Water properties under nano-scale confinement.

Water is the universal solvent and plays a critical role in all known geological and biological processes. Confining water in nano-scale domains, as encountered in sedimentary rocks, in biological, and in engineered systems, leads to the deviations in water's physicochemical properties relative to those measured for the non-confined phase. In our comprehensive analysis, we demonstrate that nano-scale confinement leads to the decrease in the melting/freezing point temperature, density, and surface tension of confined water. With increasing degree of spatial confinement the population of networked water, as evidenced by alterations in the O-H stretching modes, increases. These analyses were performed on two groups of mesoporous silica materials, which allows to separate pore size effects from surface chemistry effects. The observed systematic effects of nano-scale confinement on the physical properties of water are driven by alterations to water's hydrogen-bonding network-influenced by water interactions with the silica surface - and has implications for how we understand the chemical and physical properties of liquids confined in porous materials.

Concerted Metal Cation Desorption and Proton Transfer on Deprotonated Silica Surfaces.

The adsorption equilibrium constants of monovalent and divalent cations to material surfaces in aqueous media are central to many technological, natural, and geochemical processes. Cation adsorption-desorption is often proposed to occur in concert with proton transfer on hydroxyl-covered mineral surfaces, but to date this cooperative effect has been inferred indirectly. This work applies density functional theory-based molecular dynamics simulations of explicit liquid water/mineral interfaces to calculate metal ion desorption free energies. Monodentate adsorption of Na+, Mg2+, and Cu2+ on partially deprotonated silica surfaces are considered. Na+ is predicted to be unbound, while Cu2+ exhibits binding free energies to surface SiO- groups that are larger than those of Mg2+. The predicted trends agree with competitive adsorption measurements on fumed silica surfaces. As desorption proceeds, Cu2+ dissociates one of the H2O molecules in its first solvation shell, turning into Cu2+(OH-)(H2O)3, while Mg remains Mg2+(H2O)6. The protonation state of the SiO- group at the initial binding site does not vary monotonically with cation desorption.

Adsorption of copper (II) on mesoporous silica: the effect of nano-scale confinement.

Nano-scale spatial confinement can alter chemistry at mineral-water interfaces. These nano-scale confinement effects can lead to anomalous fate and transport behavior of aqueous metal species. When a fluid resides in a nanoporous environments (pore size under 100 nm), the observed density, surface tension, and dielectric constant diverge from those measured in the bulk. To evaluate the impact of nano-scale confinement on the adsorption of copper (Cu2+), we performed batch adsorption studies using mesoporous silica. Mesoporous silica with the narrow distribution of pore diameters (SBA-15; 8, 6, and 4 nm pore diameters) was chosen since the silanol functional groups are typical to surface environments. Batch adsorption isotherms were fit with adsorption models (Langmuir, Freundlich, and Dubinin-Radushkevich) and adsorption kinetic data were fit to a pseudo-first-order reaction model. We found that with decreasing pore size, the maximum surface area-normalized uptake of Cu2+ increased. The pseudo-first-order kinetic model demonstrates that the adsorption is faster as the pore size decreases from 8 to 4 nm. We attribute these effects to the deviations in fundamental water properties as pore diameter decreases. In particular, these effects are most notable in SBA-15 with a 4-nm pore where the changes in water properties may be responsible for the enhanced Cu mobility, and therefore, faster Cu adsorption kinetics.

Ten tips for becoming a Time Lord

BACKGROUND: There is evidence that extended waiting is the most important cause of patient dissatisfaction with a visit to their general practice. While waiting is sometimes unavoidable in primary care, sometimes its causes are systemic and modifiable. Our experience is that some doctors rarely run late and yet seem to meet their patients' needs. We call these colleagues 'Time Lords'. OBJECTIVE: The aim of this article is to revise and share tips to help others become Time Lords. DISCUSSION: We describe four tips that depend on good preparation. A further six involve maximising the value of consulting time. Waiting is sometimes unavoidable in general practice. Our patients accept this and so must we. However, we can do much to improve our patients' satisfaction by taking waiting as seriously as they do and minimising it.

Subtle Effects of Aliphatic Alcohol Structure on Water Extraction and Solute Aggregation in Biphasic Water/n-Dodecane.

Organic phase aggregation behavior of 1-octanol and its structural isomer, 2-ethylhexanol, in a biphasic n-dodecane-water system is studied with a combination of physical measurement, small-angle X-ray scattering (SAXS), and atomistic molecular dynamic simulations. Physical properties of the organic phases are probed following their mixing and equilibration with immiscible water phases. Studies reveal that the interfacial tension decreases as a function of increasing alcohol concentration over the solubility range of the alcohol with no evidence for a critical aggregate concentration (cac). An uptake of water into the organic phases is quantified, as a function of alcohol content, by Karl Fischer titrations. The extraction of water into dodecane was further assessed as a function of alcohol concentration via the slope-analysis method sometimes employed in chemical separations. This method provides a qualitative understanding of solute (water/alcohol) aggregation in the organic phase. The physical results are supported by analyses of SAXS data that reveals an emergence of aggregates in n-dodecane at elevated alcohol concentrations. The observed aggregate structure is dependent on the alcohol tail group geometry, consistent with surfactant packing parameter. The formation of these aggregates is discussed at a molecular level, where alcohol-alcohol and alcohol-water H-bonding interactions likely dominate the occurrence and morphology of the aggregates.

Partitioning of naturally-occurring radionuclides (NORM) in Marcellus Shale produced fluids influenced by chemical matrix.

Naturally-occurring radioactive materials (NORM) associated with unconventional drilling produced fluids from the Marcellus Shale have raised environmental concerns. However, few investigations into the fundamental chemistry of NORM in Marcellus Shale produced fluids have been performed. Thus, we performed radiochemical experiments with Marcellus Shale produced fluids to understand the partitioning behavior of major radioelements of environmental health concern (uranium (U), thorium (Th), radium (Ra), lead (Pb), and polonium (Po)). We applied a novel radiotracer, (203)Pb, to understand the behavior of trace-levels of (210)Pb in these fluids. Ultrafiltration experiments indicated U, Th, and Po are particle reactive in Marcellus Shale produced fluids and Ra and Pb are soluble. Sediment partitioning experiments revealed that >99% of Ra does not adsorb to sediments in the presence of Marcellus Shale produced fluids. Further experiments indicated that although Ra adsorption is related to ionic strength, the concentrations of heavier alkaline earth metals (Ba, Sr) are stronger predictors of Ra solubility.

Understanding the Radioactive Ingrowth and Decay of Naturally Occurring Radioactive Materials in the Environment: An Analysis of Produced Fluids from the Marcellus Shale.

BACKGROUND: The economic value of unconventional natural gas resources has stimulated rapid globalization of horizontal drilling and hydraulic fracturing. However, natural radioactivity found in the large volumes of "produced fluids" generated by these technologies is emerging as an international environmental health concern. Current assessments of the radioactivity concentration in liquid wastes focus on a single element-radium. However, the use of radium alone to predict radioactivity concentrations can greatly underestimate total levels. OBJECTIVE: We investigated the contribution to radioactivity concentrations from naturally occurring radioactive materials (NORM), including uranium, thorium, actinium, radium, lead, bismuth, and polonium isotopes, to the total radioactivity of hydraulic fracturing wastes. METHODS: For this study we used established methods and developed new methods designed to quantitate NORM of public health concern that may be enriched in complex brines from hydraulic fracturing wastes. Specifically, we examined the use of high-purity germanium gamma spectrometry and isotope dilution alpha spectrometry to quantitate NORM. RESULTS: We observed that radium decay products were initially absent from produced fluids due to differences in solubility. However, in systems closed to the release of gaseous radon, our model predicted that decay products will begin to ingrow immediately and (under these closed-system conditions) can contribute to an increase in the total radioactivity for more than 100 years. CONCLUSIONS: Accurate predictions of radioactivity concentrations are critical for estimating doses to potentially exposed individuals and the surrounding environment. These predictions must include an understanding of the geochemistry, decay properties, and ingrowth kinetics of radium and its decay product radionuclides.

Monitoring radionuclides in subsurface drinking water sources near unconventional drilling operations: a pilot study.

Unconventional drilling (the combination of hydraulic fracturing and horizontal drilling) to extract oil and natural gas is expanding rapidly around the world. The rate of expansion challenges scientists and regulators to assess the risks of the new technologies on drinking water resources. One concern is the potential for subsurface drinking water resource contamination by naturally occurring radioactive materials co-extracted during unconventional drilling activities. Given the rate of expansion, opportunities to test drinking water resources in the pre- and post-fracturing setting are rare. This pilot study investigated the levels of natural uranium, lead-210, and polonium-210 in private drinking wells within 2000 m of a large-volume hydraulic fracturing operation--before and approximately one-year following the fracturing activities. Observed radionuclide concentrations in well waters tested did not exceed maximum contaminant levels recommended by state and federal agencies. No statistically-significant differences in radionuclide concentrations were observed in well-water samples collected before and after the hydraulic fracturing activities. Expanded monitoring of private drinking wells before and after hydraulic fracturing activities is needed to develop understanding of the potential for drinking water resource contamination from unconventional drilling and gas extraction activities.

The eCollaborative: using a quality improvement collaborative to implement the National eHealth Record System in Australian primary care practices.

QUALITY PROBLEM: The new national patient-controlled electronic health record is an important quality improvement, and there was a pressing need to pilot its use in Australian primary care practices. Implementation of electronic health records in other countries has met with mixed success. INITIAL ASSESSMENT: New work was required in general practices participating in the national electronic health record. National implementers needed to engage with small private general practices to test the changes before general introduction. CHOICE OF SOLUTION: The National E-health Transition Authority contracted the Improvement Foundation Australia to conduct a quality improvement collaborative based on 9 years of experience with the Australian Primary Care Collaborative Program. IMPLEMENTATION: Aims, measures and change ideas were addressed in a collaborative programme of workshops and supported activity periods. Data quality measures and numbers of health summaries uploaded were collected monthly. Challenges such as the delay in implementation of the electronic health summary were met. EVALUATION: Fifty-six practices participated. Nine hundred and twenty-nine patients registered to participate, and 650 shared health summaries were uploaded. Five hundred and nineteen patient views occurred. Four hundred and twenty-one plan/do/study/act cycles were submitted by participating practices. LESSONS LEARNED: The collaborative methodology was adapted for implementing innovation and proved useful for engaging with multiple small practices, facilitating low-risk testing of processes, sharing ideas among participants, development of clinical champions and development of resources to support wider use. Email discussion between participants and system designers facilitated improvements. Data quality was a key challenge for this innovation, and quality measures chosen require development. Patient participants were partners in improvement.

A simple-rapid method to separate uranium, thorium, and protactinium for U-series age-dating of materials.

Uranium-series dating techniques require the isolation of radionuclides in high yields and in fractions free of impurities. Within this context, we describe a novel-rapid method for the separation and purification of U, Th, and Pa. The method takes advantage of differences in the chemistry of U, Th, and Pa, utilizing a commercially-available extraction chromatographic resin (TEVA) and standard reagents. The elution behavior of U, Th, and Pa were optimized using liquid scintillation counting techniques and fractional purity was evaluated by alpha-spectrometry. The overall method was further assessed by isotope dilution alpha-spectrometry for the preliminary age determination of an ancient carbonate sample obtained from the Lake Bonneville site in western Utah (United States). Preliminary evaluations of the method produced elemental purity of greater than 99.99% and radiochemical recoveries exceeding 90% for U and Th and 85% for Pa. Excellent purity and yields (76% for U, 96% for Th and 55% for Pa) were also obtained for the analysis of the carbonate samples and the preliminary Pa and Th ages of about 39,000 years before present are consistent with (14)C-derived age of the material.

Improving primary care in Australia through the Australian Primary Care Collaboratives Program: a quality improvement report.

PROBLEM: Effective and affordable health systems have good primary care. Access, equity, care of chronic conditions and quality are key priorities in primary care in Australia. DESIGN: A large-scale quality improvement collaborative addressing diabetes, coronary heart disease (CHD), access, chronic obstructive pulmonary disease (COPD), patient self-management, Aboriginal health and diabetes prevention. SETTING: General practices and Aboriginal medical services across Australia. KEY MEASURES FOR IMPROVEMENT: Sample measures are reported. STRATEGY FOR CHANGE: The Improvement Foundation (Australia) adapted collaborative strategies used in the UK. Health service teams attended three workshops, separated by activity periods and followed by 12 months of further work. Teams were supported by local collaborative program managers to make changes and report measures. Services received feedback about improvement compared with their wave. EFFECTS OF CHANGE: 1185 health services participated in 13 waves between 2005 and 2011. 83% of Australian divisions of general practice participated, and 262 support staff received quality improvement training. Key measures show improvement in all topics except access. 397,111 patients were on the disease registers of participating health services. LESSONS LEARNT: The collaborative methodology is transferable to primary care in Australia. Results may reflect improved data recording and disease coding, as well as changes in clinical care. Team dynamics and local support are important success factors. Collaboratives are a useful tool in a program of clinical quality improvement. The APCC will work with the new primary healthcare organisations which are part of health reforms in Australia to improve data reporting, improve diabetes care and entrench quality improvement in the emerging environment.

The Australian Primary Care Collaboratives Program: improving diabetes care.

PROBLEM: Diabetes is a major, growing health problem often managed in primary care but with suboptimal control of risk factors. DESIGN: A large-scale quality improvement collaborative implemented in seven waves. SETTING: General practices and Aboriginal medical services across Australia. KEY MEASURES FOR IMPROVEMENT: Percentage of patients in each health service with haemoglobin A1C (HbA1C), total cholesterol and blood pressure at target. STRATEGY FOR CHANGE: Health services attended three 2-day workshops, separated by 3-month activity periods and followed by 12 months of further improvement work. Local collaborative program managers supported teams to report measures and plan/do/study/act (PDSA) cycles monthly. Health services received feedback about changes in their measures in comparison with their wave. EFFECTS OF CHANGE: 743 health services participated in seven waves between 2004 and 2009 serving approximately 150,000 people with diabetes. Mean numbers of patients at target HbA1c levels improved by 50% from 25% at baseline to 38% at month 18. Lipid and blood pressure measures showed similar improvement. LESSONS LEARNT: Engagement in the Program and results demonstrated that the collaborative methodology is transferable to Australian primary care. The results may reflect improved data recording and disease coding, and changes in clinical care. Internal evaluation should be built into improvement projects from the start to facilitate improvements and reporting. Enthusing, training and resourcing practice teams appeared to be the key to rapid change. Local support of practice teams was instrumental in improvement. Early investment to facilitate automatic measure collection ensured good data reporting.

Evaluation of high-throughput genotoxicity assays used in profiling the US EPA ToxCast chemicals.

Three high-throughput screening (HTS) genotoxicity assays-GreenScreen HC GADD45a-GFP (Gentronix Ltd.), CellCiphr p53 (Cellumen Inc.) and CellSensor p53RE-bla (Invitrogen Corp.)-were used to analyze the collection of 320 predominantly pesticide active compounds being tested in Phase I of US. Environmental Protection Agency's ToxCast research project. Between 9% and 12% of compounds were positive for genotoxicity in the assays. However, results of the varied tests only partially overlapped, suggesting a strategy of combining data from a battery of assays. The HTS results were compared to mutagenicity (Ames) and animal tumorigenicity data. Overall, the HTS assays demonstrated low sensitivity for rodent tumorigens, likely due to: screening at a low concentration, coverage of selected genotoxic mechanisms, lack of metabolic activation and difficulty detecting non-genotoxic carcinogens. Conversely, HTS results demonstrated high specificity, >88%. Overall concordance of the HTS assays with tumorigenicity data was low, around 50% for all tumorigens, but increased to 74-78% (vs. 60% for Ames) for those compounds producing tumors in rodents at multiple sites and, thus, more likely genotoxic carcinogens. The aim of the present study was to evaluate the utility of HTS assays to identify potential genotoxicity hazard in the larger context of the ToxCast project, to aid prioritization of environmentally relevant chemicals for further testing and assessment of carcinogenicity risk to humans.

Learning from four years of collaborative access work in Australia.

BACKGROUND: Through the three years of the first phase of the Australian Primary Care Collaborative there was considerable adaptation of the work to improve access translated from the UK to the Australian environment. Changes in four areas are described. MEASURES: 'third available appointment' was retained as a measure of delay. A patient satisfaction survey was revised and a new measure added looking at unmet demand. Team: requests from practices resulted in the production of a set of 'team principles' designed to help practices build capacity for improvement in their teams. Name: the name of the topic seemed to be a barrier for some practices. After much thought, the name of the improvement topic was changed from 'Better Access' to 'Access and Care Redesign'. The product: the content of the access topic was revised. Change ideas were divided into 'foundation work', which all practices were expected to do to improve access to care for patients. Once this was completed, practices were encouraged to select a 'pathway' which best suited their situation. CONCLUSION: Four possible changes are offered for consideration to those planning to do access work with general practices based on the learning from the Australian Primary Care Collaborative.

Development and validation of a higher throughput screening approach to genotoxicity testing using the GADD45a-GFP GreenScreen HC assay.

There is a pressing need to develop rapid yet accurate screening assays for the identification of genotoxic liability and for early hazard assessment in drug discovery. The GADD45a-GFP human cell-based genotoxicity assay (GreenScreen HC) has been reformatted to test 12 compounds per 96-well microplate in a higher throughput, automated screening mode and the protocol applied to the analysis of 1266 diverse, pharmacologically active compounds. Testing from a fixed starting concentration of 100 AmicroM and over 3 serial dilutions, the hit rates for genotoxicity (7.3%) and cytotoxicity (33%) endpoints of the assay have been determined in a much wider chemical space than previously reported. The degree of interference from color, autofluorescence, and low solubility has also been assessed. The assay results have been compared to an in silico approach to genotoxicity assessment using Derek for Windows software. Where carcinogenicity data were available, GreenScreen HC demonstrated a higher specificity than in silico methods while identifying genotoxic species that were not highlighted for genotoxic liability in structure-activity relationship software. Higher throughput screening from a fixed, low concentration reduces sensitivity to less potent genotoxins, but the maintenance of the previously reported high specificity is essential in early hazard assessment where misclassification can lead to the needless rejection of potentially useful compounds in drug development.

Assessment of the genotoxicity of S9-generated metabolites using the GreenScreen HC GADD45a-GFP assay.

Genotoxicity can be assessed by monitoring expression of a GADD45a-GFP reporter in the human lymphoblastoid cell line TK6. A flow cytometric method has been developed to effectively distinguish GFP fluorescence from coloured and fluorescent test samples as well from the S9 liver extracts used to generate metabolites from pro-genotoxins. The method includes the use of propidium iodide exclusion for the determination of cellular viability. This paper describes the method development, the derivation of decision thresholds for the identification of genotoxins using the method, and presents data from a 56-compound validation study of the method. The results illustrate that the method permitted the detection of the majority of pro-genotoxins tested and, importantly, the high specificity of the GADD45a-GFP assay was maintained.

Clear and present danger? The use of a yeast biosensor to monitor changes in the toxicity of industrial effluents subjected to oxidative colour removal treatments.

Discharges of coloured effluents into surface waters provide conspicuous evidence of the impact of industry on the environment. The textile industry is an obvious candidate for sources of such discharges. Conventional treatment methods appear to alleviate this situation by removing colour, however the affect on toxicity is less obvious. The objective of this study was to examine the changes in effluent toxicity during the course of two alternative wastewater treatment methods, ozonation and electrochemical oxidation, using a novel toxicity biosensor, GreenScreen EM. The biosensor is capable of measuring both general acute toxicity (cytotoxicity), and more specifically genotoxicity, that is damage to a cell's DNA structure, replication or distribution, caused by substances that may be mutagenic and/or carcinogenic. The biosensor utilises a modified strain of the brewers yeast Saccharomyces cerevisiae, incorporating a gene encoding green fluorescent protein (GFP) linked to the inducible promoter of the DNA damage responsive RAD54 gene. Upon exposure to a genotoxin, the production of GFP is up-regulated in parallel with RAD54, and the resulting cellular fluorescence provides a measure of genotoxicity. Acute toxicity is simultaneously determined by monitoring relative total growth of the cell culture during incubation. The results presented in this paper show that a reduction in colouration does not necessarily correspond to a reduction in effluent toxicity.