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Objective: The authors aimed to gain information on (1) the challenges for recovering students on a university campus and (2) the most helpful components of a collegiate recovery program. Participants: The 15 students in the study were all in recovery from substance abuse. They entered the university and also entered the campus recovery program either in fall 2002 or fall 2003. Methods: Semistructured interviews were conducted with students multiple times during their first academic year. Results: Participants identified several challenges on the university campus. Many believed they would have dropped out of school or relapsed without the support of the recovery program, and they described aspects of the program that were particularly important to them. Conclusions: Support from a campus recovery program is essential for many recovering students. There are a variety of recovery program components that can foster the sense of community that was so important to the students in this study. [ABSTRACT FROM AUTHOR]

Motile plant-associated bacteria use chemotaxis and dedicated chemoreceptors to navigate gradients in their surroundings and to colonize host plant surfaces. Here, we characterize a chemoreceptor that we named Tlp2 in the soil alphaproteobacterium Azospirillum brasilense . We show that the Tlp2 ligand-binding domain is related to the 4-helix bundle family and is conserved in chemoreceptors found in the genomes of many soil- and sediment-dwelling alphaproteobacteria. The promoter of tlp2 is regulated in an NtrC- and RpoN-dependent manner and is most upregulated under conditions of nitrogen fixation or in the presence of nitrate. Using fluorescently tagged Tlp2 (Tlp2-YFP), we show that this chemoreceptor is present in low abundance in chemotaxis-signaling clusters and is prone to degradation. We also obtained evidence that the presence of ammonium rapidly disrupts Tlp2-YFP localization. Behavioral experiments using a strain lacking Tlp2 and variants of Tlp2 lacking conserved arginine residues suggest that Tlp2 mediates chemotaxis in gradients of nitrate and nitrite, with the R159 residue being essential for Tlp2 function. We also provide evidence that Tlp2 is essential for root surface colonization of some plants (teff, red clover, and cowpea) but not others (wheat, sorghum, alfalfa, and pea). These results highlight the selective role of nitrate sensing and chemotaxis in plant root surface colonization and illustrate the relative contribution of chemoreceptors to chemotaxis and root surface colonization.IMPORTANCEBacterial chemotaxis mediates host-microbe associations, including the association of beneficial bacteria with the roots of host plants. Dedicated chemoreceptors specify sensory preferences during chemotaxis. Here, we show that a chemoreceptor mediating chemotaxis to nitrate is important in the beneficial soil bacterium colonization of some but not all plant hosts tested. Nitrate is the preferred nitrogen source for plant nutrition, and plants sense and tightly control nitrate transport, resulting in varying nitrate uptake rates depending on the plant and its physiological state. Nitrate is thus a limiting nutrient in the rhizosphere. Chemotaxis and dedicated chemoreceptors for nitrate likely provide motile bacteria with a competitive advantage to access this nutrient in the rhizosphere., Competing Interests: The authors declare no conflict of interest.

Tryptase is a serine protease that is released from mast cells during allergic responses. Tryptase inhibitors are being explored as treatments for allergic inflammation in the skin and respiratory system, most notably asthma. Here we report direct tryptase inhibition by natural product compounds. Candidate inhibitors were identified by computational screening of a large (98,000 compounds) virtual library of natural product compounds for tryptase enzymatic site binding. Biochemical assays were used to validate the predicted anti-tryptase activity in vitro, revealing a high (four out of six) success rate for predicting binding using the computational docking model. We further assess tryptase inhibition by a biflavonoid scaffold, whose structure-activity relationship is partially defined by assessing the potency of structurally similar analogs.

Biotransformation of fluorotelomer (FT) compounds, such as 8:2 FT alcohol (FTOH) is now recognized to be a source of perfluorooctanoic acid (PFOA) as well as other perfluoroalkyl acids. In this study, microbially mediated hydrolysis of FT industrial intermediates 8:2 FT acrylate (8:2 FTAC) and 8:2 FT methacrylate (8:2 FTMAC) was evaluated in aerobic soils for up to 105d. At designated times, triplicate microcosms were sacrificed by sampling the headspace for volatile FTOHs followed by sequential extraction of soil for the parent monomers as well as transient and terminal degradation products. Both FTAC and FTMAC were hydrolyzed at the ester linkage as evidenced by 8:2 FTOH production. 8:2 FTAC and FTMAC degraded rapidly with half-lives ⩽5d and 15d, respectively. Maximum 8:2 FTOH levels were 6-13mol% within 3-6d. Consistent with the known biotransformation pathway of 8:2 FTOH, FT carboxylic acids and perfluoroalkyl carboxylic acids were subsequently generated including up to 10.3mol% of PFOA (105d). A total mass balance (parent plus metabolites) of 50-75mol% was observed on the last sampling day. 7:2 sFTOH, a direct precursor to PFOA, unexpectedly increased throughout the incubation period. The likely, but unconfirmed, concomitant production of acrylic acids was proposed as altering expected degradation patterns. Biotransformation of 8:2 FTAC, 8:2 FTMAC, and previously reported 8:2 FT-stearate for the same soils revealed the effect of the non-fluorinated terminus group linked to the FT chain on the electronic differences that affect microbially-mediated ester cleavage rates., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Determination of the chemical clearance rate from human blood is a critical component of toxicokinetic exposure assessment. Analysis of temporal biomonitoring data without consideration of ongoing exposure results in calculation of apparent elimination half-life values that are longer than the intrinsic value. The intrinsic elimination half-life is solely a function of the rate of elimination while the apparent elimination half-life reflects the processes of both elimination and ongoing exposure. Confusion between intrinsic and apparent half-life values can lead to misinterpretation of biomonitoring data and can result in exaggerated predictions in subsequent modeling efforts. This work provides a review of the first-order equations that have been developed to calculate intrinsic and apparent half-life values and the potential bias that can result from confusing these two values. Published human biomonitoring data for perfluorooctanoic acid (PFOA) are analyzed using these equations to provide examples of low, medium and high bias in determination of the intrinsic elimination half-life from plasma or serum, the components of blood typically analyzed for PFOA. An approach is also provided to estimate the extent of exposure reduction that is indicated by declining longitudinal or cross-sectional biomonitoring data. Based on the evaluation methodology presented in this work, the intrinsic elimination half-life of PFOA in humans is 2.4years, representing the average of independent estimates of 2.5years (95% CI, 2.4-2.7) and 2.3years (95% CI, 2.1-2.4). The declining concentration of PFOA in blood of the general USA adult population represents an estimated exposure reduction of 20-30% over the period 1999-2008., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The toxicokinetics of 6:2 fluorotelomer alcohol (6:2 FTOH) and its terminal perfluorinated and polyfluorinated metabolites (PFBA, PFHxA, PFHpA and 5:3 Acid) have been calculated from laboratory studies of rats and from a biomonitoring study of humans. In vitro studies with mouse, rat and human hepatocytes indicate qualitatively similar metabolic pathways of 6:2 FTOH. In a one-day inhalation study of 6:2 FTOH in rats, PFBA, PFHxA, PFHpA and 5:3 Acid were determined to be the major metabolites in plasma with calculated elimination half-lives of 1.3-15.4h and metabolic yields up to 2.7 mol%. In five-day and 23-day inhalation studies and a 90-day oral study of 6:2 FTOH, the plasma or serum concentration profile of 5:3 Acid was several-fold higher than concentrations observed in the single day study, resulting in an estimated elimination half-life of 20-30 d. In contrast, the concentrations of PFBA, PFHxA and PFHpA showed little or no concentration increase with repeated exposure. Elimination half-lives of PFHxA, PFHpA and 5:3 Acid in humans were estimated from a study of professional ski wax technicians who were occupationally exposed to aerosolized and volatilized components of fluorinated glide wax. The resulting human elimination half-life values of PFHxA, PFHpA and 5:3 Acid were 32, 70 and 43 d, respectively. Based on a one compartment toxicokinetic model, current environmental air concentrations of 6:2 FTOH are estimated to result in plasma concentrations of PFHxA, PFHpA and 5:3 Acid that are less than or equal to typical LOQ values, in agreement with extant biomonitoring results., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Major fluorinated chemical manufacturers have developed new short-chain per- and polyfluorinated substances with more favorable environmental, health and safety profiles. This study provides the first evaluation of the elimination half-life of perfluorohexanoic acid (PFHxA) from the blood of humans. PFHxA biomonitoring data were obtained from a recently published study of professional ski wax technicians. These data were analyzed to provide estimates of the apparent half-life of PFHxA from humans, and comparisons were made with kinetic studies of PFHxA elimination from mice, rats and monkeys. The apparent elimination half-life of PFHxA in highly exposed humans ranged between 14 and 49 d with a geomean of 32 d. The half-lives of PFHxA in mice, rats, monkeys and humans were proportional to body weight with no differences observed between genders, indicating similar volumes of distribution and similar elimination mechanisms among mammalian species. Compared to long-chain perfluoroalkyl acid analogs, PFHxA is rapidly cleared from biota. The consistent weight-normalized elimination half-lives for PFHxA in mammalian species indicates that results obtained from animal models are suitable for establishment of PFHxA benchmark dose and reference dose hazard endpoints for use in human risk assessments., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Dynamic cell-to-cell interactions are a prerequisite to many biological processes, including development and biofilm formation. Flagellum induced motility has been shown to modulate the initial cell-cell or cell-surface interaction and to contribute to the emergence of macroscopic patterns. While the role of swimming motility in surface colonization has been analyzed in some detail, a quantitative physical analysis of transient interactions between motile cells is lacking. We examined the Brownian dynamics of swimming cells in a crowded environment using a model of motorized adhesive tandem particles. Focusing on the motility and geometry of an exemplary motile bacterium Azospirillum brasilense, which is capable of transient cell-cell association (clumping), we constructed a physical model with proper parameters for the computer simulation of the clumping dynamics. By modulating mechanical interaction ('stickiness') between cells and swimming speed, we investigated how equilibrium and active features affect the clumping dynamics. We found that the modulation of active motion is required for the initial aggregation of cells to occur at a realistic time scale. Slowing down the rotation of flagellar motors (and thus swimming speeds) is correlated to the degree of clumping, which is consistent with the experimental results obtained for A. brasilense.

Unlabelled: Elevated intracellular levels of the bacterial second messenger c-di-GMP are known to suppress motility and promote sessility. Bacterial chemotaxis guides motile cells in gradients of attractants and repellents over broad concentration ranges, thus allowing bacteria to quickly adapt to changes in their surroundings. Here, we describe a chemotaxis receptor that enhances, as opposed to suppresses, motility in response to temporary increases in intracellular c-di-GMP. Azospirillum brasilense's preferred metabolism is adapted to microaerophily, and these motile cells quickly navigate to zones of low oxygen concentration by aerotaxis. We observed that changes in oxygen concentration result in rapid changes in intracellular c-di-GMP levels. The aerotaxis and chemotaxis receptor, Tlp1, binds c-di-GMP via its C-terminal PilZ domain and promotes persistent motility by increasing swimming velocity and decreasing swimming reversal frequency, which helps A. brasilense reach low-oxygen zones. If c-di-GMP levels remain high for extended periods, A. brasilense forms nonmotile clumps or biofilms on abiotic surfaces. These results suggest that association of increased c-di-GMP levels with sessility is correct on a long-term scale, while in the short-term c-di-GMP may actually promote, as opposed to suppress, motility. Our data suggest that sensing c-di-GMP by Tlp1 functions similar to methylation-based adaptation. Numerous chemotaxis receptors contain C-terminal PilZ domains or other sensory domains, suggesting that intracellular c-di-GMP as well as additional stimuli can be used to modulate adaptation of bacterial chemotaxis receptors., Importance: To adapt and compete under changing conditions, bacteria must not only detect and respond to various environmental cues but also be able to remain sensitive to further changes in the environmental conditions. In bacterial chemotaxis, chemosensory sensitivity is typically brought about by changes in the methylation status of chemotaxis receptors capable of modulating the ability of motile cells to navigate in gradients of various physicochemical cues. Here, we show that the ubiquitous second messenger c-di-GMP functions to modulate chemosensory sensitivity of a bacterial chemotaxis receptor in the alphaproteobacterium Azospirillum brasilense. Binding of c-di-GMP to the chemotaxis receptor promotes motility under conditions of elevated intracellular c-di-GMP levels. Our results revealed that the role of c-di-GMP as a sessile signal is overly simplistic. We also show that adaptation by sensing an intracellular metabolic cue, via PilZ or other domains, is likely widespread among bacterial chemotaxis receptors.

Multimedia mass balance models of chemical fate in the environment have been used for over 3 decades in a regulatory context to assist decision making. As these models become more comprehensive, reliable, and accepted, there is a need to recognize and adopt principles of Good Modeling Practice (GMP) to ensure that multimedia models are applied with transparency and adherence to accepted scientific principles. We propose and discuss 6 principles of GMP for applying existing multimedia models in a decision-making context, namely 1) specification of the goals of the model assessment, 2) specification of the model used, 3) specification of the input data, 4) specification of the output data, 5) conduct of a sensitivity and possibly also uncertainty analysis, and finally 6) specification of the limitations and limits of applicability of the analysis. These principles are justified and discussed with a view to enhancing the transparency and quality of model-based assessments., (Copyright © 2012 SETAC.)

A next-generation mobile automobile air-conditioning (MAC) refrigerant, HFO-1234yf (CF(3) CF = CH(2)), is being developed with improved environmental characteristics. In the atmosphere, it ultimately forms trifluoroacetic acid (TFA(A); CF(3)COOH), which is subsequently scavenged by precipitation and deposited on land and water as trifluoroacetate (TFA; CF(3)COO(-)). Trifluoroacetate is environmentally stable and has the potential to accumulate in terminal water bodies, that is, aquatic systems receiving inflow but with little or no outflow and with high rates of evaporation. Previous studies have estimated the emission rates of HFO-1234yf and have modeled the deposition concentrations and rates of TFA across North America. The present study uses multimedia modeling and geographic information system (GIS)-based modeling to assess the potential concentrations of TFA in terminal water bodies over extended periods. After 10 years of emissions, predicted concentrations of TFA in terminal water bodies across North America are estimated to range between current background levels (i.e., 0.01-0.22 µg/L) and 1 to 6 µg/L. After 50 years of continuous emissions, aquatic concentrations of 1 to 15 µg/L are predicted, with extreme concentrations of up to 50 to 200 µg/L in settings such as the Sonoran Desert along the California/Arizona (USA) border. Based on the relative insensitivity of aquatic organisms to TFA, predicted concentrations of TFA in terminal water bodies are not expected to impair aquatic systems, even considering potential emissions over extended periods., (Copyright © 2012 SETAC.)

The Che1 chemotaxis-like pathway of Azospirillum brasilense contributes to chemotaxis and aerotaxis, and it has also been found to contribute to regulating changes in cell surface adhesive properties that affect the propensity of cells to clump and to flocculate. The exact contribution of Che1 to the control of chemotaxis and flocculation in A. brasilense remains poorly understood. Here, we show that Che1 affects reversible cell-to-cell clumping, a cellular behavior in which motile cells transiently interact by adhering to one another at their nonflagellated poles before swimming apart. Clumping precedes and is required for flocculation, and both processes appear to be independently regulated. The phenotypes of a ΔaerC receptor mutant and of mutant strains lacking cheA1, cheY1, cheB1, or cheR1 (alone or in combination) or with che1 deleted show that Che1 directly mediates changes in the flagellar swimming velocity and that this behavior directly modulates the transient nature of clumping. Our results also suggest that an additional receptor(s) and signaling pathway(s) are implicated in mediating other Che1-independent changes in clumping identified in the present study. Transient clumping precedes the transition to stable clump formation, which involves the production of specific extracellular polysaccharides (EPS); however, production of these clumping-specific EPS is not directly controlled by Che1 activity. Che1-dependent clumping may antagonize motility and prevent chemotaxis, thereby maintaining cells in a metabolically favorable niche.

8:2 fluorotelomer alcohol (8:2 FTOH) inhalation exposure was investigated to (1) compare plasma metabolites to oral data, (2) conduct a route-to-route extrapolation (oral to inhalation), (3) develop a human equivalent air concentration (HEC) from a 90-day oral sub-chronic study in rats using BMD analysis, and (4) calculate a margin of exposure (MOE) between the HEC and measured air concentrations. Male and female rats were exposed nose-only for 6h at 3 or 30mg/m(3). Blood was collected at 1, 3 and 6h during exposure and 6 and 18h post exposure. Alcohol, perfluorocarboxylic acid and polyfluorinated acid metabolites were determined in plasma by LC-MS/MS. 8:2 FTOH was

Sex-, species-, and chain length-dependent renal elimination is the hallmark of mammalian elimination of perfluorocarboxylates (PFCAs) and has been extensively studied for almost 30 years. In this review, toxicokinetic data of PFCAs (chain lengths ranging from 4 to 10) in different species are compared with an emphasis on their relevance to renal elimination. PFCAs vary in their affinities to bind to serum albumins in plasma, which is an important factor in determining the renal clearance of PFCAs. PFCA-albumin binding has been well characterized and is summarized in this review. The mechanism of the sex-, species-, and chain length-dependent renal PFCA elimination is a research area that has gained continuous interest since the beginning of toxicological studies of PFCAs. It is now recognized that organic anion transport proteins play a key role in PFCA renal tubular reabsorption, a process that is sex-, species-, and chain length-dependent. Recent studies on the identification of PFCA renal transport proteins and characterization of their transport kinetics have greatly improved our understanding of the PFCA renal transport mechanism at the molecular level. A mathematical representation of this renal tubular reabsorption mechanism has been incorporated in physiologically based pharmacokinetic (PBPK) modeling of perfluorooctanoate (PFOA). Improvement of PBPK models in the future will require more accurate and quantitative characterization of renal transport pathways of PFCAs. To that end, a basolateral membrane efflux pathway for the reabsorption of PFCAs in the kidney is discussed in this review, which could provide a future research direction toward a better understanding of the mechanisms of PFCA renal elimination.

This work assessed the usefulness of a current air quality model (American Meteorological Society/Environmental Protection Agency Regulatory Model [AERMOD]) for predicting air concentrations and deposition of perfluorooctanoate (PFO) near a manufacturing facility. Air quality models play an important role in providing information for verifying permitting conditions and for exposure assessment purposes. It is important to ensure traditional modeling approaches are applicable to perfluorinated compounds, which are known to have unusual properties. Measured field data were compared with modeling predictions to show that AERMOD adequately located the maximum air concentration in the study area, provided representative or conservative air concentration estimates, and demonstrated bias and scatter not significantly different than that reported for other compounds. Surface soil/grass concentrations resulting from modeled deposition flux also showed acceptable bias and scatter compared with measured concentrations of PFO in soil/grass samples. Errors in predictions of air concentrations or deposition may be best explained by meteorological input uncertainty and conservatism in the PRIME algorithm used to account for building downwash. In general, AERMOD was found to be a useful screening tool for modeling the dispersion and deposition of PFO in air near a manufacturing facility.

The ability of microbes to rapidly sense and adapt to environmental changes plays a major role in structuring microbial communities, in affecting microbial activities, as well as in influencing various microbial interactions with the surroundings. The bacterial chemotaxis signal transduction system is the sensory perception system that allows motile cells to respond optimally to changes in environmental conditions by allowing cells to navigate in gradients of diverse physicochemical parameters that can affect their metabolism. The analysis of complete genome sequences from microorganisms that occupy diverse ecological niches reveal the presence of multiple chemotaxis pathways and a great diversity of chemoreceptors with novel sensory specificities. Owing to its role in mediating rapid responses of bacteria to changes in the surroundings, bacterial chemotaxis is a behavior of interest in applied microbiology as it offers a unique opportunity for understanding the environmental cues that contribute to the survival of bacteria. This chapter explores the diversity of bacterial chemotaxis and suggests how gaining further insights into such diversity may potentially impact future drug and pesticides development and could inform bioremediation strategies.

The environment contains various direct and indirect sources of perfluorooctanoic acid (PFOA). The present study uses a dynamic multispecies environmental fate model to analyze the potential formation of perfluorooctanoate (PFO), the anion of PFOA, in the environment from fluorotelomer acrylate polymer (FTacrylate) emitted to landfills and wastewater, residual fluorotelomer alcohol (8:2 FTOH) in FTacrylate, and residual PFOA in FTacrylate. A multispecies version of the SimpleBox model, which is capable of determining the fate of a chemical and its degradation products, was developed for this purpose. An uncertainty analysis on the chemical-specific input parameters was performed to examine for uncertainty in modeled concentrations. In 2005, residual 8:2 FTOH made up 80% of the total contribution of FTacrylate use to PFO concentrations in global oceans, and residual PFOA in FTacrylate contributed 15% to PFO concentrations from FTacrylate use in global oceans. After hundreds of years, however, the main source of PFO from total historical FTacrylate production is predicted to be FTacrylate degrading in soil following land application of sludge from sewage treatment plants, followed by FTacrylate still present in landfills. Uncertainty in modeled PFO concentrations was up to a factor of 3.3. Current FTacrylate use contributes less than 1% of the PFO in seawater, but because direct PFOA emission sources are reduced and PFOA continues to be formed from FTacrylate in soil and in landfills, this fraction grows over time.

Perfluorinated acids, including perfluorinated carboxylates (PFCAs), and perfluorinated sulfonates (PFASs), are environmentally persistent and have been detected in a variety of wildlife across the globe. The most commonly detected PFAS, perfluorooctane sulfonate (PFOS), has been classified as a persistent and bioaccumulative substance. Similarities in chemical structure and environmental behavior of PFOS and the PFCAs that have been detected in wildlife have generated concerns about the bioaccumulation potential of PFCAs. Differences between partitioning behavior of perfluorinated acids and persistent lipophilic compounds complicate the understanding of PFCA bioaccumulation and the subsequent classification of the bioaccumulation potential of PFCAs according to existing regulatory criteria. Based on available research on the bioaccumulation of perfluorinated acids, five key points are highlighted in this review: (1) bioconcentration and bioaccumulation of perfluorinated acids are directly related to the length of each compound's fluorinated carbon chain; (2) PFASs are more bioaccumulative than PFCAs of the same fluorinated carbon chain length; (3) PFCAs with seven fluorinated carbons or less (perfluorooctanoate (PFO) and shorter PFCAs) are not considered bioaccumulative according to the range of promulgated bioaccumulation,"B", regulatory criteria of 1000-5000 L/kg; (4) PFCAs with seven fluorinated carbons or less have low biomagnification potential in food webs, and (5) more research is necessary to fully characterize the bioaccumulation potential of PFCAs with longer fluorinated carbon chains (>7 fluorinated carbons), as PFCAs with longer fluorinated carbon chains may exhibit partitioning behavior similar to or greater than PFOS. The bioaccumulation potential of perfluorinated acids with seven fluorinated carbons or less appears to be several orders of magnitude lower than "legacy" persistent lipophilic compounds classified as bioaccumulative. Thus, although many PFCAs are environmentally persistent and can be present at detectable concentrations in wildlife, it is clear that PFCAs with seven fluorinated carbons or less (including PFO) are not bioaccumulative according to regulatory criteria.

Biodegradation of fluorinated polymers is of interest to assess them as a potential source of perfluorocarboxylates (PFCAs) in the environment. A fluoroacrylate polymer product test substance was studied in four aerobic soils over two years to assess whether the fluorotelomer alcohol (FTOH) side chains covalently bonded to the polymer backbone may be transformed to form PFCAs. The test substance itself was not directly measured; instead, nine analytes were determined to evaluate biodegradation. Terminal biotransformation products measured included perfluorooctanoate (PFO), perfluorononanoate (PFN), perfluorodecanoate (PFD), perfluoroundecanoate (PFU), and pentadecafluorodecanoate (7-3 acid). The molar concentration of 8-2 fluorotelomer alcohol (8-2 FTOH) in the test substance, fluoroacrylate polymer and residual unreacted raw materials and impurities ("residuals") were compared with the molar concentrations of the terminal biotransformation products for mass balance and kinetic assessments. Over the two year time frame of the experimental study, the fluoroacrylate polymer showed a slight extent of potential biodegradation under the experimental conditions of the study. A biodegradation half-life of 1200-1700 years was calculated for the fluoroacrylate polymer based on the rate of formation of PFO in aerobic soils. When the degradation rates of the fluoroacrylate polymer and residuals were applied to estimated total historic fluoroacrylate polymer production, use and disposal, the biodegradation of fluoroacrylate polymer and residuals is calculated to contribute less than 5 tonnes of PFO per year globally to PFCAs present in the environment.

This study reports on an investigation of the presence of polyfluorinated chemicals in a spatially and temporally integrated set of biological samples representing an Arctic food web. Zooplankton, Arctic cod, and seal tissues from the western Canadian Arctic were analyzed for perfluoroalkyl sulfonates [PFAS], perfluorocarboxylates [PFCAs], and other polyfluorinated acids. Perfluorooctane sulfonate [PFOS] was found in all samples [0.20-34 ng/g] and in the highest concentrations. PFCAs from nine to 12 carbons were quantified in most of the samples [0.28-6.9 ng/g]. PFCAs with carbon chain lengths of eight or less were not detected. Likewise, 8-2 fluorotelomer acid [8-2 FTA] and 8-2 fluorotelomer unsaturated acid [8-2 FTUA], products of fluorotelomer environmental transformation, were not detected. 2H,2H,3H,3H, heptadecafluoro decanoic acid [7-3 Acid], an additional metabolite from fluorotelomer biological transformation, was detected only in seal liver tissue [0.5-2.5 ng/g]. The ratios of branched to linear PFOS isomers in fish and seal tissue were not similar and did not match that of technical PFOS as manufactured. No branched PFCA isomers were detected in any samples. It is concluded that differing pharmacokinetics complicate the use of branched to linear ratios of PFCAs in attributing their presence to a specific manufacturing process. A statistical analysis of the data revealed significant correlations between PFOS and the PFCAs detected as well as among the PFCAs themselves. The 7-3 Acid was not correlated with either PFCAs or PFAS, which suggests that it may have a different exposure pathway.

A high spatial and temporal resolution atmospheric model is used to evaluate the potential contribution of fluorotelomer alcohol (FTOH) and perfluorocarboxylate (PFCA) emissions associated with the manufacture, use, and disposal of DuPont fluorotelomer-based products in North America to air concentrations of FTOH, perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in North America and the Canadian Arctic. A bottom-up emission inventory for PFCAs and FTOHs was developed from sales and product composition data. A detailed FTOH atmospheric degradation mechanism was developed to simulate FTOH degradation to PFCAs and model atmospheric transport of PFCAs and FTOHs. Modeled PFCA yields from FTOH degradation agree with experimental smog-chamber results supporting the degradation mechanism used. Estimated PFCA and FTOH air concentrations and PFCA deposition fluxes are compared to monitoring data and previous global modeling. Predicted FTOH air concentrations are generally in agreement with available monitoring data. Overall emissions from the global fluorotelomer industry are estimated to contribute approximately 1-2% of the PFCAs in North American rainfall, consistent with previous global emissions estimates. Emission calculations and modeling results indicate that atmospheric inputs of PFCAs in North America from fluorotelomer-based products will decline by an order of magnitude in the near future as a result of current industry commitments to reduce manufacturing emissions and lower the residual fluorotelomer alcohol raw material and trace PFCA product content.

The potential for airborne emissions to undergo long-range transport or to be removed from the atmosphere is influenced by their physical-chemical properties. When perfluorooctanate (PFO) enters the environment, its physical-chemical properties can vary significantly, depending on whether it exists as an acid, a salt, or a dissociated ion. A summary of the physical-chemical properties of the three most likely environmental states: ammonium perfluorooctanoate (APFO), perfluorooctanoic acid (PFOA) and the dissociated perfluorooctanoate anion (PFO(-)) is presented to illustrate the distinct environmental properties of each. The most volatile species, PFOA, is shown to have a pH-dependent air-water partitioning coefficient (K(aw)). The variability of K(aw) with pH influences the potential for vapor formation from aqueous environments, including rain events. Using the pH-dependent K(aw) and measured rain and air concentrations, it is shown that vapor-phase PFOA is not likely to be present above measurable levels of 0.2 ng m(-3) (12 parts per quadrillion v/v) during a rain event. Because rain concentrations determined in this work are comparable to measurements in other parts of North America, it is unlikely that rain events are a significant source of vapor-phase PFOA for the general North American region. It is shown that PFOA exists primarily in the particle phase in ambient air near direct sources of emissions and is efficiently scavenged by rain droplets, making wet deposition an important removal mechanism for emissions originating as either PFOA or APFO. Washout ratios of particle-associated PFO were determined to range between 1 x 10(5) and 5 x 10(5), in the same range as other semi-volatile compounds for which wet deposition is an important mechanism for atmospheric removal and deposition onto soils and water bodies.

The long-term (1950-2050) global fate of perfluorooctanoate (PFO) is investigated using the global distribution model, GloboPOP. The model is used to test the hypotheses that direct PFO emissions can account for levels observed in the global oceans and that ocean water transport to the Arctic is an important global distribution pathway. The model emission scenarios are derived from historical and projected PFO emissions solely from direct sources. Modeled ocean water concentrations compare favorably to observed PFO concentrations in the world's oceans and thus ocean inventories can be accounted for by direct sources. The model results support the hypothesis that long-range ocean transport of PFO to the Arctic is important and estimate a net PFO influx of approximately 8-23 tons per year flowing into the model's Northern Polar zone in 2005, an amount at least 1 order of magnitude greater than estimated PFO flux to the Arctic from potential indirect sources such as atmospheric transport and degradation of fluorotelomer alcohols. Modeled doubling times of ocean water concentrations in the Arctic between 1975 and 2005 of approximately 7.5-10 years are in good agreement with doubling times of PFO in Arctic biota estimated from monitoring data. The model is further applied to predict future trends in PFO contamination levels using forecasted (2005-2050) direct emissions, including substantial reductions committed to by industry. Modeled ocean water concentrations in zones near to sources decline markedly after 2005, whereas modeled concentrations in the Arctic are predicted to continue to increase until approximately 2030 and show no significant decrease for the remaining 20 years of the model simulation. Since water is the primary exposure medium for Arctic biota, these model results suggest that concentrations in Arctic biota may continue to rise long after direct emissions have been substantially reduced or eliminated.

The Root Zone Water Quality Model (RZWQM) and Pesticide Root Zone Model (PRZM) are currently being considered by the Office of Pesticide Programs (OPP) in the United States Environmental Protection Agency (US EPA) for Tier II screening of pesticide leaching to groundwater (November 2005). The objective of the present research was to compare RZWQM and PRZM based on observed conservative tracer and pesticide pore water and soil concentrations collected in two unique groundwater leaching studies in North Carolina and Georgia. These two sites had been used previously by the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Environmental Model Validation Task Force (EMVTF) in the validation of PRZM. As in the FIFRA EMVTF PRZM validation, 'cold' modelling using input parameters based on EPA guidelines/databases and 'site-specific' modelling using field-measured soil and hydraulic parameters were performed with a recently released version of RZWQM called RZWQM-NAWQA (National Water Quality Assessment). Model calibration was not performed for either the 'cold' or 'site-specific' modelling. The models were compared based on predicted pore water and soil concentrations of bromide and pesticides throughout the soil profile. Both models tended to predict faster movement through the soil profile than observed. Based on a quantitative normalised objective function (NOF), RZWQM-NAWQA generally outperformed or was equivalent to PRZM in simulating pore water and soil concentrations. Both models were more successful in predicting soil concentrations (i.e. NOF < 1.0 for site-specific data, which satisfies site-specific applicability) than they were at predicting pore water concentrations., (Copyright (c) 2006 Society of Chemical Industry)

As part of a process to improve confidence in the results of regulatory modeling, predictions of the pesticide root zone model (PRZM) 3.12 were compared with measured data collected in nine different field leaching studies. Reasonable estimates of leaching were obtained with PRZM 3.12 in homogeneous soils where preferential flow is not significant. The PRZM 3.12 usually did a good job of predicting movement of bromide in soil (soil and soil pore-water concentrations were generally within a factor of two of predicted values). For simulations based on the best choices for input parameters, predictions of soil pore-water concentrations for pesticides were usually within a factor of three and soil pore-water estimates within a factor of 11. When the model input parameters were calibrated to improve the simulation of hydrology, predicted pesticide concentrations in soil pore water were usually within a factor of two of measured concentrations. Because of the sensitivity of leaching to degradation rate, the most accurate predictions were obtained with pesticides with relatively slow degradation rates. When conservative assumptions were used to define input pesticide parameters, predictions of pesticide concentrations were usually a factor of two greater than when using the best estimate of input parameters without any built-in conservatism.

Occipital visual evoked potentials (VEPs) were recorded in response to low-contrast, low spatial-frequency chromatic, and achromatic gratings. Fast Fourier Transform (FFT) and time-domain analysis were used to reveal differences in harmonic content and amplitude of chromatic and achromatic response components over a wide range of temporal frequencies. The chromatic ON/OFF VEP is dominated by the fundamental component indicating that onset and offset responses are different. This type of response is typical of neurons with sustained type response characteristics. Conversely, the achromatic onset VEP contains a predominant second harmonic component in addition to the fundamental. This similarity between onset and offset responses suggests that transient mechanisms are responsible for the generation of achromatic components. Frequency analysis of VEPs elicited by phase-reversing stimuli reveals that all of the response energy is concentrated at the second harmonic of the stimulating frequency. The magnitude of the second harmonic component is maximal for achromatic stimuli and undergoes a distinct minimum for isoluminant, chromatic stimuli. This behavior indicates that under the stimulus conditions used, magnocellular neurons with transient characteristics dominate the reversal VEP.

Chromatic and achromatic visual function were investigated using psychophysical and evoked potential techniques in 32 patients with multiple sclerosis (MS) or optic neuritis. There was no evidence for either chromatic or achromatic vision being selectively damaged. There was, however, some evidence that demyelination of the optic nerve causes a visual defect in which the transmission of high temporal frequencies is imparied. In some patients either a red or blue deficit was evident, but overall there was no evidence of a wavelength specific colour vision defect in our patient group. Reduction of chromatic sensitivity as determined psychophysically had a statistically significant correlation with the amplitude and latency of the chromatic visual evoked potential.

One cause of post-operative morbidity in the elective repair of abdominal aortic aneurysms is the development of a paralytic or 'adynamic' ileus. In a series of 20 consecutive patients undergoing such a procedure, the maintenance of small bowel motility and absorptive capacity in the immediate post-operative period was assessed using barium sulphate and xylose passed down a naso-duodenal tube sited at the time of surgery. This simple study demonstrated that small bowel function was preserved in all cases, and hence that patients could be fed enterally via naso-duodenal tube (in particular using very low residue formulae) rather than using costly parenteral regimens, should an ileus persist.

This report describes genetic, endocrine, and histological findings in a 31-yr-old 45,X/46,Xdel(Y)(q12) male with gynecomastia and azoospermia. A preponderance of 45,X cells was found in all tissues studied. Endocrine data suggested an abnormal Leydig cell-pituitary gonadotroph axis, although the basal testosterone level and the response to short term administration of hCG were normal. Testicular histology showed Leydig cell hyperplasia and seminiferous tubule atrophy. These findings are compared to 17 similar cases in the literature. A characteristic of all these cases is a morphologically abnormal Y-chromosome, which probably results in the 45,X cell line. The masculinizing genes on the remaining Y-chromosomes are functionally intact and promote a male phenotype in infancy and adolescence. Azoospermia is usually present, and gynecomastia or hypogonadism occurs later in life. Comparison with other nonmasculinized 45,X/46,XY cases supports existing theories regarding the function of the various segments of the Y-chromosome.

In vitro properties of somatic cell hybrids between non-malignant B82 mouse fibroblasts and human chronic granulocytic leukemia spleen cells include lack of cell density-dependent growth inhibition and growth in soft agar. These phenotypic expressions of cell transformation appear linked to the retention by the cells of chromosome 7 from the human leukemic genome.

In humans the XY ovary is degenerative, there being scant evidence of persistence of that organ beyond the perinatal period. Here we describe indications of functional ovarian tissue in a 17-year-old female with male karyotype, H-Y+ cellular phenotype, and some signs of the Turner syndrome. Her gonads were removed after the onset of secondary amenorrhea. Histological examination revealed a degenerative right ovary devoid of germ cells and follicles, and a left streak gonad. There was no trace of testicular development in either side.

A method for the determination of encapsulated d-limonene dimercaptan (d-LDM), a possible marker for Cannabis sativa L. sprayed with herbicide, has been developed. The methodology includes a single-step extraction, followed by gas chromatography with flame photometric detector (FDP) using n-octadecyl mercaptan (n-octadecylthiol) as an internal standard. A liner relationship was obtained from spiked samples with an average coefficient of variation of 9.0 per cent. The method has been used to determine part-per-million levels of LDM in actual field experiments in Mexico. The FDP limit was found to be 7 ng for d-LDM.

Patterns of chromosome segregation were studied in 2 different intraspecific mouse cell hybrids: (1) A9 x B82, formed by fusing 2 cell lines of heteroploid fibroblasts, and (2) UWE, originating from the fusion of A9 cells with euploid foetal erythrocytes. Detailed analyses of Giemsa (G)-banded chromosomes and chromosome arms of both parental and hybrid cells were made for each hybrid type, in order to determine the specificity of the losses and to assess the influence of ploidy and cell differentiation. Unlike the A9 x B82 hybrids, which revealed a significant chromosome loss under selective tissue culture pressures only after 9 months, the UWE hybrids showed a sharp reduction in the total chromosome number during the initial 2 months under similar pressures. However, with no additional cloning, UWE remained karyotypically stable after that time. This rapid chromosomal segregation in UWE hybrids may be caused by properties of the parental foetal erythrocytes. In UWE cells, the majority of the chromosome arms were retained or duplicated. Less than a quarter of the total number of chromosome arms were segregated or lost, and these were all chromosome arms with abnormal mouse G-banding patterns, present only in the heteroploid A9 parental cells. In two of the four A9 x B82 hybrid lines, there was marked segregation of chromosome arms whose banding patterns were identical to those of wild type mouse telocentric chromosomes. For both types of intraspecific cell hybrids, two thirds or more of the chromosome arms had banding patterns which were the same as those of the wild type genome.

An 18 year old white female presented with short stature and amenorrhoea. Her height was 135 cm, weight 46.6 kg; she had a broad neck, a high arched palate, short fifth metacarpals bilaterally, short third, fourth and fifth metatarsals bilaterally and minimal breast development. Although the clinical picture strongly suggested Turner's syndrome, investigations revealed: (a) normal female 46,XX chromosomal pattern on analyses of skin, lymphocytes and ovarian tissue; (b) undetectable serum growth hormone levels; (c) pre-pubertal oestradiol-17 beta levels; (d) only very occasional primordial follicles on ovarian biopsy with a thickened capsule; and (e) basal LH and FSH levels of 6.8 to 9.6 mIU/ml which rose after LRH injection to 90 and 26 mIU/ml, respectively. The patient has the unusual combination of growth hormone deficiency, gonadal dysgenesis and Turner stigmata with a normal chromosomal complement.

Hybrids between A9 (HGPRT-) and B82 (TK-), mouse heteroploid fibroblast lines, were obtained through continuous cultivation and clonal selection; such hybrids showed marked segregation and by conventional stains displayed chromosome numbers and distribution similar to that of either parental type. Detailed analyses by Giemsa (G)- and centromeric-banding of these parental lines, and of 4 of the reduced hybrids, maintained in culture for up to 5 years, revealed the following points: (1) The distribution of the majority of individual chromosomal classes was similar for 3 of the hybrid cell lines. (2) Over two-thirds of the chromosomal arms in both the parental lines and hybrid lines were identical to normal mouse telocentric chromosomes. (3) For 2 of the hybrid lines, segregation was particularly marked with respect to those chromosomal arms whose G-banding patterns were identical to the wild-type genome; this indicated that segregation had occurred at the expense of redundant chromosomal material introduced by cell fusion. These banded studies demonstrated that segregation chiefly accounted for the sharp reduction in chromosome numbers while recombination accounted for the chromosome heterogeneity of the hybrid cells as compared to the parental genomes.