Single Nucleotide Polymorphism Analysis of European Archaeological M. leprae DNA

Background: Leprosy was common in Europe eight to twelve centuries ago but molecular confirmation of this has been lacking. We have extracted M. leprae ancient DNA (aDNA) from medieval bones and single nucleotide polymorphism (SNP) typed the DNA, this provides insight into the pattern of leprosy transmission in Europe and may assist in the understanding of M. leprae evolution. Methods and Findings: Skeletons have been exhumed from 3 European countries (the United Kingdom, Denmark and Croatia) and are dated around the medieval period (476 to 1350 A.D.). we tested for the presence of 3 previously identified single nucleotide polymorphisms (SNPs) in 10 aDNA extractions. M. leprae aDNA was extracted from 6 of the 10 bone samples. SNP analysis of these 6 extractions were compared to previously analysed European SNP data using the same PCR assays and were found to be the same. Testing for the presence of SNPs in M. leprae DNA extracted from ancient bone samples is a novel approach to analysing European M. leprae DNA and the findings concur with the previously published data that European M. leprae strains fall in to one group (SNP group 3). Conclusions: These findings support the suggestion that the M. leprae genome is extremely stable and show that archaeological M. leprae DNA can be analysed to gain detailed information about the genotypic make-up of European leprosy, which may assist in the understanding of leprosy transmission worldwide

Knockdown of piRNA pathway proteins results in enhanced Semliki forest virus production in mosquito cells

The exogenous siRNA pathway is important in restricting arbovirus infection in mosquitoes. Less is known about the role of the PIWI-interacting RNA pathway, or piRNA pathway, in antiviral responses. Viral piRNA-like molecules have recently been described following infection of mosquitoes and derived cell lines with several arboviruses. The piRNA pathway has thus been suggested to function as an additional small RNA-mediated antiviral response to the known infection-induced siRNA response. Here we show that piRNA-like molecules are produced following infection with the naturally mosquito-borne Semliki Forest virus in mosquito cell lines. We show that knockdown of piRNA pathway proteins enhances the replication of this arbovirus and defines the contribution of piRNA pathway effectors, thus characterizing the antiviral properties of the piRNA pathway. In conclusion, arbovirus infection can trigger the piRNA pathway in mosquito cells, and knockdown of piRNA proteins enhances virus production

Computer aided design of solvent blends for hybrid cooling and antisolvent crystallization of active pharmaceutical ingredients

Choosing a solvent and an antisolvent for a new crystallization process is challenging due to the sheer number of possible solvent mixtures and the impact of solvent composition and crystallization temperature on process performance. To facilitate this choice, we present a general computer aided mixture/blend design (CAMbD) formulation for the design of optimal solvent mixtures for the crystallization of pharmaceutical products. The proposed methodology enables the simultaneous identification of the optimal process temperature, solvent, antisolvent, and composition of solvent mixture. The SAFT-γ Mie group-contribution approach is used in the design of crystallization solvents; based on an equilibrium model, both the crystal yield and solvent consumption are considered. The design formulation is implemented in gPROMS and applied to the crystallization of lovastatin and ibuprofen, where a hybrid approach combining cooling and antisolvent crystallization is compared to each method alone. For lovastatin, the use of a hybrid approach leads to an increase in crystal yield compared to antisolvent crystallization or cooling crystallization. Furthermore, it is seen that using less volatile but powerful crystallization solvents at lower temperatures can lead to better performance. When considering ibuprofen, the hybrid and antisolvent crystallization techniques provide a similar performance, but the use of solvent mixtures throughout the crystallization is critical in maximizing crystal yields and minimizing solvent consumption. We show that our more general approach to rational design of solvent blends brings significant benefits for the design of crystallization processes in pharmaceutical and chemical manufacturing

Whose Research Is This? - Participatory Secondary Data Analysis with People Living with Dementia

Drawing on our approach and findings from a secondary interrogation of an existing qualitative dataset, this work set out to challenge assumptions of practice through using participatory methods. Our approach brought two key aspects together: applying the theories of Douglas’s Cultural Theory of Risk and Tronto’s Ethic of Care, and a collaboration with people living with dementia as co-analysts in the co-production (interpretation) of knowledge and representing the experiences within the qualitative dataset. The research generated an understanding of relational care and the subtle ways in which relationships change for someone with dementia. In this case, we describe the processes we followed and reflect on the demands and challenges, experienced as researchers, in focusing on reflexivity, multiple voicing, literary styling, and performance. In our description of how we had to relinquish any sense of a concluding authoritative voice, we highlight the innovation in this participatory secondary data analysis and encourage others to engage with this dialogue

Work Package Report 6: Shared, plural and cultural values of ecosystems – 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 participants’ 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 ‘services’ or ‘benefits’. 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 ‘services’. 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 ‘intangible’ 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

A pilot dose-response study of the acute effects of haskap berry extract (Lonicera caerulea L.) on cognition, mood and blood pressure in older adults

Purpose Haskap (Lonicera caerulea L. or blue honeysuckle) is a plant native to the low-lying wet areas and mountains of Siberia and northeastern Asia, but is now cultivated in Canada. The dark blue berries are rich in anthocyanins, particularly cyanidin-3-O-glucoside. Previously, anthocyanin-rich fruits have been observed to benefit cognitive performance during the immediate postprandial period following a single acute dose. However, no study has currently examined the potential for haskap berries to influence cognitive performance. Here, we investigate the acute cognitive benefits of an anthocyanin-rich haskap berry extract. Methods A double-blind, counterbalanced, crossover intervention study compared the acute effects of three separate haskap berry extract doses, containing 100mg, 200mg, and 400mg anthocyanins, with a sugar-matched placebo. Participants were an opportunity sample of 20 older adults, aged 62-81 years. Measures of cognition, mood, and blood pressure were recorded at baseline and 1.5 hours postprandially. Results Compared to placebo, the 400mg dose elicited significantly lower diastolic blood pressure and heart rate. Both 200mg and 400mg doses elicited significantly higher word recall, with the 400mg dose also significantly improving word recognition scores, on an episodic memory task. However, mood, working memory and executive function task results were more equivocal. Conclusions The findings provide evidence for improvements in episodic memory and blood pressure following acute supplementation with haskap berry extract, with higher doses appearing most effective. The cognitive findings concur with previous literature that suggests episodic memory effects, and not executive function effects, are most prevalent in older adults following anthocyanin-rich berry supplementation. The blood pressure outcome is consistent with a vasodilatory mechanism of action

Concurrent use of prescription drugs and herbal medicinal products in older adults: A systematic review

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The use of herbal medicinal products (HMPs) is common among older adults. However, little is known about concurrent use with prescription drugs as well as the potential interactions associated with such combinations. Objective Identify and evaluate the literature on concurrent prescription and HMPs use among older adults to assess prevalence, patterns, potential interactions and factors associated with this use. Methods Systematic searches in MEDLINE, PsycINFO, EMBASE, CINAHL, AMED, Web of Science and Cochrane from inception to May 2017 for studies reporting concurrent use of prescription medicines with HMPs in adults (≥65 years). Quality was assessed using the Joanna Briggs Institute checklists. The Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre) three stage approach to mixed method research was used to synthesise data. Results Twenty-two studies were included. A definition of HMPs or what was considered HMP was frequently missing. Prevalence of concurrent use by older adults varied widely between 5.3% and 88.3%. Prescription medicines most combined with HMPs were antihypertensive drugs, beta blockers, diuretics, antihyperlipidemic agents, anticoagulants, analgesics, antihistamines, antidiabetics, antidepressants and statins. The HMPs most frequently used were: ginkgo, garlic, ginseng, St John’s wort, Echinacea, saw palmetto, evening primrose oil and ginger. Potential risks of bleeding due to use of ginkgo, garlic or ginseng with aspirin or warfarin was the most reported herb-drug interaction. Some data suggests being female, a lower household income and less than high school education were associated with concurrent use. Conclusion Prevalence of concurrent prescription drugs and HMPs use among older adults is substantial and potential interactions have been reported. Knowledge of the extent and manner in which older adults combine prescription drugs will aid healthcare professionals can appropriately identify and manage patients at risk.Peer reviewedFinal Published versio

A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD