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Purpose Radionuclide therapy with 177 Lu-DOTATATE is well established for patients with advanced somatostatin receptor–positive neuroendocrine tumors with a standard schedule of 7.4 GBq at four occasions. However, this approach does not consider individual variability affecting the tumor radiation dose or dose to organs at risk. Therefore, it is important to assess more personalized strategies. The aim of this phase II trial was to evaluate individualized 177 Lu-DOTATATE for which the number of cycles varied based on renal dosimetry. Methods Patients were eligible if they had a progressive, somatostatin receptor–positive neuroendocrine tumor with a Ki 67 labeling index < 20%. They received cycles of 7.4 GBq of 177 Lu-DOTATATE at 10 ± 2-week intervals until a predefined radiation dose to the kidneys was reached. The primary endpoint was objective tumor response (RECIST v 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity (CTCAE v. 4.0). Results Ninety-six patients who had received a median of 5 cycles (range 1–9) were evaluable for efficacy. The objective tumor response was 16% partial response, 66% stable disease, and 19% progressive disease. The median PFS and OS were 29 months and 47 months, respectively, and were significantly associated with kidney dose, performance status, and Ki 67 levels but not with tumor origin. The overall toxicity was mild, and the most common events were grade 1–2 anemia, thrombocytopenia, fatigue, nausea, and diarrhea. Grade 3–4 toxicity occurred in < 10% of patients and was mostly hematological, with no grade 3–4 renal toxicity. Conclusion Individualized treatment with 177 Lu-DOTATATE based on renal dosimetry is clearly feasible with low toxicity and promising efficacy, showing the potential to further improve outcome beyond the standard approach, and should be further assessed in randomized trials. Trial registration EudraCT 2011–000,240-16. NCT01456078. https://clinicaltrials.gov/ct2/show/NCT01456078

A multi-year study was conducted in the eutrophic Lafayette River, a sub-tributary of the lower Chesapeake Bay during which uptake of inorganic and organic nitrogen (N) and C compounds was measured during multiple seasons and years when different dinoflagellate species were dominant. Seasonal dinoflagellate blooms included a variety of mixotrophic dinoflagellates including Heterocapsa triquetra in the late winter, Prorocentrum minimum in the spring, Akashiwo sanguinea in the early summer, and Scrippsiella trochoidea and Cochlodinium polykrikoides in late summer and fall. Results showed that no single N source fueled algal growth, rather rates of N and C uptake varied on seasonal and diurnal timescales, and within blooms as they initiated and developed. Rates of photosynthetic C uptake were low yielding low assimilation numbers during much of the study period and the ability to assimilate dissolved organic carbon augmented photosynthetic C uptake during bloom and non-bloom periods. The ability to use dissolved organic C during the day and night may allow mixotrophic bloom organisms a competitive advantage over co-occurring phytoplankton that are restricted to photoautotrophic growth, obtaining N and C during the day and in well-lit surface waters.

Modes of floral presentation in some angiosperms attract flies that eat and/or oviposit on seasonal fruiting bodies of fungi. Mushroom mimesis by orchid flowers has been speculated in the geoflorous, Indo-Malaysian-Australasian, genus Corybas s.l. for decades but most studies remain fragmentary and are often inconclusive. Here we report the roles of fungus gnats as pollinators of Corybas geminigibbus and C. shanlinshiensis in southwestern Yunnan, China, combining results of field observations, lab analyses, and manipulative experiments. Hand pollination experiments suggested both species were self-compatible but incapable of mechanical self-pollination, thereby requiring pollinators for fruit production. A female of a Phthinia sp. (Mycetophilidae) carried a pollinarium of C. geminigibbus dorsally on its thorax. Two females and one male of Exechia sp. (Mycetophilidae) visiting flowers of C. shanlinshiensis carried dorsal depositions of pollinaria on their thoraces. Mycetophilid eggs were not found in the flowers of either species. The comparative fragrance analyses of these flowers and three co-fruiting mushroom species did not suggest that either orchid species was a brood-site mimic. This is the first confirmation of the dispersal of pollinaria of Corybas species by fungus gnats in subtropical-temperate Asia.

Examination of dinitrogen (N₂) fixation in the Eastern Tropical South Pacific oxygen deficient zone has raised questions about the range of diazotrophs in the deep sea and their quantitative importance as a source of new nitrogen globally. However, technical considerations in the deployment of stable isotopes in quantifying N₂ fixation rates have complicated interpretation of this research. Here, we report the findings of a comprehensive survey of N₂ fixation within, above and below the Eastern Tropical South Pacific oxygen deficient zone. N₂ fixation rates were measured using a robust 15N tracer method (bubble removal) that accounts for the slow dissolution of N₂ gas and calculated using a conservative approach. N₂ fixation was only detected in a subset of samples (8 of 125 replicated measurements) collected within suboxic waters (< 20 μmol O₂ kg−1) or at the oxycline. Most of these detectable rates were measured at nearshore stations, or where surface productivity was high. These findings support the hypothesis that low oxygen/high organic carbon conditions favor non-cyanobacterial diazotrophs. Nevertheless, this study indicates that N₂ fixation is neither widespread nor quantitatively important throughout this region.

The aim of this standard operational procedure is to standardize the methodology employed for the evaluation of pre- and post-treatment absorbed dose calculations in 90Y microsphere liver radioembolization. Basic assumptions include the permanent trapping of microspheres, the local energy deposition method for voxel dosimetry, and the patient–relative calibration method for activity quantification.The identity of 99mTc albumin macro-aggregates (MAA) and 90Y microsphere biodistribution is also assumed. The large observed discrepancies in some patients between 99mTc-MAA predictions and actual 90Y microsphere distributions for lesions is discussed. Absorbed dose predictions to whole non-tumoural liver are considered more reliable and the basic predictors of toxicity. Treatment planning based on mean absorbed dose delivered to the whole non-tumoural liver is advised, except in super-selective treatments.Given the potential mismatch between MAA simulation and actual therapy, absorbed doses should be calculated both pre- and post-therapy. Distinct evaluation between target tumours and non-tumoural tissue, including lungs in cases of lung shunt, are vital for proper optimization of therapy. Dosimetry should be performed first according to a mean absorbed dose approach, with an optional, but important, voxel level evaluation. Fully corrected 99mTc-MAA Single Photon Emission Computed Tomography (SPECT)/computed tomography (CT) and 90Y TOF PET/CT are regarded as optimal acquisition methodologies, but, for institutes where SPECT/CT is not available, non-attenuation corrected 99mTc-MAA SPECT may be used. This offers better planning quality than non dosimetric methods such as Body Surface Area (BSA) or mono-compartmental dosimetry. Quantitative 90Y bremsstrahlung SPECT can be used if dedicated correction methods are available.The proposed methodology is feasible with standard camera software and a spreadsheet. Available commercial or free software can help facilitate the process and improve calculation time.

Biological nitrogen fixation (BNF) was investigated above and within the oxygen-depleted waters of the oxygen-minimum zone of the Eastern Tropical North Pacific Ocean. BNF rates were estimated using an isotope tracer method that overcame the uncertainty of the conventional bubble method by directly measuring the tracer enrichment during the incubations. Highest rates of BNF (~4 n M  day −1 ) occurred in coastal surface waters and lowest detectable rates (~0.2 n M  day −1 ) were found in the anoxic region of offshore stations. BNF was not detectable in most samples from oxygen-depleted waters. The composition of the N 2 -fixing assemblage was investigated by sequencing of nifH genes. The diazotrophic assemblage in surface waters contained mainly Proteobacterial sequences (Cluster I nifH ), while both Proteobacterial sequences and sequences with high identities to those of anaerobic microbes characterized as Clusters III and IV type nifH sequences were found in the anoxic waters. Our results indicate modest input of N through BNF in oxygen-depleted zones mainly due to the activity of proteobacterial diazotrophs.

In coastal urban areas, tidal flooding brings water carrying nutrients and particles back from land to estuarine and coastal waters. A statistical model to predict nutrient loads during tidal flooding events can help estimate nutrient loading from previous and future flooding events and adapt nutrient reduction strategies. We measured concentrations of dissolved inorganic nitrogen and phosphorus in floodwater at seven sentinel sites during 15 tidal flooding events from January 2019 to September 2020. The study area was the Lafayette River watershed in Norfolk, VA, USA, which is prone to tidal flooding and is predicted to experience more frequent and intense flooding in the future. We calculated the difference in dissolved inorganic nitrogen (ΔDIN) or phosphorus (ΔDIP) concentrations between floodwater and those measured in the estuary prior to tidal flooding for each sentinel site and flooding event. We calculated the correlations between ΔDIN and ΔDIP with corresponding data on precipitation, wind, flooding intensity, average estuarine nutrient concentrations, population density, income, land elevation, land use, and land coverage. Using the variables with the highest R 2 values for the linear regression with either ΔDIN or ΔDIP, we built multi-variable random forest regression models. ΔDIN showed the strongest correlations with floodwater nutrient concentrations, water level, and water temperature. ΔDIP also had a strong correlation with floodwater nutrient concentrations and water temperature, but had also a strong correlation wind speed. Models indicated that inputs per flooding event ranged from − 5000 to 7500 kg N, for DIN, while those for DIP ranged from 2000 to 23,000 kg P, with net inputs of > 5000 kg N and > 100,000 kg P, respectively. Removing the dissolved nutrient concentration in floodwater variables from the models, we were able to calculate loads from events that occurred all the way back to 1946. Predicted DIN load per single flooding event ranged from ~ 0 to 1.5 × 10 5  kg N and showed a significant linear regression with time. Predicted DIP load estimates per single flooding event ranged from >  − 1.0 × 10 5 to < 1.5 × 10 5  kg P, with a significant positive trend over time. The positive trend in these load values over time shows that they have and will continue to be an increasing problem for the water quality of the local water systems. These results indicate that further action should be taken to control the input of dissolved nutrients during tidal flooding events in urban coastal areas.

Recent work has suggested that the oxygen deficient zone (ODZ) and overlying surface waters of the eastern tropical South Pacific (ETSP) is a potential niche for dinitrogen (N₂) fixation. Rates of dinitrogen fixation were measured in the ETSP above and within the ODZ in July 2013 using a modified 15N₂ bubble addition method, wherein a bubble was added, mixed, and then removed, and the isotopic enrichment of the dissolved N₂ was measured directly for each incubation. N₂ fixation rates in the euphotic zone ranged from below detection to 3.9 nmol L−1 d−1 and were below detection at all depths surveyed within the ODZ. Depth-integrated rates ranged from below detection to 289.7 μmol m−2 d−1. DNA and RNA of diverse nifH genes were detected at both surface waters and in the ODZ. However, the results of this study suggest that N₂ fixation rates were low and contribute little to N cycling in the ETSP.

Due to sea level rise, tidal flooding is now common in low-lying coastal systems around the world. Yet, the contribution of tidal flooding to non-point source nutrient loads and their impact on the quality of adjacent waters remains poorly constrained. Here, we quantified dissolved nutrient loading and Enterococcus abundance during annual autumnal king tides (i.e., perigean spring tides), between 2017 and 2021, in a sub-watershed of the lower Chesapeake Bay. To calculate nutrient loading from tidal flooding, we used geospatial inundation depths from a street-level hydrodynamic model to estimate floodwater volumes during each of the five sampling events and the difference between nutrient concentrations in floodwater and pre-flood measurements. Results showed that dissolved nutrient concentrations were higher in floodwaters than in estuarine waters and resulted in dissolved nitrogen and phosphorus loads that reached 58.4 × 103 kg and 14.4 × 103 kg, respectively. We compared our load estimates to the tributary-specific total and land-based federal allocations (i.e., total maximum daily loads (TMDL)) for total nitrogen (TN) and total phosphorus (TP). Even the more conservative calculations indicate that inputs of dissolved nutrients during a single tidal flooding event can exceed 100% of the annual load allocation. Additionally, more than 80% of the floodwater samples collected each year showed Enterococcus abundance that exceeded the threshold for recreational water use in Virginia (104 MPN 100 ml−1). Failing to account for non-point source loading of nutrients and contaminants from tidal flooding as sea level rises could result in worsening eutrophication and deterioration of coastal economies and the health of coastal communities around the world.