Self-harm in people with learning disabilities

Section A A systematic literature review on the experiences of people with learning disabilities who self-harm. Quality assessment of 12 qualitative papers was guided by the CASP. Through thematic synthesis of these paper three central themes were developed: (1) Negative experiences, (2) The act of self-harm, and (3) A different response. Self-harm took place in a negative context which affected an individual’s self-view and created overwhelming emotions. Responses to self-harm could be experienced as punitive or uncaring which furthered the individual’s negative experiences. Responses which reduced self-harming behaviour were identified. The implications for clinical practice and research were discussed. Section B Presented here, is a study exploring how professionals in the care sector work with people with learning disabilities who self-harm. Interviews were conducted with 11 participants and data analysis, informed by critical realist grounded theory methodology, produced four main concepts: a caring vocation, a distressing experience, navigating distress, and powerlessness. A preliminary model of how professionals navigate distress when working with people with learning disabilities who self-harmed was developed. It considered both personal and systemic contexts which influence and are influenced by this process. Implications for clinical practice and research were discussed

Estimated dose exposure of the neonate to buprenorphine and its metabolite norbuprenorphine via breastmilk during maternal buprenorphine substitution treatment

Objective: The aim of the present study was to estimate the dose of buprenorphine and its primary metabolite norbuprenorphine that a breastfed infant would receive during maternal maintenance treatment with buprenorphine. Study Design: Seven pregnant opioid-dependent women taking buprenorphine (median, 7mg/day; range, 2.4–24 mg) and who intended to breastfeed were recruited. After lactation was established, several milk samples were collected from each subject over a 24-hour dose interval, and buprenorphine and norbuprenorphine concentrations were measured by liquid chromatography–tandem mass spectrometry. The average concentration (Cavg) across the dose interval was estimated as for both buprenorphine and norbuprenorphine (as buprenorphine equivalents). Absolute infant dose (AID), defined as Cavg daily milk intake, and relative infant dose (RID), defined as 100 AID/weight-adjusted maternal daily dose, via milk were calculated, assuming a milk intake of 0.15 L/kg/day. The infant’s health and progress were assessed directly and by questionnaire on the study day. Results: Mean (95% confidence interval) norbuprenorphine concentration in milk and AID values (1.94 [0.79–3.08] μg/L and 0.29 [0.12–0.46] μg/kg/day, respectively) were approximately half those for buprenorphine (3.65[1.61–5.7] μg/L and 0.55 [0.24–0.85] μg/kg/day, respectively). Similarly, the mean RID values were 0.18% (0.11–0.25%) for norbuprenorphine and 0.38% (0.23–0.53%) for buprenorphine. The breastfed infants showed no adverse effects, were all in good health, and were progressing as expected. Conclusion: Thus the dose of buprenorphine and norbuprenorphine received via milk is unlikely to cause any acute adverse effects in the breastfed infant

Phase behavior and structure of model colloid-polymer mixtures confined between two parallel planar walls

Using Gibbs ensemble Monte Carlo simulations and density functional theory we investigate the fluid-fluid demixing transition in inhomogeneous colloid-polymer mixtures confined between two parallel plates with separation distances between one and ten colloid diameters covering the complete range from quasi two-dimensional to bulk-like behavior. We use the Asakura-Oosawa-Vrij model in which colloid-colloid and colloid-polymer interactions are hard-sphere like, whilst the pair potential between polymers vanishes. Two different types of confinement induced by a pair of parallel walls are considered, namely either through two hard walls or through two semi-permeable walls that repel colloids but allow polymers to freely penetrate. For hard (semi-permeable) walls we find that the capillary binodal is shifted towards higher (lower) polymer fugacities and lower (higher) colloid fugacities as compared to the bulk binodal; this implies capillary condensation (evaporation) of the colloidal liquid phase in the slit. A macroscopic treatment is provided by a novel symmetric Kelvin equation for general binary mixtures, based on the proximity in chemical potentials of statepoints at capillary coexistence and the reference bulk coexistence. Results for capillary binodals compare well with those obtained from the classic version of the Kelvin equation due to Evans and Marini Bettolo Marconi [J. Chem. Phys. 86, 7138 (1987)], and are quantitatively accurate away from the fluid-fluid critical point, even at small wall separations. For hard walls the density profiles of polymers and colloids inside the slit display oscillations due to packing effects for all statepoints. For semi-permeable walls either similar structuring or flat profiles are found, depending on the statepoint considered.Comment: 15 pages, 13 figure

Modelling colloids with Baxter's adhesive hard sphere model

The structure of the Baxter adhesive hard sphere fluid is examined using computer simulation. The radial distribution function (which exhibits unusual discontinuities due to the particle adhesion) and static structure factor are calculated with high accuracy over a range of conditions and compared with the predictions of Percus--Yevick theory. We comment on rigidity in percolating clusters and discuss the role of the model in the context of experiments on colloidal systems with short-range attractive forces.Comment: 14 pages, 7 figures. (For proceedings of "Structural arrest in colloidal systems with short-range attractive forces", Messina, December 2003

Universal law of fractionation for slightly polydisperse systems

By perturbing about a general monodisperse system, we provide a complete description of two-phase equilibria in any system which is slightly polydisperse in some property (e.g., particle size, charge, etc.). We derive a universal law of fractionation which is corroborated by comprehensive experiments on a model colloid-polymer mixture. We furthermore predict that phase separation is an effective method of reducing polydispersity only for systems with a skewed distribution of the polydisperse property

Entropic Interactions in Suspensions of Semi-Flexible Rods: Short-Range Effects of Flexibility

We compute the entropic interactions between two colloidal spheres immersed in a dilute suspension of semi-flexible rods. Our model treats the semi-flexible rod as a bent rod at fixed angle, set by the rod contour and persistence lengths. The entropic forces arising from this additional rotational degree of freedom are captured quantitatively by the model, and account for observations at short range in a recent experiment. Global fits to the interaction potential data suggest the persistence length of fd-virus is about two to three times smaller than the commonly used value of $2.2 \mu {m}$.Comment: 4 pages, 5 figures, submitted to PRE rapid communication

Diffusive Evolution of Stable and Metastable Phases II: Theory of Non-Equilibrium Behaviour in Colloid-Polymer Mixtures

By analytically solving some simple models of phase-ordering kinetics, we suggest a mechanism for the onset of non-equilibrium behaviour in colloid-polymer mixtures. These mixtures can function as models of atomic systems; their physics therefore impinges on many areas of thermodynamics and phase-ordering. An exact solution is found for the motion of a single, planar interface separating a growing phase of uniform high density from a supersaturated low density phase, whose diffusive depletion drives the interfacial motion. In addition, an approximate solution is found for the one-dimensional evolution of two interfaces, separated by a slab of a metastable phase at intermediate density. The theory predicts a critical supersaturation of the low-density phase, above which the two interfaces become unbound and the metastable phase grows ad infinitum. The growth of the stable phase is suppressed in this regime.Comment: 27 pages, Latex, eps

Can Polymer Coils be modeled as "Soft Colloids"?

We map dilute or semi-dilute solutions of non-intersecting polymer chains onto a fluid of ``soft'' particles interacting via a concentration dependent effective pair potential, by inverting the pair distribution function of the centers of mass of the initial polymer chains. A similar inversion is used to derive an effective wall-polymer potential; these potentials are combined to successfully reproduce the calculated exact depletion interaction induced by non-intersecting polymers between two walls. The mapping opens up the possibility of large-scale simulations of polymer solutions in complex geometries.Comment: 4 pages, 3 figures ReVTeX[epsfig,multicol,amssymb] references update

Structure of polymeric nanoparticles encapsulating a drug – pamoic acid ion pair by scanning transmission electron microscopy

Drug-delivery systems based on polymeric nanoparticles are useful for improving drug bioavailability and/or delivery of the active ingredient for example directly to the cancerous tumour. The physical and chemical characterization of a functionalized nanoparticle system is required to measure drug loading and dispersion but also to understand and model the rate and extent of drug release to help predict performance. Many techniques can be used, however, difficulties related to structure determination and identifying the precise location of the drug fraction make mathematical prediction complex and in many published examples the final conclusions are based on assumptions regarding an expected structure. Cryogenic scanning transmission electron microscopy imaging in combination with electron energy loss spectroscopy techniques are used here to address this issue and provide a multi-modal approach to the characterisation of a self-assembled polymeric nanoparticle system based upon a polylactic acid - polyethylene glycol (PLA-PEG) block copolymer containing a hydrophobic ion-pair between pamoic acid and an active pharmaceutical ingredient (API). Results indicate a regular dispersion of spherical nanoparticles of 88 ± 9 nm diameter. The particles are shown to have a multi-layer structure consisting of a 25 nm radius hydrophobic core of PLA and pamoic acid-API material with additional enrichment of the pamoic acid-API material within the inner core (that can be off-centre), surrounded by a 9 nm dense PLA-PEG layer all with a low-density PEG surface coating of around 10 nm thickness. This structure suggests that release of the API can only occur by diffusion through or degradation of the dense, 9 nm thick PLA-PEG layer either of which is a process consistent with the previously reported steady release kinetics of the API and counter ion from these nanoparticle formulations. Establishing accurate measures of product structure enables a link to performance by providing appropriate physical parameters for future mathematical modelling of barriers controlling API release in these nanoparticle formulations