Skip to main content

Characterization of heavy users of skin care products among Norwegian women from 2003 to 2011

Abstract

Background

Several ingredients in personal care products (PCPs) have been classified as endocrine disruptors (EDs) and concern has been raised whether use of PCPs can affect human health. We aimed to characterize Norwegian female users of skin care products and compare life style characteristics between heavy users and non-users.

Methods

This cross-sectional study consisted of 114 202 women (age 41–76 years) participating in the Norwegian Women and Cancer study, a large population-based prospective cohort study. Based on self-reported questionnaire data, we classified the study subjects into five groups according to a calculated percentage of skin area creamed per day. Life-style characteristics were then compared between heavy users (using body lotion twice a day) and non-users. Change in use from 2003 to 2011 was assessed through repeated measurements (n = 8484).

Results

Heavy users of skin care products had a significantly lower BMI, higher level of physical activity, higher income, higher alcohol consumption, fewer children and a shorter total time of breastfeeding than non-users (p < 0.001). There were significantly fewer current smokers and more former smokers among heavy users than among non-users (p < 0.01). Current and earlier use of oral contraceptives, hormone replacement therapy or hormonal intra-uterine device were significantly more common among heavy users than among non-users (p < 0.01). The use of skin care products was, to a moderate extent (weighted kappa 0.52), consistent over time from 2003 to 2011, and as many as 91.5% of the women were classified into the same user group ±1 category in 2003 and 2011.

Conclusions

Heavy users of skin care products differ significantly from non-users on BMI, degree of daily physical activity, income, number of children, use of hormonal pharmaceuticals, smoking and alcohol consumption. Use of skin care products is common among women aged 41–76 years in Norway, and the use is consistent over time.

Peer Review reports

Background

The use of personal care products (PCPs), such as skin care products, deodorant and tooth paste are currently a part of many people’s daily hygiene routine. Some of the ingredients in PCPs have been identified as endocrine disruptors (EDs), i.e. molecules that are able to affect and interfere with the hormonal system of humans or wildlife. After dermal application of PCPs, possible EDs are easily absorbed by the epidermis into the subcutaneous tissue and the central blood circulation and concern has therefore been raised whether the use of PCPs can affect human health.

Of possible EDs in PCPs, frequently mentioned are ultraviolet-filters (UV-filters), triclosan, phthalates and parabens [1]. Some of the UV-filters found in sunscreen products show endocrine disruptive activity in vitro and/or in vivo [2]. Triclosan has been a preservative in PCPs since the late 1960s, and has been detected in human fluids like urine, serum and breast milk [3]. Triclosan can bind to both the estrogen and the androgen receptor, but in vitro and in vivo consequences of this have been diverse [3]. Phthalates, also called plasticizers, are a group of molecules increasing the softness of plastics. Phthalates can appear in fragrances and hair products as fixatives [4], but also leak from packaging material into the product. Their endocrine disrupting mechanism has been suggested to be interference with testosterone production or the testosterone action [1]. Parabens have been one of the most frequently used preservatives in PCPs since the beginning of the 20th century [5]. Parabens are able to bind to the estrogen receptor [6], and the affinity increases with the length of the alkyl chain. Long chained parabens (isopropylparaben, isobutylparaben, phenylparaben, benzylparaben and pentylparaben) have been banned in PCPs within the European Union (EU) during the last years, and the concentrations for propyl- and butylparaben in PCPs have recently been reduced [7].

In our recent study [8], we found elevated concentrations of methylparaben (MP) in blood samples from Norwegian women frequently using skin care products (defined as creams and lotions for skin care), indicating that everyday use may keep the concentration of parabens continuously high in blood, despite a short half-life. A recent Swedish study found a correlation between urinary concentrations of parabens and the use of PCPs, and a US study found a correlation between urinary concentrations of some phenols and phthalate metabolites and the use of PCPs in both adults and children, suggesting that the use of PCPs is an important source of exposure to several EDs [4, 9].

PCPs often contain a complex mixture of EDs, and as there is limited knowledge about the collective effect of these chemicals on human health, population studies addressing the association between PCP use and hormonally related diseases are needed. As a first step in this process, it is important to characterize the heavy users of these products.

Between 2003 and 2011, more than 100 000 women in the Norwegian Women and Cancer (NOWAC) study answered questionnaires covering a large number of lifestyle factors including the use of skin care products. The aim of this study was to describe and compare lifestyle characteristics between heavy users of skin care products and non-users. To the best of our knowledge, published studies on use of skin care products have not involved a sample of this size, nor a characterization of the participants regarding life style characteristics and endocrine events in a woman’s life such as menarche, pregnancy, breastfeeding and menopause, which are important factors for hormonally related diseases.

Methods

Study cohort

NOWAC is a population based prospective cohort study, initiated in 1991 with the aim of investigating the etiology of different cancers among Norwegian women [10]. More than 170 000 Norwegian women aged 30–70 years when entering the study have been enrolled in the study so far. The participating women are randomly chosen from the National Population Registry in Norway, and invited to participate in the survey through an invitation letter sent to their home address. All participants have answered a detailed questionnaire on current health status, diet, medication use, physical activity and other lifestyle habits at enrollment. The questionnaires have been distributed in series and the questions in the different series have varied a little over years. The external validity of the NOWAC study has been thoroughly evaluated and found satisfactory and without selection bias [11].

Assessment of use of skin care products

In the distributed questionnaires, the participants were asked how often they use skin care products named as body lotion, hand cream and facial cream (never/seldom, 1–3 times per month, once a week, 2–4 times per week, 5–6 times per week, 1 time/day and 2 or more times/day). We converted the reported frequency of a certain cream type into a percentage of body surface covered in cream. Use of body lotion once per day was set equivalent to 91% of the body surface covered in cream, hand cream 6% and facial cream 3% (Additional file 1: Table S1). When the use of each of these was reported once per day, 100% of the body surface was covered in cream. Further, using body lotion once per week corresponds to a seventh of 91%, i.e., 13% of the body surface covered in cream per day. These conversions were similar to our previous article [8]. Total body area creamed per day was calculated as the sum of the percentage surface area covered by body lotion, hand cream and facial cream. If a study subject had answered at least one question on use of skin care products, a missing value on the other cream or lotion questions was interpreted as “never/seldom” (n = 1776). By this procedure, we could have underestimated the use of skin care products for these women, however, running the analyses without these subjects did not change the results and they were therefore included.

Assessment of life style characteristics

The age of the woman at the time of filling in the questionnaire was extracted from the National Population Registry. The women were asked to report their current weight (kg) and height (cm) in the questionnaire, and body mass index (BMI, kg/m2) was calculated. The women were also asked how many years of education they had in total and the yearly income of their household. Overall current physical activity level (including both recreational and occupational activity) was recorded on a rating scale from 1 (very low) to 10 (very high), which has been validated against a combined heart rate and movement sensor according to the European Prospective Investigation into Cancer and Nutrition protocol [12]. Questions about smoking history and current smoking were combined into a variable for smoking status (never, former and current). The participants were asked whether they were absolutists or how often they drink different types of alcohol (beer, wine or strong spirits); never/seldom, 1–3 times/month, 1 time/week, 2–4 times/week, 5–6 times/week, 1 time/day and ≥2 times/day). The recorded frequency was later converted to a combined equivalent of alcohol consumption in grams of pure alcohol per day, described in more detail by Dumeaux et al. [13]. Age at first birth was calculated from the birth year of the woman and the birth year of the child, which was requested in the questionnaire. The women were asked about how many children they had, and how many months they had been breastfeeding throughout their life-course. Age at menarche and menopause was also inquired. Questions on use of oral contraceptives (OC), hormone replacement therapy (HRT) and hormone releasing intrauterine device (IUD) was included in the questionnaire (current use, former use and never used). Sunscreen use in Norway, during vacation in southern latitudes and at Easter holiday was recorded, as well as showering with and without soap (never/seldom, 2–3 times/month, 1 time/week, 2–3 times/week, 4–6 times/week, 1 time/day and >1 time/day). Perfume use was also recorded (never/seldom, 2–3 times/month, 1 time/week, 2–3 times/week, 4–6 times/week, 1 time/day and >1 time/day).

Study sample

In total, 114 794 women have returned the questionnaires that included questions on skin care product use between 2003 and 2011 (205 519 invited, 55.9% response rate). After excluding participants with missing values for all three cream questions (body lotion, hand cream and facial cream) (n = 569), age of birth <12 years (n = 8), age at menarche ≥30 years (n = 3) and age at menopause <16 years (n = 12), there were 114 202 women included in the analysis of skin care product use. Of the women answering the questionnaire in 2003, 8899 women have also filled in a follow-up questionnaire in 2011, where 8484 had answered at least one question on use of products for skin care.

Statistical methods

Descriptive data is presented as frequencies, percentages, means with standard deviations (SDs) and medians with 25th and 75th percentiles. Statistical assessment of differences between user groups was carried out using one-way analysis of variance (ANOVA) or Kruskal-Wallis test for continuous variables, and chi-square test for categorical variables. When overall significant differences were found, comparisons between individual groups were carried out with t-test, Mann-Whitney test or chi-squared test, respectively. We analyzed trends across categories of a variable by assigning equally spaced values (1, 2, 3, 4 and 5) to user groups of skin care products and treating the variable as a continuous variable in a linear regression analysis. Pearson’s correlation coefficient (rP) was calculated for some variables. In the sub-sample of women with repeated information on use of skin care products, we studied change over time (from 2003 to 2011). From a two-way contingency table of the two responses, we present the proportion of women on the diagonal (absolute agreement) and on the diagonal ±1 category as PA and PA ±1, respectively. The symmetry was assessed by calculating the proportion of study subjects with second assessment category being higher than the first assessment category. Weighted kappa (κw) was also estimated (Cicchetti–Allison weights). STATA (version 13.0, StataCorp LP, College Station, Texas, USA) was used for the statistical analyses.

Results

The mean age of the 114 202 women was 54.8 years (range 41–76 years), and they were born between 1928 and 1963 (mean 1950). In total, 26.7% of the women used body lotion at least once per day (Table 1). Hand cream use was more common, with 52.2% reporting use once a day or more. Facial cream was by far the most frequently applied cream, used daily or more by 82.9% of the women.

Table 1 Use of skin care products in the study sample (n = 114 202). The NOWAC study, 2003–2011, Tromsø, Norway

Total percentage of body surface creamed every day ranged from non-users of skin care products to women creaming an equivalent of 200% of their body surface every day (Table 2). Use of body lotion twice a day yields a percentage of 182% (Additional file 1: Table S1). Based on their calculated percentage of body surface creamed per day, the women were categorized into five groups: non users (0% body surface creamed per day, n = 2131), light users (0.001–34.99%, n = 43 239), moderate users (35–64.99%, n = 28 455), frequent users (65–114.99%, n = 38 037) and heavy users (115–200%, n = 2340). There were no observations with a total percentage of creamed body surfaces between 115 and 182%, so all women characterized as heavy users of skin care products used body lotion twice a day (Additional file 1: Figure S1 and Table 2). Of the heavy users, 77.0% used hand cream and 85.7% used face cream twice a day (Table 2).

Table 2 Frequency (%) of skin care product use in the five different user groups (n = 114 202). The NOWAC study, 2003–2011, Tromsø, Norway

Among non-users, 39.9% reported sunscreen use in Norway, 38.3% in southern latitudes and 37.5% during Easter holiday, whereas in the more frequent user groups (frequent and heavy users), up to 79.0% of the women used sunscreen in these occasions (Table 3). Daily perfume use was more common among frequent and heavy users of skin care products (47.6 and 35.4%, respectively), than among non-users (16.6%). Showering with soap was more common among heavy users (median 30 times/month) than among non-users (median 10 times/month) (Table 3). Use of body lotion was moderately correlated to showering (rP = 0.27, p < 0.01), and less to physical activity (rP = 0.13, p < 0.01).

Table 3 Use of other personal care products in five different user groups of skin care products (n = 114 202). The NOWAC study, 2003–2011, Tromsø, Norway

Table 4 provides information on demographics and life style characteristics in the user groups. Use of skin care products was significantly associated with all investigated variables (p ≤ 0.01), except age at menarche (p = 0.36). For significant variables, we compared differences between non-users and heavy users. Heavy users of skin care products had significantly higher education, higher household income, higher level of physical activity and higher intake of alcohol than non-users (p < 0.01). Likewise, heavy users reported significantly lower BMI (mean difference: −3.47 kg/m2), less children and fewer months of total breastfeeding as compared to non-users (p < 0.01). Age at menopause did not differ significantly between heavy users and non-users (p = 0.56), neither did age at first birth (p = 0.58). There were significantly fewer current smokers and more former smokers among heavy users than among non-users (p < 0.01). Current or earlier use of OCs, HRT or IUD was significantly more common among heavy users than among non-users (p < 0.01). Likewise, comparison of non/light versus frequent/heavy users were significant for all these variables (p ≤ 0.01), except for use of hormone IUD at time of answering the questionnaire (p = 0.33).

Table 4 Demographics and life style characteristics in the five different user groups. The NOWAC study, 2003–2011, Tromsø, Norway

Noteworthy, BMI decreased linearly with increased use of skin care products (p for trend <0.01), and physical activity increased linearly with increased cream use (p for trend <0.01).

Characteristics according to use of body lotion, hand cream and facial cream are provided in Additional file 1: Tables S2–S4. Moderate, frequent and heavy users of body lotion were the same individuals as those categorized as moderate, frequent and heavy users of skin care products (Additional file 1: Table S3). The same variables that characterize heavy users of skin care products and body lotion, also describe heavy users of facial cream (Additional file 1: Table S4), whereas hand cream users differed mainly in BMI, physical activity, smoking status and use of synthetic hormones (Additional file 1: Table S4).

Comparison of cream use in 2003 and 2011

In total, 8484 women answered questions on cream use in 2003 and in 2011 (Table 5). A majority of the women reported use of skin care products so similar they were categorized in the same group both years (absolute agreement PA = 59.9%, Table 6) and 91.5% are within ± 1 category (PA±1 = 91.5%), while 25.6% of the women recorded increased use and 14.5% decreased use in 2011. Absolute agreement was highest for facial cream (PA = 66.6%) and lowest for hand cream (PA = 40.6%). Likewise, weighted kappa was highest for facial cream (κw = 0.59) and lowest for hand cream (κw = 0.51) (Table 6).

Table 5 User group among women answering question both in 2003 and in 2011 (n = 8484). The NOWAC study, 2003–2011, Tromsø, Norway
Table 6 Agreement between reported use of skin care products in 2003 and 2011. The NOWAC study, 2003–2011, Tromsø, Norway

Discussion

In this nationally representative study sample of more than 114 000 Norwegian women, we have assessed lifestyle characteristics in relation to use of skin care products. Our findings indicate that women classified as heavy users (using body lotions twice a day or more) have a distinctively different lifestyle than non-users, with higher income, higher level of physical activity, lower BMI, fewer children, higher alcohol consumption and a greater tendency to use hormones (OCs, HRT and IUD) during their life span. Smoking was also differently distributed – it was, to a larger extent, a former habit among heavy users compared to non-users, who were more often current smokers. The lack of difference in age at menarche and age at menopause is consistent with the impression that the differences mainly occur within characteristics that the women can affect themselves. Characteristics of heavy users of body lotion, facial cream and hand cream were mainly in agreement with the characteristics of heavy users of total skin care products.

The agreement between 2003 and 2011 was moderate (κw = 0.52) [14], and the habit of using skin care products is therefore clearly established among women aged 41–76 years in Norway. At what time in life creaming habits are established in Norway is not studied here, but other studies show that the use of skin care products is widespread among adolescents and children in other European countries [15, 16].

An important strength of this study is the large, population based study sample reflecting cream use among Norwegian women (41–76 years old) in recent time. To the best of our knowledge, this is the largest study conducted on use of skin care products in comparison to other life style factors. Limitations include no data on deodorant use, a cohort not including younger women and exposure classification based on self-reported data. However, it is previously shown [8] that self-reported use of skin care products is highly correlated with paraben concentrations in plasma samples from the same cohort and we therefore consider the risk of exposure misclassification as acceptable. As it is unclear whether dermal absorption of EDs on specific areas or continuously elevated concentrations of EDs in plasma is of importance for endocrine related diseases, our lack of ability to differentiate between frequent low exposure (e.g. daily application of facial cream) and less frequent higher exposure (e.g. use of body lotion once a week), when using the conversion table, can be seen upon as a weakness. However, based on our previous study [8], it is the calculated daily percentage of exposed skin area that determines plasma concentration for parabens, and our exposure classification is therefore a valid measure of systemic uptake.

Conclusion

Heavy users of skin care products differ significantly from non-users on BMI, degree of daily physical activity, income, number of children, use of hormonal pharmaceuticals, smoking and alcohol consumption. Use of skin care products is common among women aged 41–76 years in Norway, and the use is consistent over time to a moderate extent.

Abbreviations

ANOVA:

Analysis of variance

BMI:

Body mass index

EDs:

Endocrine disruptor

HRT:

Hormone replacement therapy

IUD:

Hormone releasing intrauterine device

NOWAC:

Norwegian women and cancer study

OCs:

Oral contraceptives

PA and PA ±1:

Describes the symmetry in a two-way contingency table of repeated measurements, i.e. PA is the proportion of participants with absolute agreement between the two measurements and PA+1 is the proportion of women with absolute agreement ±1 category

PCPs:

Personal care products

rp:

Person’s correlation coefficient

SD:

Standard deviation

UV-filters:

Ultraviolet filters

κw:

Weighted kappa

References

  1. Witorsch RJ, Thomas JA. Personal care products and endocrine disruption: A critical review of the literature. Crit Rev Toxicol. 2010;40 Suppl 3:1–30.

    Article  CAS  PubMed  Google Scholar 

  2. Krause M, Klit A, Blomberg Jensen M, Soeborg T, Frederiksen H, Schlumpf M, Lichtensteiger W, Skakkebaek NE, Drzewiecki KT. Sunscreens: are they beneficial for health? An overview of endocrine disrupting properties of UV-filters. Int J Androl. 2012;35(3):424–36.

    Article  CAS  PubMed  Google Scholar 

  3. Witorsch RJ. Critical analysis of endocrine disruptive activity of triclosan and its relevance to human exposure through the use of personal care products. Crit Rev Toxicol. 2014;44(6):535–55.

    Article  CAS  PubMed  Google Scholar 

  4. Philippat C, Bennett D, Calafat AM, Picciotto IH. Exposure to select phthalates and phenols through use of personal care products among Californian adults and their children. Environ Res. 2015;140:369–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. The Danish Environmental Protection Agency: Survey of Parabens In: List of Undesirable Substances (LOUS). Copenhagen: Danish Ministry of the Environment; 2012. http://www2.mst.dk/Udgiv/publications/2013/04/978-87-93026-02-5.pdf.

  6. Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL, Tong W, Shi L, Perkins R, Sheehan DM. The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol Sci. 2000;54(1):138–53.

    Article  CAS  PubMed  Google Scholar 

  7. Scientific Comittee on Consumer Safery. Opinion on Parabens. Updated request for a scientific opinion on propyl- and butylparaben, COLIPA n° P82. Luxembourg: European Union; 2013.

    Google Scholar 

  8. Sandanger TM, Huber S, Moe MK, Braathen T, Leknes H, Lund E. Plasma concentrations of parabens in postmenopausal women and self-reported use of personal care products: the NOWAC postgenome study. J Expo Sci Environ Epidemiol. 2011;21(6):595–600.

    Article  CAS  PubMed  Google Scholar 

  9. Larsson K, Ljung Bjorklund K, Palm B, Wennberg M, Kaj L, Lindh CH, Jonsson BA, Berglund M. Exposure determinants of phthalates, parabens, bisphenol A and triclosan in Swedish mothers and their children. Environ Int. 2014;73:323–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lund E, Dumeaux V, Braaten T, Hjartaker A, Engeset D, Skeie G, Kumle M. Cohort profile: The Norwegian Women and Cancer Study--NOWAC--Kvinner og kreft. Int J Epidemiol. 2008;37(1):36–41.

    Article  PubMed  Google Scholar 

  11. Lund E, Kumle M, Braaten T, Hjartaker A, Bakken K, Eggen E, Gram TI. External validity in a population-based national prospective study--the Norwegian Women and Cancer Study (NOWAC). Cancer Causes Control. 2003;14(10):1001–8.

    Article  PubMed  Google Scholar 

  12. Parr CL, Hjartaker A, Lund E, Veierod MB. Meat intake, cooking methods and risk of proximal colon, distal colon and rectal cancer: the Norwegian Women and Cancer (NOWAC) cohort study. Int J Cancer. 2013;133(5):1153–63.

    Article  CAS  PubMed  Google Scholar 

  13. Dumeaux V, Lund E, Hjartaker A. Use of oral contraceptives, alcohol, and risk for invasive breast cancer. Cancer Epidemiol Biomarkers Prev. 2004;13(8):1302–7.

    CAS  PubMed  Google Scholar 

  14. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159–74.

    Article  CAS  PubMed  Google Scholar 

  15. Biesterbos JW, Dudzina T, Delmaar CJ, Bakker MI, Russel FG, von Goetz N, Scheepers PT, Roeleveld N. Usage patterns of personal care products: important factors for exposure assessment. Food Chem Toxicol. 2013;55:8–17.

    Article  CAS  PubMed  Google Scholar 

  16. Manova E, von Goetz N, Keller C, Siegrist M, Hungerbuhler K. Use patterns of leave-on personal care products among Swiss-German children, adolescents, and adults. Int J Environ Res Public Health. 2013;10(7):2778–98.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are grateful to all participating women in the Norwegian Women and Cancer study (NOWAC). We also thank Tonje Braathen, Bente Augdal and Nicolle Mode for their contribution in data delivery.

Funding

This project was financed from UiT – the Arctic University of Norway through funding of a 4 year PhD position.

Availability of data and materials

As part of our ethical approval, we do not have the rights to make the data publicly available, but the authors can be contacted by reviewers etc. regarding data requests.

Authors’ contribution

EL is the principal investigator of the NOWAC study, and TMS designed this particular study. BA and CR performed the statistical analysis. MBV and TMS contributed to the statistical analysis and interpretation of data. BA, MBV, CR and TMS drafted the manuscript. All authors critically revised the manuscript for important intellectual content and approved the final manuscript. TMS is the study guarantor.

Competing interest

The authors declare that they have no competing interests.

Consent for publications

“Not applicable”.

Ethics approval and consent to participate

Women received an invitation letter that requested written informed consent to be completed and returned in a prepaid envelope together with the comprehensive questionnaire. Only those who consented were included in the study cohort. The national Data Inspection Boards and responsible Medical Ethical Committees approved the study.

The studies were approved by the Regional Committee for Medical Research Ethics, Norway.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Boel Aniansson.

Additional file

Additional file 1: Table S1.

Conversion table of type and frequency of skin care product into percentage body area creamed per day. The NOWAC study, 2003–2011, Tromsø, Norway. Table S2. Demographics and life style characteristics in the five different user groups of body lotion. The NOWAC study, 2003–2011, Tromsø, Norway. Table S3. Demographics and life style characteristics in the five different user groups of facial cream. The NOWAC study, 2003–2011, Tromsø, Norway. Table S4. Demographics and life style characteristics in the five different user groups of hand cream. The NOWAC study, 2003–2011, Tromsø, Norway. Figure S1. Distribution of the calculated total percentage of body surface creamed per day (n = 114 202). The NOWAC study, 2003–2011, Tromsø, Norway. (DOCX 208 kb)

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aniansson, B., Veierød, M.B., Rylander, C. et al. Characterization of heavy users of skin care products among Norwegian women from 2003 to 2011. Arch Public Health 74, 53 (2016). https://doi.org/10.1186/s13690-016-0165-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13690-016-0165-5

Keywords