Living with a long-term condition: understanding well-being for individuals with thrombophilia or asthma

range of literature has explored the experience of living with a long-term condition (LTC), and frequently treats such experiences and conditions as problematic. In contrast, other research has demonstrated that it may be possible to adapt and achieve well-being, even when living with such a condition. This tends to focus on meaning and the qualitative experience of living with an LTC, and offers alternative perspectives, often of the same or similar conditions. As a result of these conflicting views, this study chose to consider two conditions which, though they may lead to life-threatening illness on occasion, do not appear to impact significantly the lives of all those affected on a daily basis. The aim of this research was to explore and explain how people make sense of two long-term, potentially life-threatening health conditions, namely, thrombophilia and asthma. In doing so, it specifically considered the contribution made by information about the condition. A constructivist grounded theory approach was adopted; this enabled the generation of a theory regarding how people make sense of their LTC, whilst acknowledging the social circumstances in which this was situated. Semi-structured interviews were conducted with 16 participants who had given consent to take part in the research. The findings demonstrate that participants undergo a two-stage process * gaining knowledge and living with a long-term condition . The theory based on these findings indicates that those who are knowledgeable about their condition, making informed decisions in relation to it, and accept their condition are able to live with it, whilst those who do not accept their condition do not fully adapt to it or integrate it into their live

Arctic hydroclimate variability during the last 2000 years : current understanding and research challenges

Reanalysis data show an increasing trend in Arctic precipitation over the 20th century, but changes are not homogenous across seasons or space. The observed hydro-climate changes are expected to continue and possibly accelerate in the coming century, not only affecting pan-Arctic natural ecosystems and human activities, but also lower latitudes through the atmospheric and ocean circulations. However, a lack of spatiotemporal observational data makes reliable quantification of Arctic hydroclimate change difficult, especially in a long-term context. To understand Arctic hydroclimate and its variability prior to the instrumental record, climate proxy records are needed. The purpose of this review is to summarise the current understanding of Arctic hydroclimate during the past 2000 years. First, the paper reviews the main natural archives and proxies used to infer past hydroclimate variations in this remote region and outlines the difficulty of disentangling the moisture from the temperature signal in these records. Second, a comparison of two sets of hydroclimate records covering the Common Era from two data-rich regions, North America and Fennoscandia, reveals inter- and intra-regional differences. Third, building on earlier work, this paper shows the potential for providing a high-resolution hydroclimate reconstruction for the Arctic and a comparison with last-millennium simulations from fully coupled climate models. In general, hydroclimate proxies and simulations indicate that the Medieval Climate Anomaly tends to have been wetter than the Little Ice Age (LIA), but there are large regional differences. However, the regional coverage of the proxy data is inadequate, with distinct data gaps in most of Eurasia and parts of North America, making robust assessments for the whole Arctic impossible at present. To fully assess pan-Arctic hydroclimate variability for the last 2 millennia, additional proxy records are required.Peer reviewe

How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins?

Variations on the statement "the variant surface glycoprotein (VSG) coat that covers the external face of the mammalian bloodstream form of Trypanosoma brucei acts a physical barrier" appear regularly in research articles and reviews. The concept of the impenetrable VSG coat is an attractive one, as it provides a clear model for understanding how a trypanosome population persists; each successive VSG protects the plasma membrane and is immunologically distinct from previous VSGs. What is the evidence that the VSG coat is an impenetrable barrier, and how do antibodies and other extracellular proteins interact with it? In this review, the nature of the extracellular surface of the bloodstream form trypanosome is described, and past experiments that investigated binding of antibodies and lectins to trypanosomes are analysed using knowledge of VSG sequence and structure that was unavailable when the experiments were performed. Epitopes for some VSG monoclonal antibodies are mapped as far as possible from previous experimental data, onto models of VSG structures. The binding of lectins to some, but not to other, VSGs is revisited with more recent knowledge of the location and nature of N-linked oligosaccharides. The conclusions are: (i) Much of the variation observed in earlier experiments can be explained by the identity of the individual VSGs. (ii) Much of an individual VSG is accessible to antibodies, and the barrier that prevents access to the cell surface is probably at the base of the VSG N-terminal domain, approximately 5 nm from the plasma membrane. This second conclusion highlights a gap in our understanding of how the VSG coat works, as several plasma membrane proteins with large extracellular domains are very unlikely to be hidden from host antibodies by VSG.The authors’ lab is funded by the Wellcome Trust (093008/Z10/Z) and the Medical Research Council (MR/L008246/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It was first available from PLOS via http://dx.doi.org/10.1371/journal.ppat.100525

Metrics for Transparency

Transparency is a novel non-functional requirement for software systems. It is acclaimed to improve the quality of service since it gives users access to information concerning the system's processes, clarifying who is responsible if something goes wrong. Thus, it is believed to support people's right to a secure and private processing of their personal data. We define eight quality metrics for transparency and we demonstrate the usage and the effectiveness of the metrics by assessing transparency on the Microsoft HealthVault, an on-line platform for users to collect, store, and share medical records

Enrichment of the tumour immune microenvironment in patients with desmoplastic colorectal liver metastasis

Background Patients with resected colorectal liver metastasis (CRLM) who display only the desmoplastic histopathological growth pattern (dHGP) exhibit superior survival compared to patients with any non-desmoplastic growth (non-dHGP). The aim of this study was to compare the tumour microenvironment between dHGP and non-dHGP. Methods The tumour microenvironment was investigated in three cohorts of chemo-naive patients surgically treated for CRLM. In cohort A semi-quantitative immunohistochemistry was performed, in cohort B intratumoural and peritumoural T cells were counted using immunohistochemistry and digital image analysis, and in cohort C the relative proportions of individual T cell subsets were determined by flow cytometry. Results One hundred and seventeen, 34, and 79 patients were included in cohorts A, B, and C, with dHGP being observed in 27%, 29%, and 15% of patients, respectively. Cohorts A and B independently demonstrated peritumoural and intratumoural enrichment of cytotoxic CD8+ T cells in dHGP, as well as a higher CD8+/CD4+ ratio (cohort A). Flow cytometric analysis of fresh tumour tissues in cohort C confirmed these results; dHGP was associated with higher CD8+ and lower CD4+ T cell subsets, resulting in a higher CD8+/CD4+ ratio. Conclusion The tumour microenvironment of patients with dHGP is characterised by an increased and distinctly cytotoxic immune infiltrate, providing a potential explanation for their superior survival

An Oligopeptide Transporter of Mycobacterium tuberculosis Regulates Cytokine Release and Apoptosis of Infected Macrophages

Background: The Mycobacterium tuberculosis genome encodes two peptide transporters encoded by Rv3665c-Rv3662c and Rv1280c-Rv1283c. Both belong to the family of ABC transporters containing two nucleotide-binding subunits, two integral membrane proteins and one substrate-binding polypeptide. However, little is known about their functions in M. tuberculosis. Here we report functional characterization of the Rv1280c-Rv1283c-encoded transporter and its substrate-binding polypeptide OppA(MTB). Methodology/Principal Findings: OppA(MTB) was capable of binding the tripeptide glutathione and the nonapeptide bradykinin, indicative of a somewhat broad substrate specificity. Amino acid residues G109, N110, N230, D494 and F496, situated at the interface between domains I and III of OppA, were required for optimal peptide binding. Complementaton of an oppA knockout mutant of M. smegmatis with OppA(MTB) confirmed the role of this transporter in importing glutathione and the importance of the aforesaid amino acid residues in peptide transport. Interestingly, this transporter regulated the ability of M. tuberculosis to lower glutathione levels in infected compared to uninfected macrophages. This ability was partly offset by inactivation of oppD. Concomitantly, inactivation of oppD was associated with lowered levels of methyl glyoxal in infected macrophages and reduced apoptosis-inducing ability of the mutant. The ability to induce the production of the cytokines IL-1 beta, IL-6 and TNF-alpha was also compromised after inactivation of oppD. Conclusions: Taken together, these studies uncover the novel observations that this peptide transporter modulates the innate immune response of macrophages infected with M. tuberculosis

Associations between general self-efficacy and health-related quality of life among 12-13-year-old school children: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>While research on school children's health has mainly focused on risk factors and illness, few studies have examined aspects of health promotion. Thus, this study focuses on health promotional factors including general self-efficacy (GSE) and health-related quality of life (HRQOL). GSE refers to a global confidence in coping ability across a wide range of demanding situations, and is related to health. The purpose of this study was to examine associations between GSE and HRQOL, and associations between HRQOL and socio-demographic characteristics. Knowledge of these associations in healthy school children is currently lacking.</p> <p>Methods</p> <p>During 2006 and 2007, 279 school children in the seventh grade across eastern Norway completed a survey assessing their GSE and HRQOL. The children were from schools that had been randomly selected using cluster sampling. T-tests were computed to compare mean subscale values between HRQOL and socio-demographic variables. Single and multiple regression analyses were performed to explore associations among GSE, HRQOL and socio-demographic variables.</p> <p>Results</p> <p>Regression analyses showed a significant relationship between increasing degrees of GSE and increasing degrees of HRQOL. In analyses adjusted for socio-demographic variables, boys scored higher than girls on self-esteem. School children from single-parent families had lower scores on HRQOL than those from two-parent families, and children who had relocated within the last five years had lower scores on HRQOL than those who had not relocated.</p> <p>Conclusion</p> <p>The strong relationship between GSE and HRQOL indicates that GSE might be a resource for increasing the HRQOL for school children.</p