Increased potential of a cationic liposome-based delivery system:enhancing stability and sustained immunological activity in pre-clinical development

The combination of dimethyl dioctadecyl ammonium bromide (DDA) and the synthetic cord factor trehalose dibehenate (TDB) with Ag85B-ESAT-6 (H1 fusion protein) has been found to promote strong protective immune responses against Mycobacterium tuberculosis. The development of a vaccine formulation that is able to facilitate the requirements of sterility, stability and generation of a vaccine product with acceptable composition, shelf-life and safety profile may necessitate selected alterations in vaccine formulation. This study describes the implementation of a sterilisation protocol and the use of selected lyoprotective agents in order to fulfil these requirements. Concomitantly, close analysis of any alteration in physico-chemical characteristics and parameters of immunogenicity have been examined for this promising DDA liposome-based tuberculosis vaccine. The study addresses the extensive guidelines on parameters for non-clinical assessment, suitable for liposomal vaccines and other vaccine delivery systems issued by the World Health Organisation (WHO) and the European Medicines Agency (EMEA). Physical and chemical stability was observed following alteration in formulations to include novel cryoprotectants and radiation sterilisation. Immunogenicity was maintained following these alterations and even improved by modification with lysine as the cryoprotective agent for sterilised formulations. Taken together, these results outline the successful alteration to a liposomal vaccine, representing improved formulations by rational modification, whilst maintaining biological activity.

An analysis of the effectiveness of a behavioural based safety intervention in a UK paper mill

This research examines a behavioural based safety (BBS) intervention within a paper mill in the South East of England. Further to this intervention two other mills are examined for the purposes of comparison — one an established BBS programme and the other an improving safety management system through management ownership. BBS programmes have become popular within the UK, but most of the research about their efficacy is carried out by the BBS providers themselves. This thesis aims to evaluate a BBS intervention from a standpoint which is not commercially biased in favour of BBS schemes. The aim of a BBS scheme is to either change personnel behaviours or attitudes, which in turn will positively affect the organisation's safety culture. The research framework involved a qualitative methodology in order to examine the effects of the intervention on the paper mill's safety culture. The techniques used were questionnaires and semi structured interviews, in addition to observation and discussions which were possible because of the author's position as participant observer. The results demonstrated a failure to improve any aspect of the mill's safety culture, which worsened following the BBS intervention. Issues such as trust, morale, communication and support of management showed significant signs of negative workforce response. The paper mill where the safety management system approach was utilised demonstrated a significantly improved safety culture and achieved site ownership from middle managers and supervisors. Research has demonstrated that a solid foundation is required prior to successfully implementing a BBS programme. For a programme to work there must be middle management support in addition to senior management commitment. If a trade union actively distances itself from BBS, it is also unlikely to be effective. This thesis proposes that BBS observation programmes are not suitable for the papermaking industry, particularly when staffing levels are low due to challenging economic conditions. Observers are not available when there are high hazard situations and this suggests that BBS implementation is not the correct intervention for the paper industry.

Organic synthesis and fungicidal activity of oxylipin-based compounds

Previous research has shown that the naturally occurring reactive electrophilic species (RES), 12-oxophytodienoic acid (OPDA), not only serves as a precursor for jasmonic acid but is also a potent antifungal compound. However, both the low amount present in plants and the multistep synthesis required to produce this compound on a scale viable for agrochemical use currently limits its practical value. The aim of this research was to generate a range of molecular mimics of OPDA with a minimum number of synthetic steps and screen for antifungal activity. Synthetic 4-octyl-cyclopentenone containing the cyclopentenone ring and an eight carbon alkyl chain was found to show the highest in vitro antifungal activity against C. herbarum and B. cinerea with minimum inhibition concentration (MIC) of 100-200µM. This indicates that structurally simplified 4-octyl-cyclopentenone can be successfully synthesised to mimic the antifungal activity of OPDA against specific fungal strains. Application of 4-octyl-cyclopentenone could act as surfactant by disrupting and disorganising the lipid membrane non-specifically, resulting in the leakage of potassium ions, which was the proposed mode of action of this compound. However, the sensitivity of fungi to this compound is not correlated to the lipid composition of fungal spores. (E)-2-alkenals were also studied for their antimicrobial activity and (E)-2-undecenal was found to have the highest antimicrobial activity against a range of pathogens. The hydrophilic moiety (the a,ß-unsaturated carbonyl group), common to both (E)-2-undecenal and 4-octyl-cyclentenone is essential to their bioactivity, and the hydrophobic moiety plays an important role in their antimicrobial activities. 4-Octyl-cyclopentenone showed no visible toxicity to the test plant, Arabidopsis thaliana, suggesting that its high antifungal activity against Botrytis and Cladosporium could be exploited for commercialisation as a new generation of agrochemical.

Imidazolium-based warheads strongly influence activity of water-soluble peptidic transglutaminase inhibitors

New peptidic water-soluble inhibitors are reported. In addition to the carboxylate moiety, a new polar warhead was explored. Depending on the size of its substituents, the newly appended imidazolium scaffold designed to enhance the hydrophilic character of the inhibitors could induce a good inhibition for tissue transglutaminase (TG2) and blood coagulation factor XIIIa (FXIIIa). Correlated with the narrow tunnel that hosts the target catalytic cysteine residue, the various modulations suggest a bent conformation of the ligands as the binding pattern mode. Analogues in the dialkylsulfonium series were also tested and showed specificity for TG2 over FXIIIa. © 2013 Elsevier Masson SAS. All rights reserved.

Is pregnancy a teachable moment for diet and physical activity behaviour change? An interpretative phenomenological analysis of the experiences of women during their first pregnancy

OBJECTIVES: Pregnancy may provide a 'teachable moment' for positive health behaviour change, as a time when women are both motivated towards health and in regular contact with health care professionals. This study aimed to investigate whether women's experiences of pregnancy indicate that they would be receptive to behaviour change during this period. DESIGN: Qualitative interview study. METHODS: Using interpretative phenomenological analysis, this study details how seven women made decisions about their physical activity and dietary behaviour during their first pregnancy. RESULTS: Two women had required fertility treatment to conceive. Their behaviour was driven by anxiety and a drive to minimize potential risks to the pregnancy. This included detailed information seeking and strict adherence to diet and physical activity recommendations. However, the majority of women described behaviour change as 'automatic', adopting a new lifestyle immediately upon discovering their pregnancy. Diet and physical activity were influenced by what these women perceived to be normal or acceptable during pregnancy (largely based on observations of others) and internal drivers, including bodily signals and a desire to retain some of their pre-pregnancy self-identity. More reasoned assessments regarding benefits for them and their baby were less prevalent and influential. CONCLUSIONS: Findings suggest that for women who conceived relatively easily, diet and physical activity behaviour during pregnancy is primarily based upon a combination of automatic judgements, physical sensations, and perceptions of what pregnant women are supposed to do. Health professionals and other credible sources appear to exert less influence. As such, pregnancy alone may not create a 'teachable moment'. Statement of contribution What is already known on this subject? Significant life events can be cues to action with relation to health behaviour change. However, much of the empirical research in this area has focused on negative health experiences such as receiving a false-positive screening result and hospitalization, and in relation to unequivocally negative behaviours such as smoking. It is often suggested that pregnancy, as a major life event, is a 'teachable moment' (TM) for lifestyle behaviour change due to an increase in motivation towards health and regular contact with health professionals. However, there is limited evidence for the utility of the TM model in predicting or promoting behaviour change. What does this study add? Two groups of women emerged from our study: the women who had experienced difficulties in conceiving and had received fertility treatment, and those who had conceived without intervention. The former group's experience of pregnancy was characterized by a sense of vulnerability and anxiety over sustaining the pregnancy which influenced every choice they made about their diet and physical activity. For the latter group, decisions about diet and physical activity were made immediately upon discovering their pregnancy, based upon a combination of automatic judgements, physical sensations, and perceptions of what is normal or 'good' for pregnancy. Among women with relatively trouble-free conception and pregnancy experiences, the necessary conditions may not be present to create a 'teachable moment'. This is due to a combination of a reliance on non-reflective decision-making, perception of low risk, and little change in affective response or self-concept.

A projektalapú szervezetek projektmarketing-tevékenységének sajátos kontextusa (Contextual features of project marketing activity of the project-based organisations)

Ez a tanulmány a projektvezetési szakirodalomban kialakult ismeretanyagot szem előtt tartva (noha tételesen nem hivatkozva arra) tárja fel azt a sajátos és tipikusnak nevezhető kontextust, amelyben a projektalapú szervezetek projektmarketing tevékenysége megnyilvánul. A tanulmány célja tehát nem magának a projektmarketingnek a kérdéskörére irányul, hanem elsősorban annak projektspecifikus kontextusára. Jellegét illetően a tanulmány spekulatív jellegű, vagyis lényegét tekintve nem empirikus kutatási eredményekből levont következtetésekre épül. _____ Traditional approach to project marketing focuses on process-related aspects of the marketing efforts of project- based organisations. This paper is different. Unlike to the traditional approach it highlights the decisive contextual features of project marketing, bearing in mind the typical project business from the point of view of project-based organisations. These features include: a) instead of physically existing products project-based organisations need to sell their ability to create the project outcome physically; b) the project outcome and the conditions of implementation are defined by the project client; c) project clients are involved in creating the project outcome; d) project implementation strategy applied in a client organisation may vary project by project. These determining contextual features shape to a great extent the actual competitive position of the project-based organisations which may vary project by project even in relation to the very same project client.

The effects of a family-based educational intervention on the prevention of lead poisoning in children

The effects of lead exposure may endure through one's lifetime and can negatively effect educational performance. While the link between the cause and effects of lead poisoning has been identified, the application of lead health education as the mechanism of disease prevention has not. The purpose of this study was to examine whether caregiver participation in a family-based educational intervention can result in decreased lead exposure in low socioeconomic children. ^ Participants (n = 50) were caregivers of children 12 to 36 months of age. They were randomly selected from an urban clinic and randomly assigned to either a treatment or control group. The experimental design of this study involved two clinic visits. Parents in the treatment group were given the educational intervention during the first clinic visit while those in the control group were given the intervention during the second clinic visit. The intervention was reinforced with a lead education brochure coupled with a video on childhood lead poisoning. One instrument was used to test parental knowledge of lead poisoning both pre- and post-intervention. Blood lead levels in pediatric participants were tested using two blood lead screens approximately three to four months apart determined by well-child check-up schedules. ^ Findings from the analysis of variance showed the interaction between the change in blood lead level between the children's first and second clinic visits and the treatment level. This demonstrated a significant interaction between the differences of first and second clinic visits blood lead levels and the presence or absence of the educational intervention. ^ The findings from an analysis of covariance support that caregivers in the treatment group have significantly higher scores on the second clinic visit scores on the CLKT than the caregivers in the control group. These data suggest that the educational treatment is effective in increasing the knowledge of caregivers about the dangers of lead poisoning and the strategies for lead poisoning prevention. ^ Conclusions indicate that the education of adult caregivers can affect blood lead levels of children, the educational treatment increased the knowledge of caregivers, caregivers were able to carry out procedures taught, and caregivers retained knowledge over time. ^

The Effects of a Family-Based Educational Intervention on the Prevention of Lead Poisoning in Children

Parents completed a survey measuring their knowledge of lead poisoning. Children, 24 to 36 months old received two blood lead level screens. Parents in the treatment group showed significantly higher scores on the posttest, and their children showed greater decreased blood lead levels than participants in the control group.

A Systematic Review of Internet-Based Worksite Wellness Approaches for Cardiovascular Disease Risk Management: Outcomes, Challenges & Opportunities

Context The internet is gaining popularity as a means of delivering employee-based cardiovascular (CV) wellness interventions though little is known about the cardiovascular health outcomes of these programs. In this review, we examined the effectiveness of internet-based employee cardiovascular wellness and prevention programs. Evidence Acquisition We conducted a systematic review by searching PubMed, Web of Science and Cochrane library for all published studies on internet-based programs aimed at improving CV health among employees up to November 2012. We grouped the outcomes according to the American Heart Association (AHA) indicators of cardiovascular wellbeing – weight, BP, lipids, smoking, physical activity, diet, and blood glucose. Evidence Synthesis A total of 18 randomized trials and 11 follow-up studies met our inclusion/exclusion criteria. Follow-up duration ranged from 6 – 24 months. There were significant differences in intervention types and number of components in each intervention. Modest improvements were observed in more than half of the studies with weight related outcomes while no improvement was seen in virtually all the studies with physical activity outcome. In general, internet-based programs were more successful if the interventions also included some physical contact and environmental modification, and if they were targeted at specific disease entities such as hypertension. Only a few of the studies were conducted in persons at-risk for CVD, none in blue-collar workers or low-income earners. Conclusion Internet based programs hold promise for improving the cardiovascular wellness among employees however much work is required to fully understand its utility and long term impact especially in special/at-risk populations.

A theory-informed approach to developing visually mediated interventions to change behaviour using an asthma and physical activity intervention exemplar

Funding for this study was received from the Chief Scientist Office for Scotland. We would like to thank Asthma UK and Asthma UK Scotland for facilitating the advertisement of the study pilot and consultative user group. Thanks to Dr Mark Grindle for his helpful discussions concerning narrative. Thanks also to Mr Mark Haldane who designed the characters, backgrounds, and user interface used within the 3D computer animation. Particular thanks to the participants of the consultative user group for their enthusiasm, comments, and suggestions at all stages of the intervention design.

The feasibility and acceptability of trial procedures for a pragmatic randomised controlled trial of a structured physical activity intervention for people diagnosed with colorectal cancer : findings from a pilot trial of cardiac rehabilitation versus usual care (no rehabilitation) with an embedded qualitative study

Funding This work is supported by the National Institute for Health Research—Health Service and Development Research, Project reference number: NIHR—HS&DR Project:12/5001/09.

The Physical Activity 4 Everyone Cluster Randomized Trial : 2-Year Outcomes of a School Physical Activity Intervention Among Adolescents

Acknowledgments The Physical Activity 4 Everyone intervention trial was funded by the New South Wales Ministry of Health through the New South Wales Health Promotion Demonstration Research Grants Scheme and conducted by Hunter New England Population Health (a unit of the Hunter New England Local Health District), in collaboration with the University of Newcastle and University of Wollongong. Infrastructure support was provided by Hunter Medical Research Institute. The research team acknowledges the importance of making research data publically available. Access to the accelerometer data from this study may be made available to external collaborators following the development of data transfer agreements. Further results arising from the study can be found at www.goodforkids.nsw.gov.au/high-schools/.