SummaryBackgroundData suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival.MethodsFOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m2 oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m2 oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary endpoint was overall survival, analysed in the intention-to-treat population, using a two-stage meta-analysis of pooled individual patient data. All three trials have completed 2 years of follow-up. FOXFIRE is registered with the ISRCTN registry, number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov, numbers NCT00724503 (SIRFLOX) and NCT01721954 (FOXFIRE-Global).FindingsBetween Oct 11, 2006, and Dec 23, 2014, 549 patients were randomly assigned to FOLFOX alone and 554 patients were assigned FOLFOX plus SIRT. Median follow-up was 43·3 months (IQR 31·6–58·4). There were 411 (75%) deaths in 549 patients in the FOLFOX alone group and 433 (78%) deaths in 554 patients in the FOLFOX plus SIRT group. There was no difference in overall survival (hazard ratio [HR] 1·04, 95% CI 0·90–1·19; p=0·61). The median survival time in the FOLFOX plus SIRT group was 22·6 months (95% CI 21·0–24·5) compared with 23·3 months (21·8–24·7) in the FOLFOX alone group. In the safety population containing patients who received at least ...

Polycentric governance and stakeholder participation in natural resource management have potential benefits for both human and environmental well-being. Researchers and decision-makers have attempted to conceptualise the ecological, social and political potential of such semi-formal approaches to urban green space management. However, few studies have quantified the actual benefits in terms of biodiversity and associated ecosystem service provision, or the factors that mediate levels of participation.The links between biodiversity potential, site access and user participation were explored in a case study comprising ten established examples of organised social-ecological initiatives in the inner-city area of Greater Manchester. At the micro-scale, the case study quantified the levels of community involvement (measured in volunteer hours month¯¹) in local green commons and the biodiversity potential (assessed using floristic and structural diversity as a surrogate) of the ten sites. Descriptive analysis identified that site spatial and design characteristics affected all three measures and subsequent correlational analyses revealed a high degree of synergy between site use and biodiversity.

Common approaches to mapping green infrastructure in urbanised landscapes invariably focus on measures of land use or land cover and associated functional or physical traits. However, such onedimensional perspectives do not accurately capture the character and complexity of the landscapes in which urban inhabitants live. The new approach presented in this paper demonstrates how open-source, high spatial and temporal resolution data with global coverage can be used to measure and represent the landscape qualities of urban environments. Through going beyond simple metrics of quantity, such as percentage green and blue cover, it is now possible to explore the extent to which landscape quality helps to unpick the mixed evidence presented in the literature on the benefits of urban nature to human well-being. Here we present a landscape approach, employing remote sensing, GIS and data reduction techniques to map urban green infrastructure elements in a large U.K. city region. Comparison with existing urban datasets demonstrates considerable improvement in terms of coverage and thematic detail. The characterisation of landscapes, using census tracts as spatial units, and subsequent exploration of associations with social-ecological attributes highlights the further detail that can be uncovered by the approach. For example, eight urban landscape types identified for the case study city exhibited associations with distinct socioeconomic conditions accountable not only to quantities but also qualities of green and blue space. The identification of individual landscape features through simultaneous measures of land use and land cover demonstrated unique and significant associations between the former and indicators of human health and ecological condition. The approach may therefore provide a promising basis for developing further insight into processes and characteristics that affect human health and well-being in urban areas, both in the United Kingdom and beyond.

10An acoustic community is defined as an aggregation of species that produces sound by using 11 internal or extra-body sound-producing tools. Such communities occur in aquatic (freshwater and 12 marine) and terrestrial environments. An acoustic community is the biophonic component of a 13 soundtope and is characterized by its acoustic signature, which results from the distribution of 14 sonic information associated with signal amplitude and frequency. Distinct acoustic communities

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