‘Multi-Epitope-Targeted’ Immune-Specific Therapy for a Multiple Sclerosis-Like Disease via Engineered Multi-Epitope Protein Is Superior to Peptides

Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS) yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and “epitope spread”, have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such “multi-epitope-targeting” approach in murine experimental autoimmune encephalomyelitis (EAE) associated with a single (“classical”) or multiple (“complex”) anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc) encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as “multi-epitope-targeting” agents. Y-MSPc was superior to peptide(s) in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells). Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of “classical” or “complex EAE” or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a “multi-epitope-targeting” strategy is required for effective immune-specific therapy of organ-specific autoimmune diseases associated with complex and dynamic pathogenic autoimmunity, such as MS; our data further demonstrate that the “multi-epitope-targeting” approach to therapy is optimized through specifically designed multi-epitope-proteins, rather than myelin peptide cocktails, as “multi-epitope-targeting” agents. Such artificial multi-epitope proteins can be tailored to other organ-specific autoimmune diseases

Understanding the Use of Crisis Informatics Technology among Older Adults

Mass emergencies increasingly pose significant threats to human life, with a disproportionate burden being incurred by older adults. Research has explored how mobile technology can mitigate the effects of mass emergencies. However, less work has examined how mobile technologies support older adults during emergencies, considering their unique needs. To address this research gap, we interviewed 16 older adults who had recent experience with an emergency evacuation to understand the perceived value of using mobile technology during emergencies. We found that there was a lack of awareness and engagement with existing crisis apps. Our findings characterize the ways in which our participants did and did not feel crisis informatics tools address human values, including basic needs and esteem needs. We contribute an understanding of how older adults used mobile technology during emergencies and their perspectives on how well such tools address human values.Comment: 10 page

Exploring older adults' understandings of disaster preparedness : a New Zealand perspective : a thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Psychology at Massey University, Manawatū, New Zealand

Individual preparedness for a disaster has centred on educating and encouraging people to protect themselves against injury and damage to assist with response and recovery after a disaster. Research on factors influencing individual disaster preparedness has focused on demographic and psychological variables, while socio-cultural contexts have received less attention. These omissions may help explain why more vulnerable population groups are disproportionately affected. Older adults are a rapidly increasing population group who are a vulnerable group at greater risk of negative effects during and after a disaster; however, little attention has been given to older adults’ perspectives about disaster preparedness. This thesis is presented as four papers written for submission to peer reviewed journals, and explores older adults’ meanings and experiences about disaster preparedness from a social constructionist perspective. A series of 26 qualitative interviews using a narrative methodology was undertaken in 2012 with participants located in Wellington and Christchurch (median ages 84, and 80), New Zealand. Participants were recruited through a home support agency. Inductive thematic analysis of the data sets was undertaken, which attended to the influences of personal and socio-cultural contexts on disaster preparedness. The first paper provides a conceptual argument for use of qualitative methodologies to further explore understandings of disaster preparedness. The second paper focuses on older adults’ household disaster preparedness in Wellington, which identified that older adults accepted personal responsibility for assembling and maintaining their survival kits. Practical concerns such as the ability to refill water bottles, monitor stock rotation, and ensure adequate medication supplies were identified to be difficult for some. Preparedness was also associated with the quality of supportive social relationships that could provide assistance. The third paper is also based on the Wellington study, and provides a broader discussion about everyday preparedness. Meanings and experiences of preparedness were concerned with managing health decline, preparing for death, and the interpersonal complexity of negotiating their personal and social needs to remain independent in the community. The fourth paper discusses older adults’ experiences of preparedness during the Canterbury earthquake sequence (2010-2012). Disaster preparedness was primarily linked to the importance of social relationships; and a concern regarding a lack of age appropriate safety messages about personal protection. This thesis contributes to the literature on disaster preparedness by identifying age specific influences, which relate to managing personal health, social support and socio-cultural norms of independence. Some participants lacked informational, health and social resources, which would enable preparedness actions and the ability to respond effectively. The research from the Wellington and Christchurch studies identifies the need for coordinated, multidisciplinary age specific disaster preparedness planning to assist individual and community resilience

Older adults' experiences of a flood disaster : making sense of an extraordinary event : a thesis presented in partial fulfilment of the requirements for the degree of Master of Arts in Psychology at Massey University, Palmerston North, New Zealand

Disasters occur within the routines of everyday life and have a disruptive and destructive impact on human lives. To understand how older individuals make sense of a disaster, nine older adults in Kaitaia, New Zealand were interviewed about their experience of a flood they experienced in July 2007. These interviews were conducted with four residents living in a rest home and five pensioners living independently who were evacuated from their homes. The two groups differed in the levels of support and assistance received before, during, and after the disaster. The rest home residents experienced little disruption and did not require relocation; the pensioners experienced major disruption and relocation. Thematic analysis was used to describe how these older adults’ accounted for their experiences of the flood. The narratives were influenced by the participants’ identity as either dependent rest home residents or pensioners living independently in the community. The analysis revealed that their accounts of the disaster were incorporated and integrated into the personal and social context of each person’s life story. Narrative themes that emerged from the analysis for the pensioner group were: coping with limited assistance, the importance of treasured possessions, and social support and community. The pensioner themes reflected their vulnerability to a disaster and the challenges they faced during the post disaster recovery phase. Themes for the rest home residents were ageing and dependency, and the importance of protection, care, and trust. These themes reflected the dependent world of the rest home residents and the security of being cared for