Associated Factors of Atrophic Gastritis Diagnosed by Double-Contrast Upper Gastrointestinal Barium X-Ray Radiography: A Cross-Sectional Study Analyzing 6,901 Healthy Subjects in Japan

Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning o...

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Published inPloS one Vol. 9; no. 10; p. e111359
Main Authors Yamamichi, Nobutake, Hirano, Chigaya, Shimamoto, Takeshi, Minatsuki, Chihiro, Takahashi, Yu, Nakayama, Chiemi, Matsuda, Rie, Fujishiro, Mitsuhiro, Konno-Shimizu, Maki, Kato, Jun, Kodashima, Shinya, Ono, Satoshi, Niimi, Keiko, Mochizuki, Satoshi, Tsuji, Yosuke, Sakaguchi, Yoshiki, Asada-Hirayama, Itsuko, Takeuchi, Chihiro, Yakabi, Seiichi, Kakimoto, Hikaru, Wada, Ryoichi, Mitsushima, Toru, Ichinose, Masao, Koike, Kazuhiko
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 24.10.2014
Public Library of Science (PLoS)
Subjects
Online AccessGet full text
ISSN1932-6203
1932-6203
DOI10.1371/journal.pone.0111359

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Abstract Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection. We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach. Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H2-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects. The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.
AbstractList Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection. We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach. Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients ([beta]) and odds ratio (OR) demonstrated that serum HP IgG ([beta] = 1.499, OR = 4.48), current smoking ([beta] = 0.526, OR = 1.69), age ([beta] = 0.401, OR = 1.49), low serum pepsinogen I/II ratio ([beta] = 0.339, OR = 1.40), and male gender ([beta] = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H.sub.2 -receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects. The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.
Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection.BACKGROUNDDouble-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection.We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach.METHODSWe evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach.Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H2-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects.RESULTSOf the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H2-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects.The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.CONCLUSIONSThe presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.
Background Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection. Methods We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach. Results Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H2-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects. Conclusions The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.
Background Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection. Methods We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach. Results Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients ([beta]) and odds ratio (OR) demonstrated that serum HP IgG ([beta] = 1.499, OR = 4.48), current smoking ([beta] = 0.526, OR = 1.69), age ([beta] = 0.401, OR = 1.49), low serum pepsinogen I/II ratio ([beta] = 0.339, OR = 1.40), and male gender ([beta] = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H.sub.2 -receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects. Conclusions The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.
Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection. We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach. Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H2-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects. The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.
Background Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection. Methods We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach. Results Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects ( p <0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H 2 -receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects. Conclusions The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.
Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection.We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach.Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H2-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects.The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.
Audience Academic
Author Asada-Hirayama, Itsuko
Tsuji, Yosuke
Kato, Jun
Yakabi, Seiichi
Konno-Shimizu, Maki
Mitsushima, Toru
Hirano, Chigaya
Nakayama, Chiemi
Matsuda, Rie
Kodashima, Shinya
Takahashi, Yu
Fujishiro, Mitsuhiro
Mochizuki, Satoshi
Minatsuki, Chihiro
Koike, Kazuhiko
Sakaguchi, Yoshiki
Takeuchi, Chihiro
Wada, Ryoichi
Yamamichi, Nobutake
Shimamoto, Takeshi
Niimi, Keiko
Ichinose, Masao
Kakimoto, Hikaru
Ono, Satoshi
AuthorAffiliation Okayama University, Japan
2 Department of Gastroenterology, Kameda Medical Center Makuhari, Chiba, Japan
1 Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
3 Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
AuthorAffiliation_xml – name: 1 Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
– name: 2 Department of Gastroenterology, Kameda Medical Center Makuhari, Chiba, Japan
– name: Okayama University, Japan
– name: 3 Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
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  surname: Yamamichi
  fullname: Yamamichi, Nobutake
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  fullname: Mochizuki, Satoshi
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  fullname: Tsuji, Yosuke
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/25343257$$D View this record in MEDLINE/PubMed
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: NY CH TS TM MI. Performed the experiments: NY CH CM Y. Takahashi CN RM MKS. Analyzed the data: NY TS SK SO KN SM Y. Tsuji YS IAH CT SY HK RW. Contributed reagents/materials/analysis tools: NY CH TM. Contributed to the writing of the manuscript: NY CH TS MF JK MI KK.
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Snippet Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been...
Background Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It...
Background Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It...
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Adult
Adults
Age
Aged
Aged, 80 and over
Analysis
Background radiation
Barium
Biology and Life Sciences
Body mass
Body mass index
Body size
Cancer
Cancer screening
Chronic Disease
Contrast Media
Cross-Sectional Studies
Diagnosis
Diagnostic imaging
Endoscopy
Female
Gastric cancer
Gastric juice
Gastritis
Gastritis, Atrophic - complications
Gastritis, Atrophic - diagnostic imaging
Gastritis, Atrophic - microbiology
Gastroenterology
Gastrointestinal Tract - diagnostic imaging
Gender
Healthy Volunteers
Helicobacter infections
Helicobacter Infections - complications
Helicobacter Infections - diagnostic imaging
Helicobacter Infections - microbiology
Helicobacter pylori
Helicobacter pylori - physiology
Histamine
Histamine H2 Antagonists - therapeutic use
Humans
Immunoglobulin G
Infections
Internal medicine
Japan
Male
Mathematical analysis
Medical screening
Medicine
Medicine and Health Sciences
Middle Aged
Mortality
Mucosa
Multivariate Analysis
Proton pump inhibitors
Proton Pump Inhibitors - therapeutic use
Radiography
Smoking
Statistical analysis
Stomach
Stomach cancer
Ulcers
X-ray radiography
X-Rays
Young Adult
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Title Associated Factors of Atrophic Gastritis Diagnosed by Double-Contrast Upper Gastrointestinal Barium X-Ray Radiography: A Cross-Sectional Study Analyzing 6,901 Healthy Subjects in Japan
URI https://www.ncbi.nlm.nih.gov/pubmed/25343257
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https://pubmed.ncbi.nlm.nih.gov/PMC4208837
https://doaj.org/article/eef1b4ca03664dbd8f4f32c533803bf4
http://dx.doi.org/10.1371/journal.pone.0111359
Volume 9
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