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BackgroundRelapsed high‐grade glioma has dismal outcomes. Mebendazole has shown promising activity against glioma in in‐vitro and in‐vivo studies. Hence, we undertook a phase 1 study to repurpose mebendazole in the treatment of glioblastoma.MethodsWe conducted a phase 1 study (accelerated titrated design 4) of mebendazole in patients with recurrent glioblastoma (GBM). Patients eligible for re‐irradiation were enrolled in arm A1 (radiation with concurrent temozolomide 75 mg/m2 daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m2 day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m2 day 1‐5, every 4 weekly + mebendazole). The primary endpoint of phase 1 was to identify the MTD of mebendazole in each combination.Findings11 patients were enrolled in the whole study. MTD of mebendazole was not reached in arm A1 and C1 and hence the recommended dose for phase 2 was 1600 mg TDS (4800 mg) per day. The MTD of mebendazole in combination with CCNU was 1600 mg TDS (4800 mg) per day and the dose recommended for phase 2 was 800 mg TDS (2400 mg) per day. The three most common adverse events seen in the study were anemia (n = 9, 81.8%), nausea (n = 7, 63.6%), and fatigue (n = 6, 55.5%).InterpretationThe recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide‐radiation combination while the dose of 800 mg TDS needs to be used with single‐agent CCNU.

The United Nation’s Sustainable Development Goal Life Below Water (SDG-14) aims to “conserve and sustainably use the oceans, seas, and marine resources for sustainable development”. Within SDG-14, targets 14.1 and 14.2 deal with marine pollution and the adverse impacts of human activities on aquatic systems. Here, we present a remote-sensing-based analysis of short-term changes in the Vembanad-Kol wetland system in the southwest of India. The region has experienced high levels of anthropogenic pressures, including from agriculture, industry, and tourism, leading to adverse ecological and socioeconomic impacts with consequences not only for achieving the targets set out in SDG-14, but also those related to water quality (SDG-6) and health (SDG-3). To move towards the sustainable management of coastal and aquatic ecosystems such as Lake Vembanad, it is important to understand how both natural and anthropogenic processes affect water quality. In 2020, a unique opportunity arose to study water quality in Lake Vembanad during a period when anthropogenic pressures were reduced due to a nationwide lockdown in response to the global pandemic caused by SARS-CoV-2 (25 March–31 May 2020). Using Sentinel-2 and Landsat-8 multi-spectral remote sensing and in situ observations to analyse changes in five different water quality indicators, we show that water quality improved in large areas of Lake Vembanad during the lockdown in 2020, especially in the more central and southern regions, as evidenced by a decrease in total suspended matter, turbidity, and the absorption by coloured dissolved organic matter, all leading to clearer waters as indicated by the Forel-Ule classification of water colour. Further analysis of longer term trends (2013–2020) showed that water quality has been improving over time in the more northern regions of Lake Vembanad independent of the lockdown. The improvement in water quality during the lockdown in April–May 2020 illustrates the importance of addressing anthropogenic activities for the sustainable management of coastal ecosystems and water resources.

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Citizen science aims to mobilise the general public, motivated by curiosity, to collect scientific data and contribute to the advancement of scientific knowledge. In this article, we describe a citizen science network that has been developed to assess the water quality in a 100 km long tropical lake-estuarine system (Vembanad Lake), which directly or indirectly influences the livelihood of around 1.6 million people. Deterioration of water quality in the lake has resulted in frequent outbreaks of water-associated diseases, leading to morbidity and occasionally, to mortality. Water colour and clarity are easily measurable and can be used to study water quality. Continuous observations on relevant spatial and temporal scales can be used to generate maps of water colour and clarity for identifying areas that are turbid or eutrophic. A network of citizen scientists was established with the support of students from 16 colleges affiliated with three universities of Kerala (India) and research institutions, and stakeholders such as houseboat owners, non-government organisations (NGOs), regular commuters, inland fishermen, and others residing in the vicinity of Vembanad Lake and keen to contribute. Mini Secchi disks, with Forel-Ule colour scale stickers, were used to measure the colour and clarity of the water. A mobile application, named “TurbAqua,” was developed for easy transmission of data in near-real time. In-situ data from scientists were used to check the quality of a subset of the citizen observations. We highlight the major economic benefits from the citizen network, with stakeholders voluntarily monitoring water quality in the lake at low cost, and the increased potential for sustainable monitoring in the long term. The data can be used to validate satellite products of water quality and can provide scientific information on natural or anthropogenic events impacting the lake. Citizens provided with scientific tools can make their own judgement on the quality of water that they use, helping toward Sustainable Development Goal 6 of clean water. The study highlights potential for world-wide application of similar citizen-science initiatives, using simple tools for generating long-term time series data sets, which may also help monitor climate change.

14 15Oxygen minimum zones (OMZs) are large, low-oxygen areas in the global oceans. Although 16OMZs represent a serious threat to ecosystem functioning and services, our capability of modelling 17 the main biogeochemical processes driving OMZ dynamic are still limited. Here we performed a 18 full sensitivity analysis of a complex ecosystem model to rank the most important biogeochemical 19 parameters influencing the simulation of the OMZ at an oligotrophic site in the open Arabian Sea. 20We applied a one-dimensional configuration of the European Regional Seas Ecosystem Model 21 (ERSEM) -here advanced by including denitrification -coupled with the General Ocean 22Turbulence Model (GOTM). The coupled model was skilled in simulating the vertical gradients of 23 climatological data of oxygen and nutrients. The sensitivity analysis of the model was carried out in 24 two steps: i) a preliminary Morris screening analysis of 207 ERSEM parameters, which selected the 25 three most influential groups of parameters; and ii) a subsequent Monte Carlo sampling-based 26 2 analysis for ranking the importance of the 38 parameters within the three selected groups. Overall, 27 the four most important parameters for the simulation of the minimum oxygen concentration were 28 found to be: 1) the cubic half saturation constant for oxygenic control of denitrification; 2) the 29 parameter regulating the fraction of ingested matter excreted by heterotrophic nanoflagellates; 3) 30 the bacterial efficiency at low oxygen levels; and 4) the specific rate of bacterial release of capsular 31 material. Based on these findings, and assuming that the ranking of the model parameters reflects 32 the relevance of the process they characterize, we present a conceptual model describing the most 33 important biogeochemical processes affecting the OMZ at the study site. Our results suggest that 34 including bacteria explicitly in ecosystem models is useful to simulate and predict OMZs, provided 35 that efforts are invested in estimating parameters characterizing the microbial loop in marine 36 ecosystems. 37 38

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