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On 16 September 1987, the main chlorofluorocarbon-producing and -consuming countries signed the Montreal Protocol, despite the absence of a scientific consensus on the mechanisms of ozone depletion over Antarctica. We argue in this article that the rapid diffusion from late 1985 onwards of satellite images showing the Antarctic ozone hole played a significant role in this diplomatic outcome. Whereas negotiators claimed that they chose to deliberately ignore the Antarctic ozone hole during the negotiations since no theory was able yet to explain it, the images still loomed large for many of the actors involved. In Western countries, the National Aeronautics and Space Administration's (NASA) satellite visualizations were diffused through the general press and television stations. Other popular and mass media outlets followed quickly. In describing the circulation and appropriation processes of these images within and beyond the scientific and negotiation arenas, we show that the ozone hole images did play an important part in ozone diplomacy in the two years leading up to the signing of the Montreal Protocol, both in the expert and diplomatic arenas and as public diplomacy tools. We conclude by encouraging scholars to engage with new visual archives and to contribute to the development of the vibrant new field of research on visual diplomacy.

Cytosolic glutamine synthetase (GS1) is the enzyme mainly responsible of ammonium assimilation and reassimilation in maize leaves. The agronomic potential of GS1 in maize kernel production was investigated by examining the impact of an overexpression of the enzyme in the leaf cells. Transgenic hybrids exhibiting a three-fold increase in leaf GS activity were produced and characterized using plants grown in the field. Several independent hybrids overexpressing Gln1-3, a gene encoding cytosolic (GS1), in the leaf and bundle sheath mesophyll cells were grown over five years in different locations. On average, a 3.8% increase in kernel yield was obtained in the transgenic hybrids compared to controls. However, we observed that such an increase was simultaneously dependent upon both the environmental conditions and the transgenic event for a given field trial. Although variable from one environment to another, significant associations were also found between two GS1 genes (Gln1-3 and Gln1-4) polymorphic regions and kernel yield in different locations. We propose that the GS1 enzyme is a potential lead for producing high yielding maize hybrids using either genetic engineering or marker-assisted selection. However, for these hybrids, yield increases will be largely dependent upon the environmental conditions used to grow the plants., (© 2021. The Author(s).)

Purpose: Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need., Patients and Methods: Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing., Results: Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class-refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class-refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4., Conclusion: Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class-refractory and extramedullary disease.

Background: Although manganese (Mn) is an essential nutrient, recent research has revealed that excess Mn in early childhood may have adverse effects on neurodevelopment., Methods: We estimated daily total Mn intake due to breast milk at average body weights by reviewing reported concentrations of breast milk Mn and measurements of body weight and breast milk intake at 3 weeks, 4.25 months, 7 months, and 18 months. We compared these figures to the Mn content measured in 44 infant, follow-up, and toddler formulas purchased in the United States and France. We calculated Mn content of formula products made with ultra-trace elemental analysis grade water (0 μg Mn/L) and with water containing 250 μg Mn/L, a concentration which is relatively high but less than the World Health Organization Health-based value of 400 μg Mn/L or the United States Environmental Protection Agency Health Advisory of 350 μg Mn/L., Results: Estimated mean daily Mn intake from breast milk ranged from 1.2 μg Mn/kg/day (3 weeks) to 0.16 μg Mn/kg/day (18 months), with the highest intakes at the youngest age stage we considered, 3 weeks. Estimated daily Mn intake from formula products reconstituted with 0 μg Mn/L water ranged from 130 μg Mn/kg/day (3 weeks) to 4.8 μg Mn/kg/day (18 months) with the highest intakes at 3 weeks. Formula products provided 28-520 times greater than the mean daily intake of Mn from breast milk for the 4 age stages that we considered. Estimated daily Mn intake from formula products reconstituted with water containing 250 μg Mn/L ranged from 12 μg Mn/kg/day to 170 μg Mn/kg/day, which exceeds the United States Environmental Protection Agency Reference Dose of 140 μg Mn/kg/day for adults., Conclusions: Mn deficiency is highly unlikely with exclusive breast milk or infant formula feeding, but established tolerable daily intake levels for Mn may be surpassed by some of these products when following labeled instructions., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Exposure to high levels of manganese (Mn) in children has recently been associated with adverse neurodevelopmental effects. Current infant formula regulations for Mn content were set between 1981 (United States), 2006 (European Union, France), and 2007 (Codex Alimentarius) prior to the publication of much of the growing body of research on the developmental neurotoxicity of Mn. In this study, we sought to measure the concentrations of Mn in some infant formulas and young child nutritional beverages available on the United States (US) and French markets using ion beam analysis by particle induced X-ray emission (PIXE) spectrometry and then compare the analytical results to concentrations reported in the literature for breast milk and applicable infant formula regulations and guidelines. We were particularly interested in measuring Mn concentrations in product types for which there is very little data from previous surveys, especially soy-based, rice-based, goat-milk based, chocolate-flavored, and nutritional beverages for young children that are not regulated as infant or follow-on formulas (e.g. "toddler formulas" and "toddler powders"). We purchased 44 infant formulas and young child nutritional beverage products in the US and France with varying protein sources (cow-milk, goat-milk, soy, rice) labelled for birth to 3 years. We selected these samples using maximum variation sampling to explore market extremes to facilitate comparisons to regulatory limits. Since this sampling method is non-probabilistic, other inferences cannot be made beyond this set of samples to the overall markets. We used ion beam analysis to measure the concentrations of Mn in each product. The range of measured Mn concentrations in the products is 160-2,800 μg/L, substantially higher than the 3-6 μg/L mean Mn concentration reported in human breast milk. All products satisfied national and Codex Alimentarius Commission (CAC) international standards for minimum Mn content in infant formulas; however, 7/25 of the products purchased in the US exceeded the CAC Guidance Upper Level of 100 μg Mn/kcal for infant formula., Competing Interests: EJM’s affiliation is with Better Life Laboratories, a nonprofit organization that conducts scientific research and provides technical expertise, equipment, and training to help needy people around the world. Better Life Laboratories received no specific funding for this project from any donors. Donors to Better Life Laboratories provided no input in choosing the subject matter of this project, the hypotheses that were tested, the individual samples that were analyzed, the method of analysis, the research findings, or the manner of disseminating the results. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To present the 12-month prevalence of DSM-IV major depressive disorder (MDD) and severe MDD; to examine sociodemographic correlates and comorbidity; and to describe impairment and service use., Method: Data are from the National Comorbidity Survey-Adolescent Supplement (NCS-A), a nationally representative survey of 10,123 adolescents aged 13 to 18 years that assesses DSM-IV disorders using the Composite International Diagnostic Interview (CIDI) Version 3.0. One parent or surrogate of each participating adolescent was also asked to complete a self-administered questionnaire., Results: Lifetime and 12-month prevalence of MDD were 11.0% and 7.5%, respectively. The corresponding rates of severe MDD were 3.0% and 2.3%. The prevalence of MDD increased significantly across adolescence, with markedly greater increases among females than among males. Most cases of MDD were associated with psychiatric comorbidity and severe role impairment, and a substantial minority reported suicidality. The prevalence of severe MDD was about one-fourth of that of all MDD cases; estimates of impairment and clinical correlates were of 2- to 5-fold greater magnitude for severe versus mild/moderate depression, with markedly higher rates for suicidal thoughts and behaviors. Treatment in any form was received by the majority of adolescents with 12-month DSM-IV MDD (60.4%), but only a minority received treatment that was disorder-specific or from the mental health sector., Conclusion: Findings underscore the important public health significance of depression among US adolescents and the urgent need to improve screening and treatment access in this population., (Published by Elsevier Inc.)

During toxic spring and fall blooms produced by the dinoflagellate Alexandrium in the Thau lagoon (Mediterranean Sea), we monitored the presence of Amoebophryidae (Syndiniales), a group of parasites virulent toward a wide range of dinoflagellate hosts. A PCR-biased approach unveiled the presence of at least 10 different parasitic groups during Alexandrium proliferation. However, fluorescent in situ hybridization failed to reveal parasitic infection inside Alexandrium cells in field populations. In contrast, several co-occurring, less abundant thecate dinoflagellate species were infected by Amoebophryidae, showing up to 10% of infected cells. We concluded that Alexandrium populations were not infected by these local parasites, at least during our survey. In order to check this resistance capacity on a more global scale, we cross-infected several Alexandrium strains isolated from the Thau lagoon with one strain of the parasite Amoebophrya sp. originating from Salt Pond, MA, USA. All of these hosts were strongly infected by the North American parasite, leading to the conclusion that blooming Alexandrium in the Thau lagoon were not particularly resistant to this kind of parasite. These results provide additional evidence that dinoflagellates may become invasive when they successfully escaped their natural enemies in time and/or space (the "enemy release" hypothesis)., (Copyright © 2011 Institut Pasteur. All rights reserved.)

A method to calibrate the elements of large arrays devoted to underwater applications is presented. The goal is to measure the sensitivity and directivity of the elements over their full bandwidth. The main constraint comes from the bounded geometry of the experimental setups that limits the duration of the time windows available for analyzing the received signals. Using a short wideband pulse is detrimental to obtaining high signal-to-noise ratios. A classical method for handling this problem is time-delay spectrometry (TDS), which is based on the transmission of a linear frequency- modulated signal combined with a sliding frequency filter. An alternative, hybrid method based on the transmission of a sequence of time-frequency-limited signals is proposed. This hybrid method is shown to provide the same spectral density as TDS in the frequency scanning, but the filtering process is quite different. The transmitted signals are designed to take advantage of the coherent sums of the received signals to track the time of flight of the direct paths between the source and the elements. In addition, a fitting process based on the calibration geometry of data acquisition enables the boundaries of the interference-free time windows to be precisely delineated. An example of the application is described.