Processing of the VP1/2A Junction Is Not Necessary for Production of Foot-and-Mouth Disease Virus Empty Capsids and Infectious Viruses: Characterization of “Self-Tagged” Particles

The foot-and-mouth disease virus (FMDV) capsid protein precursor, P1-2A, is cleaved by 3C(pro) to generate VP0, VP3, VP1, and the peptide 2A. The capsid proteins self-assemble into empty capsid particles or viruses which do not contain 2A. In a cell culture-adapted strain of FMDV (O1 Manisa [Lindholm]), three different amino acid substitutions (E83K, S134C, and K210E) were identified within the VP1 region of the P1-2A precursor compared to the field strain (wild type [wt]). Expression of the O1 Manisa P1-2A (wt or with the S134C substitution in VP1) plus 3C(pro), using a transient expression system, resulted in efficient capsid protein production and self-assembly of empty capsid particles. Removal of the 2A peptide from the capsid protein precursor had no effect on capsid protein processing or particle assembly. However, modification of E83K alone abrogated particle assembly with no apparent effect on protein processing. Interestingly, the K210E substitution, close to the VP1/2A junction, completely blocked processing by 3C(pro) at this cleavage site, but efficient assembly of “self-tagged” empty capsid particles, containing the uncleaved VP1-2A, was observed. These self-tagged particles behaved like the unmodified empty capsids in antigen enzyme-linked immunosorbent assays and integrin receptor binding assays. Furthermore, mutant viruses with uncleaved VP1-2A could be rescued in cells from full-length FMDV RNA transcripts encoding the K210E substitution in VP1. Thus, cleavage of the VP1/2A junction is not essential for virus viability. The production of such engineered self-tagged empty capsid particles may facilitate their purification for use as diagnostic reagents and vaccines

Evaluating the clinical and cost effectiveness of a behaviour change intervention for lowering cardiovascular disease risk for people with severe mental illnesses in primary care (PRIMROSE study):study protocol for a cluster randomised controlled trial

BACKGROUND: People with severe mental illnesses die up to 20 years earlier than the general population, with cardiovascular disease being the leading cause of death. National guidelines recommend that the physical care of people with severe mental illnesses should be the responsibility of primary care; however, little is known about effective interventions to lower cardiovascular disease risk in this population and setting. Following extensive peer review, funding was secured from the United Kingdom National Institute for Health Research (NIHR) to deliver the proposed study. The aim of the trial is to test the effectiveness of a behavioural intervention to lower cardiovascular disease risk in people with severe mental illnesses in United Kingdom General Practices. METHODS/DESIGN: The study is a cluster randomised controlled trial in 70 GP practices for people with severe mental illnesses, aged 30 to 75 years old, with elevated cardiovascular disease risk factors. The trial will compare the effectiveness of a behavioural intervention designed to lower cardiovascular disease risk and delivered by a practice nurse or healthcare assistant, with standard care offered in General Practice. A total of 350 people will be recruited and followed up at 6 and 12 months. The primary outcome is total cholesterol level at the 12-month follow-up and secondary outcomes include blood pressure, body mass index, waist circumference, smoking status, quality of life, adherence to treatments and services and behavioural measures for diet, physical activity and alcohol use. An economic evaluation will be carried out to determine the cost effectiveness of the intervention compared with standard care. DISCUSSION: The results of this pragmatic trial will provide evidence on the clinical and cost effectiveness of the intervention on lowering total cholesterol and addressing multiple cardiovascular disease risk factors in people with severe mental illnesses in GP Practices. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13762819 . Date of Registration: 25 February 2013. Date and Version Number: 27 August 2014 Version 5

What's in a virus? Folk understandings of hepatitis C infection and infectiousness among injecting drug users in Kings Cross, Sydney

BACKGROUND: To explore folk understandings of blood borne virus infection and infectiousness among injecting drug users in Kings Cross, Sydney. METHODS: Observational fieldwork was conducted in Kings Cross over a four month period. In-depth interviews with 24 current injectors and 4 key informants recruited from King Cross were undertaken. RESULTS: Hepatitis C (HCV) generated different meanings from HIV. HIV was considered "the dreaded" and generated fear of infection and dire disease progression. Whereas HCV was considered non-desirable but less threatening than HIV. The risks of transmitting HCV through sharing injecting paraphernalia was poorly understood. Some believed HCV infection was linked to poor hygiene and dirty water. Jaundice was mistakenly thought to indicate HCV infection and was used to gauge infectiousness. Many were confused about their current hepatitis C serostatus. Some participants thought they had a "dormant antibody" or that they had a "mild case" of infection. Participants were unsure what this meant for their own health or for their potential to infect others. CONCLUSION: Participants displayed confusion about transmission risks for hepatitis C, conflating blood awareness and hygiene health promotion messages. Participants' reliance on the symptom of jaundice to gauge serostatus places them at risk of transmitting and contracting HCV. Participants were confused about what a positive HCV diagnosis meant for their own health and their ability to infect others. Education is needed to debunk misconceptions about jaundice and clarify medical terms such as 'antibody' at the time of diagnosis. Further clarification of messages about injecting hygiene and blood awareness are also required

Global patterns of sex- and age-specific variation in seabird bycatch

Fisheries bycatch is a major threat to seabird populations, and understanding sex- and age-biases in bycatch rates is important for assessing population-level impacts. We analysed 44 studies to provide the first global assessment of seabird bycatch by sex and age, and used generalised models to investigate the effects of region and fishing method. Bycatch was highly biased by sex (65% of 123 samples) and age (92% of 114 samples), with the majority of samples skewed towards males and adults. Bycatch of adults and males was higher in subpolar regions, whereas there was a tendency for more immatures and females to be killed in subtropical waters. Fishing method influenced sex- and age-ratios only in subpolar regions. Sex- and age-biases are therefore common features of seabird bycatch in global fisheries that appear to be associated largely with differences in at-sea distributions. This unbalanced mortality influences the extent to which populations are impacted by fisheries, which is a key consideration for at-risk species. We recommend that researchers track individuals of different sex and age classes to improve knowledge of their distribution, relative overlap with vessels, and hence susceptibility to bycatch. This information should then be incorporated in ecological risk assessments of effects of fisheries on vulnerable species. Additionally, data on sex, age and provenance of bycaught birds should be collected by fisheries observers in order to identify regions and fleets where bycatch is more likely to result in population-level impacts, and to improve targeting of bycatch mitigation and monitoring of compliance

Spaces of Ageing: the distinctive geographies of residential complexes

Abstract Where and how people live in later life is of vital importance to their wellbeing. Yet there has been very little critical attention in gerontology to the growth of large residential complexes being built by developers on urban fringes across Australia. There is no coherent policy relating to older people’s accommodation, and a general absence in understanding the capacity of these purpose built environments to meet the needs of older people. Further, there is a lack of research that represents the intricate interplay of factors that informs the provision of residential complexes. This research aims to address the critical need to understand the reality of older people’s lives within these spaces of ageing. It seeks to do this by exploring the experiences and meaning older people resident in these complexes attach to these spaces, as well as investigating the views and knowledge of those responsible for their design and production. A spatial framework, directly informed by Henri Lefebvre’s theory of social space, provides a holistic means to integrate both the structural and humanistic dimensions of space. This framework guided an exploration of the working knowledge of the professionals involved in the production of residential complexes, as well as how older people use, and create meaning in this living environment. The qualitative research design facilitated the analysis of interviews with professionals and older people, as well as documents and working papers in order to gain a rich understanding of the different dimensions that make up the production of, and life within, residential complexes. The research identified a broad range of implications in relation to the policy and practice of building residential complexes for older people. Of particular note is that the working knowledge of those responsible for the provision of residential complexes is underpinned by a stereotypical approach to ageing which affects their attitudes and assumptions. This is part of a complex array of factors including ageism, the dominance of business acumen, and humanism all resulting in a cultural acceptance of older people’s accommodation as separate. These findings prompt consideration of who is planning for whom, and who benefits? Findings suggest that for older people residential complexes are an ambiguous place, characterised by tensions. For some residents, the space provides both security and community, enabling them to engage with occupations and relationships. However, for others, the space is limiting, compromising their ability to retain meaning in their lives. In this way, residential complexes are both an enabling and a constraining environment. These findings highlight the inherent difficulty of providing one dominant model for a population with a broad range of needs, experiences and expectations. Whatever their age older people continue to produce space, and this is not only about keeping the past alive, but keeping in touch with the whole of their lives. This entails continuing to form relationships and connecting to the environment, whether that is a garden, the bush or inner city life; and through the signification of objects as both an expression of connection, loss and absence. To reinforce the heterogeneity of older people, place and space for some was not important. This research has important implications for developing policy on ageing and planning the built environment, as well for the application of the theory of social space. Of note is the power and pervasiveness of ageism within professions responsible for the conception and production of residential complexes, and the strength of the dissonance between accommodation, support and care for older people. Important insights were gained about older people’s use and meaning of their space, notably the need to recognise micro agency and occupation throughout the life course. This thesis draws attention to the complexity of place and space in regard to older people and their living environments and challenges research that adopts a more singular approach. Finally, use of Lefebvre’s work to drive the approach adopted in this study is a major strength. In particular, the operationalisation of Lefebvre’s triad of social space in a social context provides a theoretical contribution to social theory, one to be taken up by gerontology and social science

Addressing older women's homelessness: service and housing models

There is limited understanding of the nature and extent of older women’s homelessness in Australia and how it can be alleviated. The aim of this project is to ascertain the combination of program and housing models that is likely to be most effective in addressing older women’s homelessness. The data comprise interviews and correspondence with 14 Australian and international stakeholders. The findings draw on insight from housing, gerontology and gender studies, and highlight the need to match welfare and housing programs with the diverse life experiences and current needs of older women. Alongside flagship models of practice in housing provision are assumptions within housing and homelessness sectors of what older women need. There is a lack of understanding that most older women in housing crisis have limited knowledge of the welfare sector, and with provision of mainstream housing (and community aged care if needed) will live independently. Traditional homelessness programs and specialised supportive housing, associated with both seniors and homelessness sectors, are appropriate for women who have lived with ongoing disruption and substantive health concerns. Addressing older women’s homelessness in Australia requires a range of services and housing responses, with increased attention given to a discourse of housing – affordable, secure housing – rather than continued discourse of homelessnes

Ageism: designed and planned for older Australians?

This study draws attention to ageist stereotypes and assumptions of older people held by professionals involved in the policy, design and planning of the built environment, in particular residential complexes.Data was collected as part of a larger study concerned with the growth in specialised spaces for older people segregated from the community. The first stage of the study explored the views and experiences of professionals through interviews and working documents. Analysis revealed policy and practice was underpinned by ageist assumptions. These findings provide evidence of the pervasive nature of ageism in our society and how it is inextricably linked to purpose built housing for older people. Indeed the built environment can be seen to be both as a cause and effect of ageism

Preventing first time homelessness amongst older Australians

This project examined older people’s homelessness in Australia, with a particular focus on the experience of becoming homeless for the first time in later life. This research project drew on individual client case records and interviews with professionals working in the Assistance with Care and Housing for the Aged (ACHA) program. The program is designed to assist disadvantaged older people who are at risk of homelessness or who are homeless. Those with a conventional housing history who faced homelessness were typically renters, and faced critical housing incidents such as being served a Notice to Vacate or family breakdown, or faced a lack of affordable housing options. Some also lived in housing with inappropriate design, making it unsafe to continue their residency. Key intervention strategies used to resettle older people were found to include: Assessing an individual’s circumstances, needs and goals at initial contact (using a person-centred and holistic framework). Investigating whether the residency can be maintained through use of advocacy, negotiation with landlords, and brokerage of services. Providing affordable or accessible housing options such as social housing, private housing or caravan parks where the older person can maintain a long term tenancy. Providing supports to assist the older person to remain independent in the community or providing practical assistance such as whitegoods and assistance with moving. An essential component in all circumstances is access to housing. However there is a shortage of affordable and appropriate stock, particularly the private rental market, to facilitate older people ageing in place. Transitional or long-term additional rent subsidies for private renters may make it a more sustainable tenure. Landlords could also help sustain tenancies for older people by permitting modifications to their properties. The breakdown in intergenerational family housing arrangements and its link with homelessness might be addressed by better understanding the role of carer stress, overcrowding, tension, conflict or elder abuse in the development of housing crises. Additional resources or the provision of alternative family housing may also serve to prevent these relationship breakdowns

Understanding daily life of older people in a residential complex: the contribution of Lefebvre's social space

This article contributes to the theoretical and applied understanding of daily life and the meaning of home for older people living in purpose-built, age-segregated complexes. Whilst gerontology has embraced spatial perspectives, it often fails to capture their diverse and changing nature. This article considers findings from a larger qualitative study that explored the geography of residential complexes in Brisbane, Australia, through the lens of Henri Lefebvre's theory of social space. Data relating to Lefebvre's concepts of spatial practice and spaces of representation clearly capture the routines, activities, attachments and imaginations that help or hinder older people connecting to their living environment. Talking with older people gave a rich account of how they use, think about and produce space and highlighted the tensions in providing this form of specialised housing. As well as providing theoretical insights, a nuanced understanding of social space informs policy and public discussion of older people's living environments