The health impact of hazardous waste landfills and illegal dumps contaminated sites: An epidemiological study at ecological level in Italian Region.

Background and aim: The implementation of idoneous management of hazardous waste, in contrast to illegal practices, is one of the environment and health priorities of the WHO. The aim of the present study, based on a collaborative agreement between the Italian National Health Institute and a Prosecution Office located in Naples North, was to evaluate the health effects of illegal landfills and burning of urban and hazardous waste in the territory of the Prosecution Office. Methods: The municipalities included in the study territory were investigated with respect to the regional population. Regression analyses were performed in the study area between four classes of an environmental municipal indicator of waste risk (MRI) previously defined, computing the relative risks (RRs) in 2-4 MRI classes, with respect to the first MRI class (the least impacted). The prevalence of reproductive outcomes and cause-specific mortality and hospitalization were analyzed in the general population and in the 0-19-year-old population using SAS software. Results: An increase of mortality and hospitalization risk in both the genders of the whole area, with respect to regional population, were found for overall all cancer cases, cancer of the stomach, the liver, the lung and the kidney, and ischemic heart diseases. An increase of mortality for leukemias in the 0-19-year-old population and in hospitalization risk for certain conditions originating in the perinatal period were observed. Correlation between MRI and the risk of mortality from breast tumors in women (MRI class 2: RR = 1.06; MRI class 3: RR = 1.15; MRI class 4: RR = 1.11) and between MRI and the risk of hospitalization from testis tumors (MRI class 2: RR = 1.25; MRI class 3: RR = 1.31; MRI class 4: RR = 1.32) were found. The hospitalization risk from breast tumors and asthma exceeded significantly in both genders of three and four MRI classes. Among the 0-19-year-old population, correlation between MRI and hospitalization from leukemias (MRI class 2: RR = 1.48; MRI class 3: RR = 1.60; MRI class 4: RR = 1.41) and between MRI and the prevalence of preterm birth (MRI class 2: RR = 1.17; MRI class 3: RR = 1.08; MRI class 4: RR = 1.25) were found. Conclusion: A correlation between health outcomes and the environmental pressure by uncontrolled waste sites was found. Notwithstanding the limitation of the study, the results promote implementing the actions of environmental remediation and the prosecution of illegal practices.

Investigation and Systematic Risk Assessment in a Typical Contaminated Site of Hazardous Waste Treatment and Disposal.

A total of 214 sampling sites of a hazardous waste disposal center were surveyed in a two-stage pollution investigation, including soil boreholes and groundwater monitoring wells. Results showed that chemical oxygen demand (COD) (4.00-2930.00 mg/L), fluoride (0.07-9.08 mg/L), chromium (0.12-1.20 µg/L), nickel (0.15-459.00 µg/L), lead (0.10-10.20 µg/L), cadmium (Cd) (0.05-16.40 µg/L), and beryllium (0.06-3.48 µg/L) were detected in groundwater samples. For soils, Cd in soil (78.7 mg/kg) exceeded the risk screening value (65 mg/kg) for soil contamination of the second type of development land (GB36600-2018), and there remained the risk of leakage in the landfill detection investigation. Then, a health risk assessment was carried out. Based on the definitions of the groundwater exposure pathway (HJ 25.3-2019) and the pollution investigation of groundwater, the carcinogenic and non-carcinogenic risks of groundwater were generally considered to be negligible. The carcinogenic risk and non-carcinogenic risk of the concerned pollutant in soil for risk assessment (Cd) under the condition of reutilization exceeded the corresponding acceptable levels (1E-06 and 1). The (non-)carcinogenic risk of Cd mainly came from oral intake of soil and inhalation of soil particles under two conditions of reutilization and non-utilization, so on-site workers and surrounding residents should be properly protected from the mouth and nose to minimize the intake of pollutants from the soil and soil particles. The area of soil contaminated by Cd was about 630.58 m2, and the amount of pollution was about 1261.16 m3. The heavy metal pollution was only distributed in the depth range of 0-2 m, and the suggested risk control value of soil pollutants under the condition of reutilization for Cd was 56 mg/kg. Based on different pollution characteristics of soil, groundwater, and the landfill, targeted control measures were proposed.

The release of contaminants from steel slags and natural aggregates: Evaluation of toxicity and genotoxicity.

Steel slags (SS) are the major waste produced by iron and steel industry. Slags may be reused as recycled materials, instead of natural aggregates (NA), to reduce the final disposal in a landfill and the exploitation of raw materials. However, the reuse of SS may generate a potential release of toxic compounds for the environment and humans. The purpose of this study was to evaluate the toxicity and genotoxicity of SS, in comparison with NA, by using an integrated chemical-biological approach to enable their safe reuse in engineering applications. Leaching solutions from samples were obtained by using short-term leaching tests (CEN EN 12457-2, 2004) usually adopted for the evaluation of waste recovery and final disposal. Chemical analyses of leachates were performed according to the Italian legislation on waste recovery (Ministerial Decree 186/2006). The leaching solutions were assayed by using toxicity test on Daphnia magna. Moreover, mutagenicity/genotoxicity tests on Salmonella typhimurium, Allium cepa, and human leucocytes and fibroblasts were carried out. The releases of pollutants from all samples were within the limits of the Italian legislation for waste recovery. Despite the effects that SS and NA could have on different cells, in terms of toxicity and genotoxicity, globally, SS do not seem to be any more hazardous than NA. This ecotoxicological assessment, never studied before, is important for promoting further studies that may support the decision-making process regarding the use of such types of materials.

New Method of Destroying Waste Anesthetic Gases Using Gas-Phase Photochemistry.

BACKGROUND: The inhalation anesthetics are potent greenhouse gases. To reduce the global environmental impact of the health care sector, technologies are sought to limit the release of waste anesthetic gas into the atmosphere. METHODS: Using a photochemical exhaust gas destruction system, removal efficiencies for nitrous oxide, desflurane, and sevoflurane were measured at various inlet concentrations (25% and 50%; 1.5%, 3.0%, and 6.0%; and 0.5%, 1.0%, and 2.0%, respectively) with flow rates ranging from 0.25 to 2.0 L/min. To evaluate the economic competitiveness of the anesthetic waste gas destruction system, its price per ton of carbon dioxide equivalent was calculated and compared to other greenhouse gas abatement technologies and current market prices. RESULTS: All inhaled anesthetics evaluated demonstrate enhanced removal efficiencies with decreasing flow rates (P < .0001). Depending on the anesthetic and its concentration, the photochemical exhaust gas destruction system exhibits a constant first-order removal rate, k. However, there was not a simple relation between the removal rate k and the species concentration. The costs for removing a ton of carbon dioxide equivalents are <$0.005 for desflurane, <$0.114 for sevoflurane, and <$49 for nitrous oxide. CONCLUSIONS: Based on this prototype study, destroying sevoflurane and desflurane with this photochemical anesthetic waste gas destruction system design is efficient and cost-effective. This is likely also true for other halogenated inhalational anesthetics such as isoflurane. Due to differing chemistry of nitrous oxide, modifications of this prototype photochemical reactor system are necessary to improve its removal efficiency for this gas.

Adverse health effects for populations living near waste incinerators with special attention to hazardous waste incinerators. A review of the scientific literature.

Incinerators of municipal, hazardous and medical wastes are sources of emissions of toxic pollutants, being polychlorinated dibenzo-p-dioxins and dibenzofurans, as well as a number of heavy metals of special concern. Moreover, waste incineration also generates ashes that must be properly disposed. In all countries, waste management is currently being an issue of tremendous importance. While the treatment and disposal of municipal solid waste (MSW) is a problem in the entire world, in industrialized countries, the management of hazardous waste (HW) is an additional issue of important concern. While the available scientific information on the environmental impact and the health risks of MSWIs is quite considerable, that related with the potential adverse health effects for the populations living near HWIs is much more reduced. In this paper, we have reviewed the information on health effects-including the incidence of cancer and cancer mortality-for the people residing in the vicinity of HWIs. For a better understanding of the problem, some studies on cancer and other adverse health effects near MSWIs have been also reviewed. Special attention has been paid to the HWI of Constantí (Catalonia, Spain) on which the most complete information among all HWIs in the entire world is available. In our conclusions, a series of important issues/questions are raised: is really safe the limit value of 0.1 ng TEQ/Nm3 for PCDD/Fs to protect human health? Where are the evidences on this? On the other hand, to date, risk assessment studies have been only focused on certain substances; heavy metals and PCDD/Fs. Studies have not included those chemicals that are not routinely analyzed, being even some of them probably unknown right now. Moreover, what about potential interactions among chemicals in order to estimate the carcinogenic and non-carcinogenic risks for the population living near incinerators? Complete epidemiological studies are clearly necessary.

The exposure to water with cigarette residue changes the anti-predator response in female Swiss albino mice.

Recent studies have shown that cigarette consumption affects much more than human health. Smoked cigarette butt (SCB) disposal into the environment can bring little-known negative biological consequences to mammals, since it contains many organic and inorganic toxic chemical constituents. Thus, we aim at assessing whether the ingestion of water with leached SCB for 60 days by female Swiss mice changes their defensive behavioral response to potential predators (cats and snakes). We worked with the following groups of animals: control (pollutant-free water), water with environmental concentration of SCB (1.9 µg/L of nicotine), and concentration 1000 times higher (EC1000×). Our data show that the treatments did not cause locomotor, visual, auditory, and olfactory deficit in the animals. However, we observed that the animals exposed to the pollutants did not present behavioral differences in the test session with or without the snake. On the other hand, animals in all groups showed defensive behavior when the test was conducted with the cat in the apparatus. However, female mice presented weaker response than the control. Thus, our data point towards the potential neurotoxic damage caused to mice who have ingested water with SCB residues, even at low concentrations.

Hazardous waste and health impact: a systematic review of the scientific literature.

Waste is part of the agenda of the European Environment and Health Process and included among the topics of the Sixth Ministerial Conference on Environment and Health. Disposal and management of hazardous waste are worldwide challenges. We performed a systematic review to evaluate the evidence of the health impact of hazardous waste exposure, applying transparent and a priori defined methods. The following five steps, based on pre-defined systematic criteria, were applied. 1. Specify the research question, in terms of "Population-Exposure-Comparators-Outcomes" (PECO). POPULATION: people living near hazardous waste sites; Exposure: exposure to hazardous waste; Comparators: all comparators; Outcomes: all diseases/health disorders. 2. Carry out the literature search, in Medline and EMBASE. 3. Select studies for inclusion: original epidemiological studies, published between 1999 and 2015, on populations residentially exposed to hazardous waste. 4. Assess the quality of selected studies, taking into account study design, exposure and outcome assessment, confounding control. 5. Rate the confidence in the body of evidence for each outcome taking into account the reliability of each study, the strength of the association and concordance of results.Fifty-seven papers of epidemiological investigations on the health status of populations living near hazardous waste sites were selected for the evidence evaluation. The association between 95 health outcomes (diseases and disorders) and residential exposure to hazardous waste sites was evaluated. Health effects of residential hazardous waste exposure, previously partially unrecognized, were highlighted. Sufficient evidence was found of association between exposure to oil industry waste that releases high concentrations of hydrogen sulphide and acute symptoms. The evidence of causal relationship with hazardous waste was defined as limited for: liver, bladder, breast and testis cancers, non-Hodgkin lymphoma, asthma, congenital anomalies overall and anomalies of the neural tube, urogenital, connective and musculoskeletal systems, low birth weight and pre-term birth; evidence was defined as inadequate for the other health outcomes. The results, although not conclusive, provide indications that more effective public health policies on hazardous waste management are urgently needed. International, national and local authorities should oppose and eliminate poor, outdated and illegal practices of waste disposal, including illegal transboundary trade, and increase support regulation and its enforcement.

Assessing the impact of hazardous waste on children's health: The exposome paradigm.

Assessment of the health impacts related to hazardous waste is a major scientific challenge with multiple societal implications. Most studies related to associations between hazardous waste and public health do not provide established of mechanistic links between environmental exposure and disease burden, resulting in ineffective waste management options. The exposome concept comes to overhaul the nature vs. nurture paradigm and embraces a world of dynamic interactions between environmental exposures, endogenous exposures and genetic expression in humans. In this context, the exposome paradigm provides a novel tool for holistic hazardous waste management. Waste streams and the related contamination of environmental media are not viewed in isolation, but rather as components of the expotype, the vector of exposures an individual is exposed to over time. Thus, a multi-route and multi-pathway exposure estimation can be performed setting a realistic basis for integrated health risk assessment. Waste management practices are thus assessed not only regarding their technological edge and efficacy but also their effects on human health at the individual and community level, considering intra-subject variability in the affected population. The effectiveness of the exposome approach is demonstrated in the case of Athens, the capital of Greece, where the health effects associated to long term and short term exposure to two major waste management facilities (landfill and plastic recycling) are presented. Using the exposome analysis tools, we confirmed that proximity to a landfill is critical for children neurodevelopment. However, this effect is significantly modified by parameters such as parental education level, socioeconomic status and nutrition. Proximity to a plastics recycling plant does not pose significant threats under normal operating conditions; yet, in the case of an accidental fire, release of persistent carcinogenic compounds (dioxins and furans) even for a short period results in increased lifelong risk, especially for breast feeding neonates.

Human exposure to environmental pollutants after a tire landfill fire in Spain: Health risks.

In May 2016, a fire occurred in one of the largest landfills in Europe (Seseña, Toledo, Spain), where 70,000-90,000tons of tires had been illegally accumulated for >15years. Because of the proximity of population nuclei and the duration of the episode (>20days), we conducted a preliminary human health risk assessment study just after the tire fire. Samples of air and soil were collected in 3 areas surrounding the landfill (El Quiñón, at only 500m, and Seseña Nuevo and Seseña Viejo, both at 4km), as well as in background sites. In addition, samples of crops (barley, wheat, cabbage and lettuce) were also obtained from local farmers. The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and a number of trace elements (As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, Tl, and V) were analyzed in all the samples. The concentrations of all the target pollutants, excepting PAHs, were relatively similar at the different sampling zones, irrespective of the distance to the landfill. In turn, a significant increase of PAHs was noted near the tire landfill, with air levels up to 6-times higher than those found at 4km (134 vs. 19.5-22.7ng/m3). Similarly, PAH concentrations in lettuce were relatively higher than those typically found in monitoring programs of food safety. Because of the increase of airborne PAHs, cancer risks due to exposure to environmental pollutants for the population living at El Quiñón, near the landfill, were between 3- and 5-times higher than those estimated for the inhabitants of Seseña. After this preliminary study, further investigations, focused only on PAHs, but more extensive in terms of number of samples, should be conducted to assure that PAHs have been progressively degraded through time.

Managing risks of noncancer health effects at hazardous waste sites: A case study using the Reference Concentration (RfC) of trichloroethylene (TCE).

A method for determining a safety range for non-cancer risks is proposed, similar in concept to the range used for cancer in the management of waste sites. This safety range brings transparency to the chemical specific Reference Dose or Concentration by replacing their "order of magnitude" definitions with a scientifically-based range. EPA's multiple RfCs for trichloroethylene (TCE) were evaluated as a case study. For TCE, a multi-endpoint safety range was judged to be 3 µg/m(3) to 30 µg/m,(3) based on a review of kidney effects found in NTP (1988), thymus effects found in Keil et al. (2009) and cardiac effects found in the Johnson et al. (2003) study. This multi-endpoint safety range is derived from studies for which the appropriate averaging time corresponds to different exposure durations, and, therefore, can be applied to both long- and short-term exposures with appropriate consideration of exposure averaging times. For shorter-term exposures, averaging time should be based on the time of cardiac development in humans during fetal growth, an average of approximately 20-25 days.

Environmental pollution from illegal waste disposal and health effects: a review on the "triangle of death".

The term "triangle of death" was used for the first time by Senior and Mazza in the journal The Lancet Oncology referring to the eastern area of the Campania Region (Southern Italy) which has one of the worst records of illegal waste dumping practices. In the past decades, many studies have focused on the potential of illegal waste disposal to cause adverse effects on human health in this area. The great heterogeneity in the findings, and the bias in media communication has generated great healthcare doubts, anxieties and alarm. This paper addresses a review of the up-to-date literature on the "triangle of death", bringing together the available information on the occurrence and severity of health effects related to illegal waste disposal. The Scopus database was searched using the search terms "waste", "Campania", "Naples", "triangle of death" and "human biomonitoring". Despite the methodological and sampling heterogeneity between the studies, this review examines the evidence from published data concerning cancer incidence, childhood mortality and birth defects, so that the current situation, knowledge gaps and research priorities can be established. The review aims to provide a contribution to the scientific community, and to respond to the concerns of the general population.

Incidence of soft tissue sarcomas in an Italian area affected by illegal waste dumping sites.

The aim of the present study was to investigate the possible association between occurrence of soft tissue sarcomas (STS) and residence in an Italian area affected by illegal practices of dumping and setting fire to both hazardous and solid urban wastes. Standardized incidence ratios (SIRs) were computed separately for STS and some specific STS subtypes. The analysis was performed for the total population and for specific age groups, namely, children, adolescents, and adults. In adults, no significant increase in STS was found other than for gastrointestinal stromal tumors in males. A nonsignificant increase in incidence of STS was observed for male children and female adolescents. The results of the present study do not allow conclusions for a causal association. In the absence of previous epidemiological studies on this issue, further investigations are needed.

Hazard property classification of waste according to the recent propositions of the EC using different methods.

Hazard classification of waste is a necessity, but the hazard properties (named "H" and soon "HP") are still not all defined in a practical and operational manner at EU level. Following discussion of subsequent draft proposals from the Commission there is still no final decision. Methods to implement the proposals have recently been proposed: tests methods for physical risks, test batteries for aquatic and terrestrial ecotoxicity, an analytical package for exhaustive determination of organic substances and mineral elements, surrogate methods for the speciation of mineral elements in mineral substances in waste, and calculation methods for human toxicity and ecotoxicity with M factors. In this paper the different proposed methods have been applied to a large assortment of solid and liquid wastes (>100). Data for 45 wastes - documented with extensive chemical analysis and flammability test - were assessed in terms of the different HP criteria and results were compared to LoW for lack of an independent classification. For most waste streams the classification matches with the designation provided in the LoW. This indicates that the criteria used by LoW are similar to the HP limit values. This data set showed HP 14 'Ecotoxic chronic' is the most discriminating HP. All wastes classified as acute ecotoxic are also chronic ecotoxic and the assessment of acute ecotoxicity separately is therefore not needed. The high number of HP 14 classified wastes is due to the very low limit values when stringent M factors are applied to total concentrations (worst case method). With M factor set to 1 the classification method is not sufficiently discriminating between hazardous and non-hazardous materials. The second most frequent hazard is HP 7 'Carcinogenic'. The third most frequent hazard is HP 10 'Toxic for reproduction' and the fourth most frequent hazard is HP 4 "Irritant - skin irritation and eye damage". In a stepwise approach, it seems relevant to assess HP 14 first, then, if the waste is not classified as hazardous, to assess subsequently HP 7, HP 10 and HP 4, and then if still not classified as hazardous, to assess the remaining properties. The elements triggering the HP 14 classification in order of importance are Zn, Cu, Pb, Cr, Cd and Hg. Progress in the speciation of Zn and Cu is essential for HP 14. Organics were quantified by the proposed method (AFNOR XP X30-489) and need no speciation. Organics can contribute significantly to intrinsic toxicity in many waste materials, but they are only of minor importance for the assessment of HP 14 as the metal concentrations are the main HP 14 classifiers. Organic compounds are however responsible for other toxicological characteristics (hormone disturbance, genotoxicity, reprotoxicity…) and shall be taken into account when the waste is not HP 14 classified.

[SENTIERI Project: rationale and objectives]. / Razionale e obiettivi del Progetto SENTIERI.

The Istituto Superiore di Sanità (National Institute of Health-ISS), in partnership with a network of Italian national and regional scientific institutions, initiated the SENTIERI Project (Epidemiological Study of Residents in Italian Contaminated Sites-NPCSs), the objectives, methods and initial results of which were published by Epidemiologia & Prevenzione in 2010 and 2011. In the course of 2013, some of the SENTIERI Project findings were published in international scientific journals, and the "SENTIERI approach" was among those sanctioned by the World Health Organization to conduct an initial description of the health status of residents of contaminated sites. The present Report, set up jointly by ISS and the Italian Network of Cancer Registries (AIRTUM), as anticipated in the 2011 Report, aims to provide, for each of the 18 National Priority Contaminated Sites included in the SENTIERI Project where the Italian Association of Cancer Registries is active, a mortality update to 2010, analyses of cancer incidence (1996-2005 in 17 NPCSs) and of hospital discharges (2005-2010), as is explained in detail in Chapter 2, pertaining to the project's materials and methods. The results of the analyses for each NPCS are presented in Chapter 3, while Chapter 4 includes a critical appraisal, a discussion of the methodological approach and a series of concluding remarks. The second section of the Report takes an in-depth look at important issues of public health and scientific research in contaminated sites. This Report represents an important step towards implementing a permanent epidemiological surveillance system in Italy's contaminated sites, the ultimate goal of the SENTIERI Project.

[SENTIERI Project: materials and methods]. / Materiali e metodi del Progetto SENTIERI.

The Report considers three health outcomes - mortality, cancer incidence and hospital discharges - studied using homogenous methods and using data from official sources, namely the National Institute of Statistics (Istat), Italian Network of Cancer Registries (AIRTUM) and the Health Ministry. The timeframes of observation are: 2003-2010 for mortality, 1996-2005 for cancer incidence and 2005-2010 for hospital discharges. The causes of death are those examined by the SENTIERI Project. Hospital discharges are analysed with reference to the main diagnosis. The study of cancer incidence applies to the sites selected by AIRTUM. Statistical parameters (SMR, Standardized Mortality Ratio; SIR, Standardized Incidence Ratio; SHR, Standardized Hospitalization Ratio) were computed with a 90% confidence interval; the estimators were adjusted for age and socioeconomic status.

Characterization and environmental risk assessment of heavy metals found in fly ashes from waste filter bags obtained from a Chinese steel plant.

The environmental risk of exposure to six heavy metals (Cu, Pb, Zn, Cr, Ni, and Cd) found in fly ashes from waste filter bags obtained from a steel plant was estimated based on the mineralogical compositions, total concentrations and speciation of the metals in the fly ashes. The results indicated that the fly ashes mainly consisted of hematite, magnetite, cyanite, spinel, coesite and amorphous materials. The concentrations of Zn and Pb were much higher than that of other materials. After Zn and Pb, Ni was present in the highest concentration, followed by Cu, Cr and Cd. Each heavy metal was distributed differently in fly ashes. The levels of Zn, Cd and Pb in the active fraction were very high, and ranged from 64.83 to 81.96%, 34.48 to 82.4% and 6.92 to 79.65% respectively, while Cu, Cr and Ni were mainly present in the residual fraction. The risk assessment code (RAC) values of fly ashes showed that the Zn and Cd present in the H3 sample presented a very high risk, with RAC values greater than 50%. The Cu present in the H3 sample, Cd in the H2 sample and Zn in the H4 and H5 samples presented a high risk. The Pb present in the H2 sample, Cd in the H4 sample, Ni in the H1 and H5 samples, and Zn in the H1 sample presented a medium risk. A low risk was presented by the Cu present in the H1, H2, H4 and H5 samples, the Pb in the H1, H3 and H5 samples, the Cd in the H1 and H5 samples, and the Ni in the H2 sample. No risk was presented by Cr in any sample.

Environmental and occupational exposure to chemicals and telomere length in human studies.

Telomeres are complexes of tandem repeats of DNA (5'-TTAGGG-3') and protein that cap eukaryotic chromosomes and play a critical role in chromosome stability. Telomeres shorten with aging and this process can be accelerated by increased oxidative stress and episodes of inflammation. Evidence is rapidly growing that telomere length (TL) may be affected by environmental chemicals that have frequently been associated with chronic diseases. In this article, we review the published data on TL in relation to environmental and occupational exposure to several chemicals based on our own and others' studies. The environmental and occupational exposures associated with shorter TL include traffic-related air pollution (ie, particulate matter (PM), black carbon (BC), and benzene and toluene), polycyclic aromatic hydrocarbons (PAHs), N-nitrosamines, pesticides, lead, exposure in car mechanical workshops, and hazardous waste exposure. Arsenic, persistent organic pollutants (POPs) and short-term exposure to PM are associated with longer TL. We discuss the possible reasons for the differences in results, including time- and dose-related issues, study design, and possible mechanisms involved in telomere regulation. We also discuss the future directions and challenges for TL-related environmental and occupational health research, such as investigation of TL in subpopulations of blood leukocytes, and the study of genetic and epigenetic factors that may regulate telomere integrity using longitudinal designs.