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- ItemImpact of mucus modulation by N-acetylcysteine on nanoparticle toxicity(Amsterdam : Elsevier, 2023) Meziu, Enkeleda; Shehu, Kristela; Koch, Marcus; Schneider, Marc; Kraegeloh, AnnetteHuman respiratory mucus is a biological hydrogel that forms a protective barrier for the underlying epithelium. Modulation of the mucus layer has been employed as a strategy to enhance transmucosal drug carrier transport. However, a drawback of this strategy is a potential reduction of the mucus barrier properties, in particular in situations with an increased exposure to particles. In this study, we investigated the impact of mucus modulation on its protective role. In vitro mucus was produced by Calu-3 cells, cultivated at the air-liquid interface for 21 days and used for further testing as formed on top of the cells. Analysis of confocal 3D imaging data revealed that after 21 days Calu-3 cells secrete a mucus layer with a thickness of 24 ± 6 μm. Mucus appeared to restrict penetration of 500 nm carboxyl-modified polystyrene particles to the upper 5–10 μm of the layer. Furthermore, a mucus modulation protocol using aerosolized N-acetylcysteine (NAC) was developed. This treatment enhanced the penetration of particles through the mucus down to deeper layers by means of the mucolytic action of NAC. These findings were supported by cytotoxicity data, indicating that intact mucus protects the underlying epithelium from particle-induced effects on membrane integrity. The impact of NAC treatment on the protective properties of mucus was probed by using 50 and 100 nm amine-modified and 50 nm carboxyl-modified polystyrene nanoparticles, respectively. Cytotoxicity was only induced by the amine-modified particles in combination with NAC treatment, implying a reduced protective function of modulated mucus. Overall, our data emphasize the importance of integrating an assessment of the protective function of mucus into the development of therapy approaches involving mucus modulation.
- ItemSafe-by-Design part II: A strategy for balancing safety and functionality in the different stages of the innovation process(Amsterdam : Elsevier, 2021) Tavernaro, Isabella; Dekkers, Susan; Soeteman-Hernández, Lya G.; Herbeck-Engel, Petra; Noorlander, Cornelle; Kraegeloh, AnnetteManufactured nanomaterials have the potential to impact an exceedingly wide number of industries and markets ranging from energy storage, electronic and optical devices, light-weight construction to innovative medical approaches for diagnostics and therapy. In order to foster the development of safer nanomaterial-containing products, two main aspects are of major interest: their functional performance as well as their safety towards human health and the environment. In this paper a first proposal for a strategy is presented to link the functionality of nanomaterials with safety aspects. This strategy first combines information on the functionality and safety early during the innovation process and onwards, and then identifies Safe-by-Design (SbD) actions that allow for optimisation of both aspects throughout the innovation process. The strategy encompasses suggestions for the type of information needed to balance functionality and safety to support decision making in the innovation process. The applicability of the strategy is illustrated using a literature-based case study on carbon nanotube-based transparent conductive films. This is a first attempt to identify information that can be used for balancing functionality and safety in a structured way during innovation processes.
- ItemAMPA-15N - Synthesis and application as standard compound in traceable degradation studies of glyphosate(Amsterdam : Elsevier, 2021) Wirth, Marisa A.; Longwitz, Lars; Kanwischer, Marion; Gros, Peter; Leinweber, Peter; Werner, ThomasStable isotope labeling of pollutants is a valuable tool to investigate their environmental transport and degradation. For the globally most frequently used herbicide glyphosate, such studies have, so far, been hampered by the absence of an analytical standard for its labeled metabolite AMPA-15N, which is formed during the degradation of all commercially available glyphosate isotopologues. Without such a standard, detection and quantitation of AMPA-15N, e.g. with LC-MS/MS, is not possible. Therefore, a synthetic pathway to AMPA-15N from benzamide-15N via the hemiaminal was developed. AMPA-15N was obtained in sufficient yield and purity to be used as a standard compound for LC-MS/MS analysis. Suitable MS-detection settings as well as a calibration using the internal standard (IS) approach were established for Fmoc-derivatized AMPA-15N. The use of different AMPA isotopologues as IS was complicated by the parallel formation of [M+H]+ and [M]+• AMPA-Fmoc precursor ions in ESI-positive mode, causing signal interferences between analyte and IS. We recommend the use of either AMPA-13C-15N, AMPA-13C-15N-D2 or a glyphosate isotopologue as IS, as they do not affect the linearity of the calibration curve. As a proof of concept, the developed analysis procedure for AMPA-15N was used to refine the results from a field lysimeter experiment investigating leaching and degradation of glyphosate-2-13C-15N. The newly enabled quantitation of AMPA-15N in soil extracts showed that similar amounts (0.05 - 0.22 mg·kg-1) of the parent herbicide glyphosate and its primary metabolite AMPA persisted in the topsoil over the study period of one year, while vertical transport through the soil column did not occur for either of the compounds. The herein developed analysis concepts will facilitate future design and execution of experiments on the environmental fate of the herbicide glyphosate.
- ItemCorona crisis fuels racially profiled hate in social media networks(Amsterdam : Elsevier, 2020) Stechemesser, Annika; Wenz, Leonie; Levermann, Anders[No abstract available]
- ItemSafe-by-Design part I: Proposal for nanospecific human health safety aspects needed along the innovation process(Amsterdam : Elsevier, 2020) Dekkers, S.; Wijnhoven, S.W.P.; Braakhuis, H.M.; Soeteman-Hernandez, L.G.; Sips, A.J.A.M.; Tavernaro, I.; Kraegeloh, A.; Noorlander, C.W.Safe-by-Design aims to reduce uncertainties and/or increase the human health and environmental safety from already early in the innovation process onwards and will thereby contribute to increased innovation efficiency, economic viability, interdisciplinary collaboration, consumers trust and improve sustainability. Since most innovators or designers are neither toxicologists nor risk assessors, considering human health safety aspects within their innovation process may be challenging. This paper provides sets of questions that can help innovators to assess nanospecific human health safety aspects of their product or material along the various stages of the innovation process. Addressing these questions will facilitate innovators to identify which type of information may support decisions on how to address potential human health risks in the innovation process. The identified information on the human health safety aspects can help innovators to decide if further investments in the product or material are beneficial. It may allow them to rank, prioritize and choose safer alternatives early in the innovation process. This may enable innovators to better anticipate on potential safety issues in an early stage, preventing these safety issues to become an innovation killer in a later stage of the innovation process. This approach to identify potential nanospecific human health risks should be considered as complementary to current regulations. The applicability of this approach was evaluated using a few industrial case studies. To determine if the approach is applicable to the innovation of a broader group of nanomaterials and nano-enabled products, more experience within various industrial sectors is needed.
- ItemGlobal, regional, and national burden of mortality associated with non-optimal ambient temperatures from 2000 to 2019: a three-stage modelling study(Amsterdam : Elsevier, 2021) Zhao, Qi; Guo, Yuming; Ye, Tingting; Gasparrini, Antonio; Tong, Shilu; Overcenco, Ala; Urban, Aleš; Schneider, Alexandra; Entezari, Alireza; Vicedo-Cabrera, Ana Maria; Zanobetti, Antonella; Analitis, Antonis; Zeka, Ariana; Tobias, Aurelio; Nunes, Baltazar; Alahmad, Barrak; Armstrong, Ben; Forsberg, Bertil; Pan, Shih-Chun; Íñiguez, Carmen; Ameling, Caroline; De la Cruz Valencia, César; Åström, Christofer; Houthuijs, Danny; Dung, Do Van; Royé, Dominic; Indermitte, Ene; Lavigne, Eric; Mayvaneh, Fatemeh; Acquaotta, Fiorella; de'Donato, Francesca; Di Ruscio, Francesco; Sera, Francesco; Carrasco-Escobar, Gabriel; Kan, Haidong; Orru, Hans; Kim, Ho; Holobaca, Iulian-Horia; Kyselý, Jan; Madureira, Joana; Schwartz, Joel; Jaakkola, Jouni J. K.; Katsouyanni, Klea; Hurtado Diaz, Magali; Ragettli, Martina S.; Hashizume, Masahiro; Pascal, Mathilde; de Sousa Zanotti Stagliorio Coélho, Micheline; Valdés Ortega, Nicolás; Ryti, Niilo; Scovronick, Noah; Michelozzi, Paola; Matus Correa, Patricia; Goodman, Patrick; Nascimento Saldiva, Paulo Hilario; Abrutzky, Rosana; Osorio, Samuel; Rao, Shilpa; Fratianni, Simona; Dang, Tran Ngoc; Colistro, Valentina; Huber, Veronika; Lee, Whanhee; Seposo, Xerxes; Honda, Yasushi; Guo, Yue Leon; Bell, Michelle L.; Li, ShanshanBackground: Exposure to cold or hot temperatures is associated with premature deaths. We aimed to evaluate the global, regional, and national mortality burden associated with non-optimal ambient temperatures. Methods: In this modelling study, we collected time-series data on mortality and ambient temperatures from 750 locations in 43 countries and five meta-predictors at a grid size of 0·5° × 0·5° across the globe. A three-stage analysis strategy was used. First, the temperature–mortality association was fitted for each location by use of a time-series regression. Second, a multivariate meta-regression model was built between location-specific estimates and meta-predictors. Finally, the grid-specific temperature–mortality association between 2000 and 2019 was predicted by use of the fitted meta-regression and the grid-specific meta-predictors. Excess deaths due to non-optimal temperatures, the ratio between annual excess deaths and all deaths of a year (the excess death ratio), and the death rate per 100 000 residents were then calculated for each grid across the world. Grids were divided according to regional groupings of the UN Statistics Division. Findings: Globally, 5 083 173 deaths (95% empirical CI [eCI] 4 087 967–5 965 520) were associated with non-optimal temperatures per year, accounting for 9·43% (95% eCI 7·58–11·07) of all deaths (8·52% [6·19–10·47] were cold-related and 0·91% [0·56–1·36] were heat-related). There were 74 temperature-related excess deaths per 100 000 residents (95% eCI 60–87). The mortality burden varied geographically. Of all excess deaths, 2 617 322 (51·49%) occurred in Asia. Eastern Europe had the highest heat-related excess death rate and Sub-Saharan Africa had the highest cold-related excess death rate. From 2000–03 to 2016–19, the global cold-related excess death ratio changed by −0·51 percentage points (95% eCI −0·61 to −0·42) and the global heat-related excess death ratio increased by 0·21 percentage points (0·13–0·31), leading to a net reduction in the overall ratio. The largest decline in overall excess death ratio occurred in South-eastern Asia, whereas excess death ratio fluctuated in Southern Asia and Europe. Interpretation: Non-optimal temperatures are associated with a substantial mortality burden, which varies spatiotemporally. Our findings will benefit international, national, and local communities in developing preparedness and prevention strategies to reduce weather-related impacts immediately and under climate change scenarios. Funding: Australian Research Council and the Australian National Health and Medical Research Council. © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
- ItemThe environmental footprint of health care: a global assessment(Amsterdam : Elsevier, 2020) Lenzen, Manfred; Malik, Arunima; Li, Mengyu; Fry, Jacob; Weisz, Helga; Pichler, Peter-Paul; Chaves, Leonardo Suveges Moreira; Capon, Anthony; Pencheon, DavidBackground: Health-care services are necessary for sustaining and improving human wellbeing, yet they have an environmental footprint that contributes to environment-related threats to human health. Previous studies have quantified the carbon emissions resulting from health care at a global level. We aimed to provide a global assessment of the wide-ranging environmental impacts of this sector. Methods: In this multiregional input-output analysis, we evaluated the contribution of health-care sectors in driving environmental damage that in turn puts human health at risk. Using a global supply-chain database containing detailed information on health-care sectors, we quantified the direct and indirect supply-chain environmental damage driven by the demand for health care. We focused on seven environmental stressors with known adverse feedback cycles: greenhouse gas emissions, particulate matter, air pollutants (nitrogen oxides and sulphur dioxide), malaria risk, reactive nitrogen in water, and scarce water use. Findings: Health care causes global environmental impacts that, depending on which indicator is considered, range between 1% and 5% of total global impacts, and are more than 5% for some national impacts. Interpretation: Enhancing health-care expenditure to mitigate negative health effects of environmental damage is often promoted by health-care practitioners. However, global supply chains that feed into the enhanced activity of health-care sectors in turn initiate adverse feedback cycles by increasing the environmental impact of health care, thus counteracting the mission of health care. Funding: Australian Research Council, National eResearch Collaboration Tools and Resources project. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
- ItemPopulation ageing and deaths attributable to ambient PM2·5 pollution: a global analysis of economic cost(Amsterdam : Elsevier, 2021) Yin, Hao; Brauer, Michael; Zhang, Junfeng (Jim); Cai, Wenjia; Navrud, Ståle; Burnett, Richard; Howard, Courtney; Deng, Zhu; Kammen, Daniel M.; Schellnhuber, Hans Joachim; Chen, Kai; Kan, Haidong; Chen, Zhan-Ming; Chen, Bin; Zhang, Ning; Mi, Zhifu; Coffman, D'Maris; Cohen, Aaron J.; Guan, Dabo; Zhang, Qiang; Gong, Peng; Liu, ZhuBackground: The health impacts of ambient air pollution impose large costs on society. Although all people are exposed to air pollution, the older population (ie, those aged ≥60 years) tends to be disproportionally affected. As a result, there is growing concern about the health impacts of air pollution as many countries undergo rapid population ageing. We investigated the spatial and temporal variation in the economic cost of deaths attributable to ambient air pollution and its interaction with population ageing from 2000 to 2016 at global and regional levels. Methods: In this global analysis, we developed an age-adjusted measure of the value of a statistical life-year (VSLY) to estimate the economic cost of deaths attributable to ambient PM2·5 pollution using Global Burden of Diseases, Injuries, and Risk Factors Study 2017 data and country-level socioeconomic information. First, we estimated the global age-specific and cause-specific mortality and years of life lost (YLLs) attributable to PM2·5 pollution using the global exposure mortality model and global estimates of exposure at 0·1° × 0·1° (about 11 km × 11 km at the equator) resolution. Second, for each year between 2000 and 2016, we translated the YLLs within each age group into a health-related cost using a country-specific, age-adjusted measure of VSLY. Third, we decomposed the major driving factors that contributed to the temporal change in health costs related to PM2·5. Finally, we did a sensitivity test to analyse the variability of the estimated health costs to four alternative valuation measures. We identified the uncertainty intervals (UIs) from 1000 draws of the parameters and concentration–response functions by age, cause, country, and year. All economic values are reported in 2011 purchasing power parity-adjusted US dollars. All simulations were done with R, version 3.6.0. Findings: Globally, in 2016, PM2·5 was estimated to have caused 8·42 million (95% UI 6·50–10·52) attributable deaths, which was associated with 163·68 million (116·03–219·44) YLLs. In 2016, the global economic cost of deaths attributable to ambient PM2·5 pollution for the older population was US$2·40 trillion (1·89–2·93) accounting for 59% (59–60) of the cost for the total population ($4·09 trillion [3·19–5·05]). The economic cost per capita for the older population was $2739 (2160–3345) in 2016, which was 10 times that of the younger population (ie, those aged <60 years). By assessing the factors that contributed to economic costs, we found that increases in these factors changed the total economic cost by 77% for gross domestic product (GDP) per capita, 21% for population ageing, 16% for population growth, −41% for age-specific mortality, and −0·4% for PM2·5 exposure. Interpretation: The economic cost of ambient PM2·5 borne by the older population almost doubled between 2000 and 2016, driven primarily by GDP growth, population ageing, and population growth. Compared with younger people, air pollution leads to disproportionately higher health costs among older people, even after accounting for their relatively shorter life expectancy and increased disability. As the world's population is ageing, the disproportionate health cost attributable to ambient PM2·5 pollution potentially widens the health inequities for older people. Countries with severe air pollution and rapid ageing rates need to take immediate actions to improve air quality. In addition, strategies aimed at enhancing health-care services, especially targeting the older population, could be beneficial for reducing the health costs of ambient air pollution. Funding: National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Qiushi Foundation.
- ItemAmbient carbon monoxide and daily mortality: a global time-series study in 337 cities(Amsterdam : Elsevier, 2021) Chen, Kai; Breitner, Susanne; Wolf, Kathrin; Stafoggia, Massimo; Sera, Francesco; Vicedo-Cabrera, Ana M.; Guo, Yuming; Tong, Shilu; Lavigne, Eric; Matus, Patricia; Valdés, Nicolás; Kan, Haidong; Jaakkola, Jouni J. K.; Ryti, Niilo R. I.; Huber, Veronika; Scortichini, Matteo; Hashizume, Masahiro; Honda, Yasushi; Nunes, Baltazar; Madureira, Joana; Holobâcă, Iulian Horia; Fratianni, Simona; Kim, Ho; Lee, Whanhee; Tobias, Aurelio; Íñiguez, Carmen; Forsberg, Bertil; Åström, Christofer; Ragettli, Martina S.; Guo, Yue-Liang Leon; Chen, Bing-Yu; Li, Shanshan; Milojevic, Ai; Zanobetti, Antonella; Schwartz, Joel; Bell, Michelle L.; Gasparrini, Antonio; Schneider, AlexandraBackground Epidemiological evidence on short-term association between ambient carbon monoxide (CO) and mortality is inconclusive and limited to single cities, regions, or countries. Generalisation of results from previous studies is hindered by potential publication bias and different modelling approaches. We therefore assessed the association between short-term exposure to ambient CO and daily mortality in a multicity, multicountry setting. Methods We collected daily data on air pollution, meteorology, and total mortality from 337 cities in 18 countries or regions, covering various periods from 1979 to 2016. All included cities had at least 2 years of both CO and mortality data. We estimated city-specific associations using confounder-adjusted generalised additive models with a quasi-Poisson distribution, and then pooled the estimates, accounting for their statistical uncertainty, using a random-effects multilevel meta-analytical model. We also assessed the overall shape of the exposure–response curve and evaluated the possibility of a threshold below which health is not affected. Findings Overall, a 1 mg/m3 increase in the average CO concentration of the previous day was associated with a 0·91% (95% CI 0·32–1·50) increase in daily total mortality. The pooled exposure–response curve showed a continuously elevated mortality risk with increasing CO concentrations, suggesting no threshold. The exposure–response curve was steeper at daily CO levels lower than 1 mg/m3, indicating greater risk of mortality per increment in CO exposure, and persisted at daily concentrations as low as 0·6 mg/m3 or less. The association remained similar after adjustment for ozone but was attenuated after adjustment for particulate matter or sulphur dioxide, or even reduced to null after adjustment for nitrogen dioxide. Interpretation This international study is by far the largest epidemiological investigation on short-term CO-related mortality. We found significant associations between ambient CO and daily mortality, even at levels well below current air quality guidelines. Further studies are warranted to disentangle its independent effect from other traffic-related pollutants.
- ItemArticulating the effect of food systems innovation on the Sustainable Development Goals(Amsterdam : Elsevier, 2021) Herrero, Mario; Thornton, Philip K.; Mason-D'Croz, Daniel; Palmer, Jeda; Bodirsky, Benjamin L.; Pradhan, Prajal; Barrett, Christopher B.; Benton, Tim G.; Hall, Andrew; Pikaar, Ilje; Bogard, Jessica R.; Bonnett, Graham D.; Bryan, Brett A.; Campbell, Bruce M.; Christensen, Svend; Clark, Michael; Fanzo, Jessica; Godde, Cecile M.; Jarvis, Andy; Loboguerrero, Ana Maria; Mathys, Alexander; McIntyre, C. Lynne; Naylor, Rosamond L.; Nelson, Rebecca; Obersteiner, Michael; Parodi, Alejandro; Popp, Alexander; Ricketts, Katie; Smith, Pete; Valin, Hugo; Vermeulen, Sonja J.; Vervoort, Joost; van Wijk, Mark; van Zanten, Hannah HE; West, Paul C.; Wood, Stephen A.; Rockström, JohanFood system innovations will be instrumental to achieving multiple Sustainable Development Goals (SDGs). However, major innovation breakthroughs can trigger profound and disruptive changes, leading to simultaneous and interlinked reconfigurations of multiple parts of the global food system. The emergence of new technologies or social solutions, therefore, have very different impact profiles, with favourable consequences for some SDGs and unintended adverse side-effects for others. Stand-alone innovations seldom achieve positive outcomes over multiple sustainability dimensions. Instead, they should be embedded as part of systemic changes that facilitate the implementation of the SDGs. Emerging trade-offs need to be intentionally addressed to achieve true sustainability, particularly those involving social aspects like inequality in its many forms, social justice, and strong institutions, which remain challenging. Trade-offs with undesirable consequences are manageable through the development of well planned transition pathways, careful monitoring of key indicators, and through the implementation of transparent science targets at the local level.