Assessment of potential human health risks in aquatic products based on the heavy metal hazard decision tree.

BACKGROUND: Naturally existing and human-produced heavy metals are released into the environment and cannot be completely decomposed by microorganisms, but they continue to accumulate in water and sediments, causing organisms to be exposed to heavy metals. RESULTS: This study designs and proposes heavy metal hazard decision trees for aquatic products, which are divided into seven categories including pelagic fishes, inshore fishes, other fishes, crustaceans, shellfish, cephalopods, and algae. Based on these classifications, representative fresh and processed seafood products are at the root of the heavy metal hazard decision trees. This study uses 2,107 cases of eating 556 cooked fresh or processed seafood product samples. The constructions of the proposed decision trees consist of 12 heavy metals, which include inorganic arsenic (iAs), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), strontium (Sr), thallium (Tl), and zinc (Zn). The heavy metal concentrations in cooked fresh and processed seafood product samples are subjected to a food safety risk assessment. CONCLUSIONS: The results indicate the relationships among the seven categories of aquatic products, the relationships among 12 heavy metals in aquatic products, and the relationships among potential human health risks. Finally, the proposed heavy metal hazard decision trees for aquatic products can be used as a reference model for researchers and engineers.

Probabilistic risk assessment of patulin in imported apple juice and apple-containing beverages in Taiwan.

BACKGROUND: In Taiwan, nearly 90% of apples and raw ingredients for apple-based products are imported. Apple juices (137 samples) and apple-containing beverages (35 samples) were collected in Taiwan from imported food and analyzed for patulin content. RESULTS: The results revealed that the incidence levels of patulin for apple juice and apple-containing beverages are 5.84% and 5.71%. The mean contamination levels were 1.7 and 1.4 µg kg-1 for apple juice and apple-containing beverages. One sample exceeded 50 µg kg-1 , the maximum permissible limit according to the Taiwan Sanitation Standard for the Tolerance of Mycotoxins in Foods. The estimated intake of patulin for consumers ranged from 5.4 to 18.0 ng kg-1 body weight per day for apple juice and between 6.1 and 11.2 ng kg-1 body weight for apple-containing beverages. The highest average patulin intake was observed among infants aged 0-3 years, followed by children aged 4-12 years old. Finally, the hazard index (HI) for the 50th, 90th, and 95th percentiles are 0.0186, 0.1201, and 0.2048, respectively, for infants aged 0-3 years. CONCLUSION: The dietary intake of patulin from imported apple juices and apple-containing beverages is well below the safety levels and does not present a risk for adult and children consumers. However, it is important to point out that we only analyzed imported apple juices and apple-containing beverages. More studies are necessary to establish if the HI for patulin will still remain below 1 when other foods and beverages are included in the risk calculations. © 2020 Society of Chemical Industry.

Assessing Risk-Based Upper Limits of Melamine Migration from Food Containers.

Melamine contamination of food has become a major food safety issue because of incidents of infant disease caused by exposure to this chemical. This study was aimed at establishing a safety limit in Taiwan for the degree of melamine migration from food containers. Health risk assessment was performed for three exposure groups (preschool children, individuals who dine out, and elderly residents of nursing homes). Selected values of tolerable daily intake (TDI) for melamine were used to calculate the reference migration concentration limit (RMCL) or reference specific migration limit (RSML) for melamine food containers. The only existing values of these limits for international standards today are 1.2 mg/L (0.2 mg/dm2 ) in China and 30 mg/L (5 mg/dm2 ) in the European Union. The factors used in the calculations included the specific surface area of food containers, daily food consumption rate, body weight, TDI, and the percentile of the population protected at a given migration concentration limit (MCL). The results indicate that children are indeed at higher risk of melamine exposure at toxic levels than are other groups and that the 95th percentile of MCL (specific surface area = 5) for children aged 1-6 years should be the RMCL (0.07 mg/dm2 ) for protecting the sensitive and general population.

Probabilistic framework for assessing the arsenic exposure risk from cooked fish consumption.

Geogenic arsenic (As) contamination of groundwater is a major ecological and human health problem in southwestern and northeastern coastal areas of Taiwan. Here, we present a probabilistic framework for assessing the human health risks from consuming raw and cooked fish that were cultured in groundwater As-contaminated ponds in Taiwan by linking a physiologically based pharmacokinetics model and a Weibull dose-response model. Results indicate that As levels in baked, fried, and grilled fish were higher than those of raw fish. Frying resulted in the greatest increase in As concentration, followed by grilling, with baking affecting the As concentration the least. Simulation results show that, following consumption of baked As-contaminated fish, the health risk to humans is <10(-6) excess bladder cancer risk level for lifetime exposure; as the incidence ratios of liver and lung cancers are generally acceptable at risk ranging from 10(-6) to 10(-4), the consumption of baked As-contaminated fish is unlikely to pose a significant risk to human health. However, contaminated fish cooked by frying resulted in significant health risks, showing the highest cumulative incidence ratios of liver cancer. We also show that males have higher cumulative incidence ratio of liver cancer than females. We found that although cooking resulted in an increase for As levels in As-contaminated fish, the risk to human health of consuming baked fish is nevertheless acceptable. We suggest the adoption of baking as a cooking method and warn against frying As-contaminated fish. We conclude that the concentration of contaminants after cooking should be taken into consideration when assessing the risk to human health.

Differential accumulation of trace elements in ventral and dorsal muscle tissues in tilapia and milkfish with different feeding habits from the same cultured fishery pond.

There were many studies that reported the concentrations of trace elements in fish and assessed the human health risk through consumption of contaminated fish. However, fish species with different feeding habits may accumulate toxic elements differentially in their muscle. In this study, we conducted a field survey to analyze concentrations of ten trace elements in water, sediment, artificial feed, and different part of muscles either with or without skin of two species of fish, tilapia and milkfish. The results of this study showed that the ventral and dorsal muscles with skin contained higher concentrations of metals than those without skin for both species of fish. Tilapia lives in the bottom layer, the ventral part therefore contacts closely with sediment. A higher metal concentration in ventral muscle was obtained in this study when compared to dorsal muscle for tilapia. The estimated Metal Pollution Index (MPI) of tilapia is higher than that of milkfish. Our results indicated that metal concentrations in muscle of tilapia are mainly originated from sediment. However, sources of metal concentrations in muscle of milkfish can be from sediment and artificial feed.

Probabilistic benefit-risk analysis of fish: Nutritional benefit versus methylmercury-contaminated risk.

This paper carries out probabilistic approach to quantify the benefit-risk analysis for foods (BRAFO) of omega-3 polyunsaturated fatty acid and methylmercury (MeHg) for the people who eat the mercury-contaminated fish in Taiwan. We applied the hazard quotient (HQ) model to assess the risk of developmental neuropsychological impairment effect and the desirable dose index (DI) model to quantify the health benefits. Besides, we also applied the disability adjusted life years (DALY) model to assess the number of years lost by incidence of affected infants' intelligence quotient (IQ) and coronary heart disease (CHD) or Stroke for adult. The results of this study show that although the risk of cod and scad are higher, Taiwan residents do not need to reduce intake rate based on benefit considerations. Furthermore, according to the benefits of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), this study suggests that more intake of saury and salmon.

Quantitative microbiological risk assessments for Salmonella spp. contaminated taiwanese salty chicken in the taiwanese population.

The aim of the study is to develop Salmonella spp. Quantitative microbial risk assessments (QMRA) and to evaluate the risk of Salmonellosis illness in the Taiwanese population after consumption of Taiwanese salty chicken (TSC). We assume that Salmonella spp. May contaminate the fresh raw chicken used in TSC. After transport to the diner, fresh raw chicken is received, cleaned, and surface-washed by diner staff. The TSC is then cooked and sold to consumers. We set four different cross-contamination scenarios to evaluate the contamination level of Salmonella spp. In TSC. We used a Monte Carlo simulation method, a probabilistic analysis method, and exceedance risk to evaluate the risk of Salmonellosis illness. When the exceedance risk was 5 %, and taking the Taiwanese population above 19 years old as an example, the rate of contracting Salmonellosis from the consumption of TSC will be 2.94 % (2.94 million per 100 million people) if the chef does not clean their hands, knives, or cutting boards. However, if the chef washes their hands, knives, and cutting boards with cold water and soap, the illness rate of Salmonellosis from consuming TSC will be 1.93E-04 % (193 per 100 million people). Sensitivity analysis indicates that the most important risk factor in the QMRAs of TSC is the temperature of the fresh raw chicken during transportation, following which were the Salmonella spp. Residual. If the staff of the diner separates the cooking tools used for raw ingredients and those for cooked food, the illness risk of Salmonellosis will be very low.

Use of seasonal influenza virus titer and respiratory symptom score to estimate effective human contact rates.

BACKGROUND: We linked viral titers and respiratory symptom scores for seasonal influenza to estimate the effective contact rate among schoolchildren. METHODS: We analyzed 274 diary-based questionnaires. In addition, 2 sets of influenza data from published studies were used to investigate the relationship between viral titer, total symptom score, and normalized contact rate in children. RESULTS: The mean number (SD) of contacts for children in grades 7 to 9 ranged from 9.44 ± 8.68 to 11.18 ± 7.98 person⁻¹ day⁻¹; contact behavior was similar across school grades. The mean number of contacts was 5.66 ± 6.23 person⁻¹ day⁻¹ (range, 0 to 44 person⁻¹ day⁻¹) for the age group of 13 to 19 years. Estimated contact age, household size, contact duration, and contact frequency were the variables most strongly associated with total number of contacts. We also found that a reduction in total respiratory symptom scores among infected individuals had a positive correlation with an increase in the normalized contact rate. CONCLUSIONS: The relationship between daily virus titer and respiratory symptom score can be used to estimate the effective contact rate in explaining the spread of an airborne transmissible disease. The present findings can be incorporated into population-dynamic models of influenza transmission among schoolchildren.

Assessing trends and predictors of tuberculosis in Taiwan.

BACKGROUND: Variety of environmental and individual factors can cause tuberculosis (TB) incidence change. The purpose of this study was to assess the characteristics of TB trends in the period 2004 - 2008 in Taiwan by month, year, gender, age, temperature, seasonality, and aborigines. METHODS: The generalized regression models were used to examine the potential predictors for the monthly TB incidence in regional and national scales. RESULTS: We found that (i) in Taiwan the average TB incidence was 68 per 100,000 population with mortality rate of 0.036 person-1 yr-1, (ii) the highest TB incidence rate was found in eastern Taiwan (116 per 100,000 population) with the largest proportion of TB relapse cases (8.17%), (iii) seasonality, aborigines, gender, and age had a consistent and dominant role in constructing TB incidence patterns in Taiwan, and (iv) gender, time trend, and 2-month lag maximum temperature showed strong association with TB trends in aboriginal subpopulations. CONCLUSIONS: The proposed Poisson regression model is capable of forecasting patterns of TB incidence at regional and national scales. This study suggested that assessment of TB trends in eastern Taiwan presents an important opportunity for understanding the time-series dynamics and control of TB infections, given that this is the typical host demography in regions where these infections remain major public health problems.

A probabilistic transmission and population dynamic model to assess tuberculosis infection risk.

The purpose of this study was to examine tuberculosis (TB) population dynamics and to assess potential infection risk in Taiwan. A well-established mathematical model of TB transmission built on previous models was adopted to study the potential impact of TB transmission. A probabilistic risk model was also developed to estimate site-specific risks of developing disease soon after recent primary infection, exogenous reinfection, or through endogenous reactivation (latently infected TB) among Taiwan regions. Here, we showed that the proportion of endogenous reactivation (53-67%) was larger than that of exogenous reinfection (32-47%). Our simulations showed that as epidemic reaches a steady state, age distribution of cases would finally shift toward older age groups dominated by latently infected TB cases as a result of endogenous reactivation. A comparison of age-weighted TB incidence data with our model simulation output with 95% credible intervals revealed that the predictions were in an apparent agreement with observed data. The median value of overall basic reproduction number (R0) in eastern Taiwan ranged from 1.65 to 1.72, whereas northern Taiwan had the lowest R0 estimate of 1.50. We found that total TB incidences in eastern Taiwan had 25-27% probabilities of total proportion of infected population exceeding 90%, whereas there were 36-66% probabilities having exceeded 20% of total proportion of infected population attributed to latently infected TB. We suggested that our Taiwan-based analysis can be extended to the context of developing countries, where TB remains a substantial cause of elderly morbidity and mortality.

Assessing nitrate contamination and its potential health risk to Kinmen residents.

Kinmen is located in the southwest of Mainland China. Groundwater supplies 50% of the domestic water use on the island. Residents of Kinmen drink groundwater over the long term because surface water resources are limited. Nitrate-N pollution is found and distributed primarily in the western part of groundwater aquifer whereas saline groundwater is distributed to the northeastern Kinmen. This work applied the DRASTIC model to construct the vulnerability map of Kinmen groundwater. MT3D was then used to evaluate the contamination potential of nitrate-N. The health risk associated with the ingestion of nitrate-N contaminated groundwater is also assessed. The results from DRASTIC model showed that the upland crop and grass land have high contamination potential, whereas the forest, reservoir and housing land have low contamination potential. The calibrated MT3D model inversely determined the high strength sources (0.09-2.74 kg/m(2)/year) of nitrate contaminant located in the west to the north west area and required 2-5 years travel time to reach the monitoring wells. Simulated results of MT3D also showed that both the continuous and instantaneous contaminant sources of nitrate-N release may cause serious to moderate nitrate contamination in the western Kinmen and jeopardize the domestic use of groundwater. The chronic health hazard quotient (HQ) associated with the potential non-carcinogenic risk of drinking nitrate-N contaminated groundwater showed that the assessed 95th percentile of HQ is 2.74, indicating that exposure to waterborne nitrate poses a potential non-cancer risk to the residents of the island. Corrective measures, including protecting groundwater recharge zones and reducing the number of agricultural and non-agricultural nitrogen sources that enters the aquifer, should be implemented especially in the western part of Kinmen to assure a sustainable use of groundwater resources.

Dietary Exposure of the Taiwan Population to Mercury Content in Various Seafood Assessed by a Total Diet Study.

This paper examines the health risks of exposure to methylmercury (MeHg) through the consumption of mercury-contaminated seafood in Taiwan, based on the total diet study (TDS) method. Samples of seafood (n = 140) were purchased at fishing harbors or supermarkets and classified into seven categories (pelagic fish, inshore fish, farmed fish, shellfish, cephalopods, crustaceans, and algae). For each sample, we analyzed raw and cooked versions and compared the concentration difference. Total mercury (THg) was detected at the highest rate and in the highest concentrations in pelagic fish, followed by inshore fish and other farmed fish. The average concentration of THg was higher after cooking. In a 75th percentile scenario, the hazard indices for children aged 1 to 3 years and children aged 4 to 6 years were higher than 100% of the provisional tolerable weekly intake. Taking into consideration the risk assessment results, MeHg concentrations, and the nutritional composition of fish, we have provided weekly consumption advisories for children aged 1 to 3 years, children aged 4 to 6 years, and childbearing women aged 19 to 49 years. The weekly consumption advisories for childbearing women are 35 g/week of pelagic fish and 245 g/week of inshore fish based on the risk results from MeHg and the potential benefits from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake.

Levels of heavy metal cadmium in rice (Oryza sativa L.) produced in Taiwan and probabilistic risk assessment for the Taiwanese population.

Cadmium (Cd) is a toxic pollutant that is widely spread through industrial production and agricultural practices. Epidemiological data has revealed that lifetime exposure to environmentally relevant levels of Cd increases the risk of developing various organ diseases, including chronic kidney, heart, and lung diseases, as well as nervous tissue disorders. This study assessed Cd levels in rice to determine the health risks associated with rice consumption in various age-gender subgroups in Taiwan. The distribution of Cd concentration, the lifetime average daily dose (LADD), and the hazard index (HI) were estimated by Monte Carlo simulation. In the general population, the 50th percentile LADD of Cd for male rice consumers between the ages of 19-65 years was 0.06 µg/kg body weight per day, and the hazard index (HI) 50th, 90th, and 95th percentiles were 0.16, 0.69, and 1.54, respectively. According to the HI heat map for the exposure of the general population to Cd from rice in Taiwan, the highest exposure to Cd was noted in the Yilan area (HI 0.64). Therefore, rice production in the Yilan area should be further monitored to evaluate the levels of Cd contamination.

Microbial Risk Assessment of Escherichia coli O157:H7 in Beef Imported from the United States of America to Taiwan.

Outbreaks of foodborne illness caused by pathogenic Escherichia coli (E. coli) O157:H7, which are attributable to the consumption of undercooked beef, have occurred in many countries. In Taiwan, the production of domestic beef accounts for only 5% of the total amount of beef sold. Therefore, we applied different contextual assumptions to develop a quantitative microbial risk assessment of E. coli O157:H7 and evaluated the risk of illness in the Taiwanese population consuming beef imported from the United States of America. The probability distribution showed that, in males aged 19-65 years in the Taiwanese population, for example, when rare beef was consumed 100 servings, there was a 90% probability of randomly intaking seven colony forming units of E. coli O157:H7. When medium beef was consumed 10,000 servings, there was a 90% probability of randomly intaking two colony forming units of E. coli O157:H7. When the exceedance risk was 5%, the rate of foodborne illnesses caused by consuming rare beef contaminated with E. coli O157:H7 was 10-28 cases per 1 million individuals. For medium beef, this rate was 6-13 per 100 million individuals. Sensitivity analyses indicated that the amount of E. coli O157:H7 remaining in beef products after cooking was the most important risk factor, followed by the amount of beef products consumed. Proper cooking of imported beef consumed by the Taiwanese public reduces the incidence of foodborne disease to almost zero, without risk of harm to health.

Risk Assessment of the Dietary Phosphate Exposure in Taiwan Population Using a Total Diet Study.

Phosphorus and calcium are essential nutrients for the human body. However, excessive intake of phosphates and a low calcium:phosphorus ratio can lead to disorders in calcium-phosphorus metabolism, kidney disease, or osteoporosis. In this study, a total diet study (TDS) was used. The total phosphorus concentrations of foods were combined with the average dietary consumption to calculate the estimated daily intake, which was compared with the maximum tolerable daily intake (MTDI) to assess the resulting health risk of total phosphorus exposure. The calcium concentration in food and total calcium intake were also analyzed and estimated to calculate the calcium:phosphorus ratio. In conclusion, the phosphate exposure risks for the Taiwanese population are acceptable. However, the calcium:phosphorus ratio in the Taiwanese population (0.51-0.63) is lower than the reference calcium:phosphorus ratio (1.25).

Assessing dietary exposure risk to neonicotinoid residues among preschool children in regions of Taiwan.

Neonicotinoids (NEOs) are a class of pesticides widely used worldwide. This study analyzed post-cooking residues of NEO pesticides and assessed their potential health risks for preschool children (0-6 years old) by conducting a total diet study (TDS). It involved food sampling, preparation, analysis of pesticide residues, estimation of food consumption data, and assessment of food safety risks. Food sampling was conducted between March and June 2015. A total of 128 food samples were obtained from 4 parts of Taiwan. After the food had been prepared, the 128 samples were aggregated into 32 composite food items and the NEO residues analyzed. Acetamiprid had the highest detection rate of the NEO residues (59.4%), and the concentrations ranged from not detected to 80.5 µg/kg. The estimated daily intake (EDI) of NEO residues among preschool children was found to be lower than the adjusted acceptable daily intake (ADI) even for highly exposed groups. The results showed that NEO pesticides were primarily detected in preserved fruits, cherry tomato, rape, bell fruit, and baby bok choy. The main health risk posed by detected NEO residues at high consumption rates for preschool children was attributed to acetamiprid (34.20 %ADI) and imidacloprid (23.69 %ADI), respectively. Therefore, this research implicates that the present level of NEO residues in the diets for preschool children in Taiwan does not exceed 100 %ADI.

Health risk of consuming heavy metals in farmed tilapia in central Taiwan.

Taiwan is a small island nation, and many aquaculture sites are located near industrial parks. Anthropogenic activities may contaminate fish ponds. Therefore, we investigated the concentrations of eight metal elements in tilapia tissues (muscle and scale) at two fisheries. We compared the difference in metal content in tilapia at these two fisheries with that in non-contaminated fish at the Fisheries Research Institute. Probabilistic risk analysis was carried out to assess the health risk for people who eat contaminated tilapia. The predicted 95th percentiles of the hazard quotient and excess lifetime cancer risk for residents consuming contaminated tilapia were found to be in the range of 3.1-9.2 and 1.03 x 10(-5)-1.85 x 10(-5), respectively.

Assessing Aflatoxin Exposure Risk from Peanuts and Peanut Products Imported to Taiwan.

Aflatoxins are highly toxic and cause disease in livestock and humans. In order to assess Taiwan population exposure to aflatoxin from peanuts and peanut products, a total of 1089 samples of peanut candy, peanut butter, and peanuts etc. were collected in the period from 2011 to 2017 and analyzed using a liquid chromatography/tandem mass spectrometer. The overall mean contamination levels of aflatoxin in peanuts and peanut products were 2.40 µg/kg of aflatoxin B1, 0.41 µg/kg of aflatoxin B2, 0.19 µg/kg of aflatoxin G1, and 0.03 µg/kg of aflatoxin G2. We use margin of exposure (MOE) as a tool to improve food safety management. According to MOE levels of aflatoxins in peanuts and peanut products from China, Indonesia, Thailand, the United States, and the Philippines were above the safe lower limit of 10,000, indicating an absence of public health or safety risk for the majority of the population. However, products from Vietnam were under the MOE safe lower limit, suggesting that regulatory actions must be continued to avoid excessive consumer exposure.

Using disease-burden method to evaluate the strategies for reduction of aflatoxin exposure in peanuts.

Aflatoxin is a fungal secondary metabolite with high toxicity that is capable of contaminating various types of food crops. It has been identified as a Group 1 human carcinogen by the International Agency for Research on Cancer. Chronic aflatoxin exposure has caused worldwide concern as a matter of public food safety. Peanuts and peanut products are the major sources of aflatoxin exposure. Therefore, some reduction interventions have been developed to minimize contamination throughout the peanut production chain. The purpose of this study is to estimate the efficacy of interventions in reducing the health impact of hepatocellular carcinoma caused by aflatoxin contamination in peanuts. The estimated total Disability-Adjusted Life Years (DALYs) were calculated using FDA-iRISK software. Six aflatoxin reduction strategies were evaluated, including good agricultural practice (GAP), biocontrol, Purdue Improved Crop Storage packaging, basic processing, ozonolysis, and ultraviolet irradiation. The results indicated that basic processing could prevent huge public health loss of 4,079.7-21,833 total DALYs per year. In addition, GAP and biocontrol were both found to be effective strategies in the farm field. Meanwhile, the other three interventions had limited effectiveness in reducing total DALYs. In conclusion, this study could help farmers, processing plants, and government policy makers to alleviate aflatoxin contamination issues in the peanut production chain.

Association Between Ambient Air Pollution and Elevated Risk of Tuberculosis Development.

BACKGROUND: Broad-scale evidence has shown the significant association between ambient air pollutants and the development of tuberculosis (TB). However, the impact of air quality on the risk of TB in Taiwan is still poorly understood. OBJECTIVE: To develop a probabilistic integrated population-level risk assessment approach for evaluating the contribution of ambient air pollution exposure to the risk of TB development among different regions of Taiwan. MATERIALS AND METHODS: A Bayesian-based probabilistic risk assessment model was implemented to link exposure concentrations of various air pollutants quantified in a probabilistic manner with the population-based exposure-response models developed by using an epidemiological investigation. RESULTS: The increment of the risk of TB occurred in a region with a higher level of air pollution, indicating a strong relationship between ambient air pollution exposures and TB incidences. Carbon monoxide (CO) exposure showed the highest population attributable fraction (PAF), followed by nitrogen oxides (NOX) and nitrogen dioxide (NO2) exposures. In a region with higher ambient air pollution, it is most likely (80% risk probability) that the contributions of CO exposure to development of TB were 1.6-12.2% (range of median PAFs), whereas NOX and NO2 exposures contributed 1.2-9.8% to developing TB. CONCLUSION: Our findings provide strong empirical support for the hypothesis and observations from the literature that poor air quality is highly likely to link aetiologically to the risk of TB. Therefore, substantial reductions in CO, NOX, and NO2 exposures are predicted to have health benefits to susceptible and latently infected individuals that provide complementary mitigation efforts in reducing the burden of TB. Considering that people continue to be exposed to both TB bacilli and ambient air pollutants, our approach can be applied for different countries/regions to identify which air pollutants contribute to a higher risk of TB in order to develop potential mitigation programs.