Disturbance and temporal partitioning of the activated sludge metacommunity.

The resilience of microbial communities to press disturbances and whether ecosystem function is governed by microbial composition or by the environment have not been empirically tested. To address these issues, a whole-ecosystem manipulation was performed in a full-scale activated sludge wastewater treatment plant. The parameter solids retention time (SRT) was used to manipulate microbial composition, which started at 30 days, then decreased to 12 and 3 days, before operation was restored to starting conditions (30-day SRT). Activated sludge samples were collected throughout the 313-day time series in parallel with bioreactor performance ('ecosystem function'). Bacterial small subunit (SSU) rRNA genes were surveyed from sludge samples resulting in a sequence library of >417,000 SSU rRNA genes. A shift in community composition was observed for 12- and 3-day SRTs. The composition was altered such that r-strategists were enriched in the system during the 3-day SRT, whereas K-strategists were only present at SRTs⩾12 days. This shift corresponded to loss of ecosystem functions (nitrification, denitrification and biological phosphorus removal) for SRTs⩽12 days. Upon return to a 30-day SRT, complete recovery of the bioreactor performance was observed after 54 days despite an incomplete recovery of bacterial diversity. In addition, a different, yet phylogenetically related, community with fewer of its original rare members displaced the pre-disturbance community. Our results support the hypothesis that microbial ecosystems harbor functionally redundant phylotypes with regard to general ecosystem functions (carbon oxidation, nitrification, denitrification and phosphorus accumulation). However, the impacts of decreased rare phylotype membership on ecosystem stability and micropollutant removal remain unknown.

On the correlation between single-frequency impedance measurements and human skin permeability to water.

The objective of this study was to quantitatively compare measurements of tritiated water permeability with impedance determined at either 100 or 1000 Hz using an LCR databridge on the same pieces of skin. A previously published expression based on a simple circuit of a parallel resistor and constant phase element (CPE) was used to relate (RPARA) measured at different frequencies to the DC resistance (RskinA) and the steady-state skin permeability of tritiated water (kp). Using this analysis, kp and (RPARA) data from three laboratories were shown to be consistent with each other, and kp and (RskinA) estimated from (RPARA) were linearly correlated. Compared with urea and mannitol, which are known to permeate skin through a polar pathway, the value of kp for water was found to be about two times larger than expected for transport through only the polar pathway, suggesting an approximately equal contribution from the lipophilic pathway. Equations relating kp to (RPARA) and (RskinA) were used to compare on a consistent basis proposed tests for identifying and excluding damaged skin from chemical absorption studies. The criterion of 20 kΩ cm2 for (RskinA) corresponds to a tritiated water permeability of 3.2×10(-3) cm/h, which should exclude damaged skin without screening undamaged but higher permeability skin samples from study.

Community woodstove changeout and impact on ambient concentrations of polycyclic aromatic hydrocarbons and phenolics.

A large woodstove changeout program was carried out in Libby, Montana, with the goal of reducing ambient levels of PM2.5. This provided researchers the opportunity to measure ambient concentrations of phenolic and polycyclic aromatic hydrocarbons (PAHs) before, during, and after the changeout of nearly 1200 stoves to evaluate the effectiveness of the intervention. Starting in the heating season of 2004/2005 and ending in the heating season of 2007/2008, 19 compounds were measured every three days using a high-volume polyurethane foam (PUF) sampler followed by gas chromatography and mass spectrometry analysis. Some of the organic species with the highest measured concentrations were also signature chemical markers for wood combustion. When comparing the measurements conducted during the heating season of 2004/2005 (prechangeout) to those of the heating season of 2007/2008 (postchangeout), there was a 64% average reduction in the measured concentrations of phenolics and PAHs, while the PM2.5 mass dropped by only 20% over the same time period. The results of this four year sampling program suggest that the Libby woodstove changeout program was successful in reducing overall concentrations of the measured phenolic and PAH compounds.

Improved bioequivalence assessment of topical dermatological drug products using dermatopharmacokinetics.

PURPOSE: A dermatopharmacokinetic (DPK) approach, in which drug levels in the stratum corneum (SC) are measured as a function of time post-application and post-removal of the product using tape-strip sampling in vivo in humans, has been considered for the comparative assessment of topical bioavailability. Its application to-date has been limited by contradictory results and concerns that variability in the method necessitates large numbers of treatment sites and volunteers. The objective of this study was to test whether a revised protocol could better assess bioequivalence. METHODS: A blinded study of three 1% econazole nitrate cream products, for which the SC is the site of action, was conducted to examine several modifications to the DPK methodology. In addition to protocol changes designed to reduce experimental variability, bioequivalence was assessed at a single uptake time and a single clearance time measured in duplicate in each subject. RESULTS: Conclusive determinations of bioequivalence were achieved with only four treatment sites per product in each of 14 volunteers, which was less than one-third the number required in a previous DPK investigation. CONCLUSIONS: Comparative bioequivalence can be assessed conclusively with fewer treatment sites in fewer subjects with robust methods that should be less sensitive to inter-laboratory differences.

Optimizing metrics for the assessment of bioequivalence between topical drug products.

PURPOSE: Stratum corneum tape stripping post-application of a drug product followed by analysis of the active agent in this tissue layer is an approach being seriously considered for the comparative assessment of topical bioavailability. Key issues revolve around how best to perform this experiment and interpret the data. METHODS: Using previously published results from a comparative study of three 0.025% tretinoin gel products, alternative data analysis approaches are presented that may render the technique more accessible to the evaluation of new and generic topical dosage forms. RESULTS: For the tretinoin gel study, the conclusions for bioequivalence from measurements of drug levels at only one uptake and one clearance time were the same as those from the original study, which required measurements at eight different treatment times. Furthermore, comparisons of drug levels at one uptake and one clearance time discriminated differences in bioequivalence for clearance and uptake, which had previously been missed. Half-life estimates, derived from time course data of drug clearance, can be related to lag time for drug penetration through the SC. CONCLUSIONS: This new data analysis demonstrates that comparative bioequivalence might be assessed more easily.

Lung cancer and internal lung doses among plutonium workers at the Rocky Flats Plant: a case-control study.

The authors conducted a nested case-control study of the association between lung cancer mortality and cumulative internal lung doses among a cohort of workers employed at the Rocky Flats Plant in Colorado from 1951 to 1989. Cases (n = 180) were individually matched with controls (n = 720) on age, sex, and birth year. Annual doses to the lung from plutonium, americium, and uranium isotopes were calculated for each worker with an internal dosimetry model. Lung cancer risk was elevated among workers with cumulative internal lung doses of more than 400 mSv in several different analytical models. The dose-response relation was not consistent at high doses. Restricting analysis to those employed for 15-25 years produced a statistically significant linear trend with dose (chi-square = 67.2, p < 0.001), suggesting a strong healthy worker survivor effect. The association between age at first internal lung dose and lung cancer mortality was statistically significant (odds ratio = 1.05, 95% confidence interval: 1.01, 1.10). No associations were found between lung cancer mortality and cumulative external penetrating radiation dose or cumulative exposures to asbestos, beryllium, hexavalent chromium, or nickel.

Uncertainty in measurements of dermal absorption of pesticides.

Dermal absorption experiments form an important component in the assessment of risk from exposure to pesticides and other substances. Much dermal absorption data is gathered in rat experiments carried out using a certain standard protocol. Uncertainties in these data arise from many sources and can be quite large. For example, measurements of the systemic absorption of hexaconazole differed by more than an order of magnitude within a single experiment. Two diniconazole studies produced quite different results, due to minor differences in protocol and in chemical formulation. Limits of detection can also prevent accurate measurement when the amounts absorbed are small. These examples illustrate the need for measuring and reporting uncertainties in estimates that are based on these data. The most direct way to estimate uncertainty is to compute the sample standard deviations of replicate measurements. By pooling these estimates across dose and duration groups for which they are similar, the number of degrees of freedom is increased, and more precise confidence intervals can be obtained. In particular, the ratio of upper to lower 95% confidence limits was reduced by as much as ten-fold for hexaconazole, seven-fold for uniconazole, and nearly four-fold for propiconazole.