The potential for estradiol and ethinylestradiol degradation in English rivers

Water samples were collected in spring, summer, and winter from English rivers in urban/industrial (River Aire and River Calder, Yorkshire, UK) and rural environments (River Thames, Oxfordshire, UK) to study the biodegradation potential of the key steroid estrogen 17beta-estradiol (E2) and its synthetic derivate ethinylestradiol (EE2). Microorganisms in the river water samples were capable of transforming E2 to estrone (E1) with half-lives of 0.2 to 9 d when incubated at 20 degrees C. The E1 was then further degraded at similar rates. The most rapid biodegradation rates were associated with the downstream summer samples of the River Aire and River Calder. E2 degradation rates were similar for spiking concentrations throughout the range of 20 ng/L to 500 microg/L. Microbial cleavage of the steroid ring system was demonstrated by release of radiolabeled CO2 from the aromatic ring of E2 (position 4). When E2 was degraded, the loss of estrogenicity, measured by the yeast estrogen screen (YES) assay, closely followed the loss of the parent molecule. Thus, apart from the transient formation of E1, the degradation of E2 does not form other significantly estrogenic intermediates. The E2 could also be degraded when incubated with anaerobic bed sediments. Compared to E2, EE2 was much more resistant to biodegradation, but both E2 and EE2 were susceptible to photodegradation, with half-lives in the order of 10 d under ideal conditions.     

Pyrethroid sorption to Sacramento River suspended solids and bed sediments

Sorption of pyrethroid insecticides to solid materials will typically dominate the fate and transport of these hydrophobic compounds in aquatic environments. Batch reactor isotherm experiments were performed with bifenthrin and λ-cyhalothrin with suspended material and bed sediment collected from the Sacramento River, California, USA. These batch reactor experiments were performed with low spiking concentrations and a long equilibration time (28?d) to be more relevant to environmental conditions. Sorption to suspended material and bed sediment was compared to examine the role of differential sorption between these phases in the environmental transport of pyrethroids. The equilibrium sorption data were fit to the Freundlich isotherm model and fit with r(2) >?0.87 for all experiments. Freundlich exponents ranged from 0.72?±?0.19 to 1.07?±?0.050, indicating sorption nonlinearity for some of the experimental conditions and linearity for others over the concentration range tested. The Freundlich capacity factors were larger for the suspended solids than for the bed sediments, and the suspended material had a higher specific surface area and higher organic carbon content compared to the bed sediment. Calculated organic carbon-normalized distribution coefficients were larger than those previously reported in the literature, by approximately an order of magnitude, and ranged from 10(6.16) to 10(6.68) at an equilibrium aqueous concentration of 0.1?μg/L. Higher than expected sorption of pyrethroids to the tested materials may be explained by sorption to black carbon and/or mineral surfaces.     

Trace metals in sediments and potential availability to Anadara granosa

Trace metals in the sediments non-residual fraction and their relative abundance in various sedimentary components from the culture bed of Anadara granosa were investigated. High levels of Cd (40%), Ni (40%), and Pb (43%) were associated with the sediment exchangeable phase (EP). The sediment moderately reducible phase (MRP) was more predominant than the easily reducible phase (ERP) and the organic sulphide phase (OSP) in the sorption of available trace metals. However, this area was not considered to be heavily impacted by trace metal pollution. Since there was no significant concentration gradients observed in sediments and bivalves collected from all stations, trace metal enrichment factors were determined. A. granosa collected from this area was enriched by Zn, Cu, Pb, Ni, Cd, and Ni.     

Contaminated suspended sediments toxic to an Antarctic filter feeder: aqueous- and particulate-phase effects

Disturbances such as dredging, storms, and bioturbation result in the resuspension of sediments. This may affect sessile organisms that live on hard substrates directly above the sediment. Localized sediment contamination exists around many Antarctic research stations, often resulting in elevated contamination loads in marine sediments. To our knowledge, the potential impact of resuspended contaminated sediments on sessile fauna has not been considered, so in the present study, we assessed the sensitivity of Antarctic spirorbid polychaetes to aqueous metals and to metal-contaminated sediments that had been experimentally resuspended. Worms were first exposed to aqueous metals, both singly and in combination, over 10 d. Spirorbid mortality was tolerant to copper (median lethal concentration [LC50], 570 microg/L), zinc (LC50, > 4,910 microg/L), and lead (LC50, > 2,905 microg/L); however, spirorbid behavior responded to copper concentrations as low as 20 microg/L. When in combination, zinc significantly reduced mortality caused by copper. A novel technique was used to resuspend sediments spiked with four concentrations of three metals (up to 450 microg/g dry wt of copper, 525 micro/g dry wt of lead, and 2,035 microg/g dry wt of zinc). The response of spirorbids to unfiltered suspended sediment solutions and filtered solutions (aqueous metal exposure) was measured. Suspended sediments were toxic to filter-feeding spirorbids at concentrations approximating those found in contaminated Antarctica areas. Toxicity resulted both from aqueous metals and from metals associated with the suspended sediments, although suspended clean sediments had no impact. To our knowledge, the present study is the first to show that resuspension of contaminated sediments can be an important pathway for toxicity to Antarctic hard substrate organisms. Based on the present results, current sediment-quality guidelines used in the evaluation of Australian sediments may be applicable to Antarctic ecosystems.     

Relationships between Cd and Zn partitioning and geochemical composition in sediments from Chinese rivers

Adsorption isotherm experiments were conducted to determine the distribution coefficients (Kd) for Cd and Zn between water and sediments from twelve rivers in eastern China. The low metal concentration (<10(-10) M) added into the sediment-water system enabled the direct measurements of linear adsorption isotherms. When other solution parameters, such as ionic strength, were controlled, sediment geochemical characteristics were the major factors affecting metal distribution. The Kd was highly dependent on the total organic carbon contents and Fe-Mn oxide at pH = 7.0, and was affected significantly by the carbonate content in the sediments due to its control of pH. The Kd of the Huanghe sediments, which had the highest carbonate concentration (13.1%), increased sharply for both Cd and Zn when the pH increased. A quantitative model using the experimentally obtained phase distribution coefficients (Kd)i was applied to study the effects of different geochemical phases in the sediment on metal distributions. The (Kd)i of carbonate was correlated significantly with the carbonate content in the sediment, whereas the (Kd)i of total organic carbon (TOC) and Fe-Mn oxide phases were highly pH dependent. Using the (Kd)i for each geochemical phase, the calculation showed that about 91% and 85% of sorbed Cd and Zn, respectively, added to the batch reactors were distributed among the three major geochemical phases: TOC, Fe-Mn oxide, and carbonate. Total organic carbon was the most important binding phase for Cd, and Fe-Mn oxide for Zn. Furthermore, adsorption experiments with simulated sediments show the importance of interactions between different geochemical phases on metal partitioning.     

Desorption kinetics and mobility of some radionuclides in sediments

The desorption kinetics of five radionuclides, 85Sr, 137Cs, 60Co, 54Mn, and 65Zn, were studied for several coastal sediments, a few limnetic sediments, and one subsoil, using various aqueous solutions for extraction in batch systems. In a 2-wk desorption experiment, greater than 90% of most radionuclides sorbed were extracted by 6N-HCl, whereas in 1N-HCl approximately 30% of the 137Cs was retained within the sediments and a soil due to its fixation following intraparticle diffusion. For longer desorption periods (6 wk), reversible sorption with sediments could be seen for the 137Cs compared with the other four radionuclides in seawater. The EDTA-2Na solution extracted greater than 70% of 65Zn, 54Mn, and 60Co, and the ammonium oxalate extracted greater than 60% of 54Mn and 60Co. Readily exchangeable cations extracted by ammonium acetate were greater than 80% for 85Sr, approximately 50% for 137Cs, and 40% for 60Co and 54Mn. Many of the distribution coefficients for these radionuclides in coastal sediments obtained by desorption experiments were one order of magnitude or more larger than those obtained by the adsorption experiments. For 85Sr, larger-than-expected distribution coefficients were obtained in the desorption experiments, an indication of the irreversible formation of metal-oxyhydroxides during a slow reaction. Using batch and column diffusion experiments, it was recognized that 60Co and 54Mn are less strongly associated with coastal sediments under suboxic conditions, and their migration rates are greater in deeper layers of sediment than in the top layer, an indication that a single Kd model is inappropriate to forecast the behavior of radionuclides near sediment surface layers.     

The potential and limits for clinical trials for early Alzheimer’s disease and some recommendations

Recommendations for clinical trials methods for ‘pre-dementia,’ ‘prodromal,’ or early Alzheimer’s disease are discussed. Early AD can be considered as subsets of both ‘amnestic MCI’ and ‘probable AD.’ In principle, it can be operationalized using recently proposed, new research criteria for AD that specifically does not require impairment in non-memory cognitive function and activities of daily living, and consequently does not require the presence of dementia. The criteria also require patients to show abnormal putative biomarkers but require validation. Trials in early AD should be done when models of drug action and response suggest that the drug in development likely would be effective in early AD and clinical effects could be expected in a relatively short time. Biomarkers should be used as stratification or explanatory variables that may help to explain clinical outcomes from early AD trials rather than as inclusion/exclusion criteria in order to avoid pseudospecificity. Trials should be multicentered, double-blinded, randomized, placebo-controlled, generally with dose-ranging of two doses if indicated. Duration of trials should be based on expected onsets and durations of effects, and generally should be less than one year. Crossover trials should be considered when appropriate. Primary outcomes should specifically assess memory and include repeated assessments. Potential secondary outcomes could include self- and observer-rated health-related quality of life and global impressions of change in lieu of activities of daily living. Onset of dementia should not be an endpoint because many patients would be on the cusp of dementia and dementia onset is influenced by numerous biological and environmental factors. Inferences that can be made from trials results will likely involve the effects of the test drug on memory and self-rated global function. Disease modification is not likely to be inferred except in trials over two years in duration in which a change in a biomarker can be used as an adjunctive assessment. Models and simulations using existing clinical trials databases would be helpful in planning early AD trials.     

The association between bed occupancy rates and hospital quality in the English National Health Service

We study whether hospitals that exhibit systematically higher bed occupancy rates are associated with lower quality in England over 2010/11–2017/18. We develop an economic conceptual framework to guide our empirical analysis and run regressions to inform possible policy interventions. First, we run a pooled OLS regression to test if high bed occupancy is associated with, and therefore acts as a signal of, lower quality, which could trigger additional regulation. Second, we test whether this association is explained by exogenous demand–supply factors such as potential demand, and unavoidable costs. Third, we include determinants of bed occupancy (beds, length of stay, and volume) that might be associated with quality directly, rather than indirectly through bed occupancy. Last, we use a within-between random-effects specification to decompose these associations into those due to variations in characteristics between hospitals and variations within hospitals. We find that bed occupancy rates are positively associated with overall and surgical mortality, negatively associated with patient-reported health gains, but not associated with other indicators. These results are robust to controlling for demand–supply shifters, beds, and volume. The associations reduce by 12%-25% after controlling for length of stay in most cases and are explained by variations in bed occupancy between hospitals.

     

Access to information and support for health: some potential issues and solutions for an ageing population

Computer illiteracy is diminishing as a new generation of retirees become the younger old and display more up-to-date knowledge and skills. However, there are questions about whether this group will be able to continue to update their skills as they get older, and whether it is appropriate to develop technology solutions specifically for this age group or to concentrate on accessible designs for the whole population. We propose that older people may be empowered through involvement in the design and provision of accessible information and technology solutions and through training opportunities in information seeking skills. Access, involvement and training need to be provided in everyday locations, and training needs to be closely related to people's physical, cognitive and information needs and those of the particular communities where they live. These issues are explored using evidence from a number of research projects conducted by the authors.     

The relative bioavailability of levonorgestrel and ethinylestradiol when administered in tablet and capsule form

The relative bioavailability of levonorgestrel (LNG) and ethinylestradiol (EE2) administered as a conventional tablet (150/30) or capsule has been assessed in a randomized two-period crossover study in 9 healthy volunteer women. Serum concentrations were monitored for 24h post-dosing. There was no significant difference in any of the pharmacokinetic parameters determined for either steroid. Hence the relative bioavailability is similar after tablet and capsule formulations.     

The use of bed distribution and service population indexes for hospital bed allocation.

To provide an empirical base for bed reallocation within a hospital planning jurisdiction in Canada, this article proposes a population-based method to measure the distribution of acute care beds for each district and the service load for each hospital. The measure for the bed distribution (BDI) is the number of beds per 1,000 age-sex-adjusted number of residents in a district, while the service load of a hospital is measured by the number of persons being served per bed (SPI). The number of beds allocated to each district, or the number of persons served by each hospital, was estimated by applying the hospital service population model, which employs both relevance- and commitment-index methods. The method thus proposed was applied to Alberta data. It appears that both BDI and SPI measures are stable across the variation of methods or data sources, yet sensitive enough to detect changes over the years. Using these indexes, potentially over- or underbedded districts and over- or underloaded hospitals can be identified for further investigation so that possible reallocation of acute care beds among the hospitals may take place.     

Plasma levels and pharmacokinetics of norethindrone and ethinylestradiol administered in solution and as tablets to women

Twenty-four normal adult female volunteers were dosed orally with a solution and tablet formulation containing the contraceptive combination of norethindrone (NET, 1.0 mg) and ethinylestradiol (EE₂, 0.12 mg) in a crossover bioequivalence study. Blood was sampled sequentially following single oral doses and the plasma separated for analysis of NET and EE₂ by specific radioimmunoassays. Comparisons of both drugs following a dose in solution and tablets were made with respect to the following parameters: (a) plasma concentrations at each sample time; (b) maximum plasma concentration (Cp_max); (c) time to maximum plasma concentration (T_max); (d) total area under the plasma concentration vs. time curve (AUC), and (e) plasma half-life ($\text{t}\text{1}\text{2}$). It was found that the tablet and solution doses were bioequivalent with respect to EE₂ absorption. However, absorption of NET from solution and tablet doses exhibited significant differences with respect to plasma levels at certain time points as well as AUC (which were higher following the tablet dose), but Cp_max, T_max and $\text{t}\text{1}\text{2}$ were not significantly different. Pharmacokinetic analysis of both drugs following the tablet dose was carried out using a two-compartment open model. The absorption rate constant (k_a) and peripheral to central compartment transfer rate constant (k₂₁) were similar for NET and EE₂, but statistically significant differences were observed with respect to the distribution rate constant (α), the central to peripheral transfer rate constant (k₁₂), the overall elimination rate constant (k_el), and volume or distribution ($\text{V}{}_1\text{F}$). The elimination rate constant (β) for both drugs showed a difference of borderline statistical significance.     

The impact of aging on long-term care in Europe and some potential policy responses.

The article examines recent data on the impact of increasing numbers of elderly people in Europe on expenditures for long-term care services. After reviewing recent and projected future costs of long-term care, the authors examine current national strategies for long-term care as well as potential policy options that could reduce future expenditures due to aging. Although long-term care expenditures in Europe will rise over the next several decades, countries can adopt a variety of strategies--many of them in social sectors outside the health system--to reduce or mitigate the overall effects of likely long-term care needs.     

Assessment of feminization of male fish in English rivers by the Environment Agency of England and Wales

In recent years there has been considerable concern over the ability of substances discharged into the environment to disrupt the normal endocrine function of wildlife. In particular, the apparent widespread feminization of male fish in rivers has received significant attention from regulators in the United Kingdom, the United States, Europe, and Japan. The U.K. and European epidemiological data sets have demonstrated that the occurrence of feminized fish is associated with effluent discharges and that the incidence and severity is positively correlated with the proportion of treated sewage effluent in receiving waters. Although weakly estrogenic substances may contribute to the overall effect, studies have concluded that steroid estrogens are the principal and most potent estrogenic components of domestic sewage. Extensive laboratory data sets confirm that steroid estrogens are capable of eliciting the effects observed in wild fish at concentrations that have been measured in effluents and in the environment. Based on evaluation of the available information, the Environment Agency (England and Wales) has concluded that the weight of evidence for endocrine disruption in fish is sufficient to develop a risk management strategy for estrogenically active effluents that discharge to the aquatic environment.