A novel liposomal drug delivery system for PMMA bone cements

The population in developed countries is ageing and the number of people experiencing joint-related conditions, such as osteoarthritis, is expected to increase. Joint replacements are currently the most effective treatment for severe joint conditions and although many of these procedures are successful, infection developing after the procedure is still an issue, requiring complex and expensive revisions. Whilst incorporating a powdered antibiotic within the bone cement can reduce infection rates, the powder frequently agglomerates, resulting in poor antibiotic release characteristics and compromised mechanical performance of the cement. To overcome these issues, a novel delivery system consisting of antibiotic-loaded nano-sized liposomes was developed for inclusion into polymethyl methacrylate (PMMA) bone cement. This system was tested in a commercial cement (Palacos R) and consistently delivered a higher percentage (22%) of the incorporated antibiotic when compared to the powdered antibiotic cement (9%), meaning less antibiotic needs to be incorporated than with conventional cement. The novel system resulted in a controlled and gradual release of antibiotic over a longer, 30-day period and enhanced the toughness, bending strength and Vickers hardness of the cement, without altering its polymerization or molecular structure. This new material has the potential to significantly reduce infections in cemented joint replacements leading to enhanced patient quality of life and reduced healthcare costs

A feasibility trial to examine the social norms approach for the prevention and reduction of licit and illicit drug use in European University and college students.

Background: Incorrect perceptions of high rates of peer alcohol and tobacco use are predictive of increased personal use in student populations. Correcting misperceptions by providing feedback has been shown to be an effective intervention for reducing licit drug use. It is currently unknown if social norms interventions are effective in preventing and reducing illicit drug use in European students. The purpose of this paper is to describe the design of a multi-site cluster controlled trial of a web-based social norms intervention aimed at reducing licit and preventing illicit drug use in European university students. Methods/Design: An online questionnaire to assess rates of drug use will be developed and translated based on existing social norms surveys. Students from sixteen universities in seven participating European countries will be invited to complete the questionnaire. Both intervention and control sites will be chosen by convenience. In each country, the intervention site will be the university that the local principal investigator is affiliated with. We aim to recruit 1000 students per site (baseline assessment). All participants will complete the online questionnaire at baseline. Baseline data will be used to develop social norms messages that will be included in a web-based intervention. The intervention group will receive individualized social norms feedback. The website will remain online during the following 5 months. After five months, a second survey will be conducted and effects of the intervention on social norms and drug use will be measured in comparison to the control site. Discussion: This project is the first cross-national European collaboration to investigate the feasibility of a social norms intervention to reduce licit and prevent illicit drug use among European university students. Final trial registration number DRKS00004375 on the ‘German Clinical Trials Register’.This study is funded by the European Commission, Directorate General Justice, Freedom and Security (JLS/2009-2010/DPIP/AG

AMPK and uterine artery vasodilation

Genes near adenosine monophosphate-activated protein kinase-α1 (PRKAA1) have been implicated in the greater uterine artery (UtA) blood flow and relative protection from fetal growth restriction seen in altitude-adapted Andean populations. Adenosine monophosphate-activated protein kinase (AMPK) activation vasodilates multiple vessels but whether AMPK is present in UtA or placental tissue and influences UtA vasoreactivity during normal or hypoxic pregnancy remains unknown. We studied isolated UtA and placenta from near-term C57BL/6J mice housed in normoxia (n = 8) or hypoxia (10% oxygen, n = 7-9) from day 14 to day 19, and placentas from non-labouring sea level (n = 3) or 3100 m (n = 3) women. Hypoxia increased AMPK immunostaining in near-term murine UtA and placental tissue. RT-PCR products for AMPK-α1 and -α2 isoforms and liver kinase B1 (LKB1; the upstream kinase activating AMPK) were present in murine and human placenta, and hypoxia increased LKB1 and AMPK-α1 and -α2 expression in the high- compared with low-altitude human placentas. Pharmacological AMPK activation by A769662 caused phenylephrine pre-constricted UtA from normoxic or hypoxic pregnant mice to dilate and this dilatation was partially reversed by the NOS inhibitor l-NAME. Hypoxic pregnancy sufficient to restrict fetal growth markedly augmented the UtA vasodilator effect of AMPK activation in opposition to PE constriction as the result of both NO-dependent and NO-independent mechanisms. We conclude that AMPK is activated during hypoxic pregnancy and that AMPK activation vasodilates the UtA, especially in hypoxic pregnancy. AMPK activation may be playing an adaptive role by limiting cellular energy depletion and helping to maintain utero-placental blood flow in hypoxic pregnancy.Funding for these studies was provided by the Wellcome Trust (084804/2/08/Z) to G.J.B., the British Heart Foundation and the Wellcome Trust to D.A.G., the Biotechnology and Biological Sciences Research Council (BBSRC) to A.L.F., a UK Wellcome Trust Programme Grant (WT081195MA) to A.M.E. and A.D.M., a BBSRC studentship and in vivo skills award to J.S.H., a National Health Medical Research Council and Centre for Trophoblast Research fellowship to A.N.S.-P., and a NIH RO1 grant (HLBI-079647) to L.G.M. along with sabbatical support from Wake Forest University.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1113/JP27099

The factor structure and psychometric properties of the Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM) in Norwegian clinical and non-clinical samples

Background The Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM) is a 34-item instrument developed to monitor clinically significant change in out-patients. The CORE-OM covers four domains: well-being, problems/symptoms, functioning and risk, and sums up in two total scores: the mean of All items, and the mean of All non-risk items. The aim of this study was to examine the psychometric properties of the Norwegian translation of the CORE-OM. Methods A clinical sample of 527 out-patients from North Norwegian specialist psychiatric services, and a non-clinical sample of 464 persons were obtained. The non-clinical sample was a convenience sample consisting of friends and family of health personnel, and of students of medicine and clinical psychology. Students also reported psychological stress. Exploratory factor analysis (EFA) was employed in half the clinical sample. Confirmatory (CFA) factor analyses modelling the theoretical sub-domains were performed in the remaining half of the clinical sample. Internal consistency, means, and gender and age differences were studied by comparing the clinical and non-clinical samples. Stability, effect of language (Norwegian versus English), and of psychological stress was studied in the sub-sample of students. Finally, cut-off scores were calculated, and distributions of scores were compared between clinical and non-clinical samples, and between students reporting stress or no stress. Results The results indicate that the CORE-OM both measures general (g) psychological distress and sub-domains, of which risk of harm separates most clearly from the g factor. Internal consistency, stability and cut-off scores compared well with the original English version. No, or only negligible, language effects were found. Gender differences were only found for the well-being domain in the non-clinical sample and for the risk domain in the clinical sample. Current patient status explained differences between clinical and non-clinical samples, also when gender and age were controlled for. Students reporting psychological distress during last week scored significantly higher than students reporting no stress. These results further validate the recommended cut-off point of 1 between clinical and non-clinical populations. Conclusions The CORE-OM in Norwegian has psychometric properties at the same level as the English original, and could be recommended for general clinical use. A cut-off point of 1 is recommended for both genders

Random Walks on Stochastic Temporal Networks

In the study of dynamical processes on networks, there has been intense focus on network structure -- i.e., the arrangement of edges and their associated weights -- but the effects of the temporal patterns of edges remains poorly understood. In this chapter, we develop a mathematical framework for random walks on temporal networks using an approach that provides a compromise between abstract but unrealistic models and data-driven but non-mathematical approaches. To do this, we introduce a stochastic model for temporal networks in which we summarize the temporal and structural organization of a system using a matrix of waiting-time distributions. We show that random walks on stochastic temporal networks can be described exactly by an integro-differential master equation and derive an analytical expression for its asymptotic steady state. We also discuss how our work might be useful to help build centrality measures for temporal networks.Comment: Chapter in Temporal Networks (Petter Holme and Jari Saramaki editors). Springer. Berlin, Heidelberg 2013. The book chapter contains minor corrections and modifications. This chapter is based on arXiv:1112.3324, which contains additional calculations and numerical simulation

Comparison of algorithms that detect drug side effects using electronic healthcare databases

The electronic healthcare databases are starting to become more readily available and are thought to have excellent potential for generating adverse drug reaction signals. The Health Improvement Network (THIN) database is an electronic healthcare database containing medical information on over 11 million patients that has excellent potential for detecting ADRs. In this paper we apply four existing electronic healthcare database signal detecting algorithms (MUTARA, HUNT, Temporal Pattern Discovery and modified ROR) on the THIN database for a selection of drugs from six chosen drug families. This is the first comparison of ADR signalling algorithms that includes MUTARA and HUNT and enabled us to set a benchmark for the adverse drug reaction signalling ability of the THIN database. The drugs were selectively chosen to enable a comparison with previous work and for variety. It was found that no algorithm was generally superior and the algorithms’ natural thresholds act at variable stringencies. Furthermore, none of the algorithms perform well at detecting rare ADRs

Measuring body composition in overweight individuals by dual energy x-ray absorptiometry

BACKGROUND: Dual energy x-ray absorptiometry (DXA) is widely used for body composition measurements in normal-weight and overweight/obese individuals. The limitations of bone densitometers have been frequently addressed. However, the possible errors in assessing body composition in overweight individuals due to incorrect positioning or limitations of DXA to accurately assess both bone mineral density and body composition in obese individuals have not received much attention and are the focus of this report. DISCUSSION: We discuss proper ways of measuring overweight individuals and point to some studies where that might not have been the case. It appears that currently, the most prudent approach to assess body composition of large individuals who cannot fit under the scanning area would be to estimate regional fat, namely the regions of thigh and/or abdomen. Additionally, using two-half body scans, although time consuming, may provide a relatively accurate measurement of total body fat, however, more studies using this technique are needed to validate it. SUMMARY: Researchers using bone densitometers for body composition measurements need to have an understanding of its limitations in overweight individuals and address them appropriately when interpreting their results. Studies on accuracy and precision in measurements of both bone and soft tissue composition in overweight individuals using available densitometers are needed

Impact of a parent-child sexual communication campaign: results from a controlled efficacy trial of parents

<p>Abstract</p> <p>Background</p> <p>Prior research supports the notion that parents have the ability to influence their children's decisions regarding sexual behavior. Yet parent-based approaches to curbing teen pregnancy and STDs have been relatively unexplored. The Parents Speak Up National Campaign (PSUNC) is a multimedia campaign that attempts to fill this void by targeting parents of teens to encourage parent-child communication about waiting to have sex. The campaign follows a theoretical framework that identifies cognitions that are targeted in campaign messages and theorized to influence parent-child communication. While a previous experimental study showed PSUNC messages to be effective in increasing parent-child communication, it did not address how these effects manifest through the PSUNC theoretical framework. The current study examines the PSUNC theoretical framework by 1) estimating the impact of PSUNC on specific cognitions identified in the theoretical framework and 2) examining whether those cognitions are indeed associated with parent-child communication</p> <p>Methods</p> <p>Our study consists of a randomized efficacy trial of PSUNC messages under controlled conditions. A sample of 1,969 parents was randomly assigned to treatment (PSUNC exposure) and control (no exposure) conditions. Parents were surveyed at baseline, 4 weeks, 6 months, 12 months, and 18 months post-baseline. Linear regression procedures were used in our analyses. Outcome variables included self-efficacy to communicate with child, long-term outcome expectations that communication would be successful, and norms on appropriate age for sexual initiation. We first estimated multivariable models to test whether these cognitive variables predict parent-child communication longitudinally. Longitudinal change in each cognitive variable was then estimated as a function of treatment condition, controlling for baseline individual characteristics.</p> <p>Results</p> <p>Norms related to appropriate age for sexual initiation and outcome expectations that communication would be successful were predictive of parent-child communication among both mothers and fathers. Treatment condition mothers exhibited larger changes than control mothers in both of these cognitive variables. Fathers exhibited no exposure effects.</p> <p>Conclusions</p> <p>Results suggest that within a controlled setting, the "wait until older norm" and long-term outcome expectations were appropriate cognitions to target and the PSUNC media materials were successful in impacting them, particularly among mothers. This study highlights the importance of theoretical frameworks for parent-focused campaigns that identify appropriate behavioral precursors that are both predictive of a campaign's distal behavioral outcome and sensitive to campaign messages.</p