Constructing embodied identity in a 'new' ageing population: a qualitative study of the pioneer cohort of childhood liver transplant recipients in the UK

Medical innovations have created a future of survivorship for many groups of people with a variety of conditions that were previously untreatable or untreated. This has led not only to an expansion of medical activity in a whole variety of new areas but also to the emergence of new groups of individuals defined or defining themselves through their experiences, diagnosis and treatment. Through analysis of in-depth interviews with 27 of the now-adult survivors of the pioneer cohort of children receiving liver transplants in Britain in the early 1980s and 1990s, this paper presents how this group not only illustrate the capacities of modern medicine and healthcare to transform the survival prospects of a more diversified population, but also create new narratives of embodied identity. Specifically, we examine how childhood identities were shaped in three settings; home, hospital and school. At home, parents appeared to shape their child’s identity through controlling tightly a daily medical regime focused on the concept of ‘body as machine’, celebrating their survival as a transplant recipient, yet at the same time socialising their child as a ‘normal’ child, albeit one who had a serious illness. The hospital appeared instrumental in shaping parents’ focus on their child’s body, and offered a way, through other patients with liver disease, for children to feel ‘normal’ in their difference. It was in school, through interaction with ‘healthy’ children and teachers, that corporeality and embodiment appeared most salient, and where social identity was negotiated and more often held in contention. Adult survivors of childhood liver transplant straddle the different discourses of normality and difference as their embodied experiences shape their narratives of identity and shed light on an underexplored aspect of the relationship between medicine and society

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway

Circulating Markers Reflect Both Anti- and Pro-Atherogenic Drug Effects in ApoE-Deficient Mice

Background: Current drug therapy of atherosclerosis is focused on treatment of major risk factors, e.g. hypercholesterolemia while in the future direct disease modification might provide additional benefits. However, development of medicines targeting vascular wall disease is complicated by the lack of reliable biomarkers. In this study, we took a novel approach to identify circulating biomarkers indicative of drug efficacy by reducing the complexity of the in vivo system to the level where neither disease progression nor drug treatment was associated with the changes in plasma cholesterol.Results: ApoE-/- mice were treated with an ACE inhibitor ramipril and HMG-CoA reductase inhibitor simvastatin. Ramipril significantly reduced the size of atherosclerotic plaques in brachiocephalic arteries, however simvastatin paradoxically stimulated atherogenesis. Both effects occurred without changes in plasma cholesterol. Blood and vascular samples were obtained from the same animals. In the whole blood RNA samples, expression of MMP9, CD14 and IL-1RN reflected pro and anti-atherogenic drug effects. In the plasma, several proteins, e.g. IL-1β, IL-18 and MMP9 followed similar trends while protein readout was less sensitive than RNA analysis.Conclusion: In this study, we have identified inflammation-related whole blood RNA and plasma protein markers reflecting anti-atherogenic effects of ramipril and pro-atherogenic effects of simwastatin in a mouse model of atherosclerosis. This opens an opportunity for early, non-invasive detection of direct drug effects on atherosclerotic plaques in complex in vivo systems

Generation of bivalent chromatin domains during cell fate decisions

<p>Abstract</p> <p>Background</p> <p>In self-renewing, pluripotent cells, bivalent chromatin modification is thought to silence (H3K27me3) lineage control genes while 'poising' (H3K4me3) them for subsequent activation during differentiation, implying an important role for epigenetic modification in directing cell fate decisions. However, rather than representing an equivalently balanced epigenetic mark, the patterns and levels of histone modifications at bivalent genes can vary widely and the criteria for identifying this chromatin signature are poorly defined.</p> <p>Results</p> <p>Here, we initially show how chromatin status alters during lineage commitment and differentiation at a single well characterised bivalent locus. In addition we have determined how chromatin modifications at this locus change with gene expression in both ensemble and single cell analyses. We also show, on a global scale, how mRNA expression may be reflected in the ratio of H3K4me3/H3K27me3.</p> <p>Conclusions</p> <p>While truly 'poised' bivalently modified genes may exist, the original hypothesis that all bivalent genes are epigenetically premarked for subsequent expression might be oversimplistic. In fact, from the data presented in the present work, it is equally possible that many genes that appear to be bivalent in pluripotent and multipotent cells may simply be stochastically expressed at low levels in the process of multilineage priming. Although both situations could be considered to be forms of 'poising', the underlying mechanisms and the associated implications are clearly different.</p

The Morphology of Galaxies in the Baryon Oscillation Spectroscopic Survey

We study the morphology of luminous and massive galaxies at 0.3<z<0.7 targeted in the Baryon Oscillation Spectroscopic Survey (BOSS) using publicly available Hubble Space Telescope imaging from COSMOS. Our sample (240 objects) provides a unique opportunity to check the visual morphology of these galaxies which were targeted based solely on stellar population modelling. We find that the majority (74+/-6%) possess an early-type morphology (elliptical or S0), while the remainder have a late-type morphology. This is as expected from the goals of the BOSS target selection which aimed to predominantly select slowly evolving galaxies, for use as cosmological probes, while still obtaining a fair fraction of actively star forming galaxies for galaxy evolution studies. We show that a colour cut of (g-i)>2.35 selects a sub-sample of BOSS galaxies with 90% early-type morphology - more comparable to the earlier Luminous Red Galaxy (LRG) samples of SDSS-I/II. The remaining 10% of galaxies above this cut have a late-type morphology and may be analogous to the "passive spirals" found at lower redshift. We find that 23+/-4% of the early-type galaxies are unresolved multiple systems in the SDSS imaging. We estimate that at least 50% of these are real associations (not projection effects) and may represent a significant "dry merger" fraction. We study the SDSS pipeline sizes of BOSS galaxies which we find to be systematically larger (by 40%) than those measured from HST images, and provide a statistical correction for the difference. These details of the BOSS galaxies will help users of the data fine-tune their selection criteria, dependent on their science applications. For example, the main goal of BOSS is to measure the cosmic distance scale and expansion rate of the Universe to percent-level precision - a point where systematic effects due to the details of target selection may become important.Comment: 18 pages, 11 figures; v2 as accepted by MNRA

Living well to the end:a phenomenological analysis of life in extra care housing

OBJECTIVES: To understand older adults' experiences of moving into extra care housing which offers enrichment activities alongside social and healthcare support. DESIGN: A longitudinal study was conducted which adopted a phenomenological approach to data generation and analysis. METHODS: Semi-structured interviews were conducted in the first 18 months of living in extra care housing. Interpretative phenomenological analysis was used because its commitment to idiography enabled an in-depth analysis of the subjective lived experience of moving into extra care housing. Themes generated inductively were examined against an existential-phenomenological theory of well-being. RESULTS: Learning to live in an extra care community showed negotiating new relationships was not straightforward; maintaining friendships outside the community became more difficult as capacity declined. In springboard for opportunity/confinement, living in extra care provided new opportunities for social engagement and a restored sense of self. Over time horizons began to shrink as incapacities grew. Seeking care illustrated reticence to seek care, due to embarrassment and a sense of duty to one's partner. Becoming aged presented an ontological challenge. Nevertheless, some showed a readiness for death, a sense of homecoming. CONCLUSIONS: An authentic later life was possible but residents required emotional and social support to live through the transition and challenges of becoming aged. Enhancement activities boosted residents' quality of life but the range of activities could be extended to cater better for quieter, smaller scale events within the community; volunteer activity facilitators could be used here. Peer mentoring may help build new relationships and opportunities for interactive stimulation. Acknowledging the importance of feeling-empathic imagination-in caregiving may help staff and residents relate better to each other, thus helping individuals to become ontologically secure and live well to the end

A Taxonomy and Results from a Comprehensive Review of 28 Maternal Health Voucher Programmes

It is increasingly clear that Millennium Development Goal 4 and 5 will not be achieved in many low- and middle-income countries with the weakest gains among the poor. Recognizing that there are large inequalities in reproductive health outcomes, the post-2015 agenda on universal health coverage will likely generate strategies that target resources where maternal and newborn deaths are the highest. In 2012, the United States Agency for International Development convened an Evidence Summit to review the knowledge and gaps on the utilization of financial incentives to enhance the quality and uptake of maternal healthcare. The goal was to provide donors and governments of the low- and middle-income countries with evidenceinformed recommendations on practice, policy, and strategies regarding the use of financial incentives, including vouchers, to enhance the demand and supply of maternal health services. The findings in this paper are intended to guide governments interested in maternal health voucher programmes with recommendations for sustainable implementation and impact. The Evidence Summit undertook a systematic review of five financing strategies. This paper presents the methods and findings for vouchers, building on a taxonomy to catalogue knowledge about voucher programme design and functionality. More than 120 characteristics under five major categories were identified: programme principles (objectives and financing); governance and management; benefits package and beneficiary targeting; providers (contracting and service pricing); and implementation arrangements (marketing, claims processing, and monitoring and evaluation). Among the 28 identified maternal health voucher programmes, common characteristics included: a stated objective to increase the use of services among the means-tested poor; contracted-out programme management; contracting either exclusively private facilities or a mix of public and private providers; prioritizing community-based distribution of vouchers; and tracking individual claims for performance purposes. Maternal voucher programmes differed on whether contracted providers were given training on clinical or administrative issues; whether some form of service verification was undertaken at facility or communitylevel; and the relative size of programme management costs in the overall programme budget. Evidence suggests voucher programmes can serve populations with national-level impact. Reaching scale depends on whether the voucher programme can: (i) keep management costs low, (ii) induce a large demand-side response among the bottom two quintiles, and (iii) achieve a quality of care that translates a greater number of facility-based deliveries into a reduction in maternal morbidity and mortality

Stellar masses of SDSS-III/BOSS galaxies at z ~ 0.5 and constraints to galaxy formation models

We calculate stellar masses for ∼400 000 massive luminous galaxies at redshift ∼0.2–0.7 using the first two years of data from the Baryon Oscillation Spectroscopic Survey (BOSS). Stellar masses are obtained by fitting model spectral energy distributions to u, g, r, i, z magnitudes, and simulations with mock galaxies are used to understand how well the templates recover the stellar mass. Accurate BOSS spectroscopic redshifts are used to constrain the fits. We find that the distribution of stellar masses in BOSS is narrow (Δlog M ∼ 0.5 dex) and peaks at about log M/M⊙ ∼ 11.3 (for a Kroupa initial stellar mass function), and that the mass sampling is uniform over the redshift range 0.2–0.6, in agreement with the intended BOSS target selection. The galaxy masses probed by BOSS extend over ∼1012 M⊙, providing unprecedented measurements of the high-mass end of the galaxy mass function. We find that the galaxy number density above ∼2.5 × 1011 M⊙ agrees with previous determinations. We perform a comparison with semi-analytic galaxy formation models tailored to the BOSS target selection and volume, in order to contain incompleteness. The abundance of massive galaxies in the models compare fairly well with the BOSS data, but the models lack galaxies at the massive end. Moreover, no evolution with redshift is detected from ∼0.6 to 0.4 in the data, whereas the abundance of massive galaxies in the models increases to redshift zero. Additionally, BOSS data display colour–magnitude (mass) relations similar to those found in the local Universe, where the most massive galaxies are the reddest. On the other hand, the model colours do not display a dependence on stellar mass, span a narrower range and are typically bluer than the observations. We argue that the lack of a colour–mass relation for massive galaxies in the models is mostly due to metallicity, which is too low in the models

Applying a new concept of embedding qualitative research: An example from a quantitative study of carers of people in later stage dementia

BACKGROUND: Qualitative methods are increasingly included in larger studies to provide a richer understanding of people's experience. This paper explores the potential of using a novel approach to embedded qualitative design as part of an observational study examining the effectiveness of home support for people in later stage dementia in England. The method involved collecting and analysing unsolicited conversational comments made by participants as they completed standardised measures. An evaluation of the method is presented using the voices of participants to illustrate its potential. METHODS: The conversations of 17 carers recruited to an observational study were audio recorded to gather commentary made while completing a structured interview. Data were interrogated using thematic analysis to investigate the feasibility of conducting an embedded qualitative study, the potential richness of the material and participants' reactions to formal questioning and participating in research. RESULTS: The findings revealed that qualitative data were available from this approach. Analysis generated three themes from carers: conflicting carer emotions; the importance of maintaining normality and agency within day-to-day life; and tensions between these desires and making use of formal services. Important issues for carers were revealed establishing the benefit of using the method. The advantages of exploiting unsolicited conversation included enhancing understanding of people's lived experience, reducing participant burden in research and easing the process of data collection. In addition, it provided an opportunity to evaluate individuals' experience of the research process. CONCLUSIONS: The findings demonstrate how unsolicited comments during structured interviews may appear incidental but can reveal important aspects of living with dementia. The method also emphasised methodological challenges for research in dementia, including the influence and impact of the research context. Further research is required to evaluate the method with other groups including people with dementia themselves