Safety, biodistribution and radiation dosimetry of the Arg-Gly-Asp peptide 99m Tc-maraciclatide in healthy volunteers.

BACKGROUND: 99m Tc-Maraciclatide is a radiolabelled RGD (Arg-Gly-Asp) peptide that binds with high affinity to α v ß 3 and α v ß 5 integrins, common receptors upregulated in disease states involving angiogenesis and inflammation. As such, it holds promise as a novel diagnostic imaging agent for a range of pathological conditions. The present study provides the safety, biodistribution and radiation dosimetry of 99m Tc-maraciclatide in healthy volunteers. METHODS: A phase 1, randomised, placebo-controlled study assessed the safety, biodistribution and radiation dosimetry of 99m Tc-maraciclatide in healthy volunteers. Participants were randomised into three groups receiving 99m Tc-maraciclatide and three chemical amounts of maraciclatide in an escalating dose protocol. Eight participants in each group received the required amount of maraciclatide via intravenous injection, with the remaining two receiving a placebo. Biodistribution was assessed by acquiring scintigraphic images at time points up to 24 h after a bolus injection of 99m Tc-maraciclatide. 99m Tc-maraciclatide activity in plasma and urine was measured up to 7 days post-administration. RESULTS: 99m Tc-maraciclatide was safe and well tolerated, with no serious adverse events reported. Initial uptakes of 99m Tc were highest in the gastrointestinal tract (20%), liver (15%), and lungs (9%). Similarly, the regions with the highest normalised cumulated activities were the contents of the urinary bladder and voided urine (3.4 ±â€…0.4 MBq*h/MBq), the combined walls of the small intestine and upper and lower large intestine (0.9 ±â€…0.2 MBq*h/MBq), liver (0.8 ±â€…0.2 MBq*h/MBq), lung (0.4 ±â€…0.1 MBq*h/MBq). The main route of 99m Tc excretion was renal (55%), with a systemic urinary clearance of approximately 6.7 ml/min/kg. The pharmacokinetic analysis gave a mean apparent terminal elimination half-life of the unlabelled molecular maraciclatide of approximately 1 h, independent of dose. The mean ED per unit injected activity was 7.8 ±â€…0.8 µSv/MBq. CONCLUSION: 99m Tc-maraciclatide is a safe radiopharmaceutical formulation with a dosimetry profile similar to other 99m Tc-based imaging agents.

Migration, belonging, and the sustainability of atoll islands through a changing climate.

Climate change might catalyze and exacerbate the trend of outmigration from low-lying atoll islands. There is speculation that migration away from atolls may not stop until such islands are abandoned. Yet migration creates both opportunities and risks for the sustainability of atoll communities. There is a trade-off between reduced demographic pressure on increasingly fragile atoll island environments and the financial and human resources necessary to adapt to climate change that can result from migration. Here we propose and analyze belonging as the centripetal force that makes migration a process that enhances the sustainability of atoll populations. We examine the relationship between migration, belonging, and the sustainability of populations on atoll islands based on data collected in three atoll islands in the Pacific: the island state of Niue; Namdrik Atoll in the Republic of the Marshall Islands; and Budibudi atoll (Laughlan Islands) in Papua New Guinea. In each case, belonging binds the people who live in and migrate from these places into a collective commitment to their continuity, yet it does so to different degrees according to the economic opportunities available to migrants and the infrastructure that enables extended communities to remain connected.

Research priorities for the sustainability of coral-rich western Pacific seascapes.

Nearly a billion people depend on tropical seascapes. The need to ensure sustainable use of these vital areas is recognised, as one of 17 policy commitments made by world leaders, in Sustainable Development Goal (SDG) 14 ('Life below Water') of the United Nations. SDG 14 seeks to secure marine sustainability by 2030. In a time of increasing social-ecological unpredictability and risk, scientists and policymakers working towards SDG 14 in the Asia-Pacific region need to know: (1) How are seascapes changing? (2) What can global society do about these changes? and (3) How can science and society together achieve sustainable seascape futures? Through a horizon scan, we identified nine emerging research priorities that clarify potential research contributions to marine sustainability in locations with high coral reef abundance. They include research on seascape geological and biological evolution and adaptation; elucidating drivers and mechanisms of change; understanding how seascape functions and services are produced, and how people depend on them; costs, benefits, and trade-offs to people in changing seascapes; improving seascape technologies and practices; learning to govern and manage seascapes for all; sustainable use, justice, and human well-being; bridging communities and epistemologies for innovative, equitable, and scale-crossing solutions; and informing resilient seascape futures through modelling and synthesis. Researchers can contribute to the sustainability of tropical seascapes by co-developing transdisciplinary understandings of people and ecosystems, emphasising the importance of equity and justice, and improving knowledge of key cross-scale and cross-level processes, feedbacks, and thresholds.

Climate change affects multiple dimensions of well-being through impacts, information and policy responses.

The consequences of climate change and responses to climate change interact with multiple dimensions of human well-being in ways that are emerging or invisible to decision makers. We examine how elements of well-being-health, safety, place, self and belonging-are at risk from climate change. We propose that the material impacts of a changing climate, discourses and information on future and present climate risks, and policy responses to climate change affect all these elements of well-being. We review evidence on the scale and scope of these climate change consequences for well-being and propose policy and research priorities that are oriented towards supporting well-being though a changing climate.

Nature-based solutions for atoll habitability.

Atoll societies have adapted their environments and social systems for thousands of years, but the rapid pace of climate change may bring conditions that exceed their adaptive capacities. There is growing interest in the use of 'nature-based solutions' to facilitate the continuation of dignified and meaningful lives on atolls through a changing climate. However, there remains insufficient evidence to conclude that these can make a significant contribution to adaptation on atolls, let alone to develop standards and guidelines for their implementation. A sustained programme of research to clarify the potential of nature-based solutions to support the habitability of atolls is therefore vital. In this paper, we provide a prospectus to guide this research programme: we explain the challenge climate change poses to atoll societies, discuss past and potential future applications of nature-based solutions and outline an agenda for transdisciplinary research to advance knowledge of the efficacy and feasibility of nature-based solutions to sustain the habitability of atolls. This article is part of the theme issue 'Nurturing resilient marine ecosystems'.

Three ways social identity shapes climate change adaptation.

Adaptation to climate change is inescapably influenced by processes of social identity-how people perceive themselves, others, and their place in the world around them. Yet there is sparse evidence into the specific ways in which identity processes shape adaptation planning and responses. This paper proposes three key ways to understand the relationship between identity formation and adaptation processes: (a) how social identities change in response to perceived climate change risks and threats; (b) how identity change may be an objective of adaptation; and (c) how identity issues can constrain or enable adaptive action. It examines these three areas of focus through a synthesis of evidence on community responses to flooding and subsequent policy responses in Somerset county, UK and the Gippsland East region in Australia, based on indepth longitudinal data collected among those experiencing and enacting adaptation. The results show that adaptation policies are more likely to be effective when they give individuals confidence in the continuity of their in-groups, enhance the self-esteem of these groups, and develop their sense of self-efficacy. These processes of identity formation and evolution are therefore central to individual and collective responses to climate risks.

Testing the presence of marine protected areas against their ability to reduce pressures on biodiversity.

Marine protected areas (MPAs) are the preferred tool for preventing marine biodiversity loss, as reflected in international protected area targets. Although the area covered by MPAs is expanding, there is a concern that opposition from resource users is driving them into already low-use locations, whereas high-pressure areas remain unprotected, which has serious implications for biodiversity conservation. We tested the spatial relationships between different human-induced pressures on marine biodiversity and global MPAs. We used global, modeled pressure data and the World Database on Protected Areas to calculate the levels of 15 different human-induced pressures inside and outside the world's MPAs. We fitted binomial generalized linear models to the data to determine whether each pressure had a positive or negative effect on the likelihood of an area being protected and whether this effect changed with different categories of protection. Pelagic and artisanal fishing, shipping, and introductions of invasive species by ships had a negative relationship with protection, and this relationship persisted under even the least restrictive categories of protection (e.g., protected areas classified as category VI under the International Union for Conservation of Nature, a category that permits sustainable use). In contrast, pressures from dispersed, diffusive sources (e.g., pollution and ocean acidification) had positive relationships with protection. Our results showed that MPAs are systematically established in areas where there is low political opposition, limiting the capacity of existing MPAs to manage key drivers of biodiversity loss. We suggest that conservation efforts focus on biodiversity outcomes and effective reduction of pressures rather than prescribing area-based targets, and that alternative approaches to conservation are needed in areas where protection is not feasible.

Evaluación de la Presencia de Áreas Marinas Protegidas contra sus Capacidades de Reducir las Presiones sobre la Biodiversidad Resumen Las áreas marinas protegidas (AMPs) son la herramienta preferida para prevenir la pérdida de biodiversidad marina, como se ve reflejado en los objetivos internacionales para las áreas protegidas. Mientras que el área que ocupan las MPAs está expandiéndose, existe una preocupación de que la oposición de los usuarios de recursos los esté llevando hacia localidades que ya son de bajo uso mientras que las áreas de alta presión permanecen sin protección, lo que tiene implicaciones serias para la conservación de la biodiversidad. Analizamos las relaciones espaciales entre diferentes presiones inducidas por humanos sobre la biodiversidad marina y las áreas marinas protegidas del mundo. Utilizamos datos mundiales de presiones modeladas y la Base de Datos de Áreas Protegidas para calcular los niveles de 15 diferentes presiones inducidas por humanos dentro y fuera de las MPAs del mundo. Ajustamos los modelos lineales binomiales y generalizados a los datos para determinar si cada una de las presiones tenía un efecto positivo o negativo sobre la probabilidad de que un área estuviera protegida y si este efecto cambió con diferentes categorías de protección. La pesca pelágica y artesanal, las embarcaciones, y la introducción de especies invasoras por parte de los barcos tuvieron una relación negativa con la protección y esta relación persistió incluso bajo las categorías más restrictivas de protección (es decir, áreas protegidas clasificadas bajo la categoría VI de la Unión Internacional para la Conservación de la Naturaleza, una categoría que permite el uso sostenible). Como contraste, las presiones surgidas de fuentes dispersadas y difusivas (por ejemplo, la contaminación y la acidificación del océano) tuvieron relaciones positivas con la protección. Nuestros resultados muestran que las MPAs están establecidas sistemáticamente en áreas en donde hay una baja oposición política, lo que limita la capacidad de las MPAs existentes para manejar los causantes más importantes de la pérdida de la biodiversidad. Sugerimos que los esfuerzos de conservación se enfoquen en los resultados de biodiversidad y en la reducción efectiva de las presiones en lugar de ordenar objetivos basados en el área y que se necesitan estrategias alternativas a la conservación en áreas en donde la protección no es viable.

The Dynamics of Trust in the Shanghai Water Supply Regime.

Trust in natural resource managers and planners is recognized as a crucial component of the public's perception of environmental risks, including the risk of consuming water in cities. Although China is famous for its dubious water quality, public perception of the performance of water suppliers in China has scarcely been considered. Yet this is important, not least because improvements in urban water quality are most likely if the public perceives that there is a risk, which is a function of their levels of trust. We, therefore, examine the Shanghai public's trust in urban water authorities through analysis of the results from a face-to-face questionnaire that 5007 residents responded to. We find that although respondents show a moderate level of overall trust in water suppliers, they have less trust in the honesty and fairness of these organizations. In addition, we find that hukou status and education help explain the differences in people's trust in Shanghai's water authorities, and that these are more influential than factors such as gender and age. For water managers in Shanghai, this implies trust can be improved through a greater effort at public relations and increased transparency about decision making and levels of pollution.

Structural and Psycho-Social Limits to Climate Change Adaptation in the Great Barrier Reef Region.

Adaptation, as a strategy to respond to climate change, has limits: there are conditions under which adaptation strategies fail to alleviate impacts from climate change. Research has primarily focused on identifying absolute bio-physical limits. This paper contributes empirical insight to an emerging literature on the social limits to adaptation. Such limits arise from the ways in which societies perceive, experience and respond to climate change. Using qualitative data from multi-stakeholder workshops and key-informant interviews with representatives of the fisheries and tourism sectors of the Great Barrier Reef region, we identify psycho-social and structural limits associated with key adaptation strategies, and examine how these are perceived as more or less absolute across levels of organisation. We find that actors experience social limits to adaptation when: i) the effort of pursuing a strategy exceeds the benefits of desired adaptation outcomes; ii) the particular strategy does not address the actual source of vulnerability, and; iii) the benefits derived from adaptation are undermined by external factors. We also find that social limits are not necessarily more absolute at higher levels of organisation: respondents perceived considerable opportunities to address some psycho-social limits at the national-international interface, while they considered some social limits at the local and regional levels to be effectively absolute.

An ill wind? Climate change, migration, and health.

BACKGROUND: Climate change is projected to cause substantial increases in population movement in coming decades. Previous research has considered the likely causal influences and magnitude of such movements and the risks to national and international security. There has been little research on the consequences of climate-related migration and the health of people who move. OBJECTIVES: In this review, we explore the role that health impacts of climate change may play in population movements and then examine the health implications of three types of movements likely to be induced by climate change: forcible displacement by climate impacts, resettlement schemes, and migration as an adaptive response. METHODS: This risk assessment draws on research into the health of refugees, migrants, and people in resettlement schemes as analogs of the likely health consequences of climate-related migration. Some account is taken of the possible modulation of those health risks by climate change. DISCUSSION: Climate-change-related migration is likely to result in adverse health outcomes, both for displaced and for host populations, particularly in situations of forced migration. However, where migration and other mobility are used as adaptive strategies, health risks are likely to be minimized, and in some cases there will be health gains. CONCLUSIONS: Purposeful and timely policy interventions can facilitate the mobility of people, enhance well-being, and maximize social and economic development in both places of origin and places of destination. Nevertheless, the anticipated occurrence of substantial relocation of groups and communities will underscore the fundamental seriousness of human-induced climate change.

Monitoring tumor response to antiangiogenic sunitinib therapy with 18F-fluciclatide, an 18F-labeled αVbeta3-integrin and αV beta5-integrin imaging agent.

UNLABELLED: Arginine-glycine-aspartate (RGD)-binding α(V)ß(3)-integrin and α(V)ß(5)-integrin play key roles in tumor angiogenesis. We examined an (18)F-labeled small peptide (fluciclatide [United States Adopted Name (ASAN)-approved, International Nonproprietary Name (INN)-proposed name], previously referred to as AH111585) containing an RGD sequence. Fluciclatide binds with a high (nM) affinity to α(V)ß(3)-integrin and α(V)ß(5)-integrin, which are highly expressed on tumors and the tumor neovasculature. In this study, (18)F-fluciclatide was used to examine the response of human glioblastoma xenografts to treatment with the antiangiogenic agent sunitinib. METHODS: U87-MG tumor uptake of (18)F-fluciclatide was determined by small-animal PET after longitudinal administration of the antiangiogenic agent sunitinib (a 2-wk dosing regimen). Tumor sizes were measured throughout the study, and tumor volumes were calculated. Tumor microvessel density (MVD) after therapy was also analyzed. RESULTS: Dynamic small-animal PET of (18)F-fluciclatide uptake after administration of the clinically relevant antiangiogenic agent sunitinib revealed a reduction in the tumor uptake of (18)F-fluciclatide compared with that in vehicle-treated controls over the 2-wk dosing regimen. Skeletal muscle, used as a reference tissue, showed equivalent (18)F-fluciclatide uptake in both therapy and control groups. A reduction in tumor MVD was also observed after treatment with the antiangiogenic agent. No significant changes in tumor volume were observed in the 2 groups. CONCLUSION: The data demonstrated that (18)F-fluciclatide detected changes in tumor uptake after acute antiangiogenic therapy markedly earlier than any significant volumetric changes were observable. These results suggest that this imaging agent may provide clinically important information for guiding patient care and monitoring the response to antiangiogenic therapy.

Use of a novel Arg-Gly-Asp radioligand, 18F-AH111585, to determine changes in tumor vascularity after antitumor therapy.

UNLABELLED: Despite the recent development of various radiolabeled Arg-Gly-Asp (RGD) peptides for imaging the alphavbeta3 integrin receptor, relatively little attention has been focused on the ability of these radiotracers to monitor changes in tumor vascularity after antitumor therapies. This study describes the favorable in vivo kinetics and tumor-targeting properties of 18F-AH111585, a novel 18F-RGD peptide, and its ability to monitor tumor vascularity noninvasively. METHODS: Mice bearing Lewis lung carcinoma (LLC) tumors or Calu-6 non-small cell lung tumor xenografts were used for in vivo biodistribution and small-animal PET imaging studies. In addition, some animals were treated with either low-dose paclitaxel or the vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor ZD4190. Tumor uptake of 18F-AH111585 and microvessel density were then assessed. RESULTS: Biodistribution of 18F-AH111585 demonstrated rapid clearance from the blood and key background organs and good tumor accumulation, with 1.5 percentage injected dose per gram (%ID/g) present at 2 h after injection in LLC tumors. Small-animal PET imaging of Calu-6 tumors allowed visualization of tumors above background tissue, with mean baseline uptake of 2.2 %ID/g. Paclitaxel therapy reduced the microvessel density in LLC tumor-bearing mice and resulted in significantly reduced 18F-AH111585 tumor uptake (P<0.05). ZD4190 therapy resulted in a significant (31.8%) decrease in 18F-AH111585 uptake in Calu-6 tumors, compared with the vehicle control-treated Calu-6 tumors, which had a 26.9% increase in 18F-AH111585 uptake over the same period (P<0.01). CONCLUSION: 18F-AH111585 is a promising 18F-labeled RGD tracer that offers a new approach to noninvasively image tumor vasculature. This tracer may reveal important information in the assessment of the impact of antitumor therapies, in particular those that predominantly target tumor blood vessels.

Methods for 18F-labeling of RGD peptides: comparison of aminooxy [18F]fluorobenzaldehyde condensation with 'click labeling' using 2-[18F]fluoroethylazide, and S-alkylation with [18F]fluoropropanethiol.

Three strategies for chemoselective labeling of RGD peptides with (18)F have been compared. Aminooxy [(18)F]fluorobenzaldehyde conjugation provided 40 +/- 12% decay-corrected radiochemical yield using a fully automated method. An one-pot protocol for 'click labeling' of the RGD scaffold with 2-[(18)F]fluoroethylazide afforded 47 +/- 8% decay-corrected radiochemical yield. Attempted conjugation with 3-[(18)F]fluoropropanethiol led to extensive decomposition and was therefore found unsuitable for labeling of the RGD peptide investigated. The results suggest that 'click labeling' of RGD peptides provides an attractive alternative to aminooxy aldehyde condensation, however, 2-[(18)F]-fluoroethylazide may be too small to allow separation of large (18)F-labeled RGD peptides from their precursors.

Rural industries and water pollution in China.

Water pollution from small rural industries is a serious problem throughout China. Over half of all river sections monitored for water quality are rated as being unsafe for human contact, and this pollution is estimated to cost several per cent of GDP. While China has some of the toughest environmental protection laws in the world, the implementation of these laws in rural areas is not effective. This paper explains the reasons for this implementation gap. It argues that the factors that have underpinned the economic success of rural industry are precisely the same factors that cause water pollution from rural industry to remain such a serious problem in China. This means that the control of rural water pollution is not simply a technical problem of designing a more appropriate governance system, or finding better policy instruments or more funding. Instead, solutions lie in changes in the model that underpins rural development in China.

Vulnerability to climate variability and change in East Timor.

This paper presents the results of a preliminary study of climate vulnerability in East Timor. It shows the results of projections of climate change in East Timor. The country's climate may become hotter, drier, and increasingly variable. Sea levels are likely to rise. The paper then considers the implications of these changes on three natural resources--water, soils, and the coastal zone--and finds all to be sensitive to changes in climate and sea level. Changes in the abundance and distribution of these resources is likely to cause a reduction in agricultural production and food security, and sea-level rise is likely to damage coastal areas, including Dili, the capital city.

Ten key questions about the management of water in the Yellow River basin.

Water is scarce in many regions of the world, clean water is difficult to find in most developing countries, there are conflicts between irrigation needs and urban demands, and there is wide debate over appropriate means of resolving these problems. Similarly, in China, there is limited understanding of the ways in which people, groups, and institutions contribute to, are affected by, and respond to changes in water quantity and quality. We use the example of the Yellow River basin to argue that these social, managerial, and policy dimensions of the present water problems are significant and overshadow the physical ones. Despite this, they receive relatively little attention in the research agenda, particularly of the lead agencies in the management of the Yellow River basin. To this end, we ask ten research questions needed to address the policy needs of water management in the basin, split into two groups of five. The first five relate to the importance of water in this basin and the changes that have affected water problems and will continue to do so. The second five questions represent an attempt to explore possible solutions to these problems.