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4. The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins

Author

Silventoinen, K., primary, Jelenkovic, A., additional, Yokoyama, Y., additional, Sund, R., additional, Sugawara, M., additional, Tanaka, M., additional, Matsumoto, S., additional, Bogl, L. H., additional, Freitas, D. L., additional, Maia, J. A., additional, Hjelmborg, J. v. B., additional, Aaltonen, S., additional, Piirtola, M., additional, Latvala, A., additional, Calais-Ferreira, L., additional, Oliveira, V. C., additional, Ferreira, P. H., additional, Ji, F., additional, Ning, F., additional, Pang, Z., additional, Ordoñana, J. R., additional, Sánchez-Romera, J. F., additional, Colodro-Conde, L., additional, Burt, S. A., additional, Klump, K. L., additional, Martin, N. G., additional, Medland, S. E., additional, Montgomery, G. W., additional, Kandler, C., additional, McAdams, T. A., additional, Eley, T. C., additional, Gregory, A. M., additional, Saudino, K. J., additional, Dubois, L., additional, Boivin, M., additional, Brendgen, M., additional, Dionne, G., additional, Vitaro, F., additional, Tarnoki, A. D., additional, Tarnoki, D. L., additional, Haworth, C. M. A., additional, Plomin, R., additional, Öncel, S. Y., additional, Aliev, F., additional, Medda, E., additional, Nisticò, L., additional, Toccaceli, V., additional, Craig, J. M., additional, Saffery, R., additional, Siribaddana, S. H., additional, Hotopf, M., additional, Sumathipala, A., additional, Rijsdijk, F., additional, Jeong, H.-U., additional, Spector, T., additional, Mangino, M., additional, Lachance, G., additional, Gatz, M., additional, Butler, D. A., additional, Gao, W., additional, Yu, C., additional, Li, L., additional, Bayasgalan, G., additional, Narandalai, D., additional, Harden, K. P., additional, Tucker-Drob, E. M., additional, Christensen, K., additional, Skytthe, A., additional, Kyvik, K. O., additional, Derom, C. A., additional, Vlietinck, R. F., additional, Loos, R. J. F., additional, Cozen, W., additional, Hwang, A. E., additional, Mack, T. M., additional, He, M., additional, Ding, X., additional, Silberg, J. L., additional, Maes, H. H., additional, Cutler, T. L., additional, Hopper, J. L., additional, Magnusson, P. K. E., additional, Pedersen, N. L., additional, Dahl Aslan, A. K., additional, Baker, L. A., additional, Tuvblad, C., additional, Bjerregaard-Andersen, M., additional, Beck-Nielsen, H., additional, Sodemann, M., additional, Ullemar, V., additional, Almqvist, C., additional, Tan, Q., additional, Zhang, D., additional, Swan, G. E., additional, Krasnow, R., additional, Jang, K. L., additional, Knafo-Noam, A., additional, Mankuta, D., additional, Abramson, L., additional, Lichtenstein, P., additional, Krueger, R. F., additional, McGue, M., additional, Pahlen, S., additional, Tynelius, P., additional, Rasmussen, F., additional, Duncan, G. E., additional, Buchwald, D., additional, Corley, R. P., additional, Huibregtse, B. M., additional, Nelson, T. L., additional, Whitfield, K. E., additional, Franz, C. E., additional, Kremen, W. S., additional, Lyons, M. J., additional, Ooki, S., additional, Brandt, I., additional, Nilsen, T. S., additional, Harris, J. R., additional, Sung, J., additional, Park, H. A., additional, Lee, J., additional, Lee, S. J., additional, Willemsen, G., additional, Bartels, M., additional, van Beijsterveldt, C. E. M., additional, Llewellyn, C. H., additional, Fisher, A., additional, Rebato, E., additional, Busjahn, A., additional, Tomizawa, R., additional, Inui, F., additional, Watanabe, M., additional, Honda, C., additional, Sakai, N., additional, Hur, Y.-M., additional, Sørensen, T. I. A., additional, Boomsma, D. I., additional, and Kaprio, J., additional

Published
2019
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5. The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins

Author

Silventoinen, K., Jelenkovic, A., Yokoyama, Y., Sund, R., Sugawara, M., Tanaka, M., Matsumoto, S., Bogl, L. H., Freitas, D. L., Maia, J. A., Hjelmborg, J. v. B., Aaltonen, S., Piirtola, M., Latvala, A., Calais-Ferreira, L., Oliveira, V. C., Ferreira, P. H., Ji, F., Ning, F., Pang, Z., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Burt, S. A., Klump, K. L., Martin, N. G., Medland, S. E., Montgomery, G. W., Kandler, C., McAdams, T. A., Eley, T. C., Gregory, A. M., Saudino, K. J., Dubois, L., Boivin, M., Brendgen, M., Dionne, G., Vitaro, F., Tarnoki, A. D., Tarnoki, D. L., Haworth, C. M. A., Plomin, R., Oncel, S. Y., Aliev, F., Medda, E., Nistico, L., Toccaceli, V., Craig, J. M., Saffery, R., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Jeong, H. -U., Spector, T., Mangino, M., Lachance, G., Gatz, M., Butler, D. A., Gao, W., Yu, C., Li, L., Bayasgalan, G., Narandalai, D., Harden, K. P., Tucker-Drob, E. M., Christensen, K., Skytthe, A., Kyvik, K. O., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Cozen, W., Hwang, A. E., Mack, T. M., He, M., Ding, X., Silberg, J. L., Maes, H. H., Cutler, T. L., Hopper, J. L., Magnusson, P. K. E., Pedersen, N. L., Dahl Aslan, A. K., Baker, L. A., Tuvblad, C., Bjerregaard-Andersen, M., Beck-Nielsen, H., Sodemann, M., Ullemar, V., Almqvist, C., Tan, Q., Zhang, D., Swan, G. E., Krasnow, R., Jang, K. L., Knafo-Noam, A., Mankuta, D., Abramson, L., Lichtenstein, P., Krueger, R. F., McGue, M., Pahlen, S., Tynelius, P., Rasmussen, F., Duncan, G. E., Buchwald, D., Corley, R. P., Huibregtse, B. M., Nelson, T. L., Whitfield, K. E., Franz, C. E., Kremen, W. S., Lyons, M. J., Ooki, S., Brandt, I., Nilsen, T. S., Harris, J. R., Sung, J., Park, H. A., Lee, J., Lee, S. J., Willemsen, G., Bartels, M., Van Beijsterveldt, C. E. M., Llewellyn, C. H., Fisher, A., Rebato, E., Busjahn, A., Tomizawa, R., Inui, F., Watanabe, M., Honda, C., Sakai, N., Hur, Y. -M., Sørensen, T. I. A., Boomsma, D. I., Kaprio, J., Silventoinen, K., Jelenkovic, A., Yokoyama, Y., Sund, R., Sugawara, M., Tanaka, M., Matsumoto, S., Bogl, L. H., Freitas, D. L., Maia, J. A., Hjelmborg, J. v. B., Aaltonen, S., Piirtola, M., Latvala, A., Calais-Ferreira, L., Oliveira, V. C., Ferreira, P. H., Ji, F., Ning, F., Pang, Z., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Burt, S. A., Klump, K. L., Martin, N. G., Medland, S. E., Montgomery, G. W., Kandler, C., McAdams, T. A., Eley, T. C., Gregory, A. M., Saudino, K. J., Dubois, L., Boivin, M., Brendgen, M., Dionne, G., Vitaro, F., Tarnoki, A. D., Tarnoki, D. L., Haworth, C. M. A., Plomin, R., Oncel, S. Y., Aliev, F., Medda, E., Nistico, L., Toccaceli, V., Craig, J. M., Saffery, R., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Jeong, H. -U., Spector, T., Mangino, M., Lachance, G., Gatz, M., Butler, D. A., Gao, W., Yu, C., Li, L., Bayasgalan, G., Narandalai, D., Harden, K. P., Tucker-Drob, E. M., Christensen, K., Skytthe, A., Kyvik, K. O., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Cozen, W., Hwang, A. E., Mack, T. M., He, M., Ding, X., Silberg, J. L., Maes, H. H., Cutler, T. L., Hopper, J. L., Magnusson, P. K. E., Pedersen, N. L., Dahl Aslan, A. K., Baker, L. A., Tuvblad, C., Bjerregaard-Andersen, M., Beck-Nielsen, H., Sodemann, M., Ullemar, V., Almqvist, C., Tan, Q., Zhang, D., Swan, G. E., Krasnow, R., Jang, K. L., Knafo-Noam, A., Mankuta, D., Abramson, L., Lichtenstein, P., Krueger, R. F., McGue, M., Pahlen, S., Tynelius, P., Rasmussen, F., Duncan, G. E., Buchwald, D., Corley, R. P., Huibregtse, B. M., Nelson, T. L., Whitfield, K. E., Franz, C. E., Kremen, W. S., Lyons, M. J., Ooki, S., Brandt, I., Nilsen, T. S., Harris, J. R., Sung, J., Park, H. A., Lee, J., Lee, S. J., Willemsen, G., Bartels, M., Van Beijsterveldt, C. E. M., Llewellyn, C. H., Fisher, A., Rebato, E., Busjahn, A., Tomizawa, R., Inui, F., Watanabe, M., Honda, C., Sakai, N., Hur, Y. -M., Sørensen, T. I. A., Boomsma, D. I., and Kaprio, J.

Published
2019

6. The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins

Author

Silventoinen, K, Jelenkovic, A, Yokoyama, Y, Sund, R, Sugawara, M, Tanaka, M, Matsumoto, S, Bogl, L H, Freitas, D L, Maia, J A, Hjelmborg, J V B, Aaltonen, S, Piirtola, M, Latvala, A, Calais-Ferreira, L, Oliveira, V C, Ferreira, P H, Ji, F, Ning, F, Pang, Z, Ordoñana, J R, Sánchez-Romera, J F, Colodro-Conde, L, Burt, S A, Klump, K L, Martin, N G, Medland, S E, Montgomery, G W, Kandler, C, McAdams, T A, Eley, T C, Gregory, A M, Saudino, K J, Dubois, L, Boivin, M, Brendgen, M, Dionne, G, Vitaro, F, Tarnoki, A D, Tarnoki, D L, Haworth, C M A, Plomin, R, Öncel, S Y, Aliev, F, Medda, E, Nisticò, L, Toccaceli, V, Craig, J M, Saffery, R, Siribaddana, S H, Hotopf, M, Sumathipala, A, Rijsdijk, F, Jeong, H-U, Spector, T, Mangino, M, Lachance, G, Gatz, M, Butler, D A, Gao, W, Yu, C, Li, L, Bayasgalan, G, Narandalai, D, Harden, K P, Tucker-Drob, E M, Christensen, K, Skytthe, A, Kyvik, K O, Derom, C A, Vlietinck, R F, Loos, R J F, Cozen, W, Hwang, A E, Mack, T M, He, M, Ding, X, Silberg, J L, Maes, H H, Cutler, T L, Hopper, J L, Magnusson, P K E, Pedersen, N L, Dahl Aslan, A K, Baker, L A, Tuvblad, C, Bjerregaard-Andersen, M, Beck-Nielsen, H, Sodemann, M, Ullemar, V, Almqvist, C, Tan, Q, Zhang, D, Swan, G E, Krasnow, R, Jang, K L, Knafo-Noam, A, Mankuta, D, Abramson, L, Lichtenstein, P, Krueger, R F, McGue, M, Pahlen, S, Tynelius, P, Rasmussen, F, Duncan, G E, Buchwald, D, Corley, R P, Huibregtse, B M, Nelson, T L, Whitfield, K E, Franz, C E, Kremen, W S, Lyons, M J, Ooki, S, Brandt, I, Nilsen, T S, Harris, J R, Sung, J, Park, H A, Lee, J, Lee, S J, Willemsen, Gonneke, Bartels, Meike, van Beijsterveldt, C.E.M., Llewellyn, C H, Fisher, A, Rebato, E, Busjahn, A, Tomizawa, R, Inui, F, Watanabe, M, Honda, C, Sakai, N, Hur, Y-M, Sørensen, T I A, Boomsma, D.I., Kaprio, J, Silventoinen, K, Jelenkovic, A, Yokoyama, Y, Sund, R, Sugawara, M, Tanaka, M, Matsumoto, S, Bogl, L H, Freitas, D L, Maia, J A, Hjelmborg, J V B, Aaltonen, S, Piirtola, M, Latvala, A, Calais-Ferreira, L, Oliveira, V C, Ferreira, P H, Ji, F, Ning, F, Pang, Z, Ordoñana, J R, Sánchez-Romera, J F, Colodro-Conde, L, Burt, S A, Klump, K L, Martin, N G, Medland, S E, Montgomery, G W, Kandler, C, McAdams, T A, Eley, T C, Gregory, A M, Saudino, K J, Dubois, L, Boivin, M, Brendgen, M, Dionne, G, Vitaro, F, Tarnoki, A D, Tarnoki, D L, Haworth, C M A, Plomin, R, Öncel, S Y, Aliev, F, Medda, E, Nisticò, L, Toccaceli, V, Craig, J M, Saffery, R, Siribaddana, S H, Hotopf, M, Sumathipala, A, Rijsdijk, F, Jeong, H-U, Spector, T, Mangino, M, Lachance, G, Gatz, M, Butler, D A, Gao, W, Yu, C, Li, L, Bayasgalan, G, Narandalai, D, Harden, K P, Tucker-Drob, E M, Christensen, K, Skytthe, A, Kyvik, K O, Derom, C A, Vlietinck, R F, Loos, R J F, Cozen, W, Hwang, A E, Mack, T M, He, M, Ding, X, Silberg, J L, Maes, H H, Cutler, T L, Hopper, J L, Magnusson, P K E, Pedersen, N L, Dahl Aslan, A K, Baker, L A, Tuvblad, C, Bjerregaard-Andersen, M, Beck-Nielsen, H, Sodemann, M, Ullemar, V, Almqvist, C, Tan, Q, Zhang, D, Swan, G E, Krasnow, R, Jang, K L, Knafo-Noam, A, Mankuta, D, Abramson, L, Lichtenstein, P, Krueger, R F, McGue, M, Pahlen, S, Tynelius, P, Rasmussen, F, Duncan, G E, Buchwald, D, Corley, R P, Huibregtse, B M, Nelson, T L, Whitfield, K E, Franz, C E, Kremen, W S, Lyons, M J, Ooki, S, Brandt, I, Nilsen, T S, Harris, J R, Sung, J, Park, H A, Lee, J, Lee, S J, Willemsen, Gonneke, Bartels, Meike, van Beijsterveldt, C.E.M., Llewellyn, C H, Fisher, A, Rebato, E, Busjahn, A, Tomizawa, R, Inui, F, Watanabe, M, Honda, C, Sakai, N, Hur, Y-M, Sørensen, T I A, Boomsma, D.I., and Kaprio, J

Abstract

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Published
2019
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8. FRANKENSTEIN'S MONKEY.

Author

MCADAMS, T. S.

Subjects
MONKEYS, ZONE of proximal development, ANTIQUE dealers
Abstract

The article, titled "Frankenstein's Monkey," tells the story of a chimpanzee named Baldwin who escapes from a research facility and embarks on a journey in the forest. Baldwin, who possesses the ability to write and communicate through sign language, shares his experiences and thoughts through his narration. The article also mentions a researcher named Lorraine and her colleague Rudy, who is working on rehabilitating a gorilla named Jane. The narrative explores themes of redemption, sin, and the complex relationships between humans and animals. [Extracted from the article]

Published
2021

9. Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region : An individual-based pooled analysis of 40 twin cohorts

Author

Silventoinen, K., Jelenkovic, A., Sund, R., Yokoyama, Y., Hur, Y. -M, Cozen, W., Hwang, A. E., Mack, T. M., Honda, C., Inui, F., Iwatani, Y., Watanabe, M., Tomizawa, R., Pietilainen, K. H., Rissanen, A., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Piirtola, M., Aaltonen, S., Oncel, S. Y., Aliev, F., Rebato, E., Hjelmborg, J. B., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Cutler, T. L., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Song, Y. -M, Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D'Ippolito, C., Duncan, G. E., Buchwald, D., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. -U, Swan, G. E., Krasnow, R., Magnusson, P. K. E., Pedersen, N. L., Dahl Aslan, Anna K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Spector, T. D., Mangino, M., Lachance, G., Burt, S. A., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Huibregtse, B. M., Bartels, M., Van Beijsterveldt, C. E. M., Willemsen, G., Goldberg, J. H., Rasmussen, F., Tarnoki, A. D., Tarnoki, D. L., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Hopper, J. L., Sung, J., Maes, H. H., Turkheimer, E., Boomsma, D. I., Sørensen, T. I. A., Kaprio, J., Silventoinen, K., Jelenkovic, A., Sund, R., Yokoyama, Y., Hur, Y. -M, Cozen, W., Hwang, A. E., Mack, T. M., Honda, C., Inui, F., Iwatani, Y., Watanabe, M., Tomizawa, R., Pietilainen, K. H., Rissanen, A., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Piirtola, M., Aaltonen, S., Oncel, S. Y., Aliev, F., Rebato, E., Hjelmborg, J. B., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Cutler, T. L., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Song, Y. -M, Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D'Ippolito, C., Duncan, G. E., Buchwald, D., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. -U, Swan, G. E., Krasnow, R., Magnusson, P. K. E., Pedersen, N. L., Dahl Aslan, Anna K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Spector, T. D., Mangino, M., Lachance, G., Burt, S. A., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Huibregtse, B. M., Bartels, M., Van Beijsterveldt, C. E. M., Willemsen, G., Goldberg, J. H., Rasmussen, F., Tarnoki, A. D., Tarnoki, D. L., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Hopper, J. L., Sung, J., Maes, H. H., Turkheimer, E., Boomsma, D. I., Sørensen, T. I. A., and Kaprio, J.

Abstract

Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m2)], but factors modifying these variance components are poorly understood. Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity. Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs). Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI. Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.

Published
2017
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10. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

Author

Jelenkovic, A., Hur, Y. -M, Sund, R., Yokoyama, Y., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Aaltonen, S., Heikkilä, K., Öncel, S.Y., Aliev, F., Rebato, E., Tarnoki, A. D., Tarnoki, D. L., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Ordoñana, J. R., Sánchez-Romera, J. F., Colodro-Conde, L., Cozen, W., Hwang, A. E., Mack, T. M., Sung, J., Song, Y. -M, Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D’Ippolito, C., Duncan, G. E., Buchwald, D., Derom, C. A., Vlietinck, R. F., Loos, R. J., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. -U, Swan, G. E., Krasnow, R., Magnusson, P. K., Pedersen, N. L., Dahl-Aslan, Anna K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Lichtenstein, P., Spector, T. D., Mangino, M., Lachance, G., Bartels, M., Van Beijsterveldt, T. C., Willemsen, G., Alexandra Burt, S., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Hjelmborg, J. V. B., Goldberg, J. H., Iwatani, Y., Watanabe, M., Honda, C., Inui, F., Rasmussen, F., Huibregtse, B. M., Boomsma, D. I., Sørensen, T. I. A., Kaprio, J., Silventoinen, K., Jelenkovic, A., Hur, Y. -M, Sund, R., Yokoyama, Y., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Aaltonen, S., Heikkilä, K., Öncel, S.Y., Aliev, F., Rebato, E., Tarnoki, A. D., Tarnoki, D. L., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Ordoñana, J. R., Sánchez-Romera, J. F., Colodro-Conde, L., Cozen, W., Hwang, A. E., Mack, T. M., Sung, J., Song, Y. -M, Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D’Ippolito, C., Duncan, G. E., Buchwald, D., Derom, C. A., Vlietinck, R. F., Loos, R. J., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. -U, Swan, G. E., Krasnow, R., Magnusson, P. K., Pedersen, N. L., Dahl-Aslan, Anna K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Lichtenstein, P., Spector, T. D., Mangino, M., Lachance, G., Bartels, M., Van Beijsterveldt, T. C., Willemsen, G., Alexandra Burt, S., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Hjelmborg, J. V. B., Goldberg, J. H., Iwatani, Y., Watanabe, M., Honda, C., Inui, F., Rasmussen, F., Huibregtse, B. M., Boomsma, D. I., Sørensen, T. I. A., Kaprio, J., and Silventoinen, K.

Abstract

Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.

Published
2016
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11. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

Author

University of Helsinki, Department of Social Research, University of Helsinki, Department of Public Health, University of Helsinki, Clinicum, Jelenkovic, Aline, Hur, Yoon-Mi, Sund, Reijo, Yokoyama, Y., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Aaltonen, Sari, Heikkilä, Kauko, Oncel, S. Y., Aliev, F., Rebato, E., Tarnoki, A. D., Tarnoki, D. L., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Cozen, W., Hwang, A. E., Mack, T. M., Sung, J., Song, Y. M., Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D'Ippolito, C., Duncan, G. E., Buchwald, D., Derom, C. A., Vlietinck, R. F., Loos, R. J., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. U., Swan, G. E., Krasnow, R., Magnusson, P. K., Pedersen, N. L., Dahl-Aslan, A. K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Lichtenstein, P., Spector, T. D., Mangino, M., Lachance, G., Bartels, M., van Beijsterveldt, T. C., Willemsen, G., Burt, S. A., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Hjelmborg, J. V., Goldberg, J. H., Iwatani, Y., Watanabe, M., Honda, C., Inui, F., Rasmussen, F., Huibregtse, B. M., Boomsma, D. I., Sorensen, T. I., Kaprio, Jaakko, Silventoinen, Karri, University of Helsinki, Department of Social Research, University of Helsinki, Department of Public Health, University of Helsinki, Clinicum, Jelenkovic, Aline, Hur, Yoon-Mi, Sund, Reijo, Yokoyama, Y., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Aaltonen, Sari, Heikkilä, Kauko, Oncel, S. Y., Aliev, F., Rebato, E., Tarnoki, A. D., Tarnoki, D. L., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Cozen, W., Hwang, A. E., Mack, T. M., Sung, J., Song, Y. M., Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D'Ippolito, C., Duncan, G. E., Buchwald, D., Derom, C. A., Vlietinck, R. F., Loos, R. J., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. U., Swan, G. E., Krasnow, R., Magnusson, P. K., Pedersen, N. L., Dahl-Aslan, A. K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Lichtenstein, P., Spector, T. D., Mangino, M., Lachance, G., Bartels, M., van Beijsterveldt, T. C., Willemsen, G., Burt, S. A., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Hjelmborg, J. V., Goldberg, J. H., Iwatani, Y., Watanabe, M., Honda, C., Inui, F., Rasmussen, F., Huibregtse, B. M., Boomsma, D. I., Sorensen, T. I., Kaprio, Jaakko, and Silventoinen, Karri

Abstract

Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.

Published
2016

13. Attentional threat avoidance and familial risk are independently associated with childhood anxiety disorders

Author

Brown, H, McAdams, T, Lester, K, Goodman, R, Clark, D, and Eley, T

Abstract

Background: Twin studies in children reveal that familial aggregation of anxiety disorders is due to both genetic and environmental factors. Cognitive biases for threat information are considered a robust characteristic of childhood anxiety. However, little is known regarding the underlying aetiology of such biases and their role in anxiety disorders. Method: A face version of the dot-probe task measuring attentional biases for negative (anger, fear, sad, disgust) and positive (happy) facial expressions was completed by 600, 8-year-old twins; the largest study of its kind. Twin correlations for attentional bias scores were compared to estimate genetic and environmental effects. Parent-report diagnostic interviews identified children with an anxiety disorder. Indices of inferred genetic and familial risk for anxiety disorders were created for each child. Data were analysed using a series of logistic regressions. Results: Anxious children showed greater attentional avoidance of negative faces than nonanxious children; t (548) = 2.55, p

Published
2013

14. Shared genetic influences do not explain the association between parent-offspring relationship quality and offspring internalizing problems: results from a Children-of-Twins study.

Author

Hannigan, L. J., Rijsdijk, F. V., Ganiban, J. M., Reiss, D., Spotts, E. L., Neiderhiser, J. M., Lichtenstein, P., McAdams, T. A., and Eley, T. C.

Subjects
CHILD Behavior Checklist, CONFLICT (Psychology), FRIENDSHIP, GENETICS, INTERPERSONAL relations, MENTAL illness, MOTHER-infant relationship, PARENTING, PATHOLOGICAL psychology, SELF-evaluation, TWINS
Abstract

Background: Associations between parenting and child outcomes are often interpreted as reflecting causal, social influences. However, such associationsmay be confounded by genes common to children and their biological parents. To the extent that these shared genes influence behaviours in both generations, a passive genetic mechanismmay explain links between them. Here we aim to quantify the relative importance of passive genetic v. social mechanisms in the intergenerational association between parent-offspring relationship quality and offspring internalizing problems in adolescence. Methods: We used a Children-of-Twins (CoT) designwith data fromthe parent-based Twin andOffspring Study of Sweden (TOSS) sample [909 adult twin pairs and their offspring; offspringmean age 15.75 (2.42) years], and the child-based Swedish Twin Study of CHild and Adolescent Development (TCHAD) sample [1120 adolescent twin pairs; mean age 13.67 (0.47) years]. A composite of parent-report measures (closeness, conflict, disagreements, expressions of affection) indexed parent- offspring relationship quality in TOSS, and offspring self-reported internalizing symptoms were assessed using the Child Behavior Checklist (CBCL) in both samples. Results: A social transmissionmechanism explained the intergenerational association [r = 0.21 (0.16-0.25)] in our best-fitting model. Apassive genetic transmission pathwaywas not found to be significant, indicating that parental genetic influences on parent-offspring relationship quality and offspring genetic influences on their internalizing problemswere non-overlapping. Conclusion: These results indicate that this intergenerational association is a product of social interactions between children and parents, within which bidirectional effects are highly plausible. Results fromgenetically informative studies of parentingrelated effects should be used to help refine early parenting interventions aimed at reducing risk for psychopathology. [ABSTRACT FROM AUTHOR]

Published
2018
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15. Duck Circles.

Author

McAdams, T. S.

Subjects
WILDLIFE refuges
Published
2019

16. The CODATwins Project: the cohort description of collaborative project of development of anthropometrical measures in twins to study macro-environmental variation in genetic and environmental effects on anthropometric traits

Author

Silventoinen, K., Jelenkovic, A., Sund, R., Honda, C., Aaltonen, S., Yokoyama, Y., Tarnoki, AD, Tarnoki, D. L., Ning, F., Ji, F., Pang, Z., Ordoñana, J. R., Sánchez-Romera, J. F., Colodro-Conde, L., Burt, S. A., Klump, K. L., Medland, S. E., Montgomery, G. W., Kandler, C., McAdams, T. A., Eley, T. C., Gregory, A. M., Saudino, K. J., Dubois, L., Boivin, M., Haworth, C. M. A., Plomin, R., Öncel, S. Y., Aliev, F., Stazi, M. A., Fagnani, C., D'Ippolito, C., Craig, J., Saffery, R., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Spector, T., Mangino, M., Lachance, G., Gatz, M., Butler, D. A., Bayasgalan, G., Narandalai, D., Freitas, D. L., Maia, J. A., Harden, K. P., Tucker-Drob, E. M., Christensen, K., Skytthe, A., Kyvik, K. O., Hong, C., Chong, Y., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Cozen, W., Hwang, A. E., Mack, T. M., He, M., Ding, X., Chang, B., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Aujard, K., Magnusson, P. K. E., Pedersen, N. L., Aslan, A. K. D., Song, Y.- M., Yang, S., Lee, K., Baker, L. A., Tuvblad, C., Bjerregaard-Andersen, M., Beck-Nielsen, H., Sodemann, M., Heikkilä, K., Tan, Q., Zhang, D., Swan, G. E., Krasnow, R., Jang, K. L., Knafo-Noam, A., Mankuta, D., Abramson, L., Lichtenstein, P., Krueger, R. F., McGue, M., Pahlen, S., Tynelius, P., Duncan, G. E., Buchwald, D., Corley, R. P., Huibregtse, B. M., Nelson, T. L., Whitfield, K. E., Franz, C. E., Kremen, W. S., Lyons, M. J., Ooki, S., Brandt, I., Nilsen, T. S., Inui, F., Watanabe, M., Bartels, M., van Beijsterveldt, T. C. E. M., Wardle, J., Llewellyn, C. H., Fisher, A., Rebato, E., Martin, N. G., Iwatani, Y., Hayakawa, K., Rasmussen, F., Sung, J., Harris, J. R., Willemsen, G., Busjahn, A., Goldberg, J. H., Boomsma, D. I., Hur, Y. - M., Sørensen, T. I. A., Kaprio, J., Silventoinen, K., Jelenkovic, A., Sund, R., Honda, C., Aaltonen, S., Yokoyama, Y., Tarnoki, AD, Tarnoki, D. L., Ning, F., Ji, F., Pang, Z., Ordoñana, J. R., Sánchez-Romera, J. F., Colodro-Conde, L., Burt, S. A., Klump, K. L., Medland, S. E., Montgomery, G. W., Kandler, C., McAdams, T. A., Eley, T. C., Gregory, A. M., Saudino, K. J., Dubois, L., Boivin, M., Haworth, C. M. A., Plomin, R., Öncel, S. Y., Aliev, F., Stazi, M. A., Fagnani, C., D'Ippolito, C., Craig, J., Saffery, R., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Spector, T., Mangino, M., Lachance, G., Gatz, M., Butler, D. A., Bayasgalan, G., Narandalai, D., Freitas, D. L., Maia, J. A., Harden, K. P., Tucker-Drob, E. M., Christensen, K., Skytthe, A., Kyvik, K. O., Hong, C., Chong, Y., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Cozen, W., Hwang, A. E., Mack, T. M., He, M., Ding, X., Chang, B., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Aujard, K., Magnusson, P. K. E., Pedersen, N. L., Aslan, A. K. D., Song, Y.- M., Yang, S., Lee, K., Baker, L. A., Tuvblad, C., Bjerregaard-Andersen, M., Beck-Nielsen, H., Sodemann, M., Heikkilä, K., Tan, Q., Zhang, D., Swan, G. E., Krasnow, R., Jang, K. L., Knafo-Noam, A., Mankuta, D., Abramson, L., Lichtenstein, P., Krueger, R. F., McGue, M., Pahlen, S., Tynelius, P., Duncan, G. E., Buchwald, D., Corley, R. P., Huibregtse, B. M., Nelson, T. L., Whitfield, K. E., Franz, C. E., Kremen, W. S., Lyons, M. J., Ooki, S., Brandt, I., Nilsen, T. S., Inui, F., Watanabe, M., Bartels, M., van Beijsterveldt, T. C. E. M., Wardle, J., Llewellyn, C. H., Fisher, A., Rebato, E., Martin, N. G., Iwatani, Y., Hayakawa, K., Rasmussen, F., Sung, J., Harris, J. R., Willemsen, G., Busjahn, A., Goldberg, J. H., Boomsma, D. I., Hur, Y. - M., Sørensen, T. I. A., and Kaprio, J.

Published
2015

18. Aetiological influences on stability and change in emotional and behavioural problems across development: a systematic review.

Author

Hannigan, L. J., Walaker, N., Waszczuk, M. A., McAdams, T. A., and Eley, T. C.

Subjects
ADOLESCENT psychopathology, PATHOLOGICAL psychology, MENTAL depression risk factors, EFFECT of environment on human beings, ANXIETY, GENETICS
Abstract

Emotional and behavioural problems in childhood and adolescence can be chronic and are predictive of future psychiatric problems. Understanding what factors drive the development and maintenance of these problems is therefore crucial. Longitudinal behavioural genetic studies using twin, sibling or adoption data can be used to explore the developmental aetiology of stability and change in childhood and adolescent psychopathology. We present a systematic review of longitudinal, behavioural genetic analyses of emotional and behavioural problems between ages 0 to 18 years. We identified 58 studies, of which 19 examined emotional problems, 30 examined behavioural problems, and 9 examined both. In the majority of studies, stability in emotional and behavioural problems was primarily genetically influenced. Stable environmental factors were also widely found, although these typically played a smaller role. Both genetic and environmental factors were involved in change across development. We discuss the findings in the context of the wider developmental literature and make recommendations for future research. [ABSTRACT FROM AUTHOR]

Published
2017
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22. Southland Coyote Reports.

Author

McADAMS, T. S.

Subjects
NATIVE American studies
Abstract

This article from the Sierra Nevada Review recounts three separate stories involving Coyote, a character who engages in various interactions and experiences. In the first story, Coyote attends a party with professors and attempts to impress an American Indian Studies professor by speaking Nahuatl and showcasing his dancing skills. In the second story, Coyote encounters a Young Evangelist who offers him money for bus fare, but Coyote feels guilty for taking more than what was given. In the third story, Coyote uses his power to transform people into coyotes and later helps them build a house, resulting in his arrest for destruction of public property. These stories provide insights into Coyote's character and his interactions with others. [Extracted from the article]

Published
2019

25. Incidence of Pathogenic Microorganisms in Aquacultured Rainbow Trout (Oncorhynchus mykiss).

Author

James Mcadams, T., Reinhart, Robert G., Fernandes, Custy F., Flick Jr., George J., Smith, Stephen A., Hackney, Cameron R., Libey, George S., and Ankenman Granata, L.

Subjects
*PATHOGENIC microorganisms, *RAINBOW trout, *ONCORHYNCHUS, *ENTEROBACTERIACEAE, *GRAM-positive bacteria, *PSEUDOTUBERCULOSIS
Abstract

Quantitative levels of six known pathogens (Listeria ,monocytogenes, Clostridium botulinum, Salmonella species, Vibrio cholerae, Yersinia enterocolitica, and Y. pseudotuberculosis) and aerobic plate counts were measured at five aquaculture facilities. The farmed rainbow trout (Oncorhynchus mykiss) and trout fillets were sampled at two different growing seasons to monitor for microbial hazards. Listeria spp. was identified in both whole trout and trout fillets from all five facilities sampled from both growing seasons. Presumptive Clostridium botulinum spores were also identified from all five facilities for both seasons. The growing season did not affect pathogen levels and there was no evidence that any one aquacultural system was superior to the others. Salmonella spp., Vibrio cholerae, and Yersinia spp. were not isolated from any of the trout samples analyzed. [ABSTRACT FROM AUTHOR]

Published
2005
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28. LETTERS TO FORTUNE.

Author

Herman, John, Beauchamp, Andrew, Gilbert, Maureen, Vivirito, Jill M., Rao, Srikumar S., McAdams, T. K., Farley, Shawn, Murry, Charles, McGrath, Jim, Takefman, Earl, and Ross, Ken

Subjects
LETTERS to the editor, FAMILY-work relationship, TAXATION, CAREER development, PUBLIC administration
Abstract

Several letters to the editor are presented including "Is Your Family Wrecking Your Career?" in the March 17, 1997 issue, "What's New on the Tax Front? More Than You Think" in the March 17, 1997 issue and "Hilton vs. ITT: It Ought to Be No Contest" in the March 3, 1997 issue.

Published
1997

34. pH is a potent modulator of erythroid differentiation.

Author

McAdams TA, Miller WM, and Papoutsakis ET

Subjects
Anion Exchange Protein 1, Erythrocyte analysis, Antigens, CD blood, Antigens, CD34 blood, Antigens, Differentiation, B-Lymphocyte blood, Blotting, Western, Cell Culture Techniques, Cell Differentiation physiology, Colony-Forming Units Assay, Erythropoietin pharmacology, Flow Cytometry, Hemoglobins analysis, Humans, Hydrogen-Ion Concentration, Immunoenzyme Techniques, Receptors, Transferrin, Erythroid Precursor Cells cytology
Abstract

Physiological parameters such as pH and oxygen tension probably play significant roles in the regulation of haemopoiesis in the bone marrow microenvironment, but these roles have yet to be characterized in detail. We have found that changes in culture pH (0.2 units) can cause significant changes in the culture composition of mature cells and colony-forming cells (CFCs), especially in the presence of erythropoietin (Epo). Peripheral blood (PB) CD34+ cells cultured at different pH values (7.15-7.6) were characterized using total cell counts, colony assays, morphological analysis. haemoglobin staining, flow cytometry, immunocytochemical staining, and Western blots. Cultures performed at high (7.6) pH contained greater numbers of haemoglobin-positive and band-3-positive cells. and acquired these erythroid differentiation markers sooner than standard (7.35) and low (7.1) pH cultures. Flow cytometry using CD71 and CD45RA antigens also indicated that erythroid differentiation proceeds faster at high pH and is blocked at an intermediate stage by low pH. Morphological data confirmed that high pH cultures had been shifted towards late-stage erythroid compartments as compared to low and standard pH cultures. These findings have important implications both in elucidating the regulatory role of pH in the bone marrow microenvironment and for the design of in vitro systems to study the development of erythroid cells.

Published
1998
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35. Culture materials affect ex vivo expansion of hematopoietic progenitor cells.

Author

LaIuppa JA, McAdams TA, Papoutsakis ET, and Miller WM

Subjects
Antigens, CD34, Cell Adhesion, Cell Division, Cells, Cultured, Culture Media, Serum-Free, Eyeglasses, Humans, Metals, Polymers, Biocompatible Materials, Hematopoietic Stem Cells cytology
Abstract

Ex vivo expansion of hematopoietic cells is important for applications such as cancer treatment, gene therapy, and transfusion medicine. While cell culture systems are widely used to evaluate the biocompatibility of materials for implantation, the ability of materials to support proliferation of primary human cells in cultures for reinfusion into patients has not been addressed. We screened a variety of commercially available polymer (15 types), metal (four types), and glass substrates for their ability to support expansion of hematopoietic cells when cultured under conditions that would be encountered in a clinical setting. Cultures of peripheral blood (PB) CD34+ cells and mononuclear cells (MNC) were evaluated for expansion of total cells and colony-forming unit-granulocyte monocyte (CFU-GM; progenitors committed to the granulocyte and/or monocyte lineage). Human hematopoietic cultures in serum-free medium were found to be extremely sensitive to the substrate material. The only materials tested that supported expansion at or near the levels of polystyrene were tissue culture polystyrene, Teflon perfluoroalkoxy, Teflon fluorinated ethylene propylene, cellulose acetate, titanium, new polycarbonate, and new polymethylpentene. MNC were less sensitive to the substrate materials than the primitive CD34+ progenitors, although similar trends were seen for expansion of the two cell populations on the substrates tested. CFU-GM expansion was more sensitive to substrate materials than was total cell expansion. The detrimental effects of a number of the materials on hematopoietic cultures appear to be caused by protein adsorption and/or leaching of toxins. Factors such as cleaning, sterilization, and reuse significantly affected the performance of some materials as culture substrates. We also used PB CD34+ cell cultures to examine the biocompatibility of gas-permeable cell culture and blood storage bags and several types of tubing commonly used with biomedical equipment. While many of the culture bag materials gave satisfactory results, all of the tubing materials severely inhibited total cell and CFU-GM expansion. Taken together, our results show that many materials approved for blood contact or considered biocompatible are not suitable for use with hematopoietic cells cultured in serum-free medium. As hematopoietic cultures are scaled up for a variety of clinical applications, it will be essential to carefully examine the biocompatibility of all materials involved.

Published
1997
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36. Variations in culture pH affect the cloning efficiency and differentiation of progenitor cells in ex vivo haemopoiesis.

Author

McAdams TA, Miller WM, and Papoutsakis ET

Subjects
Antigens, CD34, Cell Differentiation, Cells, Cultured, Clone Cells, Culture Media, Cytokines pharmacology, Humans, Hydrogen-Ion Concentration, Methylcellulose chemistry, Hematopoietic Stem Cells cytology
Abstract

Haemopoietic cultures may experience pH variations of as much as 0.5 units depending on culture duration and cell density. Since pH is a potent modulator of cellular proliferation and differentiation, we examined its effects on the performance of both semisolid and liquid haemopoietic cultures. Culture pH was found to have substantial effects both on progenitor cloning efficiency (as measured in liquid cultures) and on progenitor cell differentiation (as measured in methylcellulose cultures). Liquid cultures were conducted with both peripheral blood (PB) mononuclear cells (MNCs) and cord blood (CB) MNCs using growth factor combinations that promote either erythroid expansion (IL-3/IL-6/SCF/Epo) or granulocyte/macrophage expansion (IL-3/IL-6/SCF/G-CSF/GM-CSF). Reduced pH was found to have either a positive or neutral effect on the expansion and cloning efficiency of progenitors in ex vivo liquid cultures. Cloning efficiencies of PB BFU-E in the erythroid combination were 9-fold higher at low pH (7.1) when compared to high pH (7.6). A small pH increase of 0.2 units over physiological values consistently produced significant reductions (42-85%) in cloning efficiencies for all cell types and cytokine combinations tested. Methylcellulose cultures conducted using CB MNC and PB MNC indicated that differentiation of CFU-GM into progeny was optimal between pH 7.2 and 7.4. The differentiation of erythroid progenitors (BFU-E) progressively increased as pH was increased from 6.95 (no colonies detected) to 7.4 (maximum colonies detected), to 7.6 (maximum haemoglobin content). Methylcellulose cultures using PB CD34+ cells exhibited similar patterns to the MNC cultures. We conclude that even small variations in pH substantially affected the performance of human haemopoietic cultures. The erythroid lineage was particularly sensitive, with its extent of differentiation increasing with increasing pH. PB progenitors are more sensitive to pH variations than CB progenitors.

Published
1997
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37. Comparison of whole serum-deprived media for ex vivo expansion of hematopoietic progenitor cells from cord blood and mobilized peripheral blood mononuclear cells.

Author

Sandstrom CE, Collins PC, McAdams TA, Bender JG, Papoutsakis ET, and Miller WM

Subjects
Cell Division, Cells, Cultured, Female, Humans, Pregnancy, Cell Separation methods, Culture Media, Fetal Blood cytology, Hematopoietic Stem Cells cytology, Leukocytes, Mononuclear cytology
Abstract

A whole serum-deprived (WSD) medium was developed and optimized for expansion of colony-forming cells (CFC) in cord blood (CB) mononuclear cell (MNC) cultures. This medium was compared with four commercially available WSD media (commercial media), three WSD media whose compositions have been publicly disclosed (public media), two serum-containing media, and two basal media, for cell and CFC expansion in 10-day CB and mobilized peripheral blood (PB) MNC cultures supplemented with interleukin-3 (IL-3), IL-6, and stem cell factor (SCF). Selected WSD media and both serum-containing media gave significant CFC expansion in CBMNC and PBMNC cultures. The serum-containing human long-term medium gave the greatest cell (3.0-fold) and CFC (25-fold) expansions in CBMNC cultures, whereas our medium maintained the most cells (93% of input) and gave the greatest CFC expansion (6.1-fold) for PBMNC cultures. Of the commercial media, Progenitor-34 gave the greatest cell expansion (1.2-fold) and X VIVO-10 gave the greatest CFC expansion (11-fold) for CBMNC cultures, and Progenitor-34 maintained the most cells (83% of input) and gave the greatest CFC expansion (3.1-fold) for PBMNC cultures. Of the public media (including ours), our medium gave the greatest cell (1.4-fold) and CFC (6.1-fold) expansion for CBMNC cultures. Although there were slight correlations between cell and CFC expansion in 10-day CBMNC and PBMNC cultures (r2 of 0.848 and 0.594, respectively), the correlations did not give reliable predictions for medium selection. In addition, the different media favored expansion of different CFC types and performed differently for cultures using different cell sources (CB versus PB). Taken together, these results suggest that media must be carefully screened for the cell source to be cultured and the cell type(s) to be produced (e.g. total cells, CFC).

Published
1996
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38. Hematopoietic cell culture therapies (Part I): Cell culture considerations.

Author

McAdams TA, Miller WM, and Papoutsakis ET

Subjects
Animals, Biocompatible Materials, Bioreactors, Biotechnology trends, Bone Marrow Transplantation, Cell Culture Techniques methods, Cytokines pharmacology, Cytokines physiology, Hematopoiesis drug effects, Hematopoiesis physiology, Hematopoietic System drug effects, Hematopoietic System physiology, Humans, Hematopoietic System cytology
Abstract

Hematopoietic cell culture, or ex vivo expansion of hematopoietic cells, is a rapidly growing area of tissue engineering with many potential applications in bone-marrow transplantation, gene therapy and the production of blood products. Hematopoietic cultures are considerably more complex than established animal cell culture technologies owing to the presence of many cell types at various differentiation stages, and stringent medium and growth factor requirements. Culture parameters, such as pH, oxygen tension, seeding density and feeding schedules, significantly affect the proliferation and differentiation of hematopoietic cells. A number of bioreactor systems are currently under development.

Published
1996
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39. Ex vivo expansion of primitive hematopoietic cells for cellular therapies: An overview.

Author

McAdams TA, Sandstrom CE, Miller WM, Bender JG, and Papoutsakis ET

Abstract

Sources of hematopoietic cells for bone marrow transplantation are limited by the supply of compatible donors, the possibility of viral infection, and autologous (patient) marrow that is depleted from prior chemo- or radiotherapy or has cancerous involvement. Anex vivo system to amplify hematopoietic progenitor cells could increase the number of patients eligible for autologous transplant, allow use of cord blood hematopoietic cells to repopulate an adult, reduce the amount of bone marrow and/or mobilized peripheral blood stem and progenitor cells required for transplantation, and reduce the time to white cell and platelet engraftment. The cloning of hematopoietic growth factors and the identification of appropriate conditions has enabled the development of successfulex vivo hematopoietic cell cultures. Purification systems based on the CD34 marker (which is expressed by the most primitive hematopoietic cells) have proven an essential tool for research and clinical applications. Present methods for hematopoietic cultures (HC) on stromal (i.e. accessory cells that support hematopoiesis) layers in flasks lack a well-controlled growth environment. Several bioreactor configurations have been investigated, and a first generation of reactors and cultures has reached the clinical trial stage. Our research suggests that perfusion conditions improve substantially the performance of hematopoietic reactors. We have designed and tested a perfusion bioreactor system which is suitable for the culture of non-adherent cells (without stromal cells) and readily scaleable for clinical therapies. Eliminating the stromal layer eliminates the need for a stromal cell donor, reduces culture time, and simplifies the culture system. In addition, we have compared the expansion characteristics of both mononuclear and CD34(+) cells, since the latter are frequently assumed to give a superior performance for likely transplantation therapies.

Published
1995
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