20 research outputs found
CD27 costimulation contributes substantially to the expansion of functional memory CD8+ T cells after peptide immunization
No full textNaive T cells require signals from multiple costimulatory receptors to acquire full effector function and differentiate to long-lived memory cells. The costimulatory receptor, CD27, is essential for optimal T-cell priming and memory differentiation in a variety of settings although whether CD27 is similarly required during memory CD8+ T-cell re-activation remains controversial. We have used OVA and anti-CD40 to establish a memory CD8+ T-cell population and report here that their secondary expansion, driven by peptide and anti-CD40, polyI:C or LPS requires CD27. Furthermore, antigenic peptide and a soluble form of the CD27 ligand, CD70 (sCD70), is sufficient for secondary memory CD8+ T-cell accumulation at multiple anatomical sites, dependent on CD80/86. Prior to boost, resting effector- and central-memory CD8+ T cells both expressed CD27 with greater expression on central memory cells. Nonetheless both populations upregulated CD27 after TCR engagement and accumulated in proportion after boosting with antigen and sCD70. Mechanistically, sCD70 increased the frequency of divided and cytolytic memory T cells, conferred resistance to apoptosis and enabled retardation of tumor growth in vivo. These data demonstrate the central role played by CD27/70 during secondary CD8+ T-cell activation to a peptide antigen, and identify sCD70 as an immunotherapeutic adjuvant for anti-tumor immunit
The role of death receptor 3 in inflammatory arthritis
No full textThis paper looks at the effects of dust allergen and LPS concentrations on biomarkers of asthma in adults with house dust mite-sensitive asthma
Issues in the Issuance of Enhanced Annuities
No full textTwo forces are about to create a growing market for Individual Annuities in the U. S. and Canada. First, the Post War Baby Boom (born 1946 to 1964) is inexorably moving into retirement. Second, there is a strong move away from Employer-sponsored Defined Benefit pension plans to Defined Contribution pension plans. This trend could even extend (in the U.S.) into the provision of Social Security benefits. Under these arrangements, participants must find a way to mitigate their “longevity” risk (and the investment risk, although this is not the topic of this paper). The most obvious answer is to buy a life annuity. However, at this time in the U. S. and Canada, persons who voluntarily apply to buy a life annuity are generally assumed to be in extremely good health and annuity rates are determined using very low mortality assumptions (high life expectancy assumptions). While there is a growing market in “Enhanced/Impaired Annuities”, especially in the U.K., the present pricing structure for annuities in the U. S. and Canada means that a large proportion of the population cannot get a “fair value” annuity given their less-than-preferred health profile. This paper looks at reasons for this market reality in the U. S. and Canada. It also reviews the underwriting and marketing of life annuities in the United Kingdom where “enhanced” life annuities are available for a broader cross-section of the marketplace.Individual Annuities, Defined Benefit Pension Plan, Defined Contribution Pension Plan, Retirement Income Security, Life Expectancy, Impaired Mortality
Well-Being Throughout the Senior Years: An Issues Paper on Key Events and Transitions in Later Life
No full textSocial Development Canada’s mission is “to strengthen Canada’s social foundations by supporting the well-being of individuals, families and communities and their participation through citizen focused policies, programs and services” (Social Development Canada 2005a). Well-being is a concept that goes beyond good health to encompass physical and mental fitness as well as social fitness (being able to perform one’s social roles and the demands of everyday living adequately). As people age, they experience a number of transitions in their lives. They may retire, change residence, loose a spouse, become a caregiver, and/or develop a health problem or disability. These transitions, especially when they occur around the same time, may impact on their well-being and independence and prevent them from being contributing members of society. This paper summarizes the research on what we currently know about the key events and transitions experienced by seniors, their impacts, and the resources seniors have or need to successfully cope with these events throughout the senior years. It will also review what we know about opportunities, gaps or barriers in accessing social support programs and service delivery designed to assist seniors in coping successfully with adverse events and life transitions. Issues to be considered include availability, access and costs of community support and home health care services. Finally, the paper will attempt to provide potential policy research directions to address current knowledge gaps. This is an extensive literature, and we have limited the scope by focusing on the last 10 years of Canadian research published in Journals and by Statistics Canada. We have favored research based on national studies in this review, though there are many excellent case studies and qualitative studies that add texture to our knowledge. Recognizing that the senior population is a very heterogeneous group, this review will examine (where the research permits) differences by senior life-course stages, and other target groups such as women, the disabled, visible minority, immigrants, Aboriginal peoples, sub-regions, low income, and persons living alone. This review of the literature has shown that while we have basic information about many of the transitions in seniors’ lives, there is very little information about the various life course stages or about various sub groups of society.health and well-being, retirement, marital transitions, care-giving, homecare
Well-Being Throughout the Senior Years: An Issues Paper on Key Events and Transitions in Later Life
No full textSocial Development Canada’s mission is “to strengthen Canada’s social foundations by supporting the well-being of individuals, families and communities and their participation through citizen focused policies, programs and services” (Social Development Canada 2005a). Well-being is a concept that goes beyond good health to encompass physical and mental fitness as well as social fitness (being able to perform one’s social roles and the demands of everyday living adequately). As people age, they experience a number of transitions in their lives. They may retire, change residence, loose a spouse, become a caregiver, and/or develop a health problem or disability. These transitions, especially when they occur around the same time, may impact on their well-being and independence and prevent them from being contributing members of society. This paper summarizes the research on what we currently know about the key events and transitions experienced by seniors, their impacts, and the resources seniors have or need to successfully cope with these events throughout the senior years. It will also review what we know about opportunities, gaps or barriers in accessing social support programs and service delivery designed to assist seniors in coping successfully with adverse events and life transitions. Issues to be considered include availability, access and costs of community support and home health care services. Finally, the paper will attempt to provide potential policy research directions to address current knowledge gaps. This is an extensive literature, and we have limited the scope by focusing on the last 10 years of Canadian research published in Journals and by Statistics Canada. We have favored research based on national studies in this review, though there are many excellent case studies and qualitative studies that add texture to our knowledge. Recognizing that the senior population is a very heterogeneous group, this review will examine (where the research permits) differences by senior life-course stages, and other target groups such as women, the disabled, visible minority, immigrants, Aboriginal peoples, sub-regions, low income, and persons living alone. This review of the literature has shown that while we have basic information about many of the transitions in seniors’ lives, there is very little information about the various life course stages or about various sub groups of society.health and well-being, retirement, marital transitions, care-giving, homecare
Stasis Amidst Change: Canadian Pension Reform in an Age of Retrenchment
No full textFaced with aging populations and especially heightened fiscal constraints, large scale pension reforms were implemented in many affluent democracies during the 1990s. Canadian reforms, by contrast, were quite modest and old age security benefits emerged largely unscathed. Drawing on the comparative experience of other OECD nations, we highlight four characteristics of the Canadian pension system and the policy environment to account for this relative stability:(1) the comparatively modest scale of Canadian public sector pension expenditures; (2) relatively greater reliance on general revenue as opposed to payroll taxes to finance these expenditures; (3) the availability of other expenditure targets, notably health care, post-secondary education and social assistance, that could be cut with less political backlash; and (4) a pension design that allocates the public sector share disproportionately to the bottom end of the income distribution, precluding the emergence of the oppositional politics that fueled public debate elsewhere.aging population; pension reform
Memory, tradition, and Christianization of the Peloponnese
No full textThis work examines the use of memory and tradition in the Christianization of the Peloponnese based on the evidence of the location and topography of churches. The different processes of conversion in the area have already been discussed, and the focus of this work is to show the extent of continuation of religious practice from the Roman to Late Antique periods. A diachronic analysis of the evidence for towns and sanctuaries from the fourth to seventh centuries is presented. It is argued that throughout the different Christianization processes memory and tradition were managed by the church in terms of its location, architecture, and rituals. It is likely that the church consciously maintained certain traditions of place, imagery, and action in order to retain and use memory traces from the established religious structures, which helped situate the Christian church as a central element of community life and identity. Therefore, it is contended that an essential element of the Christianization process was to maintain earlier memories and traditions not only to enable an efficiently unobtrusive conversion for its long-term success but also to ensure the maintenance of existing social structures, which in turn sustained the church.Peer reviewe
An experiment in contextualised comparative hermeneutics : a reading of Genesis 1-11 in the context of parallel Qur'anic material and Christian mission amongst Muslims in Elswick, Newcastle upon Tyne.
No full textPolicy Change in the Canadian Welfare State: Comparing the Canada Pension Plan and Unemployment Insurance
No full textFocusing on Canada, this paper explores the politics of social policy retrenchment and restructuring in two policy areas: old-age pensions, especially the Canada Pension Plan (CPP), and Employment Insurance (EI) [formerly Unemployment Insurance (UI)]. Drawing on historical institutionalism and the literature on ideas and policy change, the paper explains key differences between these two policy areas. The analysis shows that institutional factors like federalism explain some of the differences between the policy areas and programs at stake. Yet, to complement this analysis, the paper also highlights the political consequences of changing ideas and assumptions among policy-makers, which vary strongly from one program to another. In other words, ideational and institutional factors combined to produce distinct patterns of policy change. Overall, the paper suggests that scholars can draw a clear analytical line between ideational and institutional factors before combining them to explain specific episodes of policy change. From a methodological standpoint, the paper also demonstrates the added value of systematic comparisons between distinct policy areas located within the same country.Ideas, institutions, unemployment, pensions, Canada
The structure of immature tick-borne encephalitis virus supports the collapse model of flavivirus maturation
No full textWe present structures of three immature tick-borne encephalitis virus (TBEV) isolates. Our atomic models of the major viral components, the E and prM proteins, indicate that the pr domains of prM have a critical role in holding the heterohexameric prM3E3 spikes in a metastable conformation. Destabilization of the prM furin-sensitive loop at acidic pH facilitates its processing. The prM topology and domain assignment in TBEV is similar to the mosquito-borne Binjari virus, but is in contrast to other immature flavivirus models. These results support that prM cleavage, the collapse of E protein ectodomains onto the virion surface, the large movement of the membrane domains of both E and M, and the release of the pr fragment from the particle render the virus mature and infectious. Our work favors the collapse model of flavivirus maturation warranting further studies of immature flaviviruses to determine the sequence of events and mechanistic details driving flavivirus maturation.Peer reviewe
