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One of the largest petrochemical complexes of southern Europe is located in Tarragona County (Catalonia, Spain). Despite environmental monitoring is routinely conducted in the area, the long-term occurrence of airborne trace elements has been poorly investigated. In the present study, the concentrations of arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb) and vanadium (V) were analysed in air samples collected in El Morell, a town potentially impacted by the petrochemical. Air samples were simultaneously collected in the town of Cambrils, as a background site. Meteorological data and retro trajectories analysis were used to evaluate the impact of the petrochemical industry on the levels of trace elements in air. Subsequently, human health risks due to inhalation exposure to the trace elements were also assessed. Except for V, air concentrations were significantly higher near the oil refinery than the background levels. Human health risks were also estimated to be higher in the vicinity of the petrochemical complex. In turn, air inhalation of Pb and V was higher than their dietary intakes. The present data should be considered only as preliminary, since the sampling was taken during only three weeks, which is an insufficient period to extract reliable conclusions. Further long-term studies should be focused on assessing the influence of temporary variables, such as meteorological conditions and fugitive or sporadic emissions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

While the link between exposure to high levels of ambient particulate matter (PM) and increased incidences of respiratory and cardiovascular diseases is widely recognized, recent epidemiological studies have shown that low PM concentrations are equally associated with adverse health effects. As DNA methylation is one of the main mechanisms by which cells regulate and stabilize gene expression, changes in the methylome could constitute early indicators of dysregulated signaling pathways. So far, little is known about PM-associated DNA methylation changes in the upper airways, the first point of contact between airborne pollutants and the human body. Here, we focused on cells of the upper respiratory tract and assessed their genome-wide DNA methylation pattern to explore exposure-associated early regulatory changes. Using a mobile epidemiological laboratory, nasal lavage samples were collected from a cohort of 60 adults that lived in districts with records of low (Simmerath) or moderate (Stuttgart) PM 10 levels in Germany. PM 10 concentrations were verified by particle measurements on the days of the sample collection and genome-wide DNA methylation was determined by enzymatic methyl sequencing at single-base resolution. We identified 231 differentially methylated regions (DMRs) between moderately and lowly PM 10 exposed individuals. A high proportion of DMRs overlapped with regulatory elements, and DMR target genes were involved in pathways regulating cellular redox homeostasis and immune response. In addition, we found distinct changes in DNA methylation of the HOXA gene cluster whose methylation levels have previously been linked to air pollution exposure but also to carcinogenesis in several instances. The findings of this study suggest that regulatory changes in upper airway cells occur at PM 10 levels below current European thresholds, some of which may be involved in the development of air pollution-related diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Particulate matter (PM) may play a role in differential distribution and transmission rates of SARS-CoV-2. For public health surveillance, identification of factors affecting the transmission dynamics concerning the endemic (persistent sporadic) and epidemic (rapidly clustered) component of infection can help to implement intervention strategies to reduce the disease burden. The aim of this study is to assess the effect of long-term residential exposure to outdoor PM ≤ 10 μm (PM 10 ) concentrations on SARS-CoV-2 incidence and on its spreading dynamics in Marche region (Central Italy) during the first wave of the COVID-19 pandemic (February to May 2020), using the endemic-epidemic spatio-temporal regression model for individual-level data. Environmental and climatic factors were estimated at 10 km 2 grid cells. 10-years average exposure to PM 10 was associated with an increased risk of new endemic (Rate Ratio for 10 μg/m 3 increase 1.14, 95%CI 1.04-1.24) and epidemic (Rate Ratio 1.15, 95%CI 1.08-1.22) infection. Male gender, older age, living in Nursing Homes and Long-Term Care Facilities residence and socio-economic deprivation index increased Rate Ratio (RR) in epidemic component. Lockdown increased the risk of becoming positive to SARS-CoV-2 as concerning endemic component while it reduced virus spreading in epidemic one. Increased temperature was associated with a reduction of endemic and epidemic infection. Results showed an increment of RR for exposure to increased levels of PM 10 both in endemic and epidemic components. Targeted interventions are necessary to improve air quality in most polluted areas, where deprived populations are more likely to live, to minimize the burden of endemic and epidemic COVID-19 disease and to reduce unequal distribution of health risk., (Copyright © 2022 Elsevier Inc. All rights reserved.)

SARS-CoV-2 virus (COVID-19) pandemic has impacted several countries, with also some differences at local levels. When lockdown restrictions were imposed, the concentrations of some air pollutants were reduced, as reported in some other cities in the world. This was often considered a positive by-product of the pandemic. However, often literature reporting the connection of air quality (AQ) and lockdown, suffers of limited and incomplete data analysis, not considering, for example, some confounding factors. This work presents a methodology, and the results of its application, to assess the impact of pandemic restrictions on AQ (in particular nitrogen oxides, NO 2 and particulate matter, PM 10 ) in spring 2020 in Brescia, located in one of the most affected areas in terms of virus diffusion and in one of the most polluted areas in Europe (Po Valley, Italy). In particular, the proposed methodology integrates data and AQ modelling simulations to distinguish between the changes in the PM 10 and NO 2 pollutants concentration that occurred due to the restriction measures and due to other factors, like spatial-temporal characteristics (for example the seasonality), meteorological factors, and governmental actions that were introduced in the past to improve the air quality. Results show that NO 2 is strongly dependent to traffic emission. On the contrary, although the expected decrease in PM 10 concentrations, the results highlight that the reduction of transport emission would not help to avoid severe air pollution, due to the other pollution sources that contribute to its origin. The results presented for the first time in this work are of particular interest because they may be used as a basis to investigate in more details the sources that can impact on the air quality in Brescia, with the aim to propose effective measures able to reduce it., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Among various air pollutants, particulate matter (PM) is the most harmful and representative pollutant. Although several studies have shown a link between particulate pollution and obesity, the conclusions are still inconsistent., Methods: We conducted a systematic review and meta-analysis to pool the effect of PM exposure on obesity. Five databases (including PubMed, Web of Science, Scopus, Embase, and Cochrane) were searched for relevant studies up to Jan 2022. Adjusted risk ratio (RR) with corresponding 95% confidence interval (CI) were retrieved from individual studies and pooled with random effect models by STATA software. Besides, we tested the stability of results by Egger's test, Begg's test, funnel plot, and using the trim-and-fill method to modify the possible asymmetric funnel graph. The NTP-OHAT guidelines were followed to assess the risk of bias. Then the GRADE was used to evaluate the certainty of evidence., Results: 26 studies were included in this meta-analysis. 19 studies have shown that PM 2.5 can increase the risk of obesity per 10 μg/m 3 increment (RR: 1.159, 95% CI: 1.111-1.209), while 15 studies have indicated that PM 10 increase the risk of obesity per 10 μg/m 3 increment (RR: 1.092, 95% CI: 1.070-1.116). Besides, 5 other articles with maternal exposure showed that PM 2.5 increases the risk of obesity in children (RR: 1.06, 95% CI: 1.02-1.11). And we explored the source of heterogeneity by subgroup analysis, which suggested associations between PM and obesity tended to vary by region, age group, participants number, etc. The analysis results showed publication bias and other biases are well controlled, but most certainties of the evidence were low, and more research is required to reduce these uncertainties., Conclusion: Exposure to PM 2.5 and PM 10 with per 10 μg/m 3 increment could increase the risk of obesity in the global population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Absract In developed countries, age-related macular degeneration (AMD) is a leading cause of irreversible blindness in adults. The key pathways of AMD are suggested to be excessive oxidative stress and inflammation in the central retina. Because air pollution has been found capable of inducing oxidative stress and inflammation, it may play a role in development of AMD. This study investigated the association between ambient air pollution and AMD in 15,115 middle-aged and older adults (≥40 years) from Korean National Health and Nutrition Examination Survey 2008-2012. After controlling for important confounders, ambient NO 2 and CO in current-to-5 prior years and PM 10 in 2-to-5 prior years were significantly associated with higher prevalence of early AMD, while O 3 in current-to-5 prior years was significantly associated with lower prevalence of early AMD. When modeled air pollution within administrative division units, its ORs with an IQR increase in NO 2 , CO, and O 3 at current year were 1.24 (95% CI: 1.05-1.46), 1.22 (95% CI: 1.09-1.38), and 0.80 (95% CI: 0.70-0.92), respectively. Overall, results from air pollution at local/town units were consistent with those at administrative division units. Long-term exposures to ambient air pollution may play a role in the risk of AMD in middle-aged and older adults., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aerosol samplers are generally classified into particulate matter (PM 2.5 or PM 10 ) and total suspended particle (TSP) samplers. As changing the cutoff size is cumbersome, it necessitates either replacing the particle size separator or adjusting the sampling flow rate. In this study, a novel high-volume aerosol-sampling inlet with an adjustable cutoff size was developed. Its performance was evaluated at a sampling flow rate of 1000 L/min of road dust. The cyclone separator installed with the newly developed inlet absorbed airflow from all directions. The cutoff size of this inlet was easily adjustable using the guide vane angle. For the guide vane angles of 29°, 42°, and 90° (at a 2 km/h freestream velocity), the cutoff sizes were 2.59, 9.92, and 26.2 μm, respectively. At the 90° angle of the guide vanes and the free stream velocity of 2 km/h, no rotational airflow occurred inside the cyclone separator to allow TSP sampling. Increasing the freestream velocity to 16 km/h at angles of 29° and 42° decreased the cutoff size by 0.12 and 0.45 μm, respectively; finely adjusting these angles further reduced the cutoff size to 0.04 and 0.07 μm, respectively. Thus, an almost constant cutoff size was possible. The developed inlet allowed sampling of PM 2.5 , PM 10 , or TSP using a single device., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This work investigates the impact of COVID-19 restrictive measures on the mass concentrations of PM 1 and PM 10 , and their chemical components (water-soluble ions, organic and elemental carbon, and major and trace metals) at an urban site in the western Mediterranean. The evolution of gaseous pollutants (NO x , O 3 and some volatile organic compounds) was also analyzed. The concentrations measured during the lockdown in 2020 were compared to those obtained during the same period over the preceding five years. The average decrease in the levels of NO x and traffic-related volatile organic compounds was higher than 50 %, while O 3 concentrations did not exhibit significant variations during the study period. Our results show that temporal variations in PM 1 and PM 10 concentrations were strongly affected by the frequency of Saharan dust events. When these episodes were excluded from the analysis period, a 35 % decrease in PM 1 and PM 10 levels was observed. Traffic restrictions during the lockdown led to important reductions in the concentrations of elemental carbon and metals derived from road dust (e.g. Ca and Fe) and break wear (e.g. Cu). Regarding secondary inorganic aerosols, nitrate showed the largest reductions as a consequence of the drop in local emissions of NO x ., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies conducted in several OECD countries have shown that chronic exposure to elevated levels of air pollutants (especially PM 2.5 , PM 10 and NOx), might negatively impact COVID-19 morbidity and mortality rates. The aim of this study was to examine the association between chronic exposure to air pollution in Israeli cities and towns, their demographic and socioeconomic status, and COVID-19 morbidity, during the three local morbidity waves., Methods: We examined the associations between: (a) annual average concentrations of NOx, CO, PM 10 , PM 2.5 and SO 2 in 2016-2019, and demographic and socioeconomic parameters, and (b) COVID-19 positive cases in 279 Israeli cities and towns, in the four state-wide morbidity peaks: 1 st wave peak: March 31 st , 2020; 2 nd wave peaks: July 24 th and September 27 th , 2020, and the 3 rd wave peak: January 17 th , 2021, which occurred after the beginning of the nationwide vaccination campaign. These associations were calculated using both Spearman correlations and multivariate linear regressions., Results: We found statistically significant positive correlations between the concentrations of most pollutants in 2016-19 and COVID-19 morbidity rate at the first three timepoints but not the 4t h (January 17 th , 2021). Population density and city/town total population were also positively associated with the COVID-19 morbidity rates at these three timepoints, but not the 4 th , in which socioeconomic parameters were more dominant - we found a statistically significant negative correlation between socioeconomic cluster and COVID-19 morbidity. In addition, all multivariate models including PM 2.5 concentrations were statistically significant, and PM 2.5 concentrations were positively associated with the COVID-19 morbidity rates in all models., Conclusions: We found a nationwide association between population chronic exposure to five main air pollutants in Israeli cities and towns, and COVID-19 morbidity rates during two of the three morbidity waves experienced in Israel. The widespread morbidity that was related to socioeconomic factors during the 3 rd wave, emphasizes the need for special attention to morbidity prevention in socioeconomically vulnerable populations and especially in large household communities. Nevertheless, this ecological study has several limitations, such as the inability to draw conclusions about causality or mechanisms of action. The growing body of evidence, regarding association between exacerbated COVID-19 morbidity and mortality rates and long-term chronic exposure to elevated concentrations of air pollutants should serve as a wake-up call to policy makers regarding the urgent need to reduce air pollution and its harmful effects., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The composition of PM 10 , including molecular markers of biomass burning (levoglucosan, mannosan and galactosan), was determined at a residential site in southeastern Spain during winter and early spring. The average PM 10 concentration was 25.0 μg m -3 , being organic carbon (OC, 6.77 μg m -3 ), NO 3 - (2.02 μg m -3 ), SO 4 2- (1.36 μg m -3 ) and Ca 2+ (1.01 μg m -3 ) the main components. Levoglucosan was the dominant anhydrosugar (143 ng m -3 ), accounting for 81% of the total concentration of monosaccharide anhydrides. The average contribution of biomass combustion to OC, estimated from the levoglucosan data, was 23%. This value agreed well with that calculated by Positive Matrix Factorization (PMF, 25%). The PMF model resolved six factors that were assigned to road traffic (28%), secondary aerosols (27%), soil dust (14%), fresh sea salt (13%), aged sea salt (10%) and biomass burning (8%). This model was used to estimate the OC/Levoglucosan and PM 10 /Levoglucosan emission ratios for the study area., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The pandemic caused by coronavirus COVID-19 is having a worldwide impact that affects health, the economy and indirectly affects the air pollution in cities. In Portugal, the number of cases increased continually (32700 confirmed cases as of May 31, 2020), which has affected the health system and caused movement restrictions which in turn affects the air pollution in the country. This article analyses the indirect effect produced by this pandemic on air pollution in Portugal, by comparison of data from a period of movement restriction of the citizens by the government - COVID lockdown period (March-May 2020) with data from baseline conditions (mean of the mirrored periods from the five previous years (March-May from 2015 to 2019)). Air quality data - in particular NO 2 and PM 10 hourly concentration - from more than 20 monitoring stations spread over mainland Portugal was used to perform this evaluation. The mean reduction observed on pollutant concentrations was higher for NO 2 (41%) than for PM 10 (18%). For NO 2 , mean reductions were more significant in traffic (reaching values higher than 60% in some monitoring stations) and background urban sites than in rural stations. The reduction of NO 2 concentration observed in traffic sites were compared to the estimation of traffic contribution by the incremental method, suggesting that this latter approach is not consistent (lower in same sites and higher in others) and alerting to the careful use of this approach in future works., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The present work aims to study the role of air pollutants in relation to the number of deaths per each Italian province affected by COVID-19. To do that, specific mortality from COVID-19 has been standardized for each Italian province and per age group (10 groups) ranging from 0 to 9 years to >90 years, based on the 2019 national population figures. The link between air pollutants and COVID-19 mortality among Italian provinces was studied implementing a linear regression model, whereas the wide set of variables were examined by means of LISA (Local Indicators of Spatial Autocorrelation), relating the spatial component of COVID-19 related data with a mix of environmental variables as explanatory variables. As results, in some provinces, namely the Western Po Valley provinces, the SMR (Standardized Mortality Ratio) is much higher than expected, and the presence of PM 10 was independently associated with the case status. Furthermore, the results for LISA on SMR and PM 10 demonstrate clusters of high-high values in the wide Metropolitan area of Milan and the Po Valley area respectively, with a certain level of overlap of the two distributions in the area strictly considered Milan. In conclusion, this research appears to find elements to confirm the existence of a link between pollution and the risk of death due to the disease, in particular, considering land take and air pollution, this latter referred to particulate (PM 10 ). For this reason, we can reiterate the need to act in favour of policies aimed at reducing pollutants in the atmosphere, by means of speeding up the already existing plans and policies, targeting all sources of atmospheric pollution: industries, home heating and traffic., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Studies in air pollution epidemiology are of paramount importance in diagnosing and improve life quality. To explore new methods or modify existing ones is critical to obtain better results. Most air pollution epidemiology studies use the Generalized Linear Model, especially the default version of R, Splus, SAS, and Stata softwares, which use maximum likelihood estimators in parameter optimization. Also, a smooth time function (usually spline) is generally used as a pre-processing step to consider seasonal and long-term tendencies. This investigation introduces a new approach to GLM, proposing the estimation of the free coefficients through bio-inspired metaheuristics - Particle Swarm Optimization (PSO), Genetic Algorithms, and Differential Evolution, as well as the replacement of the spline function by a simple normalization procedure. The considered case studies comprise three important cities of São Paulo state, Brazil with distinct characteristics: São Paulo, Campinas, and Cubatão. We considered the impact of particles with an aerodynamic diameter less than 10 μm (PM 10 ), ambient temperature, and relative humidity in the number of hospital admissions for respiratory diseases (ICD-10, J00 to J99). The results showed that the new approach (especially PSO) brings performance gains compared to the default version of statistical software like R., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Australia is a highly developed country with low population density. Capital cities are situated mainly around the coastline and are subjected to different meteorological conditions. This complex set of drivers is expected to result in varying trends in particulate matter (PM) mass concentrations in urban ambient air across the country. Thus, the aim of this study was to determine the long-term trends in PM 10 and PM 2.5 concentrations in capital cities, and to analyse the factors that influenced such trends. The spatial variability of PM concentrations within the capital cities was first established to identify representative stations. Then trends were determined using the Mann-Kendall trend test, Sen's slope, and the generalised additive model. The results show that, in general, the PM concentrations in Australian cities are relatively low (12.1-21.7 μg m -3 mean daily PM 10 and 4.6-8.7 μg m -3 mean daily PM 2.5 ) and within the WHO daily limit 95% of the time. Over the past two decades, very small declines of 8.0 × 10 -5 -1.1 × 10 -3  μg m -3 .yr -1 for PM 10 and 7.7 × 10 -5 -2.6 × 10 -3  μg m -3 .yr -1 for PM 2.5 were observed while some stations exhibited increase in concentration based on available data; more stations showed a significant monotonic decline for PM 10 than PM 2.5 . This is attributed to the effectiveness of the implemented emission reduction policies particularly for vehicle exhaust and power generation, given the simultaneous increase in the demand for energy and the number of vehicles over the last two decades. Regarding climate, in the coastal cities of Sydney and Brisbane, high rainfall and strong winds aid in maintaining low PM concentrations despite the significant anthropogenic emissions, while higher PM levels in Darwin can be attributed to its tropical savannah climate, which makes it prone to bushfires and necessitates regular prescribed burnings. PM concentrations increase when exceptional events such as bushfires and dust storms are induced by the extreme climate variability. Further reduction of PM concentrations in Australian cities is unlikely, considering the expanding urbanisation and the changing climate., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The number of studies on air pollution with birth defects as the primary outcome has increased dramatically over the past two decades, but the potential role of specific air pollutants in congenital limb anomalies remains unclear., Objectives: To evaluate associations between preconception and first-trimester PM 10 exposure and polydactyly and syndactyly in a population-based case-control study., Methods: Polydactyly cases (n = 2605), syndactyly cases (n = 595), and controls without any birth defects (n = 7950) born between 2010 and 2015 were selected from the Maternal and Child Health Certificate Registry of Liaoning Province. The monthly mean PM 10 concentrations were obtained from 75 air monitoring stations, and the exposure assessment was based on the mean concentration of all stations in mother's residential city. A multivariable logistic regression model was constructed to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs)., Results: PM 10 exposure was positively associated with the risks of polydactyly (preconception: aOR T3 vs. T1  = 1.95, 95% CI 1.56-2.45, aOR = 1.06, 95% CI 1.01-1.10 [per 10-μg/m 3 increment]; first-trimester: aOR T3 vs. T1  = 2.51, 95% CI 2.00-3.15) and syndactyly (preconception: aOR T3 vs. T1  = 2.86, 95% CI 1.98-4.13, aOR = 1.11, 95% CI 1.03-1.20 [per 10-μg/m 3 increment]; first-trimester: aOR T3 vs. T1  = 3.10, 95% CI 2.11-4.56). Analyses based on single month exposure windows basically showed similar positive associations. Additionally, these findings were robust in sensitivity analyses and broadly consistent across subgroups., Conclusion: Our study suggest that preconception and first-trimester PM 10 exposures are related to increased risks of polydactyly and syndactyly., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The severe cases of COVID-19 infections in Italy, and notably in Lombardy (mainly in Brescia and Bergamo areas), registered at the beginning of March 2020, occurred after a period of PM 10 pollution, that exceeded the concentration of 50 μg/m 3 (the attention limit) for several days. The two events were supposed to be correlated, also based on the limited information available about the new virus. Despite that clear indications about the role of particulate matter (PM) in the virus mechanism dispersion cannot be found in literature, some researchers supposed that PM can act as virus carrier, promoting its diffusion through the air. This paper, for the first time, analyses the PM 10 situation in Lombardy (from 10th February to March 27, 2020), several days before the sanitary emergency explosion. The data of the detected infection cases are reported and discussed parallelly. As a comparison, the situation of Piedmont, located near to the Lombardy is also presented. Data are reported for Brescia, Bergamo, Cremona, Lodi, Milano, Monza-Brianza, Pavia (Lombardy), Alessandria, Vercelli, Novara, Biella, Asti, and Torino (Piedmont). The results show that it is not possible to conclude that COVID-19 diffusion mechanism also occurs through the air, by using PM 10 as a carrier. In particular, it is shown that Piedmont cities, presenting lower detected infections cases in comparison to Brescia and Bergamo in the investigated period, had most sever PM 10 pollution events in comparison to Lombardy cities. This first study may serve as a reference to better understand and predict the factors affecting the COVID-19 diffusion and transmission routes, focusing on the role of air particulate matter in the atmosphere., Competing Interests: Declaration of competing interest The author declares that she has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Exposure to fine particles in the atmosphere can adversely affect health and even lead to premature death. Recently, South Korea has attracted attention because of its rapid increase in the concentration of Particulate Matter (PM)., Objectives: We estimated the economic benefits of reducing PM 10 in Seoul, South Korea, based on MODerate-resolution Imaging Spectroradiometer (MODIS) Aerosol Optical Depth (AOD). Based on the retrieved PM 10 data, we estimated its effects on overall health in each district of Seoul, Korea between 2014 and 2015., Methods: The relationships between MODIS AOD and ground-based PM 10 data were identified in different seasons in South Korea between 2012 and 2013 using the linear regression model. The health benefits were estimated by the Benefits Mapping and Analysis Program (Benmap) using the scenarios from the World Health Organization (WHO)., Results: The correlation between MODIS AOD and PM 10 concentration differed with the season. There was a higher correlation between MODIS AOD and PM 10 concentration in winter (R = 0.57) than there was in other seasons. Based on the MODIS AOD, the average annual PM 10 concentration in Seoul was higher in 2014 than it was in 2015, at values of 45.7 μg/m 3 , and 41.6 μg/m 3 , respectively. The greatest economic benefit of reducing PM 10 concentration (WHO annual standard of 20 μg/m 3 ) was in 2014. This benefit was estimated to be 7022 (95% CI: 599, 20496), 2617 (95% CI: 216, 7750), and 1328 (95% CI: -159, 4679) billion KRW for all-cause, cardiovascular, and respiratory mortalities in 2014 and 2015, respectively., Conclusions: These results demonstrate that, despite considerable improvements in air quality in recent decades, there is still a need for countermeasures to prevent economic loss due to air pollution in Seoul., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Exposure to urban particulate matter (PM) is correlated with increases in the emergence of health services due to adverse events and deaths and is mainly related to cardiorespiratory complications. The translocation of particles from the lung into circulation has been proposed as a factor that may trigger systemic effects. Monocytes may be exposed to PM, and if the monocytes are activated, then they are likely to adhere to endothelial cells in a distant organ due to the expression of receptors for adhesion molecules. In the present study, we evaluated the expression of receptors for adhesion molecules (sLe x , PSGL-1, LFA-1, VLA-4 and α V β 3 ) in monocytes (U937 cells) exposed for 3 or 18 h to PM 10 (0.001, 0.003, 0.010, 0.030, 0.300, 3 or 30 µg/mL). Exposed cells were co-cultured with human endothelial cells that were naive or previously exposed to the same particles. When U937 cells were exposed to PM 10 , similar levels of expression for early and late receptors for adhesion molecules were observed from 30 ng/mL as those induced by TNF-α. Cells exposed to particles at concentrations above 30 ng/mL were more adhesive to naive or exposed human endothelial cells. Taken together, our results suggest that it is plausible that activated monocytes may play a role in systemic effects induced by PM 10 due to the size distribution of the particles and the concentrations required to trigger the expression of receptors for adhesion molecules in monocytes., (Copyright © 2018. Published by Elsevier Inc.)

Particulate matter (PM) composition has a key role in a wide range of health outcomes, such as asthma, chronic obstructive pulmonary disease, lung cancer, cardiovascular disease, and death, among others. Montcada i Reixac, a municipality located in the Barcelona metropolitan area (Catalonia, Spain), for its location and orography, is an interesting case- study to investigate air pollution. The area is also characterized by the presence of different industrial emission sources, including a cement factory and a large waste management plant, as well as an intense traffic. In this study, PM 10 levels, trace elements, ions, and carbonaceous particles were determined for a long time period (2013-2016) in this highly polluted area. PM 10 samples were collected during six consecutive days in two campaigns (cold and warm) per year. A number of elements (As, Ba, Be, Bi, Ca, Cd, Ce, Co, Cr, Cs, Cu, Dy, Er, Eu, Fe, Ga, Gd, Ge, Hf, Hg, Ho, K, La, Li, Hg, Mg, Mn, Mo, Nb, Nd, Ni, Pb, Pr, Rb, Sb, Sc, Se, Sm, Sn, Sr, Tb, Th, Ti, Tl, U, V, W, Y, Yb, and Zr), ions (Cl - , SO 4 2- , NO 3 - , and NH 4 + ), and carbonaceous content (total carbon, organic plus elemental carbon, and CO 3 2- ), were analysed. These data were used to identify the PM 10 main components: mineral matter, sea spray, secondary inorganic aerosols, organic matter plus elemental carbon, trace elements or indeterminate fraction. Although a clear seasonality (cold vs. warm periods) was found, there were no differences between working days and weekends. Obviously, the cement plant influences the surrounding environment. However, no differences in trace elements related with the cement plant activity (Al, Ca, Ni and V) between weekdays and weekends were noted. However, some traffic-related elements (i.e., Co, Cr, Mn, and Sb) showed significantly higher concentrations in weekdays., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The content of metal(loid)s in particulate matter (PM) is of special concern due to their contribution to overall (PM) toxicity. In this study, the bioaccessibility and human health risk of potentially toxic metal(loid)s associated with PM 10 were investigated in two areas of the Cantabrian region (northern Spain) with different levels of exposure: an industrial area mainly influenced by a ferromanganese alloy plant; and an urban area consisting mainly of residential and commercial activities, but also affected, albeit to a lesser extent by the ferroalloy plant. Total content and bioaccessible fractions in simulated lung fluids (SLFs) of Fe, Mn, Zn, Ni, Cu, Sb, Mo, Cd and Pb were determined by ICP-MS. Gamble's solution and artificial lysosomal fluid (ALF) were used to mimic different conditions inside the human respiratory system. A health risk assessment was performed based on the United States Environmental Protection Agency's (USEPA) methodology. Most metal(loid)s showed moderate and high bioaccessibility in Gamble's solution and ALF, respectively. Despite the high variability between the samples, metal(loid) bioaccessibility was found to be higher on average at the industrial site, suggesting a greater hazard to human health in the proximity of the main metal(loid) sources. Based on the results of the risk assessment, the non-carcinogenic risk associated with Mn exposure was above the safe limit (HQ> 1) under all the studied scenarios at the industrial site and under some specific scenarios at the urban location. The estimated carcinogenic inhalation risk for Cd exposure at the industrial site was found to be within the range between 1.0 × 10 -6 to 1.0 × 10 -4 (uncertainty range) under some scenarios. The results obtained in this study indicate that Mn and Cd inhalation exposure occurring in the vicinities of the studied areas may pose a human health risk., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Particulate matter (PM) has been recognized as one of the key risk factors of lung cancer. However, spatial and temporal patterns of this association remain unclear. Spatiotemporal analyses incorporate the spatial and temporal structure of the data within random effects models, generating more accurate evaluations of PM-lung cancer associations at a scale that can better inform lung cancer prevention programs., Methods: We conducted a critical review of spatial and temporal analyses of PM and lung cancer. The databases of PubMed, Web of Science and Scopus were searched for potential articles published until September 30, 2017. We included studies that applied spatial and temporal analyses to evaluate the associations of PM 2.5 (inhalable particles with diameters that are 2.5 µm and smaller) and PM 10 (inhalable particles with diameters that are 10 µm and smaller) with lung cancer., Results: We identified 17 articles eligible for the review. Of these, 11 focused on PM 2.5 , five on PM 10 , and one on both. These studies suggested a significant positive association between PM 2.5 exposure and the risk of lung cancer. Relative risks of lung cancer mortality ranged from 1.08 (95% confidence interval (CI): 1.07-1.09) to 1.60 (95%CI: 1.09-2.33) for 10 µg/m 3 increase in PM 2.5 exposure. The association between PM 10 and lung cancer had been less well researched and the results were not consistent. In terms of the analysis methods, 16 papers undertook spatial analysis and one paper employed temporal analysis. No paper included spatial and temporal analyses simultaneously and considered spatiotemporal uncertainty into model predictions. Among the 16 papers with spatial analyses, thirteen studies presented maps, while only five and 11 studies utilized spatial exploration and modeling methods, respectively., Conclusions: Advanced spatial and temporal epidemiological methods were seldom applied to PM-lung cancer associations. Further research is urgently needed to develop and employ robust and comprehensive spatiotemporal analysis methods for the evaluation of PM-lung cancer associations and the support of lung cancer prevention strategies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Endocrine disrupting chemicals (EDCs) from the environment are associated with reproductive abnormalities (i.e. decreased sperm concentration; increased endometriosis) and alterations of the cardiovascular system (i.e. increased blood pressure and risk of coronary disease). Some phthalates esters have been identified as EDCs, for which inhalation is considered as one of the routes of exposure. However, only little is known regarding inhalational exposure to EDCs via urban airborne particles. In the present study, we report the monthly concentration of 8 phthalate esters measured in PM 10 and PM 2.5 collected and recovered during 7 months in a highly populated area of Mexico City. Using the levels of PM 10 and PM 2.5 reported by the automatized network of environmental monitoring of Mexico City for the sampling site, we estimated exposure levels for people of different ages and gender. Two endocrine disrupting compounds, the phthalate esters DEHP and DnBP, were found on the particles in higher concentrations during the warmer months of the year. The highest concentration was reported for DEHP (229.7μg/g of particles) in PM 2.5 collected in May 2013. After calculations of the DEHP concentration in the atmosphere, and using the respiratory flow rate, we determined males were potentially exposed to larger quantities of DEHP, reaching up to 18ng/8h in April 2013. Despite the concentrations of phthalates seem to be rather small, a comprehensive characterization of its presence is necessary in order to evaluate the overall exposure to these compounds, providing a clear view of exposure on children, adolescents and pregnant women., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Particle matter (PM) and its associated compounds are a serious problem for urban air quality and a threat to human health. In the present study, we assessed the intraurban variation of PM, and characterized the human health risk associated to the inhalation of particles measured on PM filters, considering different land use areas in the urban area of Cordoba city (Argentina) and different age groups. To assess the intraurban variation of PM, a biomonitoring network of T. capillaris was established in 15 sampling sites with different land use and the bioaccumulation of Co, Cu, Fe, Mn, Ni, Pb and Zn was quantified. After that, particles were collected by instrumental monitors placed at the most representative sampling sites of each land use category and an inhalation risk was calculated. A remarkable intraurban difference in the heavy metals content measured in the biomonitors was observed, in relation with the sampling site land use. The higher content was detected at industrial areas as well as in sites with intense vehicular traffic. Mean PM 10 levels exceeded the standard suggested by the U.S. EPA in all land use areas, except for the downtown. Hazard Index values were below EPA's safe limit in all land use areas and in the different age groups. In contrast, the carcinogenic risk analysis showed that all urban areas exceeded the acceptable limit (1 × 10 -6 ), while the industrial sampling sites and the elder group presented a carcinogenic risk higher that the unacceptable limit. These findings validate the use of T. capillaris to assess intraurban air quality and also show there is an important intraurban variation in human health risk associated to different land use., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Temperature must be controlled when estimating the associations of short-term exposure to air pollution and mortality. Given that multi-country studies have implied temperature has lagged effects, we aim to explore confounding by temperature-lag-response and investigate PM 10 -lag-mortality relation in 7 cities, Korea., Methods: In a simulation study, we compared the performance of different methods to control for: the same day temperature, a lagged temperature and distributed lags of temperature. In a real data study, we explored PM 10 -lag-mortality relation in 7 cities using these different methods., Results: We confirmed that a model with insufficient control of temperature offers a biased estimate of PM 10 risk. The degree of bias was from -82% to 95% in simulation settings. A real data study shows estimates among different models by temperature adjustments and PM 10 lag variables ranging from -0.3% to 0.4% increase in the risk of all-cause mortality, with a 10μg/m 3 increase in PM 10 . Controlling for temperature as distributed lags for 21 days provided 0.25% (95% CI: 0.1, 0.4) increase in the risk of all-cause mortality., Conclusions: A lag structure of temperature can confound the air pollution-lag-response relation. Temperature-lag-response relation should be evaluated when estimating air pollution-lag-response relation. As a corollary, air pollution and temperature risk in mortality can be estimated using the same regression model., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Estimating exposure to particulate matter (PM 10 ) air pollution concentrations in Australia is challenging due to relatively few monitoring sites relative to the geographic distribution of the population. We modelled daily ground-level PM 10 concentrations for the period 2006-2011 for Australia using linear mixed models with satellite remote-sensed AOD, land-use and geographical variables as predictors. The variation in daily PM 10 explained by the model was 51% for Australia overall, and ranged from 51% for Tasmania to 78% for South Australia. Cross-validation indicated that the models were most suitable for prediction in New South Wales and Victoria and least suitable for prediction in Western Australia, the Australian Capital Territory and Tasmania. Most of the variation in PM 10 concentrations was explained by temporal rather than spatial variation. The inclusion of AOD and other predictors did not substantially improve model performance. Temporal models were sufficient to account for daily PM 10 variation recorded by statutory monitors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

There is limited evidence available worldwide about the quantitative relationship between particulate matter with an aerodynamic diameter of less than 10µm (PM 10 ) and years of life lost (YLL) caused by respiratory diseases (RD), especially regarding long-term time series data. We investigated the quantitative exposure-response association between PM 10 and the disease burden of RD. We obtained the daily concentration of ambient pollutants (PM 10 , nitrogen dioxide and sulphur dioxide), temperature and relative humidity data, as well as the death monitoring data from 2001 to 2010 in Tianjin. Then, a time series database was built after the daily YLL of RD was calculated. We applied a generalized additive model (GAM) to estimate the burden of PM 10 on daily YLL of RD and to determine the effect (the increase of daily YLL) of every 10μg/m 3 increase in PM 10 on health. We found that every 10μg/m 3 increase in PM 10 was associated with the greatest increase in YLL of 0.84 (95% CI: 0.45, 1.23) years at a 2-day (current day and previous day, lag01) moving average PM 10 concentration for RD. The association between PM 10 and YLL was stronger in females and the elderly (≥65 years of age). The association between PM 10 and YLL of RD differed according to district. These findings also provide new epidemiological evidence for respiratory disease prevention., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Events of severe air pollution occurred frequently in China recently, thus understanding of the air pollution characteristics and its health risks is very important. In this work, we analyzed a two-year dataset (March 2014 - February 2016) including daily concentrations of six criteria pollutants (PM 2.5 , PM 10 , CO, SO 2 , NO 2 , and O 3 ) from 18 cities in Henan province. Results reveal the serious air pollution status in Henan province, especially the northern part, and Zhengzhou is the city with the worst air quality. Annual average PM 2.5 concentrations exceed the second grade of Chinese Ambient Air Quality Standard (75μg/m 3 ) at both 2014 and 2015. PM 2.5 is typically the major pollutant, but ozone pollution can be significant during summer. Furthermore, as the commonly used air quality index (AQI) neglects the mutual health effects from multiple pollutants, we introduced the aggregate air quality index (AAQI) and health-risk based air quality index (HAQI) to evaluate the health risks. Results show that based on HAQI, the current AQI system likely significantly underestimate the health risks of air pollution, highlighting that the general public may need stricter health protection measures. The population-weighted two-year average HAQI data further demonstrates that all population in the studied cities in Henan province live with polluted air - 72% of the population is exposed to air that is unhealthy for sensitive people, while 28% of people is exposed to air that can be harmful to healthy people; and the health risks are much greater during winter than during other seasons. Future works should further improve the HAQI algorithm, and validate the links between the clinical/epidemiologic data and the HAQI values., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Endocrine disrupting chemicals represent a broad class of compounds, are widespread in the environment and can pose severe health effects., Objectives: The objective of this study was to investigate and compare the overall estrogen and androgen activating potential of PM10 air samples at an urban, rural and industrial location in Flanders, using a human in vitro cell bioassay., Methods: PM10 samples were collected on glass fiber filters every six days between April 2013 and January 2014 using a high-volume sampler. Extraction was executed with a hexane/acetone mixture before analysis using a recombinant estrogen- or androgen responsive human carcinoma cell line. Results were expressed as bioanalytical equivalents (BEQs) per cubic meter of air., Results: High fluctuations in estrogenic activity were observed during the entire sampling period, with median BEQs of 32.1, 35.9 and 31.1 fg E2-Eq m(-)³ in the industrial, urban and rural background area, respectively. Estrogenic activity was measured in 70% of the samples, while no androgenic activity was observed in any of the samples. The estrogenic activity in the industrial area was positively correlated with the airborne concentration of the sum of the non-carcinogenic PAHs pyrene and fluoranthene (rho=0.48; p<0.01) and the sum of the carcinogenic PAHs (rho=0.36; p=0.05)., Conclusions: This study showed that no androgenic activity was present in PM10 and that although the median estrogenic activity was rather low and comparable in the three locations, high fluctuations in estrogenic response exist over time. While atmospheric PAHs contributed to the observed estrogenic response, especially in the industrial area, the chemicals responsible for the majority of estrogenic activity remain to be identified., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Asthma, one of the most common chronic diseases in the world and a leading cause of hospitalization among children, has been associated with outdoor air pollution. We applied the wastewater-based epidemiology (WBE) approach to study the association between the use of salbutamol, a short-acting beta-agonist used to treat acute bronchospasm, and air pollution in the population of Milan, Italy. Composite 24-h samples of untreated wastewater were collected daily and analyzed for human metabolic residues of salbutamol by liquid chromatography tandem mass spectrometry. Corresponding daily outdoor concentrations of particular matter up to 10µm (PM10) and 2.5µm (PM2.5) in aerodynamic diameter, nitrogen dioxide, ozone, sulfur dioxide, and benzene were collected from the public air monitoring network. Associations at different lag times (0-10 days) were assessed by a log-linear Poisson regression model. We found significant direct associations between defined daily doses (DDD) of salbutamol and mean daily concentrations of PM10 and PM2.5 up to nine days of lag time. The highest rate ratio, and 95% confidence interval (CI), of DDD of salbutamol was 1.06 (95% CI: 1.02-1.10) and 1.07 (95% CI: 1.02-1.12) at seven days of lag time and for an increase of 10 μg/m(3) of PM10 and PM2.5, respectively. Reducing the mean daily PM10 concentration in Milan from 50 to 30μg/m(3) means that 852 (95% CI: 483-1504) daily doses of salbutamol per day would not be used. These results confirm the association between asthma and outdoor PM10 and PM2.5 and prove the potential of the WBE approach to quantitatively estimate the relation between environmental exposures and diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system, characterized by recurrent relapses of inflammation that cause mild to severe disability. Exposure to airborne particulate matter (PM) has been associated with acute increases in systemic inflammatory responses and neuroinflammation. In the present study, we hypothesize that exposure to PM<10μm in diameter (PM10) might increase the occurrence of MS-related hospitalizations., Methods: We obtained daily concentrations of PM10 from 53 monitoring sites covering the study area and we identified 8287 MS-related hospitalization through hospital admission-discharge records of the Lombardy region, Italy, between 2001 and 2009. We used a Poisson regression analysis to investigate the association between exposure to PM10 and risk of hospitalization., Results: A higher RR of hospital admission for MS relapse was associated with exposure to PM10 at different time intervals. The maximum effect of PM10 on MS hospitalization was found for exposure between days 0 and 7: Hospital admission for MS increased 42% (95%CI 1.39-1.45) on the days preceded by one week with PM10 levels in the highest quartile. The p-value for trend across quartiles was<0.001., Conclusions: These data support the hypothesis that air pollution may have a role in determining MS occurrence and relapses. Our findings could open new avenues for determining the pathogenic mechanisms of MS and potentially be applied to other autoimmune diseases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

While there is growing evidence that air pollution reduces fetal growth, results are inconclusive with respect to the gestational window of effect. We investigated maternal exposure to particulate matter (PM10) in association with birth weight and fetus growth with a focus on the shape of the association and gestational age at birth as a potential effect modifier. The study population consisted of 525,635 singleton live births in Flanders (Belgium) between 1999 and 2009. PM10 exposure at maternal residence was averaged over various time windows. We used robust linear and logistic regression to estimate the effect of PM10 on birth weight and small for gestational age (SGA). Segmented regression models were applied for non-linear associations. Among moderately preterm (32-36 weeks) and term (>36 weeks) births, we found significant lower birth weight for all studied time windows. The estimated reduction in birth weight for a 10 µg/m(3) increase in average PM10 during pregnancy was 39.0 g (95% confidence interval [CI]: 26.4, 51.5 g) for moderately preterm births and 24.0 g (95% CI: 20.9, 27.2g) for term births. The corresponding odds ratios for SGA were 1.19 (95% CI: 1.07, 1.32) and 1.09 (95% CI: 1.06, 1.12) respectively. Segmented regression models showed stronger effects of PM10 on fetal growth at lower concentrations. Maternal PM10 exposure was significantly associated with a reduction in fetal growth among term and moderately preterm births, with a tendency of stronger effects for the latter and a flattening out of the slope at higher PM10 concentrations., (Copyright © 2015. Published by Elsevier Inc.)

Background: China has experienced increasingly severe levels of air pollution in the past decades, yet studies on the health effects of air pollution in China at a national study level, remain limited. This study assess the sub-chronic effect of ambient air pollution on respiratory mortality in the 32 largest Chinese cities., Methods: We employ two-way fixed effects panel data analysis and monthly air pollution and mortality panel data. We estimate associations between monthly respiratory mortality and air pollution; pollution is defined as particulate matter with aerodynamic diameter <10μm. We adjust for city characteristics, seasonality (monthly effects), and weather conditions (precipitation and temperature). We examine the associations between monthly injury mortality and air pollution to check for robustness., Results: The results show positive and statistically significant associations of air pollution with respiratory mortality. During the study period (2006-2010) a 10μg/m(3) increase in monthly PM10 concentration is associated with a 1.05% (95% CI, 0.08-2.04%) increase in adult respiratory mortality rate. The air pollution effect is the most salient in northern cities (with central heating system) during the cold season (October-April); a 10μg/m(3) increase in monthly PM10 concentrations is associated with a 1.62% (95% CI, 0.22-3.46%) increase in the elderly respiratory mortality rate. There is no statistically significant association between the young adult respiratory mortality and air pollution., Conclusions: The elderly respiratory mortality rate in China is positively and statistically significantly associated with air pollution. The effect is largest in northern cities during cold months when coal is burned for heating., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The Bayan Obo mine, located in Inner Mongolia, China, is the largest light rare earth body ever found in the world. The research for rare earth elements (REEs) enrichment in atmospheric particulates caused by mining and ore processing is fairly limited so far. In this paper, atmospheric particulates including total suspended particulate (TSP) matter and particles with an equivalent aerodynamic diameter less than 10 μm (PM10) were collected around the Bayan Obo mine region, in August 2012 and March 2013, to analyze the levels and distributions of REEs in particles. The total concentrations of REEs for TSP were 149.8 and 239.6 ng/m(3), and those for PM10 were 42.8 and 68.9 ng/m(3), in August 2012 and March 2013, respectively. Enrichment factor was calculated for all 14 REEs in the TSP and PM10 and the results indicated that REEs enrichment in atmosphere particulates was caused by anthropogenic sources and influenced by the strong wind in springtime. The spatial distribution of REEs in TSP showed a strong gradient concentration in the prevailing wind direction. REE chondrite normalized patterns of TSP and PM10 were similar and the normalized curves inclined to the right side, showing the conspicuous fractionation between the light REEs and heavy REE, which supported by the chondrite normalized concentration ratios calculated for selected elements (La(N)/Yb(N), La(N)/Sm(N), Gd(N)/Yb(N))., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Many studies have investigated the potential role of ozone exposure in cardiovascular mortality and morbidity. The effects on specific cardiovascular outcome and the role of individual susceptibility are less studied. This paper focuses on the short-term effects of ozone on acute coronary events and it investigates comorbidities as indicators of personal susceptibility., Setting and Patients: This study was conducted in five urban areas of the Tuscany region (Italy) covering the period January 2002-December 2005. Air quality and meteorological data from urban background monitoring sites were collected. Hospital admissions for acute myocardial infarction and out-of-hospital coronary deaths were extracted from administrative database., Design: Both time series and case-crossover designs were applied. The confounding effects of some time-dependent variables, such as temperature, were taken into account. Some potential susceptibility factors were investigated. Pooled estimates were derived from random-effect meta-analysis., Results: During the warm season 4555 hospitalized acute myocardial infarctions and 1931 out-of-hospital coronary deaths occurred. Authors estimated a 6.3% (95% confidence interval, 1.2%, 11.7%) increase in out-of-hospital coronary deaths for a 10 μg/m3 increase in ozone (lag 0-5). Results also suggested higher risks for females, elderly, and patients previously hospitalized for cerebrovascular and artery diseases., Conclusions: This study adds further evidence to the relation between cardiovascular diseases and ozone exposure, showing an adverse effect on out-of-hospital coronary deaths, but not on hospitalized acute myocardial infarctions. Some susceptible subgroups, such as females, elderly, and patients affected by some chronic diseases, are likely to be at major risk., (© 2013 Elsevier Inc. All rights reserved.)