Molecular investigations into vaginal immunization with HIV gp41 antigenic construct H4A in a quick release solid dosage form

A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential. In the current study, we explored for the first time the use of a quick release, freeze-dried, solid dosage system for practical vaginal administration of a protein antigen. These solid dosage forms overcome the common problem associated with leakage and poor retention of vaginally administered antigen solutions. Mice were immunized vaginally with H4A, an HIV gp41 envelope based recombinant protein, using quick release, freeze-dried solid rods, and the immune responses compared to a control group immunized via subcutaneous H4A injection. Vaginally immunized mice failed to elicit robust immune responses. Our detailed investigations, involving cytokine analysis, the stability of H4A in mouse cervicovaginal lavage, and elucidation of the state of H4A protein in the immediate-release dosage form, revealed that antigen instability in vaginal fluid, the state of the antigen in the dosage form, and the cytokine profile induced are all likely to have contributed to the observed lack of immunogenicity. These are important factors affecting vaginal immunization and provide a rational basis for explaining the typically poor and variable elicitation of immunity at this site, despite the presence of immune responsive cells within the vaginal mucosae. In future mucosal vaccine studies, a more explicit focus on antigen stability in the dosage form and the immune potential of available antigen-responsive cells is recommended.

Evaluation of the quality and promotion of open learning materials

In the UK, Open Learning has been used in industrial training for at least the last decade. Trainers and Open Learning practitioners have been concerned about the quality of the products and services being delivered. The argument put forward in this thesis is that there is ambiguity amongst industrialists over the meanings of `Open Learning' and `Quality in Open Learning'. For clarity, a new definition of Open Learning is proposed which challenges the traditional learner-centred approach favoured by educationalists. It introduces the concept that there are benefits afforded to the trainer/employer/teacher as well as to the learner. This enables a focussed view of what quality in Open Learning really means. Having discussed these issues, a new quantitative method of evaluating Open Learning is proposed. This is based upon an assessment of the degree of compliance with which products meet Parts 1 & 2 of the Open Learning Code of Practice. The vehicle for these research studies has been a commercial contract commissioned by the Training Agency for the Engineering Industry Training Board (EITB) to examine the quality of Open Learning products supplied to the engineering industry. A major part of this research has been the application of the evaluation technique to a range of 67 Open Learning products (in eight subject areas). The findings were that good quality products can be found right across the price range - so can average and poor quality ones. The study also shows quite convincingly that there are good quality products to be found at less than 50. Finally the majority (24 out of 34) of the good quality products were text based.

An evaluation of the effectiveness of intervention strategies for the promotion of health and safety performance in small firms

Recognition of the contribution of small firms to the UK economy has grown considerably since 1995 when this research first began. The poor record of small firms in managing health and safety effectively has caused concern, and efforts made to improve knowledge and awareness of the target group through various initiatives have had some success. This research thesis attempts to identify the range of intervention routes and methods available to reach the target group, and to consider ways of evaluating the outcome of such efforts. Various interventions were tested with small firms, including a Workshop; use of Questionnaires; short postal Reply Slip survey; leading to a closer evaluation of a specific industry- the Licensed Trade. Attitudes and beliefs of the sample were identified, and observations carried out to consider actions taken by workers and others in the workplace. These empirical research findings were used to develop the theme of Primary and Secondary interventions intended to change behaviours, and to confirm assumptions about what small firms currently do to manage health and safety risks. Guidance for small firms was developed as a Secondary intervention tool to support Primary interventions, such as inspection or insurance provision.

Logics, thresholds, strategic power, and the promotion of liberalisation by governments: a case study from British Higher Education

Liberalisation has become an increasingly important policy trend, both in the private and public sectors of advanced industrial economies. This article eschews deterministic accounts of liberalisation by considering why government attempts to institute competition may be successful in some cases and not others. It considers the relative strength of explanations focusing on the institutional context, and on the volume and power of sectoral actors supporting liberalisation. These approaches are applied to two attempts to liberalise, one successful and one unsuccessful, within one sector in one nation – higher education in Britain. Each explanation is seen to have some explanatory power, but none is sufficient to explain why competition was generalised in the one case and not the other. The article counsels the need for scholars of liberalisation to be open to multiple explanations which may require the marshalling of multiple sources and types of evidence.

Role of the transgenic human thyrotropin receptor A-subunit in thyroiditis induced by A-subunit immunization and regulatory T cell depletion

Transgenic BALB/c mice that express intrathyroidal human thyroid stimulating hormone receptor (TSHR) A-subunit, unlike wild-type (WT) littermates, develop thyroid lymphocytic infiltration and spreading to other thyroid autoantigens after T regulatory cell (Treg) depletion and immunization with human thyrotropin receptor (hTSHR) adenovirus. To determine if this process involves intramolecular epitope spreading, we studied antibody and T cell recognition of TSHR ectodomain peptides (A–Z). In transgenic and WT mice, regardless of Treg depletion, TSHR antibodies bound predominantly to N-terminal peptide A and much less to a few downstream peptides. After Treg depletion, splenocytes from WT mice responded to peptides C, D and J (all in the A-subunit), but transgenic splenocytes recognized only peptide D. Because CD4+ T cells are critical for thyroid lymphocytic infiltration, amino acid sequences of these peptides were examined for in silico binding to BALB/c major histocompatibility complex class II (IA–d). High affinity subsequences (inhibitory concentration of 50% < 50 nm) are present in peptides C and D (not J) of the hTSHR and mouse TSHR equivalents. These data probably explain why transgenic splenocytes do not recognize peptide J. Mouse TSHR mRNA levels are comparable in transgenic and WT thyroids, but only transgenics have human A-subunit mRNA. Transgenic mice can present mouse TSHR and human A-subunit-derived peptides. However, WT mice can present only mouse TSHR, and two to four amino acid species differences may preclude recognition by CD4+ T cells activated by hTSHR-adenovirus. Overall, thyroid lymphocytic infiltration in the transgenic mice is unrelated to epitopic spreading but involves human A-subunit peptides for recognition by T cells activated using the hTSHR.

Health promotion for chronic obstructive pulmonary disease

Peter, a 45 year old male, enters the pharmacy and asks, 'do you have something to stop a cough?' On questioning you find out that Peter has an irritating cough that has been off and on for the past few weeks since winter started. He coughs up phlegm every now and then, mostly upon waking. He has tried some cough mixture that he bought at the supermarket but is looking for something stronger. He states that he does not have any medical history or allergies and does not take any medication. He does feel that he can't exercise as much as he used to as he gets more breathless these days.

Interactive online health promotion interventions : a “health check”

As an increasingly popular medium by which to access health promotion information, the Internet offers significant potential to promote (often individualized) health-related behavioral change across broad populations. Interactive online health promotion interventions are a key means, therefore, by which to empower individuals to make important well being and treatment decisions. But how ldquohealthyrdquo are interactive online health promotion interventions? This paper discusses a literature review (or ldquohealth checkrdquo) of interactive online health interventions. It highlights the types of interactive interventions currently available and identifies areas in which research attention is needed in order to take full advantage for the Internet for effective health promotion.

Decomposing the sales promotion bump accounting for cross-category effects

Extant research on the decomposition of unit sales bumps due to price promotions considers these effects only within a single product category. This article introduces a framework that accommodates specific cross-category effects. Empirical results based on daily data measured at the item/SKU level show that the effects of promotions on sales in other categories are modest. Between-category complementary effects (20%) are, on average, substantially larger than between-category substitution effects (11%). Hence, a promotion of an item has an average net spin-off effect of (20 - 11 =) 9% of its own effect. The number of significant cross-category effects is low, which means that we expect that, most of the time, it is sufficient to look at within-category effects only. We also find within-category complementary effects, which implies that competitive items within the category may benefit from a promotion. We find small stockpiling effects (6%), modest cross-item effects (22%), and substantial category-expansion effects (72%). The cross-item effects are the result of cross-item substitution effects within the category (26%) and within-category complementary effects (4%). Approximately 15% (= 11% / 72%) of the category-expansion effect is due to between-category substitution effects of dependent categories.

Interactive online health promotion interventions:a “health check”

As an increasingly popular medium by which to access health promotion information, the Internet offers significant potential to promote (often individualized) health-related behavioral change across broad populations. Interactive online health promotion interventions are a key means, therefore, by which to empower individuals to make important well being and treatment decisions. But how ldquohealthyrdquo are interactive online health promotion interventions? This paper discusses a literature review (or ldquohealth checkrdquo) of interactive online health interventions. It highlights the types of interactive interventions currently available and identifies areas in which research attention is needed in order to take full advantage for the Internet for effective health promotion.

Context matters:combined influence of participation and intellectual stimulation on the promotion-focus/employee creativity relationship

In this paper, we examined the interactive effects of two contexts—participation and intellectual stimulation, and promotion focus on creativity. On the basis of a multi-organization sample of 213 employees, we tested and found that although promotion focus was positively related to creativity, the relationship between promotion focus and creativity was most positive when both participation and leader intellectual stimulation were high. We discuss the way contexts in combination influence employee creativity for promotion-oriented individuals, through increasing decision latitude as well as stimulating and promoting creativity. Copyright © 2011 John Wiley & Sons, Ltd.

Study of the potential role of the community pharmacist in health promotion

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Sulphate-promotion and structure-sensitivity in hydrocarbon combustion over Rh2/AlO3 catalysts

A series of Rh2/AlO3 catalysts have been prepared using untreated or pre-sulphated alumina supports. The effect of support sulphation on catalyst activity towards propene and propane combustion has been explored as a function of Rh loading. Light-off temperatures for the total oxidation of both hydrocarbons decrease with increasing Rh content, associated with a transition from small oxidic clusters to large metallic Rh particles. Sulphate promotes both propene and propane combustion equally, with the magnitude of promotion exhibiting only a weak loading dependence. Enhanced catalytic performance is accompanied by Rh reduction and sintering. © 2006 Elsevier B.V. All rights reserved.

Effect of Cu and Sn promotion on the catalytic deoxygenation of model and algal lipids to fuel-like hydrocarbons over supported Ni catalysts

The ability of Cu and Sn to promote the performance of a 20% Ni/Al2O3 catalyst in the deoxygenation of lipids to fuel-like hydrocarbons was investigated using model triglyceride and fatty acid feeds, as well as algal lipids. In the semi-batch deoxygenation of tristearin at 260 °C a pronounced promotional effect was observed, a 20% Ni-5% Cu/Al2O3 catalyst affording both higher conversion (97%) and selectivity to C10-C17 alkanes (99%) in comparison with unpromoted 20% Ni/Al2O3 (27% conversion and 87% selectivity to C10-C17). In the same reaction at 350 °C, a 20% Ni-1% Sn/Al2O3 catalyst afforded the best results, giving yields of C10-C17 and C17 of 97% and 55%, respectively, which contrasts with the corresponding values of 87 and 21% obtained over 20% Ni/Al2O3. Equally encouraging results were obtained in the semi-batch deoxygenation of stearic acid at 300 °C, in which the 20% Ni-5% Cu/Al2O3 catalyst afforded the highest yields of C10-C17 and C17. Experiments were also conducted at 260 °C in a fixed bed reactor using triolein − a model unsaturated triglyceride − as the feed. While both 20% Ni/Al2O3 and 20% Ni-5% Cu/Al2O3 achieved quantitative yields of diesel-like hydrocarbons at all reaction times sampled, the Cu-promoted catalyst exhibited higher selectivity to longer chain hydrocarbons, a phenomenon which was also observed in experiments involving algal lipids as the feed. Characterization of fresh and spent catalysts indicates that Cu enhances the reducibility of Ni and suppresses both cracking reactions and coke-induced deactivation.