Designing an Analytic Deliberative Process for Environmental Health Policy Making in the U.S. Nuclear Weapons Complex

Using a National Research Council Report as a centerpiece, Drs. Tuler and Webler evaluate the effectiveness of a conceptual approach to risk policy-making

Public Participation in Hazard Management: The Use of Citizen Panels in the U.S.

After discussing the need for citizen participation in Risk management and a method of facilitating such participation as developed in Germany, the authors discuss and analyze its subsequent modification and use in a sewage sludge management project in New Jersey

Delivering more inclusive public participation in coastal flood management: a case study in Suffolk, UK

Ongoing problems achieving local population acceptance of coastal flood strategies threaten their implementation. A lack of meaningful engagement by all elements of potentially affected populations is seen as instrumental in this problem. This research assumes that multiple discourses exist on involvement with flood management, but that most are not engaged in decision-making. The aim is therefore to identify, and develop an approach for engaging with, all discourses related to flood management decision-making. Q methodology and follow-up interviews were used to identify both discourses and issues with current engagement strategies related to involvement in flood management in a case study population, controlled to allow for potential bias subject to the validity of the information deficit model, based in the Alde and Ore Estuary, Suffolk, UK. The five discourses included people who are knowledgeable; politically aware; sceptical and pragmatic; sceptical and locally attuned; and engaged or disengaged; in their perspectives on flood management. A workshop was subsequently held to identify engagement strategies that could engage with all discourses. Involvement of participants representing the range of existing discourses is argued to be necessary to lead to effective recommendations for more inclusive engagement approaches

Organizing Public Participation: A Critical Review of Three Handbooks

Handbooks and guidebooks give advice to would-be practitioners on how to do public participation well. They offer a cookbook solution to the troubled official who is pressed to implement a state-of-the-art program, but is inexperienced in doing so. Although I have reservations about taking a cookbook approach too far, I also believe it does have a place in the field at the moment. In this review I attempt to build awareness about the availability of these handbooks and manuals. Doing so is an important step in promoting learning and the betterment of public participation. Better public participation can lead to a better state of public affairs. If we trust in the reasonableness of the publics--and I assert that the vast majority of us in this field do--then we also trust that better public participation also moves us closer to realizing the principles of sustainability and balance

Beyond Science: Deliberation and Analysis in Public Decision Making

I agree very much with most of Carolyn Raffensperger’s argument. Understanding Risk does stand out for its willingness to admit that we need to rethink our assumptions about the privileged role that scientists and “experts” play in public decision making on topics of risk and environment. Involving publics in meaningful ways with scientists can make better science, but only if the scientists allow this to happen. I agree with Carolyn when she writes that this might require scientists engaging in inductive reasoning — some- thing many of them have been trained not to do! Surely the scientific method is powerful. Deductive reasoning is powerful. We do not need to abandon it in order to recognize that building a definition of the problem “from the ground up” might be a competent and politically expedient way to proceed. Still, I disagree that this is the main message to take from the report. The debate about why to involve lay people in public decision making may have matured, in a sense, via the status a National Research Council committee has, but Understanding Risk does not provide anything new to that debate

Integrating multiple criteria decision analysis in participatory forest planning

Forest planning in a participatory context often involves multiple stakeholders with conflicting interests. A promising approach for handling these complex situations is to integrate participatory planning and multiple criteria decision analysis (MCDA). The objective of this paper is to analyze strengths and weaknesses of such an integrated approach, focusing on how the use of MCDA has influenced the participatory process. The paper outlines a model for a participatory MCDA process with five steps: stakeholder analysis, structuring of the decision problem, generation of alternatives, elicitation of preferences, and ranking of alternatives. This model was applied in a case study of a planning process for the urban forest in Lycksele, Sweden. In interviews with stakeholders, criteria for four different social groups were identified. Stakeholders also identified specific areas important to them and explained what activities the areas were used for and the forest management they wished for there. Existing forest data were combined with information from interviews to create a map in which the urban forest was divided into zones of different management classes. Three alternative strategic forest plans were produced based on the zonal map. The stakeholders stated their preferences individually by the Analytic Hierarchy Process in inquiry forms and a ranking of alternatives and consistency ratios were determined for each stakeholder. Rankings of alternatives were aggregated; first, for each social group using the arithmetic mean, and then an overall aggregated ranking was calculated from the group rankings using the weighted arithmetic mean. The participatory MCDA process in Lycksele is assessed against five social goals: incorporating public values into decisions, improving the substantive quality of decisions, resolving conflict among competing interests, building trust in institutions, and educating and informing the public. The results and assessment of the case study support the integration of participatory planning and MCDA as a viable option for handling complex forest-management situations. Key issues related to the MCDA methodology that need to be explored further were identified: 1) The handling of place-specific criteria, 2) development of alternatives, 3) the aggregation of individual preferences into a common preference, and 4) application and evaluation of the integrated approach in real case studies

Rolle von endothelialen Cytochrom-P450-Epoxygenasen in der Regulation der Angiogenese

Cytochrome P450 epoxygenases of the 2C family (CYP2C) are highly expressed in the endothelium and metabolize arachidonic acid to different regioisomers of epoxyeicosatrienoic acids (EET). They have a number of roles in the regulation of vascular tone and homeostasis by activating different signal transduction pathways and have recently been reported to be involved in proliferation and angiogenesis. However, the exact mechanisms by which epoxygenases regulate angiogenesis are still unclear. Therefore, the initial aim of the present study was to characterize the relevance of major signalling molecules that are involved in angiogenesis and to investigate possible signalling pathways involved. Initially the effect of CYP2C9 overexpression on expression levels of EphB4, a tyrosine kinase that plays a role in a number of developmental processes, was investigated. EphB4 protein expression was increased in CYP2C9 overexpressing cells without any effects on expression levels of its ligand ephrinB2. To clarify whether EphB4 is a critical determinant of CYP2C9-induced angiogenesis, endothelial cell sprouting was assessed using a collagen gel-based in vitro angiogenesis assay. Following transfection with EphB4 antisense or scrambled oligonucleotides, capillary-like structures were clearly present after 24 hours in cells overexpressing CYP2C9, while EphB4 downregulation abolished CYP2C9-induced sprouting. In addition stimulation of human umbilical vein endothelial cells with VEGF resulted in an increase in CYP2C expression and a subsequent increase of 11,12-EET production; an effect that was abolished by the CYP epoxygenases inhibitor MSPPOH as well as when cells were infected with a dominant negative mutant of AMPK. In vivo 11,12-EET treatment increased EphB4 expression in mesenteric arteries as well as in Matrigel plugs; an effect that was abolished when plugs were impregnated at the same time with small interfering RNA (siRNA) for EphB4. Furthermore, impregnation of Matrigel plugs with VEGF resulted in endothelial cell and smooth muscle cell recruitment into a Matrigel plug and this effect was mediated by CYP2C9-derived EETs as it was prevented by 14,15-EEZE. When infiltration of EET impregnated plugs with endothelial cells and pericytes/smooth muscle cells in vivo was compared to the effects seen in VEGF treated plugs, it was apparent that only EET treatment resulted in the formation of tube like structures that were covered by smooth muscle cells. Therefore, the final aim of the study was to further define the consequences of EET signalling in vivo as well as to characterize its physiological relevance. This hypothesis could be assessed by isolectin injection through the tail-vein where isolectin was taken up only by the EET-impregnated plug. Moreover ultrasound measurements revealed accumulation of contrast agent in EET impregnated plugs compared to control plugs. Taken together our findings emphasize that CYP2C plays a crucial role in the vessel formation process by modulating the effects mediated by two important control elements of the angiogenic response, namely VEGF and EphB4. CYP2C-derived EETs not only participate as second messengers in the angiogenic response, but have the potential to influence much more than angiogenesis by enhancing smooth muscle cell/pericyte recruitment to endothelial cell tubes to promote vascular maturation.Im nativen Endothel exprimierte Cytochrom P450 Epoxygenasen der 2C Familie (CYP2C) synthetisieren aus Arachidonsäure verschiedene Regioisomere der Epoxyeicosatriensäure (EET), welche eine wichtige Rolle bei der Regulation des vaskulären Tonus und der Homöostase spielen. Obwohl schon beschrieben wurde, dass Enzyme der CYP2C Familie an Prozessen der Proliferation und Angiogenese beteiligt sind, ist der genaue molekulare Mechanismus ihrer Wirkung noch weitestgehend ungeklärt. Deswegen war das primäre Ziel der vorliegenden Arbeit die Identifizierung von Signaltransduktionsmolekülen, die an der CYP-induzierten Angiogenese beteiligt sind, sowie die nachfolgende Charakterisierung möglicher daran beteiligten Signaltransduktionskaskaden. Zunächst wurde der Einfluss von CYP2C9 auf die Expression von EphB4, einer für eine Reihe von Entwicklungsprozessen wichtigen Tyrosinkinase, untersucht. In CYP2C9-überexprimierenden Zellen war die EphB4-Proteinexpression erhöht ohne einen Einfluss auf die Expression des Liganden ephrinB2 zu haben. Dieser Effekt war EET-vermittelt und konnte durch den CYP Epoxygenase Inhibitor MSPPOH, den PI3K Inhibitor LY 294002 oder gleichzeitige Transfektion mit einer dominant negativen Akt Mutante aufgehoben werden. Des weiteren führte die Stimulation von Zellen humaner Nabelschnurvenen mit VEGF sowohl zu einer Steigerung der CYP2C-Expression als auch zur vermehrten 11,12-EET Bildung; ein Effekt, der sowohl durch den Epoxygenase Inhibitor MSPPOH als auch durch gleichzeitige Infektion der Zellen mit einer dominant negativen Mutante der AMPK hemmbar war. Darüber hinaus sollte die physiologische Bedeutung dieser in vitro Befunde in vivo weiter konkretisiert werden und die Relevanz für den Angiogeneseprozess erörtert werden. Ein entscheidender Schritt für die Blutgefässbildung ist die Proliferation und Differenzierung von Endothelzellen, was zur Bildung von vaskulären röhrenartigen Gebilden (engl. „Tubes“) führt. Es konnte gezeigt werden, dass CYP2C an der VEGF-, nicht aber an der bFGF-vermittelten Ausbildung dieser Strukturen beteiligt ist, da der EET-Antagonist 14,15-EEZE beispielsweise in bFGF-behandelten Zellen keinerlei Effekt hatte. Auch in vivo führte die Imprägnierung eines Matrigel Plugs mit VEGF zur Wachstumsfaktor-spezifischen Rekrutierung von Endothel- als und in geringerem Ausmass auch zur Rekrutierung von glatten Muskelzellen bzw. Perizyten. Des weitern sollte der Einfluss von EETs auf die Reifung von Gefässen untersucht werden. Die Einwanderung von Endothelzellen und Pericyten/glatten Muskelzellen in vivo in einen EET-impregnierten Plug war vergleichbar mit der in VEGF-behandelte Plugs. Aber nur die EET-Behandlung führte zur Ausbildung von vaskulären „Tubes“, die auch mit glatten Muskelzellen verkleidet waren. Ebenso wurde durch die Schwanzvene von Mäusen injiziertes Isolektin nur durch die EET-impregnierten Plugs, nicht aber durch VEGF-imprägnierte Plugs aufgenommen. Weiterhin konnte durch Ultraschallmessungen ein erhöhtes Anfluten von Kontrastmittel im EET-behandelten Plug im Vergleich zur Kontrolle verzeichnet werden, was ein weiterer Hinweis für die Ausbildung von perfundierten, funktionsfähigen Gefässstrukturen ist. Zusammenfassend lässt sich sagen, dass EETs über die Modulation zweier wichtiger Stellglieder der angiogenen Antwort, nämlich VEGF und EphB4, eine Rolle bei der Regulation von Rezeptoren und Signaltransduktionsmolekülen spielen, die essentiell für die normale Blutgefässentwicklung und Gefässreifung sind. Die von CYP2C-stammenden EETs sind nicht nur als sekundäre Botenstoff an der angiogenen Antwort, die durch eine Vielzahl von Faktoren ausgelöst wird, beteiligt, sondern haben zudem das Potential sowohl Endothelzellen als auch Perizyten/glatte Muskelzellen z

What constitutes a successful biodiversity corridor? A Q-study in the Cape Floristic Region, South Africa

‘Success’ is a vigorously debated concept in conservation. There is a drive to develop quantitative, comparable metrics of success to improve conservation interventions. Yet the qualitative, normative choices inherent in decisions about what to measure — emerging from fundamental philosophical commitments about what conservation is and should be — have received scant attention. We address this gap by exploring perceptions of what constitutes a successful biodiversity corridor in the Cape Floristic Region, South Africa, an area of global biodiversity significance. Biodiversity corridors are particularly illustrative because, as interventions intended to extend conservation practices from protected areas across broader landscapes, they represent prisms in which ideas of conservation success are contested and transformed. We use Q method to elicit framings of success among 20 conservation scientists, practitioners and community representatives, and find three statistically significant framings of successful corridors: ‘a last line of defence for biodiversity under threat,’ ‘a creative process to develop integrative, inclusive visions of biodiversity and human wellbeing,’ and ‘a stimulus for place-based cultural identity and economic development.’ Our results demonstrate that distinct understandings of what a corridor is — a planning tool, a process of governing, a territorialized place — produce divergent framings of ‘successful’ corridors that embody diverse, inherently contestable visions of conservation. These framings emerge from global conservation discourses and distinctly local ecologies, politics, cultures and histories. We conclude that visions of conservation success will be inherently plural, and that in inevitably contested and diverse social contexts success on any terms rests upon recognition of and negotiation with alternative visions

How To Do Environmental Decision Making: Varying Perspectives on the U.S. National Research Council’s Understanding Risk Report

There are two reasons why public participation in decision making about risk and environmental management persists as an important, timely issue. First, people still disagree about whether lay people should be involved in these decisions at all. This is the question of “why?” Second, there is uncertainty about how to best involve, meaningfully, diverse lay people and scientists in an efficient, effective decision making process. This is the question of “how?

Pharmacokinetics, pharmacodynamics and adverse event profile of GSK2256294, a novel soluble epoxide hydrolase inhibitor.

AIMS: Endothelial-derived epoxyeicosatrienoic acids may regulate vascular tone and are metabolized by soluble epoxide hydrolase enzymes (sEH). GSK2256294 is a potent and selective sEH inhibitor that was tested in two phase I studies. METHODS: Single escalating doses of GSK2256294 2-20 mg or placebo were administered in a randomized crossover design to healthy male subjects or obese smokers. Once daily doses of 6 or 18 mg or placebo were administered for 14 days to obese smokers. Data were collected on safety, pharmacokinetics, sEH enzyme inhibition and blood biomarkers. Single doses of GSK2256294 10 mg were also administered to healthy younger males or healthy elderly males and females with and without food. Data on safety, pharmacokinetics and biliary metabolites were collected. RESULTS: GSK2256294 was well-tolerated with no serious adverse events (AEs) attributable to the drug. The most frequent AEs were headache and contact dermatitis. Plasma concentrations of GSK2256294 increased with single doses, with a half-life averaging 25-43 h. There was no significant effect of age, food or gender on pharmacokinetic parameters. Inhibition of sEH enzyme activity was dose-dependent, from an average of 41.9% on 2 mg (95% confidence interval [CI] -51.8, 77.7) to 99.8% on 20 mg (95% CI 99.3, 100.0) and sustained for up to 24 h. There were no significant changes in serum VEGF or plasma fibrinogen. CONCLUSIONS: GSK2256294 was well-tolerated and demonstrated sustained inhibition of sEH enzyme activity. These data support further investigation in patients with endothelial dysfunction or abnormal tissue repair, such as diabetes, wound healing or COPD.LY is funded by a Wellcome Trust-GSK Translational Medicine and Therapeutics (TMAT) Studentship and a Raymond and Beverley Sackler Fellowship. IW is a British Heart Foundation Senior Clinical Fellow and both JC and IW are supported by the Cambridge NIHR Biomedical Research Centre. Funding for the two studies (NCT01762774 and NCT02006537) was provided by GSK. Partial funding for study 1 was provided by the Innovate UK Stratified Medicines programme (ERICA Consortium).This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/bcp.1285