1,084 research outputs found
L-configuration re-attachment of distal biceps tendon rupture
In distal biceps tendon ruptures, re-attachment to the radial tuberosity should ensure adequate tendon to bone contact for optimal healing
Modeling of pneumococcal serogroup 10 capsular polysaccharide molecular conformations provides insight into epitopes and observed cross-reactivity.
Streptococcus pneumoniae is an encapsulated gram-negative bacterium and a significant human pathogen. The capsular polysaccharide (CPS) is essential for virulence and a target antigen for vaccines. Although widespread introduction of pneumococcal conjugate vaccines (PCVs) has significantly reduced disease, the prevalence of non-vaccine serotypes has increased. On the basis of the CPS, S. pneumoniae serogroup 10 comprises four main serotypes 10A, 10B, 10C, and 10F; as well as the recently identified 10D. As it is the most prevalent, serotype 10A CPS has been included as a vaccine antigen in the next generation PCVs. Here we use molecular modeling to provide conformational rationales for the complex cross-reactivity reported between serotypes 10A, 10B, 10C, and 10F anti-sera. Although the highly mobile phosphodiester linkages produce very flexible CPS, shorter segments are conformationally defined, with exposed ÎČ-D-galactofuranose (ÎČ DGalf) side chains that are potential antibody binding sites. We identify four distinct conformational epitopes for the immunodominant ÎČ DGalf that assist in rationalizing the complex asymmetric cross-reactivity relationships. In particular, we find that strongly cross-reactive serotypes share common epitopes. Further, we show that human intelectin-1 has the potential to bind the exposed exocyclic 1,2-diol of the terminal ÎČ DGalf in each serotype; the relative accessibility of three- or six-linked ÎČ DGalf may play a role in the strength of the innate immune response and hence serotype disease prevalence. In conclusion, our modeling study and relevant serological studies support the inclusion of serotype 10A in a vaccine to best protect against serogroup 10 disease
Structural analysis of the O-acetylated O-polysaccharide isolated from Salmonella Paratyphi A and used for vaccine preparation
Salmonella paratyphi A is increasingly recognized as a common cause of enteric fever cases and there are no licensed vaccines against this infection. Antibodies directed against the O-polysaccharide of the lipopolysaccharide of Salmonella are protective and conjugation of the O-polysaccharide to a carrier protein represents a promising strategy for vaccine development. O-Acetylation of S. paratyphi A O-polysaccharide is considered important for the immunogenicity of S. paratyphi A conjugate vaccines. Here, as part of a programme to produce a bivalent conjugate vaccine against both S. typhi and S. paratyphi A diseases, we have fully elucidated the O-polysaccharide structure of S. paratyphi A by use of HPLC\u2013SEC, HPAEC\u2013PAD/CD, GLC, GLC\u2013MS, 1D and 2D-NMR spectroscopy. In particular, chemical and NMR studies identified the presence of O-acetyl groups on C-2 and C-3 of rhamnose in the lipopolysaccharide repeating unit, at variance with previous reports of O-acetylation at a single position. Moreover HR-MAS NMR analysis performed directly on bacterial pellets from several strains of S. paratyphi A also showed O-acetylation on C-2 and C-3 of rhamnose, thus this pattern is common and not an artefact from O-polysaccharide purification. Conjugation of the O-polysaccharide to the carrier protein had little impact on O-acetylation and therefore should not adversely affect the immunogenicity of the vaccine
What are shared and social values of ecosystems?
The theoretical framework outlined in this paper was developed initially through a series of expert workshops as part of the Valuing Nature Network â BRIDGE: From Values to Decisions project, funded by the UK Natural Environment Research Council (NERC). It was developed further through the follow-on phase of the UK National Ecosystem Assessment (Work Package 6: Shared, Plural and Cultural Values) funded by the UK Department of the Environment, Food and Rural Affairs (Defra), the Welsh Government, NERC, the Economic and Social Research Council (ESRC), and the Arts and Humanities Research Council (AHRC).Peer reviewedPublisher PD
The eventization of leisure and the strange death of alternative Leeds
The communicative potential of city spaces as leisure spaces is a central assumption of political activism and the creation of alternative, counter-cultural and subcultural scenes. However, such potential for city spaces is limited by the gentrification, privatization and eventization of city centres in the wake of wider societal and cultural struggles over leisure, work and identity formation. In this paper, we present research on alternative scenes in the city of Leeds to argue that the eventization of the city centre has led to a marginalization and of alternative scenes on the fringes of the city. Such marginalization has not caused the death of alternative Leeds or political activism associated with those scenesâbut it has changed the leisure spaces (physical, political and social) in which alternative scenes contest the mainstream
Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation.
The pathogenic bacterium Shigella is a leading cause of diarrheal disease and mortality, disproportionately affecting young children in low-income countries. The increasing prevalence of antibiotic resistance in Shigella necessitates an effective vaccine, for which the bacterial lipopolysaccharide O-antigen is the primary target. S. flexneri serotype 6 has been proposed as a multivalent vaccine component to ensure broad protection against Shigella. We have previously explored the conformations of S. flexneri O-antigens from serogroups Y, 2, 3, and 5 that share a common saccharide backbone (serotype Y). Here we consider serogroup 6, which is of particular interest because of an altered backbone repeat unit with non-stoichiometric O-acetylation, the antigenic and immunogenic importance of which have yet to be established. Our simulations show significant conformational changes in serogroup 6 relative to the serotype Y backbone. We further find that O-acetylation has little effect on conformation and hence may not be essential for the antigenicity of serotype 6. This is corroborated by an in vivo study in mice, using Generalized Modules for Membrane Antigens (GMMA) as O-antigen delivery systems, that shows that O-acetylation does not have an impact on the immune response elicited by the S. flexneri serotype 6 O-antigen
Work Package Report 6: Shared, plural and cultural values of ecosystems â Summary
Key findings:
Finding 1: Shared values resulting from deliberative, group-based valuation are different from individual values. Case study evidence suggests that they are more informed, considered, confident and reflective of participantsâ deeper-held, transcendental values. Deliberated, group-based monetary values may be a better reflection of real welfare impacts than non-deliberated individual values, if derived through a carefully designed and managed process. Although more research is needed to expand the currently small evidence base on deliberative monetary methods, group deliberation has the potential to significantly enhance elicitation of values.
Finding 2: The ethical, moral and justice dimensions of many environmental issues necessitate approaches that allow for the elicitation of shared and plural values. Key ethical concerns include: 1) providing a space and opportunity for people to identify values that they may find difficult to articulate (e.g. spiritual, identity); 2) recognising that some values cannot be traded without discussion and negotiation (e.g. the legal or felt rights of local people, intrinsic values of other species); and 3) understanding that it is often difficult to isolate valuation from decision-making processes because people feel there are strong ethical or moral issues at stake that need to be debated (e.g. the justice of the process, fairness in the distribution of benefits or disbenefits, responsibility, and issues of sustainability and future generations).
Finding 3: Catalyst and/or conflict points can play a key role in the emergence and articulation of values at a societal or community level that have not previously been outwardly or explicitly articulated. Catalyst and conflict points can be symbolic and are often linked to wider contested issues and meanings about who is involved in decision-making, whose voice counts and who receives the benefits or disbenefits of environmental change. These catalyst points can potentially be connected to feelings of powerlessness that give rise to concern and protest. By recognising transcendental societal and communal values (the deeper-held and overarching values held by society and communities), it becomes possible to make these values explicit and incorporate them in decision-making to better anticipate and manage conflicts.
Finding 4: There is a diversity of ways in which shared, plural, cultural and social values are used, but they are rarely conceptualised. The UK NEAFO provides a clear theoretical framework that distinguishes and categorises different dimensions and types of shared values. The proposed range of value types was both identifiable and distinguishable within case study results. This suggests that the framework provides a useful basis for operationalizing shared values for decision-making.
Finding 5: Shared and social values in the sense of value to society is conceptualised very differently by conventional economics and other disciplines. Neoclassical economists have generally undertaken valuation by equating social value with the aggregate of individual values. They consider values as fundamentally commensurable. In contrast, literature from other disciplines consistently considers values as plural, not just in the sense that multiple things have value, but also that there are multiple dimensions to value that cannot necessarily be captured in a single metric. Within mainstream economics, the difficulties associated with commensurability and aggregating values have long been recognised, but have also been neglected. An interesting area for future debate between economic and non-economic views on values may be the normative nature of value-aggregation.
Finding 6: A mixed method approach is required to elicit the multiple dimensions of shared values and to translate deeper-held, transcendental values into contextual values and preferences. Monetary valuation is limited to quantifying values. Other methods are needed to understand their meaning or content, and the communal, societal and transcendental values that underpin them. Psychometric, non-analytical and interpretive methods (e.g. storytelling) can reveal those shared values. They can be combined with deliberative-analytical methods (e.g. deliberative monetary valuation and multi-criteria analysis) to provide a comprehensive valuation that can quantify values, understand their individual and shared meanings and significance, and better include ethical dimensions.
Finding 7: Deliberative and social learning processes help people to understand the values held by others; they can lead to increased sharing of values and/or to greater acceptance of the decisions emerging from such processes. Deliberation clearly affects what values participants express compared to non-deliberated processes. There is also a growing body of theoretical and empirical research suggesting that deliberation has the potential to affect how people understand and shape the values of others. Although rarely considered in the economic literature, the concept of social learning helps to explain some of the processes involved in deliberation. The extent to which deliberation or social learning helps participants express and shape values will depend upon the frequency and depth of interactions and the timescale over which interactions occur. Only a shift in cultural values (e.g. less emphasis on material wealth), reflected in other societal institutions (e.g. changes in the indicators used to measure national progress) is likely to achieve sustainable outcomes in the long-term.
Finding 8: Media analysis is a promising avenue for characterising different types of shared values at a large scale, as well as assessing the conflicts between the communal values of different sectors of society. There has been a marked increase in public interest in environmental issues over the last decade, which is reflected in their increased media coverage. Media content and discourse analysis is able to distinguish and characterise the plurality of cultural, societal and transcendental values and their interrelationships, and can offer a picture of the self- and other-regarding values that underpin environmental issues and conflicts. Social media can provide a further forum for understanding societal and communal values surrounding environmental issues.
Finding 9: Aesthetic and spiritual values of ecosystems have a strong non-instrumental component. While they benefit human well-being, they should not simply be classified as just âservicesâ or âbenefitsâ. Many spiritual discourses about nature resist talk of consequentialist benefits and economic analysis. These discourses counter assertions of the disenchantment of the world, which is associated with an instrumental environmental ethic and the commodification of nature. Allowing the possibility of enchantment can be a richer way of understanding our experience of nature and alerts us to the limitations of using economic models for valuation and informing decisions about these profound cultural ecosystem âservicesâ. Faith communities have experience of using these non-utilitarian values in their own decision-making and provide models that could be adapted for use in environmental decision-making.
Finding 10: Subjective well-being measures provide a useful means of assessing âintangibleâ cultural ecosystem services and their benefits. Different user groups associate common elements of subjective well-being with environmental settings, providing opportunities for development of standardised measures. In the UK NEAFO, key facets of well-being associated with places in nature across different user groups included: engagement with nature (incorporating elements of connectedness, getting to know nature and the beauty of nature, and taking care of a place); therapeutic benefits (including physical and mental aspects of health); place identity (including a sense of place and belonging); spiritual value (in the sense of feeling connected or responsible to something larger than oneself); social bonding with others; and transformative and memorable experiences. Further empirical work with different user groups and environmental settings would allow for the continued development of a standardised tool for large-scale non-monetary assessment of cultural ecosystem services
Early childhood education in differing contexts:The impact of the COVID-19 global health pandemic within four countries
The recent Covidâ19 global health pandemic has negatively affected the political and economic development of communities around the world. This article shares the lessons from our multiâcountry project Safe, Inclusive Participative Pedagogy: Improving Early Childhood Education in Fragile Contexts (UKRI GCRF) on how children in communities in Brazil, Eswatini, South Africa, and Scotland have experienced the effects of the pandemic. This article benefits from having coâauthors from various countries, bringing their own located knowledge to considerations of childrenâs rights and early childhood education in the wake of the pandemic. The authors discuss different perspectives on childrenâs human rights within historical, social, and cultural contexts and, by doing so, will discuss how the global pandemic has placed a spotlight on the previous inequalities within early years education and how the disparity of those with capital (economic and social) have led to an even greater disproportion of children needing health and educational support
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