The influence of regulatory T cells and mobilisation regimens on graft versus malignancy, graft versus host disease and relapse in haematopoietic progenitor cell transplantation

Regulatory T cells (Tregs) are key players in controlling immune responses, limiting autoimmune disease and allergies, and attenuating immune responses to tumours and pathogens. Understanding and harnessing the suppressive effects of Tregs in autologous and allogeneic haematopoietic progenitor cell (HPC) transplantation presents a significant challenge due to lack of consensus over optimal markers to uniquely identify Tregs and variation in centre-specific factors including disease mix, conditioning regimens, graft origin and manipulation and prophylaxis and treatment of graft versus host disease (GVHD). This study aimed to determine if CD3+CD4+CD125highCD127lowFoxP3+ Treg quantification, assessed flow cytometrically, in grafts or in the post-transplant peripheral blood of patients who received transplants for malignant disease, could provide a useful predictor for disease relapse in autologous (n=85) and allogeneic patients (n=75) and falling chimerism and/or incidence of GVHD in the latter group. The impact of Treg numbers were quantified in HPC harvests, in transplant grafts and in recipients’ peripheral blood during immune reconstitution. Additionally, a simplified Treg assessment protocol using the marker tumour necrosis factor receptor-2 (TNFR2) with CD3, CD4 and CD25 was assessed.In autologous donors, significantly higher Tregs relative to CD34 HPCs were noted in harvests mobilised with the more novel regimen, granulocyte-colony stimulating factor (G-CSF) plus Plerixafor than with G-CSF alone or used in combination with cyclophosphamide. In allogeneic harvests Treg numbers following G-CSF mobilisation were significantly lower than in non-mobilised harvests. Lower absolute Treg numbers in donor lymphocyte infusion (DLI) doses were significantly associated with successful outcome in terms of restoration of donor chimerism and resolution of relapse. Cryopreservation of mobilised cells at the time of initial transplant for later use for DLI has thus been incorporated into practice at this Trust as this is expedient in terms of clinical result, convenience and cost. Interestingly although mobilisation regimens influenced Treg levels in harvests, no correlation was apparent between Treg doses transplanted or peripheral blood levels during immune reconstitution post autologous or allogeneic transplantation or with falling chimerism and/or incidence and severity of GVHD in allogeneic patients during the first year post transplant. Extending this follow-up time would be an interesting area of further study as the majority of patients who relapse do so beyond one year

The Impact of Short Breaks on Families with a Disabled Child: Report One of the Quantitative Phase

This document reports on a cross-sectional sample of families with a disabled child using short breaks in England; it describes the characteristics of children and families using short breaks, the nature and quantity of the short breaks they are using, their experiences of and satisfaction with short breaks and which factors are associated with a range of outcomes for family carers, disabled children and their siblings. This report uses both quantitative data derived from standardised questions and qualitative data from family members’ written responses to open-ended questions in the survey instruments

The impacts of short break provision on disabled children and families: an international literature review

For over 30 years, short breaks have been part of the landscape of support provision for families with a disabled child. Historically, the term ‘respite care’ has been used in much of the research literature concerning short breaks for families with a disabled child. However, ‘short breaks’ has become the preferred term, partly due to the negative connotations of family carers requiring ‘respite’ from their children, and partly because short breaks now encompass a much wider range of supports than out-of-home placement in specialist residential facilities (Cramer and Carlin, 2008). As such, the term ‘short breaks’ will be used throughout this review, with the exception of direct quotes from research studies where the term ‘respite’ is used by study participants or study authors

Social as much as environmental: the drivers of tree biomass in smallholder forest landscape restoration programmes

A major challenge for forest landscape restoration initiatives is the lack of quantitative evidence on how social factors drive environmental outcomes. Here we conduct an interdisciplinary quantitative analysis of the environmental and social drivers of tree biomass accumulation across 639 smallholder farms restoring native tree species in Mexico, Uganda and Mozambique. We use environmental and social data to assess the relative effects of key hypothesised drivers on aboveground biomass accumulation at the farm-level over ten years. We supplement this with a qualitative analysis of perspectives from local farmers and agroforestry technicians on the potential causal mechanisms of the observed social effects. We find that the material wellbeing of farmers (e.g. assets) and access to agroforestry knowledge explain as much variation in biomass as water availability. Local perspectives suggest that this is caused by the higher adaptive capacity of some farmers and their associated ability to respond to social-ecological shocks and stresses. Additionally, the variation in biomass between farms increased over time. Local perspectives suggested that this was caused by emergent exogenous and stochastic influences which cannot be reliably predicted in technical analyses and guidance. To deal with this persistent uncertainty, local perspectives emphasised the need for flexible and adaptive processes at the farm- and village-levels. The consistency of these findings across three countries suggests these findings are relevant to similar forest restoration interventions. Our findings provide novel quantitative evidence of a social-ecological pathway where the adaptive capacity of local land users can improve ecological processes. Our findings emphasize the need for forest restoration programmes to prioritise investment in the capabilities of local land users, and to ensure that rules support, rather than hinder, adaptive management

Sustaining Precarious Transnational Families: The Significance of Remittances From Canada's Seasonal Agricultural Workers Program

Accelerating flows of remittances are dwarfing global development aid. This study deepens our understanding of remittance impacts on the families of workers who come to Canada annually for several months under the Seasonal Agricultural Workers Program (SAWP). Interviews with SAWP workers, their spouses, adult children and teachers in Mexico deepen our understanding of the impacts of these remittances. They demonstrate that the remittances are often literally a lifeline to transnational family survival, allowing them to pay for basic needs such as shelter, food, and medical care. Yet, at the same time, the remittances do not allow most of these workers and their families to escape deep poverty and significant precarity, including new forms of precarity generated by the SAWP. Instead, SAWP remittances help reduce poverty, at least temporarily, to more moderate levels while precarious poverty expands through globalneoliberal underdevelopment

A review of the social impacts of culture and sport

This research, funded from the Culture and Sport Evidence (CASE) programme, reviews the current evidence base on the social impacts of sport and culture. Using a systematic review of relevant literature, this research focuses principally on four main types of social impact: (i) improved health, (ii) reduced crime, (iii) increased social capital and (iv) improved education outcomes. In addition, links to subjective wellbeing (SWB) are examined; and a category 'multiple social impacts' reports on literature where more than one social impact is considered