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Background Resistance to osimertinib in advanced EGFR- mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications. Methods This is a prospective single-centre study with the primary objective of characterising resistance mechanisms to osimertinib in advanced EGFR- mutated NSCLC patients treated both in first- and in second-line. Next-Generation Sequencing analysis was conducted on paired tissue biopsies and plasma samples. A concordance analysis between tissue and plasma was performed. Results Sixty-five advanced EGFR -mutated NSCLC patients treated with osimertinib in first- ( n  = 56) or in second-line ( n  = 9) were included. We managed to perform tissue and liquid biopsies in 65.5% and 89.7% of patients who experienced osimertinib progression, respectively. Acquired resistance mechanisms were identified in 80% of 25 patients with post-progression samples, with MET amplification ( n  = 8), EGFR C797S ( n  = 3), and SCLC transformation ( n  = 2) the most frequently identified. The mean concordance rates between tissue and plasma for the EGFR activating mutation and for the molecular resistance mechanisms were 87.5% and 22.7%, respectively. Conclusions Resistance to osimertinib demonstrated to be highly heterogeneous, with MET amplification the main mechanism. Plasma genotyping is a relevant complementary tool which might integrate tissue analysis for the study of resistance mechanisms.

Background: Trastuzumab has recently shown efficacy in the treatment of HER2-positive advanced gastric adenocarcinoma. Although antibody-based therapies target the metastatic disease, HER2 status is usually evaluated in the primary tumour because metastatic sites are rarely biopsied. The aim of this study was to compare HER2 status in primary and paired metastatic sites of gastric adenocarcinoma. Methods: The HER2 status was assessed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in 72 secondary lesions of gastric adenocarcinoma and in the corresponding primary tumours. Results: Concordance of FISH results, evaluable in 68 primary and matched metastatic sites, was 98.5%. Concordance of IHC results, available in 39 of the 72 paired cases, was 94.9%. Only one case showed discordance between primary tumour and metastasis, being negative by both IHC and FISH in the primary and showing HER2 overexpression and amplification in the corresponding pancreatic lymph node metastasis. Conclusion: The high concordance observed between HER2 results obtained by both IHC and FISH on primary tumours and corresponding metastases suggests that in gastric cancer HER2 status is maintained in most cases unchanged during the metastatic process.

Correction to: British Journal of Cancer (2011) 104, 1372–1376. doi:10.1038/bjc.2011.121 Upon publication earlier in Volume 104, the corresponding author noted that one of the co-authors’ names had been incorrectly spelled. S Cavalli had instead been presented as ‘S Capelli’. The authors and publishers are now happy to correct this mistake – the full, correct authorship is shown above.

Benthic biogeochemical processes and their interactions are affected by multiple factors including organic matter load, season, and hydrology. We analyzed benthic biogeochemistry in two canals in the urban area of Venice (Italy), to assess the effects of contrasting tidal conditions on organic matter processing in the heavily modified lagoonal ecosystem. We measured sediment oxygen demand, bacterial sulfate reduction, denitrification, dissimilative nitrate reduction to ammonia, dissolved inorganic carbon, and inorganic nutrient fluxes across the sediment-water interface under different seasonal (late winter and summer) and tidal (spring and neap tide) conditions. Sediments were highly organic and strongly reduced. Organic matter mineralization was mainly driven by bacterial sulfate reduction, whereas denitrification was limited by both nitrate availability and competition with dissimilatory nitrate reduction to ammonium. While the elevated benthic metabolism can be largely explained by organic enrichment, contrasting tidal conditions can be a significant driver of intra-seasonal variability of benthic biogeochemistry. Under neap tide, dissolved inorganic carbon production increased up to threefold, sulfides attained up to 6.4 mM in porewater, denitrification became inefficient, and the ratio of nitrogen recycling to dissipation increased by ~70 % compared to spring tide. Additionally, increased efflux of inorganic nitrogen from sediments fed back to promote further eutrophication. We infer that human modifications to reduce fortnightly tidal flushing can impact benthic processes, impairing sediment functioning and water quality.

The introduction of the short-necked clam Tapes philippinarum into the Sacca di Goro has over a short period made this coastal environment one of the top European clam production sites. In recent years, this activity has been seriously impacted due to the appearance in the lagoon of large macroalgal beds and the occurrence of dystrophic events causing anoxia and massive deaths of molluscs in the cultivated areas. Tapes cultivation sites now cover more than one third of the lagoon surface at densities sometimes attaining 2000-2500 adult individuals m^sup -2^; such densities and the harvesting methods, based on sediment dredging, probably have a strong impact on the benthic system. Whilst a number of studies have reported water-sediment interface induced modifications due to oyster or mussel farming there have been few attempts to quantify how clam farming affects biogeochemical cycles of oxygen and nutrients, in particular in the Sacca di Goro. Two areas, a farmed and a control one, were compared for benthic fluxes and results were correlated with clam biomass. Oxygen, carbon dioxide, ammonium, reactive silica and phosphorus fluxes were stimulated several fold by the presence of Tapes due to the clams, respiration and excretion activities, but also to the reducing conditions in the surface sediments. On average, the whole lagoon dark sediment O^sub 2^ demand and CO^sub 2^ production were stimulated by a factor of, respectively, 1.8 and 3.3, whilst nutrient release was 6.5 times higher for NH^sub 4^^sup +^ and 4.6 times higher for PO^sub 4^^sup 3-^. Our results indicate that clam farmers should carefully consider sustainable densities of Tapes in order to prevent the risk of sediment and water anoxia. Rapid nutrient recycling (up to 4000 μmol NH^sub 4^^sup +^ m^sup -2^ h^sup -1^ and 150 μmol PO^sub 4^^sup 3-^ m^sup -2^ h^sup -1^) stimulated by the high biodegradability of clam faeces and pseudofaeces could in turn favour macroalgal growth.[PUBLICATION ABSTRACT]

Lakes, ponds, and reservoirs (hereafter: “lakes”) are important sources of the greenhouse gases carbon dioxide (CO 2 ) and methane (CH 4 ). Emissions of CO 2 and CH 4 from lakes are regulated in part by in-lake processes, including the production and storage of gases in the lower parts of the water column (bottom waters). However, while substantial efforts have been made to improve estimates of greenhouse gas emissions from lakes, limited data on gas concentrations along depth profiles have prevented the incorporation of bottom-water processes in global emission estimates. Here, we present GHG-depths: the largest existing dataset of depth-profile CO 2 and CH 4 measurements worldwide, including 522 lakes across 38 countries and all seven continents. These data include contributions from 45 research teams and 56 published studies, totaling 2558 discrete sampling events. As global change continues to alter biogeochemical cycling in lakes, these data can help improve mechanistic models to better predict greenhouse gas production and emission from lakes worldwide.

Growth patterns and bloom formation of the green seaweed Ulva rigida were analysed in the eutrophic Sacca di Goro lagoon (Po River Delta, Italy). Variations of standing biomasses and elemental composition of Ulva were analysed through an annual cycle with respect to nitrogen, phosphorus and iron. Growth rates, nutrient and iron uptake and nitrate storage by macroalgal thalli were also assessed with field experiments during the formation of a spring bloom. The control of Ulva growth and the bloom formation depended on multiple factors, especially on nitrogen availability and iron deficiency. In the nitrate rich waters of the Sacca di Goro lagoon, nitrate accumulation in Ulva thalli was inversely related with Fe uptake, indicating an influence of Fe limitation on N acquisition. Since length and magnitude of nitrate luxury uptake are inversely related to the size of the intracellular nitrate pools, in nitrate rich waters the fast growing Ulva may face risk of N-limitation not only when exposed to low N concentrations or at high biomass levels, but also when exposed to pulsed dissolved nitrate concentrations at low iron availability. The potential Fe limitation could be affected by processes controlled by geochemical reactions and by macroalgal growth and decomposition. Both Fe oxidation during the active macroalgal growth and the formation of insoluble FeS and FeS^sub 2^ during bloom collapse can result in a drastic decrease of soluble iron. Thus, a potential limitation of Fe to macroalgae can occur, determining positive feedbacks and potentially controlling the extent of bloom development and persistence.[PUBLICATION ABSTRACT]

Manipulative experiments to test the short-term effect of oxygen depletion events on microbial activity and benthic fluxes in organic-rich sediments were carried out in March and June 2004. Oxic-anoxic transitions were induced by prolonged dark incubation of sealed sediment cores collected in phytotreatment ponds. Benthic fluxes of oxygen (O₂), carbon dioxide (CO₂), inorganic nutrients, and free sulfides were measured before (oxic) and after (anoxic) the transition occurred. A multifactorial design was employed for monitoring esoenzymatic activity, heterotrophic bacterial production, total prokaryotic abundance, actively respiring bacterial cells, and the biochemical composition of sedimentary organic matter. The oxic to anoxic transition resulted in a significant increase of esoenzymatic activity and bacterial production in March, due to the profound modification of the benthic community and the release of labile organic compounds which followed the onset of anoxia. In parallel, net efflux rates of dissolved inorganic carbon (DIC) and ammonium (NH₄ ⁺) sharply decreased, soluble reactive phosphorus (SRP) influx reversed, and sulfide was buffered within the oxidized sediments. From March to June, ponds evolved toward oxygen deficit and reducing conditions in the upper sediment horizon, losing benthic fauna and biogeochemical buffering capacity. Thus, the oxic to anoxic transition had a much smaller effect on microbial activity and net flux exchange, while S²⁻ was consistently delivered from the sediment to the water column. Overall data from this study suggest that the short-term response of benthic microbial activity and solute fluxes to anoxic events may have a significant impact on sediment biogeochemistry (e.g., at the oxic-anoxic interface), and that this impact may vary greatly depending on the sediment features, mainly its organic content and redox condition.