Exposure Assessment and Monitoring of Antiblastic Drugs Preparation in Health Care Settings: A Systematic Review.

Several antiblastic drugs (ADs) are classified as carcinogenic, mutagenic, and/or toxic for reproduction. Despite established guidelines and safe handling technologies, ADs contamination of the work environments could occur in healthcare settings, leading to potential exposure of healthcare staff. This systematic review aims to investigate the main techniques and practices for assessing ADs occupational exposure in healthcare settings. The reviewed studies unveil that workplace contamination by ADs appears to be a still-topical problem in healthcare settings. These issues are linked to difficulties in guaranteeing: (i) the adherence to standardized protocols when dealing with ADs, (ii) the effective use of personal protective equipment by operators involved in the administration or management of ADs, (iii) a comprehensive training of the healthcare personnel, and (iv) a thorough health surveillance of exposed workers. A "multi-parametric" approach emerges as a desirable strategy for exposure assessment. In parallel, exposure assessment should coincide with the introduction of novel technologies aimed at minimizing exposure (i.e., risk management). Assessment must consider various departments and health operators susceptible to ADs contamination, with a focus extended beyond worst-case scenarios, also considering activities like surface cleaning and logistical tasks related to ADs management. A comprehensive approach in ADs risk assessment enables the evaluation of distinct substance behaviors and subsequent exposure routes, affording a more holistic understanding of potential risks.

An In-Field Assessment of the P.ALP Device in Four Different Real Working Conditions: A Performance Evaluation in Particulate Matter Monitoring.

This study aimed to assess the performance, in terms of precision and accuracy, of a prototype (called "P.ALP"-Ph.D. Air Quality Low-cost Project) developed for monitoring PM2.5 concentration levels. Four prototypes were co-located with reference instrumentation in four different microenvironments simulating real-world and working conditions, namely (i) office, (ii) home, (iii) outdoor, and (iv) occupational environments. The devices were evaluated for a total of 20 monitoring days (approximately 168 h) under a wide range of PM2.5 concentrations. The performances of the prototypes (based on the light-scattering working principle) were tested through different statistical methods. After the data acquisition and data cleaning processes, a linear regression analysis was performed to assess the precision (by comparing all possible pairs of devices) and the accuracy (by comparing the prototypes against the reference instrumentation) of the P.ALP. Moreover, the United States Environmental Protection Agency (US EPA) criteria were applied to assess the possible usage of this instrumentation, and to evaluate the eventual error trends of the P.ALP in the data storage process, Bland-Altman plots were also adopted. The outcomes of this study underlined that the P.ALP performed differently depending on the microenvironment in which it was tested and, consequently, on the PM2.5 concentrations. The device can monitor PM2.5 variations with acceptable results, but the performance cannot be considered satisfactory at extremely low and remarkably high PM2.5 concentrations. Thanks to modular components and open-source software, the tested device has the potential to be customized and adapted to better fit specific study design needs, but it must be implemented with ad hoc calibration factors depending on the application before being used in field.

Evolution and Applications of Recent Sensing Technology for Occupational Risk Assessment: A Rapid Review of the Literature.

Over the last decade, technological advancements have been made available and applied in a wide range of applications in several work fields, ranging from personal to industrial enforcements. One of the emerging issues concerns occupational safety and health in the Fourth Industrial Revolution and, in more detail, it deals with how industrial hygienists could improve the risk-assessment process. A possible way to achieve these aims is the adoption of new exposure-monitoring tools. In this study, a systematic review of the up-to-date scientific literature has been performed to identify and discuss the most-used sensors that could be useful for occupational risk assessment, with the intent of highlighting their pros and cons. A total of 40 papers have been included in this manuscript. The results show that sensors able to investigate airborne pollutants (i.e., gaseous pollutants and particulate matter), environmental conditions, physical agents, and workers' postures could be usefully adopted in the risk-assessment process, since they could report significant data without significantly interfering with the job activities of the investigated subjects. To date, there are only few "next-generation" monitors and sensors (NGMSs) that could be effectively used on the workplace to preserve human health. Due to this fact, the development and the validation of new NGMSs will be crucial in the upcoming years, to adopt these technologies in occupational-risk assessment.

Dynamic Olfactometry and Oil Refinery Odour Samples: Application of a New Method for Occupational Risk Assessment.

Refineries are characterized by relevant odour impacts, and the control and monitoring of this pollutant have become increasingly important. Dynamic olfactometry, a sensorial analysis that involves human examiners, is currently the most common technique to obtain odour quantification. However, due to the potential presence of hazardous pollutants, the conduction of occupational risk assessment is necessary to guarantee examiners' safety. Nevertheless, the occupational risk for olfactometric examiners, specifically correlated with oil refineries emissions, has not been investigated yet. Therefore, this paper applies a new methodology of risk assessment for workers involved in dynamic olfactometry, focusing on odorous refineries emissions. The chemical characterization of refinery emissions was obtained by TD-GC-MS, analysing odorous samples collected at different refinery odour sources. A database of chemical pollutants emitted from a refinery plant was built up, and the minimum dilution values to be adopted during the analysis of refinery odorous samples was calculated. In particular, this evaluation highlighted that, in this scenario, a non-negligible carcinogenic risk may exist for panellists exposed to refineries' samples, and the carcinogenic risk is sometimes higher than what is acceptable. Therefore, a minimum dilution value between 1.01 and 5, according to the specific sample, must be set to guarantee the examiners' safety.

Toxicological assessment method for evaluating the occupational risk of dynamic olfactometry assessors.

The paper aims to propose a new method to evaluate the occupational exposure risk for examiners involved in dynamic olfactometry. Indeed, examiners are possibly exposed to hazardous pollutants potentially present in odorous samples. A standardized method to evaluate the examiners' occupational safety is not yet available and the existing models present some critical aspect if applied to real odorous samples (no uniform reference concentrations applied and presence of compounds for which no toxicity threshold is available). A deepening of assessment procedure to evaluate the occupation exposure risk for olfactometric assessors is necessary. This paper proposes a standardized approach for risk assessment in dynamic olfactometry. The proposed approach allows the quantification synthetic and conservative risk indices. In this model, the use of the hazard index for the odorous mixture was proposed to assess the non-carcinogenic risk; the calculation of the inhalation risk was applied to estimate the carcinogenic risk. Different databases can be used to retrieve proper occupational exposure limits, according to the proposed hierarchical basis. These implementations allow obtaining the complete characterization of real samples which can be used to calculate the minimum dilution factor for protecting the panellists' health.

Features and Practicability of the Next-Generation Sensors and Monitors for Exposure Assessment to Airborne Pollutants: A Systematic Review.

In the last years, the issue of exposure assessment of airborne pollutants has been on the rise, both in the environmental and occupational fields. Increasingly severe national and international air quality standards, indoor air guidance values, and exposure limit values have been developed to protect the health of the general population and workers; this issue required a significant and continuous improvement in monitoring technologies to allow the execution of proper exposure assessment studies. One of the most interesting aspects in this field is the development of the "next-generation" of airborne pollutants monitors and sensors (NGMS). The principal aim of this review is to analyze and characterize the state of the art and of NGMS and their practical applications in exposure assessment studies. A systematic review of the literature was performed analyzing outcomes from three different databases (Scopus, PubMed, Isi Web of Knowledge); a total of 67 scientific papers were analyzed. The reviewing process was conducting systematically with the aim to extrapolate information about the specifications, technologies, and applicability of NGMSs in both environmental and occupational exposure assessment. The principal results of this review show that the use of NGMSs is becoming increasingly common in the scientific community for both environmental and occupational exposure assessment. The available studies outlined that NGMSs cannot be used as reference instrumentation in air monitoring for regulatory purposes, but at the same time, they can be easily adapted to more specific applications, improving exposure assessment studies in terms of spatiotemporal resolution, wearability, and adaptability to different types of projects and applications. Nevertheless, improvements needed to further enhance NGMSs performances and allow their wider use in the field of exposure assessment are also discussed.

Carbon Nanotubes: Probabilistic Approach for Occupational Risk Assessment.

In this study, the occupational risk assessment of carbon nanotubes (CNTs) was performed by means of a probabilistic approach. Chronic and subchronic inhalation exposure studies were retrieved during the hazard identification phase of the study. These studies were then used to obtain a guidance value (BMCh, expressed as a lognormal distribution with geometric mean ± geometric standard deviation = 10.0 ± 4.2 µg/m3) for occupational inhalation exposure to CNTs. An exposure scenario was selected from the scientific literature: three different work events (WEs) related to the production of conductive films were considered: (WE1) manufacturing of single walled carbon nanotubes films during normal operation using local exhaust ventilation (LEV); (WE2) manufacturing of SWCNT film without LEV; and (WE3) cleaning of one of the reactors. For each WE, a probability distribution function was applied, considering exposure expressed as mass concentration, as derived from three different measurement techniques. The ratio of the exposure and the BMCh distributions (i.e., the risk characterization ratio-RCR) was used to calculate the probability of occurrence of a relevant occupational risk. All the considered WEs indicated the presence of a risk (i.e., RCR distributions ≥ 1); however, only WE2 resulted in a statistically significant level of risk.

Retrospective Exposure Assessment Methods Used in Occupational Human Health Risk Assessment: A Systematic Review.

As part of the assessment and management of chemical risk and occupational hygiene, retrospective exposure assessment (REA) to chemical agents can be defined as the estimate of exposure associated with a person's work history. The fundamental problem underlying the reconstruction of the exposure is that of transforming this type of information in quantitative terms to obtain an accurate estimate. REA can follow various approaches, some of which are technically complicated and both time and resource consuming. The aim of this systematic review is to present the techniques mainly used for occupational REA. In order to carry out this evaluation, a systematic review of the scientific literature was conducted. Forty-four studies were identified (published from 2010 to date) and analyzed. In exposure reconstruction studies, quantitative approaches should be preferable, especially when estimates will be used in the context of health impact assessment or epidemiology, although it is important to stress how, ideally, the experimental data available for the considered scenario should be used whenever possible as the main starting information base for further processing. To date, there is no single approach capable of providing an accurate estimate of exposure for each reasonably foreseeable condition and situation and the best approach generally depends on the level of information available for the specific case. The use of a combination of different reconstruction techniques can, therefore, represent a powerful tool for weighting and integrating data obtained through qualitative and quantitative approaches, in order to obtain the best possible estimate.

Toxic trace metals in size-segregated fine particulate matter: Mass concentration, respiratory deposition, and risk assessment.

To characterise the mass concentration, size-distribution, and respiratory deposition of selected trace metals (Cr, Mn, Fe, Ni, Cu, Zn, Ba, and Pb) in size-segregated PM2.5, a long-term monitoring campaign was undertaken at an urban background site in Como (Northern Italy). 96-h aerosol samples were collected weekly, from May 2015 to March 2016, using a 13-stage low pressure impactor and analysed via laser ablation-inductively coupled plasma-mass spectrometry. Significantly higher levels of trace metals were generally found during the heating season (two to more than four times) compared to the non-heating period at all size ranges, especially for concentrations in PM0.1-1. Distinct distribution profiles characterised the different elements, even though the corresponding heating and non-heating shapes always exhibited similar features, with negligible seasonal shifts in the average mass median aerodynamic diameters. Fe, Ba, and Cu had >70% of their mass in PM1-2.5, whereas Pb, Zn, and Ni showed higher contributions in the accumulation mode (>60%). Finally, broad size-distributions were found for Cr and Mn. The multiple-path particle dosimetry model estimated the overall deposition fractions in human airways varying between 27% (Pb) and 48% (Ba). The greatest deposition variability was always registered in the head region of the respiratory system, with the highest contributions for those metals predominantly accumulated in the PM2.5 coarse modes. In contrast, the deposition in the deepest respiratory tract maintained nearly constant proportions over time, becoming notably important for Pb, Ni, and Zn (∼13%) with respect to their total deposition. The comparison with national limits established for Pb and Ni suggested the absence of significant risks for the local population, as expected, with average concentrations two orders of magnitude lower than the corresponding annual limit and objective value. Similar findings were reported for all the other metals, for which the estimated hazard quotients were always well <1.

Commuters' Personal Exposure Assessment and Evaluation of Inhaled Dose to Different Atmospheric Pollutants.

Several studies evaluating exposure to pollutants in microenvironments (MEs) are available in the scientific literature, but studies that evaluate the inhaled doses of pollutants are few in number. Therefore, this study aimed to evaluate the exposure of commuters to different pollutants (i.e., nitrogen dioxide [NO2] and fractionated particulate matter [PM], including ultrafine particles [UFPs]) using miniaturized and portable real-time monitoring instruments in selected MEs; the inhaled doses of these pollutants were estimated for each of these MEs. Measurements were performed along a typical commute, considering different traffic and nontraffic MEs. Experimental data were collected over four working weeks in two different seasons (winter and summer). Different portable and miniaturized instruments were used to evaluate PM and NO2 exposure. Furthermore, physiological parameters were evaluated using a heart rate monitor. The principal results show that higher exposure levels were measured in Underground (for all PM fractions and NO2) and in Car (UFP), while lower levels were measured in Car (PM and NO2) and in Train (UFP). In contrast, higher values of the inhaled cumulative dose were estimated in environments defined as Other, followed by Walking (ht), while lower values were observed in Walking (lt) and in Car.

[Chemical risks in research laboratories]. / I rischi nei laboratori di ricerca: i rischi di tipo chimico.

SUMMARY: Research laboratories represent peculiar employment realities, generally characterized by the use of reduced volumes of several chemicals, often used in mixture, thus defining a potential exposure to multiple chemical agents. Methods. The aim of the study is to provide a brief review of the most widely used methods for assessing chemical risk in laboratories, with particular emphasis on their limits and advantages. Results. The approach most often used for assessing chemical risk in research laboratories involves the use of a qualitative modeling approach for risk assessment or quantitative exposure assessment tools. Conclusions. Chemical risk assessment algorithms represent a useful solution for the purposes of the initial screening for the assessment of chemical risk in research laboratories: their ease of use makes them easily accessible, but on the other hand does not allow to take into proper consideration the particularities of the assessed exposure scenarios. Regarding the exposure estimation models, although these instruments have a wide range of applicability, there is no solid and complete validation, which evaluates the accuracy and reliability for this peculiar type of exposure scenarios.

Probabilistic approach for the risk assessment of nanomaterials: A case study for graphene nanoplatelets.

An experimental probabilistic approach for health risk assessment was applied for graphene nanoplatelets (GNPs). The hazard assessment indicated a low level of toxicity for the GNPs. The benchmark dose method, based on sub-chronic and chronic inhalation exposure studies, was used to quantify a guidance value (BMCh) for occupational inhalation exposure to GNPs, expressed as a lognormal distribution with a geometric mean ±â€¯geometric standard deviation of 0.212 ±â€¯7.79 mg/m3 and 9.37 × 104 ±â€¯7.6 particle/cm3. Exposure scenarios (ES) were defined based on the scientific literature for large-scale production (ES1) and manufacturing (ES2) of GNPs; a third ES, concerning in-lab handling of GNPs (ES3) was based on results of experiments performed for this study. A probability distribution function was then assumed for each ES. The risk magnitude was calculated using a risk characterization ratio (RCR), defined as the ratio of the exposure distributions and the BMCh distribution. All three ES resulted in RCR distributions ≥1 (i.e. risk present); however, none of the ES had a statistically significant level of risk at a 95% confidence interval. A sensitivity analysis indicated that ∼75% of the variation in the RCR distributions was due to uncertainties in the BMCh calculation.

Precision and Accuracy of a Direct-Reading Miniaturized Monitor in PM2.5 Exposure Assessment.

The aim of this study was to evaluate the precision, accuracy, practicality, and potential uses of a PM2.5 miniaturized monitor (MM) in exposure assessment. These monitors (AirBeam, HabitatMap) were compared with the widely used direct-reading particulate matter monitors and a gravimetric reference method for PM2.5. Instruments were tested during 20 monitoring sessions that were subdivided in two different seasons to evaluate the performance of sensors across various environmental and meteorological conditions. Measurements were performed at an urban background site in Como, Italy. To evaluate the performance of the instruments, different analyses were conducted on 8-h averaged PM2.5 concentrations for comparison between direct-reading monitors and the gravimetric method, and minute-averaged data for comparison between the direct-reading instruments. A linear regression analysis was performed to evaluate whether the two measurement methods, when compared, could be considered comparable and/or mutually predictive. Further, Bland-Altman plots were used to determine whether the methods were characterized by specific biases. Finally, the correlations between the error associated with the direct-reading instruments and the meteorological parameters acquired at the sampling point were investigated. Principal results show a moderate degree of agreement between MMs and the reference method and a bias that increased with an increase in PM2.5 concentrations.

Miniaturized Monitors for Assessment of Exposure to Air Pollutants: A Review.

Air quality has a huge impact on different aspects of life quality, and for this reason, air quality monitoring is required by national and international regulations. Technical and procedural limitations of traditional fixed-site stations for monitoring or sampling of air pollutants are also well-known. Recently, a different type of miniaturized monitors has been developed. These monitors, due to their characteristics (e.g., low cost, small size, high portability) are becoming increasingly important for individual exposure assessment, especially since this kind of instrument can provide measurements at high spatial and temporal resolution, which is a notable advantage when approaching assessment of exposure to environmental contaminants. The aim of this study is indeed to provide information regarding current knowledge regarding the use of miniaturized air pollutant sensors. A systematic review was performed to identify original articles: a literature search was carried out using an appropriate query for the search of papers across three different databases, and the papers were selected using inclusion/exclusion criteria. The reviewed articles showed that miniaturized sensors are particularly versatile and could be applied in studies with different experimental designs, helping to provide a significant enhancement to exposure assessment, even though studies regarding their performance are still sparse.

Accuracy Evaluation of Three Modelling Tools for Occupational Exposure Assessment.

OBJECTIVES: The objective of this study is to evaluate the accuracy and robustness of three exposure-modelling tools [STOFFENMANAGER® v.6, European Centre for Ecotoxicology and Toxicology of Chemical Target Risk Assessment v.3.1 (ECETOC TRA v.3.1), and Advanced REACH Tool (ART v.1.5)], by comparing available measured data for exposure to organic solvents and pesticides in occupational exposure scenarios (ESs). METHODS: Model accuracy was evaluated by comparing the predicted and the measured values, expressed as an underestimation or overestimation factor (PRED/EXP), and by regression analysis. Robustness was quantitatively described by the so-called variable 'Uncertainty Factor' (UF), which was attributed to each model's input: a higher UF score indicates greater model uncertainty and poorer robustness. RESULTS: ART was the most accurate model, with median PRED/EXP factors of 1.3 and 0.15 for organic solvent and pesticide ESs, respectively, and a significant correlation (P < 0.05) among estimated and measured data. As expected, Tier 1 model ECETOC TRA demonstrated the worst performance in terms of accuracy, with median PRED/EXP factors of 2.0 for organic solvent ESs and 3545 for pesticide ESs. Simultaneously, STOFFENMANAGER® showed a median UF equal to 2.0, resulting in the most robust model. DISCUSSION: ECETOC TRA was not considered acceptable in terms of accuracy, confirming that this model is not appropriate for the evaluation of the selected ESs for pesticides. Conversely, STOFFENMANAGER® was the best choice, and ART tended to underestimate the exposure to pesticides. For organic solvent ESs, there were no cases of strong underestimation, and all models presented overall acceptable results; for the selected ESs, ART showed the best accuracy. Stoffenmanager was the most robust model overall, indicating that even with a mistake in ES interpretation, predicted values would remain acceptable. CONCLUSION: ART may lead to more accurate results when well-documented ESs are available. In other situations, Stoffenmanager appears to be a safer alternative because of its greater robustness, particularly when entry data uncertainty is difficult to assess. ECETOC TRA cannot be directly compared to higher tiered models because of its simplistic nature: the use of this tool should be limited only to exceptional cases in which a strong conservative and worst-case evaluation is necessary.

Assessment of indoor air quality in office buildings across Europe - The OFFICAIR study.

The European project OFFICAIR aimed to broaden the existing knowledge regarding indoor air quality (IAQ) in modern office buildings, i.e., recently built or refurbished buildings. Thirty-seven office buildings participated in the summer campaign (2012), and thirty-five participated in the winter campaign (2012-2013). Four rooms were investigated per building. The target pollutants were twelve volatile organic compounds, seven aldehydes, ozone, nitrogen dioxide and particulate matter with aerodynamic diameter <2.5µm (PM2.5). Compared to other studies in office buildings, the benzene, toluene, ethylbenzene, and xylene concentrations were lower in OFFICAIR buildings, while the α-pinene and d-limonene concentrations were higher, and the aldehyde, nitrogen dioxide and PM2.5 concentrations were of the same order of magnitude. When comparing summer and winter, significantly higher concentrations were measured in summer for formaldehyde and ozone, and in winter for benzene, α-pinene, d-limonene, and nitrogen dioxide. The terpene and 2-ethylhexanol concentrations showed heterogeneity within buildings regardless of the season. Considering the average of the summer and winter concentrations, the acetaldehyde and hexanal concentrations tended to increase by 4-5% on average with every floor level increase, and the nitrogen dioxide concentration tended to decrease by 3% on average with every floor level increase. A preliminary evaluation of IAQ in terms of potential irritative and respiratory health effects was performed. The 5-day median and maximum indoor air concentrations of formaldehyde and ozone did not exceed their respective WHO air quality guidelines, and those of acrolein, α-pinene, and d-limonene were lower than their estimated thresholds for irritative and respiratory effects. PM2.5 indoor concentrations were higher than the 24-h and annual WHO ambient air quality guidelines.

Development of an exposure measurement database on five lung carcinogens (ExpoSYN) for quantitative retrospective occupational exposure assessment.

BACKGROUND: SYNERGY is a large pooled analysis of case-control studies on the joint effects of occupational carcinogens and smoking in the development of lung cancer. A quantitative job-exposure matrix (JEM) will be developed to assign exposures to five major lung carcinogens [asbestos, chromium, nickel, polycyclic aromatic hydrocarbons (PAH), and respirable crystalline silica (RCS)]. We assembled an exposure database, called ExpoSYN, to enable such a quantitative exposure assessment. METHODS: Existing exposure databases were identified and European and Canadian research institutes were approached to identify pertinent exposure measurement data. Results of individual air measurements were entered anonymized according to a standardized protocol. RESULTS: The ExpoSYN database currently includes 356 551 measurements from 19 countries. In total, 140 666 personal and 215 885 stationary data points were available. Measurements were distributed over the five agents as follows: RCS (42%), asbestos (20%), chromium (16%), nickel (15%), and PAH (7%). The measurement data cover the time period from 1951 to present. However, only a small portion of measurements (1.4%) were performed prior to 1975. The major contributing countries for personal measurements were Germany (32%), UK (22%), France (14%), and Norway and Canada (both 11%). CONCLUSIONS: ExpoSYN is a unique occupational exposure database with measurements from 18 European countries and Canada covering a time period of >50 years. This database will be used to develop a country-, job-, and time period-specific quantitative JEM. This JEM will enable data-driven quantitative exposure assessment in a multinational pooled analysis of community-based lung cancer case-control studies.

Modelling of occupational respirable crystalline silica exposure for quantitative exposure assessment in community-based case-control studies.

We describe an empirical model for exposure to respirable crystalline silica (RCS) to create a quantitative job-exposure matrix (JEM) for community-based studies. Personal measurements of exposure to RCS from Europe and Canada were obtained for exposure modelling. A mixed-effects model was elaborated, with region/country and job titles as random effect terms. The fixed effect terms included year of measurement, measurement strategy (representative or worst-case), sampling duration (minutes) and a priori exposure intensity rating for each job from an independently developed JEM (none, low, high). 23,640 personal RCS exposure measurements, covering a time period from 1976 to 2009, were available for modelling. The model indicated an overall downward time trend in RCS exposure levels of -6% per year. Exposure levels were higher in the UK and Canada, and lower in Northern Europe and Germany. Worst-case sampling was associated with higher reported exposure levels and an increase in sampling duration was associated with lower reported exposure levels. Highest predicted RCS exposure levels in the reference year (1998) were for chimney bricklayers (geometric mean 0.11 mg m(-3)), monument carvers and other stone cutters and carvers (0.10 mg m(-3)). The resulting model enables us to predict time-, job-, and region/country-specific exposure levels of RCS. These predictions will be used in the SYNERGY study, an ongoing pooled multinational community-based case-control study on lung cancer.

Review of agri-environment indexes and stewardship payments.

Agri-environment programs aim to secure environmental and social stewardship services through payments to farmers. A critical component of many agri-environment programs is an agri-environment index (AEI) used to quantify benefits and target investments. An AEI will typically comprise multiple indicators, which are weighted and combined using a utility function, to measure the benefit of investment options (e.g., projects, farms, regions). This article presents a review of AEIs with 11 case studies from agri-environment programs in the United States, Australia, and the United Kingdom. We identify a generic procedure used to define AEIs and explore the implications of alternative methodological approaches. We conclude that AEIs have become an extremely important policy instrument and make suggestions for their improvement.