Synthetic nanoparticle-based vaccines against respiratory pathogens

Avian influenza A H5N1 is rapidly gaining the potential to be the next influenza pandemic threat. Human cases of H5N1 have proven to be approximately 60% fatal with a growing number of strains becoming resistant to antiviral treatments. Therefore, there is a strong need for new research to develop a pandemic H5N1 avian influenza vaccine. In this work, a synthetic polyanhydride nanoparticle-based vaccine (or nanovaccine) platform for respiratory pathogens such as H5N1 was designed. In particular, the work focused on the design of a subunit vaccine based on antigens specific to H5N1 avian influenza. Intranasal administration of vaccines can increase the availability of antigens due to the large, permeable surface area of the lung and can avoid the harsh environments of the gastrointestinal tract. Despite these advantages, antigen delivered alone is often not immunogenic and requires the use of an adjuvant. Polyanhydride nanoparticles have been shown to be a promising platform for intranasal immunization with many beneficial properties including sustained release, cell internalization, and immunomodulation, which may be suitable for vaccines against respiratory pathogens such as H5N1 avian influenza. The deposition and persistence of intranasally delivered nanovaccines at early time points was investigated with an eye towards examining the role of the initial fate of these particles on the induction of long-lasting memory responses and protective immunity. Polyanhydride nanoparticles were found to prolong the presence of antigen up to 63 days post-immunization leading to an enhancement of antibody titer, avidity, and epitope specificity. Furthermore, the long-lasting memory responses of particle-based vaccines were examined by utilizing an adoptive transfer model of antigen-specific CD8+ T cells and a model antigen (ovalbumin). Polyanhydride nanovaccines were shown to enhance the development of memory T cells capable of responding to challenge. Next, the stability and release kinetics of a nanoparticle-encapsulated H5 hemagglutinin trimer (H53) were investigated to rationally determine the optimal polyanhydride chemistries suitable for protein stabilization. Results suggested that while several polyanhydride chemistries preserved the antigenicity of H53 upon release, formulations that provided a mildly acidic microenvironment enhanced structural stability. The insights gained from these studies were utilized to identify a lead candidate nanovaccine based on H53. The lead candidate nanovaccine was tested using in vivo experiments in a rodent model to define the immune response and it was observed that the nanovaccine formulation induced virus neutralizing titers as well as enhanced CD4+ T cell responses. Finally, the efficacy of the nanovaccine was evaluated with live viral challenge and demonstrated full protection. Together, the studies described herein indicate that polyanhydride nanovaccines represent a promising platform for a next generation vaccine against H5N1 avian influenza

The interaction of continuing professional development and identity : the experiences of women professional accountants in Canada

PhD ThesisContinuing professional development (CPD) is a requirement for accountants to maintain their professional designation, ideally it may be used to assist in progression within the field; yet there is very little research on CPD for accountants and research that has focused on the interaction of experiences and identity is particularly scarce. This thesis, underpinned by a feminist view, undertook an interpretive analysis of oral history interviews provided by sixteen women in British Columbia. This study found that CPD, rather than assisting in building the professional identity and improving a professional’s standing, may work to maintain the status quo in the accounting field and retain the gendered hierarchy within the accounting profession. The study provides further support to indicate that professional identity both influences, and is influenced by, other identities and further explores the differences between identity, habitus and roles. Capitals available to women that should aid in their progression in the accounting field are dependent both on their place within the accounting field itself and their position in other fields; the need for capitals goes beyond what is necessary within the field itself as the interaction with other identities and other fields plays an important role in the quest for, as well as successful utilization of capitals. The need for capitals is also affected by an accounting field that is not homogenous and heterogeneous subfields are influential in identification of successful capitals. The manner in which CPD is used relates to a professional’s place within the field, with those already near the top of the field focusing more on social capitals and those nearer the middle or bottom of the field focusing on the cultural capitals provided. The structured and structuring aspects of CPD work within the professional accounting field to maintain the gendered and hierarchal nature of the field

A Woman's Place: The Cuban Revolution and Gender Inequality in the Home

iv, 100 leaves ; 29 cm. Includes bibliographical references (leaves 93-100).This thesis is an empirical study of changes in Cuban women's public and private lives from the 1959 Revolution to 1990. It describes the colonial gender ideology that has influenced present-day male and female relations, behaviors, and gender roles, and has perpetuated sexual stereotypes. It also discusses how this ideology has prevented women's full equality in the home and gives examples from interviews, films, and literature to show where these inequalities in the home are still evident. The interviews, films, and literature utilized in this study represent both Cuban and North American perceptions of women's status in Cuban society and in the home. In using these sources, the author is able to examine Cuban women's postrevolutionary roles, relations, and experiences in the most balanced way possible without first-hand travel to Cuba. The author includes Cuban women's (and a few men's) voices as much as possible through the use of previously conducted interviews. This study concludes that Cuban gender inequality still exists in both the public and the private spheres, though more acutely in the private, and that this is the result primarily of the perpetuation of Spanish gender ideology. This ideology has placed women in a subordinate position vis-a-vis men and has assigned men and women unequal roles in society and the home. Women traditionally have been associated with la casa (the home) and men with la calle (the street), which has made it difficult for women to escape their domestic obligations

Dietitians’ perceptions and experience of blenderised feeds for paediatric tube-feeding

Objective: There is an emerging interest in the use of blenderised food for tube-feeding (BFTF). This survey explored paediatric dietitians' perceptions and experiences of BFTF use. Design: A web-based questionnaire was distributed to the Paediatric group of the British Dietetic Association. The survey captured dietitians' personal opinions and experience supporting children on BFTF, and the perceptions of carers. Results: Of the 77 respondents, 19 were aware of professional guidelines and 63 had never received training on BFTF. Thirty-four would not recommend BFTF and 11 would advise against its use; yet 43 would recommend it to supplement commercial feeds. Fifty-seven would change their perception about BFTF if there were evidence-based guidelines. Forty-four would feel confident to support a patient using BFTF. Forty-three had previous experience supporting a patient with BFTF. The main concerns perceived by dietitians, pertinent to the use of BFTF, were nutritional inadequacy (n=71), tube blockages (n=64) and increased infection risk (n=59) but these were significantly higher than those experienced by themselves in clinical practice (p<0.001 for all three). A reduction in reflux and vomiting and increased carer involvement were the main perceived and observed benefits by both dietitians and carers. Conclusions: The use of these feeds for tube-fed children is increasingly being seen as a viable choice. Dietitians experienced significantly fewer issues with the use of BFTF in clinical practice compared with their self-reported apprehensions in the survey. Well-controlled studies are now needed to objectively assess the benefits, risks, costs and practicality of BFTF

Bullous hemorrhagic lichen sclerosus of the breast: a report of two cases and review of the literature

Lichen sclerosus (LS) is a chronic dermatologic condition characterized by atrophic porcelain-appearing plaques that can cause intense discomfort and eventually lead to destruction of local architecture. Lichen sclerosus most commonly arises in the anogenital area, but up to 20% of cases can present on extragenital skin. Rarely, LS can also present with hemorrhage and bullae; the mechanism by which this occurs is unknown. We report two cases of bullous hemorrhagic LS of the breast arising in 66-year-old and 77-year-old women. Bullous hemorrhagic LS of the breast is exceedingly rare, with few reported cases, and presents a diagnostic challenge to clinicians

Deciding what kind of course to take: Factors that influence modality selection in accounting continuing professional development

This study used a cross sectional sample created by self-selection from a researchers' email invitation to accountants in Canada to determine which modalities accountants preferred when selecting Continuing Professional Development (CPD), and the selection factors they used in making those choices. The survey contacted 32,000 accountants in Canada and a total of 428 accountants from across Canada completed the online survey. Live seminars and live webinars were the highest ranked and accountants preferred synchronous over asynchronous courses. The factors most important to accountants are content, cost and CPD hour requirements. The ranking of selection factors for synchronous courses in general did not differ from those for asynchronous courses with the exception of self-paced courses where the selection factors of “pace” and “time away from work” were ranked higher than for other courses. The results of the study indicate a continuing need for providers to ensure that courses are relevant and accessible to accountants. Further research is suggested into the differences noted between genders as well as other categorical differences. Work-life balance was a recurring theme that should also be explored further. Pedagogical use in the design of modalities is a further avenue for future research

Otoconia as Test Masses in Biological Accelerometers: What Can We Learn About Their Formation from Evolutionary Studies and from Work in Microgravity?

This paper reviews previous findings and introduces new material about otolith end organs that help us to understand their functioning and development. In particular, we consider the end organs as biological accelerometers. The otoconia are dealt with as test masses whose substructure and evolutionary trend toward calcite may prove significant in understanding formation requirements. Space-flight helps illuminate the influence of gravity, while right-left asymmetry is suggested by study of certain rat strains