Uncertainty and equifinality in environmental modelling of organic pollutants with specific focus on cyclic volatile methyl siloxanes.

Multi-media fate and transport models (MFTMs) are invaluable tools in understanding and predicting the likely behaviour of organic pollutants in the environment. However, some parameters describing the properties of both the environmental system and the chemical pollutant under consideration are uncertain and or variable in space and time. Furthermore, model performance is often evaluated using sparse data sets on chemical concentrations in different media. This can result in equifinality - the phenomenon in which several different combinations of model parameters can result in similar predictions of environmental concentrations. We explore this idea for MFTMs for the first time using, as examples, three cyclic volatile methyl siloxanes (cVMS: D4, D5 and D6) and the QWASI lake model applied to Tokyo Bay. Monte Carlo simulation was employed with parameters selected from probability distributions representing estimated uncertainty in a large number of iterations. This generated distributions of predicted chemical concentrations in water (CW) and sediment (CS) which represent the aleatory uncertainty envelope but which also demonstrate significant equifinality. For all three compounds, the uncertainty implied in the CW was lower (coefficient of variation, CV, of the order of 20%) than for CS (CV ca. 45%), reflecting the propensity of cVMS compounds to sorb to sediment and the sensitivity of the model to KOC. Confidence intervals were particularly high for the persistence of D5 and D6 in sediment which both ranged between approximately 1.7 years and approximately 26 years for Tokyo Bay. Predicted concentration distributions matched observations well for D5 and D6 not for D4. Equifinality could be reduced by better constraining acceptable parameter sets using additional measured data from different environmental compartments.

Feasibility, effectiveness and cost-effectiveness of a telephone-based weight loss program delivered via a hospital outpatient setting.

Engaging patients in a group-based weight loss program is a challenge for the acute-care hospital outpatient setting. To evaluate the feasibility, effectiveness and cost-effectiveness of a telephone-based weight loss service and an existing face-to-face, group-based service a non-randomised, two-arm feasibility trial was used. Patients who declined a two-month existing outpatient group-based program were offered a six-month research-based telephone program. Outcomes were assessed at baseline, two months (both groups) and six months (telephone program only) using paired t tests and linear regression models. Cost per healthy life year gained was calculated for both programs. The telephone program achieved significant weight loss (-4.1 ± 5.0 %; p = 0.001) for completers (n = 35; 57 % of enrolees) at six months. Compared to the group-based program (n = 33 completers; 66 %), the telephone program was associated with greater weight loss (mean difference [95%CI] -2.0 % [-3.4, -0.6]; p = 0.007) at two months. The cost per healthy life year gained was $33,000 and $85,000, for the telephone and group program, respectively. Telephone-delivered weight management services may be effective and cost-effective within an acute-care hospital setting, likely more so than usual (group-based) care.

Development and application of a catchment scale pesticide fate and transport model for use in drinking water risk assessment.

This paper describes the development and application of IMPT (Integrated Model for Pesticide Transport), a parameter-efficient tool for predicting diffuse-source pesticide concentrations in surface waters used for drinking water supply. The model was applied to a small UK headwater catchment with high frequency (8h) pesticide monitoring data and to five larger catchments (479-1653km(2)) with sampling approximately every 14days. Model performance was good for predictions of both flow (Nash Sutcliffe Efficiency generally >0.59 and PBIAS <10%) and pesticide concentrations, although low sampling frequency in the larger catchments is likely to mask the true episodic nature of exposure. The computational efficiency of the model, along with the fact that most of its parameters can be derived from existing national soil property data mean that it can be used to rapidly predict pesticide exposure in multiple surface water resources to support operational and strategic risk assessments.

Anthelmintic drug residues in beef: UPLC-MS/MS method validation, European retail beef survey, and associated exposure and risk assessments.

Anthelmintic drugs are widely used to control parasitic infections in cattle. The ProSafeBeef project addressed the need for data on the exposure of European consumers of beef to potentially harmful drug residues. A novel analytical method based on matrix solid-phase dispersive extraction and ultra-performance liquid chromatography-tandem mass spectrometry was validated for 37 anthelmintic drugs and metabolites in muscle (assay decision limits, CCα, = 0.15-10.2 µg kg⁻¹). Seven European countries (France, Spain, Slovenia, Ireland, Italy, Belgium and Portugal) participated in a survey of retail beef purchased in local shops. Of 1061 beef samples analysed, 26 (2.45%) contained detectable residues of anthelmintic drugs (0.2-171 µg kg⁻¹), none above its European Union maximum residue limit (MRL) or action level. Residues detected included closantel, levamisole, doramectin, eprinomectin, moxidectin, ivermectin, albendazole and rafoxanide. In a risk assessment applied to mean residue concentrations across all samples, observed residues accounted for less than 0.1% of the MRL for each compound. An exposure assessment based on the consumption of meat at the 99th percentile of consumption of adults in 14 European countries demonstrated that beef accounted for less than 0.02% of the acceptable daily intake for each compound in each country. This study is the first of its kind to apply such a risk-based approach to an extensive multi-residue survey of veterinary drug residues in food. It has demonstrated that the risk of exposure of the European consumer to anthelmintic drug residues in beef is negligible, indicating that regulation and monitoring is having the desired effect of limiting residues to non-hazardous concentrations.

Development of micro-electrode array based tests for neurotoxicity: assessment of interlaboratory reproducibility with neuroactive chemicals.

Neuronal assemblies within the nervous system produce electrical activity that can be recorded in terms of action potential patterns. Such patterns provide a sensitive endpoint to detect effects of a variety of chemical and physical perturbations. They are a function of synaptic changes and do not necessarily involve structural alterations. In vitro neuronal networks (NNs) grown on micro-electrode arrays (MEAs) respond to neuroactive substances as well as the in vivo brain. As such, they constitute a valuable tool for investigating changes in the electrophysiological activity of the neurons in response to chemical exposures. However, the reproducibility of NN responses to chemical exposure has not been systematically documented. To this purpose six independent laboratories (in Europe and in USA) evaluated the response to the same pharmacological compounds (Fluoxetine, Muscimol, and Verapamil) in primary neuronal cultures. Common standardization principles and acceptance criteria for the quality of the cultures have been established to compare the obtained results. These studies involved more than 100 experiments before the final conclusions have been drawn that MEA technology has a potential for standard in vitro neurotoxicity/neuropharmacology evaluation. The obtained results show good intra- and inter-laboratory reproducibility of the responses. The consistent inhibitory effects of the compounds were observed in all the laboratories with the 50% Inhibiting Concentrations (IC(50)s) ranging from: (mean ± SEM, in µM) 1.53 ± 0.17 to 5.4 ± 0.7 (n = 35) for Fluoxetine, 0.16 ± 0.03 to 0.38 ± 0.16 µM (n = 35) for Muscimol, and 2.68 ± 0.32 to 5.23 ± 1.7 (n = 32) for Verapamil. The outcome of this study indicates that the MEA approach is a robust tool leading to reproducible results. The future direction will be to extend the set of testing compounds and to propose the MEA approach as a standard screen for identification and prioritization of chemicals with neurotoxicity potential.

An assessment of the risk to surface water ecosystems of groundwater P in the UK and Ireland.

A good quantitative understanding of phosphorus (P) delivery is essential in the design of management strategies to prevent eutrophication of terrestrial freshwaters. Most research to date has focussed on surface and near-surface hydrological pathways, under the common assumption that little P leaches to groundwater. Here we present an analysis of national patterns of groundwater phosphate concentrations in England and Wales, Scotland, and the Republic of Ireland, which shows that many groundwater bodies have median P concentrations above ecologically significant thresholds for freshwaters. The potential risk to receptor ecosystems of high observed groundwater P concentrations will depend on (1) whether the observed groundwater P concentrations are above the natural background; (2) the influence of local hydrogeological settings (pathways) on the likelihood of significant P transfers to the receptor; (3) the sensitivity of the receptor to P; and, (4) the relative magnitude of P transfers from groundwater compared to other P sources. Our research suggests that, although there is often a high degree of uncertainty in many of these factors, groundwater has the potential to trigger and/or maintain eutrophication under certain scenarios: the assumption of groundwater contribution to river flows as a ubiquitous source of dilution for P-rich surface runoff must therefore be questioned. Given the regulatory importance of P concentrations in triggering ecological quality thresholds, there is an urgent need for detailed monitoring and research to characterise the extent and magnitude of different groundwater P sources, the likelihood for P transformation and/or storage along aquifer-hyporheic zone flow paths and to identify the subsequent risk to receptor ecosystems.

Incorporating uncertainty into predictions of diffuse-source phosphorus transfers (using readily available data).

Phosphorus (P) is a limiting nutrient in many freshwater ecosystems and increases in its availability can lead to eutrophication. Effective management of P in freshwaters requires quantitative estimates of P supply from all significant sources. A simple GIS-based model, capable of predicting total diffuse source phosphorus export from catchments using readily available data, has been developed. The model is based on the idea of export coefficients but includes the effects of topography (slope and cumulative area), soil type (using the U.K. Hydrology of Soil Types (HOST) classification) and climate (hydrologically effective rainfall) as well as land use. Uncertainty in key model parameters is accounted for using Monte Carlo simulation which involves random sampling from probability density functions in a large number of iterations. This reduces the need for subjective optimisation of export coefficients. The model has been applied to the Greens Burn catchment, Scotland and predicts P exports within the confidence limits of the measured values.

A modelling assessment of the atmospheric fate of volatile methyl siloxanes and their reaction products.

Volatile methyl siloxanes break down in the atmosphere by reacting with OH radicals to form OH-substituted silanols. As the silanols become increasingly OH substituted they are increasingly likely to be removed from the atmosphere by wet and dry deposition. A simple equilibrium partitioning model was constructed to explore the relative rates of removal by different mechanisms (reaction vs. deposition) for siloxanes and their resultant silanols. A mass balance is calculated for the parent siloxane molecule and for each silanol, characterised by the number of OH substitutions. The model includes the effect of incomplete equilibrium between the vapour, adsorbed and dissolved phases of silanols in the atmosphere using a non-equilibrium factor (epsilon) expressing relative departure from equilibrium. Model results show: (1) maximum vapour-phase concentrations for non-substituted siloxanes and single-OH-substituted silanols; (2) maximum dissolved-phase and adsorbed-phase concentrations for two-OH-substituted silanols; (3) >99% of the original material will be removed in wet deposition and <1% in dry deposition as silanols. For increasing OH-substitutions, the decreasing concentration of precursor molecules (as a consequence of combined removal processes) means that concentrations are negligible, in all phases, beyond three or four substitutions. Predictions were relatively insensitive to assumed departures from phase equilibrium. Predictions of silanol hydrolysis in liquid water droplets suggest that the mix of diol chain lengths in precipitation may not be in thermodynamic equilibrium and will depend on atmospheric residence time and pH.

Management of urethritis in health maintenance organization members receiving care at a multispecialty group practice in Massachusetts.

BACKGROUND: Cost containment has led to a concern that health maintenance organization-insured patients presenting with complaints of urethritis may be treated without being tested. GOAL: To determine the proportion of men presenting with symptoms of urethritis who are tested for Chlamydia trachomatis and Neisseria gonorrhoeae. STUDY DESIGN: Reviews were performed on 196 randomly selected patient records with an outpatient visit and a diagnostic code consistent with urethritis between 1995 and 1997. Data were collected on demographics, diagnostic testing, and treatment. RESULTS: Diagnostic testing for C trachomatis and N gonorrhoeae was performed, respectively, in 92.3% and 83.2% of the men presenting at an initial visit with complaints of urethritis. Altogether, 98.2% of the patients who met the Centers for Disease Control criteria for documenting urethritis were tested for C trachomatis and N gonorrhoeae. CONCLUSION: Diagnostic testing for C trachomatis and N gonorrhoeae is nearly universal in this multispecialty group practice setting, facilitating surveillance and public health efforts.

The development and implementation of a hospital safety and sanitation task force.

We have found that the above activities are facilitated by utilizing a computerized filing program. The computer formal provides quick, concise reports and statistical data analysis. The formation catalogued can be easily analysis. The information catalogued can be easily categorized and analyzed. The time invested in organizational meetings concerning committee membership, guideline review and creating an efficient incident coding scheme was essential to the success of the project. Problems seem to arise when several different departments share a common space for different activities. For example, medication room sanitation throughout the hospital was suboptimal probably related to the fact that Nursing, Pharmacy and General Stores all utilized the area. No individual department felt it was their sole responsibility to ensure appropriate sanitation. Through the efforts of the task force, we were able to facilitate cooperation among the departments with each doing their share. As a result, medication rooms are now cleaner, neater and therefore safer. Additional incidents have been corrected since the original tabulation of this report. A priority goal is to facilitate corrective action in a more timely manner. It is critical that surveys should not be intended to be "white glove inspections" with criticisms placed on specific departments. This can be accomplished by informing department managers of the intent of the surveys and by allowing staff to participate in all activities. In addition, the support and cooperation of administration is a major factor in the potential success of a program of this nature. As a result of the interdisciplinary team approach, the general safety environment for patients, visitors, employees and volunteers has significantly been improved at our institution.