Our data suggest that systematic implementation of a program to increase use of advance directives reduces health care services utilization without affecting satisfaction or mortality.

SummaryExpansion and acquisition of Th1 cell effector function requires metabolic reprogramming; however, the signals instructing these adaptations remain poorly defined. Here we found that in activated human T cells, autocrine stimulation of the complement receptor CD46, and specifically its intracellular domain CYT-1, was required for induction of the amino acid (AA) transporter LAT1 and enhanced expression of the glucose transporter GLUT1. Furthermore, CD46 activation simultaneously drove expression of LAMTOR5, which mediated assembly of the AA-sensing Ragulator-Rag-mTORC1 complex and increased glycolysis and oxidative phosphorylation (OXPHOS), required for cytokine production. T cells from CD46-deficient patients, characterized by defective Th1 cell induction, failed to upregulate the molecular components of this metabolic program as well as glycolysis and OXPHOS, but IFN-γ production could be reinstated by retrovirus-mediated CD46-CYT-1 expression. These data establish a critical link between the complement system and immunometabolic adaptations driving human CD4+ T cell effector function.

In economically developed countries there is a rapidly increasing number of older people living and dying in care homes. The relative isolation of nursing care homes from the development of palliative care, the poor retention and recruitment of staff, and the lack of medical cover, hinder the provision of quality end-of-life care. End-of-life care strategies internationally highlight the benefit of using tools to help improve end-of-life care in care homes. All seven private nursing care homes within one district in Scotland undertook to implement, as a package, two end-of-life care tools, namely, the Gold Standards Framework for Care Homes (GSFCH) and an adapted Liverpool Care Pathway for Care Homes (LCP). A model of high facilitation, visiting the homes every 10-14 days with significant in-house staff training, was used to implement the 18-month programme. The notes of 228 residents who had died prior to and during the project were examined, alongside a staff audit looking at the effect that the project had on practice. A nurse researcher undertook qualitative interviews of bereaved relatives, pre-/post-implementation. This paper reports the results of an in-depth evaluation of professional practices and residents outcomes. There was a highly statistically significant increase in use of Do Not Attempt Resuscitation (DNAR) documentation, advance care planning and use of the LCP. An apparent reduction in unnecessary hospital admissions and a reduction in hospital deaths from 15% deaths pre-study to 8% deaths post-study were also found. Further work is needed to assess the optimum input required for successful implementation.

The purpose of this study was to promote quality end-of-life care in eight independent nursing homes using an ‘integrated care pathway (ICP) for the last days of life’ document. Action research methodology underpinned the design of this study in order to promote collaboration between staff in the nursing homes and the research team, empower staff in the practice of quality end-of-life care, and promote sustainable development of end-of-life care once the study finished. Considerable barriers within the nursing home context highlighted initial difficulties. This is reported elsewhere (Watson et al., in press) (Bridges Initiative, 2004). However, key champions appointed in each nursing home and their subsequent support was a major part of facilitating the ICP implementation. This paper reports the qualitative analysis from the summative evaluation of the study. One overarching pattern of ‘dying being more central to care in the nursing homes’ emerged as a result of the study; five themes that contributed to this shift were: greater ‘openness’ around death and dying; recognising dying and taking responsibility; better ‘teamwork’; critically using palliative care knowledge to influence practice; more meaningful communication.

BackgroundThe Fas pathway is a major regulator of T cell homeostasis, however, the T cell population that is controlled by the Fas pathway in vivo is poorly defined. Although CD4 and CD8 single positive (SP) T cells are the two major T cell subsets in the periphery of wild type mice, the repertoire of mice bearing loss-of-function mutation in either Fas (lpr mice) or Fas ligand (gld mice) is predominated by CD4−CD8− double negative αβ T cells that also express B220 and generally referred to as B220+DN T cells. Despite extensive analysis, the basis of B220+DN T cell lymphoproliferation remains poorly understood. In this study we re-examined the issue of why T cell lymphoproliferation caused by gld mutation is predominated by B220+DN T cells.Methodology and Principal FindingsWe combined the following approaches to study this question: Gene transcript profiling, BrdU labeling, and apoptosis assays. Our results show that B220+DN T cells are proliferating and dying at exceptionally high rates than SP T cells in the steady state. The high proliferation rate is restricted to B220+DN T cells found in the gut epithelium whereas the high apoptosis rate occurred both in the gut epithelium and periphery. However, only in the periphery, apoptosis of B220+DN T cell is Fas-dependent. When the Fas pathway is genetically impaired, apoptosis of peripheral B220+DN T cells was reduced to a baseline level similar to that of SP T cells. Under these conditions of normalized apoptosis, B220+DN T cells progressively accumulate in the periphery, eventually resulting in B220+DN T cell lymphoproliferation.Conclusions/SignificanceThe Fas pathway plays a critical role in regulating the tissue distribution of DN T cells through targeting and elimination of DN T cells from the periphery in the steady state. The results provide new insight into pathogenesis of DN T cell lymphoproliferation.

it cannot be presumed that the implementation of a care pathway for the last days of life in nursing homes is straightforward. This study suggests that an action research framework was extremely useful in highlighting and overcoming some obstacles when developing evidence-based practice. Action at both local and public policy level is required to fully address barriers that prevent quality end-of-life care in nursing homes.

In humanitarian emergency settings there is need for low cost and rapidly deployable interventions to protect vulnerable children, in- and out-of-school, from diarrhoeal diseases. Handwashing with soap can greatly reduce diarrhoea but interventions specifically targeting children's handwashing behaviour in humanitarian settings have not been tested. Traditional children's handwashing promotion interventions have been school-focused, resource-intensive and reliant on health-based messaging. However, recent research from non-humanitarian settings and targeting adults suggests that theory-based behaviour change interventions targeting specific motives may be more effective than traditional handwashing interventions. In this proof-of-concept study we test, for the first time, the distribution of a modified soap bar, designed to appeal to the motives of play and curiosity, in a household-level, rapidly deployable, handwashing promotion intervention for older children in a humanitarian setting - an internally displaced persons camp in Iraqi Kurdistan. Out of five total blocks within the camp, one was assigned to intervention and one to control. 40 households from each assigned block were then randomly chosen for inclusion in the study and the practice of handwashing with soap at key times was measured at baseline and four weeks after intervention delivery. Children in intervention households received transparent soaps with embedded toys, delivered within a short, fun, and interactive household session with minimal, non-health-based, messaging. The control group received plain soap delivered in a short standard, health-based, hygiene promotion session. At the 4-week follow-up, children in the intervention group were 4 times more likely to wash their hands with soap after key handwashing occasions than expected in the counterfactual (if there had been no intervention) based on the comparison to children in the control group (adjusted RR = 3.94, 95% CI 1.59-9.79). We show that distributing soaps with toys embedded inside, in a rapidly deployable intervention, can improve child handwashing behaviour in a humanitarian emergency context. Further studies are needed to determine the longer-term behavioural and health impact of such an intervention when delivered at a greater scale in a humanitarian context.

The involvement of "people with experience" in research has developed considerably in the last decade. However, involvement as co-analysts at the point of data analysis and synthesis has received very little attention-in particular, there is very little work that involves people living with dementia as co-analysts. In this qualitative secondary data analysis project, we (a) analyzed data through two theoretical lenses: Douglas's cultural theory of risk and Tronto's Ethic of Care, and (b) analyzed data in workshops with people living with dementia. The design involved cycles of presenting, interpreting, representing and reinterpreting the data, and findings between multiple stakeholders. We explore ways of involving people with experience as co-analysts and explore the role of reflexivity, multiple voicing, literary styling, and performance in participatory data analysis.