-gain aversion

    PubMed Central

    Lim, Seung-Lark; Bruce, Amanda S.

    2015-01-01

    We developed a novel decision-making paradigm that allows us to apply prospect theory in behavioral economics to body mass. 67 healthy young adults completed self-report measures and two decision-making tasks for weight-loss, as well as for monetary rewards. We estimated risk-related preference and loss aversion parameters for each individual, separately for weight-loss and monetary rewards choice data. Risk-seeking tendency for weight-loss was positively correlated with body mass index in individuals who desired to lose body weight, whereas the risk-seeking for momentary rewards was not. Risk-seeking for weight-loss was correlated to excessive body shape preoccupations, while aversion to weight-gain was correlated with self-reports of behavioral involvement for successful weight-loss. We demonstrated that prospect theory can be useful in explaining the decision-making process related to body mass. Applying prospect theory is expected to advance our understanding of decision-making mechanisms in obesity, which might prove helpful for improving healthy choices. PMID:25852628

  2. Prospect theory and body mass: characterizing psychological parameters for weight-related risk attitudes and weight-gain aversion.

    PubMed

    Lim, Seung-Lark; Bruce, Amanda S

    2015-01-01

    We developed a novel decision-making paradigm that allows us to apply prospect theory in behavioral economics to body mass. 67 healthy young adults completed self-report measures and two decision-making tasks for weight-loss, as well as for monetary rewards. We estimated risk-related preference and loss aversion parameters for each individual, separately for weight-loss and monetary rewards choice data. Risk-seeking tendency for weight-loss was positively correlated with body mass index in individuals who desired to lose body weight, whereas the risk-seeking for momentary rewards was not. Risk-seeking for weight-loss was correlated to excessive body shape preoccupations, while aversion to weight-gain was correlated with self-reports of behavioral involvement for successful weight-loss. We demonstrated that prospect theory can be useful in explaining the decision-making process related to body mass. Applying prospect theory is expected to advance our understanding of decision-making mechanisms in obesity, which might prove helpful for improving healthy choices.

  3. Yucca Mountain transportation routes: Preliminary characterization and risk analysis; Volume 2, Figures [and] Volume 3, Technical Appendices

    SciTech Connect

    Souleyrette, R.R. II; Sathisan, S.K.; di Bartolo, R.

    1991-05-31

    This report presents appendices related to the preliminary assessment and risk analysis for high-level radioactive waste transportation routes to the proposed Yucca Mountain Project repository. Information includes data on population density, traffic volume, ecologically sensitive areas, and accident history.

  4. Exploration of the spatial-Composite Risk Index (CRI) for the characterization of toxicokinetics in petrochemical active areas.

    PubMed

    Olawoyin, Richard

    2013-08-01

    The spatial modeling of the petrochemical active regions in the Niger Delta (ND), Nigeria was carried out through the analysis exploration and extraction of geospatial data and resultant risk maps were generated. The pollutants assessed include; heavy metals, polychlorinated aromatic hydrocarbons (PAHs), benzene-toluene-ethylene-xylene (BTEX), and total petroleum hydrocarbons (TPHs) and properties of the pollutants such as bioaccumulation, persistence and toxicity were used to calculate the Hazard Index (HI) and thus created a ranking system. The Composite Risk Index (CRI) was developed successively considering the concentrations of all pollutants and the computed HI using the samples collected in ND areas of Nigeria. The carcinogenic PAHs showed spatial abundance in the areas sampled and elevated levels of soil heavy metals were also observed. In this study, mathematical tool such as the artificial neural network (ANN) self-organizing map (SOM) and geostatistical analysis such as kriging were applied to develop the risk map of the areas which represent the spatial spread of the CRI. The results show that the application of spatially developed integral risk map for pollutant assessment is effective and facilitates with decision making with regards the environment and humans exposed in this region. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Characterizing the risk of respiratory syncytial virus in infants with older siblings: a population-based birth cohort study.

    PubMed

    Jacoby, P; Glass, K; Moore, H C

    2017-01-01

    From a population-based birth cohort of 245 249 children born in Western Australia during 1996-2005, we used linkage of laboratory and birth record datasets to obtain data including all respiratory syncytial virus (RSV) detections during infancy from a subcohort of 87 981 singleton children born in the Perth metropolitan area from 2000 to 2004. Using log binomial regression, we found that the risk of infant RSV detection increases with the number of older siblings, with those having ⩾3 older siblings experiencing almost three times the risk (relative risk 2·83, 95% confidence interval 2·46-3·26) of firstborn children. We estimate that 45% of the RSV detections in our subcohort were attributable to infection from an older sibling. The sibling effect was significantly higher for those infants who were younger during the season of peak risk (winter) than those who were older. Although older siblings were present in our cohort, they had very few RSV detections which could be temporally linked to an infant's infection. We conclude that RSV infection in older children leads to less severe symptoms but is nevertheless an important source of infant infection. Our results lend support to a vaccination strategy which includes family members in order to provide maximum protection for newborn babies.

  6. Characterization of 9p24 risk locus and colorectal adenoma and cancer: gene-environment interaction and meta-analysis

    PubMed Central

    Kocarnik, Jonathan D.; Hutter, Carolyn M.; Slattery, Martha L.; Berndt, Sonja I.; Hsu, Li; Duggan, David J.; Muehling, Jill; Caan, Bette J.; Beresford, Shirley A.A.; Rajkovic, Aleksandar; Sarto, Gloria E.; Marshall, James R.; Hammad, Nazik; Wallace, Robert B.; Makar, Karen W.; Prentice, Ross L.; Potter, John D.; Hayes, Richard B.; Peters, Ulrike

    2010-01-01

    Background A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive. Methods We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from four studies (total 3891 cases, 4490 controls): the Women’s Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case-control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene-environment interactions. Results SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19; 95% CI 1.01–1.40; p-trend 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11; 95% CI 0.99–1.25; p-trend 0.07), and not associated in DALS and MinnCCS. Evaluating for gene-environment interactions yielded no consistent results across the studies. A meta-analysis of seventeen studies (including these four) gave an OR per A allele of 1.07 (95% CI 1.03–1.12; p-trend 0.001). Conclusions Our results suggest the A allele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies. Impact If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia. PMID:20978172

  7. Paneth cell marker expression in intestinal villi and colon crypts characterizes dietary induced risk for mouse sporadic intestinal cancer.

    PubMed

    Wang, Donghai; Peregrina, Karina; Dhima, Elena; Lin, Elaine Y; Mariadason, John M; Augenlicht, Leonard H

    2011-06-21

    Nutritional and genetic risk factors for intestinal tumors are additive on mouse tumor phenotype, establishing that diet and genetic factors impact risk by distinct combinatorial mechanisms. In a mouse model of dietary-induced sporadic small and large intestinal cancer in WT mice in which tumor etiology, lag, incidence, and frequency reflect >90% of intestinal cancer in Western societies, dietary-induced risk altered gene expression profiles predominantly in villus cells of the histologically normal mucosa, in contrast to targeting of crypt cells by inheritance of an Apc(1638N) allele or homozygous inactivation of p21(Waf1/cip1), and profiles induced by each risk factor were distinct at the gene or functional group level. The dietary-induced changes in villus cells encompassed ectopic expression of Paneth cell markers (a lineage normally confined to the bottom of small intestinal crypts), elevated expression of the Wnt receptor Fzd5 and of EphB2 (genes necessary for Paneth cell differentiation and localization to the crypt bottom), and increased Wnt signaling in villus cells. Ectopic elevation of these markers was also present in the colon crypts, which are also sites of sporadic tumors in the nutritional model. Elevating dietary vitamin D(3) and calcium, which prevents tumor development, abrogated these changes in the villus and colon cells. Thus, common intestinal cancer driven by diet involves mechanisms of tumor development distinct from those mechanisms that cause tumors induced by the rare inheritance of a mutant adenomatous polyposis coli (Apc) allele. This is fundamental for understanding how common sporadic tumors arise and in evaluating relative risk in the population.

  8. Identification and Characterization of a Novel Association between Dietary Potassium and Risk of Crohn's Disease and Ulcerative Colitis.

    PubMed

    Khalili, Hamed; Malik, Sakshi; Ananthakrishnan, Ashwin N; Garber, John J; Higuchi, Leslie M; Joshi, Amit; Peloquin, Joanna; Richter, James M; Stewart, Kathleen O; Curhan, Gary C; Awasthi, Amit; Yajnik, Vijay; Chan, Andrew T

    2016-01-01

    Recent animal studies have identified that dietary salt intake may modify the risk and progression of autoimmune disorders through modulation of the IL-23/TH17 pathway, which is critical in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD). We conducted a prospective study of U.S. women enrolled in the Nurses' Health Study (NHS) and NHSII who provided detailed and validated information on diet and lifestyle beginning in 1984 in NHS and 1991 in NHSII. We confirmed incident cases of UC and CD reported through 2010 in NHS and 2011 in NHSII. We used Cox proportional hazards models to calculate hazard ratios and 95% confidence intervals. In a case-control study nested within these cohorts, we evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes involved in TH17 pathway and dietary potassium on risk of CD and UC. In a cohort of healthy volunteers, we also assessed the effect of supplemental potassium on development of naïve and memory T cells, differentiated with TGFβ1 or TH17 conditions. Among a total of 194,711 women over a follow-up of 3,220,247 person-years, we documented 273 cases of CD and 335 cases of UC. Dietary intake of potassium (Ptrend = 0.005) but not sodium (Ptrend = 0.44) was inversely associated with risk of CD. Although, both dietary potassium and sodium were not significantly associated with risk of UC, there was a suggestion of an inverse association with dietary potassium (Ptrend = 0.08). The association of potassium with risk of CD and UC appeared to be modified by loci involved in the TH17 pathway that have previously been associated with susceptibility to CD, particularly SNP rs7657746 (IL21) (Pinteraction = 0.004 and 0.01, respectively). In vitro, potassium enhanced the expression of Foxp3 in both naïve and memory CD4+ T cells via activating Smad2/3 and inhibiting Smad7 in TH17 cells. Dietary potassium is inversely associated with risk of CD with both in vitro and gene

  9. Characterizing Associations and SNP-Environment Interactions for GWAS-Identified Prostate Cancer Risk Markers—Results from BPC3

    PubMed Central

    Lindstrom, Sara; Schumacher, Fredrick; Siddiq, Afshan; Travis, Ruth C.; Campa, Daniele; Berndt, Sonja I.; Diver, W. Ryan; Severi, Gianluca; Allen, Naomi; Andriole, Gerald; Bueno-de-Mesquita, Bas; Chanock, Stephen J.; Crawford, David; Gaziano, J. Michael; Giles, Graham G.; Giovannucci, Edward; Guo, Carolyn; Haiman, Christopher A.; Hayes, Richard B.; Halkjaer, Jytte; Hunter, David J.; Johansson, Mattias; Kaaks, Rudolf; Kolonel, Laurence N.; Navarro, Carmen; Riboli, Elio; Sacerdote, Carlotta; Stampfer, Meir; Stram, Daniel O.; Thun, Michael J.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Weinstein, Stephanie J.; Yeager, Meredith; Henderson, Brian; Ma, Jing; Le Marchand, Loic; Albanes, Demetrius; Kraft, Peter

    2011-01-01

    Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade) and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10−28). Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test), where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade <8) tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined. PMID:21390317

  10. Isolation and characterization of mercury-resistant bacteria from sediments of Tagus Estuary (Portugal): implications for environmental and human health risk assessment.

    PubMed

    Figueiredo, Neusa L L; Canário, João; Duarte, Aida; Serralheiro, Maria Luísa; Carvalho, Cristina

    2014-01-01

    Mercury (Hg) contamination of aquatic systems has been recognized as a global and serious problem affecting both human and environmental health. In the aquatic ecosystems, mercurial compounds are microbiologically transformed with methylation responsible for generation of methylmercury (MeHg) and subsequent biomagnification in food chain, consequently increasing the risk of poisoning for humans and wildlife. High levels of Hg, especially MeHg, are known to exist in Tagus Estuary as a result of past industrial activities. The aim of this study was to isolate and characterize Hg-resistant bacteria from Tagus Estuary. Mercury-resistant (Hg-R) bacteria were isolated from sediments of two hotspots (Barreiro and North Channel) and one reserve area (Alcochete). Mercury contamination in these areas was examined and bacterial susceptibility to Hg compounds evaluated by determination of minimal inhibitory concentrations (MIC). The isolates characterization was based on morphological observation and biochemical testing. Bacteria characteristics, distribution, and Hg resistance levels were compared with metal levels. Barreiro and North Channel were highly contaminated with Hg, containing 126 and 18 μg/g total Hg, respectively, and in Alcochete, contamination was lower at 0.87 μg/g total Hg. Among the isolates there were aerobic and anaerobic bacteria, namely, sulfate-reducing bacteria, and Hg resistance levels ranged from 0.16 to 140 μg/ml for Hg(2+) and from 0.02 to 50.1 μg/ml for MeHg. The distribution of these bacteria and the resistance levels were consistent with Hg contamination along the depth of the sediments. Overall, results show the importance of the characterization of Tagus Estuary bacteria for ecological and human health risk assessment.

  11. Methicillin-resistant Staphylococcus aureus in HIV patients: risk factors associated with colonization and/or infection and methods for characterization of isolates - a systematic review.

    PubMed

    Ferreira, Dennis de Carvalho; Silva, Glaucilene Rodrigues da; Cavalcante, Fernanda Sampaio; Carmo, Flavia Lima do; Fernandes, Leonardo Alexandre; Moreira, Suelen; Passos, Mauro Romero Leal; Colombo, Ana Paula Vieira; Santos, Katia Regina Netto dos

    2014-11-01

    Staphylococcus aureus is an important cause of infections and HIV-infected individuals are frequently susceptible to this pathogen. The aim of this study was to perform a systematic review to identify both the risk factors associated with colonization/infection by methicillin-resistant S. aureus in HIV patients and the methods used for characterization of isolates. An electronic search of articles published between January 2001 and December 2013 was first conducted. Among 116 studies categorized as being at a quality level of A, B or C, only 9 studies were considered to have high methodological quality (level A). The majority of these studies were retrospective (4/9 studies). The risk factors associated with colonization/infection by S. aureus were use of antimicrobials (4/9 studies), previous hospitalization (4/9 studies) and low CD4+ T lymphocyte counts (<200 cells/μl) (3/9 studies). Culture in mannitol salt agar (3/9 studies) and the latex agglutination test (5/9 studies) were the main methods used for bacterial phenotypic identification. Genotypic profiles were accessed by pulsed-field gel electrophoresis (6/9 studies) and USA300 was the most prevalent lineage (5/9 studies). Most isolates were resistant to erythromycin (3/9 studies) and susceptible to vancomycin (4/9 studies). Ultimately, use of antimicrobials and previous hospitalization were the main risk factors for colonization/infection by methicillin-resistant S. aureus in HIV-infected individuals. However, the numbers of evaluated patients, the exclusion and inclusion criteria and the characterization of the S. aureus isolates were not uniform, which made it difficult to establish the characteristics associated with HIV patients who are colonized/infected by S. aureus.

  12. Methicillin-resistant Staphylococcus aureus in HIV patients: Risk factors associated with colonization and/or infection and methods for characterization of isolates – a systematic review

    PubMed Central

    Ferreira, Dennis de Carvalho; da Silva, Glaucilene Rodrigues; Cavalcante, Fernanda Sampaio; do Carmo, Flavia Lima; Fernandes, Leonardo Alexandre; Moreira, Suelen; Passos, Mauro Romero Leal; Colombo, Ana Paula Vieira; dos Santos, Katia Regina Netto

    2014-01-01

    Staphylococcus aureus is an important cause of infections and HIV-infected individuals are frequently susceptible to this pathogen. The aim of this study was to perform a systematic review to identify both the risk factors associated with colonization/infection by methicillin-resistant S. aureus in HIV patients and the methods used for characterization of isolates. An electronic search of articles published between January 2001 and December 2013 was first conducted. Among 116 studies categorized as being at a quality level of A, B or C, only 9 studies were considered to have high methodological quality (level A). The majority of these studies were retrospective (4/9 studies). The risk factors associated with colonization/infection by S. aureus were use of antimicrobials (4/9 studies), previous hospitalization (4/9 studies) and low CD4+ T lymphocyte counts (<200 cells/μl) (3/9 studies). Culture in mannitol salt agar (3/9 studies) and the latex agglutination test (5/9 studies) were the main methods used for bacterial phenotypic identification. Genotypic profiles were accessed by pulsed-field gel electrophoresis (6/9 studies) and USA300 was the most prevalent lineage (5/9 studies). Most isolates were resistant to erythromycin (3/9 studies) and susceptible to vancomycin (4/9 studies). Ultimately, use of antimicrobials and previous hospitalization were the main risk factors for colonization/infection by methicillin-resistant S. aureus in HIV-infected individuals. However, the numbers of evaluated patients, the exclusion and inclusion criteria and the characterization of the S. aureus isolates were not uniform, which made it difficult to establish the characteristics associated with HIV patients who are colonized/infected by S. aureus. PMID:25518036

  13. Characterization of the ecological interactions of Roundup Ready 2 Yield® soybean, MON 89788, for use in ecological risk assessment

    PubMed Central

    Horak, Michael J; Rosenbaum, Eric W; Phillips, Samuel L; Kendrick, Daniel L; Carson, David; Clark, Pete L; Nickson, Thomas E

    2015-01-01

    Abstract As part of an ecological risk assessment, Roundup Ready 2 Yield® soybean (MON 89788) was compared to a conventional control soybean variety, A3244, for disease and arthropod damage, plant response to abiotic stress and cold, effects on succeeding plant growth (allelopathic effects), plant response to a bacterial symbiont, and effects on the ability of seed to survive and volunteer in a subsequent growing season. Statistically significant differences between MON 89788 and A3244 were considered in the context of the genetic variation known to occur in soybean and were assessed for their potential impact on plant pest (weed) potential and adverse environmental impact. The results of these studies revealed no effects of the genetic modification that would result in increased pest potential or adverse environmental impact of MON 89788 compared with A3244. This paper illustrates how such characterization studies conducted in a range of environments where the crop is grown are used in an ecological risk assessment of the genetically modified (GM) crop. Furthermore, risk assessors and decision makers use this information when deciding whether to approve a GM crop for cultivation in—or grain import into—their country. PMID:26177011

  14. Characterization of the ecological interactions of Roundup Ready 2 Yield® soybean, MON 89788, for use in ecological risk assessment.

    PubMed

    Horak, Michael J; Rosenbaum, Eric W; Phillips, Samuel L; Kendrick, Daniel L; Carson, David; Clark, Pete L; Nickson, Thomas E

    2015-01-01

    As part of an ecological risk assessment, Roundup Ready 2 Yield® soybean (MON 89788) was compared to a conventional control soybean variety, A3244, for disease and arthropod damage, plant response to abiotic stress and cold, effects on succeeding plant growth (allelopathic effects), plant response to a bacterial symbiont, and effects on the ability of seed to survive and volunteer in a subsequent growing season. Statistically significant differences between MON 89788 and A3244 were considered in the context of the genetic variation known to occur in soybean and were assessed for their potential impact on plant pest (weed) potential and adverse environmental impact. The results of these studies revealed no effects of the genetic modification that would result in increased pest potential or adverse environmental impact of MON 89788 compared with A3244. This paper illustrates how such characterization studies conducted in a range of environments where the crop is grown are used in an ecological risk assessment of the genetically modified (GM) crop. Furthermore, risk assessors and decision makers use this information when deciding whether to approve a GM crop for cultivation in-or grain import into-their country.

  15. Characterization of Apps and Other e-Tools for Medication Use: Insights Into Possible Benefits and Risks.

    PubMed

    van Kerkhof, Linda Wilhelmina Maria; van der Laar, Catharina Walthera Egbertha; de Jong, Charlie; Weda, Marjolein; Hegger, Ingrid

    2016-04-06

    In the past years, an enormous increase in the number of available health-related applications (apps) has occurred, from approximately 5800 in 2011 to over 23,000 in 2013, in the iTunes store. However, little is still known regarding the use, possible effectiveness, and risks of these applications. In this study, we focused on apps and other e-tools related to medicine use. A large subset of the general population uses medicines and might benefit from tools that aid in the use of medicine. The aim of the present study was to gain more insight into the characteristics, possible risks, and possible benefits of health apps and e-tools related to medication use. We first made an inventory of apps and other e-tools for medication use (n=116). Tools were coded by two independent researchers, based on the information available in the app stores and websites. Subsequently, for one type of often downloaded apps (aimed at people with diabetes), we investigated users' experiences using an online questionnaire. Results of the inventory show that many apps for medication use are available and that they mainly offer simple functionalities. In line with this, the most experienced benefit by users of apps for regulating blood glucose levels in the online questionnaire was "information quick and conveniently available". Other often experienced benefits were improving health and self-reliance. Results of the inventory show that a minority of the apps for medication use has potentially high risks and for many of the apps it is unclear whether and how personal data are stored. In contrast, online questionnaire among users of apps for blood glucose regulation indicates that they hardly ever experience problems or doubts considering reliability and/or privacy. Although, respondents do mention to experience disadvantages of use due to incomplete apps and apps with poor ease of use. Respondents not using app(s) indicate that they might use them in the future if reliability of the apps and

  16. Characterization of Apps and Other e-Tools for Medication Use: Insights Into Possible Benefits and Risks

    PubMed Central

    van der Laar, Catharina Walthera Egbertha; de Jong, Charlie; Weda, Marjolein; Hegger, Ingrid

    2016-01-01

    Background In the past years, an enormous increase in the number of available health-related applications (apps) has occurred, from approximately 5800 in 2011 to over 23,000 in 2013, in the iTunes store. However, little is still known regarding the use, possible effectiveness, and risks of these applications. In this study, we focused on apps and other e-tools related to medicine use. A large subset of the general population uses medicines and might benefit from tools that aid in the use of medicine. Objective The aim of the present study was to gain more insight into the characteristics, possible risks, and possible benefits of health apps and e-tools related to medication use. Methods We first made an inventory of apps and other e-tools for medication use (n=116). Tools were coded by two independent researchers, based on the information available in the app stores and websites. Subsequently, for one type of often downloaded apps (aimed at people with diabetes), we investigated users’ experiences using an online questionnaire. Results Results of the inventory show that many apps for medication use are available and that they mainly offer simple functionalities. In line with this, the most experienced benefit by users of apps for regulating blood glucose levels in the online questionnaire was “information quick and conveniently available”. Other often experienced benefits were improving health and self-reliance. Results of the inventory show that a minority of the apps for medication use has potentially high risks and for many of the apps it is unclear whether and how personal data are stored. In contrast, online questionnaire among users of apps for blood glucose regulation indicates that they hardly ever experience problems or doubts considering reliability and/or privacy. Although, respondents do mention to experience disadvantages of use due to incomplete apps and apps with poor ease of use. Respondents not using app(s) indicate that they might use them

  17. Ovarian cancer patients at high risk of BRCA mutation: the constitutional genetic characterization does not change prognosis.

    PubMed

    Sabatier, Renaud; Lavit, Elise; Moretta, Jessica; Lambaudie, Eric; Noguchi, Tetsuro; Eisinger, François; Cherau, Elisabeth; Provansal, Magali; Livon, Doriane; Rabayrol, Laetitia; Popovici, Cornel; Charaffe-Jauffret, Emmanuelle; Sobol, Hagay; Viens, Patrice

    2016-10-01

    Ovarian neoplasms secondary to germline BRCA mutations had been described to have a more favourable survival. There is only few data concerning the prognosis of non mutated patients presenting clinical features evocative of BRCA alterations. We retrospectively collected data from patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. Patients considered at high risk of BRCA mutation were tested for BRCA1/2 germline mutations. We described clinical, pathological and therapeutic features and compared prognosis of BRCA mutation carriers and non-mutated patients. Out of 617 ovarian cancer patients, we identified 104 patients who were considered at high risk of mutation. The 33 mutated patients were more likely to present a personal (33 vs. 10 %, p = 0.003) or a family (42 vs. 24 %, p = 0.06) history of breast/ovarian cancers. BRCA1/2 mutation carriers and wild type patients displayed similar prognosis: median progression-free survival (PFS) of 20.9 versus 37.7 months (p = 0.21); median overall survival (OS) of 151.2 versus 122.5 months (p = 0.52). Personal history of breast cancer increased both PFS [HR = 0.45 (95CI 0.25-0.81)] and OS [HR = 0.35 (95CI 0.16-0.75)]. In multivariate analysis, this parameter was an independent prognostic feature, whereas the identification of a BRCA1/2 mutation was not. In our cohort, all patients at high risk of BRCA mutation share a similar prognosis, whatever is their germline mutation status. Prognosis seems to be more influenced by clinical history than by germline mutations identification. If it is confirmed in larger and independent series, this result suggests that the hypothesis of other BRCA pathway alterations (BRCAness phenotype) deserves to be deeply explored.

  18. Prevalence of Giardiaduodenalis among children from a central region of Cuba: molecular characterization and associated risk factors.

    PubMed

    Puebla, Luis Jerez; Núñez, Fidel A; García, Alexey Brito; Rivero, Lázara Rojas; Millán, Irais Atencio; Prado, Raúl Cordoví

    2017-06-01

    Giardia duodenalis is one of the most frequent intestinal parasitic infections in children worldwide. To date, eight main assemblages of G. duodenalis have been described, but only A and B genetic groups are known to infect humans. A cross-sectional study was conducted to determine the prevalence and risk factors of Giardia duodenalis infection in 417 preschool children from the Fomento municipality in the central region of Cuba between January and June 2013. The overall prevalence of Giardia infection was 10.79 %. Assemblage identification was carried out by the amplification of a fragment of the triose phosphate isomerase (tpi) gene. DNA from 36 of 45 (80 %) samples was successfully amplified by PCR-tpi. Assemblage B and mixed assemblages A + B represented 52.78 and 36.11 % respectively, of genotyped samples. Assemblage A accounts for only 11.11 %. Children who were cared for at home were associated with diarrhea caused by assemblage B. No associations were found between other clinical variables with infecting assemblage of Giardia. Univariate analysis identified the use of unsafe water resources (OR 2.9; CI 1.2-6.8) and-even more interestingly-keeping dogs indoor (OR 2.5; CI 1.2-5.4) were significant risk factors associated with Giardia infection among children. Multivariate analysis using introduction test logistic regression ratified the association of these two risk factors: kept dogs indoor (OR 2.8, CI 1.1-5.3), and untreated water (OR 1.4, CI 1.4-4.9) with Giardia infection. This information may be useful for an effective prevention and control programme of giardiasis in this population.

  19. Epidemiological characterization and risk factors of allergic rhinitis in the general population in Guangzhou City in china.

    PubMed

    Li, Chun Wei; Chen, De Hua; Zhong, Jia Tao; Lin, Zhi Bin; Peng, Hua; Lu, Han Gui; Yang, Yan; Yin, Jia; Li, Tian Ying

    2014-01-01

    The prevalence of allergic rhinitis (AR) in China has increased with an apparent geographic variation. The current study aims to investigate the AR prevalence/classification, diagnosis/treatment conditions, trigger factors, and risk factors in the general population of Guangzhou, the third biggest city in China. A cross-sectional survey was performed in the citizens in Guangzhou from December 2009 to March 2010 by using a stratified multistage cluster sampling method. All subjects were asked to complete a comprehensive questionnaire via a face to face interview. A total of 9,899 questionnaires were valid. The prevalence rate of AR in the general population of Guangzhou was 6.24%, with a significant higher prevalence in urban area (8.32%) versus rural area (3.43%). Among the AR subjects, most (87%) were diagnosed with intermittent AR and 87% suffered from moderate-severe symptoms. High percentages of the AR patients did not have previously physician-based diagnosis (34%) or specific medical treatment (55%). Morning time, winter season, and cold air were the most common trigger factors of AR. Family history of AR, current living place, living place during babyhood, smoking, home renovation, and pet ownership were the significant risk factors associated with AR prevalence in the population. The study demonstrated comprehensive epidemiological and clinical information about the AR in Guangzhou population. Change of living environment and lifestyles had strong impacts on the prevalence of AR. Public health policies should help the patients benefit from a proper diagnosis/treatment and specifically target the local risk factors, in order to control the AR incidence.

  20. Minocycline hepatotoxicity: Clinical characterization and identification of HLA-B∗35:02 as a risk factor.

    PubMed

    Urban, Thomas Jacob; Nicoletti, Paola; Chalasani, Naga; Serrano, José; Stolz, Andrew; Daly, Ann K; Aithal, Guruprasad P; Dillon, John; Navarro, Victor; Odin, Joseph; Barnhart, Huiman; Ostrov, David; Long, Nanye; Cirulli, Elizabeth Trilby; Watkins, Paul Brent; Fontana, Robert John

    2017-07-01

    Minocycline hepatotoxicity can present with prominent autoimmune features in previously healthy individuals. The aim of this study was to identify genetic determinants of minocycline drug-induced liver injury (DILI) in a well-phenotyped cohort of patients. Caucasian patients with minocycline DILI underwent genome-wide genotyping and were compared to unexposed population controls. Human leukocyte antigen (HLA) binding of minocycline was assessed using AutoDock Vina. Among the 25 cases, 80% were female, median age was 19years and median latency from drug start to DILI onset was 318days. At presentation, 76% had acute hepatocellular liver injury, median ALT 1,077U/L (range: 63 to 2,333), median bilirubin 4.5mg/dl (range: 0.2 to 16.7), and 90% had a +ANA. During follow-up, 50% were treated with corticosteroids and no participants died or required a liver transplant. A significant association was noted between HLA-B∗35:02 and risk for minocycline DILI; a 16% carrier frequency in DILI cases compared to 0.6% in population controls (odds ratio: 29.6, 95% CI: 7.8-89.8, p=2.5×10(-8)). Verification of HLA-B∗35:02 imputation was confirmed by sequence-based HLA typing. HLA-B∗35:02 carriers had similar presenting features and outcomes compared to non-carriers. In silico modeling studies support the hypothesis that direct binding of minocycline to this novel HLA risk allele might be an important initiating event in minocycline DILI. HLA-B∗35:02 is a rare HLA allele that was more frequently identified in the 25 minocycline DILI cases compared to population controls. If confirmed in other cohorts, this HLA allele may prove to be a useful diagnostic marker of minocycline DILI. Development of liver injury following prolonged use of minocycline for acne is a rare but potentially severe form of drug-induced liver injury. Our study demonstrates that individuals who are HLA-B∗35:02 carriers are at increased risk of developing minocycline related liver injury. These results may

  1. On the use of hierarchical probabilistic models for characterizing and managing uncertainty in risk/safety assessment.

    PubMed

    Kodell, Ralph L; Chen, James J

    2007-04-01

    A general probabilistically-based approach is proposed for both cancer and noncancer risk/safety assessments. The familiar framework of the original ADI/RfD formulation is used, substituting in the numerator a benchmark dose derived from a hierarchical pharmacokinetic/pharmacodynamic model and in the denominator a unitary uncertainty factor derived from a hierarchical animal/average human/sensitive human model. The empirical probability distributions of the numerator and denominator can be combined to produce an empirical human-equivalent distribution for an animal-derived benchmark dose in external-exposure units.

  2. Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

    PubMed Central

    Dorman, D C; Allen, S L; Byczkowski, J Z; Claudio, L; Fisher, J E; Fisher, J W; Harry, G J; Li, A A; Makris, S L; Padilla, S; Sultatos, L G; Mileson, B E

    2001-01-01

    We review pharmacokinetic and pharmacodynamic factors that should be considered in the design and interpretation of developmental neurotoxicity studies. Toxicologic effects on the developing nervous system depend on the delivered dose, exposure duration, and developmental stage at which exposure occurred. Several pharmacokinetic processes (absorption, distribution, metabolism, and excretion) govern chemical disposition within the dam and the nervous system of the offspring. In addition, unique physical features such as the presence or absence of a placental barrier and the gradual development of the blood--brain barrier influence chemical disposition and thus modulate developmental neurotoxicity. Neonatal exposure may depend on maternal pharmacokinetic processes and transfer of the xenobiotic through the milk, although direct exposure may occur through other routes (e.g., inhalation). Measurement of the xenobiotic in milk and evaluation of biomarkers of exposure or effect following exposure can confirm or characterize neonatal exposure. Physiologically based pharmacokinetic and pharmacodynamic models that incorporate these and other determinants can estimate tissue dose and biologic response following in utero or neonatal exposure. These models can characterize dose--response relationships and improve extrapolation of results from animal studies to humans. In addition, pharmacologic data allow an experimenter to determine whether exposure to the test chemical is adequate, whether exposure occurs during critical periods of nervous system development, whether route and duration of exposure are appropriate, and whether developmental neurotoxicity can be differentiated from direct actions of the xenobiotic. PMID:11250810

  3. Hydrochemical characterization of arsenic contaminated alluvial aquifers in Eastern Croatia using multivariate statistical techniques and arsenic risk assessment.

    PubMed

    Ujević Bošnjak, M; Capak, K; Jazbec, A; Casiot, C; Sipos, L; Poljak, V; Dadić, Z

    2012-03-15

    Multivariate statistical analyses, cluster, factor and discriminant analyses, were used to estimate spatial variations in groundwater chemistry in Eastern Croatia and to identify the main geochemical processes responsible for high arsenic (As) concentrations in the groundwater analyzed. Cluster analysis revealed five different groups of sampling sites linked with groundwater evolution, hydrochemical characteristics and different As content in the groundwater. Two-model factor analysis explained around 50% of total variance of the data sets and enabled identification of the different geochemical processes responsible for higher As concentrations, i.e. decoupled Fe and As reduction and desorption. Using discriminant analysis, a three-parameter discriminant function was derived: electrical conductivity, nitrate and bromide, which yielded highly accurate classification of the samples according to the concentration of As as As-safe (<10μg/L) and As contaminated (>10μg/L). A health risk assessment model was applied to calculate cumulative exposure to As as well as toxic and carcinogenic risks resulting from drinking raw groundwater contaminated by As in Eastern Croatia. Although the results obtained indicate that adverse health effects could be observed among the residents of the villages in which raw groundwater with higher As concentrations has been used, there are no reported cases of arsenicosis. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Cross exploitation of geo-databases and earth observation data for stakes characterization in the framework of multi-risk analysis and management: RASOR examples

    NASA Astrophysics Data System (ADS)

    Tholey, Nadine; Yesou, Herve; Maxant, Jerome; Montabord, Myldred; Studer, Mathias; Faivre, Robin; Rudari, Roberto; de Fraipont, Paul

    2016-04-01

    In the context of risk analysis and management, information is needed on the landscape under investigation, especially for vulnerability assessment purposes where landuse and stakes characterization is of prime importance for the knowledge and description of exposure elements in modelling scenarios. Such thematic information over at-risk areas can be extracted from available global, regional or local scale open sources databases (e.g. ESA-Globcover, Natural Earth, Copernicus core services, OSM, …) or derived from the exploitation of EO satellite images at high and very high spatial resolution (e.g. SPOT, soon Sentinel2, Pleiades, WorldView, …) over territories where this type of information is not available or not sufficiently up to date. However, EO data processing, and derived results highlight also the gap between what would be needed for a complete representation of vulnerability , i.e. a functional description of the land use, a structural description of the buildings including their functional use , and what is reasonable accessible by exploiting EO data, i.e. a biophysical description of the land cover at different spatial resolution from decametric scales to sub-metric ones, especially for urban block and building information. Potential and limits of these multi-scale and multi-sources of geo-information will be illustrated by examples related to different types of landscape and urban settlements in Asia (Indonesia), Europe (Greece), and the Caribbean (Haiti) regions, and exploited within the framework of the RASOR (Rapid Analysis and Spatialisation Of Risk) project (European Commission FP7) which is developing a platform to perform multi-hazard risk analysis to support the full cycle of disaster management.

  5. Ecological and health risk-based characterization of agricultural soils contaminated with polycyclic aromatic hydrocarbons in the vicinity of a chemical plant in China.

    PubMed

    Liu, Geng; Niu, Junjie; Guo, Wenjiong; An, Xiangsheng; Zhao, Long

    2016-11-01

    Polycyclic aromatic hydrocarbons (PAHs) from chemical plants can cause serious pollution of surrounding agricultural soils. A comprehensive study of agricultural soils was conducted in the vicinity of a chemical plant in China to characterize the soil PAH concentration, as well as their composition and sources. Human health and a screening-level ecological risk assessment were conducted for PAH contamination in agricultural soils. The results showed that the total concentrations of 16 priority PAHs ranged from 250.49 to 9387.26 ng g(-1), with an average of 2780.42 ng g(-1). High molecular weight PAHs (four to six rings) were the dominant component, accounting for more than 60% of all PAHs. Principal component analysis (PCA) and positive matrix factorization model (PMF) suggested that diesel emissions, coal combustion, coke ovens, and fuel combustion and gasoline emissions were the main sources of PAHs in agricultural soils. The ecological risk assessment results based on the effects range-low (ERL), the effects range-median (ERM), and the ecological screening levels (ESL) indicated that the exposure to ∑PAH16 was >ERL, >ERM, and ≥ERL and ESL at 78.1% of the soil sampling stations, and could induce biological effects in mammals. The Bapeq concentrations posed a potential carcinogenic risk to humans. Further risk management and control of soil PAHs in these agricultural soils is required to ensure the safety of the biocoenosis and human health.

  6. On the Impact of Extratropical Systems and Tropical Storms in the Characterization of Flood Risk for the Eastern United States

    NASA Astrophysics Data System (ADS)

    Villarini, Gabriele; Smith, James; Vecchi, Gabriel; Baeck, Mary Lynn

    2010-05-01

    Flooding in the eastern US reflects a mixture of flood generating mechanisms, with landfalling tropical cyclones and extratropical systems playing central roles. These precipitation systems represent a major risk for insured property and can lead to extensive damage through storm surge flooding, inland flooding and heavy rainfall, or extreme windspeeds. The focus of this work revolves around two main issues: 1) For a given extratropical system or landfalling tropical storm, what is the extent of the inland flooding? 2) What is the rainfall distribution and storm evolution for flood events in the eastern US? Results are presented using case studies of both extratropical systems and landfalling tropical storms in the eastern US. The results of this study could be used to feed into the next generation of cat-models and assist in the calculation of damages from inland flood damage and heavy rainfall.

  7. Minocycline Hepatotoxicity: Clinical characterization and identification of HLA-B* 35:02 as a risk factor

    PubMed Central

    Urban, Thomas Jacob; Nicoletti, Paola; Chalasani, Naga; Serrano, Jose; Stolz, Andrew; Daly, Ann K.; Aithal, Guruprasad P.; Dillon, John; Navarro, Victor; Odin, Joseph; Barnhart, Huiman; Ostrov, David; Long, Nanye; Cirulli, Elizabeth Theresa; Watkins, Paul Brent; Fontana, Robert John

    2017-01-01

    Background & Aims Minocycline hepatotoxicity can present with prominent autoimmune features in previously healthy individuals. The aim of this study was to identify genetic determinants of minocycline DILI in a well-phenotyped cohort of patients. Methods Caucasian patients with minocycline DILI underwent genome-wide genotyping and were compared to unexposed population controls. Human leukocyte antigen (HLA) binding of minocycline was assessed using AutoDock Vina. Results Amongst the 25 cases, 80% were female, median age was 19 years and median latency from drug start to DILI onset was 318 days. At presentation, 76% had acute hepatocellular liver injury, median ALT 1077 U/L (range: 63 to 2333), median bilirubin 4.5 mg/dl (range: 0.2 to 16.7), and 90% had a +ANA. During follow-up, 50% were treated with corticosteroids and no subjects died or required a liver transplant. A significant association was noted between HLA-B*35:02 and risk for minocycline-DILI; a 16% carrier frequency in DILI cases compared to 0.6% in population controls (Odds Ratio: 29.6, 95% CI: 7.8-89.8, p=2.5 × 10-8). Verification of HLA-B*35:02 imputation was confirmed by sequence-based HLA typing. HLA-B*35:02 carriers had similar presenting features and outcomes compared to non-carriers. In silico modeling studies support the hypothesis that direct binding of minocycline to this novel HLA risk allele might be an important initiating event in minocycline-DILI. Conclusion HLA-B*35:02 is a rare HLA allele that was more frequently identified in the 25 minocycline-DILI cases compared to population controls. If confirmed in other cohorts, this HLA allele may prove to be a useful diagnostic marker of minocycline DILI. PMID:28323125

  8. Polycyclic aromatic hydrocarbons (PAHs) in sediments of Zhelin Bay, the largest mariculture base on the eastern Guangdong coast, South China: Characterization and risk implications.

    PubMed

    Gu, Yang-Guang; Ke, Chang-Liang; Liu, Qi; Lin, Qin

    2016-09-15

    We investigated distribution, sources, and potential risks of polycyclic aromatic hydrocarbons (PAHs) in the surface sediments from the largest mariculture base in the eastern part of the province of Guangdong in southern China. Total concentrations of ∑PAHs were 29.38-815.46ng/g (dry weight), with a mean of 421.48ng/g. The composition of PAHs was characterized by an abundance of low molecular weight PAHs (2-3 benzenoid ring), and Phenanthrene (PHE), Anthracene (AN) and Fluoranthene (FA) were the predominant constituents. PAHs in this area appear to have mainly originated from petroleum sources and the combustion of grass, wood, and coal. PAHs in surface sediments of Zhelin Bay had a 9% incidence of causing adverse biological effects on aquatic organisms, according to the mean effects range-median quotient. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. A risk-based focused decision-management approach for justifying characterization of Hanford tank waste. June 1996, Revision 1; April 1997, Revision 2

    SciTech Connect

    Colson, S.D.; Gephart, R.E.; Hunter, V.L.; Janata, J.; Morgan, L.G.

    1997-12-31

    This report describes a disciplined, risk-based decision-making approach for determining characterization needs and resolving safety issues during the storage and remediation of radioactive waste stored in Hanford tanks. The strategy recommended uses interactive problem evaluation and decision analysis methods commonly used in industry to solve problems under conditions of uncertainty (i.e., lack of perfect knowledge). It acknowledges that problem resolution comes through both the application of high-quality science and human decisions based upon preferences and sometimes hard-to-compare choices. It recognizes that to firmly resolve a safety problem, the controlling waste characteristics and chemical phenomena must be measurable or estimated to an acceptable level of confidence tailored to the decision being made.

  10. Probabilistic risk assessment of dietary exposure to single and multiple pesticide residues or contaminants: summary of the work performed within the SAFE FOODS project.

    PubMed

    van Klaveren, Jacob D; Boon, Polly E

    2009-12-01

    This introduction to the journal's supplement on probabilistic risk assessment of single and multiple exposure to pesticide residues or contaminants summarizes the objectives and results of the work performed in work package 3 of the EU-funded project SAFE FOODS. Within this work package, we developed an electronic platform of food consumption and chemical concentration databases harmonised at raw agricultural commodity level. In this platform the databases are connected to probabilistic software to allow probabilistic modelling of dietary exposure in a standardised way. The usefulness of this platform is demonstrated in two papers, which describe the exposure to pesticides and glycoalkaloids in several European countries. Furthermore, an integrated probabilistic risk assessment (IPRA) model was developed: a new tool to integrate exposure and effect modelling, including uncertainty analyses. The use of this model was shown in a paper on the cumulative exposure to anti-androgen pesticides. Combined with a health impact prioritization system, developed within this work package to compare heath risks between chemicals, the IPRA tool can also be used to compare health risks between multiple chemicals in complex risk assessment situation such as risk-benefit and risk trade-off analyses. Both the electronic platform of databases as the IPRA model may proof to be powerful tools to tackle the challenges risk managers are or will be faced with in the future.

  11. Atherosclerotic plaque tissue characterization in 2D ultrasound longitudinal carotid scans for automated classification: a paradigm for stroke risk assessment.

    PubMed

    Acharya, U Rajendra; Mookiah, Muthu Rama Krishnan; Vinitha Sree, S; Afonso, David; Sanches, Joao; Shafique, Shoaib; Nicolaides, Andrew; Pedro, L M; Fernandes E Fernandes, J; Suri, Jasjit S

    2013-05-01

    In the case of carotid atherosclerosis, to avoid unnecessary surgeries in asymptomatic patients, it is necessary to develop a technique to effectively differentiate symptomatic and asymptomatic plaques. In this paper, we have presented a data mining framework that characterizes the textural differences in these two classes using several grayscale features based on a novel combination of trace transform and fuzzy texture. The features extracted from the delineated plaque regions in B-mode ultrasound images were used to train several classifiers in order to prepare them for classification of new test plaques. Our CAD system was evaluated using two different databases consisting of 146 (44 symptomatic to 102 asymptomatic) and 346 (196 symptomatic and 150 asymptomatic) images. Both these databases differ in the way the ground truth was determined. We obtained classification accuracies of 93.1 and 85.3 %, respectively. The techniques are low cost, easily implementable, objective, and non-invasive. For more objective analysis, we have also developed novel integrated indices using a combination of significant features.

  12. Threshold dose for peanut: risk characterization based upon published results from challenges of peanut-allergic individuals.

    PubMed

    Taylor, Steve L; Crevel, Rene W R; Sheffield, David; Kabourek, Jamie; Baumert, Joseph

    2009-06-01

    Population thresholds for peanut are unknown. However, lowest- and no-observed adverse effect levels (LOAELs and NOAELs) are published for an unknown number of peanut-allergic individuals. Publications were screened for LOAELs and NOAELs from blinded, low-dose oral challenges. Data were obtained from 185 peanut-allergic individuals (12 publications). Data were analyzed by interval-censoring survival analysis and three probability distribution models fitted to it (Log-Normal, Log-Logistic, and Weibull) to estimate the ED(10). All three models described the data well and provided ED(10)'s in close agreement: 17.6, 17.0, and 14.6 mg of whole peanut for the Log-Normal, Log-Logistic, and Weibull models, respectively. The 95% lower confidence intervals for the ED(10)'s were 9.2, 8.1, and 6.0mg of whole peanut for the Log-Normal, Log-Logistic, and Weibull models, respectively. The modeling of individual NOAELs and LOAELs identified from three different types of published studies - diagnostic series, threshold studies, and immunotherapy trials - yielded significantly different whole peanut ED(10)'s of 11.9 mg for threshold studies, 18.0mg for diagnostic series and 65.5mg for immunotherapy trials; patient selection and other biases may have influenced the estimates. These data and risk assessment models provide the type of information that is necessary to establish regulatory thresholds for peanut.

  13. Characterization of a laboratory model of computer mouse use - applications for studying risk factors for musculoskeletal disorders.

    PubMed

    Flodgren, G; Heiden, M; Lyskov, E; Crenshaw, A G

    2007-03-01

    In the present study, we assessed the wrist kinetics (range of motion, mean position, velocity and mean power frequency in radial/ulnar deviation, flexion/extension, and pronation/supination) associated with performing a mouse-operated computerized task involving painting rectangles on a computer screen. Furthermore, we evaluated the effects of the painting task on subjective perception of fatigue and wrist position sense. The results showed that the painting task required constrained wrist movements, and repetitive movements of about the same magnitude as those performed in mouse-operated design tasks. In addition, the painting task induced a perception of muscle fatigue in the upper extremity (Borg CR-scale: 3.5, p<0.001) and caused a reduction in the position sense accuracy of the wrist (error before: 4.6 degrees , error after: 5.6 degrees , p<0.05). This standardized painting task appears suitable for studying relevant risk factors, and therefore it offers a potential for investigating the pathophysiological mechanisms behind musculoskeletal disorders related to computer mouse use.

  14. Chronic dietary risk characterization for pesticide residues: a ranking and scoring method integrating agricultural uses and food contamination data.

    PubMed

    Nougadère, Alexandre; Reninger, Jean-Cédric; Volatier, Jean-Luc; Leblanc, Jean-Charles

    2011-07-01

    A method has been developed to identify pesticide residues and foodstuffs for inclusion in national monitoring programs with different priority levels. It combines two chronic dietary intake indicators: ATMDI based on maximum residue levels and agricultural uses, and EDI on food contamination data. The mean and 95th percentile of exposure were calculated for 490 substances using individual and national consumption data. The results show that mean ATMDI exceeds the acceptable daily intake (ADI) for 10% of the pesticides, and the mean upper-bound EDI is above the ADI for 1.8% of substances. A seven-level risk scale is presented for substances already analyzed in food in France and substances not currently sought. Of 336 substances analyzed, 70 pesticides of concern (levels 2-5) should be particularly monitored, 22 of which are priority pesticides (levels 4 and 5). Of 154 substances not sought, 36 pesticides of concern (levels 2-4) should be included in monitoring programs, including 8 priority pesticides (level 4). In order to refine exposure assessment, analytical improvements and developments are needed to lower the analytical limits for priority pesticide/commodity combinations. Developed nationally, this method could be applied at different geographic scales.

  15. Prospective Characterization of the Risk Factors for Transmission and Symptoms of Primary Human Herpesvirus Infections Among Ugandan Infants

    PubMed Central

    Gantt, Soren; Orem, Jackson; Krantz, Elizabeth M.; Morrow, Rhoda Ashley; Selke, Stacy; Huang, Meei-Li; Schiffer, Joshua T.; Jerome, Keith R.; Nakaganda, Annet; Wald, Anna; Casper, Corey; Corey, Lawrence

    2016-01-01

    Background. Human herpesvirus (HHV) infections are common during infancy. Primary infections are frequently asymptomatic and best studied prospectively by using direct viral detection. Methods. Oropharyngeal swab specimens were collected weekly from Ugandan newborn infants, their mothers, and other children in the household. Blood specimens were collected every 4 months. Samples were tested for herpes simplex virus (HSV) types 1 and 2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6A, HHV-6B, and HHV-8, using quantitative polymerase chain reaction. Results. Thirty-two infants, 32 mothers, and 49 other household children were followed for a median of 57 weeks. Seventeen mothers had human immunodeficiency virus type 1 (HIV) infection; no infants acquired HIV-1. The 12-month incidence of postnatal infection was 76% for HHV-6B, 59% for CMV, 47% for EBV, 8% for HSV-1, and 0% for HHV-8. The quantity of oropharyngeal shedding by contacts was associated with HHV-6A or HHV-6B transmission. Maternal HIV-1 infection was associated with EBV transmission, while breastfeeding and younger child contacts were associated with CMV transmission. Except for HSV-1, primary HHV infections were subclinical. Conclusions. By capturing exposures and acquisition events, we found that the incidence and risk factors of infection vary by HHV type. HSV-1 infection, unlike other HHV infections, caused acute clinical illness in these infants. PMID:26917575

  16. Prospective Characterization of the Risk Factors for Transmission and Symptoms of Primary Human Herpesvirus Infections Among Ugandan Infants.

    PubMed

    Gantt, Soren; Orem, Jackson; Krantz, Elizabeth M; Morrow, Rhoda Ashley; Selke, Stacy; Huang, Meei-Li; Schiffer, Joshua T; Jerome, Keith R; Nakaganda, Annet; Wald, Anna; Casper, Corey; Corey, Lawrence

    2016-07-01

    Human herpesvirus (HHV) infections are common during infancy. Primary infections are frequently asymptomatic and best studied prospectively by using direct viral detection. Oropharyngeal swab specimens were collected weekly from Ugandan newborn infants, their mothers, and other children in the household. Blood specimens were collected every 4 months. Samples were tested for herpes simplex virus (HSV) types 1 and 2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6A, HHV-6B, and HHV-8, using quantitative polymerase chain reaction. Thirty-two infants, 32 mothers, and 49 other household children were followed for a median of 57 weeks. Seventeen mothers had human immunodeficiency virus type 1 (HIV) infection; no infants acquired HIV-1. The 12-month incidence of postnatal infection was 76% for HHV-6B, 59% for CMV, 47% for EBV, 8% for HSV-1, and 0% for HHV-8. The quantity of oropharyngeal shedding by contacts was associated with HHV-6A or HHV-6B transmission. Maternal HIV-1 infection was associated with EBV transmission, while breastfeeding and younger child contacts were associated with CMV transmission. Except for HSV-1, primary HHV infections were subclinical. By capturing exposures and acquisition events, we found that the incidence and risk factors of infection vary by HHV type. HSV-1 infection, unlike other HHV infections, caused acute clinical illness in these infants. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  17. Risk characterization data manual for inactive liquid low-level waste tank systems at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    Not Available

    1992-09-01

    This manual reports the results of a risk characterization of inactive liquid low-level radioactive waste (LLLW) underground storage tanks (USTs) at the Oak Ridge National Laboratory (ORNL). Of the 39 tanks at ORNL that have been accepted into the Environmental Restoration Program, the 29 LLLW USTs that have been sampled for preliminary characterization were considered. Each tank was scored on a scale of 1 to 5 on the basis of three criteria: (1) leak characteristics, (2) location, and (3) toxicological characteristics of residual sludges and liquids. Each criterion was then weighted according to perceived importance. The criterion score multiplied by the weighting factor equaled the tank's total score for that criterion. The three weighted criterion scores for each tank were then summed for a total score for that tank. When the scores for all tanks had been weighted and summed, the tanks were ranked in descending order on the basis of their total scores. The highest possible score for a tank is 30. The descending rank order represents the recommended priorities for evaluation: the higher the score, the higher the priority for evaluation.

  18. Opioid detection in maternal and neonatal hair and meconium: characterization of an at-risk population and implications to fetal toxicology.

    PubMed

    Moller, Monique; Karaskov, Tatyana; Koren, Gideon

    2010-06-01

    Identification of maternal opioid abuse in pregnancy is often difficult to ascertain in the absence of a reliable self-report. We aimed to characterize an at-risk neonatal population for opioid exposures as well as other drugs of abuse and alcohol. From June 2007 to January 2009, 563 neonatal hair and 1318 meconium specimens were assessed for opioids and were positive in 11.4% and 17.0%, respectively. Neonates testing positive for opioids in hair or meconium analysis were also more likely to test positive for other licit and illicit substances (odds ratiohair, 1.75; 95% confidence interval, 1.03-2.97; odds ratiomeconium, 1.61; 95% confidence interval, 1.16-2.22). Specifically, a positive neonatal hair test for opioids also predicted a positive result for oxycodone. In addition, a positive meconium test result for opioids was associated with positive results for cocaine, oxycodone, methadone, benzodiazepines, and fatty acid ethyl esters (alcohol). Finally, there was a significant correlation between maternal and neonatal hair test results for opioids (Spearman rank rho = 0.657, P = 0.03). Understanding the addiction profiles of these women may lead to better clinical and social management and may largely benefit an at-risk population.

  19. Characterizing implementation strategies using a systems engineering survey and interview tool: a comparison across 10 prevention programs for drug abuse and HIV sexual risk behavior.

    PubMed

    Czaja, Sara J; Valente, Thomas W; Nair, Sankaran N; Villamar, Juan A; Brown, C Hendricks

    2016-05-17

    Although many behavioral interventions have proven to be efficacious, new methodologies are required beyond efficacy trials to understand how to adopt, implement with fidelity, and sustain behavioral interventions in community settings. In this paper, we present a new approach, based on systems engineering concepts and methods, for characterizing implementation strategies that are used to deliver evidence-based behavioral interventions in health and social service settings. We demonstrate the use of this approach with implementation strategies, used or being used for broader dissemination of 10 evidence-based prevention program projects focused on the prevention of drug or HIV sex risk behaviors. The results indicate that there are wide variations in intervention approaches and that there are challenges in program implementation including maintaining program fidelity, serving community needs, and adequate resources. The results also indicate that implementation requires a committed partnership between the program developers, implementation researchers, and community partners. In addition, there is a need for adaptability within programs to meet community needs, resources, and priorities while maintaining program fidelity. Our methodological approach enabled us to highlight challenges associated with the community implementation of health risk prevention interventions. We also demonstrate how comprehensive descriptions of interventions facilitate understanding of the requirements of program implementation and decisions about the feasibility of implementing a program in community settings.

  20. Genetic characterization of spotted fever group rickettsiae in questing ixodid ticks collected in Israel and environmental risk factors for their infection.

    PubMed

    Rose, Jessica; Nachum-Biala, Yaarit; Mumcuoglu, Kosta Y; Alkhamis, Moh A; Ben-Nun, Adi; Lensky, Itamar; Klement, Eyal; Nasereddin, Abedelmajeed; Abdeen, Ziad A; Harrus, Shimon

    2017-03-23

    This study aimed to genetically characterize spotted fever group rickettsiae (SFGR) in questing ixodid ticks from Israel and to identify risk factors associated with SFGR-positive ticks using molecular techniques and geographic information systems (GIS) analysis. 1039 ticks from the genus Rhipicephalus were collected during 2014. 109/1039 (10·49%) carried SFGR-DNA of either Rickettsia massiliae (95), 'Candidatus Rickettsia barbariae' (8) or Rickettsia conorii (6). Higher prevalence of SFGR was found in Rhipicephalus turanicus (18·00%) compared with Rhipicephalus sanguineus sensu lato (3·22%). Rickettsia massiliae was the most commonly detected species and the most widely disseminated throughout Israel (87·15% of all Rickettsia-positive ticks). GIS analysis revealed that Central and Northern coastal regions are at high risk for SFGR. The presence of ticks was significantly associated with normalized difference vegetation index and temperature variation over the course of the year. The presence of rickettsiae was significantly associated with brown type soils, higher land surface temperature and higher precipitation. The latter parameters may contribute to infection of the tick with SFGR. Health care professionals should be aware of the possible exposure of local communities and travellers to R. massillae. Molecular and geographical information can help professionals to identify areas that are susceptible to SFGR-infected ticks.

  1. PCDD/Fs and DL-PCBs intake from fish caught in Polish fishing grounds in the Baltic Sea--characterizing the risk for consumers.

    PubMed

    Struciński, Paweł; Piskorska-Pliszczyńska, Jadwiga; Maszewski, Sebastian; Góralczyk, Katarzyna; Warenik-Bany, Małgorzata; Mikołajczyk, Szczepan; Czaja, Katarzyna; Hernik, Agnieszka; Ludwicki, Jan K

    2013-06-01

    Fish and fishery products are among the primary sources of dietary exposure to dioxins. It is known that some fish species caught in the Baltic Sea contain elevated level of those compounds. Levels of dioxins and DL-PCBs in 236 Baltic fish samples (including 65 salmon, 14 sea trout, 63 sprat, 63 herring, 31 cod), and 20 cod liver samples from the Polish fishing grounds (the ICES zones 24-27), collected in the time frame of 2006-2011 as part of Polish monitoring survey have been used for risk assessment. To characterize potential health risk associated with dioxins intake, doses ingested in a single portion of fish and cod liver by adults (200g for fish, 125g for cod liver), and children (100g for fish, 25g for cod liver) were expressed as percent of Tolerable Weekly Intake (TWI) and Provisional Tolerable Monthly Intake (PTMI). Average dioxins intake estimated for fatty fish species was about 250% TWI for children, and about 170% TWI for adults, with maximum values of 436.3 and 288.0% TWI, respectively. Maximum exposure expressed as percent of PTMI was below 90% for children and below 60% in adults. For sprat and herring, mean dioxins intakes were lower, but still not at "safe" level: 100-150% TWI for children and about 70-100% for adults, with the maximum values of about 250 and 180%, respectively. Maximum exposure expressed as percent of PTMI was approximately 50% for children and 35% for adults. Intakes values calculated for practically "dioxin-free" cod are just theoretical because in calculating toxic equivalents (TEQs) an upperbound approach was applied, and vast majority of TEQs originates from the limit of quantification (LOQ) values of all non-quantified congeners. Frequent consumption of cod liver seems to be a health risk as, according to assumed scenario, dioxins intake of 100% PTMI for adults would be achieved by the 65th percentile, while for children by approximately 90th percentile of results. Serving sizes of salmonids, cod liver, and even sprat

  2. Competing Uses of Underground Systems Related to Energy Supply: Applying Single- and Multiphase Simulations for Site Characterization and Risk-Analysis

    NASA Astrophysics Data System (ADS)

    Kissinger, A.; Walter, L.; Darcis, M.; Flemisch, B.; Class, H.

    2012-04-01

    Global climate change, shortage of resources and the resulting turn towards renewable sources of energy lead to a growing demand for the utilization of subsurface systems. Among these competing uses are Carbon Capture and Storage (CCS), geothermal energy, nuclear waste disposal, "renewable" methane or hydrogen storage as well as the ongoing production of fossil resources like oil, gas, and coal. Besides competing among themselves, these technologies may also create conflicts with essential public interests like water supply. For example, the injection of CO2 into the underground causes an increase in pressure reaching far beyond the actual radius of influence of the CO2 plume, potentially leading to large amounts of displaced salt water. Finding suitable sites is a demanding task for several reasons. Natural systems as opposed to technical systems are always characterized by heterogeneity. Therefore, parameter uncertainty impedes reliable predictions towards capacity and safety of a site. State of the art numerical simulations combined with stochastic approaches need to be used to obtain a more reliable assessment of the involved risks and the radii of influence of the different processes. These simulations may include the modeling of single- and multiphase non-isothermal flow, geo-chemical and geo-mechanical processes in order to describe all relevant physical processes adequately. Stochastic approaches have the aim to estimate a bandwidth of the key output parameters based on uncertain input parameters. Risks for these different underground uses can then be made comparable with each other. Along with the importance and the urgency of the competing processes this may lead to a more profound basis for a decision. Communicating risks to stake holders and a concerned public is crucial for the success of finding a suitable site for CCS (or other subsurface utilization). We present and discuss first steps towards an approach for addressing the issue of competitive

  3. Use of the Escherichia coli Identification Microarray for Characterizing the Health Risks of Shiga Toxin-Producing Escherichia coli Isolated from Foods.

    PubMed

    Lacher, David W; Gangiredla, Jayanthi; Patel, Isha; Elkins, Christopher A; Feng, Peter C H

    2016-10-01

    More than 470 serotypes of Shiga toxin-producing Escherichia coli (STEC) have been identified, but not all cause severe illness in humans. Most STEC that cause severe diseases can adhere to epithelial cells, produce specific stx subtypes, and belong to certain serotypes; therefore, these traits appear to be critical STEC risk factors. However, testing for these traits is labor intensive, and serotyping is inadequate because of extensive variations among E. coli O and H antigen types. In the present study, the E. coli identification microarray, which tests for over 40,000 E. coli gene targets, was examined for its potential to quickly characterize STEC strains. Analysis of 47 E. coli isolates, including 31 STEC isolates, recovered from 39 foods revealed that the microarray effectively determined the presence or absence of adherence genes and identified the specific eae allele in 3 isolates. The array identified most of the stx subtypes carried by all the isolates but had some difficulties in discerning between stx2a, stx2c, and stx2d because of the genetic similarities of these subtypes. The array determined the O and H types of 68 and 96% of the isolates, respectively, and although most serotypes were unremarkable, a few known pathogenic serotypes were also found. These selected STEC traits provided a scientific basis for assessing the potential health risks of STEC strains and also showed the importance of H typing in determining health risks. However, the diversity of the STEC group, the complexity of virulence mechanisms, and the variation in pathotypes among strains continue to pose challenges to assessing the potential of STEC strains to cause severe illness.

  4. Characterization and health risk assessment of PM2.5-bound organics inside and outside of Chinese smoking lounges.

    PubMed

    Li, Lijuan; Ho, Steven Sai Hang; Chow, Judith C; Watson, John G; Lee, Frank S C; Cui, Long; Gao, Yuan; Dai, Wenting; Ho, Kin Fai; Huang, Yu; Cao, Junji

    2017-11-01

    PM2.5 samples were collected at six indoor public places that contained dedicated smoking lounges. Samples were taken in the smoking lounges, at two indoor locations outside of the lounges, and in outdoor air near the venues. Organic carbon (OC), elemental carbon (EC), and non-polar organic compounds including polycyclic aromatic hydrocarbons (PAHs), n-alkanes (n-C16 to n-C40), iso/anteiso-alkanes (C29 to C33), hopanes and phthalate esters (PAEs) were quantified. Average PM2.5 levels of 170.2 ± 85.9 μg/m(3) in the lounges exceeded limits of 25 μg/m(3) set by World Health Organization (WHO); these levels were 5.4 and 3.9 times higher than those indoors and outdoors, respectively. High ratios of OC to PM2.5, OC to EC, and PAHs diagnostic ratios in the lounges indicated contributions from environmental tobacco smoke (ETS). The maximum carbon number (Cmax) and carbon preference indices (CPI) for n-alkanes showed ETS transport from the enclosed lounges to nearby indoor non-smoking areas. Iso/anteiso-alkanes in the lounges were 876.5 ng/m(3), ∼80 times higher than outdoor levels. 17α(H)-21β(H),30-norhopane and 17α(H)-21β(H),(22R)-homohopane were much higher in the lounges than outdoor air, but they cannot be directly attributed to ETS. Estimated carcinogenic risks of PAHs in the lounges exceeded the acceptable level of 10(- 6). Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Assessment of indirect human exposure to environmental sources of nickel: oral exposure and risk characterization for systemic effects.

    PubMed

    De Brouwere, Katleen; Buekers, Jurgen; Cornelis, Christa; Schlekat, Christian E; Oller, Adriana R

    2012-03-01

    This paper describes the indirect human exposure to Ni via the oral route for the regional scale in the EU, together with a method to assess additional local exposure from industrial emissions. The approach fills a gap in the generic REACH guidance which is inadequate for assessing indirect environmental exposure of metals. Estimates of regional scale Ni dietary intake were derived from Ni dietary studies performed in the EU. Typical and Reasonable Worst Case dietary Ni intakes for the general population in the EU were below the oral Derived No Effect Level (DNEL) of Ni sulfate for systemic effects. Estimates for the Ni dietary intake at the local scale take into account the influence of aerial Ni deposition and transfer from soil to crops grown near industrial plants emitting Ni. The additional dietary exposure via this local contribution was small. Despite the use of conservative parameters for these processes, this method may underestimate dietary exposure around older industrial sites because REACH guidance does not account for historical soil contamination. Nevertheless, the method developed here can also be used as a screening tool for community-based risk assessment, as it accounts for historical soil pollution. Nickel exposure via drinking water was derived from databases on Ni tap water quality. A small proportion of the EU population (<5%) is likely to be exposed to tap water exceeding the EU standard (20 μg Ni/l). Taking into account the relative gastrointestinal absorption of Ni from water (30%) versus from solid matrices (5%), water intake constitutes, after dietary intake, the second most important pathway for oral Ni intake. Incidental ingestion of Ni from soil/dust at the regional scale, and also at the local scale, was low in comparison with dietary intake.

  6. Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma.

    PubMed

    Puig, Susana; Potrony, Miriam; Cuellar, Francisco; Puig-Butille, Joan Anton; Carrera, Cristina; Aguilera, Paula; Nagore, Eduardo; Garcia-Casado, Zaida; Requena, Celia; Kumar, Rajiv; Landman, Gilles; Costa Soares de Sá, Bianca; Gargantini Rezze, Gisele; Facure, Luciana; de Avila, Alexandre Leon Ribeiro; Achatz, Maria Isabel; Carraro, Dirce Maria; Duprat Neto, João Pedreira; Grazziotin, Thais C; Bonamigo, Renan R; Rey, Maria Carolina W; Balestrini, Claudia; Morales, Enrique; Molgo, Montserrat; Bakos, Renato Marchiori; Ashton-Prolla, Patricia; Giugliani, Roberto; Larre Borges, Alejandra; Barquet, Virginia; Pérez, Javiera; Martínez, Miguel; Cabo, Horacio; Cohen Sabban, Emilia; Latorre, Clara; Carlos-Ortega, Blanca; Salas-Alanis, Julio C; Gonzalez, Roger; Olazaran, Zulema; Malvehy, Josep; Badenas, Celia

    2016-07-01

    CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736.

  7. Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma

    PubMed Central

    Puig, Susana; Potrony, Miriam; Cuellar, Francisco; Puig-Butille, Joan Anton; Carrera, Cristina; Aguilera, Paula; Nagore, Eduardo; Garcia-Casado, Zaida; Requena, Celia; Kumar, Rajiv; Landman, Gilles; Costa Soares de Sá, Bianca; Gargantini Rezze, Gisele; Facure, Luciana; de Avila, Alexandre Leon Ribeiro; Achatz, Maria Isabel; Carraro, Dirce Maria; Duprat Neto, João Pedreira; Grazziotin, Thais C.; Bonamigo, Renan R.; Rey, Maria Carolina W.; Balestrini, Claudia; Morales, Enrique; Molgo, Montserrat; Bakos, Renato Marchiori; Ashton-Prolla, Patricia; Giugliani, Roberto; Larre Borges, Alejandra; Barquet, Virginia; Pérez, Javiera; Martínez, Miguel; Cabo, Horacio; Cohen Sabban, Emilia; Latorre, Clara; Carlos-Ortega, Blanca; Salas-Alanis, Julio C; Gonzalez, Roger; Olazaran, Zulema; Malvehy, Josep; Badenas, Celia

    2016-01-01

    Purpose: CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. Genet Med 18 7, 727–736. Methods: CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. Genet Med 18 7, 727–736. Results: Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. Genet Med 18 7, 727–736. Conclusion: The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives. Genet Med 18 7, 727–736. PMID:26681309

  8. Successful Characterization Strategies for the Active High Risk Y-12 National Security Complex 9201-5 (Alpha-5) Facility, Oak Ridge, TN - 12164

    SciTech Connect

    Birchfield, Joseph W. III; Albrecht, Linda

    2012-07-01

    Building 9201-5 (Alpha 5) was completed in May 1944 and served as a production facility for National Nuclear Security Administration (NNSA) Y-12 Weapons Plant. During the Manhattan Project, it functioned as a uranium enrichment facility. The facility was renovated and altered over the years, converting the calutrons to support other missions. Alpha 5 consists of 4 floors and a basement measuring approximately 600,000 square feet. The facility contains various pieces of equipment remaining from legacy operations. A significant amount (approximately 200,000 kgs) of mercury (Hg) has been spilled in the facility over the operational history of the building. To further complicate matters, beryllium (Be) contamination in 9201-5 is found throughout approximately sixty percent of the facility. Concentrations varying from very low (< 0.2 micrograms (μg)/100 cm{sup 2}) to areas where concentrations are relatively high, approximately 600 μg/100 cm{sup 2}, in regulated beryllium areas. The primary site related contaminants (SRCs) for the waste in this facility are enriched uranium, depleted uranium, beryllium and mercury. This facility represents the highest environmental risk for DOE-ORO EM and NNSA at Y-12 and must be quickly addressed to minimize impacts to future Y-12 missions, as well as human health and the environment. As part of the American Recovery and Reinvestment Act (ARRA), approximately 700,000 cubic feet of legacy material was removed in 2010 and 2011. In addition, characterization of the 9201-5 facility was scheduled in the winter and spring of 2011. This activity was initiated in January 2011 and was completed in July 2011. Heavy schedule pressure was further complicated by the fact that this building has active utility, security and process systems. Given these complex variables, a unique, out of the box characterization strategy was forged in an effort to bound radiological and chemical contaminants, as well as providing the appropriate level of quality to

  9. SU-E-T-365: Estimation of Neutron Ambient Dose Equivalents for Radioprotection Exposed Workers in Radiotherapy Facilities Based On Characterization Patient Risk Estimation

    SciTech Connect

    Irazola, L; Terron, J; Sanchez-Doblado, F; Domingo, C; Romero-Exposito, M; Garcia-Fuste, M; Sanchez-Nieto, B; Bedogni, R

    2015-06-15

    Purpose: Previous measurements with Bonner spheres{sup 1} showed that normalized neutron spectra are equal for the majority of the existing linacs{sup 2}. This information, in addition to thermal neutron fluences obtained in the characterization procedure{sup 3}3, would allow to estimate neutron doses accidentally received by exposed workers, without the need of an extra experimental measurement. Methods: Monte Carlo (MC) simulations demonstrated that the thermal neutron fluence distribution inside the bunker is quite uniform, as a consequence of multiple scatter in the walls{sup 4}. Although inverse square law is approximately valid for the fast component, a more precise calculation could be obtained with a generic fast fluence distribution map around the linac, from MC simulations{sup 4}. Thus, measurements of thermal neutron fluences performed during the characterization procedure{sup 3}, together with a generic unitary spectra{sup 2}, would allow to estimate the total neutron fluences and H*(10) at any point{sup 5}. As an example, we compared estimations with Bonner sphere measurements{sup 1}, for two points in five facilities: 3 Siemens (15–23 MV), Elekta (15 MV) and Varian (15 MV). Results: Thermal neutron fluences obtained from characterization, are within (0.2–1.6×10{sup 6}) cm−{sup 2}•Gy{sup −1} for the five studied facilities. This implies ambient equivalent doses ranging from (0.27–2.01) mSv/Gy 50 cm far from the isocenter and (0.03–0.26) mSv/Gy at detector location with an average deviation of ±12.1% respect to Bonner measurements. Conclusion: The good results obtained demonstrate that neutron fluence and H*(10) can be estimated based on: (a) characterization procedure established for patient risk estimation in each facility, (b) generic unitary neutron spectrum and (c) generic MC map distribution of the fast component. [1] Radiat. Meas (2010) 45: 1391 – 1397; [2] Phys. Med. Biol (2012) 5 7:6167–6191; [3] Med. Phys (2015) 42

  10. Current Chemical Risk Reduction Activities

    EPA Pesticide Factsheets

    EPA's existing chemicals programs address pollution prevention, risk assessment, hazard and exposure assessment and/or characterization, and risk management for chemicals substances in commercial use.

  11. Fact Sheet: Assessing Risks from Flame Retardants

    EPA Pesticide Factsheets

    EPA's assessing and managing risk programs address pollution prevention, risk assessment, hazard and exposure assessment and/or characterization, and risk management for chemicals substances in commercial use.

  12. Ex-vivo characterization of circulating colon cancer cells distinguished in stem and differentiated subset provides useful biomarker for personalized metastatic risk assessment.

    PubMed

    Malara, Natalia; Trunzo, Valentina; Foresta, Umberto; Amodio, Nicola; De Vitis, Stefania; Roveda, Laura; Fava, Mariagiovanna; Coluccio, MariaLaura; Macrì, Roberta; Di Vito, Anna; Costa, Nicola; Mignogna, Chiara; Britti, Domenico; Palma, Ernesto; Mollace, Vincenzo

    2016-05-12

    Circulating tumor cells (CTCs) represent one of the most interesting target in improving diagnosis, prognosis and treatment. Herein we evaluate the possibility of using an emo-cytometric approach on the evaluation of the heterogeneous population of CTCs to improve personalized metastatic risk assessment. We benchmarked ex vivo behavior of distinct subsets of circulating colon tumor cells with correspondent clinical behavior of patients from which we isolated CTCs. Isolation and CTC expansion were performed by a gradient protocol. In vitro characterization was determined by flow cytometry, immunofluorescence, western blotting and proteomic profiling. Cell sorter was performed with immunomagnetic beads. Confocal microscopy was used to evaluate tissue sections. Kaplan Mayer curves was cared for through Medcalc program. We collected heterogeneous CTCs, derived from the whole blood of seven patients affected by colon cancer, expressing CD133(pos)CD45(neg) (5 ± 1) and (2 ± 1) and CK20(pos)CD45(neg) of (29 ± 3) (11 ± 1) cells/ml in Dukes D and A stage respectively. Proliferation rate of 57 ± 16 %, expression for CXCR4(pos) of 18 ± 7 % and detectable levels of IL-6, IL-8 and SDF-1 cytokines in conditioned culture medium characterized short-time expanded-CTCs (eCTCs). ECTCs organized in tumor sphere were CD45(neg)CD133(pos) while in adhesion were CXCR4(pos)CK20(pos). These two subsets were separately injected in mice. The first group of xenografts developed superficial lesions within 2 weeks. In the second group, in absence of growing tumour, the survival of injected eCTCs was monitored through SDF-1 serum levels detection. The detection of human cancer cells expressing CK20, in mice tissues sections, suggested a different biological behaviour of injected eCTC-subsets: tumorigenic for the first and disseminating for the second. The benchmarking of the experimental data with the clinical course highlights that patients with prevalence of circulating

  13. Characterization of a family with rare deletions in CNTNAP5 and DOCK4 suggests novel risk loci for autism and dyslexia.

    PubMed

    Pagnamenta, Alistair T; Bacchelli, Elena; de Jonge, Maretha V; Mirza, Ghazala; Scerri, Thomas S; Minopoli, Fiorella; Chiocchetti, Andreas; Ludwig, Kerstin U; Hoffmann, Per; Paracchini, Silvia; Lowy, Ernesto; Harold, Denise H; Chapman, Jade A; Klauck, Sabine M; Poustka, Fritz; Houben, Renske H; Staal, Wouter G; Ophoff, Roel A; O'Donovan, Michael C; Williams, Julie; Nöthen, Markus M; Schulte-Körne, Gerd; Deloukas, Panos; Ragoussis, Jiannis; Bailey, Anthony J; Maestrini, Elena; Monaco, Anthony P

    2010-08-15

    Autism spectrum disorders (ASDs) are characterized by social, communication, and behavioral deficits and complex genetic etiology. A recent study of 517 ASD families implicated DOCK4 by single nucleotide polymorphism (SNP) association and a microdeletion in an affected sibling pair. The DOCK4 microdeletion on 7q31.1 was further characterized in this family using QuantiSNP analysis of 1M SNP array data and reverse transcription polymerase chain reaction. Extended family members were tested by polymerase chain reaction amplification of junction fragments. DOCK4 dosage was measured in additional samples using SNP arrays. Since QuantiSNP analysis identified a novel CNTNAP5 microdeletion in the same affected sibling pair, this gene was sequenced in 143 additional ASD families. Further polymerase chain reaction-restriction fragment length polymorphism analysis included 380 ASD cases and suitable control subjects. The maternally inherited microdeletion encompassed chr7:110,663,978-111,257,682 and led to a DOCK4-IMMP2L fusion transcript. It was also detected in five extended family members with no ASD. However, six of nine individuals with this microdeletion had poor reading ability, which prompted us to screen 606 other dyslexia cases. This led to the identification of a second DOCK4 microdeletion co-segregating with dyslexia. Assessment of genomic background in the original ASD family detected a paternal 2q14.3 microdeletion disrupting CNTNAP5 that was also transmitted to both affected siblings. Analysis of other ASD cohorts revealed four additional rare missense changes in CNTNAP5. No exonic deletions of DOCK4 or CNTNAP5 were seen in 2091 control subjects. This study highlights two new risk factors for ASD and dyslexia and demonstrates the importance of performing a high-resolution assessment of genomic background, even after detection of a rare and likely damaging microdeletion using a targeted approach. Copyright 2010 Society of Biological Psychiatry. Published by

  14. Characterization of a Family with Rare Deletions in CNTNAP5 and DOCK4 Suggests Novel Risk Loci for Autism and Dyslexia

    PubMed Central

    Pagnamenta, Alistair T.; Bacchelli, Elena; de Jonge, Maretha V.; Mirza, Ghazala; Scerri, Thomas S.; Minopoli, Fiorella; Chiocchetti, Andreas; Ludwig, Kerstin U.; Hoffmann, Per; Paracchini, Silvia; Lowy, Ernesto; Harold, Denise H.; Chapman, Jade A.; Klauck, Sabine M.; Poustka, Fritz; Houben, Renske H.; Staal, Wouter G.; Ophoff, Roel A.; O'Donovan, Michael C.; Williams, Julie; Nöthen, Markus M.; Schulte-Körne, Gerd; Deloukas, Panos; Ragoussis, Jiannis; Bailey, Anthony J.; Maestrini, Elena; Monaco, Anthony P.

    2010-01-01

    Background Autism spectrum disorders (ASDs) are characterized by social, communication, and behavioral deficits and complex genetic etiology. A recent study of 517 ASD families implicated DOCK4 by single nucleotide polymorphism (SNP) association and a microdeletion in an affected sibling pair. Methods The DOCK4 microdeletion on 7q31.1 was further characterized in this family using QuantiSNP analysis of 1M SNP array data and reverse transcription polymerase chain reaction. Extended family members were tested by polymerase chain reaction amplification of junction fragments. DOCK4 dosage was measured in additional samples using SNP arrays. Since QuantiSNP analysis identified a novel CNTNAP5 microdeletion in the same affected sibling pair, this gene was sequenced in 143 additional ASD families. Further polymerase chain reaction-restriction fragment length polymorphism analysis included 380 ASD cases and suitable control subjects. Results The maternally inherited microdeletion encompassed chr7:110,663,978-111,257,682 and led to a DOCK4-IMMP2L fusion transcript. It was also detected in five extended family members with no ASD. However, six of nine individuals with this microdeletion had poor reading ability, which prompted us to screen 606 other dyslexia cases. This led to the identification of a second DOCK4 microdeletion co-segregating with dyslexia. Assessment of genomic background in the original ASD family detected a paternal 2q14.3 microdeletion disrupting CNTNAP5 that was also transmitted to both affected siblings. Analysis of other ASD cohorts revealed four additional rare missense changes in CNTNAP5. No exonic deletions of DOCK4 or CNTNAP5 were seen in 2091 control subjects. Conclusions This study highlights two new risk factors for ASD and dyslexia and demonstrates the importance of performing a high-resolution assessment of genomic background, even after detection of a rare and likely damaging microdeletion using a targeted approach. PMID:20346443

  15. Characterization, heavy metal content and health risk assessment of urban road dusts from the historic center of the city of Thessaloniki, Greece.

    PubMed

    Bourliva, Anna; Christophoridis, Christophoros; Papadopoulou, Lambrini; Giouri, Katerina; Papadopoulos, Argyrios; Mitsika, Elena; Fytianos, Konstantinos

    2016-05-30

    In the present study, an investigation of the mineralogy and morphology, the heavy metal content and the health risk of urban road dusts from the second largest city of Greece was conducted. For this reason road dust samples from selected sites within the city core area were collected. No differences were observed in the mineralogy of road dusts coming from different sampling sites, and they were mainly consisted of quartz and calcite, while an elevated amorphous content was detected. Morphologically road dusts presented Ca-rich, Fe-rich and silicates particles with various shapes and sizes. The mean concentrations of Cd, Cr, Cu, Mn, Ni, Pb and Zn in road dust were 1.76, 104.9, 662.3, 336.4, 89.43, 209 and 452.8 μg g(-1), respectively. A series of spatial distribution patterns revealed that the hotspot areas were tended to associate with major road junctions and regions with high traffic. Combination of pollution indexes and statistical analyses (correlation analysis, cluster analysis and principal component analysis) revealed that road dusts have a severe influence by anthropogenic activities. In attempt to identify the source of metals through geostatistical and multivariate statistical analyses, it was concluded as follows: Cr, Cu, Fe and Zn mainly originated from tire/break wear and vehicle abrasions, while Cd, Mn and Pb were mainly related to fuel/oil leakage from automobiles along with oil lubricants and vehicle abrasion. Hazard quotient values for children based on total metal concentrations for the road dust ingestion route were lower than safe level (=1). However, the fact that the Hazard Index value for Pb (0.459) which is a particularly toxic metal, was close to safe level, renders essential further investigation in order to provide more reliable characterizations of potential health risks.

  16. Characterization of androgenetic/biparental mosaic/chimeric conceptions, including those with a molar component: morphology, p57 immnohistochemistry, molecular genotyping, and risk of persistent gestational trophoblastic disease.

    PubMed

    Lewis, Gloria H; DeScipio, Cheryl; Murphy, Kathleen M; Haley, Lisa; Beierl, Katie; Mosier, Stacy; Tandy, Sharon; Cohen, Debra S; Lytwyn, Alice; Elit, Laurie; Vang, Russell; Ronnett, Brigitte M

    2013-03-01

    Recent studies have demonstrated the value of ancillary techniques, including p57 immunohistochemistry and short tandem repeat genotyping, for distinguishing hydatidiform moles (HM) from nonmolar specimens and for subtyping HMs as complete hydatidiform moles (CHM) and partial hydatidiform moles (PHM). With rare exceptions, CHMs are p57-negative and androgenetic diploid; partial hydatidiform moles are p57-positive and diandric triploid; and nonmolar specimens are p57-positive and biparental diploid. Androgenetic/biparental mosaic/chimeric conceptions can have morphologic features that overlap with HMs but are genetically distinct. This study characterizes 11 androgenetic/biparental mosaic/chimeric conceptions identified in a series of 473 products of conception specimens subjected to p57 immunohistochemistry and short tandem repeat genotyping. Fluorescence in situ hybridization was performed on 10 to assess ploidy. All cases were characterized by hydropically enlarged, variably sized and shaped villi. In 5 cases, the villi lacked trophoblastic hyperplasia, whereas in 6 there was a focal to extensive villous component with trophoblastic hyperplasia and features of CHM. The villi lacking trophoblastic hyperplasia were characterized by discordant p57 expression within individual villi (p57-positive cytotrophoblast and p57-negative stromal cells), whereas the villous components having trophoblastic hyperplasia were uniformly p57-negative in both cell types. Short tandem repeat genotyping of at least 2 villous areas in each case demonstrated an excess of paternal alleles in all regions, with variable paternal:maternal allele ratios (usually >2:1); pure androgenetic diploidy was identified in those cases with a sufficiently sized villous component having trophoblastic hyperplasia and features of CHM. Fluorescence in situ hybridization demonstrated uniform diploidy in 7 cases, including 4 of 5 tested cases with trophoblastic hyperplasia and 3 of 5 cases without

  17. Characterizing the HIV risks and potential pathways to HIV infection among transgender women in Côte d'Ivoire, Togo and Burkina Faso

    PubMed Central

    Stahlman, Shauna; Liestman, Benjamin; Ketende, Sosthenes; Kouanda, Seni; Ky-Zerbo, Odette; Lougue, Marcel; Diouf, Daouda; Anato, Simplice; Tchalla, Jules; Bamba, Amara; Drame, Fatou Maria; Ezouatchi, Rebecca; Kouamé, Abo; Baral, Stefan D

    2016-01-01

    Introduction Transgender women are at high risk for the acquisition and transmission of HIV. However, there are limited empiric data characterizing HIV-related risks among transgender women in sub-Saharan Africa. The objective of these analyses is to determine what factors, including sexual behaviour stigma, condom use and engagement in sex work, contribute to risk for HIV infection among transgender women across three West African nations. Methods Data were collected via respondent-driven sampling from men who have sex with men (MSM) and transgender women during three- to five-month intervals from December 2012 to October 2015 across a total of six study sites in Togo, Burkina Faso and Côte d'Ivoire. During the study visit, participants completed a questionnaire and were tested for HIV. Chi-square tests were used to compare the prevalence of variables of interest between transgender women and MSM. A multilevel generalized structural equation model (GSEM) was used to account for clustering of observations within study sites in the multivariable analysis, as well as to estimate mediated associations between sexual behaviour stigma and HIV infection among transgender women. Results In total, 2456 participants meeting eligibility criteria were recruited, of which 453 individuals identified as being female/transgender. Transgender women were more likely than MSM to report selling sex to a male partner within the past 12 months (p<0.01), to be living with HIV (p<0.01) and to report greater levels of sexual behaviour stigma as compared with MSM (p<0.05). In the GSEM, sexual behaviour stigma from broader social groups was positively associated with condomless anal sex (adjusted odds ratio (AOR)=1.33, 95% confidence interval (CI)=1.09, 1.62) and with selling sex (AOR=1.23, 95% CI=1.02, 1.50). Stigma from family/friends was also associated with selling sex (AOR=1.42, 95% CI=1.13, 1.79), although no significant associations were identified with prevalent HIV infection

  18. Characterizing the HIV risks and potential pathways to HIV infection among transgender women in Côte d'Ivoire, Togo and Burkina Faso.

    PubMed

    Stahlman, Shauna; Liestman, Benjamin; Ketende, Sosthenes; Kouanda, Seni; Ky-Zerbo, Odette; Lougue, Marcel; Diouf, Daouda; Anato, Simplice; Tchalla, Jules; Bamba, Amara; Drame, Fatou Maria; Ezouatchi, Rebecca; Kouamé, Abo; Baral, Stefan D

    2016-01-01

    Transgender women are at high risk for the acquisition and transmission of HIV. However, there are limited empiric data characterizing HIV-related risks among transgender women in sub-Saharan Africa. The objective of these analyses is to determine what factors, including sexual behaviour stigma, condom use and engagement in sex work, contribute to risk for HIV infection among transgender women across three West African nations. Data were collected via respondent-driven sampling from men who have sex with men (MSM) and transgender women during three- to five-month intervals from December 2012 to October 2015 across a total of six study sites in Togo, Burkina Faso and Côte d'Ivoire. During the study visit, participants completed a questionnaire and were tested for HIV. Chi-square tests were used to compare the prevalence of variables of interest between transgender women and MSM. A multilevel generalized structural equation model (GSEM) was used to account for clustering of observations within study sites in the multivariable analysis, as well as to estimate mediated associations between sexual behaviour stigma and HIV infection among transgender women. In total, 2456 participants meeting eligibility criteria were recruited, of which 453 individuals identified as being female/transgender. Transgender women were more likely than MSM to report selling sex to a male partner within the past 12 months (p<0.01), to be living with HIV (p<0.01) and to report greater levels of sexual behaviour stigma as compared with MSM (p<0.05). In the GSEM, sexual behaviour stigma from broader social groups was positively associated with condomless anal sex (adjusted odds ratio (AOR)=1.33, 95% confidence interval (CI)=1.09, 1.62) and with selling sex (AOR=1.23, 95% CI=1.02, 1.50). Stigma from family/friends was also associated with selling sex (AOR=1.42, 95% CI=1.13, 1.79), although no significant associations were identified with prevalent HIV infection. These data suggest that

  19. Geomorphological Characterization of Atenquique Basin in the Eastern Sector of the Volcan-Nevado-Colima, Jalisco, Mexico, As an Input to the Risk Assessment of Debris Flows.

    NASA Astrophysics Data System (ADS)

    Flores-Pena, S.; Suarez-Plascencia, C.

    2014-12-01

    The Atenquique river basin drains the eastern sector of the Volcanic Complex (VC) Volcan-Nevado de Colima, located on the border of the states of Jalisco and Colima. To use the digital geomorphological analysis 1:50000 scale mapping provided by INEGI and Landsat images, manipulating it in ArcGIS 10.2 developing the DEM that was the basis for morphometric characterization. The results show that the basin is divided into five sub-basins, with the main Atenquique (SAT) and Arroyo Seco (SAS), calculating the compactness coefficient (Kc) and the coefficient of sinuosity indicate that SAT is the most prone to floods due to straight and slightly sinuous channels. However, the density of dissection shows a more developed drainage network on the SAT, with slopes up to 84° and 600 m deep. The drainage basin has its source at an altitude of 4260 m and its mouth is in the Tuxpan River at 1040 m, which has a relative height of 2800 m; has a funnel-shaped elongated west-east, its outstanding average in the sector are Mountain 44° and 10° the piedmont. The SAT has a total area of 81.8 km2, with a dendritic river network, where the first order streams reach an 82.99%, and second order streams are the 13.4% of the total, these values show that most of the slopes of the basin have incipient development valleys and steep slopes. The basin has had 3 debris flows in recent 58 years; these are formed by large volumes of rock and mud that covered the town of Atenquique and paper mill located at the mouth of the Tuxpan River, caused deaths and significant economic damage. Its genesis is associated with the end of the summer rainy season, so he also worked in the hydrological analysis in order to determine the volume of runoff in the basin. The results of this work are used as input for the determining the risk levels in the study area, and may also be used by the municipality of Tuxpan, in order to define policies to manage risk and reduce future risks to the industrial town of

  20. Methods for Addressing Uncertainty and Variability to Characterize Potential Health Risk from Trichloroethylene-Contaminated Ground Water at Beale Air Force Base in California:Integration of Uncertainty and Variability in Pharmacokinetics and Dose-Response

    SciTech Connect

    Bogen, K T

    2001-05-24

    Traditional estimates of health risk are typically inflated, particularly if cancer is the dominant endpoint and there is fundamental uncertainty as to mechanism(s) of action. Risk is more realistically characterized if it accounts for joint uncertainty and interindividual variability within a systematic probabilistic framework to integrate the joint effects on risk of distributed parameters of all (linear as well as nonlinear) risk-extrapolation models involved. Such a framework was used to characterize risks to potential future residents posed by trichloroethylene (TCE) in ground water at an inactive landfill site on Beale Air Force Base in California. Variability and uncertainty were addressed in exposure-route-specific estimates of applied dose, in pharmacokinetically based estimates of route-specific metabolized fractions of absorbed TCE, and in corresponding biologically effective doses estimated under a genotoxic/linear (MA{sub G}) vs. a cytotoxic/nonlinear (MA{sub c}) mechanistic assumption for TCE-induced cancer. Increased risk conditional on effective dose was estimated under MA{sub G} based on seven rodent-bioassay data sets, and under MA{sub c} based on mouse hepatotoxicity data. Mean and upper-bound estimates of combined risk calculated by the unified approach were <10{sup -6} and 10{sup -4}, respectively, while corresponding estimates based on traditional deterministic methods were >10{sup -5} and 10{sup -4}, respectively. It was estimated that no TCE-related harm is likely to occur due to any plausible residential exposure scenario involving the site. The systematic probabilistic framework illustrated is particularly suited to characterizing risks that involve uncertain and/or diverse mechanisms of action.

  1. Methods for Addressing Uncertainty and Variability to Characterize Potential Health Risk From Trichloroethylene-Contaminated Ground Water Beale Air Force Base in California: Integration of Uncertainty and Variability in Pharmacokinetics and Dose-Response

    SciTech Connect

    Bogen, K.T.

    1999-09-29

    Traditional estimates of health risk are typically inflated, particularly if cancer is the dominant endpoint and there is fundamental uncertainty as to mechanism(s) of action. Risk is more realistically characterized if it accounts for joint uncertainty and interindividual variability after applying a unified probabilistic approach to the distributed parameters of all (linear as well as nonlinear) risk-extrapolation models involved. Such an approach was applied to characterize risks to potential future residents posed by trichloroethylene (TCE) in ground water at an inactive landfill site on Beale Air Force Base in California. Variability and uncertainty were addressed in exposure-route-specific estimates of applied dose, in pharmacokinetically based estimates of route-specific metabolized fractions of absorbed TCE, and in corresponding biologically effective doses estimated under a genotoxic/linear (MA{sub g}) vs. a cytotoxic/nonlinear (MA{sub c}) mechanistic assumption for TCE-induced cancer. Increased risk conditional on effective dose was estimated under MA{sub G} based on seven rodent-bioassay data sets, and under MA, based on mouse hepatotoxicity data. Mean and upper-bound estimates of combined risk calculated by the unified approach were <10{sup -6} and <10{sup -4}, respectively, while corresponding estimates based on traditional deterministic methods were >10{sup -5} and >10{sup -4}, respectively. It was estimated that no TCE-related harm is likely occur due any plausible residential exposure scenario involving the site. The unified approach illustrated is particularly suited to characterizing risks that involve uncertain and/or diverse mechanisms of action.

  2. DNA multigene characterization of Fasciola hepatica and Lymnaea neotropica and its fascioliasis transmission capacity in Uruguay, with historical correlation, human report review and infection risk analysis.

    PubMed

    Bargues, María Dolores; Gayo, Valeria; Sanchis, Jaime; Artigas, Patricio; Khoubbane, Messaoud; Birriel, Soledad; Mas-Coma, Santiago

    2017-02-01

    Fascioliasis is a pathogenic disease transmitted by lymnaeid snails and recently emerging in humans, in part due to effects of climate changes, anthropogenic environment modifications, import/export and movements of livestock. South America is the continent presenting more human fascioliasis hyperendemic areas and the highest prevalences and intensities known. These scenarios appear mainly linked to altitude areas in Andean countries, whereas lowland areas of non-Andean countries, such as Uruguay, only show sporadic human cases or outbreaks. A study including DNA marker sequencing of fasciolids and lymnaeids, an experimental study of the life cycle in Uruguay, and a review of human fascioliasis in Uruguay, are performed. The characterization of Fasciola hepatica from cattle and horses of Uruguay included the complete sequences of the ribosomal DNA ITS-2 and ITS-1 and mitochondrial DNA cox1 and nad1. ITS-2, ITS-1, partial cox1 and rDNA 16S gene of mtDNA were used for lymnaeids. Results indicated that vectors belong to Lymnaea neotropica instead of to Lymnaea viator, as always reported from Uruguay. The life cycle and transmission features of F. hepatica by L. neotropica of Uruguay were studied under standardized experimental conditions to enable a comparison with the transmission capacity of F. hepatica by Galba truncatula at very high altitude in Bolivia. On this baseline, we reviewed the 95 human fascioliasis cases reported in Uruguay and analyzed the risk of human infection in front of future climate change estimations. The correlation of fasciolid and lymnaeid haplotypes with historical data on the introduction and spread of livestock into Uruguay allowed to understand the molecular diversity detected. Although Uruguayan L. neotropica is a highly efficient vector, its transmission capacity is markedly lower than that of Bolivian G. truncatula. This allows to understand the transmission and epidemiological differences between Andean highlands and non

  3. Systematic Characterization of the Computed Tomography Angiography Spot Sign in Primary Intracerebral Hemorrhage Identifies Patients at Highest Risk for Hematoma Expansion

    PubMed Central

    Delgado Almandoz, Josser E.; Yoo, Albert J.; Stone, Michael J.; Schaefer, Pamela W.; Goldstein, Joshua N.; Rosand, Jonathan; Oleinik, Alexandra; Lev, Michael H.; Gonzalez, R. Gilberto; Romero, Javier M.

    2012-01-01

    Background and Purpose The presence of active contrast extravasation (the spot sign) on computed tomography (CT) angiography has been recognized as a predictor of hematoma expansion in patients with intracerebral hemorrhage. We aim to systematically characterize the spot sign to identify features that are most predictive of hematoma expansion and construct a spot sign scoring system. Methods We retrospectively reviewed CT angiograms performed in all patients who presented to our emergency department over a 9-year period with primary intracerebral hemorrhage and had a follow-up noncontrast head CT within 48 hours of the baseline CT angiogram. Three neuroradiologists reviewed the CT angiograms and determined the presence and characteristics of spot signs according to strict radiological criteria. Baseline and follow-up intracerebral hemorrhage volumes were determined by computer-assisted volumetric analysis. Results We identified spot signs in 71 of 367 CT angiograms (19%), 6 of which were delayed spot signs (8%). The presence of any spot sign increased the risk of significant hematoma expansion (69%, OR=92, P<0.0001). Among the spot sign characteristics examined, the presence of ≥3 spot signs, a maximum axial dimension ≥5 mm, and maximum attenuation ≥180 Hounsfield units were independent predictors of significant hematoma expansion, and these were subsequently used to construct the spot sign score. In multivariate analysis, the spot sign score was the strongest predictor of significant hematoma expansion, independent of time from ictus to CT angiogram evaluation. Conclusion The spot sign score predicts significant hematoma expansion in primary intracerebral hemorrhage. If validated in other data sets, it could be used to select patients for early hemostatic therapy. PMID:19574553

  4. Robustness of RISMC Insights under Alternative Aleatory/Epistemic Uncertainty Classifications: Draft Report under the Risk-Informed Safety Margin Characterization (RISMC) Pathway of the DOE Light Water Reactor Sustainability Program

    SciTech Connect

    Unwin, Stephen D.; Eslinger, Paul W.; Johnson, Kenneth I.

    2012-09-20

    The Risk-Informed Safety Margin Characterization (RISMC) pathway is a set of activities defined under the U.S. Department of Energy (DOE) Light Water Reactor Sustainability Program. The overarching objective of RISMC is to support plant life-extension decision-making by providing a state-of-knowledge characterization of safety margins in key systems, structures, and components (SSCs). A technical challenge at the core of this effort is to establish the conceptual and technical feasibility of analyzing safety margin in a risk-informed way, which, unlike conventionally defined deterministic margin analysis, would be founded on probabilistic characterizations of uncertainty in SSC performance. In the context of probabilistic risk assessment (PRA) technology, there has arisen a general consensus about the distinctive roles of two types of uncertainty: aleatory and epistemic, where the former represents irreducible, random variability inherent in a system, whereas the latter represents a state of knowledge uncertainty on the part of the analyst about the system which is, in principle, reducible through further research. While there is often some ambiguity about how any one contributing uncertainty in an analysis should be classified, there has nevertheless emerged a broad consensus on the meanings of these uncertainty types in the PRA setting. However, while RISMC methodology shares some features with conventional PRA, it will nevertheless be a distinctive methodology set. Therefore, the paradigms for classification of uncertainty in the PRA setting may not fully port to the RISMC environment. Yet the notion of risk-informed margin is based on the characterization of uncertainty, and it is therefore critical to establish a common understanding of uncertainty in the RISMC setting.

  5. DNA multigene characterization of Fasciola hepatica and Lymnaea neotropica and its fascioliasis transmission capacity in Uruguay, with historical correlation, human report review and infection risk analysis

    PubMed Central

    Gayo, Valeria; Sanchis, Jaime; Artigas, Patricio; Khoubbane, Messaoud; Birriel, Soledad; Mas-Coma, Santiago

    2017-01-01

    Background Fascioliasis is a pathogenic disease transmitted by lymnaeid snails and recently emerging in humans, in part due to effects of climate changes, anthropogenic environment modifications, import/export and movements of livestock. South America is the continent presenting more human fascioliasis hyperendemic areas and the highest prevalences and intensities known. These scenarios appear mainly linked to altitude areas in Andean countries, whereas lowland areas of non-Andean countries, such as Uruguay, only show sporadic human cases or outbreaks. A study including DNA marker sequencing of fasciolids and lymnaeids, an experimental study of the life cycle in Uruguay, and a review of human fascioliasis in Uruguay, are performed. Methodology/Principal findings The characterization of Fasciola hepatica from cattle and horses of Uruguay included the complete sequences of the ribosomal DNA ITS-2 and ITS-1 and mitochondrial DNA cox1 and nad1. ITS-2, ITS-1, partial cox1 and rDNA 16S gene of mtDNA were used for lymnaeids. Results indicated that vectors belong to Lymnaea neotropica instead of to Lymnaea viator, as always reported from Uruguay. The life cycle and transmission features of F. hepatica by L. neotropica of Uruguay were studied under standardized experimental conditions to enable a comparison with the transmission capacity of F. hepatica by Galba truncatula at very high altitude in Bolivia. On this baseline, we reviewed the 95 human fascioliasis cases reported in Uruguay and analyzed the risk of human infection in front of future climate change estimations. Conclusions/Significance The correlation of fasciolid and lymnaeid haplotypes with historical data on the introduction and spread of livestock into Uruguay allowed to understand the molecular diversity detected. Although Uruguayan L. neotropica is a highly efficient vector, its transmission capacity is markedly lower than that of Bolivian G. truncatula. This allows to understand the transmission and

  6. Characterizing environmental risk factors for West Nile virus in Quebec, Canada, using clinical data in humans and serology in pet dogs.

    PubMed

    Rocheleau, J P; Michel, P; Lindsay, L R; Drebot, M; Dibernardo, A; Ogden, N H; Fortin, A; Arsenault, J

    2017-10-01

    The identification of specific environments sustaining emerging arbovirus amplification and transmission to humans is a key component of public health intervention planning. This study aimed at identifying environmental factors associated with West Nile virus (WNV) infections in southern Quebec, Canada, by modelling and jointly interpreting aggregated clinical data in humans and serological data in pet dogs. Environmental risk factors were estimated in humans by negative binomial regression based on a dataset of 191 human WNV clinical cases reported in the study area between 2011 and 2014. Risk factors for infection in dogs were evaluated by logistic and negative binomial models based on a dataset including WNV serological results from 1442 dogs sampled from the same geographical area in 2013. Forested lands were identified as low-risk environments in humans. Agricultural lands represented higher risk environments for dogs. Environments identified as impacting risk in the current study were somewhat different from those identified in other studies conducted in north-eastern USA, which reported higher risk in suburban environments. In the context of the current study, combining human and animal data allowed a more comprehensive and possibly a more accurate view of environmental WNV risk factors to be obtained than by studying aggregated human data alone.

  7. Characterization and environmental risk assessment of heavy metals in construction and demolition wastes from five sources (chemical, metallurgical and light industries, and residential and recycled aggregates).

    PubMed

    Gao, Xiaofeng; Gu, Yilu; Xie, Tian; Zhen, Guangyin; Huang, Sheng; Zhao, Youcai

    2015-06-01

    Total concentrations of heavy metals (Cu, Zn, Pb, Cr, Cd, and Ni) were measured among 63 samples of construction and demolition (C&D) wastes collected from chemical, metallurgical and light industries, and residential and recycled aggregates within China for risk assessment. The heavy metal contamination was primarily concentrated in the chemical and metallurgical industries, especially in the electroplating factory and zinc smelting plant. High concentrations of Cd were found in light industry samples, while the residential and recycled aggregate samples were severely polluted by Zn. Six most polluted samples were selected for deep research. Mineralogical analysis by X-ray fluorescence (XRF) spectrometry and X-ray diffraction (XRD), combined with element speciation through European Community Bureau of Reference (BCR) sequential extraction, revealed that a relatively slight corrosion happened in the four samples from electroplating plants but high transfer ability for large quantities of Zn and Cu. Lead arsenate existed in the acid extractable fraction in CI7-8 and potassium chromium oxide existed in the mobility fraction. High concentration of Cr could be in amorphous forms existing in CI9. The high content of sodium in the two samples from zinc smelter plants suggested severe deposition and erosion on the workshop floor. Large quantities of Cu existed as copper halide and most of the Zn appeared to be zinc, zinc oxide, barium zinc oxide, and zincite. From the results of the risk assessment code (RAC), the samples from the electroplating factory posed a very high risk of Zn, Cu, and Cr, a high risk of Ni, a middle risk of Pb, and a low risk of Cd. The samples from the zinc smelting plant presented a high risk of Zn, a middle risk of Cu, and a low risk of Pb, Cr, Cd, and Ni.

  8. Approaches for describing and communicating overall uncertainty in toxicity characterizations: U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) as a case study.

    PubMed

    Beck, Nancy B; Becker, Richard A; Erraguntla, Neeraja; Farland, William H; Grant, Roberta L; Gray, George; Kirman, Christopher; LaKind, Judy S; Jeffrey Lewis, R; Nance, Patricia; Pottenger, Lynn H; Santos, Susan L; Shirley, Stephanie; Simon, Ted; Dourson, Michael L

    2016-01-01

    Single point estimates of human health hazard/toxicity values such as a reference dose (RfD) are generally used in chemical hazard and risk assessment programs for assessing potential risks associated with site- or use-specific exposures. The resulting point estimates are often used by risk managers for regulatory decision-making, including standard setting, determination of emission controls, and mitigation of exposures to chemical substances. Risk managers, as well as stakeholders (interested and affected parties), often have limited information regarding assumptions and uncertainty factors in numerical estimates of both hazards and risks. Further, the use of different approaches for addressing uncertainty, which vary in transparency, can lead to a lack of confidence in the scientific underpinning of regulatory decision-making. The overarching goal of this paper, which was developed from an invited participant workshop, is to offer five approaches for presenting toxicity values in a transparent manner in order to improve the understanding, consideration, and informed use of uncertainty by risk assessors, risk managers, and stakeholders. The five approaches for improving the presentation and communication of uncertainty are described using U.S. Environmental Protection Agency's (EPA's) Integrated Risk Information System (IRIS) as a case study. These approaches will ensure transparency in the documentation, development, and use of toxicity values at EPA, the Agency for Toxic Substances and Disease Registry (ATSDR), and other similar assessment programs in the public and private sector. Further empirical testing will help to inform the approaches that will work best for specific audiences and situations. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Spatial characterization, risk assessment, and statistical source identification of the dissolved trace elements in the Ganjiang River-feeding tributary of the Poyang Lake, China.

    PubMed

    Zhang, Hua; Jiang, Yinghui; Wang, Min; Wang, Peng; Shi, Guangxun; Ding, Mingjun

    2017-01-01

    Surface water samples were collected from 20 sampling sites throughout the Ganjiang River during pre-monsoon, monsoon, and post-monsoon seasons, and the concentrations of dissolved trace elements were determined by inductively coupled plasma-mass spectrometry (ICP-MS) for the spatial and seasonal variations, risk assessment, source identification, and categorization for risk area. The result demonstrated that concentrations of the elements exhibited significant seasonality. The high total element concentrations were detected at sites close to the intensive mining and urban activities. The concentrations of the elements were under the permissible limits as prescribed by related standards with a few exceptions. The most of heavy metal pollution index (HPI) values were lower than the critical index limit, indicating the basically clean water used as habitat for aquatic life. As was identified as the priority pollutant of non-carcinogenic and carcinogenic concerns, and the inhabitants ingesting the surface water at particular site might be subjected to the integrated health risks for exposure to the mixed trace elements. Multivariate statistical analyses confirmed that Zn, As, Cd, and Tl were derived from mining and urban activities; V, Cd, and Pb exhibited mixed origin; and Co, Ni, and Cu mainly resulted from natural processes. Three categorized risk areas corresponded to high, moderate, and low risks, respectively. As a whole, the upstream of the Ganjiang River was identified as the high-risk area relatively.

  10. Characterization and environmental risk assessment of heavy metals found in fly ashes from waste filter bags obtained from a Chinese steel plant.

    PubMed

    Zhou, Yun; Ning, Xun-an; Liao, Xikai; Lin, Meiqing; Liu, Jingyong; Wang, Jianghui

    2013-09-01

    The environmental risk of exposure to six heavy metals (Cu, Pb, Zn, Cr, Ni, and Cd) found in fly ashes from waste filter bags obtained from a steel plant was estimated based on the mineralogical compositions, total concentrations and speciation of the metals in the fly ashes. The results indicated that the fly ashes mainly consisted of hematite, magnetite, cyanite, spinel, coesite and amorphous materials. The concentrations of Zn and Pb were much higher than that of other materials. After Zn and Pb, Ni was present in the highest concentration, followed by Cu, Cr and Cd. Each heavy metal was distributed differently in fly ashes. The levels of Zn, Cd and Pb in the active fraction were very high, and ranged from 64.83 to 81.96%, 34.48 to 82.4% and 6.92 to 79.65% respectively, while Cu, Cr and Ni were mainly present in the residual fraction. The risk assessment code (RAC) values of fly ashes showed that the Zn and Cd present in the H3 sample presented a very high risk, with RAC values greater than 50%. The Cu present in the H3 sample, Cd in the H2 sample and Zn in the H4 and H5 samples presented a high risk. The Pb present in the H2 sample, Cd in the H4 sample, Ni in the H1 and H5 samples, and Zn in the H1 sample presented a medium risk. A low risk was presented by the Cu present in the H1, H2, H4 and H5 samples, the Pb in the H1, H3 and H5 samples, the Cd in the H1 and H5 samples, and the Ni in the H2 sample. No risk was presented by Cr in any sample.

  11. Characterization, distribution, and risk assessment of heavy metals in agricultural soil and products around mining and smelting areas of Hezhang, China.

    PubMed

    Briki, Meryem; Ji, Hongbing; Li, Cai; Ding, Huaijian; Gao, Yang

    2015-12-01

    Mining and smelting have been releasing huge amount of toxic substances into the environment. In the present study, agricultural soil and different agricultural products (potato, Chinese cabbage, garlic bolt, corn) were analyzed to examine the source, spatial distribution, and risk of 12 elements (As, Be, Bi, Cd, Co, Cr, Cu, Hg, Ni, Pb, Sb, and Zn) in agricultural soil near mine fields, smelting fields, and mountain field around Hezhang County, west of Guizhou Province, China. Multivariate statistical analysis indicated that in mining area, As, Bi, Cd, Cu, Hg, Pb, Sb, and Zn were generated from anthropogenic sources; in smelting area, As, Be, Cd, Co, Cu, Pb, Sb, and Zn were derived from anthropogenic sources through zinc smelting ceased in 2004. The enrichment factors (EFs) and ecological risk index (RI) of soil in mining area are the most harmful, showing extremely high enrichment and very high ecological risk of As, Bi, Cd, Cu, Hg, Pb, Sb, and Zn. Zinc is the most significant enriched in the smelting area; however, mountain area has a moderate enrichment and ecological risk and do not present any ecological risk. According to spatial distribution, the concentrations depend on the nearby mining and smelting activities. Transfer factors (TFs) in the smelting area and mountain are high, implying a threat for human consumption. Therefore, further studies should be carried out taking into account the harm of those heavy metals and potential negative health effects from the consumption of agricultural products in these circumstances.

  12. Identification of a dietary pattern characterized by high-fat food choices associated with increased risk of breast cancer: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.

    PubMed

    Schulz, Mandy; Hoffmann, Kurt; Weikert, Cornelia; Nöthlings, Ute; Schulze, Matthias B; Boeing, Heiner

    2008-11-01

    Epidemiological studies conducted thus far have mainly used a single-nutrient approach which may not be sufficient in detecting diet-cancer relationships. The aim of the study was to examine the association of a food pattern based on explained variations in fatty acid intake by means of reduced rank regression with breast cancer risk. Study participants were female subjects (n 15,351) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study free of cancer at baseline and with complete dietary and outcome information followed for an average of 6.0 years. Among those, 137 incident cases of invasive breast cancer were identified. We identified a food pattern characterized by low consumption of bread, and fruit juices, and high consumption of processed meat, fish, butter and other animal fats, and margarine explaining >42 % of total variation in fatty acid intake (SFA, MUFA, n-3 PUFA, n-6 PUFA). Intake of all four fatty acid fractions was positively associated with the pattern score. Adherence to this food pattern adjusted for covariates was associated with a two-fold risk (hazard ratio 2.00; 95 % CI 1.30, 3.09) of breast cancer comparing extreme tertiles of the pattern score. There was no evidence of effect modification by menopausal status, overweight status and use of hormone replacement therapy, respectively. In conclusion, a food pattern characterized by high-fat food choices was significantly associated with increased risk of breast cancer. Given that the food pattern was high in all fatty acid fractions, we found evidence for total dietary fat rather than for specific fatty acids to be associated with breast cancer risk.

  13. Characterizing chronic and acute health risks of residues of veterinary drugs in food: latest methodological developments by the joint FAO/WHO expert committee on food additives.

    PubMed

    Boobis, Alan; Cerniglia, Carl; Chicoine, Alan; Fattori, Vittorio; Lipp, Markus; Reuss, Rainer; Verger, Philippe; Tritscher, Angelika

    2017-07-10

    The risk assessment of residues of veterinary drugs in food is a field that continues to evolve. The toxicological end-points to be considered are becoming more nuanced and in light of growing concern about the development of antimicrobial resistance, detailed analysis of the antimicrobial activity of the residues of veterinary drugs in food is increasingly incorporated in the assessment. In recent years, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has refined its approaches to provide a more comprehensive and fit-for-purpose risk assessment. This publication describes in detail the consideration of acute and chronic effects, the estimation of acute and chronic dietary exposure, current approaches for including microbiological endpoints in the risk assessment, and JECFA's considerations for the potential effects of food processing on residues from veterinary drugs. JECFA now applies these approaches in the development of health-based guidance values (i.e. safe exposure levels) for residues of veterinary drugs. JECFA, thus, comprehensively addresses acute and chronic risks by using corresponding estimates for acute and chronic exposure and suitable correction for the limited bioavailability of bound residues by the Gallo-Torres model. On a case-by-case basis, JECFA also considers degradation products that occur from normal food processing of food containing veterinary drug residues. These approaches will continue to be refined to ensure the most scientifically sound basis for the establishment of health-based guidance values for veterinary drug residues.

  14. PROCEEDINGS AND SUMMARY REPORT OF THE USEPA WORKSHOP ON MANAGING ARSENIC RISKS TO THE ENVIRONMENT: CHARACTERIZATION OF WASTE, CHEMISTRY AND TREATMENT AND DISPOSAL

    EPA Science Inventory

    The workshop "Managing Arsenic Risks to the Environment: Charaterization of Waste, Chemistry and Treatment and Disposal," was held 5/1-3/2001 in Denver, CO. This workshop was sponsored and facilitated by USEPA's ORD and OSWER. The purpose of the workshop was to achieve three goal...

  15. PROCEEDINGS AND SUMMARY REPORT OF THE USEPA WORKSHOP ON MANAGING ARSENIC RISKS TO THE ENVIRONMENT: CHARACTERIZATION OF WASTE, CHEMISTRY AND TREATMENT AND DISPOSAL

    EPA Science Inventory

    The workshop "Managing Arsenic Risks to the Environment: Charaterization of Waste, Chemistry and Treatment and Disposal," was held 5/1-3/2001 in Denver, CO. This workshop was sponsored and facilitated by USEPA's ORD and OSWER. The purpose of the workshop was to achieve three goal...

  16. Characterization of a "low-risk" cohort of grade group 2 prostate cancer patients: Results from the Shared Equal Access Regional Cancer Hospital database.

    PubMed

    McGinley, Kathleen F; Sun, Xizi; Howard, Lauren E; Aronson, William J; Terris, Martha K; Kane, Christopher J; Amling, Christopher L; Cooperberg, Matthew R; Freedland, Stephen J

    2017-08-01

    To examine if there is a subset of men with grade group 2 prostate cancer who could be potential candidates for active surveillance. We used the Shared Equal Access Regional Cancer Hospital database to identify 776 men undergoing radical prostatectomy from 2006 to 2015 with >8 biopsy cores obtained and complete information. We compared men who fulfilled low-risk disease criteria (clinical stage T1c/T2a; grade group 1; prostate-specific antigen ≤10 ng/mL) with the exception of grade group 2 versus men who met all three low-risk criteria. Logistic regression was used to test the association between grade group and radical prostatectomy pathological features. Biochemical recurrence was examined using Cox models. To examine whether there was a subset of men with low-volume grade group 2 with comparable outcomes to low-risk men, we repeated all analyses limiting the percentage of positive cores in the grade group 2 group to ≤33%, and positive cores to ≤4, ≤3 or ≤2. Grade group 2 low-risk men had increased risk of pathological grade group 3 or higher (P < 0.001), extraprostatic extension (P < 0.001), seminal vesicle invasion (P < 0.001) and higher risk of biochemical recurrence (hazard ratio = 1.76, P = 0.006). Using increasingly strict definitions of low-volume disease, at ≤2 positive cores there was no difference in adverse pathology between groups (all P > 0.2), except higher pathological grade group (P = 0.006). Biochemical recurrence was similar in men in grade group 1 and grade group 2 (hazard ratio = 1.24; P = 0.529). Among men with prostate-specific antigen ≤10 ng/mL and clinical stage T1c/T2a, those in grade group 2 with ≤2 total positive cores have similar rates of adverse pathology and biochemical recurrence as men with grade group 1. © 2017 The Japanese Urological Association.

  17. Eco-Epidemiology of Chagas Disease in an Endemic Area of Colombia: Risk Factor Estimation, Trypanosoma cruzi Characterization and Identification of Blood-Meal Sources in Bugs

    PubMed Central

    Peña-García, Víctor H.; Gómez-Palacio, Andrés M.; Triana-Chávez, Omar; Mejía-Jaramillo, Ana M.

    2014-01-01

    The Sierra Nevada de Santa Marta (SNSM) is a mountainous area in Colombia that is highly endemic to Chagas disease. We explored some eco-epidemiological attributes involved in the Chagas disease transmission scenario in three Indigenous communities. An epidemiological survey was done, where parasite infection in reservoirs and insects, Trypanosoma cruzi genotyping, identification of blood-meal sources in intradomiciliary insects using the high-resolution melting technique, and some risk factors were evaluated. The results suggest that several dwelling conditions such as thatched palm roofs and mud walls carried the highest risk of finding intradomiciliary Rhodnius prolixus, which 56.41% were infected with T. cruzi and fed with human blood. Moreover, T. cruzi Ia was the most frequent haplotype found in insects. These results indicate the existence of a domestic T. cruzi transmission cycle that does not overlap with the sylvatic cycle, and highlight the need for efficient entomological control focused to this area. PMID:25331808

  18. Characterization of field margins in intensified agro-ecosystems-why narrow margins should matter in terrestrial pesticide risk assessment and management.

    PubMed

    Hahn, Melanie; Lenhardt, Patrick P; Brühl, Carsten A

    2014-07-01

    Field margins are important seminatural habitats in agro-ecosystems, but they can be negatively affected by pesticide inputs via direct overspray and spray drift. In Germany, risk mitigation measures (like buffer zones) to reduce pesticide inputs in terrestrial noncrop habitats do not have to be put in place by farmers next to narrow field margins (<3 m width). Because data on structure, size, and width of field margins are scarce, we identified field margins in 2 German agricultural landscapes (Rhineland-Palatinate [RLP], Brandenburg [BB]; 4000 ha each) using digital orthophotos and geographical information systems. In RLP, most of the field margins were less than 3 m wide (85% of margin length and 65% of the margin area), whereas in BB narrow field margins account for 45% of the margin length and 17% of the margin area. Hedgerows were only occasionally recorded. Hence, narrow grassy field margins can represent a large part of the available seminatural habitats adjoining agricultural sites and potentially act as corridors between further habitat patches. For this reason, these margins should be protected from pesticide inputs, at least in landscapes under intensive agricultural use. Field margins are also the main, so-called nontarget habitat protected by the terrestrial risk assessment for plants and arthropods. With many (narrow) margins not considered relevant for risk management, the current practice for protecting the biodiversity from negative effects of pesticides seems questionable. More data on field margin constitution in Germany and other European countries is necessary to critically assess the current practice of pesticide risk assessment and management on a larger scale.

  19. Diabetes and Obesity as Independent Risk Factors for Osteoporosis: Updated Results from the ROIS/EMEROS Registry in a Population of Five Thousand Post-Menopausal Women Living in a Region Characterized by Heavy Environmental Pressure.

    PubMed

    Neglia, Cosimo; Argentiero, Alberto; Chitano, Giovanna; Agnello, Nadia; Ciccarese, Roberta; Vigilanza, Antonella; Pantile, Valerio; Argentiero, Domenico; Quarta, Raffaele; Rivezzi, Matteo; Di Tanna, Gian Luca; Di Somma, Carolina; Migliore, Alberto; Iolascon, Giovanni; Gimigliano, Francesca; Distante, Alessandro; Piscitelli, Prisco

    2016-11-01

    Objectives: We aimed to analyze bone mineralization and the effect of different risk factors for osteoporosis in postmenopausal women. Methods: We found 4909 postmenopausal subjects within ≥10,000 records from the ROIS/EMEROS (Ionian and Salento Osteoporosis Registry/Euro Mediterranean Registry of Osteoporosis) registry, a population study carried out in an area characterized by heavy environmental pressure between Brindisi and Taranto from 2009 to 2016. All subjects were assessed via phalangeal quantitative ultrasound (QUS) to evaluate their bone mineralization (assessed via amplitude dependent speed of sound (AD-SoS)) and the association between demineralization and the presence of other conditions or risk factors. Results: Mean age was 64 ± 9.5 years and mean body mass index (BMI) was 28.7 ± 3.5 kg/m². Pearson correlation analyses revealed a negative association between bone mineralization (AD-SoS) and BMI (p < 0.001). By using multivariate logistic regression analysis, we observed significant values of odds ratios (ORs) of osteoporosis (adjusted for age, physical activity, and the use of drugs known to increase the risk of fractures) in subjects with diabetes and obesity: 1.39 (confidence interval (CI): 1.05-1.83) and 1.46 (CI: 1.20-1.78), respectively. A statistically significant linear trend of higher ORs of osteoporosis was found for increasing values of BMI. Conclusions: Our study confirmed the high impact of obesity and type 1 and type 2 diabetes on osteoporosis.

  20. Characterization of the Human Risk of Salmonellosis Related to Consumption of Pork Products in Different E.U. Countries Based on a QMRA.

    PubMed

    Vigre, Håkan; Barfoed, Kristen; Swart, Arno N; Simons, Robin R L; Hill, Andrew A; Snary, Emma L; Hald, Tine

    2016-03-01

    In response to the European Food Safety Authority's wish to assess the reduction of human cases of salmonellosis by implementing control measures at different points in the farm-to-consumption chain for pork products, a quantitative microbiological risk assessment (QMRA) was developed. The model simulated the occurrence of Salmonella from the farm to consumption of pork cuts, minced meat, and fermented ready-to-eat sausage, respectively, and a dose-response model was used to estimate the probability of illness at consumption. The QMRA has a generic structure with a defined set of variables, whose values are changed according to the E.U. member state (MS) of interest. In this article we demonstrate the use of the QMRA in four MSs, representing different types of countries. The predicted probability of illness from the QMRA was between 1 in 100,000 and 1 in 10 million per serving across all three product types. Fermented ready-to-eat sausage imposed the highest probability of illness per serving in all countries, whereas the risks per serving of minced meat and pork chops were similar within each MS. For each of the products, the risk varied by a factor of 100 between the four MSs. The influence of lack of information for different variables was assessed by rerunning the model with alternative, more extreme, values. Out of the large number of uncertain variables, only a few of them have a strong influence on the probability of illness, in particular those describing the preparation at home and consumption.

  1. Characterizing distributions, composition profiles, sources and potential health risk of polybrominated diphenyl ethers (PBDEs) in the coastal sediments from East China Sea.

    PubMed

    Wang, Guoguang; Peng, Jialin; Zhang, Dahai; Li, Xianguo

    2016-06-01

    Sediment samples (n = 20) were collected from Yangtze River Estuary (YRE) and the adjacent East China Sea (ECS) inner shelf to explore spatial and temporal distributions, environmental fate, sources and potential health risk of polybrominated diphenyl ethers (PBDEs). Concentrations of BDE-209 and total 7 PBDEs (without BDE-209; ∑7PBDEs) ranged from 62.3 to 1758 pg g(-1) and from 36.9 to 233.6 pg g(-1) dry weight, respectively; both of the highest values occurred near the city of Wenzhou. Concentrations of BDE-209 and ∑7PBDEs both indicated a decreasing trend from inshore areas toward outer shelf. Significantly positive linear correlations were only observed between logBDE-183 concentrations and TOC/grain size (r(2) = 0.6734 and 0.5977 for TOC and grain size, respectively) as well as BDE-209 and TOC/grain size (r(2) = 0.4137 and 0.5332 for TOC and grain size, respectively) in the north of 28(°)N, indicating that YR had significant influence on the distribution of higher brominated congeners only in the north part. Depth profiles of PBDEs in a sediment core P01 (n = 1, m = 11) collected from YRE showed that the input of BDE-209 gradually increased from 1930 to 2010, while the levels of ∑7PBDEs peaked in 1986 and obviously decreased in recent years. Partial Least-Squares Regression (PLSR) revealed that PBDEs in the coastal ECS were mainly from direct discharge of local anthropogenic activities (80.7%), followed by surface runoff of contaminated soils (15.1%), microbial degradation after sedimentation (2.6%) and photodegradation during atmospheric transportation (1.6%). The cancer risk of human exposure to BDE-209 at the 95% confidence level was 3.09 × 10(-7), 1.67 × 10(-7) and 8.86 × 10(-7) for children, teens and adults, respectively, significantly lower than the threshold level (10(-6)). Hazard index (HI) calculated for non-cancer risk was also far less than 1 for the three groups, suggesting no non-cancer risk.

  2. Fuzzy risk matrix.

    PubMed

    Markowski, Adam S; Mannan, M Sam

    2008-11-15

    A risk matrix is a mechanism to characterize and rank process risks that are typically identified through one or more multifunctional reviews (e.g., process hazard analysis, audits, or incident investigation). This paper describes a procedure for developing a fuzzy risk matrix that may be used for emerging fuzzy logic applications in different safety analyses (e.g., LOPA). The fuzzification of frequency and severity of the consequences of the incident scenario are described which are basic inputs for fuzzy risk matrix. Subsequently using different design of risk matrix, fuzzy rules are established enabling the development of fuzzy risk matrices. Three types of fuzzy risk matrix have been developed (low-cost, standard, and high-cost), and using a distillation column case study, the effect of the design on final defuzzified risk index is demonstrated.

  3. Integration of Human Reliability Analysis Models into the Simulation-Based Framework for the Risk-Informed Safety Margin Characterization Toolkit

    SciTech Connect

    Boring, Ronald; Mandelli, Diego; Rasmussen, Martin; Herberger, Sarah; Ulrich, Thomas; Groth, Katrina; Smith, Curtis

    2016-06-01

    This report presents an application of a computation-based human reliability analysis (HRA) framework called the Human Unimodel for Nuclear Technology to Enhance Reliability (HUNTER). HUNTER has been developed not as a standalone HRA method but rather as framework that ties together different HRA methods to model dynamic risk of human activities as part of an overall probabilistic risk assessment (PRA). While we have adopted particular methods to build an initial model, the HUNTER framework is meant to be intrinsically flexible to new pieces that achieve particular modeling goals. In the present report, the HUNTER implementation has the following goals: • Integration with a high fidelity thermal-hydraulic model capable of modeling nuclear power plant behaviors and transients • Consideration of a PRA context • Incorporation of a solid psychological basis for operator performance • Demonstration of a functional dynamic model of a plant upset condition and appropriate operator response This report outlines these efforts and presents the case study of a station blackout scenario to demonstrate the various modules developed to date under the HUNTER research umbrella.

  4. Are additive effects of dietary surfactants on intestinal tight junction integrity an overlooked human health risk? - A mixture study on Caco-2 monolayers.

    PubMed

    Glynn, Anders; Igra, Annachiara Malin; Sand, Salomon; Ilbäck, Nils Gunnar; Hellenäs, Karl Erik; Rosén, Johan; Aspenström-Fagerlund, Bitte

    2017-08-01

    Surfactants may cause dysfunction of intestinal tight junctions (TJs), which is a common feature of intestinal autoimmune diseases. Effects of dietary surfactants on TJ integrity, measured as trans-epithelial resistance (TEER), were studied in Caco-2 cell monolayers. Cytotoxicity was assessed as apical LDH leakage. Monolayers were apically exposed for 60 min to the dietary surfactants solanine and chaconine (SC, potato glycoalkaloids, 0-0.25 mM), perfluorooctane sulfonic acid (PFOS, industrial contaminant, 0-0.8 mM), and sucrose monolaurate (SML, food emulsifier E 473, 0-2.0 mM) separately and as a mixture. Dose-response modelling of TEER EC50 showed that SC were 2.7- and 12-fold more potent than PFOS and SML, respectively. The mixture was composed of 1 molar unit SC, 2.7 units PFOS and 12 units SML ("SC TEER equivalent" proportions 1:1:1). Mixture exposure (0-0.05 mM SC equivalents) dose-response modelling suggested additive action on TJ integrity. Increasing SC and SML concentrations caused increased LDH leakage, but PFOS decreased LDH leakage at intermediate exposure concentrations. In the mixture PFOS appeared to protect from extensive SC- and SML-induced LDH leakage. Complex mixtures of surfactants in food may act additively on intestinal TJ integrity, which should be considered in risk assessment of emulsifier authorisation for use in food production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Functional characterization of the MECP2/IRAK1 lupus risk haplotype in human T cells and a human MECP2 transgenic mouse

    PubMed Central

    Koelsch, Kristi A.; Webb, Ryan; Jeffries, Matlock; Dozmorov, Mikhail G.; Frank, Mark Barton; Guthridge, Joel M.; James, Judith A.; Wren, Jonathan D.; Sawalha, Amr H.

    2013-01-01

    Genetic polymorphism in MECP2/IRAK1 on chromosome Xq28 is a confirmed and replicated susceptibility locus for lupus. High linkage disequilibrium in this locus suggests that both MECP2 and IRAK1 are candidate genes for the disease. DNA methylation changes in lupus T cells play a central role in the pathogenesis of lupus, and MeCp-2 (encoded by MECP2) is a master regulator of gene expression and is also known to recruit DNA methyltransferase 1 (DNMT1) during DNA synthesis. Using human T cells from normal individuals with either the lupus risk or the lupus protective haplotype in MECP2/IRAK1, we demonstrate that polymorphism in this locus increases MECP2 isoform 2 mRNA expression in stimulated but not unstimulated T cells. By assessing DNA methylation levels across over 485,000 methylation sites across the entire genome, we further demonstrate that the lupus risk variant in this locus is associated with significant DNA methylation changes, including in the HLA-DR and HLA-DQ loci, as well as interferon-related genes such as IFI6, IRF6, and BST2. Further, using a human MECP2 transgenic mouse, we show that overexpression of MECP2 alters gene expression in stimulated T cells. This includes overexpression of Eif2c2 that regulates the expression of multiple microRNAs (such as miR-21), and the histone demethylase Jhdm1d. In addition, we show that MECP2 transgenic mice develop antinuclear antibodies. Our data suggest that the lupus associated variant in the MECP2/IRAK1 locus has the potential to affect all 3 epigenetic mechanisms: DNA methylation, microRNA expression, and histone modification. Importantly, these data support the notion that variants within the MECP2 gene can alter DNA methylation in other genetic loci including the HLA and interferon-regulated genes, thereby providing evidence for genetic-epigenetic interaction in lupus. PMID:23428850

  6. Risk Assessment in Criminal Sentencing.

    PubMed

    Monahan, John; Skeem, Jennifer L

    2016-01-01

    The past several years have seen a surge of interest in using risk assessment in criminal sentencing, both to reduce recidivism by incapacitating or treating high-risk offenders and to reduce prison populations by diverting low-risk offenders from prison. We begin by sketching jurisprudential theories of sentencing, distinguishing those that rely on risk assessment from those that preclude it. We then characterize and illustrate the varying roles that risk assessment may play in the sentencing process. We clarify questions regarding the various meanings of "risk" in sentencing and the appropriate time to assess the risk of convicted offenders. We conclude by addressing four principal problems confronting risk assessment in sentencing: conflating risk and blame, barring individual inferences based on group data, failing adequately to distinguish risk assessment from risk reduction, and ignoring whether, and if so, how, the use of risk assessment in sentencing affects racial and economic disparities in imprisonment.

  7. Functional characterization of the MECP2/IRAK1 lupus risk haplotype in human T cells and a human MECP2 transgenic mouse.

    PubMed

    Koelsch, Kristi A; Webb, Ryan; Jeffries, Matlock; Dozmorov, Mikhail G; Frank, Mark Barton; Guthridge, Joel M; James, Judith A; Wren, Jonathan D; Sawalha, Amr H

    2013-03-01

    Genetic polymorphism in MECP2/IRAK1 on chromosome Xq28 is a confirmed and replicated susceptibility locus for lupus. High linkage disequilibrium in this locus suggests that both MECP2 and IRAK1 are candidate genes for the disease. DNA methylation changes in lupus T cells play a central role in the pathogenesis of lupus, and MeCp-2 (encoded by MECP2) is a master regulator of gene expression and is also known to recruit DNA methyltransferase 1 (DNMT1) during DNA synthesis. Using human T cells from normal individuals with either the lupus risk or the lupus protective haplotype in MECP2/IRAK1, we demonstrate that polymorphism in this locus increases MECP2 isoform 2 mRNA expression in stimulated but not unstimulated T cells. By assessing DNA methylation levels across over 485,000 methylation sites across the entire genome, we further demonstrate that the lupus risk variant in this locus is associated with significant DNA methylation changes, including in the HLA-DR and HLA-DQ loci, as well as interferon-related genes such as IFI6, IRF6, and BST2. Further, using a human MECP2 transgenic mouse, we show that overexpression of MECP2 alters gene expression in stimulated T cells. This includes overexpression of Eif2c2 that regulates the expression of multiple microRNAs (such as miR-21), and the histone demethylase Jhdm1d. In addition, we show that MECP2 transgenic mice develop antinuclear antibodies. Our data suggest that the lupus-associated variant in the MECP2/IRAK1 locus has the potential to affect all 3 epigenetic mechanisms: DNA methylation, microRNA expression, and histone modification. Importantly, these data support the notion that variants within the MECP2 gene can alter DNA methylation in other genetic loci including the HLA and interferon-regulated genes, thereby providing evidence for genetic-epigenetic interaction in lupus. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Characterization of trace metals of risk to human health in airborne particulate matter (PM2.5) at two sites in Guadalajara, Mexico.

    PubMed

    Saldarriaga-Noreña, Hugo; Hernández-Mena, Leonel; Ramírez-Muñiz, Martín; Carbajal-Romero, Patricia; Cosío-Ramírez, Ricardo; Esquivel-Hernández, Benjamín

    2009-04-01

    PM2.5 samples were collected at two locations in Guadalajara: Centro and Miravalle, during 2007. The first site (Centro) is located downtown and characterized by high vehicular traffic. Miravalle is in the southern part of the city, and influenced by emissions from high industrial and vehicular activity. Samples were collected for 24 h and the annual median concentrations of PM2.5 observed were 44.1 and 52.8 microg m(-3) at Centro and Miravalle, respectively. The concentration of PM2.5 observed at the Miravalle site was significantly higher (p < 0.002). Ca, Fe, Zn, Mg and Pb were the most abundant elements found at both sites. Miravalle showed higher annual concentrations of Ca, Pb, Cu, Cr, Sr, Ni, Mo, Fe, Mn, and Sb with levels of 1013.9, 74.9, 28.2, 9.4, 6.3, 4.4, 1.0, 628.0, 23.7 and 4.6 ng m(-3), respectively. At Centro and Miravalle quarterly and annual concentrations of Pb did not exceed 290 ng m(-3) and all values are well below those specified by air quality standards. The Principal Component Analysis (PCA), Cluster Analysis and the enrichment factor (EF) based on the concentrations of each element indicated that the main source of particulates at Centro was of geological origin, while Miravalle receives emissions from natural and anthropogenic sources. Both contribute to the chemical composition of PM2.5 in Guadalajara.

  9. Assessing the risk to green sturgeon from application of imidacloprid to control burrowing shrimp in Willapa Bay, Washington-Part I: exposure characterization.

    PubMed

    Frew, John A; Sadilek, Martin; Grue, Christian E

    2015-11-01

    Willapa Bay and Grays Harbor (WA, USA) comprise the largest region of commercial oyster cultivation on the Pacific Coast. The activities of 2 species of burrowing shrimp impair growth and survival of oysters reared on the intertidal mudflats. To maintain viable harvests, the oyster growers have proposed controlling the shrimp by applying the insecticide imidacloprid onto harvested beds. Green sturgeon (listed in the Endangered Species Act) forage on burrowing shrimp and could be exposed to imidacloprid in the sediment porewater and through consumed prey. Studies were conducted to evaluate the likelihood that green sturgeon would be exposed to imidacloprid and to characterize the subsequent environmental exposure. Comparisons between treated and untreated control beds following test application of the insecticide suggested that green sturgeon fed opportunistically on imidacloprid-impaired shrimp. The highest interpolated imidacloprid residue concentrations in field samples following chemical application were 27.8 µg kg(-1) and 31.4 µg kg(-1) in porewater and shrimp, respectively. Results from modeled branchial and dietary uptake, based on conservative assumptions, indicated that the porewater exposure route had the greatest contribution to systemic absorption of imidacloprid. The highest average daily uptake from porewater (177.9 µg kg(-1) body wt) was 9.5-fold greater than total dietary uptake (18.8 µg kg(-1) body wt). Concentrations and durations of exposure would be lower than the levels expected to elicit direct acute or chronic toxic effects.

  10. [Transmission risk of Trypanosoma cruzi in Metztitlán municipality from Hidalgo state, México, by characterization of domiciliary units and their entomologic indexes].

    PubMed

    Becerril, Marco A; Angeles-Pérez, Vidal; Noguez-García, Julio Cr; Imbert-Palafox, José L

    2010-01-01

    In order to determine the risk of transmission of Trypanosoma cruzi by triatomines in Metztitlan municipality, Hidalgo State, Mexico, entomological indexes were calculated and the characteristics of dwellings were described. A transversal, retrospective, descriptive, and observational study was performed by means of an intentional not probabilistic and expertise sampling from January to December of 2005 in 10 localities in which presence of triatomines were investigated either intra or peridomestic environmental in 699 houses. Building material and presence of infected triatomines with T. cruzi were registered to determine entomologic indexes. The triatomine species collected were: Triatoma barberi (Usinger) and T. mexicana (Herrich-Schaeffer) (Hemiptera: Reduviidae). The results indicated that natural infection index varied from 7.7% to 50%; colonization index reached 80%; infestation index varied from 7.7% to 25%; dispersion index was 70%. Stone-walled houses were more infested. We can conclude that it is necessary to establish T. cruzi transmission control measures against triatomines in localities from Metztitlan, primarily in stone-walled houses where T. barberi occurs, as it was the most important vector species in the transmission of T. cruzi in this municipality.

  11. Using a Pareto-optimal solution set to characterize trade-offs between a broad range of values and preferences in climate risk management

    NASA Astrophysics Data System (ADS)

    Garner, Gregory; Reed, Patrick; Keller, Klaus

    2015-04-01

    Integrated assessment models (IAMs) are often used to inform the design of climate risk management strategies. Previous IAM studies have broken important new ground on analyzing the effects of parametric uncertainties, but they are often silent on the implications of uncertainties regarding the problem formulation. Here we use the Dynamic Integrated model of Climate and the Economy (DICE) to analyze the effects of uncertainty surrounding the definition of the objective(s). The standard DICE model adopts a single objective to maximize a weighted sum of utilities of per-capita consumption. Decision makers, however, are often concerned with a broader range of values and preferences that may be poorly captured by this a priori definition of utility. We reformulate the problem by introducing three additional objectives that represent values such as (i) reliably limiting global average warming to two degrees Celsius and minimizing (ii) the costs of abatement and (iii) the climate change damages. We use advanced multi-objective optimization methods to derive a set of Pareto-optimal solutions over which decision makers can trade-off and assess performance criteria a posteriori. We illustrate the potential for myopia in the traditional problem formulation and discuss the capability of this multiobjective formulation to provide decision support.

  12. Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148

    PubMed Central

    Fang, Jun; Jia, Jinping; Makowski, Matthew; Xu, Mai; Wang, Zhaoming; Zhang, Tongwu; Hoskins, Jason W.; Choi, Jiyeon; Han, Younghun; Zhang, Mingfeng; Thomas, Janelle; Kovacs, Michael; Collins, Irene; Dzyadyk, Marta; Thompson, Abbey; O'Neill, Maura; Das, Sudipto; Lan, Qi; Koster, Roelof; Canzian, Federico; Kooperberg, Charles; Wang, Zhaoming; Arslan, Alan A; Bracci, Paige M; Buring, Julie; Duell, Eric J; Gallinger, Steven; Jacobs, Eric J; Kamineni, Aruna; Van Den Eeden, Stephen; Klein, Alison P; Kolonel, Laurence N; Li, Donghui; Olson, Sara H; Risch, Harvey A; Sesso, Howard D; Visvanathan, Kala; Zheng, Wei; Albanes, Demetrius; Austin, Melissa A; Boutron-Ruault, Marie-Christine; Bueno-de-Mesquita, H Bas; Cotterchio, Michelle; Gaziano, J Michael; Giovannucci, Edward L; Goggins, Michael; Gross, Myron; Hassan, Manal; Helzlsouer, Kathy J; Holly, Elizabeth A; Hunter, David J; Jenab, Mazda; Kaaks, Rudolf; Key, Timothy J; Khaw, Kay-Tee; Krogh, Vittorio; Kurtz, Robert C; LaCroix, Andrea; Le Marchand, Loic; Mannisto, Satu; Patel, Alpa V; Peeters, Petra H M; Riboli, Elio; Shu, Xiao-Ou; Sund, Malin; Thornquist, Mark; Tjønneland, Anne; Tobias, Geoffrey S; Trichopoulos, Dimitrios; Wactawski-Wende, Jean; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Hoover, Robert; Hartge, Patricia; Fuchs, Charles; Chanock, Stephen J; Stevens, Victoria; Albanes, Demetrios; Caporaso, Neil E; Brennan, Paul; McKay, James; Wu, Xifeng; Hung, Rayjean J; McLaughlin, John R; Bickeboller, Heike; Risch, Angela; Wichmann, Erich; Houlston, Richard; Mann, Graham; Hopper, John; Aitken, Joanne; Armstrong, Bruce; Giles, Graham; Holland, Elizabeth; Kefford, Richard; Cust, Anne; Jenkins, Mark; Schmid, Helen; Puig, Susana; Aguilera, Paula; Badenas, Celia; Barreiro, Alicia; Carrera, Cristina; Gabriel, Daniel; Xavier, Pol Gimenez; Iglesias-Garcia, Pablo; Malvehy, Josep; Mila, Montse; Pigem, Ramon; Potrony, Miriam; Batille, Joan-AntonPuig; Marti, Gemma Tell; Hayward, Nick; Martin, Nicholas; Montgomery, Grant; Duffy, David; Whiteman, David; Gregor, Stuart Mac; Calista, Donato; Landi, Giorgi; Minghetti, Paola; Arcangeli, Fabio; Bertazzi, Pier Alberto; Ghiorzo, Paola; Scarra, Giovanna Bianchi; Pastorino, Lorenze; Bruno, William; Andreotti, Virginia; Queirolo, Paola; Spagnolo, Francesco; Mackie, Rona; Lang, Julie; Gruis, Nelleke; van Nieuwpoort, Frans A; Out, Coby; Bergman, Wilma; Kukutsch, Nicole; Bavinck, Jan Nico Bouwes; Bakker, Bert; van der Stoep, Nienke; ter Huurne, Jeanet; van der Rhee, Han; Bekkenk, Marcel; Snels, Dyon; van Praag, Marinus; Brochez, Lieve; Gerritsen, Rianne; Crijns, Marianne; Vasen, Hans; Janssen, Bart; Ingvar, Christian; Olsson, Hakan; Jonsson, Goran; Borg, Ake; Harbst, Katja; Nielsen, Kari; Zander, Anita Schmidt; Molvern, Anders; Helsing, Per; Andresen, Per Arne; Rootwelt, Helge; Akslen, Lars A; Bressac-de Paillerets, Brigitte; Demenais, Florence; Avril, Marie-Francoise; Chaudru, Valerie; Jeannin, Patricia; Lesueur, Fabienne; Maubec, Eve; Mohamdi, Hamida; Bossard, Myriam; Vaysse, Amaury; Boitier, Francoise; Caron, Oliver; Caux, Frederic; Dalle, Stephane; Dereure, Oliviier; Leroux, Dominique; Martin, Ludovic; Mateus, Christine; Robert, Caroline; Stoppa-Lyonnet, Dominique; Thomas, Luc; Wierzbicka, Eva; Elder, David; Ming, Michael; Mitra, Nandita; Debniak, Tadeusz; Lubinski, Jan; Hocevar, Marko; Novakovic, Srdjan; Peric, Barbara; Skerl, Petra; Hansson, Johan; Hoiom, Veronica; Freidman, Eitan; Azizi, Esther; Baron-Epel, Orna; Scope, Alon; Pavlotsky, Felix; Cohen-Manheim, Irit; Laitman, Yael; Harland, Mark; Randerson-Moor, Juliette; Laye, Jon; Davies, John; Nsengimana, Jeremie; O'Shea, Sally; Chan, May; Gascoyne, Jo; Tucker, Margaret A; Goldstein, Alisa M; Yang, Xiaohong R; Stolzenberg-Solomon, Rachael S.; Kraft, Peter; Wolpin, Brian M.; Jansen, Pascal W. T. C.; Olson, Sara; McGlynn, Katherine A.; Kanetsky, Peter A.; Chatterjee, Nilanjan; Barrett, Jennifer H.; Dunning, Alison M.; Taylor, John C.; Newton-Bishop, Julia A.; Bishop, D. Timothy; Andresson, Thorkell; Petersen, Gloria M.; Amos, Christopher I.; Iles, Mark M.; Nathanson, Katherine L.; Landi, Maria Teresa; Vermeulen, Michiel; Brown, Kevin M.; Amundadottir, Laufey T.

    2017-01-01

    Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele. PMID:28447668

  13. Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148.

    PubMed

    Fang, Jun; Jia, Jinping; Makowski, Matthew; Xu, Mai; Wang, Zhaoming; Zhang, Tongwu; Hoskins, Jason W; Choi, Jiyeon; Han, Younghun; Zhang, Mingfeng; Thomas, Janelle; Kovacs, Michael; Collins, Irene; Dzyadyk, Marta; Thompson, Abbey; O'Neill, Maura; Das, Sudipto; Lan, Qi; Koster, Roelof; Stolzenberg-Solomon, Rachael S; Kraft, Peter; Wolpin, Brian M; Jansen, Pascal W T C; Olson, Sara; McGlynn, Katherine A; Kanetsky, Peter A; Chatterjee, Nilanjan; Barrett, Jennifer H; Dunning, Alison M; Taylor, John C; Newton-Bishop, Julia A; Bishop, D Timothy; Andresson, Thorkell; Petersen, Gloria M; Amos, Christopher I; Iles, Mark M; Nathanson, Katherine L; Landi, Maria Teresa; Vermeulen, Michiel; Brown, Kevin M; Amundadottir, Laufey T

    2017-05-02

    Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.

  14. Characterizing Open Water Bodies and Their Color Properties Through Optical Remote Sensing to Identify Areas of Vector-Borne Disease Risk

    NASA Astrophysics Data System (ADS)

    Podest, E.; De La Torre Juarez, M.; McDonald, K. C.; Jensen, K.; Ceccato, P.

    2014-12-01

    Predicting the risk of vector-borne disease outbreaks is a required step towards their control and eradication. Satellite observations can provide needed data to support agency decisions with respect to deployment of preventative measures and control resources. The coverage and persistence of open water is one of the primary indicators of conditions suitable for mosquito breeding habitats. This is currently a poorly measured variable due to its spatial and temporal variability across landscapes, especially in remote areas. Here we develop a methodology for monitoring these conditions through optical remote sensing images from Landsat. We pansharpen the images and apply a decision tree classification approach using Random Forests to generate 15 meter resolution maps of open water. In addition, since some mosquitos breed in clear water while others in turbid water, we classify water bodies according to their water color properties and we validate the results using field knowledge. We focus in East Africa where we assses the usefulness of these products to improve prediction of malaria outbreaks. Portions of this work were carried out at the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration.

  15. Descriptive study of California egg layer premises and analysis of risk factors for Salmonella enterica serotype enteritidis as characterized by manure drag swabs.

    PubMed

    Castellan, David M; Kinde, Hailu; Kass, Philip H; Cutler, Gregg; Breitmeyer, Richard E; Bell, Donald D; Ernst, Ralph A; Kerr, David C; Little, Herbert E; Willoughby, David; Riemann, Hans P; Ardans, Alex; Snowdon, Jill A; Kuney, Douglas R

    2004-09-01

    This cross-sectional, double-blind study reports the prevalence of Salmonella enterica serotype enteritidis (SE) on California egg layer premises using single vs. pooled manure drag swabs and presents a description of egg production and management systems in the state and an initial analysis of risk factors for SE. The study included 91% of all known eligible egg premises in California, representing the majority of eggs produced in the state. The overall prevalence of SE on California egg layer premises was 10.5%, while 1.1% of all rows sampled were positive for SE. The percentage of positive rows for SE on any premises never exceeded 25% of the 16 swabs collected per premises. A description of egg production and management on California egg layer premises is presented. Statistically significant associations for SE were not evident and were limited because of sample size and the low prevalence of SE on California egg layer premises. Several biological and management factors, such as flock health, stage of production, manure management, ventilation, and watering systems, show trend associations with premises positive for SE and require further investigation. Manure drag swabs serve as a useful tool to validate the core components of an egg quality assurance program for SE based on process control principles.

  16. Risk Assessment: A Quantitative Approach

    NASA Astrophysics Data System (ADS)

    Baert, K.; Francois, K.; de Meulenaer, B.; Devlieghere, F.

    A risk can be defined as a function of the probability of an adverse health effect and the severity of that effect, consequential to a hazard in food (Codex Alimentarius, 1999) . During a risk assessment, an estimate of the risk is obtained. The goal is to estimate the likelihood and the extent of adverse effects occurring to humans due to possible exposure(s) to hazards. Risk assessment is a scientifically based process consisting of the following steps: (1) hazard identification, (2) hazard characterization, (3) exposure assessment and (4) and risk characterization (Codex Alimentarius, 1999).

  17. Estimated exposure to EU regulated mycotoxins and risk characterization of aflatoxin-induced hepatic toxicity through the consumption of the toasted cereal flour called "gofio", a traditional food of the Canary Islands (Spain).

    PubMed

    Luzardo, Octavio P; Bernal-Suárez, María Del Mar; Camacho, María; Henríquez-Hernández, Luis Alberto; Boada, Luis D; Rial-Berriel, Cristian; Almeida-González, Maira; Zumbado, Manuel; Díaz-Díaz, Ricardo

    2016-07-01

    "Gofio" is a type of flour made from toasted grain, which is part of the staple food in the Canary Islands, Spain, in which the occurrence of Aflatoxins B1, B2, G1 and G2 (AFB1, AFB2, AFG1, AFG2), Fumonisins B1 and B2 (FB1 and FB2) Ochratoxin A (OTA), Deoxynivalenol (DNV) and Zearalenone (ZEA) was evaluated. 83% of the samples were contaminated with at least one mycotoxin and 69.2% of the analyzed samples showed co-occurrence of mycotoxins (range 2 to 8). All the concentrations were well below the established limits (maximum values of AFs=0.42 μg/kg; FBs=178.3 μg/kg; OTA=0.3 μg/kg; DON=92.5 μg/kg; and ZEA=9.9 μg/kg). The daily dietary exposure to total AFs was estimated to be 7.1% of the TDI. This value was almost double in children, and considering the upper-bound approach could reach 35% of the TDI. For the rest of mycotoxins, the consumers would be exposed to less than 2% of their TDIs. The risk characterization indicates that there is a potential risk in developing aflatoxin induced liver cancer due to gofio consumption in the subpopulation which is simultaneously exposed to other hepatocarcinogens, such as the hepatitis B virus. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Diabetes and Obesity as Independent Risk Factors for Osteoporosis: Updated Results from the ROIS/EMEROS Registry in a Population of Five Thousand Post-Menopausal Women Living in a Region Characterized by Heavy Environmental Pressure

    PubMed Central

    Neglia, Cosimo; Argentiero, Alberto; Chitano, Giovanna; Agnello, Nadia; Ciccarese, Roberta; Vigilanza, Antonella; Pantile, Valerio; Argentiero, Domenico; Quarta, Raffaele; Rivezzi, Matteo; Di Tanna, Gian Luca; Di Somma, Carolina; Migliore, Alberto; Iolascon, Giovanni; Gimigliano, Francesca; Distante, Alessandro; Piscitelli, Prisco

    2016-01-01

    Objectives: We aimed to analyze bone mineralization and the effect of different risk factors for osteoporosis in postmenopausal women. Methods: We found 4909 postmenopausal subjects within ≥10,000 records from the ROIS/EMEROS (Ionian and Salento Osteoporosis Registry/Euro Mediterranean Registry of Osteoporosis) registry, a population study carried out in an area characterized by heavy environmental pressure between Brindisi and Taranto from 2009 to 2016. All subjects were assessed via phalangeal quantitative ultrasound (QUS) to evaluate their bone mineralization (assessed via amplitude dependent speed of sound (AD-SoS)) and the association between demineralization and the presence of other conditions or risk factors. Results: Mean age was 64 ± 9.5 years and mean body mass index (BMI) was 28.7 ± 3.5 kg/m2. Pearson correlation analyses revealed a negative association between bone mineralization (AD-SoS) and BMI (p < 0.001). By using multivariate logistic regression analysis, we observed significant values of odds ratios (ORs) of osteoporosis (adjusted for age, physical activity, and the use of drugs known to increase the risk of fractures) in subjects with diabetes and obesity: 1.39 (confidence interval (CI): 1.05–1.83) and 1.46 (CI: 1.20–1.78), respectively. A statistically significant linear trend of higher ORs of osteoporosis was found for increasing values of BMI. Conclusions: Our study confirmed the high impact of obesity and type 1 and type 2 diabetes on osteoporosis. PMID:27809297

  19. Nano-objects emitted during maintenance of common particle generators: direct chemical characterization with aerosol mass spectrometry and implications for risk assessments

    NASA Astrophysics Data System (ADS)

    Nilsson, Patrik T.; Isaxon, Christina; Eriksson, Axel C.; Messing, Maria E.; Ludvigsson, Linus; Rissler, Jenny; Hedmer, Maria; Tinnerberg, Håkan; Gudmundsson, Anders; Deppert, Knut; Bohgard, Mats; Pagels, Joakim H.

    2013-11-01

    Nanotechnology gives us materials with enhanced or completely new properties. At the same time, inhalation of manufactured nano-objects has been related to an array of adverse biological effects. We characterized particle emissions, which occurred during maintenance of common metal nanoparticle generators and contrasted the properties of the emitted particles with those originally produced by the generators. A new approach using online aerosol mass spectrometry (AMS), for time- and size-resolved measurements of the particle chemical composition, was applied in combination with more conventional techniques for particle sampling and analysis, including electron microscopy. Emissions during maintenance work, in terms of mass and surface area concentration in the size range of 0.02-10 μm, were dominated by large agglomerates (1-5 μm). With AMS, we show that the particle composition depends on both generator type and maintenance task being performed and that the instrument can be used for highly time-resolved selective studies of metal nanoparticle emissions. The emitted agglomerates have a relatively high probability to be deposited in the lower respiratory tract, since the mean particle diameter coincided with a peak in the lung deposition curve. Each of these agglomerates consisted of a very high number (103-105/agglomerate) of nanometer-sized primary particles originating from the particle synthesis process. This made them possess large surface areas, one of the key properties in nanotoxicology. Similar agglomerates may be emitted in a wide range of processes when nanoparticles are manufactured or handled. The fate of such agglomerates, once deposited in the respiratory tract, is unknown and should therefore be considered in future particle toxicological studies. Our results highlight the importance of including micrometer-sized particles in exposure and emission assessments.

  20. Hazard prioritization and risk characterization of antibiotics in an irrigated Costa Rican region used for intensive crop, livestock and aquaculture farming.

    PubMed

    de la Cruz, Elba; Fournier, María Luisa; García, Fernando; Molina, Andrea; Chavarría, Guadalupe; Alfaro, Margarita; Ramírez, Fernando; Rodríguez, César

    2014-01-01

    Antibiotics alter the homeostasis of microbial communities and select for antibiotic-resistant bacteria in the wild. Thus, the accumulation of unnaturally high concentration of these substances in the environment due to their use in human activities can be regarded as a neglected form of pollution, especially in countries with agricultural-based economies. Qualitative and quantitative information on antibiotic usage in Costa Rica is scarce, hence the design and enforcement of prevention strategies and corrective measures is difficult. To address this issue, and aiming in the long run to contribute with a more rational use of pharmaceuticals in the tropics, we characterized the hazard associated with the antibiotics used during 2008 in agriculture, aquaculture, pig farming, veterinary medicine and human medicine in the major irrigation district of Costa Rica. Hazard indicators were calculated based on antibiotic use and a weighted algorithm that also considered antibiotic fate, toxicity, and resistance. Moreover, hazard quotients were computed using maximum environmental concentrations reported for Costa Rican surface waters and predicted no effect concentrations for aquatic organisms. The number of antibiotics used in the ATID during the study were n = 38 from 15 families. Antibiotic consumption was estimated at 1169-109908 g ha(-1) year(-1) and, distinctively, almost half of this figure was traced back to phenicols. Tetracyclines, with a particular contribution of oxytetracycline, were the most widely used antibiotics in agriculture and veterinary medicine. Oxytetracycline, florfenicol, chlortetracycline, sulfamethoxazole, erythromycin, ciprofloxacin, enrofloxacin, sulfamethazine, trimethoprim and tylosin, in that order showed the highest hazard indicators. Moreover, hazard quotients greater than 1 were calculated for oxacillin, doxycycline, oxytetracycline, sulfamethazine, and ciprofloxacin. Studies dealing with the ecotoxicology of tetracyclines, sulfonamides

  1. Characterizing and Communicating Risk with Exposure Reconstruction and Bayesian Analysis: Historical Locomotive Maintenance/Repair Associated with Asbestos Woven Tape Pipe Lagging.

    PubMed

    Boelter, Fred W; Persky, Jacob D; Podraza, Daniel M; Bullock, William H

    2016-02-01

    Our reconstructed historical work scenarios incorporating a vintage 1950s locomotive can assist in better understanding the historical asbestos exposures associated with past maintenance and repairs and fill a literature data gap. Air sampling data collected during the exposure scenarios and analyzed by NIOSH 7400 (PCM) and 7402 (PCME) methodologies show per