Introducing Elinor for monitoring the governance and management of area-based conservation.

Monitoring the governance and management effectiveness of area-based conservation has long been recognized as an important foundation for achieving national and global biodiversity goals and enabling adaptive management. However, there are still many barriers that prevent conservation actors, including those affected by governance and management systems from implementing conservation activities and programs and from gathering and using data on governance and management to inform decision-making across spatial scales and through time. We explored current and past efforts to assess governance and management effectiveness and barriers actors face in using the resulting data and insights to inform conservation decision-making. To help overcome these barriers, we developed Elinor, a free and open-source monitoring tool that builds on the work of Nobel Prize winner Elinor Ostrom to facilitate the gathering, storing, sharing, analyzing, and use of data on environmental governance and management across spatial scales and for areas under different governance and management types. We consider the process of codesigning and piloting Elinor with conservation scientists and practitioners and the main components of the assessment and online data system. We also consider how Elinor complements existing approaches by addressing governance and management in a single assessment at a high level for different types of area-based conservation, providing flexible options for data collection, and integrating a data system with an assessment that can support data use and sharing across different spatial scales, including global monitoring of the Global Biodiversity Framework. Although challenges will continue, the process of developing Elinor and the tool itself offer tangible solutions to barriers that prevent the systematic collection and use of governance and management data. With broader uptake, Elinor can play a valuable role in enabling more effective, inclusive, and durable area-based conservation.

Introducción de Elinor para el monitoreo de la gobernanza y la gestión de la conservación con base en zonas geográficas Resumen El monitoreo de la efectividad de la gobernanza y de la gestión de la conservación basada en zonas geográficas ha sido reconocido durante mucho tiempo como una base importante para alcanzar las metas nacionales y mundiales de la biodiversidad y permitir un manejo adaptativo. Sin embargo, todavía existen barreras que evitan que los actores de la conservación, incluidos aquellos afectados por los sistemas de gobernanza y gestión, implementen actividades y programas de conservación y recopilen y usen datos de la gobernanza y la gestión para informar las decisiones a lo largo de las escalas espaciales y a través del tiempo. Exploramos los esfuerzos hechos en la actualidad y en el pasado para evaluar la efectividad de la gobernanza y la gestión así como las barreras que los actores enfrentan al usar los datos y el conocimiento resultantes para informar la toma de decisiones de conservación. Para ayudar a derribar estas barreras desarrollamos Elinor, una herramienta de monitoreo gratuita y de software libre que parte del trabajo de la ganadora del Premio Nobel Elinor Ostrom, para facilitar la recopilación, almacenamiento, divulgación, análisis y uso de los datos sobre la gobernanza y la gestión ambiental en las escalas espaciales y para las zonas con diferentes tipos de gobernanza y gestión. Planteamos co­diseñar y pilotear Elinor con los científicos y practicantes de la conservación y usando los componentes principales del sistema de evaluación y de datos en línea. También planteamos cómo Elinor complementa las estrategias existentes al abordar la gobernanza y la gestión en una sola evaluación a un nivel elevado para diferentes tipos de conservación basada en zonas geográficas, lo que proporciona opciones flexibles para la colecta de datos, e integramos un sistema de datos con una evaluación que soporta el uso y divulgación de datos en diferentes escalas espaciales, incluido el Marco Mundial para la Biodiversidad. Aunque los retos seguirán existiendo, el proceso de desarrollo de Elinor y la propia herramienta ofrecen soluciones tangibles a las barreras que previenen la colecta sistemática y el uso de datos de la gobernanza y la gestión. Con una mayor aceptación, Elinor puede tener un papel importante en el momento de hacer posible una conservación basada en zonas geográficas más eficaz, integradora y duradera.

Evaluation of a novel device to assess obstructive sleep apnea and body position.

STUDY OBJECTIVES: Obstructive sleep apnea is a prevalent disease with well-known complications when left untreated. Advances in sleep-disordered breathing diagnosis may increase detection and appropriate treatment. The Wesper device is a recently developed portable system with specialized wearable patches that can measure respiratory effort, derived airflow, estimated air pressure, and body position. This study sought to compare the diagnostic ability of the novel Wesper device with the gold standard of polysomnography. METHODS: Patients enrolled in the study underwent simultaneous polysomnography and Wesper device testing in a sleep laboratory setting. Data were collected and scored by readers blinded to all patient information, and the primary reader was blinded to testing method. The accuracy of the Wesper device was determined by calculation of the Pearson correlation and Bland-Altman limits of agreement of apnea-hypopnea indices between testing methods. Adverse events were also recorded. RESULTS: A total of 53 patients were enrolled in the study and 45 patients were included in the final analysis. Pearson correlation between polysomnography and Wesper device apnea-hypopnea index determinations was 0.951, which met the primary endpoint goal (P = .0003). The Bland-Altman 95% limits of agreement were -8.05 and 6.38, which also met the endpoint goal (P < .001). There were no adverse events or serious adverse events noted. CONCLUSIONS: The Wesper device compares favorably with gold-standard polysomnography. Given the lack of safety concerns, we advocate for further study regarding its utility in diagnosis and management of sleep apnea in the future. CITATION: Raphelson JR, Ahmed IM, Ancoli-Israel S, et al. Evaluation of a novel device to assess obstructive sleep apnea and body position. J Clin Sleep Med. 2023;19(9):1643-1649.

Understanding change, complexities, and governability challenges in small-scale fisheries: a case study of Limbe, Cameroon, Central Africa.

Climate change, globalization, and increasing industrial and urban activities threaten the sustainability and viability of small-scale fisheries. How those affected can collectively mobilize their actions, share knowledge, and build their local adaptive capacity will shape how best they respond to these changes. This paper examines the changes experienced by small-scale fishing actors, social and governance complexities, and the sustainability challenges within the fisheries system in Limbe, Cameroon. Drawing on the fish-as-food framework, we discuss how ineffective fishery management in light of a confluence of global threats has resulted in changes to fish harvesters' activities, causing shortages in fish supply and disruptions in the fish value chain. The paper uses focus group discussions with fish harvesters and fishmongers to present three key findings. First, we show that changes in the fisheries from increased fishing activities and ineffective fishery management have disrupted fish harvesting and supply, impacting the social and economic well-being of small-scale fishing actors and their communities. Second, there are complexities in the fisheries value chain due to shortages in fish supply, creating conflicts between fisheries actors whose activities are not regulated by any specific set of rules or policies. Third, despite the importance of small-scale fisheries in Limbe, management has been abandoned by fishing actors who are not well-equipped with the appropriate capacity to design and enforce effective fishery management procedures and protections against illegal fishing activities. Empirical findings from this understudied fishery make scholarly contributions to the literature on the fish-as-food framework and demonstrate the need to support small-scale actors' fishing activities and the sustainability of the fisheries system in Limbe. Supplementary Information: The online version contains supplementary material available at 10.1007/s40152-023-00296-3.

A legal assessment of private land conservation in South America.

Privately protected areas (PPAs) are a potentially innovative conservation tool. Legal recognition is necessary for their success, especially where there are institutional challenges to nature conservation, such as in South America. Although PPAs have increased in South America since the early 2000s, there is a critical information gap pertaining to their legal frameworks. We analyzed the level of landowner commitment to and governmental support for PPAs across countries in South America that officially recognize PPAs. We analyzed the legal framework governing PPAs and reviewed literature on them. This process was done in English and Spanish. The information we gathered was validated by 16 conservation experts from 10 South American countries. Because Peru is 1 of only 2 South American countries where local communities create and manage PPAs, we studied Peruvian PPAs in more detail by examining official creation documents and interviewing 13 local conservation professionals. We found inadequate minimum duration of PPAs and vague guidelines for conducting economic activities within them and a lack of governmental support (e.g., financial and technical support) for PPAs. Support was limited to the exemption from rural property taxes, which are relatively low compared with countries outside South America. In Peru, PPAs run by individuals and communities needed different legal frameworks because they were created with different objectives and had different sizes and duration of commitments. The prompt improvement of legal frameworks across South America is necessary for PPAs to achieve their aim of being places for enduring nature conservation in the region.

Una revisión legal de la conservación voluntaria entierras privadas de América del Sur Resumen Las áreas protegidas privadas (APP) son una herramienta de conservación con potencial innovador. Para ser exitosas, las APP necesitan reconocimiento legal, especialmente cuando existen obstáculos institucionales para la conservación de la naturaleza, como sucede en América del Sur. Aunque las APP han aumentado en esta zona desde principios de la década del 2000, existe un vacío de información con respecto a sus marcos legales. Analizamos el nivel de compromiso de los terratenientes y el apoyo gubernamental hacia las APP en los países de América del Sur que reconocen de forma oficial las APP. Analizamos el encuadre legal que rige a las APP y revisamos la literatura existente sobre ellas; realizamos este proceso en inglés y en español. Dieciséis expertos de la conservación de diez países sudamericanos validaron la información recopilada. Ya que Perú es uno de los dos países de la zona en donde las comunidades locales crean y manejan las APP, nos enfocamos en sus APP y examinamos a detalle los documentos oficiales de creación y entrevistamos a 13 profesionales de la conservación locales. Encontramos una duración mínima inadecuada de las APP y directrices vagas para la realización de actividades dentro de ellas, así como una falta de apoyo gubernamental (p. ej.: apoyo económico y técnico). Este apoyo se limitaba a la exención de los impuestos sobre la propiedad rural, los cuales son relativamente bajos en comparación con los países fuera de América del Sur. En Perú, las APP a cargo de individuos y comunidades necesitaban diferentes encuadres legales porque fueron creados con diferentes objetivos y tenían diferentes tamaños y plazos para los compromisos. Se necesita una rápida mejora de los marcos legales en América del Sur para que las APP logren el objetivo de ser sitios para que perdure la conservación de la naturaleza en la región.

The MPA Guide: A framework to achieve global goals for the ocean.

Marine Protected Areas (MPAs) are conservation tools intended to protect biodiversity, promote healthy and resilient marine ecosystems, and provide societal benefits. Despite codification of MPAs in international agreements, MPA effectiveness is currently undermined by confusion about the many MPA types and consequent wildly differing outcomes. We present a clarifying science-driven framework­The MPA Guide­to aid design and evaluation. The guide categorizes MPAs by stage of establishment and level of protection, specifies the resulting direct and indirect outcomes for biodiversity and human well-being, and describes the key conditions necessary for positive outcomes. Use of this MPA Guide by scientists, managers, policy-makers, and communities can improve effective design, implementation, assessment, and tracking of existing and future MPAs to achieve conservation goals by using scientifically grounded practices.

Ubrogepant for the Acute Treatment of Migraine: Pooled Efficacy, Safety, and Tolerability From the ACHIEVE I and ACHIEVE II Phase 3 Randomized Trials.

INTRODUCTION: Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine. The efficacy and safety of ubrogepant were demonstrated in two pivotal phase 3, single-attack, randomized, placebo-controlled trials (ACHIEVE I and ACHIEVE II). METHODS: We conducted a post hoc analysis of pooled data from the ACHIEVE trials to evaluate the efficacy, safety, and tolerability of ubrogepant 50 mg (the only dose evaluated in both trials) versus placebo across a large population of participants with migraine. The coprimary efficacy outcomes were pain freedom and absence of the most bothersome migraine-associated symptom (including photophobia, phonophobia, and nausea) at 2 h post dose. Secondary outcomes included pain relief at 2 h post dose, sustained pain relief and pain freedom from 2 to 24 h, and absence of specific migraine-associated symptoms at 2 h post dose. RESULTS: A total of 2240 eligible participants were randomized to placebo (n = 1122) or ubrogepant 50 mg (n = 1118) in the ACHIEVE trials. Pain freedom at 2 h was reported in 13.0% of participants in the pooled placebo group and 20.5% in the pooled ubrogepant 50 mg group (odds ratio [OR] 1.72; 95% confidence interval [CI] 1.34, 2.22; P < 0.001). Absence of the most bothersome migraine-associated symptom at 2 h was reported by 27.6% in the pooled placebo group and by 38.7% in the pooled ubrogepant 50 mg group (OR 1.68; 95% CI 1.37, 2.05; P < 0.001). Adverse events (AEs) within 48 h after the initial or optional second dose were reported by 11.5 and 11.2% of participants in the pooled placebo and pooled ubrogepant 50 mg groups, respectively. The most common AE was nausea (1.8 and 1.9%, respectively). No serious AEs related to treatment or discontinuations due to AEs were reported. CONCLUSION: These results further support the efficacy, safety, and tolerability of ubrogepant for the acute treatment of migraine. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: ACHIEVE I: NCT02828020; ACHIEVE II: NCT02867709.

Headache characteristics and burden from chronic migraine with medication overuse headache: Cross-sectional observations from the Medication Overuse Treatment Strategy trial.

OBJECTIVE: To describe headache characteristics, medication use, disability, and quality of life in a large patient cohort from the United States who have chronic migraine (CM) and medication overuse headache (MOH). METHODS: In all, 610 adult patients were enrolled into the Medication Overuse Treatment Strategy trial from 34 healthcare clinics, including headache specialty, general neurology, and primary care clinics. Descriptive statistics characterize baseline demographics, headache characteristics, medication use, disability (Headache Impact Test 6 [HIT-6] and Migraine Functional Impact Questionnaire [MFIQ]), pain interference (PROMIS Pain Interference), and quality of life (EQ-5D-5L). Relationships with headache frequency were assessed. RESULTS: Mean age was 45 years (SD 13) and 531/608 (87.3%) were females. Mean headache days per 30 was 24.3 (SD 5.5), including 13.6 (SD 7.1) with moderate to severe headache. Daily headaches were reported by 36.1% (219/607) of patients. Acute headache medications were used on 21.5 (SD 7.5) per 30 days. The most commonly overused medications were simple analgesics (378/607, 62% of patients), combination analgesics (246/607, 41%), and triptans (128/607, 21%). HIT-6, MFIQ, PROMIS Pain Interference, and EQ-5D-5L scores demonstrated substantial negative impact from CM with MOH on patient functioning and quality of life. Higher headache frequency was associated with more moderate-severe headache days, more frequent acute headache medication use, greater headache-related disability, and lower quality of life. Only 272/606 (44.9%) were taking migraine preventive medication. CONCLUSIONS: CM with MOH is associated with a large burden on patients in the United States. Higher headache frequency is associated with greater impact on functioning, pain interference, and quality of life.

Migraine Patients With Cardiovascular Disease and Contraindications: An Analysis of Real-World Claims Data.

INTRODUCTION: Triptans, the most commonly prescribed acute treatments for migraine attacks are, per FDA labeling, contraindicated in cardiovascular (CV) disease patients and have warnings and precautions for those with CV risk factors. METHODS: Headache specialists, cardiologists, and health economics and outcomes researchers convened to identify diagnostic codes for: (1) CV diseases contraindicating triptans based on FDA labeling; (2) conditions comprising "other significant underlying CV disease"; and (3) CV risk factors included as warnings and precautions for triptans. A retrospective, cross-sectional analysis of commercially insured adult US migraine patients in the 2017 Optum® Clinformatics® Data Mart (CDM) and the 2017 IBM® Watson Health MarketScan® Commercial Claims database was used to estimate the proportion of migraine patients with CV contraindications and warnings and precautions to triptans. RESULTS: Of the 56,662 migraine patients analyzed from Optum CDM, 13.5% had ≥1 CV disease as specified in triptan labeling and an additional 8.5% had ≥1 "other CV disease" judged by the panel to constitute a "significant underlying CV disease" (total: 22.0% migraine patients). Of 176 724 migraine patients analyzed from MarketScan, 12.2% had ≥1 CV disease as specified in the labeling and an additional 8.0% had ≥1 "other significant underlying CV disease" (total: 20.2% of migraine patients). An additional 25.4% and 25.1% of migraine patients had ≥2 CV risk factors in Optum CDM and MarketScan. In total, 47.4% and 45.3% of migraine patients in both databases had a CV disease specified as a contraindication, an "other CV disease" endorsed as significant, or ≥2 CV risk factors identified as warnings and precautions to triptans. CONCLUSIONS: Analyses of more than 230,000 people with migraine showed that ≥20% of commercially insured US migraine patients have a CV condition that specifically contraindicates triptan treatment, and an additional 25% have ≥2 CV risk factors identified as warnings and precautions to triptans.

Improving marine protected area governance through collaboration and co-production.

Marine protected areas (MPAs) socio-ecological effectiveness depends on a number of management and governance elements, among which stakeholder engagement and community support play key roles. Collaborative conservation initiatives that engage stakeholders in action research and knowledge co-production processes can enhance management and governance of MPAs. To design effective strategies aimed at reconciling biodiversity conservation and management of sustainable human uses, it is key to assess how local communities respond to such initiatives and identify the set of contextual factors, institutional, local and individual, potentially affecting these responses. This paper presents the approach and results of one such initiative, spanning 6 EU countries and 11 MPAs in the Mediterranean Sea, focusing on small-scale fishers as key MPA users. Through a collaborative project, managers and fishers agreed upon specific governance interventions (e.g. increasing stakeholder engagement, engaging fishers in monitoring activities, reducing fishing efforts) to be implemented in each MPA for one year. Structured surveys queried: MPA managers on the MPA context, governance structure, feasibility and effectiveness of the tested interventions; and small-scale fishers on their perceptions of the impact of the tested interventions on a set of 9 socio-ecological variables (e.g. amount of fish caught, level of participation in decision-making, support for the MPA). Results revealed that the interventions tested were relatively feasible, effective and cost-effective. Fishers reported positive perceptions of the interventions for the 9 variables considered, especially for level of support for the MPA and for those associated with aspects of governance. Proportional odds models highlighted perceived effects are maximized under certain institutional, local and individual circumstances (e.g. old MPAs, small fisher communities, and fishers with a high proportion of income from fisheries). Findings highlight that employing good governance processes involving stakeholders may rapidly generate improved local support for conservation and provide insights for potential leverage points upon which to act to maximize perceived effectiveness and enhance support toward MPAs.

National contributions to global ecosystem values.

Current conservation templates prioritize biogeographic regions with high intensity ecosystem values, such as exceptional species richness or threat. Intensity-based targets are an important consideration in global efforts, but they do not capture all available opportunities to conserve ecosystem values, including those that accrue in low intensity over large areas. We assess six globally-significant ecosystem values-intact wilderness, freshwater availability, productive marine environments, breeding habitat for migratory wildlife, soil carbon storage, and latitudinal potential for range shift in the face of climate change-to highlight opportunities for high-impact broadly-distributed contributions to global conservation. Nations can serve as a cohesive block of policy that can profoundly influence conservation outcomes. Contributions to global ecosystem values that exceed what is predicted by a nation's area alone, can give rise to countries with the capacity to act as 'conservation superpowers', such as Canada and Russia. For these conservation superpowers, a relatively small number of national policies can have environmental repercussions for the rest of the world.

Vibegron (RVT-901/MK-4618/KRP-114V) Administered Once Daily as Monotherapy or Concomitantly with Tolterodine in Patients with an Overactive Bladder: A Multicenter, Phase IIb, Randomized, Double-blind, Controlled Trial.

BACKGROUND: Antimuscarinics have shown modest efficacy with unwanted side effects in patients with overactive bladder (OAB). Efficacy of vibegron, a new ß3-adrenergic receptor agonist, for OAB is unknown. OBJECTIVE: To evaluate the efficacy of once-daily oral vibegron in OAB patients (primary), and its safety, tolerability, and efficacy when administered alone or concomitantly with tolterodine (secondary). DESIGN, SETTING, AND PARTICIPANTS: International, phase IIb, randomized, double-blind, placebo- and active comparator-controlled, two-part superiority trial (2011-2013) in OAB-wet or OAB-dry patients aged 18-75 yr (NCT01314872). INTERVENTIONS: Part 1: once-daily oral vibegron monotherapy (3 [V3], 15 [V15], 50 [V50], or 100 [V100] mg), tolterodine extended release 4mg (TER4), or placebo for 8 wk, or combination V50/TER4 for 4 wk and then V50 for 4 wk; part 2: V100/TER4, V100, TER4, or placebo for 4 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Average daily micturitions at week 8 of part 1 (primary); urge incontinence episodes, total incontinence episodes, and urgency episodes (secondary). RESULTS AND LIMITATIONS: Overall, 1395 patients were randomized. From baseline to week 8, V50 and V100 significantly decreased average daily micturitions (least square mean difference [95% confidence interval], -0.64 [-1.11, -0.18]; p=0.007 and -0.91 [-1.37, -0.44]; p<0.001, respectively) and the number of urge incontinence episodes (-0.72 [-1.11, -0.33] and -0.71 [-1.10, -0.32], respectively; both p<0.001) versus placebo. All vibegron doses were well tolerated. The incidence of dry mouth was higher with TER4 than with vibegron monotherapy. Results are limited by the relatively short treatment duration. CONCLUSIONS: Once-daily V50 and V100 improved OAB symptoms; vibegron was well tolerated as monotherapy and concomitantly with tolterodine. Further development is warranted. PATIENT SUMMARY: Antimuscarinics, commonly used to treat overactive bladder, produce modest efficacy and unwanted side effects. In this study, a different type of drug (vibegron) was efficacious and safe, alone or with an antimuscarinic (tolterodine).

Environmental Stewardship: A Conceptual Review and Analytical Framework.

There has been increasing attention to and investment in local environmental stewardship in conservation and environmental management policies and programs globally. Yet environmental stewardship has not received adequate conceptual attention. Establishing a clear definition and comprehensive analytical framework could strengthen our ability to understand the factors that lead to the success or failure of environmental stewardship in different contexts and how to most effectively support and enable local efforts. Here we propose such a definition and framework. First, we define local environmental stewardship as the actions taken by individuals, groups or networks of actors, with various motivations and levels of capacity, to protect, care for or responsibly use the environment in pursuit of environmental and/or social outcomes in diverse social-ecological contexts. Next, drawing from a review of the environmental stewardship, management and governance literatures, we unpack the elements of this definition to develop an analytical framework that can facilitate research on local environmental stewardship. Finally, we discuss potential interventions and leverage points for promoting or supporting local stewardship and future applications of the framework to guide descriptive, evaluative, prescriptive or systematic analysis of environmental stewardship. Further application of this framework in diverse environmental and social contexts is recommended to refine the elements and develop insights that will guide and improve the outcomes of environmental stewardship initiatives and investments. Ultimately, our aim is to raise the profile of environmental stewardship as a valuable and holistic concept for guiding productive and sustained relationships with the environment.

Equity trade-offs in conservation decision making.

Conservation decisions increasingly involve multiple environmental and social objectives, which result in complex decision contexts with high potential for trade-offs. Improving social equity is one such objective that is often considered an enabler of successful outcomes and a virtuous ideal in itself. Despite its idealized importance in conservation policy, social equity is often highly simplified or ill-defined and is applied uncritically. What constitutes equitable outcomes and processes is highly normative and subject to ethical deliberation. Different ethical frameworks may lead to different conceptions of equity through alternative perspectives of what is good or right. This can lead to different and potentially conflicting equity objectives in practice. We promote a more transparent, nuanced, and pluralistic conceptualization of equity in conservation decision making that particularly recognizes where multidimensional equity objectives may conflict. To help identify and mitigate ethical conflicts and avoid cases of good intentions producing bad outcomes, we encourage a more analytical incorporation of equity into conservation decision making particularly during mechanistic integration of equity objectives. We recommend that in conservation planning motivations and objectives for equity be made explicit within the problem context, methods used to incorporate equity objectives be applied with respect to stated objectives, and, should objectives dictate, evaluation of equity outcomes and adaptation of strategies be employed during policy implementation.

Adaptive social impact management for conservation and environmental management.

Concerns about the social consequences of conservation have spurred increased attention the monitoring and evaluation of the social impacts of conservation projects. This has resulted in a growing body of research that demonstrates how conservation can produce both positive and negative social, economic, cultural, health, and governance consequences for local communities. Yet, the results of social monitoring efforts are seldom applied to adaptively manage conservation projects. Greater attention is needed to incorporating the results of social impact assessments in long-term conservation management to minimize negative social consequences and maximize social benefits. We bring together insights from social impact assessment, adaptive management, social learning, knowledge coproduction, cross-scale governance, and environmental planning to propose a definition and framework for adaptive social impact management (ASIM). We define ASIM as the cyclical process of monitoring and adaptively managing social impacts over the life-span of an initiative through the 4 stages of profiling, learning, planning, and implementing. We outline 14 steps associated with the 4 stages of the ASIM cycle and provide guidance and potential methods for social-indicator development, predictive assessments of social impacts, monitoring and evaluation, communication of results, and identification and prioritization of management responses. Successful ASIM will be aided by engaging with best practices - including local engagement and collaboration in the process, transparent communication of results to stakeholders, collective deliberation on and choice of interventions, documentation of shared learning at the site level, and the scaling up of insights to inform higher-level conservation policies-to increase accountability, trust, and perceived legitimacy among stakeholders. The ASIM process is broadly applicable to conservation, environmental management, and development initiatives at various scales and in different contexts.

Structural Basis of Catalysis in the Bacterial Monoterpene Synthases Linalool Synthase and 1,8-Cineole Synthase.

Terpenoids form the largest and stereochemically most diverse class of natural products, and there is considerable interest in producing these by biocatalysis with whole cells or purified enzymes, and by metabolic engineering. The monoterpenes are an important class of terpenes and are industrially important as flavors and fragrances. We report here structures for the recently discovered Streptomyces clavuligerus monoterpene synthases linalool synthase (bLinS) and 1,8-cineole synthase (bCinS), and we show that these are active biocatalysts for monoterpene production using biocatalysis and metabolic engineering platforms. In metabolically engineered monoterpene-producing E. coli strains, use of bLinS leads to 300-fold higher linalool production compared with the corresponding plant monoterpene synthase. With bCinS, 1,8-cineole is produced with 96% purity compared to 67% from plant species. Structures of bLinS and bCinS, and their complexes with fluorinated substrate analogues, show that these bacterial monoterpene synthases are similar to previously characterized sesquiterpene synthases. Molecular dynamics simulations suggest that these monoterpene synthases do not undergo large-scale conformational changes during the reaction cycle, making them attractive targets for structured-based protein engineering to expand the catalytic scope of these enzymes toward alternative monoterpene scaffolds. Comparison of the bLinS and bCinS structures indicates how their active sites steer reactive carbocation intermediates to the desired acyclic linalool (bLinS) or bicyclic 1,8-cineole (bCinS) products. The work reported here provides the analysis of structures for this important class of monoterpene synthase. This should now guide exploitation of the bacterial enzymes as gateway biocatalysts for the production of other monoterpenes and monoterpenoids.