Troubling stoicism:Sociocultural influences and applications to health and illness behaviour

In light of the ambiguity of meanings attributed to the concept of stoicism we critically explore its use as a label to explain and describe health and illness behaviour, juxtaposing the often negative portrayals of contemporary stoicism against its classical and philosophical origins. By reflecting critically on the term ‘stoicism’, its application and dimensionality, we show how the term has evolved from classical to contemporary times in relation to changing context, and explore different understandings of the term across medical and health literature. We attend to sociocultural factors that are seen to influence the conceptualization of stoicism such as generational influences, gender and geographies. We make the assertion that by applying the label of ‘stoicism’ as it is known today, there is a danger of too readily accepting a term that masks particular health behaviours while missing an array of sociological factors that are important to how people deal with adversity arising from chronic health problems. We therefore encourage further questioning of this term. </jats:p

The Development of a Cocktail CYP2B6, CYP2C8 &amp; CYP3A5 Inhibition Assay and a Preliminary Assessment of Utility in a Drug Discovery Setting

Abstract Tools for studying the roles of CYP2B6, CYP2C8 and CYP3A5 in drug metabolism have recently become available. The level of interest in these enzymes has been elevated because investigations have revealed substrate promiscuity and/or polymorphic expression. This study aimed to develop a single cocktail inhibition assay for the three enzymes and assess its utility in drug discovery. Bupropion hydroxylation, amodiaquine N-deethylation and midazolam 1&apos;-hydroxylation were chosen as probe reactions for CYP2B6, CYP2C8 and CYP3A5 and were analysed using LC-MS-MS. Kinetic analyses were performed to establish suitable conditions for inhibition assays, which were subsequently automated. CYP2B6, CYP2C8 and CYP3A5 IC 50 values were determined for marketed drugs and almost two hundred AZ discovery compounds from 16 separate discovery projects. For the marketed drugs, results obtained were comparable with literature values. Data were also compared with IC 50 values determined for CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. In this dataset, the majority of compounds were more potent inhibitors of CYP2C9, CYP2C19, CYP2D6 and CYP3A4 than CYP2B6, CYP2C8 or CYP3A5. The potential impact of these findings on CYP inhibition strategy is discussed

Heterotypic interactions drive antibody synergy against a malaria vaccine candidate

Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candidate, CyRPA, is essential for invasion of Plasmodium falciparum into human erythrocytes. Here we present a panel of anti-CyRPA monoclonal antibodies that strongly inhibit parasite growth in in vitro assays. Structural studies show that growth-inhibitory antibodies bind epitopes on a single face of CyRPA. We also show that pairs of non-competing inhibitory antibodies have strongly synergistic growth-inhibitory activity. These antibodies bind to neighbouring epitopes on CyRPA and form lateral, heterotypic interactions which slow antibody dissociation. We predict that such heterotypic interactions will be a feature of many immune responses. Immunogens which elicit such synergistic antibody mixtures could increase the potency of vaccine-elicited responses to provide robust and long-lived immunity against challenging disease targets

Evolutionary-thinking in agricultural weed management

Agricultural weeds evolve in response to crop cultivation. Nevertheless, the central importance of evolutionary ecology for understanding weed invasion, persistence and management in agroecosystems is not widely acknowledged. This paper calls for more evolutionarily-enlightened weed management, in which management principles are informed by evolutionary biology to prevent or minimize weed adaptation and spread. As a first step, a greater knowledge of the extent, structure and significance of genetic variation within and between weed populations is required to fully assess the potential for weed adaptation. The evolution of resistance to herbicides is a classic example of weed adaptation. Even here, most research focuses on describing the physiological and molecular basis of resistance, rather than conducting studies to better understand the evolutionary dynamics of selection for resistance. We suggest approaches to increase the application of evolutionary-thinking to herbicide resistance research. Weed population dynamics models are increasingly important tools in weed management, yet these models often ignore intrapopulation and interpopulation variability, neglecting the potential for weed adaptation in response to management. Future agricultural weed management can benefit from greater integration of ecological and evolutionary principles to predict the long-term responses of weed populations to changing weed management, agricultural environments and global climate

"I try and smile, I try and be cheery, I try not to be pushy. I try to say ‘I’m here for help’ but I leave feeling… worried’’: A qualitative study of perceptions of interactions with health professionals by community-based older adults with chronic pain

Background: Over 50% of community-dwelling older adults experience chronic pain, which threatens their quality of life. Of importance to their pain management is older people’s interaction with health professionals that, if unsatisfactory, may impair the outcome. Aims: To add to the limited research specific to older people living with chronic pain in the community, we explored how they perceive their experiences of interacting with health professionals, seeking factors that might optimise these interactions. Methods: Purposive sampling was used to recruit men and women .65 years with self-reported musculoskeletal chronic pain. Qualitative individual interviews and one group interview were undertaken with 23 participants. Data were transcribed verbatim and underwent Framework Analysis. Results: Three themes were identified. Seeking help illustrates issues around why older people in the community may or may not seek help for chronic pain, and highlights the potential involvement of social comparison. Importance of diagnosis illustrates the desire for professional validation of their condition and an aversion to vague explanations based on the person’s age. Being listened to and being heard illustrates the importance of empathic communication and understanding expectations, with due respect for the person’s age. Conclusions: In common with people of all ages, an effective partnership between an older person in pain and health professionals is essential if pain is to be reported, appropriately assessed and managed, because of the subjective nature of pain and its treatment responses. For older people with pain, perception about their age, by both parties in the partnership, is an additional factor that can unnecessarily interfere with the effectiveness of this partnership. Health professionals should engage with older adults to clarify their expectations about pain and its management, which may be influenced by perceptions about age; and to encourage expression of their concerns, which may also be affected by perceptions about age

Soils and palaeo-climate based evidence for irrigation requirements in Norse Greenland

Establishing and sustaining agricultural production was a key factor in the success of Norse settlements during the landnám colonisation across the North Atlantic. In light of the occurrence of channel features in several abandoned home-field areas of the Norse Eastern Settlement of Greenland, and the irrigation requirements of present-day Greenlandic sheep-farmers questions are raised: was irrigation used by the Norse settlers of Greenland on their home-field areas? and, if so, how frequently? Modelling of soil chemical, physical and soil-water hydraulic properties integrated with contemporary high-resolution climatic data demonstrate a frequent requirement for irrigation. Soil moisture deficits are related to the duration and intensity of winter temperature. Using the winter Dye 3 ice core δ18O record as a climatic proxy, the frequency of moisture deficits, based on comparing mean winter temperatures, indicates that there was a frequent irrigation requirement to maintain home-field productivity, increasing throughout the period of settlement until the 14th Century

Outcome of the First wwPDB Hybrid / Integrative Methods Task Force Workshop

Structures of biomolecular systems are increasingly computed by integrative modeling that relies on varied types of experimental data and theoretical information. We describe here the proceedings and conclusions from the first wwPDB Hybrid/Integrative Methods Task Force Workshop held at the European Bioinformatics Institute in Hinxton, UK, on October 6 and 7, 2014. At the workshop, experts in various experimental fields of structural biology, experts in integrative modeling and visualization, and experts in data archiving addressed a series of questions central to the future of structural biology. How should integrative models be represented? How should the data and integrative models be validated? What data should be archived? How should the data and models be archived? What information should accompany the publication of integrative models

BUGS in the Analysis of Biodiversity Experiments: Species Richness and Composition Are of Similar Importance for Grassland Productivity

The idea that species diversity can influence ecosystem functioning has been controversial and its importance relative to compositional effects hotly debated. Unfortunately, assessing the relative importance of different explanatory variables in complex linear models is not simple. In this paper we assess the relative importance of species richness and species composition in a multilevel model analysis of net aboveground biomass production in grassland biodiversity experiments by estimating variance components for all explanatory variables. We compare the variance components using a recently introduced graphical Bayesian ANOVA. We show that while the use of test statistics and the R2 gives contradictory assessments, the variance components analysis reveals that species richness and composition are of roughly similar importance for primary productivity in grassland biodiversity experiments