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1. Ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma: a randomized phase 2 trial

Author

VanderWalde, Ari, VanderWalde, Ari, Bellasea, Shay L, Kendra, Kari L, Khushalani, Nikhil I, Campbell, Katie M, Scumpia, Philip O, Kuklinski, Lawrence F, Collichio, Frances, Sosman, Jeffrey A, Ikeguchi, Alexandra, Victor, Adrienne I, Truong, Thach-Giao, Chmielowski, Bartosz, Portnoy, David C, Chen, Yuanbin, Margolin, Kim, Bane, Charles, Dasanu, Constantin A, Johnson, Douglas B, Eroglu, Zeynep, Chandra, Sunandana, Medina, Egmidio, Gonzalez, Cynthia R, Baselga-Carretero, Ignacio, Vega-Crespo, Agustin, Garcilazo, Ivan Perez, Sharon, Elad, Hu-Lieskovan, Siwen, Patel, Sapna P, Grossmann, Kenneth F, Moon, James, Wu, Michael C, Ribas, Antoni, VanderWalde, Ari, VanderWalde, Ari, Bellasea, Shay L, Kendra, Kari L, Khushalani, Nikhil I, Campbell, Katie M, Scumpia, Philip O, Kuklinski, Lawrence F, Collichio, Frances, Sosman, Jeffrey A, Ikeguchi, Alexandra, Victor, Adrienne I, Truong, Thach-Giao, Chmielowski, Bartosz, Portnoy, David C, Chen, Yuanbin, Margolin, Kim, Bane, Charles, Dasanu, Constantin A, Johnson, Douglas B, Eroglu, Zeynep, Chandra, Sunandana, Medina, Egmidio, Gonzalez, Cynthia R, Baselga-Carretero, Ignacio, Vega-Crespo, Agustin, Garcilazo, Ivan Perez, Sharon, Elad, Hu-Lieskovan, Siwen, Patel, Sapna P, Grossmann, Kenneth F, Moon, James, Wu, Michael C, and Ribas, Antoni

Abstract

In this randomized phase 2 trial, blockade of cytotoxic T-lymphocyte protein 4 (CTLA-4) with continuation of programmed death protein 1 (PD-1) blockade in patients with metastatic melanoma who had received front-line anti-PD-1 or therapy against programmed cell death 1 ligand 1 and whose tumors progressed was tested in comparison with CTLA-4 blockade alone. Ninety-two eligible patients were randomly assigned in a 3:1 ratio to receive the combination of ipilimumab and nivolumab, or ipilimumab alone. The primary endpoint was progression-free survival. Secondary endpoints included the difference in CD8 T cell infiltrate among responding and nonresponding tumors, objective response rate, overall survival and toxicity. The combination of nivolumab and ipilimumab resulted in a statistically significant improvement in progression-free survival over ipilimumab (hazard ratio = 0.63, 90% confidence interval (CI) = 0.41-0.97, one-sided P = 0.04). Objective response rates were 28% (90% CI = 19-38%) and 9% (90% CI = 2-25%), respectively (one-sided P = 0.05). Grade 3 or higher treatment-related adverse events occurred in 57% and 35% of patients, respectively, which is consistent with the known toxicity profile of these regimens. The change in intratumoral CD8 T cell density observed in the present analysis did not reach statistical significance to support the formal hypothesis tested as a secondary endpoint. In conclusion, primary resistance to PD-1 blockade therapy can be reversed in some patients with the combination of CTLA-4 and PD-1 blockade. Clinicaltrials.gov identifier: NCT03033576 .

Published
2023

2. Author Correction: Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity.

Author

Kaplan, Robert C, Kaplan, Robert C, Wang, Zheng, Usyk, Mykhaylo, Sotres-Alvarez, Daniela, Daviglus, Martha L, Schneiderman, Neil, Talavera, Gregory A, Gellman, Marc D, Thyagarajan, Bharat, Moon, Jee-Young, Vázquez-Baeza, Yoshiki, McDonald, Daniel, Williams-Nguyen, Jessica S, Wu, Michael C, North, Kari E, Shaffer, Justin, Sollecito, Christopher C, Qi, Qibin, Isasi, Carmen R, Wang, Tao, Knight, Rob, Burk, Robert D, Kaplan, Robert C, Kaplan, Robert C, Wang, Zheng, Usyk, Mykhaylo, Sotres-Alvarez, Daniela, Daviglus, Martha L, Schneiderman, Neil, Talavera, Gregory A, Gellman, Marc D, Thyagarajan, Bharat, Moon, Jee-Young, Vázquez-Baeza, Yoshiki, McDonald, Daniel, Williams-Nguyen, Jessica S, Wu, Michael C, North, Kari E, Shaffer, Justin, Sollecito, Christopher C, Qi, Qibin, Isasi, Carmen R, Wang, Tao, Knight, Rob, and Burk, Robert D

Abstract

Following publication of the original paper [1], an error was reported in the third paragraph in the section "Analysis of GMB composition and its correlates" (page 3 of the PDF). The first sentence of the text should refer to Table 2, but mistakenly refers to Table 1.

Published
2020

3. Author Correction: Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity.

Author

Kaplan, Robert C, Kaplan, Robert C, Wang, Zheng, Usyk, Mykhaylo, Sotres-Alvarez, Daniela, Daviglus, Martha L, Schneiderman, Neil, Talavera, Gregory A, Gellman, Marc D, Thyagarajan, Bharat, Moon, Jee-Young, Vázquez-Baeza, Yoshiki, McDonald, Daniel, Williams-Nguyen, Jessica S, Wu, Michael C, North, Kari E, Shaffer, Justin, Sollecito, Christopher C, Qi, Qibin, Isasi, Carmen R, Wang, Tao, Knight, Rob, Burk, Robert D, Kaplan, Robert C, Kaplan, Robert C, Wang, Zheng, Usyk, Mykhaylo, Sotres-Alvarez, Daniela, Daviglus, Martha L, Schneiderman, Neil, Talavera, Gregory A, Gellman, Marc D, Thyagarajan, Bharat, Moon, Jee-Young, Vázquez-Baeza, Yoshiki, McDonald, Daniel, Williams-Nguyen, Jessica S, Wu, Michael C, North, Kari E, Shaffer, Justin, Sollecito, Christopher C, Qi, Qibin, Isasi, Carmen R, Wang, Tao, Knight, Rob, and Burk, Robert D

Abstract

Following publication of the original paper [1], an error was reported in the third paragraph in the section "Analysis of GMB composition and its correlates" (page 3 of the PDF). The first sentence of the text should refer to Table 2, but mistakenly refers to Table 1.

Published
2020

4. Increased mucosal neutrophil survival is associated with altered microbiota in HIV infection.

Author

Hensley-McBain, Tiffany, Hensley-McBain, Tiffany, Wu, Michael C, Manuzak, Jennifer A, Cheu, Ryan K, Gustin, Andrew, Driscoll, Connor B, Zevin, Alexander S, Miller, Charlene J, Coronado, Ernesto, Smith, Elise, Chang, Jean, Gale, Michael, Somsouk, Ma, Burgener, Adam D, Hunt, Peter W, Hope, Thomas J, Collier, Ann C, Klatt, Nichole R, Hensley-McBain, Tiffany, Hensley-McBain, Tiffany, Wu, Michael C, Manuzak, Jennifer A, Cheu, Ryan K, Gustin, Andrew, Driscoll, Connor B, Zevin, Alexander S, Miller, Charlene J, Coronado, Ernesto, Smith, Elise, Chang, Jean, Gale, Michael, Somsouk, Ma, Burgener, Adam D, Hunt, Peter W, Hope, Thomas J, Collier, Ann C, and Klatt, Nichole R

Abstract

Gastrointestinal (GI) mucosal dysfunction predicts and likely contributes to non-infectious comorbidities and mortality in HIV infection and persists despite antiretroviral therapy. However, the mechanisms underlying this dysfunction remain incompletely understood. Neutrophils are important for containment of pathogens but can also contribute to tissue damage due to their release of reactive oxygen species and other potentially harmful effector molecules. Here we used a flow cytometry approach to investigate increased neutrophil lifespan as a mechanism for GI neutrophil accumulation in chronic, treated HIV infection and a potential role for gastrointestinal dysbiosis. We report that increased neutrophil survival contributes to neutrophil accumulation in colorectal biopsy tissue, thus implicating neutrophil lifespan as a new therapeutic target for mucosal inflammation in HIV infection. Additionally, we characterized the intestinal microbiome of colorectal biopsies using 16S rRNA sequencing. We found that a reduced Lactobacillus: Prevotella ratio associated with neutrophil survival, suggesting that intestinal bacteria may contribute to GI neutrophil accumulation in treated HIV infection. Finally, we provide evidence that Lactobacillus species uniquely decrease neutrophil survival and neutrophil frequency in vitro, which could have important therapeutic implications for reducing neutrophil-driven inflammation in HIV and other chronic inflammatory conditions.

Published
2019

5. Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity.

Author

Kaplan, Robert C, Kaplan, Robert C, Wang, Zheng, Usyk, Mykhaylo, Sotres-Alvarez, Daniela, Daviglus, Martha L, Schneiderman, Neil, Talavera, Gregory A, Gellman, Marc D, Thyagarajan, Bharat, Moon, Jee-Young, Vázquez-Baeza, Yoshiki, McDonald, Daniel, Williams-Nguyen, Jessica S, Wu, Michael C, North, Kari E, Shaffer, Justin, Sollecito, Christopher C, Qi, Qibin, Isasi, Carmen R, Wang, Tao, Knight, Rob, Burk, Robert D, Kaplan, Robert C, Kaplan, Robert C, Wang, Zheng, Usyk, Mykhaylo, Sotres-Alvarez, Daniela, Daviglus, Martha L, Schneiderman, Neil, Talavera, Gregory A, Gellman, Marc D, Thyagarajan, Bharat, Moon, Jee-Young, Vázquez-Baeza, Yoshiki, McDonald, Daniel, Williams-Nguyen, Jessica S, Wu, Michael C, North, Kari E, Shaffer, Justin, Sollecito, Christopher C, Qi, Qibin, Isasi, Carmen R, Wang, Tao, Knight, Rob, and Burk, Robert D

Abstract

Background: Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment.Results: Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA.Conclusions: Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

Published
2019

6. Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity.

Author

Kaplan, Robert C, Kaplan, Robert C, Wang, Zheng, Usyk, Mykhaylo, Sotres-Alvarez, Daniela, Daviglus, Martha L, Schneiderman, Neil, Talavera, Gregory A, Gellman, Marc D, Thyagarajan, Bharat, Moon, Jee-Young, Vázquez-Baeza, Yoshiki, McDonald, Daniel, Williams-Nguyen, Jessica S, Wu, Michael C, North, Kari E, Shaffer, Justin, Sollecito, Christopher C, Qi, Qibin, Isasi, Carmen R, Wang, Tao, Knight, Rob, Burk, Robert D, Kaplan, Robert C, Kaplan, Robert C, Wang, Zheng, Usyk, Mykhaylo, Sotres-Alvarez, Daniela, Daviglus, Martha L, Schneiderman, Neil, Talavera, Gregory A, Gellman, Marc D, Thyagarajan, Bharat, Moon, Jee-Young, Vázquez-Baeza, Yoshiki, McDonald, Daniel, Williams-Nguyen, Jessica S, Wu, Michael C, North, Kari E, Shaffer, Justin, Sollecito, Christopher C, Qi, Qibin, Isasi, Carmen R, Wang, Tao, Knight, Rob, and Burk, Robert D

Abstract

BackgroundHispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment.ResultsAmplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA.ConclusionsOur analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

Published
2019

7. Increased mucosal neutrophil survival is associated with altered microbiota in HIV infection.

Author

Hensley-McBain, Tiffany, Douek, Daniel C1, Hensley-McBain, Tiffany, Wu, Michael C, Manuzak, Jennifer A, Cheu, Ryan K, Gustin, Andrew, Driscoll, Connor B, Zevin, Alexander S, Miller, Charlene J, Coronado, Ernesto, Smith, Elise, Chang, Jean, Gale, Michael, Somsouk, Ma, Burgener, Adam D, Hunt, Peter W, Hope, Thomas J, Collier, Ann C, Klatt, Nichole R, Hensley-McBain, Tiffany, Douek, Daniel C1, Hensley-McBain, Tiffany, Wu, Michael C, Manuzak, Jennifer A, Cheu, Ryan K, Gustin, Andrew, Driscoll, Connor B, Zevin, Alexander S, Miller, Charlene J, Coronado, Ernesto, Smith, Elise, Chang, Jean, Gale, Michael, Somsouk, Ma, Burgener, Adam D, Hunt, Peter W, Hope, Thomas J, Collier, Ann C, and Klatt, Nichole R

Abstract

Gastrointestinal (GI) mucosal dysfunction predicts and likely contributes to non-infectious comorbidities and mortality in HIV infection and persists despite antiretroviral therapy. However, the mechanisms underlying this dysfunction remain incompletely understood. Neutrophils are important for containment of pathogens but can also contribute to tissue damage due to their release of reactive oxygen species and other potentially harmful effector molecules. Here we used a flow cytometry approach to investigate increased neutrophil lifespan as a mechanism for GI neutrophil accumulation in chronic, treated HIV infection and a potential role for gastrointestinal dysbiosis. We report that increased neutrophil survival contributes to neutrophil accumulation in colorectal biopsy tissue, thus implicating neutrophil lifespan as a new therapeutic target for mucosal inflammation in HIV infection. Additionally, we characterized the intestinal microbiome of colorectal biopsies using 16S rRNA sequencing. We found that a reduced Lactobacillus: Prevotella ratio associated with neutrophil survival, suggesting that intestinal bacteria may contribute to GI neutrophil accumulation in treated HIV infection. Finally, we provide evidence that Lactobacillus species uniquely decrease neutrophil survival and neutrophil frequency in vitro, which could have important therapeutic implications for reducing neutrophil-driven inflammation in HIV and other chronic inflammatory conditions.

Published
2019

8. Vaginal microbiota and genitourinary menopausal symptoms: a cross-sectional analysis.

Author

Mitchell, Caroline M, Mitchell, Caroline M, Srinivasan, Sujatha, Zhan, Xiang, Wu, Michael C, Reed, Susan D, Guthrie, Katherine A, LaCroix, Andrea Z, Fiedler, Tina, Munch, Matthew, Liu, Congzhou, Hoffman, Noah G, Blair, Ian A, Newton, Katherine, Freeman, Ellen W, Joffe, Hadine, Cohen, Lee, Fredricks, David N, Mitchell, Caroline M, Mitchell, Caroline M, Srinivasan, Sujatha, Zhan, Xiang, Wu, Michael C, Reed, Susan D, Guthrie, Katherine A, LaCroix, Andrea Z, Fiedler, Tina, Munch, Matthew, Liu, Congzhou, Hoffman, Noah G, Blair, Ian A, Newton, Katherine, Freeman, Ellen W, Joffe, Hadine, Cohen, Lee, and Fredricks, David N

Abstract

ObjectiveTo examine associations between the composition of the vaginal microbiota and genitourinary menopausal symptoms, serum estrogen, and vaginal glycogen.MethodsFor this cross-sectional study, 88 women aged 40 to 62 years, enrolled in a hot flash treatment trial, provided vaginal swabs and a blood sample at enrollment. Bacterial communities were characterized using 16S rRNA PCR and deep sequencing targeting the V3-V4 region. Quantities of Lactobacillus crispatus and Lactobacillus iners were measured using qPCR. Self-reported genitourinary symptoms included: presence and severity of individual symptoms and identification of most bothersome symptom. Glycogen was measured fluorometrically in swab eluate. Serum estradiol (E2) and estrone (E1) were measured by liquid chromatography/mass spectrometry. Associations between bacteria, symptoms, glycogen, and serum estrogens were tested by linear regression or Wilcoxon signed-rank test, adjusted for multiple comparisons. Comparisons between groups used Kruskall-Wallis or Fisher's exact test.ResultsOf the 88 women, 33 (38%) had a majority of Lactobacillus species, whereas 58 (66%) had any Lactobacillus detected. Over half (53%) reported at least one vulvovaginal symptom (most commonly dryness), but symptoms were not associated with the presence of Lactobacillus species. Women with Lactobacillus-dominant communities had higher unconjugated serum estrone, but no difference in vaginal glycogen levels, compared with those with non-Lactobacillus-dominant communities. Higher serum E2 and E1 were not associated with either higher vaginal glycogen or detection of individual genera.ConclusionsPresence of Lactobacillus-dominant vaginal microbiota was not associated with fewer vulvovaginal symptoms. Serum estrone was higher in women with Lactobacillus dominance, but vaginal-free glycogen was not associated with composition of the vaginal microbiota.

Published
2017

9. Vaginal microbiota and genitourinary menopausal symptoms: a cross-sectional analysis.

Author

Mitchell, Caroline M, Mitchell, Caroline M, Srinivasan, Sujatha, Zhan, Xiang, Wu, Michael C, Reed, Susan D, Guthrie, Katherine A, LaCroix, Andrea Z, Fiedler, Tina, Munch, Matthew, Liu, Congzhou, Hoffman, Noah G, Blair, Ian A, Newton, Katherine, Freeman, Ellen W, Joffe, Hadine, Cohen, Lee, Fredricks, David N, Mitchell, Caroline M, Mitchell, Caroline M, Srinivasan, Sujatha, Zhan, Xiang, Wu, Michael C, Reed, Susan D, Guthrie, Katherine A, LaCroix, Andrea Z, Fiedler, Tina, Munch, Matthew, Liu, Congzhou, Hoffman, Noah G, Blair, Ian A, Newton, Katherine, Freeman, Ellen W, Joffe, Hadine, Cohen, Lee, and Fredricks, David N

Abstract

ObjectiveTo examine associations between the composition of the vaginal microbiota and genitourinary menopausal symptoms, serum estrogen, and vaginal glycogen.MethodsFor this cross-sectional study, 88 women aged 40 to 62 years, enrolled in a hot flash treatment trial, provided vaginal swabs and a blood sample at enrollment. Bacterial communities were characterized using 16S rRNA PCR and deep sequencing targeting the V3-V4 region. Quantities of Lactobacillus crispatus and Lactobacillus iners were measured using qPCR. Self-reported genitourinary symptoms included: presence and severity of individual symptoms and identification of most bothersome symptom. Glycogen was measured fluorometrically in swab eluate. Serum estradiol (E2) and estrone (E1) were measured by liquid chromatography/mass spectrometry. Associations between bacteria, symptoms, glycogen, and serum estrogens were tested by linear regression or Wilcoxon signed-rank test, adjusted for multiple comparisons. Comparisons between groups used Kruskall-Wallis or Fisher's exact test.ResultsOf the 88 women, 33 (38%) had a majority of Lactobacillus species, whereas 58 (66%) had any Lactobacillus detected. Over half (53%) reported at least one vulvovaginal symptom (most commonly dryness), but symptoms were not associated with the presence of Lactobacillus species. Women with Lactobacillus-dominant communities had higher unconjugated serum estrone, but no difference in vaginal glycogen levels, compared with those with non-Lactobacillus-dominant communities. Higher serum E2 and E1 were not associated with either higher vaginal glycogen or detection of individual genera.ConclusionsPresence of Lactobacillus-dominant vaginal microbiota was not associated with fewer vulvovaginal symptoms. Serum estrone was higher in women with Lactobacillus dominance, but vaginal-free glycogen was not associated with composition of the vaginal microbiota.

Published
2017

10. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Author

dIRAS RA-2, Risk Assessment, Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Benjamin Neelon, Sara E, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, Nystad, Wenche, Koppelman, Gerard H, Relton, Caroline L, Jaddoe, Vincent W V, Wilcox, Allen, Melén, Erik, London, Stephanie J, dIRAS RA-2, Risk Assessment, Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Benjamin Neelon, Sara E, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, Nystad, Wenche, Koppelman, Gerard H, Relton, Caroline L, Jaddoe, Vincent W V, Wilcox, Allen, Melén, Erik, and London, Stephanie J

Published
2016

11. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Author

dIRAS RA-2, Risk Assessment, Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Benjamin Neelon, Sara E, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, Nystad, Wenche, Koppelman, Gerard H, Relton, Caroline L, Jaddoe, Vincent W V, Wilcox, Allen, Melén, Erik, London, Stephanie J, dIRAS RA-2, Risk Assessment, Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Benjamin Neelon, Sara E, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, Nystad, Wenche, Koppelman, Gerard H, Relton, Caroline L, Jaddoe, Vincent W V, Wilcox, Allen, Melén, Erik, and London, Stephanie J

Published
2016

12. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis.

Author

Joubert, Bonnie R, Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Benjamin Neelon, Sara E, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, Nystad, Wenche, Joubert, Bonnie R, Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Benjamin Neelon, Sara E, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, and Nystad, Wenche

Abstract

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.

Published
2016

13. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Author

dIRAS RA-2, Risk Assessment, Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Benjamin Neelon, Sara E, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, Nystad, Wenche, Koppelman, Gerard H, Relton, Caroline L, Jaddoe, Vincent W V, Wilcox, Allen, Melén, Erik, London, Stephanie J, dIRAS RA-2, Risk Assessment, Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Benjamin Neelon, Sara E, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, Nystad, Wenche, Koppelman, Gerard H, Relton, Caroline L, Jaddoe, Vincent W V, Wilcox, Allen, Melén, Erik, and London, Stephanie J

Published
2016

14. Body mass index associated with genome-wide methylation in breast tissue.

Author

Hair, Brionna Y, Xu, Zongli, Kirk, Erin L, Harlid, Sophia, Sandhu, Rupninder, Robinson, Whitney R, Wu, Michael C, Olshan, Andrew F, Conway, Kathleen, Taylor, Jack A, Troester, Melissa A, Hair, Brionna Y, Xu, Zongli, Kirk, Erin L, Harlid, Sophia, Sandhu, Rupninder, Robinson, Whitney R, Wu, Michael C, Olshan, Andrew F, Conway, Kathleen, Taylor, Jack A, and Troester, Melissa A

Abstract

Gene expression studies indicate that body mass index (BMI) is associated with molecular pathways involved in inflammation, insulin-like growth factor activation, and other carcinogenic processes in breast tissue. The goal of this study was to determine whether BMI is associated with gene methylation in breast tissue and to identify pathways that are commonly methylated in association with high BMI. Epigenome-wide methylation profiles were determined using the Illumina HumanMethylation450 BeadChip array in the non-diseased breast tissue of 81 women undergoing breast surgery between 2009 and 2013 at the University of North Carolina Hospitals. Multivariable, robust linear regression was performed to identify methylation sites associated with BMI at a false discovery rate q value <0.05. Gene expression microarray data was used to identify which of the BMI-associated methylation sites also showed correlation with gene expression. Gene set enrichment analysis was conducted to assess which pathways were enriched among the BMI-associated methylation sites. Of the 431,568 methylation sites analyzed, 2573 were associated with BMI (q value <0.05), 57 % of which showed an inverse correlation with BMI. Pathways enriched among the 2573 probe sites included those involved in inflammation, insulin receptor signaling, and leptin signaling. We were able to map 1251 of the BMI-associated methylation sites to gene expression data, and, of these, 226 (18 %) showed substantial correlations with gene expression. Our results suggest that BMI is associated with genome-wide methylation in non-diseased breast tissue and may influence epigenetic pathways involved in inflammatory and other carcinogenic processes.

Published
2015
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15. An Efficient Distributed Algorithm for Maximum Matching in General Graphs.

Author

ILLINOIS UNIV AT URBANA APPLIED COMPUTATION THEORY GROUP, Wu,Michael C, ILLINOIS UNIV AT URBANA APPLIED COMPUTATION THEORY GROUP, and Wu,Michael C

Abstract

Let G = (V, E) be a finite, undirected, connected graph with the set of vertices V and the set of edges E. A matching M is a subset that no two edges of M are incident on a common vertex. A maximum matching is a matching of maximum cardinality. This thesis presents an efficient distributed algorithm for finding a maximum matching in a general graph. In designing his distributed matching algorithm, the author is concerned with the communication complexity. The maximum number of message transmissions determines the efficiency of the algorithm. He concentrates on minimizing the number of messages for two reasons. First, in an actual distributed system, the communication time would likely be much greater than the processing time. Second, in commercial computer networks, common carriers often charge by the number of packets or bits rather than by time.

Published
1987

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