Skip to main content
SpringerLink
Log in

Biomarkers of Tobacco Use: Relevance to Tobacco Harm Reduction

  • Living reference work entry
  • First Online:
Biomarkers in Toxicology

  • 30 Accesses

Abstract

Cigarette smoking is associated with a large number of adverse health outcomes and continues to be a major contributor to death and disease. Although the best option for cigarette smokers concerned about their health is cessation, tobacco harm reduction is the public health concept that cigarette smokers who are unwilling or unable to quit smoking can switch to alternative non-combustible nicotine-containing products in order to reduce or minimize adverse health effects. Long-term epidemiological studies of alternative non-combustible nicotine-containing products are ideal for the evaluation of product use and clinical disease outcomes. However, in many cases such studies are not available. Biomarkers of exposure and potential harm, relevant to both combustible cigarette exposure and smoking-related diseases, are useful in the assessment of potential changes in health effects resulting from switching to alternative non-combustible nicotine-containing products.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

Abbreviations

2,3-d-TXB2:

2,3-dinor thromboxane B2

(±)-5-iPF2α-VI:

(±)-5-iso-prostaglandin F2α

8-OHdG:

8-hydroxy-2′-deoxyguanosine

8-epi-PGF2α:

8-iso-prostaglandin F2α

11-DH-TXB2:

11-dehydro-thromboxane B2

BoE:

Biomarkers of exposure

BoPH:

Biomarkers of potential harm

CDC:

Centers for Disease Control

ENDS:

Electronic nicotine delivery systems

FDA:

Food and Drug Administration

ICAM-1:

Intercellular adhesion molecule-1

IL-8:

Interleukin 8

IL-12:

Interleukin 12

IOM:

Institute of Medicine

LTE4:

Leukotriene E4

NASEM:

National Academies of Sciences, Engineering, and Medicine

PHE:

Public Health England

PRR:

Potentially reduced risk

PRE:

Potentially reduced exposure

SAMHSA:

Substance Abuse and Mental Health Services Administration

THP:

Tobacco heating products

THR:

Tobacco harm reduction

US:

United States

WBC:

White blood cells

WHO:

World Health Organization

References

  • Abrams DB, Glasser AM, Pearson JL, et al. Harm minimization and tobacco control: reframing societal views of nicotine use to rapidly save lives. Annu Rev Public Health. 2018;39:193–213.

    Article  PubMed  PubMed Central  Google Scholar 

  • Akiyama Y, Sherwood N. Systematic review of biomarker findings from clinical studies of electronic cigarettes and heated tobacco products. Toxicol Rep. 2021;8:282–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Auer R, Concha-Lozano N, Jacot-Sadowski I, et al. Heat-not-burn tobacco cigarettes: smoke by any other name. JAMA Intern Med. 2017;177(7):1050–2.

    Article  PubMed  PubMed Central  Google Scholar 

  • Balfour DJ, Benowitz NL, Colby SM, et al. Balancing consideration of the risks and benefits of e-cigarettes. Am J Public Health. 2021;19(0):e1–2.

    Google Scholar 

  • Benowitz NL, St. Helen G, Nardone N, et al. Twenty-four-hour cardiovascular effects of electronic cigarettes compared with cigarette smoking in dual users. J Am Heart Assoc. 2020;9(23):e017317.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campbell LR, Brown BG, Jones BA, et al. Study of cardiovascular disease biomarkers among tobacco consumers, part 1: biomarkers of exposure. Inhal Toxicol. 2015;27(3):149–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Centers for Disease Control and Prevention (CDC). Smoking & tobacco use fast facts. Accessed via Fast Facts | Fact Sheets | Smoking & Tobacco Use | CDC; 2021. Accessed 21 Aug 2021.

    Google Scholar 

  • Chang CM, Edwards SH, Arab A, et al. Biomarkers of tobacco exposure: summary of an FDA-sponsored public workshop. Cancer Epidemiol Biomarkers Prev. 2017;26(3):291–302.

    Article  CAS  PubMed  Google Scholar 

  • Chang CM, Cheng Y, Cho TM, et al. Biomarkers of potential harm: summary of an FDA-sponsored public workshop. Nicotine Tob Res. 2019;21(1):3–13.

    Article  CAS  PubMed  Google Scholar 

  • Cheng YC, Reyes-Guzman CM, Christensen CH, et al. Biomarkers of exposure among adult smokeless tobacco users in the Population Assessment of Tobacco and Health Study (Wave 1, 2013–2014). Cancer Epidemiol Biomarkers Prev. 2020;29(3):659–67.

    Article  PubMed  PubMed Central  Google Scholar 

  • Christensen CH, Chang JT, Rostron BL. Biomarkers of inflammation and oxidative stress among adult former smoker, current e-cigarette users results from wave 1 path study. Cancer Epidemiol Biomarkers Prev. 2021;30:1947.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cornelius ME, Loretan CG, Wang TW, Jamal A et al. Tobacco product use among adults – United States, 2020. MMWR Morb Moral Wkly Rep. 2022;71:397–405.

    Google Scholar 

  • Ding YS, Blount BC, Valentin-Blasini L, et al. Simultaneous determination of six mercapturic acid metabolites of volatile organic compounds in human urine. Chem Res Toxicol. 2009;22(6):1018–25.

    Article  CAS  PubMed  Google Scholar 

  • Djurdjevic S, Pecze L, Weitkunat R, et al. Using data on snus use in Sweden to compare different modelling approaches to estimate the population health impact of introducing a smoke-free tobacco product. BMC Public Health. 2019;19(1):1–3.

    Article  Google Scholar 

  • Drope J, Schluger N, Cahn Z, et al. The tobacco atlas. Atlanta: American Cancer Society and Vital Strategies; 2018. Available via Deaths | Tobacco Atlas. Accessed 21 Aug 2021.

    Google Scholar 

  • Food and Drug Administration (FDA). Harmful and potentially harmful constituents in tobacco products. Established list. Fed Reg. 2012;77:20034.

    Google Scholar 

  • Food and Drug Administration (FDA). CTP’s key strategic priorities. Available via CTP’s Key Strategic Priorities | FDA; 2017. Accessed 3 Sept 2021.

    Google Scholar 

  • Food and Drug Administration (FDA). FDA grants first-ever modified risk orders to eight smokeless tobacco products. Available via FDA grants first-ever modified risk orders to eight smokeless tobacco products | FDA; 2019a. Accessed 1 Sept 2021.

    Google Scholar 

  • Food and Drug Administration (FDA). What CTP does. Available via What CTP Does | FDA; 2019b. Accessed 3 Sept 2021.

    Google Scholar 

  • Food and Drug Administration (FDA). FDA Authorizes Marketing of IQOS Tobacco Heating System with ‘Reduced Exposure’ Information. Available via FDA Authorizes Marketing of IQOS Tobacco Heating System with ‘Reduced Exposure’ Information | FDA; 2020. Accessed 31 Aug 2021.

    Google Scholar 

  • Frost-Pineda K, Liang Q, Liu J, et al. Biomarkers of potential harm among adult smokers and nonsmokers in the total exposure study. Nicotine Tob Res. 2011;13(3):182–93.

    Article  CAS  PubMed  Google Scholar 

  • Gale N, McEwan M, Camacho OM, et al. Changes in biomarkers after 180 days of tobacco heating product use: a randomised trial. Intern Emerg Med. 2021a;16:2201–12.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gale N, McEwan M, Camacho OM, et al. Changes in biomarkers of exposure on switching from a conventional cigarette to the glo tobacco heating product: a randomized, controlled ambulatory study. Nicotine Tob Res. 2021b;23(3):584–91.

    Article  CAS  PubMed  Google Scholar 

  • Goniewicz ML, Gawron M, Smith DM, et al. Exposure to nicotine and selected toxicants in cigarette smokers who switched to electronic cigarettes: a longitudinal within-subjects observational study. Nicotine Tob Res. 2017;19(2):160–7.

    Article  CAS  PubMed  Google Scholar 

  • Gregg EO, Minet E, McEwan M. Urinary biomarkers of smokers’ exposure to tobacco smoke constituents in tobacco products assessment: a fit for purpose approach. Biomarkers. 2013;18(6):467–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halvorsen B, Sagen E, Ueland T, et al. Effect of smoking cessation on markers of inflammation and endothelial cell activation among individuals with high risk for cardiovascular disease. Scand J Clin Lab Invest. 2007;67:604–11.

    Article  CAS  PubMed  Google Scholar 

  • Hatsukami DK, Benowitz NL, Rennard SI, et al. Biomarkers to assess the utility of potential reduced exposure tobacco products. Nicotine Tob Res. 2006;8(4):600–22.

    Article  PubMed  Google Scholar 

  • Hatsukami DK, Joseph AM, LeSage M, et al. Developing the science base for reducing tobacco harm. Nicotine Tob Res. 2007;9(Suppl 4):S537–53.

    Article  PubMed  Google Scholar 

  • Hawk M, Coulter RW, Egan JE, et al. Harm reduction principles for healthcare settings. Harm Reduct J. 2017;14(1):1–9.

    Article  Google Scholar 

  • Haziza C, de La Bourdonnaye G, Merlet S, et al. Assessment of the reduction in levels of exposure to harmful and potentially harmful constituents in Japanese subjects using a novel tobacco heating system compared with conventional cigarettes and smoking abstinence: a randomized controlled study in confinement. Regul Toxicol Pharm. 2016a;81:489–99.

    Article  CAS  Google Scholar 

  • Haziza C, de La Bourdonnaye G, Skiada DA, et al. Evaluation of the Tobacco Heating System 2.2. Part 8: 5-Day randomized reduced exposure clinical study in Poland. Regul Toxicol Pharmacol. 2016b;81:S139–50.

    Article  CAS  PubMed  Google Scholar 

  • Haziza C, de La Bourdonnaye G, Donelli A, et al. Favorable changes in biomarkers of potential harm to reduce the adverse health effects of smoking in smokers switching to the menthol tobacco heating system 2.2 for 3 months (part 2). Nicotine Tob Res. 2020a;22:549–59.

    Article  PubMed  Google Scholar 

  • Haziza C, de La Bourdonnaye G, Donelli A, et al. Reduction in exposure to selected harmful and potentially harmful constituents approaching those observed upon smoking abstinence in smokers switching to the menthol Tobacco Heating System 2.2 for 3 Months (part 1). Nicotine Tob Res. 2020b;22:539–48.

    Article  PubMed  Google Scholar 

  • Hecht S, Carmella S, Kotandeniya D, et al. Evaluation of toxicant and carcinogen metabolites in the urine of e-cigarette users versus cigarette smokers. Nicotine Tob Res. 2015;17(6):704–9.

    Article  CAS  PubMed  Google Scholar 

  • Henley SJ, Thun MJ, Connell C, et al. Two large prospective studies of mortality among men who use snuff or chewing tobacco (United States). Cancer Causes Control. 2005;16(4):347–58.

    Article  PubMed  Google Scholar 

  • Henley SJ, Connell CJ, Richter P, et al. Tobacco-related disease mortality among men who switched from cigarettes to spit tobacco. Tob Control. 2007;16(1):22–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Igarashi A, Aida J, Kusama T, et al. Heated tobacco products have reached younger or more affluent people in Japan. J Epidemiol. 2021;31(3):187–93.

    Article  PubMed  PubMed Central  Google Scholar 

  • Institute of Medicine (IOM). Clearing the smoke: assessing the science base for tobacco harm reduction. Washington, DC; 2001.

    Google Scholar 

  • Institute of Medicine (IOM). Scientific standards for studies on modified risk tobacco products. Washington, DC; 2012.

    Google Scholar 

  • Koundouros E, Odell E, Coward P, et al. Soluble adhesion molecules in serum of smokers and non-smokers, with and without periodontitis. J Periodontal Res. 1996;31:596–9.

    Article  CAS  PubMed  Google Scholar 

  • Krautter GR, Chen PX, Borgerding MF. Consumption patterns and biomarkers of exposure in cigarette smokers switched to Snus, various dissolvable tobacco products, Dual use, or tobacco abstinence. Regul Toxicol Pharmacol. 2015;71(2):186–97.

    Article  CAS  PubMed  Google Scholar 

  • Lee PN. Circulatory disease and smokeless tobacco in Western populations: a review of the evidence. Int J Epidemiol. 2007;36(4):789–804.

    Article  PubMed  Google Scholar 

  • Lee PN, Hamling J. Systematic review of the relation between smokeless tobacco and cancer in Europe and North America. BMC Med. 2009;7(1):1–47.

    Article  CAS  Google Scholar 

  • Lowe FJ, Gregg EO, McEwan M. Evaluation of biomarkers of exposure and potential harm in smokers, former smokers and never smokers. Clin Chem Lab Med. 2009;47:311–20.

    Article  CAS  PubMed  Google Scholar 

  • Lüdicke F, Baker G, Magnette J, et al. Reduced exposure to harmful and potentially harmful smoke constituents with the tobacco heating system 2.1. Nicotine Tob Res. 2017;19(2):168–75.

    Article  PubMed  Google Scholar 

  • Lüdicke F, Picavet P, Baker G, et al. Effects of switching to the menthol Tobacco Heating System 2.2, smoking abstinence, or continued cigarette smoking on clinically relevant risk markers: a randomized, controlled, open-label, multicenter study in sequential confinement and ambulatory settings (part 2). Nicotine Tob Res. 2018;20(2):173–82.

    Article  PubMed  Google Scholar 

  • Makena P, Liu G, Chen P, et al. Urinary leukotriene E4 and 2, 3-dinor thromboxane B2 are biomarkers of potential harm in short-term tobacco switching studies. Cancer Epidemiol Biomarkers Prev. 2019;28(12):2095–105.

    Article  CAS  PubMed  Google Scholar 

  • Marano KM, Kathman SJ, Jones BA, et al. Study of cardiovascular disease biomarkers among tobacco consumers. Part 3: evaluation and comparison with the US National Health and Nutrition Examination Survey. Inhal Toxicol. 2015;27:167–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marques H, Cruz-Vicente P, Rosado T, et al. Recent developments in the determination of biomarkers of tobacco smoke exposure in biological specimens: a review. Int J Environ Res Public Health. 2021;18(4):1768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McEwan M, Gale N, Ebajemito JK, et al. A randomized controlled study in healthy participants to explore the exposure continuum when smokers switch to a tobacco heating product or an e-cigarette relative to cessation. Toxicol Rep. 2021;8:994–1001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McNeill A, Brose LS, Calder R, et al. Evidence review of e-cigarettes and heated tobacco products 2018 – A Report Commissioned by Public Health England. London; 2018.

    Google Scholar 

  • National Academies of Sciences, Engineering, and Medicine (NASEM). Public health consequences of e-cigarettes. Washington, DC: The National Academies Press; 2018.

    Google Scholar 

  • National Institute for Health Care and Excellence (NICE). Smoking: harm reduction, public health guideline [PH45]. Available via Overview | Smoking: harm reduction | Guidance | NICE; 2013. Accessed 3 Sept 2021.

    Google Scholar 

  • Naufal ZS, Marano KM, Kathman SJ, et al. Differential exposure biomarker levels among cigarette smokers and smokeless tobacco consumers in the National Health and Nutrition Examination Survey 1999–2008. Biomarkers. 2011;16(3):222–35.

    Article  CAS  PubMed  Google Scholar 

  • Nordskog BK, Brown BG, Marano KM, Campbell LR et al. Study of cardiovascular disease biomarkers among tobacco consumers, part 2, bimarkers of biological effect. Inhal Toxicol. 2015;27(3):157–66.

    Google Scholar 

  • Nutt DJ, Phillips LD, Balfour D, et al. Estimating the harms of nicotine-containing products using the MCDA approach. Eur Addict Res. 2014;20(5):218–25.

    Article  PubMed  Google Scholar 

  • O’Connell G, Graff DW, D’Ruiz CD. Reductions in biomarkers of exposure (BoE) to harmful or potentially harmful constituents (HPHCs) following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers. Toxicol Mech Methods. 2016;26(6):443–54.

    Article  PubMed  Google Scholar 

  • Odani S, Tabuchi T. Prevalence of heated tobacco product use in Japan: the 2020 JASTIS study. Tob Control. 2021; https://doi.org/10.1136/tobaccocontrol-2020-056257.

  • Ogden MW, Marano KM, Jones BA, et al. Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: part 2. Biomarkers of exposure. Biomarkers. 2015a;20(6–7):391–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ogden MW, Marano KM, Jones BA, et al. Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: part 3. Biomarkers of biological effect. Biomarkers. 2015b;20(6-7):404–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oliveri D, Liang Q, Sarkar M. Real-world evidence of differences in biomarkers of exposure to select harmful and potentially harmful constituents and biomarkers of potential harm between adult E-vapor users and adult cigarette smokers. Nicotine Tob Res. 2020;22(7):1114–22.

    Article  CAS  PubMed  Google Scholar 

  • Prasad GL, Jones BA, Chen P, et al. A cross-sectional study of biomarkers of exposure and effect in smokers and moist snuff consumers. Clin Chem Lab Med. 2016;54(4):633–42.

    Article  CAS  PubMed  Google Scholar 

  • Ramström L, Wikmans T. Mortality attributable to tobacco among men in Sweden and other European countries: an analysis of data in a WHO report. Tob Induc Dis. 2014;12(1):1–4.

    Article  Google Scholar 

  • Ramström L, Borland R, Wikmans T. Patterns of smoking and snus use in Sweden: implications for public health. Int J Environ Res Public Health. 2016;13(11):1110.

    Article  PubMed Central  Google Scholar 

  • Riedel K, Scherer G, Engl J, et al. Determination of three carcinogenic aromatic amines in urine of smokers and nonsmokers. J Anal Toxicol. 2006;30(3):187–95.

    Article  CAS  PubMed  Google Scholar 

  • Rostron BL, Chang CM, van Bemmel DM, et al. Nicotine and toxicant exposure among US smokeless tobacco users: results from 1999 to 2012 National Health and Nutrition Examination Survey Data. Cancer Epidemiol Biomarkers Prev. 2015;24(12):1829–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Round EK, Chen P, Taylor AK, et al. Biomarkers of tobacco exposure decrease after smokers switch to an e-cigarette or nicotine gum. Nicotine Tob Res. 2018;21(9):1239–47.

    Article  PubMed Central  Google Scholar 

  • Royal College of Physicians (RCP). Nicotine without smoke: Tobacco harm reduction. A report by the Tobacco Advisory Groups of the Royal College of Physicians; 2016.

    Google Scholar 

  • Sakaguchi C, Nagata Y, Kikuchi A, et al. Differences in levels of biomarkers of potential harm among users of a heat-not-burn tobacco product, cigarette smokers, and never-smokers in Japan: a post-marketing observational study. Nicotine Tob Res. 2021;23(7):1143–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scherer G. Suitability of biomarkers of biological effects (BOBEs) for assessing the likelihood of reducing the tobacco related disease risk by new and innovative tobacco products: a literature review. Regul Toxicol Pharmacol. 2018;94:203–33.

    Article  CAS  PubMed  Google Scholar 

  • Scherer G, Urban M, Engl J, et al. Influence of smoking charcoal filter tipped cigarettes on various biomarkers of exposure. Inhal Toxicol. 2006;18(10):821–9.

    Article  CAS  PubMed  Google Scholar 

  • Shahab L, Goniewicz ML, Blount BC, et al. Nicotine, carcinogen, and toxin exposure in long-term e-cigarette and nicotine replacement therapy users: a cross-sectional study. Ann Intern Med. 2017;166(6):390–400.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shepperd CJ, Newland N, Eldridge A, et al. Changes in levels of biomarkers of exposure and biological effect in a controlled study of smokers switched from conventional cigarettes to reduced-toxicant-prototype cigarettes. Regul Toxicol Pharmacol. 2015;72(2):273–91.

    Article  CAS  PubMed  Google Scholar 

  • Stewart C. Smokers in Sweden 2019, by frequency. Available via • Sweden: smokers, by frequency 2019 | Statista; 2020. Accessed 30 Aug 2021.

    Google Scholar 

  • Stokes AC, Xie W, Wilson AE, et al. Association of cigarette and electronic cigarette use patterns with levels of inflammatory and oxidative stress biomarkers among US adults: population assessment of tobacco and health study. Circulation. 2021;143(8):869–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Substance Abuse and Mental Health Services Administration (SAMHSA). 2022. https://www.samhsa.gov/find-help/harm-reduction. Accessed 17 Mar 2022.

  • US Department of Health and Human Services (USDHHS). How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease: a report of the surgeon general. Available via How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease – NCBI Bookshelf (nih.gov); 2010. Accessed 20 Aug 2021.

    Google Scholar 

  • World Health Organization. WHO framework convention on tobacco control. World Health Organization; 2003.

    Google Scholar 

  • Xue C, Chen QZ, Bian L, et al. Effects of smoking cessation with nicotine replacement therapy on vascular endothelial function, arterial stiffness, and inflammation response in healthy smokers. Angiology. 2019;70(8):719–25.

    Article  CAS  PubMed  Google Scholar 

  • Zeller M. Evolving “The Real Cost” campaign to address the rising epidemic of youth e-cigarette use. Am J Prev Med. 2019;56(2):S76–8.

    Article  PubMed  Google Scholar 

  • Zeller M, Hatsukami D, et al. The strategic dialogue on tobacco harm reduction: a vision and blueprint for action in the US. Tob Control. 2009;18(4):324–32.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. RAI Services Company, Winston-Salem, NC, USA

    Elaine K. Round

  2. Womble Bond Dickinson (US) LLP, Winston-Salem, NC, USA

    Kristin Marano

Authors
  1. Elaine K. Round
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kristin Marano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elaine K. Round .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. Sch Biomed & Health Sci, Wilkins Bldg, King's College London Franklin, London, UK

    Victor R. Preedy

  3. Department of Medicine, King Abdulaziz Med City, Riyadh, Saudi Arabia

    Rajkumar Rajendram

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Round, E.K., Marano, K. (2022). Biomarkers of Tobacco Use: Relevance to Tobacco Harm Reduction. In: Patel, V.B., Preedy, V.R., Rajendram, R. (eds) Biomarkers in Toxicology. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Cham. https://doi.org/10.1007/978-3-030-87225-0_51-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-87225-0_51-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-87225-0

  • Online ISBN: 978-3-030-87225-0

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation