Spirit, mind and body: the archaeology of monastic healing

Archaeology and material culture are used in this chapter to consider how monastic experience responded to illness, ageing and disability. The approach taken is influenced by the material study of religion, which interrogates how bodies and things engage to construct the sensory experience of religion, and by practice-based approaches in archaeology, which examine the active role of space and material culture in shaping religious agency and embodiment. The archaeology of monastic healing focuses on the full spectrum of healing technologies, from managing the body in order to prevent illness, through to the treatment of the sick and preparation of the corpse for burial

Health Outcome Prioritization in Alzheimer's Disease:Understanding the Ethical Landscape

Objective: Health outcome prioritisation is the ranking in order of desirability or importance of a set of disease related objectives and their associated cost or risk. We analyse the complex ethical landscape in which this takes place in the most common dementia, Alzheimer’s disease. Background: Dementia has been described as the greatest global health challenge in the 21st century on account of longevity gains increasing its incidence, escalating health and social care pressures. These pressures highlight ethical, social, political challenges about healthcare resource allocation, what health improvements matter to patients, and how they are measured. This study highlights the complexity of the ethical landscape, relating particularly to the balances that need to be struck when allocating resources; when measuring and prioritising outcomes; and when individual preferences are sought. Methods: Narrative review of literature published since 2007, incorporating snowball sampling where necessary. We identified, thematised and discussed key issues of ethical salience. Results: Eight areas of ethical salience for outcome prioritisation emerged: (1) Public health and distributive justice, (2) Scarcity of resources, (3) Heterogeneity and changing circumstances, (4) Knowledge of treatment, (5) Values and circumstances, (6) Conflicting priorities, (7) Communication, autonomy and Caregiver issues, (8) Disclosure of risk. Conclusion: These areas highlight the difficult balance to be struck when allocating resources, when measuring and prioritising outcomes, and when individual preferences are sought. We conclude by reflecting on how tools in social sciences and ethics can help address challenges posed by resource allocation, measuring and prioritising outcomes, and eliciting stakeholder preferences.</p

Involvement in surface antigen expression by a moonlighting FG-repeat nucleoporin in trypanosomes

Components of the nuclear periphery coordinate a multitude of activities, including macromolecular transport, cell-cycle progression, and chromatin organization. Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport, mRNA processing, and transcriptional regulation, and NPC components can define regions of high transcriptional activity in some organisms at the nuclear periphery and nucleoplasm. Lineage-specific features underpin several core nuclear functions and in trypanosomatids, which branched very early from other eukaryotes, unique protein components constitute the lamina, kinetochores, and parts of the NPCs. Here we describe a phenylalanine-glycine (FG)-repeat nucleoporin, TbNup53b, that has dual localizations within the nucleoplasm and NPC. In addition to association with nucleoporins, TbNup53b interacts with a known trans-splicing component, TSR1, and has a role in controlling expression of surface proteins including the nucleolar periphery-located, procyclin genes. Significantly, while several nucleoporins are implicated in intranuclear transcriptional regulation in metazoa, TbNup53b appears orthologous to components of the yeast/human Nup49/Nup58 complex, for which no transcriptional functions are known. These data suggest that FG-Nups are frequently co-opted to transcriptional functions during evolution and extend the presence of FG-repeat nucleoporin control of gene expression to trypanosomes, suggesting that this is a widespread and ancient eukaryotic feature, as well as underscoring once more flexibility within nucleoporin function

The Ccr4-Not Complex Interacts with the mRNA Export Machinery

The Ccr4-Not complex is a key eukaryotic regulator of gene transcription and cytoplasmic mRNA degradation. Whether this complex also affects aspects of post-transcriptional gene regulation, such as mRNA export, remains largely unexplored. Human Caf1 (hCaf1), a Ccr4-Not complex member, interacts with and regulates the arginine methyltransferase PRMT1, whose targets include RNA binding proteins involved in mRNA export. However, the functional significance of this regulation is poorly understood.Here we demonstrate using co-immunoprecipitation approaches that Ccr4-Not subunits interact with Hmt1, the budding yeast ortholog of PRMT1. Furthermore, using genetic and biochemical approaches, we demonstrate that Ccr4-Not physically and functionally interacts with the heterogenous nuclear ribonucleoproteins (hnRNPs) Nab2 and Hrp1, and that the physical association depends on Hmt1 methyltransferase activity. Using mass spectrometry, co-immunoprecipitation and genetic approaches, we also uncover physical and functional interactions between Ccr4-Not subunits and components of the nuclear pore complex (NPC) and we provide evidence that these interactions impact mRNA export.Taken together, our findings suggest that Ccr4-Not has previously unrealized functional connections to the mRNA processing/export pathway that are likely important for its role in gene expression. These results shed further insight into the biological functions of Ccr4-Not and suggest that this complex is involved in all aspects of mRNA biogenesis, from the regulation of transcription to mRNA export and turnover

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Exploring the situational complexities associated practice change in health

Purpose - The purpose of this paper is to critically examine multidisciplinary, group clinical supervision sessions and to extend current understandings of the barriers/enablers to the implementation of an innovative psychosocial intervention for distressed adults with cancer.Design/methodology/approach - Discourse analysis was used to analyse audio recordings from clinical supervision sessions delivered as part of a psychosocial intervention within the context of a randomised control trial (RCT).Findings - Examination of subject positions, representation and tensions reveals that Health Professionals can resists the pressures of systemic barriers to provide much-needed psychosocial support for distressed adults with cancer. Critical examination of multidisciplinary clinical supervision sessions describes how Health Professionals are able to construct new meanings and reposition themselves as being able to provide supportive care within the context of their everyday practices.Research limitations/implications - This paper reports only a small part of a larger analysis that aims to explore how discourse maps the current state of psychosocial care for adults with cancer and illustrates the fragility and potential for change in this area.Originality/value - Extension on the previous literature is seen within the data through the presence of positive resistance against systemic barriers. Previous exploration of clinical supervision has not collected data generated within the sessions. It is also novel in the use of discourse analysis being used in association with a randomised controlled trial to understand the situational complexities associated with bringing about practice change

Patient and health professional's perceived barriers to the delivery of psychosocial care to adults with cancer: a systematic review

Objective: To explore the barriers experienced and perceived by health professionals and patients in the delivery of psychosocial care to adults with cancer. Methods: Systematic searches were undertaken using the Psych Info, Medline and CINAHL electronic databases, up to October 2013. Research reporting health professional or patient experiences and perceptions of barriers to psychosocial care are included in the review. The systematic review includes studies that have non-experimental, exploratory and observational designs, as is appropriate to answer the review question. Included studies were critically appraised. The results of individual quantitative studies were aggregated. Qualitative content analysis was used to analyse the qualitative results. Results: Twenty-five papers met the pre-specified inclusion criteria for the final review. The most commonly perceived barrier for patients relates to receiving adequate support from elsewhere and a lack of perceived need for psychosocial care. Health professionals report barriers at an organisational level most frequently followed by cultural and then individual clinician-related barriers. Conclusions: Barriers exist on a variety of levels. People with cancer need clear appropriate information and communication about psychosocial services, including information about the role of psychosocial care in addition to existing supports. Interventions that target the complex interplay of individual, organisational and cultural factors need to be developed. Strategies that improve health professional communication skills, identify clear referral pathways, improve acceptability of interventions and clearly identify the need for services could address many of the barriers identified in this review

Implementing a psychosocial intervention in cancer care: an examination of the change process through a discourse analysis of clinical supervision

Background: Clinical practice guidelines for the psychosocial care of adults with cancer are not reflected in routine clinical care. Clinical supervision is recommended as a means to support Health Professionals in providing the recommended psychosocial support. This presentation will explore what influence clinical supervision had on the discourses of Health Professionals trained to deliver a new psychosocial Intervention to adults with cancer. Method: This was a qualitative design embedded within a step wedged randomised control trial. The study used discourse analysis to analyse audio-recorded data collected within multidisciplinary, group format clinical supervision sessions that were delivered as one element of a randomised control trial. Data was collected from November 2011 to December 2012