Relocating civil society in a politics of civic-driven change

Politics is central to development discourse, yet remains peripheral. Over some twenty years, a civil-society narrative has not fulfilled its potential to 'bring politics back in'. Reasons can be found in conceptual confusion, in selectivity in donor thinking, in policies towards civil society and in the growth-driven political economy of NGO-ism. Remedies for the political lacunae are being sought through a focus on rights, citizenship and leadership that show valuable focused progress. This article examines a comprehensive complement to such efforts referred to as civic-driven change (CDC). Originating in a grounded empirical approach, the constituent principles and elements of CDC offer a lens that can both sharpen and deepen insights and advance analysis of socio-political processes. © The Authors 2013. Development Policy Revie

Measurement of the neutrino-oxygen neutral-current interaction cross section by observing nuclear deexcitation gamma rays

We report the first measurement of the neutrino-oxygen neutral-current quasielastic (NCQE) cross section gamma It is obtained by observing nuclear deexcitation. rays which follow neutrino-oxygen interactions at the Super-Kamiokande water Cherenkov detector. We use T2K data corresponding to 3.01 x 10(20) protons on target. By selecting only events during the T2K beam window and with well-reconstructed vertices in the fiducial volume, the large background rate from natural radioactivity is dramatically reduced. We observe 43 events in the 4-30 MeV reconstructed energy window, compared with an expectation of 51.0, which includes an estimated 16.2 background events. The background is primarily nonquasielastic neutral-current interactions and has only 1.2 events from natural radioactivity. The flux-averaged NCQE cross section we measure is 1.55 x 10(-38) cm(2) with a 68% confidence interval of (1.22, 2.20) x 10(-38) cm(2) at a median neutrino energy of 630 MeV, compared with the theoretical prediction of 2.01 x 10(-38) cm(2)

Indication of Electron Neutrino Appearance from an Accelerator-Produced Off-Axis Muon Neutrino Beam

The T2K experiment observes indications of nu(mu) -> nu(mu) e appearance in data accumulated with 1.43 x 10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Delta m(23)(2)| = 2.4 x 10(-3) eV(2), sin(2)2 theta(23) = 1 and sin(2)2 theta(13) = 0, the expected number of such events is 1.5 +/- 0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7 x 10(-3), equivalent to 2.5 sigma significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2 theta(13) < 0.28(0.34) for delta(CP) = 0 and a normal (inverted) hierarchy

An evidence base to optimise methods for involving patient and public contributors in clinical trials: a mixed-methods study

BACKGROUND: In comparison with other study designs, randomised trials are regarded as particularly likely to benefit from patient and public involvement (PPI). Using mixed-methods research we investigated PPI from the perspectives of researchers and PPI contributors. METHODS: Randomised trials in receipt of funding from the Health Technology Assessment (HTA) programme between 2006 and 2010 were identified. Funding applications and board and referee comments were obtained and data relevant to PPI extracted. Chief investigators (CIs), PPI contributors and UK Clinical Research Collaboration Registered Clinical Trials Units (RCTUs) were surveyed. Interviews were conducted with researchers and PPI contributors. RESULTS: A total of 111 trials were included. Text relevant to PPI was identified in half of the trials for which the first-stage applications were available, but only one-quarter described PPI within their development. In the second stage of the application, the majority provided some text relevant to PPI, with over half having PPI in their development. Fewer than half of referees commented on PPI, and funding boards rarely provided comments in relation to PPI. Seventy-three per cent (81 of 111) of CIs responded to the survey and 98% (79 of 81) included PPI at some stage in their trial. CIs considered high impact from PPI contributors to occur more frequently in trial setup, with low or no impact being more common during trial conduct, analysis and dissemination. Only one-third of CIs provided PPI contributor contact details but all contributors contacted completed the survey. The majority of contributors felt engaged and valued by the research team. Interviews were conducted with researchers and/or PPI contributors for 28 trials identifying two main influences on perception of PPI impact: whether or not CIs expressed personal goals and plans for PPI; and the quality of their relationship with the PPI contributors. The importance of early engagement was identified, with opportunity for input thereafter limited. Three PPI roles were identified: oversight, managerial and responsive. Oversight roles, as required by funders, were associated with low impact in comparison with responsive or managerial roles. Most researchers could see some value in PPI training for researchers, although those that had received such training themselves expressed concerns about its purpose and evidence base. Training for PPI contributors was considered unnecessary, with conversational approaches preferred, although this did not appear to provide an opportunity for role negotiation. The RCTU survey response rate was 85% (39 of 46). The majority (37 of 39) reported PPI within trials co-ordinated by their unit. Trial characteristics were used by half to determine the approach to PPI. Two-thirds reported recent developments or changes in implementing plans for PPI (21 of 33). Support to PPI contributors was commonly offered through members of staff at the unit. CONCLUSIONS: PPI is occurring in the majority of trials funded by the HTA programme, but uncertainty remains about how it is assessed and valued. Early involvement, building a relationship between researchers and contributors, responsive or managerial roles, and having defined goals for PPI were associated with impact. Efficiency could be gained by utilising the RCTU network to identify and tackle challenges, and develop a risk-based approach utilising trial characteristics. Recommendations are made to trial funders and the research community. Given the difficulties for some informants in recalling PPI contributions, future research using a prospective approach would be valuable. Ethnographic research that combines observation and multi-informant interviews is likely to be informative in identifying impact. The research community needs to give further consideration to processes for selecting PPI contributors and models of implementing PPI

The Concise Guide to PHARMACOLOGY 2023/24: Catalytic receptors.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16180. Catalytic receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

Patient and public involvement (PPI) in UK surgical trials: a survey and focus groups with stakeholders to identify practices, views and experiences

Background and aims: Patient and public involvement (PPI) in the design and conduct of surgical trials historically has been absent or minimal, but it is now recommended routinely and even required by some research funders. We aimed to identify and describe current PPI practice in surgical trials in the United Kingdom, then explore the views and experiences of surgical trial staff and patient or public contributors in relation to these practices. This was part of a larger study to inform development of a robust PPI intervention aimed at improving recruitment and retention in surgical trials. Methods: Two stages: (1) Online survey to identify current PPI practice in active UK-led, adult surgical trials; (2) Focus groups and interviews with key stakeholders (surgical trial investigators, administrators and patient or public contributors) to explore their views and experiences of PPI. Results: 129 eligible surgical trial teams were identified and 71 (55%) took part in the survey. 54 stakeholders subsequently took part in focus groups or interviews. Sixty-five (92%) survey respondents reported some kind of PPI, most commonly at the design and dissemination stages and in oversight or advisory roles. The single most common PPI activity was developing participant information sheets (79%). Participants reported mixed practice and views on a variety of issues including the involvement of patients versus lay members of the public, recruitment methods, use of role descriptions and payment for PPI contributors’ time. They suggested some solutions, including the use of written role descriptions and databases of potential PPI contributors to aid recruitment. Conclusions: UK surgical trials involve patients and members of the public in a variety of different ways, most commonly at the beginning and end of the trial lifecycle and in oversight or advisory roles. These are not without challenges and there remain uncertainties about who best to involve, why and how. Future research should aim to address these

The Concise Guide to PHARMACOLOGY 2023/24: Transporters

\ua9 2023 The Authors. British Journal of Pharmacology published by John Wiley &amp; Sons Ltd on behalf of The British Pharmacological Society.The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16182. Transporters are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

The concise guide to pharmacology 2019/20: Ion channels

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14749. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

Pharmacologically Reversible, Loss of Function Mutations in the tm2 and tm4 Inner Pore Helices of Trek-1 k2p Channels

A better understanding of the gating of TREK two pore domain potassium (K2P) channels and their activation by compounds such as the negatively charged activator, flufenamic acid (FFA) is critical in the search for more potent and selective activators of these channels. Currents through wild-type and mutated human K2P channels expressed in tsA201 cells were measured using whole-cell patch-clamp recordings in the presence and absence of FFA. Mutation of the TM2.6 residue of TREK-1 to a phenylalanine (G171F) and a similar mutation of TM4.6 (A286F) substantially reduced current through TREK-1 channels. In complementary experiments, replacing the natural F residues at the equivalent position in TRESK channels, significantly enhanced current. Known, gain of function mutations of TREK-1 (G137I, Y284A) recovered current through these mutated channels. This reduction in current could be also be reversed pharmacologically, by FFA. However, an appropriate length MTS (MethaneThioSulfonate) cross-linking reagent (MTS14) restricted the activation of TREK-1_A286C channels by repeated application of FFA. This suggests that the cross-linker stabilises the channel in a conformation which blunts FFA activation. Pharmacologically reversible mutations of TREK channels will help to clarify the importance of these channels in pathophysiological conditions such as pain and depression