The Experience and Practice of Approved Social Workers in Northern Ireland

This article reports on the first extensive survey of Approved Social Worker (ASW) activity under the Mental Health (Northern Ireland) Order 1986. The integrated health and social services organizational structure, the adverse effects on individual mental health of the legacy of thirty years of civil conflict and the move from hospital to community care are significant features which have influenced the delivery of mental health social work services locally. The practice and experience of ASWs was surveyed by postal questionnaire and user and carer experience of compulsory hospital admission was investigated by a series of focus groups. The study revealed that two‐thirds of ASWs had experience of acting as an applicant in compulsory hospital admission during the past two years. Nearly half (42 per cent) of these ASWs had reported experience of between one and five admissions and one‐tenth had completed over twenty admissions in the two‐year period. In only a small minority of cases did joint face‐to‐face assessment with the General Practitioner (doctor) take place; nearly half of ASWs reported difficulties in obtaining transport; and only one‐fifth of ASWs had experience of acting as a second approved social worker. Half of ASWs reported experience of guardianship, either as applicant or in making the recommendation. Both service users and carers reported a lack of understanding about the role of the ASW and complained about the lack of alternative resources that ASWs could use to prevent hospital admissions. These findings are discussed and a number of recommendations are proposed for improvements to approved social worker practice.

Approved Social Work Training in Northern Ireland: Using Research to Examine Competence-Based Learning and Influence Policy Change

This article reports on how research activity helped describe and analyse ASW (Approved Social Worker) learning experience as well as acting as a catalyst for change and development in policy and practice in Northern Ireland. The paper contextualizes the study by outlining the legislation, the main features of the ASW role and the approach to ASW training in Northern Ireland, and by reviewing the literature on the efficacy and value of competence-based learning. While the findings do not provide conclusive evidence that a competence-based approach is inherently more effective than previous courses, they do indicate that candidates who were trained in this way were moderately more satisfied than those who had participated in non-competence based programmes. The research also highlights the importance of the interrelationship between training, practice experience and support in developing and sustaining competence. The paper concludes with a review of the recommendations arising from the study and an analysis of the developments in training and regulations relating to practice experience and re-approval of ASWs since publication of the research. The study is of contemporary interest given the proposed changes to the role of ASWs/Mental Health Officers in the context of the reviews of UK mental health law.

Drug Delivery of Aminolevulinic Acid from Topical Formulations Intended for Photodynamic Therapy

Topical photodynamic therapy is used for a variety of malignant and pre-malignant skin disorders, including Bowen's Disease and Superficial Basal Cell Carcinoma. A haem precursor, typically 5-aminolevulinic acid (ALA), acting as a prodrug, is absorbed and converted by the haem biosynthetic pathway to photoactive protoprophyrin IX (PpIX), which accumulates preferentially in rapidly dividing
cells. Cell destruction occurs when PpIx is activated by an intense light source of appropriate wavelength. Topical delivery of ALA avoids the prolonged photosensitivity reactions associated with systemic administration of photosensitisers but its clinical utility is influenced by the tissue penetration characteristics of the drug, its ease of application and the stability of the active agent in the applied dose. This review, therefore, focuses on drug delivery applications for topical, ALA-based PDT. Issues considered in detail include physical and chemical enhancement strategies for tissue penetration of ALA and subsequent intracellular accumulation of PpIX, together with formulation strategies and drug delivery design solutions appropriate to various clinical applications. The fundamental aspects of drug diffusion in
relation to the physicochemical properties of ALA are reviewed and specific consideration is given to the degradation pathways of ALA in formulated systems that, in turn, influence the design of stable topical formulations.

Biodegradation and Rhodococcus--masters of catabolic versatility.

The genus Rhodococcus is a very diverse group of bacteria that possesses the ability to degrade a large number of organic compounds, including some of the most difficult compounds with regard to recalcitrance and toxicity. They achieve this through their capacity to acquire a remarkable range of diverse catabolic genes and their robust cellular physiology. Rhodococcus appear to have adopted a strategy of hyperrecombination associated with a large genome. Notably, they harbour large linear plasmids that contribute to their catabolic diversity by acting as 'mass storage' for a large number of catabolic genes. In addition, there is increasing evidence that multiple pathways and gene homologues are present that further increase the catabolic versatility and efficiency of Rhodococcus.

Complex weathering in drylands: implications of 'stress' history for rock debris breakdown and sediment release

Weathering studies have often sought to explain features in terms of a prevailing set of environmental conditions. However, it is clear that in most present-day hot desert regions, the surface rock debris has been exposed to a range of weathering environments and processes. These different weathering conditions can arise in two ways, either from the effects of long-term climate change acting on debris that remains relatively static within the landscape or through the spatial relocation of debris from high to low altitude. Consequently, each fragment of rock may contain a unique weathering-related legacy of damage and alteration — a legacy that may greatly influence its response to present-day weathering activity. Experiments are described in which blocks of limestone, sandstone, granite and basalt are given ‘stress histories’ by subjecting them to varying numbers of heating and freezing cycles as a form of pre-treatment. These imposed stress histories act as proxies for a weathering history. Some blocks were used in a laboratory salt weathering simulation study while others underwent a 2 year field exposure trial at high, mid and low altitude sites in Death Valley, California. Weight loss and ultrasonic pulse velocity measurements suggest that blocks with stress histories deteriorate more rapidly than unstressed samples of the same rock type exposed to the same environmental conditions. Laboratory data also indicate that the result of imposing a known ‘weathering history’ on samples by pre-stressing them is an increase in the amount of fine sediment released during salt weathering over a given period of time in comparison to unstressed samples.

Effect of purinergic blockers on outward current in isolated smooth muscle cells of the sheep bladder

Freshly dispersed cells from sheep urinary bladder were voltage clamped using the whole cell and inside-out patch-clamp technique. Cibacron and Basilen blue increased outward current in a dose-dependent manner with a half-maximal response at 10(-5) M. Suramin, in concentrations to 10(-3) M, had no such effect. The Cibacron blue response was abolished in Ca2+-free physiological salt solution, suggesting that it was acting on a Ca2+-dependent current. Similarly, the Cibacron blue-sensitive current was significantly attenuated by charybdotoxin. Cibacron blue did not modulate inward current nor were its effects modified by caffeine or heparin, suggesting that its effect on outward current was not secondary to an increase in intracellular Ca2+. Application of 10(-4) M Cibacron blue to the inside membrane of excised patches caused a rapid increase in open probability of a large-conductance (300 pS) K+ channel. These results suggest that Cibacron blue is a potent activator of a Ca2+-dependent outward current in bladder smooth muscle cells in addition to its action as a purinergic blocker.

Rational design of a dual-mode optical and chemical prodrug

Purpose. The purpose of this study is to demonstrate the rational design and behaviour of the first dual mode optical and chemical prodrug, exemplified by an acetyl salicylic acid-based system. Methods. A cyclic 1,4-benzodioxinone prodrug was synthesised by reaction of 3,5-dimethoxybenzoin and acetyl salicoyl chloride with pyridine. After purification by column chromatography and recrystallization, characterization was achieved using infrared and NMR spectroscopies, mass spectrometry, elemental analysis and single crystal X-ray diffraction. Light-triggered drug liberation was characterised via UV-visible spectroscopy following low-power 365 nm irradiation for controlled times. Chemical drug liberation was characterised via UV-visible spectroscopy in pH 5.5 solution. Results. The synthetic method yielded pure prodrug, with full supporting characterisation. Light-triggered drug liberation proceeded at a rate of 8.30 10j2 sj1, while chemical, hydrolytic liberation proceeded independently at 1.89 10j3 sj1. The photochemical and hydrolytic reactions were both quantitative. Conclusions. This study demonstrates the first rational dual-mode optical and chemical prodrug, using acetyl salicylic acid as a model, acting as a paradigm for future dual-mode systems. Photochemical drug liberation proceeds 44 times faster than chemical liberation, suggesting potential use in drug-eluting medical devices where an additional burst of drug is required at the onset of infection.

Ca2+-independent phospholipase A2-dependent gating of TRPM8 by lysophospholipids

TRPM8 represents an ion channel activated by cold temperatures and cooling agents, such as menthol, that underlies the cold-induced excitation of sensory neurons. Interestingly, the only human tissue outside the peripheral nervous system, in which the expression of TRPM8 transcripts has been detected at high levels, is the prostate, a tissue not exposed to any essential temperature variations. Here we show that the TRPM8 cloned from human prostate and heterologously expressed in HEK-293 cells is regulated by the Ca(2+)-independent phospholipase A(2) (iPLA(2)) signaling pathway with its end products, lysophospholipids (LPLs), acting as its endogenous ligands. LPLs induce prominent prolongation of TRPM8 channel openings that are hardly detectable with other stimuli (e.g. cold, menthol, and depolarization) and that account for more than 90% of the total channel open time. Down-regulation of iPLA(2) resulted in a strong inhibition of TRPM8-mediated functional responses and abolished channel activation. The action of LPLs on TRPM8 channels involved either changes in the local lipid bilayer tension or interaction with the critical determinant(s) in the transmembrane channel core. Based on this, we propose a novel concept of TRPM8 regulation with the involvement of iPLA(2) stimulation. This mechanism employs chemical rather than physical (temperature change) signaling and thus may be the main regulator of TRPM8 activation in organs not exposed to any essential temperature variations, as in the prostate gland.

Counterbalancing forces in electromigration

In electromigration (EM) experiments on metallic wires, a flux of atoms can lead to motion of the centre of mass (COM) of the wire. Hence, it may be tempting to assume that the flow of current produces a net force on the wire as a whole. We point out, on the basis of known momentum-balance arguments, that the net force on a metallic wire due to a passing steady-state current is zero. This is possible, because in addition to EM driving forces, acting on scattering centres, there are counterbalancing forces, acting on the rest of the system. Drift of the COM in EM experiments occurs inevitably because the substrate keeps the crystal lattice of the wire fixed, while allowing diffusion of defects in the bulk of the wire. This drift is not evidence for a net force on the wire.

Cellular physiology of retinal and choroidal arteriolar smooth muscle cells.

Control of ocular blood flow occurs predominantly at the level of the retinal and choroidal arterioles. The present article provides an overview of the Ca2 + handling mechanisms and plasmalemmal ion channels involved in the regulation of retinal and choroidal arteriolar smooth muscle tone. Increases in global intracellular free Ca2 + ([Ca2 +]i) involve multiple mechanisms, including agonist-dependent release of Ca2 + from intracellular stores through activation of the inositol trisphosphate (IP3) pathway. Ca2 + enters by voltage-dependent L-type Ca2 + channels and novel dihydropyridine-sensitive store-operated nonselective cation channels. Ca2 + extrusion is mediated by plasmalemmal Ca2 +-ATPases and through Na+/Ca2+ exchange. Local Ca2 + transients (Ca2 + sparks) play an important excitatory role, acting as the building blocks for more global Ca2 + signals that can initiate vasoconstriction. K+ and Cl- channels may also affect cell function by modulating membrane potential. The precise contribution of each of these mechanisms to the regulation of retinal and choroidal perfusion in vivo warrants future investigation.

The myeloproliferative disorder-associated JAK2 V617F mutant escapes negative regulation by suppressor of cytokine signaling 3

The somatic JAK2 valine-to-phenylalanine (V617F) mutation has been detected in up to 90% of patients with polycythemia and in a sizeable proportion of patients with other myeloproliferative disorders such as essential thrombocythemia and idiopathic myelofibrosis. Suppressor of cytokine signaling 3 (SOCS3) is known to be a strong negative regulator of erythropoietin (EPO) signaling through interaction with both the EPO receptor (EPOR) and JAK2. We report here that JAK2 V617F cannot be regulated and that its activation is actually potentiated in the presence of SOCS3. Instead of acting as a suppressor, SOCS3 enhanced the proliferation of cells expressing both JAK2 V617F and EPOR. Additionally, although SOCS1 and SOCS2 are degraded in the presence of JAK2 V617F, turnover of SOCS3 is inhibited by the JAK2 mutant kinase and this correlated with marked tyrosine phosphorylation of SOCS3 protein. We also observed constitutive tyrosine phosphorylation of SOCS3 in peripheral blood mononuclear cells (PBMCs) derived from patients homozygous for the JAK2 V617F mutant. These findings suggest that the JAK2 V617F has overcome normal SOCS regulation by hyperphosphorylating SOCS3, rendering it unable to inhibit the mutant kinase. Thus, JAK2 V617F may even exploit SOCS3 to potentiate its myeloproliferative capacity.