Ionic Hydrogel for Accelerated Dopamine Delivery via Retrodialysis.

Local drug delivery directly to the source of a given pathology using retrodialysis is a promising approach to treating otherwise untreatable diseases. As the primary material component in retrodialysis, the semipermeable membrane represents a critical point for innovation. This work presents a new ionic hydrogel based on polyethylene glycol and acrylate with dopamine counterions. The ionic hydrogel membrane is shown to be a promising material for controlled diffusive delivery of dopamine. The ionic nature of the membrane accelerates uptake of cationic species compared to a nonionic membrane of otherwise similar composition. It is demonstrated that the increased uptake of cations can be exploited to confer an accelerated transport of cationic species between reservoirs as is desired in retrodialysis applications. This effect is shown to enable nearly 10-fold increases in drug delivery rates from low concentration solutions. The processability of the membrane is found to allow for integration with microfabricated devices which will in turn accelerate adaptation into both existing and emerging device modalities. It is anticipated that a similar materials design approach may be broadly applied to a variety of cationic and anionic compounds for drug delivery applications ranging from neurological disorders to cancer

How does reviewing the evidence change veterinary surgeons' beliefs regarding the treatment of ovine footrot? A quantitative and qualitative study

Footrot is a widespread, infectious cause of lameness in sheep, with major economic and welfare costs. The aims of this research were: (i) to quantify how veterinary surgeons’ beliefs regarding the efficacy of two treatments for footrot changed following a review of the evidence (ii) to obtain a consensus opinion following group discussions (iii) to capture complementary qualitative data to place their beliefs within a broader clinical context. Grounded in a Bayesian statistical framework, probabilistic elicitation (roulette method) was used to quantify the beliefs of eleven veterinary surgeons during two one-day workshops. There was considerable heterogeneity in veterinary surgeons’ beliefs before they listened to a review of the evidence. After hearing the evidence, seven participants quantifiably changed their beliefs. In particular, two participants who initially believed that foot trimming with topical oxytetracycline was the better treatment, changed to entirely favour systemic and topical oxytetracycline instead. The results suggest that a substantial amount of the variation in beliefs related to differences in veterinary surgeons’ knowledge of the evidence. Although considerable differences in opinion still remained after the evidence review, with several participants having non-overlapping 95% credible intervals, both groups did achieve a consensus opinion. Two key findings from the qualitative data were: (i) veterinary surgeons believed that farmers are unlikely to actively seek advice on lameness, suggesting a proactive veterinary approach is required (ii) more attention could be given to improving the way in which veterinary advice is delivered to farmers. In summary this study has: (i) demonstrated a practical method for probabilistically quantifying how veterinary surgeons’ beliefs change (ii) revealed that the evidence that currently exists is capable of changing veterinary opinion (iii) suggested that improved transfer of research knowledge into veterinary practice is needed (iv) identified some potential obstacles to the implementation of veterinary advice by farmers

An in silico model of the ubiquitin-proteasome system that incorporates normal homeostasis and age-related decline

BACKGROUND: The ubiquitin-proteasome system is responsible for homeostatic degradation of intact protein substrates as well as the elimination of damaged or misfolded proteins that might otherwise aggregate. During ageing there is a decline in proteasome activity and an increase in aggregated proteins. Many neurodegenerative diseases are characterised by the presence of distinctive ubiquitin-positive inclusion bodies in affected regions of the brain. These inclusions consist of insoluble, unfolded, ubiquitinated polypeptides that fail to be targeted and degraded by the proteasome. We are using a systems biology approach to try and determine the primary event in the decline in proteolytic capacity with age and whether there is in fact a vicious cycle of inhibition, with accumulating aggregates further inhibiting proteolysis, prompting accumulation of aggregates and so on. A stochastic model of the ubiquitin-proteasome system has been developed using the Systems Biology Mark-up Language (SBML). Simulations are carried out on the BASIS (Biology of Ageing e-Science Integration and Simulation) system and the model output is compared to experimental data wherein levels of ubiquitin and ubiquitinated substrates are monitored in cultured cells under various conditions. The model can be used to predict the effects of different experimental procedures such as inhibition of the proteasome or shutting down the enzyme cascade responsible for ubiquitin conjugation. RESULTS: The model output shows good agreement with experimental data under a number of different conditions. However, our model predicts that monomeric ubiquitin pools are always depleted under conditions of proteasome inhibition, whereas experimental data show that monomeric pools were depleted in IMR-90 cells but not in ts20 cells, suggesting that cell lines vary in their ability to replenish ubiquitin pools and there is the need to incorporate ubiquitin turnover into the model. Sensitivity analysis of the model revealed which parameters have an important effect on protein turnover and aggregation kinetics. CONCLUSION: We have developed a model of the ubiquitin-proteasome system using an iterative approach of model building and validation against experimental data. Using SBML to encode the model ensures that it can be easily modified and extended as more data become available. Important aspects to be included in subsequent models are details of ubiquitin turnover, models of autophagy, the inclusion of a pool of short-lived proteins and further details of the aggregation process

Acapsular Staphylococcus aureus with a non-functional agr regains capsule expression after passage through the bloodstream in a bacteremia mouse model

Selection pressures exerted on Staphylococcus aureus by host factors during infection may lead to the emergence of regulatory phenotypes better adapted to the infection site. Traits convenient for persistence may be fixed by mutation thus turning these mutants into microevolution endpoints. The feasibility that stable, non-encapsulated S. aureus mutants can regain expression of key virulence factors for survival in the bloodstream was investigated. S. aureus agr mutant HU-14 (IS256 insertion in agrC) from a patient with chronic osteomyelitis was passed through the bloodstream using a bacteriemia mouse model and derivative P3.1 was obtained. Although IS256 remained inserted in agrC, P3.1 regained production of capsular polysaccharide type 5 (CP5) and staphyloxanthin. Furthermore, P3.1 expressed higher levels of asp23/SigB when compared with parental strain HU-14. Strain P3.1 displayed decreased osteoclastogenesis capacity, thus indicating decreased adaptability to bone compared with strain HU-14 and exhibited a trend to be more virulent than parental strain HU-14. Strain P3.1 exhibited the loss of one IS256 copy, which was originally located in the HU-14 noncoding region between dnaG (DNA primase) and rpoD (sigA). This loss may be associated with the observed phenotype change but the mechanism remains unknown. In conclusion, S. aureus organisms that escape the infected bone may recover the expression of key virulence factors through a rapid microevolution pathway involving SigB regulation of key virulence factors.Fil: Suligoy Lozano, Carlos Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Díaz, Rocío E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Gehrke, Ana-katharina Elsa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Ring, Natalie. University of Edinburgh; Reino UnidoFil: Yebra, Gonzalo. University of Edinburgh; Reino UnidoFil: Alves, Joana. University of Edinburgh; Reino UnidoFil: Gómez, Marisa Ileana. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Wendler, Sindy. Universitätsklinikum Jena Und Medizinische Fakultät; AlemaniaFil: Fitzgerald, J. Ross. University of Edinburgh; Reino UnidoFil: Tuchscherr, Lorena. Jena University Hospital; AlemaniaFil: Löffler, Bettina. Jena University Hospital; AlemaniaFil: Sordelli, Daniel Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Noto Llana, Mariangeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Buzzola, Fernanda Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Qualitative study on the implementation of professional pharmacy services in Australian community pharmacies using framework analysis

Abbreviations: BCT, Behavioural change techniques taxonomy; BCW, Behavioural change wheel; CFIR, Consolidated framework for implementation research; EPOC, Cochrane effective practice and organisation of care; FISpH, Framework for the implementation of services in pharmacy; GIF, Generic implementation framework; KPI, Key performance indicator; TDF, Theoretical domains frameworkBackground: Multiple studies have explored the implementation process and influences, however it appears there is no study investigating these influences across the stages of implementation. Community pharmacy is attempting to implement professional services (pharmaceutical care and other health services). The use of implementation theory may assist the achievement of widespread provision, support and integration. The objective was to investigate professional service implementation in community pharmacy to contextualise and advance the concepts of a generic implementation framework previously published. Methods: Purposeful sampling was used to investigate implementation across a range of levels of implementation in community pharmacies in Australia. Twenty-five semi-structured interviews were conducted and analysed using a framework methodology. Data was charted using implementation stages as overarching themes and each stage was thematically analysed, to investigate the implementation process, the influences and their relationships. Secondary analyses were performed of the factors (barriers and facilitators) using an adapted version of the Consolidated Framework for Implementation Research (CFIR), and implementation strategies and interventions, using the Expert Recommendations for Implementing Change (ERIC) discrete implementation strategy compilation. Results: Six stages emerged, labelled as development or discovery, exploration, preparation, testing, operation and sustainability. Within the stages, a range of implementation activities/steps and five overarching influences (pharmacys' direction and impetus, internal communication, staffing, community fit and support) were identified. The stages and activities were not applied strictly in a linear fashion. There was a trend towards the greater the number of activities considered, the greater the apparent integration into the pharmacy organization. Implementation factors varied over the implementation stages, and additional factors were added to the CFIR list and definitions modified/contextualised for pharmacy. Implementation strategies employed by pharmacies varied widely. Evaluations were lacking. Conclusions: The process of implementation and five overarching influences of professional services implementation in community pharmacy have been outlined. Framework analysis revealed, outside of the five overarching influences, factors influencing implementation varied across the implementation stages. It is proposed at each stage, for each domain, the factors, strategies and evaluations should be considered. The Framework for the Implementation of Services in Pharmacy incorporates the contextualisation of implementation science for pharmacy.The study was funded as part of a University of Technology Sydney (UTS) Research Excellence Scholarship (RES), comprising of an Australian Postgraduate Award (APA) Scholarship funded by the Australian Government, plus a Top-up funded by the University of Technology Sydney, received from the primary author (JCM)

The barriers and facilitators influencing the sustainability of hospital-based interventions: a systematic review

Acknowledgements University of Stirling for providing financial support for open access costs Funding This review was funded by the Chief Scientist Office, grant number GCA/17/26. JC, PC and EAD are employed by the Nursing, Midwifery and Allied Health Professions Research Unit, which is funded by the Chief Scientist Office in Scotland.Peer reviewedPublisher PD

Comparative indoor and outdoor stability measurements of polymer based solar cells

We report comparative indoor and outdoor stability testing of organic solar cells based on a blend between a donor-acceptor polyfluorene copolymer and a fullerene derivative. The outdoor testing was conducted for a period over 12,000 hours in Sheffield, England, with a Ts80 lifetime determined in excess of 10,000 hours (420 days). Indoor lifetime testing was performed on solar cells using a solar simulator under a constant irradiance of 1000 W/m(2) for more than 650 hours. We show that under the conditions explored here, device degradation under the two sets of conditions is approximately dependent on the absorbed optical energy dose

Prestige Affects Cultural Learning in Chimpanzees

Humans follow the example of prestigious, high-status individuals much more readily than that of others, such as when we copy the behavior of village elders, community leaders, or celebrities. This tendency has been declared uniquely human, yet remains untested in other species. Experimental studies of animal learning have typically focused on the learning mechanism rather than on social issues, such as who learns from whom. The latter, however, is essential to understanding how habits spread. Here we report that when given opportunities to watch alternative solutions to a foraging problem performed by two different models of their own species, chimpanzees preferentially copy the method shown by the older, higher-ranking individual with a prior track-record of success. Since both solutions were equally difficult, shown an equal number of times by each model and resulted in equal rewards, we interpret this outcome as evidence that the preferred model in each of the two groups tested enjoyed a significant degree of prestige in terms of whose example other chimpanzees chose to follow. Such prestige-based cultural transmission is a phenomenon shared with our own species. If similar biases operate in wild animal populations, the adoption of culturally transmitted innovations may be significantly shaped by the characteristics of performers

Unplanned readmission rates, length of hospital stay, mortality, and medical costs of ten common medical conditions: a retrospective analysis of Hong Kong hospital data

<p>Abstract</p> <p>Background</p> <p>Studies on readmissions attributed to particular medical conditions, especially heart failure, have generally not addressed the factors associated with readmissions and the implications for health outcomes and costs. This study aimed to investigate the factors associated with 30-day unplanned readmission for 10 common conditions and to determine the cost implications.</p> <p>Methods</p> <p>This population-based retrospective cohort study included patients admitted to all public hospitals in Hong Kong in 2007. The sample consisted of 337,694 hospitalizations in Internal Medicine. The disease-specific risk-adjusted odd ratio (OR), length of stay (LOS), mortality and attributable medical costs for the year were examined for unplanned readmissions for 10 medical conditions, namely malignant neoplasms, heart diseases, cerebrovascular diseases, pneumonia, injury and poisoning, nephritis and nephrosis, diabetes mellitus, chronic liver disease and cirrhosis, septicaemia, and aortic aneurysm.</p> <p>Results</p> <p>The overall unplanned readmission rate was 16.7%. Chronic liver disease and cirrhosis had the highest OR (1.62, 95% confidence interval (CI) 1.39-1.87). Patients with cerebrovascular disease had the longest LOS, with mean acute and rehabilitation stays of 6.9 and 3.0 days, respectively. Malignant neoplasms had the highest mortality rate (30.8%) followed by aortic aneurysm and pneumonia. The attributed medical cost of readmission was highest for heart disease (US$3 199 418, 95$2 579 443-803 393).</p> <p>Conclusions</p> <p>Our findings showed variations in readmission rates and mortality for different medical conditions which may suggest differences in the quality of care provided for various medical conditions. In-hospital care, comprehensive discharge planning, and post-discharge community support for patients need to be reviewed to improve the quality of care and patient health outcomes.</p

Assessing the organizational context for EBP implementation: the development and validity testing of the Implementation Climate Scale (ICS)

BACKGROUND: Although the importance of the organizational environment for implementing evidence-based practices (EBP) has been widely recognized, there are limited options for measuring implementation climate in public sector health settings. The goal of this research was to develop and test a measure of EBP implementation climate that would both capture a broad range of issues important for effective EBP implementation and be of practical use to researchers and managers seeking to understand and improve the implementation of EBPs. METHODS: Participants were 630 clinicians working in 128 work groups in 32 US-based mental health agencies. Items to measure climate for EBP implementation were developed based on past literature on implementation climate and other strategic climates and in consultation with experts on the implementation of EBPs in mental health settings. The sample was randomly split at the work group level of analysis; half of the sample was used for exploratory factor analysis (EFA), and the other half was used for confirmatory factor analysis (CFA). The entire sample was utilized for additional analyses assessing the reliability, support for level of aggregation, and construct-based evidence of validity. RESULTS: The EFA resulted in a final factor structure of six dimensions for the Implementation Climate Scale (ICS): 1) focus on EBP, 2) educational support for EBP, 3) recognition for EBP, 4) rewards for EBP, 5) selection for EBP, and 6) selection for openness. This structure was supported in the other half of the sample using CFA. Additional analyses supported the reliability and construct-based evidence of validity for the ICS, as well as the aggregation of the measure to the work group level. CONCLUSIONS: The ICS is a very brief (18 item) and pragmatic measure of a strategic climate for EBP implementation. It captures six dimensions of the organizational context that indicate to employees the extent to which their organization prioritizes and values the successful implementation of EBPs. The ICS can be used by researchers to better understand the role of the organizational context on implementation outcomes and by organizations to evaluate their current climate as they consider how to improve the likelihood of implementation success. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13012-014-0157-1) contains supplementary material, which is available to authorized users