On the electrical double layer contribution to the interfacial tension of protein crystals

We study the electrical double layer at the interface between a protein crystal and a salt solution or a dilute solution of protein, and estimate the double layer's contribution to the interfacial tension of this interface. This contribution is negative and decreases in magnitude with increasing salt concentration. We also consider briefly the interaction between a pair of protein surfaces.Comment: 6 pages, 3 figures, revtex

Electroneutrality and Phase Behavior of Colloidal Suspensions

Several statistical mechanical theories predict that colloidal suspensions of highly charged macroions and monovalent microions can exhibit unusual thermodynamic phase behavior when strongly deionized. Density-functional, extended Debye-H\"uckel, and response theories, within mean-field and linearization approximations, predict a spinodal phase instability of charged colloids below a critical salt concentration. Poisson-Boltzmann cell model studies of suspensions in Donnan equilibrium with a salt reservoir demonstrate that effective interactions and osmotic pressures predicted by such theories can be sensitive to the choice of reference system, e.g., whether the microion density profiles are expanded about the average potential of the suspension or about the reservoir potential. By unifying Poisson-Boltzmann and response theories within a common perturbative framework, it is shown here that the choice of reference system is dictated by the constraint of global electroneutrality. On this basis, bulk suspensions are best modeled by density-dependent effective interactions derived from a closed reference system in which the counterions are confined to the same volume as the macroions. Linearized theories then predict bulk phase separation of deionized suspensions only when expanded about a physically consistent (closed) reference system. Lower-dimensional systems (e.g., monolayers, small clusters), depending on the strength of macroion-counterion correlations, may be governed instead by density-independent effective interactions tied to an open reference system with counterions dispersed throughout the reservoir, possibly explaining observed structural crossover in colloidal monolayers and anomalous metastability of colloidal crystallites.Comment: 12 pages, 5 figures. Discussion clarified, references adde

Binding effects in multivalent Gibbs-Donnan equilibrium

The classical Gibbs-Donnan equilibrium describes excess osmotic pressure associated with confined colloidal charges embedded in an electrolyte solution. In this work, we extend this approach to describe the influence of multivalent ion binding on the equilibrium force acting on a charged rod translocating between two compartments, thereby mimicking ionic effects on force balance during in vitro DNA ejection from bacteriophage. The subtle interplay between Gibbs-Donnan equilibrium and adsorption equilibrium leads to a non-monotonic variation of the ejection force as multivalent salt concentration is increased, in qualitative agreement with experimental observations

Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE)

Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs

Aging and ultra-slow equilibration in concentrated colloidal hard spheres

We study the dynamic behaviour of concentrated colloidal hard spheres using Time Resolved Correlation, a light scattering technique that can detect the slow evolution of the dynamics in out-of-equilibrium systems. Surprisingly, equilibrium is reached a very long time after sample initialization, the non-stationary regime lasting up to three orders of magnitude more than the relaxation time of the system. Before reaching equilibrium, the system displays unusual aging behaviour. The intermediate scattering function decays faster than exponentially and its relaxation time evolves non-monotonically with sample age.Comment: Submitted to the proceedings of the 6th EPS Liquid Matter Conference, Utrecht 2-6 July 200

Phase behaviour of charged colloidal sphere dispersions with added polymer chains

We study the stability of mixtures of highly screened repulsive charged spheres and non-adsorbing ideal polymer chains in a common solvent using free volume theory. The effective interaction between charged colloids in an aqueous salt solution is described by a screened-Coulomb pair potential, which supplements the pure hard-sphere interaction. The ideal polymer chains are treated as spheres that are excluded from the colloids by a hard-core interaction, whereas the interaction between two ideal chains is set to zero. In addition, we investigate the phase behaviour of charged colloid-polymer mixtures in computer simulations, using the two-body (Asakura-Oosawa pair potential) approximation to the effective one-component Hamiltonian of the charged colloids. Both our results obtained from simulations and from free volume theory show similar trends. We find that the screened-Coulomb repulsion counteracts the effect of the effective polymer-mediated attraction. For mixtures of small polymers and relatively large charged colloidal spheres, the fluid-crystal transition shifts to significantly larger polymer concentrations with increasing range of the screened-Coulomb repulsion. For relatively large polymers, the effect of the screened-Coulomb repulsion is weaker. The resulting fluid-fluid binodal is only slightly shifted towards larger polymer concentrations upon increasing the range of the screened-Coulomb repulsion. In conclusion, our results show that the miscibility of dispersions containing charged colloids and neutral non-adsorbing polymers increases, upon increasing the range of the screened-Coulomb repulsion, or upon lowering the salt concentration, especially when the polymers are small compared to the colloids.Comment: 25 pages,13 figures, accepted for publication on J.Phys.:Condens. Matte

Clinical effectiveness of pharmacy-led versus conventionally delivered antiviral treatment for hepatitis C in patients receiving opioid substitution therapy:a study protocol for a pragmatic cluster randomised trial

INTRODUCTION: Hepatitis C virus (HCV) infection affects 0.7% of the general population, and up to 40% of people prescribed opioid substitution therapy (OST) in Scotland. In conventional care, less than 10% of OST users are tested for HCV and less than 25% of these initiate treatment. Community pharmacists see this group frequently to provide OST supervision. This study examines whether a pharmacist-led 'test & treat' pathway increases cure rates for HCV. METHODS AND ANALYSIS: This protocol describes a cluster-randomised trial where 60 community pharmacies provide either conventional or pharmacy-led care. All pharmacies offer dried blood spot testing (DBST) for HCV. Participants have attended the pharmacy for OST for 3 months; are positive for HCV genotype 1 or 3; are not co-infected with HIV and/or hepatitis B; have no decompensated liver disease; are not pregnant. For conventional care, pharmacists refer HCV-positive participants to a local centre for assessment. In the pharmacy-led arm, pharmacists assess participants themselves in the pharmacy. Drug prescribing is by nurse prescribers (conventional arm) or pharmacist prescribers (pharmacy-led arm). Treatment in both arms is delivered as daily modified directly observed therapy in a pharmacy. Primary trial outcome is number of sustained virological responses at 12 weeks after treatment completion. Secondary trial outcomes are number of tests taken; treatment uptake; completion; adherence; re-infection. An economic evaluation will assess potential cost-effectiveness. Qualitative research interviews with clients and health professionals assess acceptability of a pharmacist-led pathway. ETHICS AND DISSEMINATION: This protocol has been ethically approved by the East of Scotland Research Ethics Committee 2 (15/ES/0086) and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Caldicott guardian approval was given on 16 December 2016 to allow NHS Tayside to pass information to the cluster community pharmacies about the HCV test status of patients that they are seeing to provide OST supervision. NHS R&D approvals have been obtained from each health board taking part in the study. Informed consent is obtained before study enrolment and only anonymised data are stored in a secured database, enabling an audit trail. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT02706223; Pre-results

Factors associated with change in objectively measured physical activity in older people:data from the Physical Activity Cohort Scotland study

Abstract Background Cross-sectional relationships between physical activity and health have been explored extensively, but less is known about how physical activity changes with time in older people. The aim of this study was to assess baseline predictors of how objectively measured physical activity changes with time in older people. Methods Longitudinal cohort study using data from the Physical Activity Cohort Scotland. A sample of community-dwelling older people aged 65 and over were recruited in 2009–2011, then followed up 2–3 years later. Physical activity was measured using Stayhealthy RT3 accelerometers over 7 days. Other data collected included baseline comorbidity, health-related quality of life (SF-36), extended Theory of Planned Behaviour Questionnaire and Social Capital Module of the General Household Survey. Associations between follow-up accelerometer counts and baseline predictors were analysed using a series of linear regression models, adjusting for baseline activity levels and follow-up time. Results Follow up data were available for 339 of the original 584 participants. The mean age was 77 years, 185 (55%) were female and mean follow up time was 26 months. Mean activity counts fell by between 2% per year (age  80, deprivation decile 5–10) from baseline values. In univariate analysis age, sex, deprivation decile, most SF-36 domains, most measures of social connectedness, most measures from the extended Theory of Planned Behaviour, hypertension, diabetes mellitus, chronic pain and depression score were significantly associated with adjusted activity counts at follow-up. In multivariate regression age, satisfactory friend network, SF-36 physical function score, and the presence of diabetes mellitus were independent predictors of activity counts at follow up after adjustment for baseline count and duration of follow up. Conclusions Health status and social connectedness, but not extended Theory of Planned Behaviour measures, independently predicted changes in physical activity in community dwelling older people