The social care needs of people affected by cancer: a qualitative study in Lincolnshire

Background People affected by cancer (PABC) can have a range of social care needs at different stages of the patient pathway. These may include emotional, practical, personal, as well as information and financial needs. The UK charity, Macmillan Cancer Support want to refocus their current social care provision and, (where need is evidenced) develop new services to better address the social care needs of PABC in Lincolnshire. In order to do this effectively Macmillan together with the Bromhead Medical Charity has commissioned the University of Lincoln to undertake this research, with a view to developing a thorough understanding of the needs of PABC in Lincolnshire to ensure that service developments are acceptable, appropriate and accessible, and in line with the specific requirements of the local population. Aim (1)To examine the social care needs of PABC in Lincolnshire (2)To provide recommendations regarding future service development and delivery. Methods A qualitative study utilising in-depth interviews (n=10). Interviews were analysed using the Framework method of qualitative data analysis (Ritchie and Spencer, 1994). Results All reported the need for emotional support (in particular around the initial diagnosis and surrounding period). This was fulfilled by friends, family, support groups and Macmillan health professionals. The need for practical and personal care support varied amongst those we interviewed with this often being dependent on the type and frequency of treatment. For most, family and friends shouldered the burden of this as opposed to social services. Some participants relied on personal income to pay for treatment and fund additional costs associated with their illness. Furthermore, expenses were also attributed to friends and family of the patient. In addition we received reports of negative experiences when dealing with the Department of Work and Pensions (DWP) and claiming for Employment Support Allowance (ESA). Information and advice was important throughout the cancer journey; the preferred format (physical or online) was influenced by personal preference. For some, they felt well informed whilst others would have liked more information. Conclusion In line with national research (Macmillan, 2015), this study shows similarities in that respondents reported a range of supportive care needs in relation to emotional, practical and personal, financial and information support. Our study offers an in-depth analysis of the social care needs of PABC in a local setting. The small sample and failure to recruit across all stages of the cancer journey would limit the extent to which the findings could be extrapolated to the wider population. At the same time, it is hoped that the recommendations offer valuable insight into areas that could further be developed to meet the needs of PABC throughout the count

Co-design methods for eliciting patient needs for wrist splint design

Wrist splints are a common treatment for rheumatoid arthritis, however, their effectiveness is compromised by patients not wearing splints as prescribed. Previous research has identified reasons for non-compliance, but typically lacks insights that could lead to improved splint design. A three-part study, using design probes, context mapping and a personalization toolkit as co-design methods for eliciting patient needs for wrist splint designs, is described. It identifies three themes and nine sub-themes for situations that affect compliance in wearing a splint. Additionally, four motivating factors to wear and 10 motivating factors not to wear a splint are presented. Nine requirements for improved splint design are established and form the basis of the design for a prototype personalization toolkit. Testing of this toolkit reveals participants are keen to wear splints whose appearance matches the clothes they are wearing or activities being undertaken. Co-design methods are shown to be capable of identifying determinants of compliance not previously discussed in the literature, as well as eliciting patient-specific needs for splint design

Giving patients what they want: proposing additive manufacture as a method to design and fabricate wrist splints

Patients with Rheumatoid Arthritis may be prescribed wrist splints as part of their treatment regime however; compliance is known to be a problem. Whilst the literature provides an insight into some of the determinants behind compliance, it does not provide comprehensive knowledge of the reasons why patients wear and do not wear wrist splints. Recently, additive manufacturing has been proposed to create wrist splints. However, before developments in AM are made further, it needs to be understood why patients do not comply and what it is about the splint itself which makes patients not want to wear them. The aim of this paper is to use generative design research methods to understand these motivators, highlight the negative features of traditional splints, and explore participants’ dreams for a future splint. This data is then used to discuss how AM can be used in the splinting process

Exhausted CD4+ T Cells during Malaria Exhibit Reduced mTORc1 Activity Correlated with Loss of T-bet Expression

CD4<sup>+</sup> T cell functional inhibition (exhaustion) is a hallmark of malaria and correlates with impaired parasite control and infection chronicity. However, the mechanisms of CD4<sup>+</sup> T cell exhaustion are still poorly understood. In this study, we show that Ag-experienced (<i>Ag-exp</i>) CD4<sup>+</sup> T cell exhaustion during <i>Plasmodium yoelii</i> nonlethal infection occurs alongside the reduction in mammalian target of rapamycin (mTOR) activity and restriction in CD4<sup>+</sup> T cell glycolytic capacity. We demonstrate that the loss of glycolytic metabolism and mTOR activity within the exhausted <i>Ag-exp</i>CD4<sup>+</sup> T cell population during infection coincides with reduction in T-bet expression. T-bet was found to directly bind to and control the transcription of various mTOR and metabolism-related genes within effector CD4<sup>+</sup> T cells. Consistent with this, <i>Ag-exp</i>Th1 cells exhibited significantly higher and sustained mTOR activity than effector T-bet- (non-Th1) <i>Ag-exp</i>T cells throughout the course of malaria. We identified mTOR to be redundant for sustaining T-bet expression in activated Th1 cells, whereas mTOR was necessary but not sufficient for maintaining IFN-γ production by Th1 cells. Immunotherapy targeting PD-1, CTLA-4, and IL-27 blocked CD4<sup>+</sup> T cell exhaustion during malaria infection and was associated with elevated T-bet expression and a concomitant increased CD4<sup>+</sup> T cell glycolytic metabolism. Collectively, our data suggest that mTOR activity is linked to T-bet in <i>Ag-exp</i>CD4<sup>+</sup> T cells but that reduction in mTOR activity may not directly underpin <i>Ag-exp</i>Th1 cell loss and exhaustion during malaria infection. These data have implications for therapeutic reactivation of exhausted CD4<sup>+</sup> T cells during malaria infection and other chronic conditions

Metabolic effects of breaking prolonged sitting with standing or light walking in older South Asians and White Europeans: a randomized acute study

Background: Prolonged sitting is common in older adults and associated with insulin resistance and poor cardiometabolic health. We investigate whether breaking prolonged sitting with regular short bouts of standing or light walking improves postprandial metabolism in older white European and South Asian adults and whether effects are modified by ethnic group. Methods: Thirty South Asian (15 women) and 30 white European (14 women) older adults (65-79 years) undertook three experimental conditions in random order. 1) Prolonged sitting: continuous sitting during a 7.5 h observation period consuming two standardised mixed meals. 2) Standing breaks: sitting interrupted with 5 mins of standing every 30 mins (accumulating 60 mins of standing over the observation period). 3) Walking Breaks: sitting interrupted with 5 mins of self-paced light walking every 30 mins (accumulating 60 mins of walking). Blood samples (glucose, insulin, triglycerides) and blood pressure were sampled regularly throughout each condition. Results: Compared with prolonged sitting, walking breaks lowered postprandial insulin by 16.3 mU/l, (95% CI 19.7, 22.0) with greater reductions (p = 0.029) seen in South Asians (22.4 mU/l; 12.4, 32.4) than White Europeans (10.3 mU/l; 5.9, 14.7). Glucose (0.3 mmol/l; 0.1, 0.5) and blood pressure (4 mmHg; 2, 6), but not triglycerides, were lower with walking breaks, with no ethnic differences. Standing breaks did not improve any outcome. Conclusions: Breaking prolonged sitting with short bouts of light walking, but not standing, resulted in clinically meaningful improvements in markers of metabolic health in older adults, with South Asians gaining a greater reduction in postprandial insulin

Karyomapping for simultaneous genomic evaluation and aneuploidy screening of preimplantation bovine embryos: The first live-born calves

In cattle breeding, the development of genomic selection strategies based on single nucleotide polymorphism (SNP) interrogation has led to improved rates of genetic gain. Additionally, the application of genomic selection to in-vitro produced (IVP) embryos is expected to bring further benefits thanks to the ability to test a greater number of individuals before establishing a pregnancy and to ensure only carriers of desirable traits are born. However, aneuploidy, a leading cause of developmental arrest, is known to be common in IVP embryos. Karyomapping is a comprehensive screening test based on SNP typing that can be used for simultaneous genomic selection and aneuploidy detection, offering the potential to maximize pregnancy rates. Moreover, Karyomapping can be used to characterize the frequency and parental origin of aneuploidy in bovine IVP embryos, which have remained underexplored to date. Here, we report the use of Karyomapping to characterize the frequency and parental origin of aneuploidy in IVP bovine embryos in order to establish an estimate of total aneuploidy rates in each parental germline. We report an estimate of genome wide recombination rate in cattle and demonstrate, for the first time, a proof of principle for the application of Karyomapping to cattle breeding, with the birth of five calves after screening. This combined genomic selection and aneuploidy screening approach was highly reliable, with calves showing 98% concordance with their respective embryo biopsies for SNP typing and 100% concordance with their respective biopsies for aneuploidy screening. This approach has the potential to simultaneously improve pregnancy rates following embryo transfer and the rate of genetic gain in cattle breeding, and is applicable to basic research to investigate meiosis and aneuploidy

Beyond sarcasm: the metalanguage and structures of mock politeness

This paper aims to cast light on the somewhat neglected area of mock politeness. The principle objectives are to describe the ways that mock politeness is talked about and performed. In order to investigate such usage, I analyse data from informal, naturally occurring conversations in a UK-based online forum. The paper introduces a range of metalinguistic expressions which are used to refer to mock polite behaviours in lay interactions and describes the different structures of mock polite behaviours. The analysis shows that both metalanguage and structure are more diverse than anticipated by previous research and, as a result, the paper argues against equating mock politeness with sarcasm and calls for further research into mock politeness as an important strategy of impoliteness

Latent Cytomegalovirus-Driven Recruitment of Activated CD4+ T Cells Promotes Virus Reactivation

Human cytomegalovirus (HCMV) infection is not cleared by the initial immune response but persists for the lifetime of the host, in part due to its ability to establish a latent infection in cells of the myeloid lineage. HCMV has been shown to manipulate the secretion of cellular proteins during both lytic and latent infection; with changes caused by latent infection mainly investigated in CD34+ progenitor cells. Whilst CD34+ cells are generally bone marrow resident, their derivative CD14+ monocytes migrate to the periphery where they briefly circulate until extravasation into tissue sites. We have analyzed the effect of HCMV latent infection on the secretome of CD14+ monocytes, identifying an upregulation of both CCL8 and CXCL10 chemokines in the CD14+ latency-associated secretome. Unlike CD34+ cells, the CD14+ latency-associated secretome did not induce migration of resting immune cell subsets but did induce migration of activated NK and T cells expressing CXCR3 in a CXCL10 dependent manner. As reported in CD34+ latent infection, the CD14+ latency-associated secretome also suppressed the anti-viral activity of stimulated CD4+ T cells. Surprisingly, however, co-culture of activated autologous CD4+ T cells with latently infected monocytes resulted in reactivation of HCMV at levels comparable to those observed using M-CSF and IL-1β cytokines. We propose that these events represent a potential strategy to enable HCMV reactivation and local dissemination of the virus at peripheral tissue sites

Seropositivity for CMV and IL-6 levels are associated with grip strength and muscle size in the elderly

BACKGROUND: Sarcopenia is an important cause of morbidity and mortality in older adults, with immunosenescence and inflammation being possible underlying mechanisms. We investigated the relationship between latent cytomegalovirus (CMV) infection, Interleukin 6 (IL-6) levels, muscle size and strength in a group of healthy older community-dwelling people. METHODS: Participants were healthy volunteers from the Lothian Birth Cohort 1936 study. Participants had IL-6 level and CMV antibody titre measured at age 70 years and grip strength and a volumetric T1-weighted MRI brain scan (allowing measurement of neck muscle cross-sectional area (CSA)) at age 73. Markers of childhood deprivation were adjusted for in the analysis due to correlations between childhood deprivation and latent CMV infection. RESULTS: 866 participants were studied; 448 men (mean age 72.48 years, sd 0.70) and 418 women (mean age 72.51 years, sd 0.72). In men, CMV seropositivity was associated with smaller neck muscle CSA (p = 0.03, partial eta squared = 0.01), even after adjustment for IL-6 levels. Neck muscle CSA was not associated with CMV seropositivity in women, or CMV antibody titre or IL-6 level in either sex. Grip strength associated negatively with IL-6 level (right grip strength p<0.00001, partial eta squared 0.032 and left grip strength p<0.00001, partial eta squared 0.027) with or without adjustment for CMV serostatus or antibody titre. CMV status and antibody titre were not significantly associated with grip strength in either hand. CONCLUSION: These findings support the hypothesis that there is a relationship between markers of immunosenescence (i.e. CMV serostatus and IL6 level) and low muscle mass and strength and longitudinal studies in older cohorts are now required to investigate these relationships further