Ca(2+) binding to c-state of adenine nucleotide translocase (ANT)-surrounding cardiolipins enhances (ANT)-Cys(56) relative mobility: A computational-based mitochondrial permeability transition study

The oxidation of critical cysteines/related thiols of adenine nucleotide translocase (ANT) is believed to be an important event of the Ca(2+)-induced mitochondrial permeability transition (MPT), a process mediated by a cyclosporine A/ADP-sensitive permeability transition pores (PTP) opening. We addressed the ANT-Cys(56) relative mobility status resulting from the interaction of ANT/surrounding cardiolipins with Ca(2+) and/or ADP by means of computational chemistry analysis (Molecular Interaction Fields and Molecular Dynamics studies), supported by classic mitochondrial swelling assays. The following events were predicted: (i) Ca(2+) interacts preferentially with the ANT surrounding cardiolipins bound to the H4 helix of translocase, (ii) weakens the cardiolipins/ANT interactions and (iii) destabilizes the initial ANT-Cys(56) residue increasing its relative mobility. The binding of ADP that stabilizes the conformation ""m"" of ANT and/or cardiolipin, respectively to H5 and H4 helices, could stabilize their contacts with the short helix h56 that includes Cys(56), accounting for reducing its relative mobility. The results suggest that Ca(2+) binding to adenine nucleotide translocase (ANT)-surrounding cardiolipins in c-state of the translocase enhances (ANT)-Cys(56) relative mobility and that this may constitute a potential critical step of Ca(2+)-induced PTP opening. (C) 2009 Elsevier B.V. All rights reserved.

Tenure, mobility and retention of nurses in Queensland, Australia: 2001 and 2004

Aim. Data were collected on tenure, mobility and retention of the nursing workforce in Queensland to aid strategic planning by the Queensland Nurses Union (QNU). Background. Shortages of nurses negatively affect the health outcomes of patients. Population rise is increasing the demand for nurses in Queensland. The supply of nurses is affected by recruitment of new and returning nurses, retention of the existing workforce and mobility within institutions. Methods. A self-reporting, postal survey was undertaken by the QNU members from the major employment sectors of aged care, public acute and community health and private acute and community health. Results. Only 60% of nurses had been with their current employer more than 5 years. In contrast 90% had been in nursing for 5 years or more and most (80%) expected to remain in nursing for at least another 5 years. Breaks from nursing were common and part-time positions in the private and aged care sectors offered flexibility. Conclusion. The study demonstrated a mobile nursing workforce in Queensland although data on tenure and future time in nursing suggested that retention in the industry was high. Concern is expressed for replacement of an ageing nursing population.

Expo 1988 Information Service Centre, Brisbane

View to service centre during Expo 1988.

Perceptions of mental health service delivery among staff and Indigenous consumers: it's still about communication

Objective: A needs analysis was undertaken to determine the quality and effectiveness of mental health services to Indigenous consumers within a health district of Southern Queensland. The study focussed on identifying gaps in the service provision for Indigenous consumers. Tools and methodologies were developed to achieve this. Method: Data were collected through the distribution of questionnaires to the target populations: district health service staff and Indigenous consumers. Questionnaires were developed through consultation with the community and the Steering Committee in order to achieve culturally appropriate wording. Of prime importance was the adaptation of questionnaire language so it would be fully understood by Indigenous consumers. Both questionnaires were designed to provide a balanced perspective of current mental health service needs for Indigenous people within the mental health service. Results: Results suggest that existing mental health services do not adequately meet the needs of Indigenous people. Conclusions: Recommendations arising from this study indicate a need for better communication and genuine partnerships between the mental health service and Indigenous people that reflect respect of cultural heritage and recognises the importance of including Indigenous people in the design and management of mental health services. Attention to the recommendations from this study will help ensure a culturally appropriate and effective mental health service for Indigenous consumers.

The octahedral manipulator: Geometry and mobility

In most Of the practical six-actuator in-parallel manipulators, the octahedral form is either taken as it stands or is approximated. Yet considerable theoretical attention is paid in the literature to more general forms. Here we touch on the general form, and describe some aspects of its behavior that vitiate strongly against its adoption as a pattern for a realistic manipulate,: We reach the conclusion that the structure for in-parallel manipulators must be triangulated as fully as possible, so leading to the octahedral form. In describing some of the geometrical properties of the general octahedron, we show how they apply to manipulators. We examine in detail the special configurations at which the 6 x 6 matrix of leg lines is singular presenting results from the point of view of geometry in preference to analysis. In extending and enlarging on some known properties, a few behavioral surprises materialize. In studying special configurations, we start with the most general situation, and every other case derives from this. Our coverage is more comprehensive than any that we have found. We bring to light material that is, we think, of significant use to a designer.

Epidermal iontophoresis: I. Development of the ionic mobility-pore model

Purpose, An integrated ionic mobility-pore model for epidermal iontophoresis is developed from theoretical considerations using both the free volume and pore restriction forms of the model for a range of solute radii (r(j)) approaching the pore radii (r(p)) as well as approximation of the pore restriction form for r(j)/r(p) < 0.4. In this model, we defined the determinants for iontophoresis as solute size (defined by MV, MW or radius), solute mobility, solute shape, solute charge, the Debye layer thickness, total current applied, solute concentration, fraction ionized, presence of extraneous ions (defined by solvent conductivity), epidermal permselectivity, partitioning rates to account for interaction of unionized and ionized lipophilic solutes with the wall of the pore and electroosmosis. Methods, The ionic mobility-pore model was developed from theoretical considerations to include each of the determinants of iontophoretic transport. The model was then used to reexamine iontophoretic flux conductivity and iontophoretic flux-fraction ionized literature data on the determinants of iontophoretic flux. Results. The ionic mobility-pore model was found to be consistent with existing experimental data and determinants defining iontophoretic transport. However, the predicted effects of solute size on iontophoresis are more consistent with the pore-restriction than free volume form of the model. A reanalysis of iontophoretic flux-conductivity data confirmed the model's prediction that, in the absence of significant electroosmosis, the reciprocal of flux is linearly related to either donor or receptor solution conductivity. Significant interaction with the pore walls, as described by the model, accounted for the reported pH dependence of the iontophoretic transport for a range of ionizable solutes. Conclusions. The ionic mobility-pore iontophoretic model developed enables a range of determinants of iontophoresis to be described in a single unifying equation which recognises a range of determinants of iontophoretic flux.

Epidermal iontophoresis: II. Application of the ionic mobility-pore model to the transport of local anesthetics

Purpose, An in vitro study was carried out to determine the iontophoretic permeability of local anesthetics through human epidermis. The relationship between physicochemical structure and the permeability of these solutes was then examined using an ionic mobility-pore model developed to define quantitative relationships. Methods. The iontophoretic permeability of both ester-type anesthetics (procaine, butacaine, tetracaine) and amide-type anesthetics (prilocaine, mepivacaine, lidocaine, bupivacaine, etidocaine, cinchocaine) were determined through excised human epidermis over 2 hrs using a constant d.c. current and Ag/AgCl electrodes. Individual ion mobilities were determined from conductivity measurements in aqueous solutions. Multiple stepwise regression was applied to interrelate the iontophoretic permeability of the solutes with their physical properties to examine the appropriateness of the ionic mobility-pore model and to determine the best predictor of iontophoretic permeability of the local anesthetics. Results. The logarithm of the iontophoretic permeability coefficient (log PCj,iont) for local anesthetics was directly related to the log ionic mobility and MW for the free volume form of the model when other conditions are held constant. Multiple linear regressions confirmed that log PCj,iont was best defined by ionic mobility (and its determinants: conductivity, pK(a) and MW) and MW. Conclusions. Our results suggest that of the properties studied, the best predictors of iontophoretic transport of local anesthetics are ionic mobility (or pK(a)) and molecular size. These predictions are consistent with the ionic mobility pore model determined by the mobility of ions in the aqueous solution, the total current, epidermal permselectivity and other factors as defined by the model.

Continuity of care and readmission in two service systems: a comparative Victorian and Groningen case-register study

Objective: We compared service consumption, continuity of care and risk of readmission in a record linkage follow-up study of cohorts of patients with schizophrenia and related disorders in Victoria (Australia) and in Groningen (The Netherlands). These areas are interesting to compare because mental health care is in a different stage of deiustitutionalization. More beds are available in Groningen and more community resources are available in Victoria. Method: The cohorts were followed for 4 years, since discharge from inpatient services using record linkage data available in the psychiatric case-registers in both areas. Survival analysis was used to study continuity of care and risk of readmission. Results: Available indicators showed a higher level of continuity of care in Victoria. While the relative risk of readmission was the same in both areas and not affected by aftercare contact after discharge, the number of days spent in hospital was much higher in the Groningen register area. Conclusion: These findings provide further support for earlier reports that the risk of readmission is predominantly affected by attributes of mental illness. However, the duration of admissions, is strongly affected by service system variables, including the provision of continuity of care.

HIV infection among women admitted to the gynaecology service of a district hospital in South Africa

Our objective was to determine the prevalence of HIV infection and disease-specific HIV prevalence among women admitted to the gynaecology service of a district hospital in South Africa over a 3-month period in 1997. This was done with the goal of developing HIV education and counselling services in this setting. HIV status was determined among 196 (96%) of 205 consecutive admissions; 82 (42%) tested HIV positive. The HIV-infected women were younger than the HIV uninfected women (mean age 27 vs 33 years, P=0.001). The disease-specific HIV prevalence was greater than or equal to 40% among women who had had abortions, pelvic inflammatory disease, or ectopic pregnancy. The length of hospital stay (mean 5.4 days) and mortality (1%) were similar in the 2 groups. Inpatient gynaecology services may be act important setting in Africa, within which to provide HIV education, counselling and care.

Providing evidence-based answers to clinical questions - A pilot information service for general practitioners

Objective: To pilot a clinical information service for general practitioners. Methods: A representative sample of 31 GPs was invited to submit clinical questions to a local academic department of general practice. Their views on the service and the usefulness of the information were obtained by telephone interview. Results: Over one month, nine GPs (29% of the sample, 45% of those stating an interest), submitted 20 enquiries comprising 45 discrete clinical questions. The median time to search for evidence, appraise it and write answers to each enquiry was 2.5 hours (range, 1.0-7.4 hours). The median interval between receipt of questions and dispatch of answers was 3 clays (range, 1-12 days). Conclusions: The GPs found the answers useful in clinical decision making; in four out of 20 cases patient management was altered.

Class attainment among British men - A multivariate extension of the CASMIN model of intergenerational class mobility

The CASMIN Project is arguably the most influential contemporary study of class mobility in the world. However, CASMIN results with respect to weak vertical status effects on class mobility have been extensively criticized. Drawing on arguments about how to model vertical mobility, Hout and Hauser (1992) show that class mobility is strongly determined by vertical socioeconomic differences. This paper extends these arguments by estimating the CASMIN model while explicitly controlling for individual determinants of socioeconomic attainment. Using the 1972 Oxford Mobility Data and the 1979 and 1983 British Election Studies, the paper employs mixed legit models to show how individual socioeconomic factors and categorical differences between classes shape intergenerational mobility. The findings highlight the multidimensionality of class mobility and its irreducibility to vertical movement up and down a stratification hierarchy.

Preliminary experiences with a single-patient trials service in general practice

Objective: To pilot a single-patient trials (SPTs) service in general practice, designed to improve decision-making about long-term medications for chronic conditions. Design: 12-week within-patient, randomised, double-blind, placebo-controlled, crossover comparison of ibuprofen with paracetamol for osteoarthritis, involving three pairs of two-week treatment periods for each participating patient. Setting and patients: Patients attending an academic general practice with a clinical diagnosis of osteoarthritis, with pain of at least a month's duration severe enough to warrant consideration of long-term non-steroidal anti-inflammatory drug (NSAID) use. Main outcome measures: Pain and stiffness; measures of overall arthritis compared with previous fortnight; preference for NSAID at the end of each two-week treatment period; use of escape analgesia; side effects; and management changes as a result of the SPTs. Results: Eight of 14 patients completed SPTs. One was a clear responder to NSAIDs, five were non-responders, and two were indefinite. Of the five who were using NSAIDs before the SPT, two continued and three ceased using them. Clinically useful information assisted decision-making for all eight participants. Medication management changed for six. Conclusions: Single-patient trials can be successfully implemented in general practice and might be a valuable method for GPs to identify patients who respond to medication for chronic stable conditions such as osteoarthritis, in which individual response to medication is variable.