A study of water binding, mobility and dehydration in contact lens hydrogels using NMR

Hydrogel polymers are used for the manufacture of soft (or disposable) contact lenses worldwide today, but have a tendency to dehydrate on the eye. In vitro methods that can probe the potential for a given hydrogel polymer to dehydrate in vivo are much sought after. Nuclear magnetic resonance (NMR) has been shown to be effective in characterising water mobility and binding in similar systems (Barbieri, Quaglia et al., 1998, Larsen, Huff et al., 1990, Peschier, Bouwstra et al., 1993), predominantly through measurement of the spin-lattice relaxation time (T1), the spinspin relaxation time (T2) and the water diffusion coefficient (D). The aim of this work was to use NMR to quantify the molecular behaviour of water in a series of commercially available contact lens hydrogels, and relate these measurements to the binding and mobility of the water, and ultimately the potential for the hydrogel to dehydrate. As a preliminary study, in vitro evaporation rates were measured for a set of commercial contact lens hydrogels. Following this, comprehensive measurement of the temperature and water content dependencies of T1, T2 and D was performed for a series of commercial hydrogels that spanned the spectrum of equilibrium water content (EWC) and common compositions of contact lenses that are manufactured today. To quantify material differences, the data were then modelled based on theory that had been used for similar systems in the literature (Walker, Balmer et al., 1989, Hills, Takacs et al., 1989). The differences were related to differences in water binding and mobility. The evaporative results suggested that the EWC of the material was important in determining a material's potential to dehydrate in this way. Similarly, the NMR water self-diffusion coefficient was also found to be largely (if not wholly) determined by the WC. A specific binding model confirmed that the we was the dominant factor in determining the diffusive behaviour, but also suggested that subtle differences existed between the materials used, based on their equilibrium we (EWC). However, an alternative modified free volume model suggested that only the current water content of the material was important in determining the diffusive behaviour, and not the equilibrium water content. It was shown that T2 relaxation was dominated by chemical exchange between water and exchangeable polymer protons for materials that contained exchangeable polymer protons. The data was analysed using a proton exchange model, and the results were again reasonably correlated with EWC. Specifically, it was found that the average water mobility increased with increasing EWe approaching that of free water. The T1 relaxation was also shown to be reasonably well described by the same model. The main conclusion that can be drawn from this work is that the hydrogel EWe is an important parameter, which largely determines the behaviour of water in the gel. Higher EWe results in a hydrogel with water that behaves more like bulk water on average, or is less strongly 'bound' on average, compared with a lower EWe material. Based on the set of materials used, significant differences due to composition (for materials of the same or similar water content) could not be found. Similar studies could be used in the future to highlight hydrogels that deviate significantly from this 'average' behaviour, and may therefore have the least/greatest potential to dehydrate on the eye.

Diffusion tensor of water in model articular cartilage

We used Monte Carlo simulations of Brownian dynamics of water to study anisotropic water diffusion in an idealised model of articular cartilage. The main aim was to use the simulations as a tool for translation of the fractional anisotropy of the water diffusion tensor in cartilage into quantitative characteristics of its collagen fibre network. The key finding was a linear empirical relationship between the collagen volume fraction and the fractional anisotropy of the diffusion tensor. Fractional anisotropy of the diffusion tensor is potentially a robust indicator of the microstructure of the tissue because, in the first approximation, it is invariant to the inclusion of proteoglycans or chemical exchange between free and collagen-bound water in the model. We discuss potential applications of Monte Carlo diffusion-tensor simulations for quantitative biophysical interpretation of MRI diffusion-tensor images of cartilage. Extension of the model to include collagen fibre disorder is also discussed.

New drugs for the treatment of coronary artery syndromes

Background: Acute coronary syndromes are a major cause of mortality and morbidity. Objectives/Methods: The objective of this evaluation is to review the clinical trials of two new drugs being developed for the treatment of acute coronary syndromes. The first drug is the anti-coagulant otamixaban, and the trial compared otamixaban with unfractionated heparin and eptifibatide in acute coronary syndromes. The second drug is the anti-platelet ticagrelor, and the trial compared ticagrelor with clopidogrel in acute coronary syndromes. Results: In the SEPIA-ACS1 TIMI 42 trial, the primary efficacy endpoint occurred in 6.2% of subjects treated with unfractionated heparin and eptifibatide, and to a significantly lesser extent with otamixaban. In the PLATO trial, the primary efficacy endpoint had occurred less in the ticagrelor group (9.8%) than in the clopidogrel group (11.7%) at 12 months. Conclusions: Two new drugs for acute coronary syndromes, otamixaban and ticagrelor, have recently been shown to have benefits in subjects undergoing percutaneous interventions compared to the present standard regimens for this condition.

Good results for early treatment of clinically isolated syndrome prior to multiple sclerosis with interferon beta-1b and glatiramer

Background: The first sign of developing multiple sclerosis is a clinically isolated syndrome that resembles a multiple sclerosis relapse. Objective/methods: The objective was to review the clinical trials of two medicines in clinically isolated syndromes (interferon β and glatiramer acetate) to determine whether they prevent progression to definite multiple sclerosis. Results: In the BENEFIT trial, after 2 years, 45% of subjects in the placebo group developed clinically definite multiple sclerosis, and the rate was lower in the interferon β-1b group. Then all subjects were offered interferon β-1b, and the original interferon β-1b group became the early treatment group, and the placebo group became the delayed treatment group. After 5 years, the number of subjects with clinical definite multiple sclerosis remained lower in the early treatment than late treatment group. In the PreCISe trial, after 2 years, the time for 25% of the subjects to convert to definite multiple sclerosis was prolonged in the glatiramer group. Conclusions: Interferon β-1b and glatiramer acetate slow the progression of clinically isolated syndromes to definite multiple sclerosis. However, it is not known whether this early treatment slows the progression to the physical disabilities experienced in multiple sclerosis.

Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis?

Background: Methotrexate alone or in combination with other agents is the standard treatment for moderate-to-severe rheumatoid arthritis. As the biological agents are expensive, they are not usually used until methotrexate has failed to give a good response. Thus, there is scope for the development of cheaper drugs that can be used instead of methotrexate or in addition to methotrexate. Objectives/methods: Pamapimod is a p38α inhibitor being developed for use in the treatment of rheumatoid arthritis. The objective was to evaluate the recent clinical trials of pamapimod in subjects with rheumatoid arthritis. Results: There is no clear cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis, but it does cause adverse effects. Conclusion: It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.

Observation of the suppression of water uptake by marine particles

A 4 week intensive measurement campaign was conducted in March–April 2007 at Agnes Water, a remote coastal site on the east coast of Australia. A Volatility-Hygroscopicity-Tandem Differential Mobility Analyser (VH-TDMA) was used to investigate changes in the hygroscopic properties of ambient particles as volatile components were progressively evaporated. Nine out of 18 VH-TDMA volatility scans detected internally mixed multi-component particles in the nucleation and Aitken modes in clean marine air. Evaporation of a volatile, organic-like component in the VH-TDMA caused significant increases in particle hygroscopicity. In 3 scans the increase in hygroscopicity was so large it was explained by an increase in the absolute volume of water uptake by the particle residuals, and not merely an increase in their relative hygroscopicity. This indicates the presence of organic components that were suppressing the hygroscopic growth of mixed particles on the timescale of humidification in the VH-TDMA (6.5 secs). This observation was supported by ZSR calculations for one scan, which showed that the measured growth factors of mixed particles were up to 18% below those predicted assuming independent water uptake of the individual particle components. The observed suppression of water uptake could be due to a reduced rate of hygroscopic growth caused by the presence of organic films or organic-inorganic interactions in solution droplets that had a negative effect on hygroscopicity.

Potential of St John's Wort for the treatment of depression : the economic perspective

The burden of rising health care expenditures has created a demand for information regarding the clinical and economic outcomes associated with complementary and alternative medicines. Meta-analyses of randomized controlled trials have found Hypericum perforatum preparations to be superior to placebo and similarly effective as standard antidepressants in the acute treatment of mild to moderate depression. A clear advantage over antidepressants has been demonstrated in terms of the reduced frequency of adverse effects and lower treatment withdrawal rates, low rates of side effects and good compliance, key variables affecting the cost-effectiveness of a given form of therapy. The most important risk associated with use is potential interactions with other drugs, but this may be mitigated by using extracts with low hyperforin content. As the indirect costs of depression are greater than five times direct treatment costs, given the rising cost of pharmaceutical antidepressants, the comparatively low cost of Hypericum perforatum extract makes it worthy of consideration in the economic evaluation of mild to moderate depression treatments.

Best practice for prevention and treatment of cardiovascular disease through an equity lens : a review

Background: Despite declining rates of cardiovascular disease (CVD) mortality in developed countries, lower socioeconomic groups continue to experience a greater burden of the disease. There are now many evidence-based treatments and prevention strategies for the management of CVD and it is essential that their impact on the more disadvantaged group is understood if socioeconomic inequalities in CVD are to be reduced. Aims: To determine whether key interventions for CVD prevention and treatment are effective among lower socioeconomic groups, to describe barriers to their effectiveness and the potential or actual impact of these interventions on the socioeconomic gradient in CVD. Methods: Interventions were selected from four stages of the CVD continuum. These included smoking reduction strategies, absolute risk assessment, cardiac rehabilitation, secondary prevention medications, and heart failure self-management programmes. Electronic searches were conducted using terms for each intervention combined with terms for socioeconomic status (SES). Results: Only limited evidence was found for the effectiveness of the selected interventions among lower SES groups and there was little exploration of socioeconomic-related barriers to their uptake. Some broad themes and key messages were identified. In the majority of findings examined, it was clear that the underlying material, social and environmental factors associated with disadvantage are a significant barrier to the effectiveness of interventions. Conclusion: Opportunities to reduce socioeconomic inequalities occur at all stages of the CVD continuum. Despite this, current treatment and prevention strategies may be contributing to the widening socioeconomic-CVD gradient. Further research into the impact of best-practice interventions for CVD upon lower SES groups is required.

Investigating challenges and opportunities of water sensitive urban design for knowledge based development of Australian cities

A new approach that is slowly replacing neoclassical models of economic growth and commodity based industrial activities, knowledge based urban development (KBUD) aims to provide opportunities for citiesw to foster knowledge creation, exchange and innovation, and is based on the concepts of both sustainable urban development and economic prosperity; sustainable uses and protection of natural resources are therefore integral parts of KBUD. As such, stormwater, which has been recognised as one of the main culprits of aquatic ecosystem pollution and as therefore a significant threat to the goal of sustainable urban development, needs to be managed in a manner that produces ecologically sound outcomes. Water sensitive urban design (WSUD) is one of the key responses to the need to better management urban stormwater runoff and supports KBUD by providing an alternative, innovative and effective strategy to traditional stormwater management.

Alkaline hydrothermal treatment of titanate nanostructures

Since its initial proposal in 1998, alkaline hydrothermal processing has rapidly become an established technology for the production of titanate nanostructures. This simple, highly reproducible process has gained a strong research following since its conception. However, complete understanding and elucidation of nanostructure phase and formation have not yet been achieved. Without fully understanding phase, formation, and other important competing effects of the synthesis parameters on the final structure, the maximum potential of these nanostructures cannot be obtained. Therefore this study examined the influence of synthesis parameters on the formation of titanate nanostructures produced by alkaline hydrothermal treatment. The parameters included alkaline concentration, hydrothermal temperature, the precursor material‘s crystallite size and also the phase of the titanium dioxide precursor (TiO2, or titania). The nanostructure‘s phase and morphology was analysed using X-ray diffraction (XRD), Raman spectroscopy and transmission electron microscopy. X-ray photoelectron spectroscopy (XPS), dynamic light scattering (non-invasive backscattering), nitrogen sorption, and Rietveld analysis were used to determine phase, for particle sizing, surface area determinations, and establishing phase concentrations, respectively. This project rigorously examined the effect of alkaline concentration and hydrothermal temperature on three commercially sourced and two self-prepared TiO2 powders. These precursors consisted of both pure- or mixed-phase anatase and rutile polymorphs, and were selected to cover a range of phase concentrations and crystallite sizes. Typically, these precursors were treated with 5–10 M sodium hydroxide (NaOH) solutions at temperatures between 100–220 °C. Both nanotube and nanoribbon morphologies could be produced depending on the combination of these hydrothermal conditions. Both titania and titanate phases are comprised of TiO6 units which are assembled in different combinations. The arrangement of these atoms affects the binding energy between the Ti–O bonds. Raman spectroscopy and XPS were therefore employed in a preliminary study of phase determination for these materials. The change in binding energy from a titania to a titanate binding energy was investigated in this study, and the transformation of titania precursor into nanotubes and titanate nanoribbons was directly observed by these methods. Evaluation of the Raman and XPS results indicated a strengthening in the binding energies of both the Ti (2p3/2) and O (1s) bands which correlated to an increase in strength and decrease in resolution of the characteristic nanotube doublet observed between 320 and 220 cm.1 in the Raman spectra of these products. The effect of phase and crystallite size on nanotube formation was examined over a series of temperatures (100.200 �‹C in 20 �‹C increments) at a set alkaline concentration (7.5 M NaOH). These parameters were investigated by employing both pure- and mixed- phase precursors of anatase and rutile. This study indicated that both the crystallite size and phase affect nanotube formation, with rutile requiring a greater driving force (essentially �\harsher. hydrothermal conditions) than anatase to form nanotubes, where larger crystallites forms of the precursor also appeared to impede nanotube formation slightly. These parameters were further examined in later studies. The influence of alkaline concentration and hydrothermal temperature were systematically examined for the transformation of Degussa P25 into nanotubes and nanoribbons, and exact conditions for nanostructure synthesis were determined. Correlation of these data sets resulted in the construction of a morphological phase diagram, which is an effective reference for nanostructure formation. This morphological phase diagram effectively provides a .recipe book�e for the formation of titanate nanostructures. Morphological phase diagrams were also constructed for larger, near phase-pure anatase and rutile precursors, to further investigate the influence of hydrothermal reaction parameters on the formation of titanate nanotubes and nanoribbons. The effects of alkaline concentration, hydrothermal temperature, crystallite phase and size are observed when the three morphological phase diagrams are compared. Through the analysis of these results it was determined that alkaline concentration and hydrothermal temperature affect nanotube and nanoribbon formation independently through a complex relationship, where nanotubes are primarily affected by temperature, whilst nanoribbons are strongly influenced by alkaline concentration. Crystallite size and phase also affected the nanostructure formation. Smaller precursor crystallites formed nanostructures at reduced hydrothermal temperature, and rutile displayed a slower rate of precursor consumption compared to anatase, with incomplete conversion observed for most hydrothermal conditions. The incomplete conversion of rutile into nanotubes was examined in detail in the final study. This study selectively examined the kinetics of precursor dissolution in order to understand why rutile incompletely converted. This was achieved by selecting a single hydrothermal condition (9 M NaOH, 160 °C) where nanotubes are known to form from both anatase and rutile, where the synthesis was quenched after 2, 4, 8, 16 and 32 hours. The influence of precursor phase on nanostructure formation was explicitly determined to be due to different dissolution kinetics; where anatase exhibited zero-order dissolution and rutile second-order. This difference in kinetic order cannot be simply explained by the variation in crystallite size, as the inherent surface areas of the two precursors were determined to have first-order relationships with time. Therefore, the crystallite size (and inherent surface area) does not affect the overall kinetic order of dissolution; rather, it determines the rate of reaction. Finally, nanostructure formation was found to be controlled by the availability of dissolved titanium (Ti4+) species in solution, which is mediated by the dissolution kinetics of the precursor.

Cognitive behaviour therapy (CBT) for the treatment of co-occurring depression and substance use : current evidence and directions for future research

Issues and Approach: The high rates of co-occurring depression and substance use, and the negative impact of this on illness course and outcomes have been well established. Despite this, few clinical trials have examined the efficacy of cognitive behaviour therapy (CBT). This paper systematically reviews these clinical trials, with an aim of providing recommendations for how future research can develop a more robust evidence base for the treatment of these common comorbidities. Leading electronic databases, including PubMed (ISI) and PsychINFO (CSA), were searched for peer-reviewed journal articles using CBT for the treatment of co-occurring depression and substance use. Of the 55 articles identified, 12 met inclusion criteria and were included in the review. ---------- Key Findings: There is only a limited evidence for the effectiveness of CBT either alone or in combination with antidepressant medication for the treatment of co-occurring depression and substance use. While there is support for the efficacy of CBT over no treatment control conditions, there is little evidence that CBT is more efficacious than other psychotherapies. There is, however, consistent evidence of improvements in both depression and substance use outcomes, regardless of the type of treatment provided and there is growing evidence that that the effects of CBT are durable and increase over time during follow up. ---------- Conclusions. Rather than declaring the ‘dodo bird verdict’ that CBT and all other psychotherapies are equally efficacious, it would be more beneficial to develop more potent forms of CBT by identifying variables that mediate treatment outcomes.