Reproductive Loss in High-Producing Dairy Cattle: Where Will It End?

¹ Department of Animal Sciences, University of Missouri, Columbia 65211

The dairy industry in the United States has changed dramatically in the last decade. Milk production per cow has increased steadily because of a combination of improved management, better nutrition, and intense genetic selection. Dairy farms are larger, and nearly 30% of the dairy cows in the United States are on farms with 500 or more cows. The shift toward more productive cows and larger herds is associated with a decrease in reproductive efficiency. Cows with the greatest milk production have the highest incidence of infertility, but epidemiological studies suggest that, in addition to milk production, other factors are probably decreasing reproductive efficiency in our dairy herds. The reproductive physiology of dairy cows has changed over the past 50 yr, and physiological adaptations to high milk production may explain part of the reproductive decline. Critical areas for new research include control of the estrous cycle, metabolic effects of lactation on reproduction, mechanisms linking disease to reproduction, and early embryonic mortality. Solving reproductive loss in dairy cows will not be easy because only a small number of research groups study reproduction in postpartum dairy cows. Therefore, the present research base will need to be expanded. For this to occur, research funding must be increased above its current level and a renewed emphasis must be placed on solving the emerging crisis of infertility in dairy cows.

Key Words: dairy cow • reproduction • ovary • lactation

Submitted on August 23, 2000
Accepted on January 26, 2001

This article has been cited by other articles:

				K. M. Cammack, M. G. Thomas, and R. M. Enns Review: Reproductive Traits and Their Heritabilities in Beef Cattle Professional Animal Scientist, October 1, 2009; 25(5): 517 - 528. [Abstract] [PDF]

				R. T. Garmo, A. D. Martin, E. Thuen, O. Havrevoll, H. Steinshamn, E. Prestlokken, A. Randby, M. Eknaes, A. Waldmann, and O. Reksen Characterization of progesterone profiles in fall-calving Norwegian Red cows J Dairy Sci, October 1, 2009; 92(10): 4919 - 4928. [Abstract] [Full Text] [PDF]

				S. Arlt, W. Padberg, M. Drillich, and W. Heuwieser Efficacy of homeopathic remedies as prophylaxis of bovine endometritis J Dairy Sci, October 1, 2009; 92(10): 4945 - 4953. [Abstract] [Full Text] [PDF]

				P. Bossaert, J. L. M. R. Leroy, S. De Campeneere, S. De Vliegher, and G. Opsomer Differences in the glucose-induced insulin response and the peripheral insulin responsiveness between neonatal calves of the Belgian Blue, Holstein-Friesian, and East Flemish breeds J Dairy Sci, September 1, 2009; 92(9): 4404 - 4411. [Abstract] [Full Text] [PDF]

				C. Huang, S. Tsuruta, J. K. Bertrand, I. Misztal, T. J. Lawlor, and J. S. Clay Trends for conception rate of Holsteins over time in the southeastern United States J Dairy Sci, September 1, 2009; 92(9): 4641 - 4647. [Abstract] [Full Text] [PDF]

				H. D. Norman, J. R. Wright, S. M. Hubbard, R. H. Miller, and J. L. Hutchison Reproductive status of Holstein and Jersey cows in the United States J Dairy Sci, July 1, 2009; 92(7): 3517 - 3528. [Abstract] [Full Text] [PDF]

				M. J. de Veth, D. E. Bauman, W. Koch, G. E. Mann, A. M. Pfeiffer, and W. R. Butler Efficacy of conjugated linoleic acid for improving reproduction: A multi-study analysis in early-lactation dairy cows J Dairy Sci, June 1, 2009; 92(6): 2662 - 2669. [Abstract] [Full Text] [PDF]

				S. Tsuruta, I. Misztal, C. Huang, and T. J. Lawlor Bivariate analysis of conception rates and test-day milk yields in Holsteins using a threshold-linear model with random regressions J Dairy Sci, June 1, 2009; 92(6): 2922 - 2930. [Abstract] [Full Text] [PDF]

				R. T. Garmo, E. Ropstad, O. Havrevoll, E. Thuen, H. Steinshamn, A. Waldmann, and O. Reksen Commencement of luteal activity in three different selection lines for milk yield and fertility in Norwegian Red cows J Dairy Sci, May 1, 2009; 92(5): 2159 - 2165. [Abstract] [Full Text] [PDF]

				H. Khatib, W. Huang, X. Wang, A. H. Tran, A. B. Bindrim, V. Schutzkus, R. L. Monson, and B. S. Yandell Single gene and gene interaction effects on fertilization and embryonic survival rates in cattle J Dairy Sci, May 1, 2009; 92(5): 2238 - 2247. [Abstract] [Full Text] [PDF]

				R. L A Cerri, H. M Rutigliano, R. C Chebel, and J. E P Santos Period of dominance of the ovulatory follicle influences embryo quality in lactating dairy cows Reproduction, May 1, 2009; 137(5): 813 - 823. [Abstract] [Full Text] [PDF]

				C. Grainger, M. J. Auldist, G. O'Brien, K. L. Macmillan, and C. Culley Effect of type of diet and energy intake on milk production of Holstein-Friesian cows with extended lactations J Dairy Sci, April 1, 2009; 92(4): 1479 - 1492. [Abstract] [Full Text] [PDF]

				P. J. Pinedo, P. Melendez, J. A. Villagomez-Cortes, and C. A. Risco Effect of high somatic cell counts on reproductive performance of Chilean dairy cattle J Dairy Sci, April 1, 2009; 92(4): 1575 - 1580. [Abstract] [Full Text] [PDF]

				J. B. Cole, D. J. Null, and P. M. VanRaden Best prediction of yields for long lactations J Dairy Sci, April 1, 2009; 92(4): 1796 - 1810. [Abstract] [Full Text] [PDF]

				G. Oikonomou, G. Arsenos, G. E. Valergakis, A. Tsiaras, D. Zygoyiannis, and G. Banos Genetic Relationship of Body Energy and Blood Metabolites with Reproduction in Holstein Cows J Dairy Sci, November 1, 2008; 91(11): 4323 - 4332. [Abstract] [Full Text] [PDF]

				M. Pedernera, S. C. Garcia, A. Horagadoga, I. Barchia, and W. J. Fulkerson Energy Balance and Reproduction on Dairy Cows Fed to Achieve Low or High Milk Production on a Pasture-Based System J Dairy Sci, October 1, 2008; 91(10): 3896 - 3907. [Abstract] [Full Text] [PDF]

				I. David, J. M. Astruc, G. Lagriffoul, E. Manfredi, C. Robert-Granie, and L. Bodin Genetic Correlation Between Female Fertility and Milk Yield in Lacaune Sheep J Dairy Sci, October 1, 2008; 91(10): 4047 - 4052. [Abstract] [Full Text] [PDF]

				G. Bertoni, E. Trevisi, X. Han, and M. Bionaz Effects of Inflammatory Conditions on Liver Activity in Puerperium Period and Consequences for Performance in Dairy Cows J Dairy Sci, September 1, 2008; 91(9): 3300 - 3310. [Abstract] [Full Text] [PDF]

				P. Bossaert, J. L. M. R. Leroy, S. De Vliegher, and G. Opsomer Interrelations Between Glucose-Induced Insulin Response, Metabolic Indicators, and Time of First Ovulation in High-Yielding Dairy Cows J Dairy Sci, September 1, 2008; 91(9): 3363 - 3371. [Abstract] [Full Text] [PDF]

				H. Khatib, C. Maltecca, R. L. Monson, V. Schutzkus, X. Wang, and J. J. Rutledge The fibroblast growth factor 2 gene is associated with embryonic mortality in cattle J Anim Sci, September 1, 2008; 86(9): 2063 - 2067. [Abstract] [Full Text] [PDF]

				R. T. Garmo, A. O. Refsdal, K. Karlberg, E. Ropstad, A. Waldmann, J. F. Beckers, and O. Reksen Pregnancy Incidence in Norwegian Red Cows Using Nonreturn to Estrus, Rectal Palpation, Pregnancy-Associated Glycoproteins, and Progesterone J Dairy Sci, August 1, 2008; 91(8): 3025 - 3033. [Abstract] [Full Text] [PDF]

				J. S. Stevenson, S. M. Tiffany, and E. K. Inskeep Maintenance of Pregnancy in Dairy Cattle After Treatment with Human Chorionic Gonadotropin or Gonadotropin-Releasing Hormone J Dairy Sci, August 1, 2008; 91(8): 3092 - 3101. [Abstract] [Full Text] [PDF]

				J. J. Windig, B. Beerda, and R. F. Veerkamp Relationship Between Milk Progesterone Profiles and Genetic Merit for Milk Production, Milking Frequency, and Feeding Regimen in Dairy Cattle J Dairy Sci, July 1, 2008; 91(7): 2874 - 2884. [Abstract] [Full Text] [PDF]

				M. L. Rhoads, J. P. Meyer, S. J. Kolath, W. R. Lamberson, and M. C. Lucy Growth Hormone Receptor, Insulin-Like Growth Factor (IGF)-1, and IGF-Binding Protein-2 Expression in the Reproductive Tissues of Early Postpartum Dairy Cows J Dairy Sci, May 1, 2008; 91(5): 1802 - 1813. [Abstract] [Full Text] [PDF]

				M Zachut, A Arieli, H Lehrer, N Argov, and U Moallem Dietary unsaturated fatty acids influence preovulatory follicle characteristics in dairy cows Reproduction, May 1, 2008; 135(5): 683 - 692. [Abstract] [Full Text] [PDF]

				C. S. McConnel, J. E. Lombard, B. A. Wagner, and F. B. Garry Evaluation of Factors Associated with Increased Dairy Cow Mortality on United States Dairy Operations J Dairy Sci, April 1, 2008; 91(4): 1423 - 1432. [Abstract] [Full Text] [PDF]

				B. J. Heins, L. B. Hansen, A. J. Seykora, D. G. Johnson, J. G. Linn, J. E. Romano, and A. R. Hazel Crossbreds of Jersey x Holstein Compared with Pure Holsteins for Production, Fertility, and Body and Udder Measurements During First Lactation J Dairy Sci, March 1, 2008; 91(3): 1270 - 1278. [Abstract] [Full Text] [PDF]

				M Mihm, P J Baker, L M Fleming, A M Monteiro, and P J O'Shaughnessy Differentiation of the bovine dominant follicle from the cohort upregulates mRNA expression for new tissue development genes Reproduction, February 1, 2008; 135(2): 253 - 265. [Abstract] [Full Text] [PDF]

				S. L. Moya, M. A. Gomez, L. A. Boyle, J. F. Mee, B. O'Brien, and S. Arkins Effects of Milking Frequency on Phagocytosis and Oxidative Burst Activity of Phagocytes from Primiparous and Multiparous Dairy Cows During Early Lactation J Dairy Sci, February 1, 2008; 91(2): 587 - 595. [Abstract] [Full Text] [PDF]

				C. Huang, S. Tsuruta, J. K. Bertrand, I. Misztal, T. J. Lawlor, and J. S. Clay Environmental Effects on Conception Rates of Holsteins in New York and Georgia J Dairy Sci, February 1, 2008; 91(2): 818 - 825. [Abstract] [Full Text] [PDF]

				D. G. B. Demetrio, R. M. Santos, C. G. B. Demetrio, and J. L. M. Vasconcelos Factors Affecting Conception Rates Following Artificial Insemination or Embryo Transfer in Lactating Holstein Cows J Dairy Sci, November 1, 2007; 90(11): 5073 - 5082. [Abstract] [Full Text] [PDF]

				M. J. Auldist, M. F. S. Pyman, C. Grainger, and K. L. Macmillan Comparative Reproductive Performance and Early Lactation Productivity of Jersey x Holstein Cows in Predominantly Holstein Herds in a Pasture-Based Dairying System J Dairy Sci, October 1, 2007; 90(10): 4856 - 4862. [Abstract] [Full Text] [PDF]

				E. Lof, H. Gustafsson, and U. Emanuelson Associations Between Herd Characteristics and Reproductive Efficiency in Dairy Herds J Dairy Sci, October 1, 2007; 90(10): 4897 - 4907. [Abstract] [Full Text] [PDF]

				E. Castaneda-Gutierrez, B. C. Benefield, M. J. de Veth, N. R. Santos, R. O. Gilbert, W. R. Butler, and D. E. Bauman Evaluation of the Mechanism of Action of Conjugated Linoleic Acid Isomers on Reproduction in Dairy Cows J Dairy Sci, September 1, 2007; 90(9): 4253 - 4264. [Abstract] [Full Text] [PDF]

				M. J. Auldist, G. O'Brien, D. Cole, K. L. Macmillan, and C. Grainger Effects of Varying Lactation Length on Milk Production Capacity of Cows in Pasture-Based Dairying Systems J Dairy Sci, July 1, 2007; 90(7): 3234 - 3241. [Abstract] [Full Text] [PDF]

				A. A. Fouladi-Nashta, C. G. Gutierrez, J. G. Gong, P. C. Garnsworthy, and R. Webb Impact of Dietary Fatty Acids on Oocyte Quality and Development in Lactating Dairy Cows Biol Reprod, July 1, 2007; 77(1): 9 - 17. [Abstract] [Full Text] [PDF]

				JJ. Ireland, F. Ward, F. Jimenez-Krassel, J.L.H. Ireland, G.W. Smith, P. Lonergan, and A.C.O. Evans Follicle numbers are highly repeatable within individual animals but are inversely correlated with FSH concentrations and the proportion of good-quality embryos after ovarian stimulation in cattle Hum. Reprod., June 1, 2007; 22(6): 1687 - 1695. [Abstract] [Full Text] [PDF]

				C. Kawashima, C. A. Montoya, Y. Masuda, E. Kaneko, M. Matsui, T. Shimizu, N. Matsunaga, K. Kida, Y.-I. Miyake, M. Suzuki, et al. Short Communication: A Positive Relationship Between the First Ovulation Postpartum and the Increasing Ratio of Milk Yield in the First Part of Lactation in Dairy Cows J Dairy Sci, May 1, 2007; 90(5): 2279 - 2282. [Abstract] [Full Text] [PDF]

				J. S. Stevenson, M. A. Portaluppi, and D. E. Tenhouse Ovarian Traits After Gonadotropin-Releasing Hormone-Induced Ovulation and Subsequent Delay of Induced Luteolysis in an Ovsynch Protocol J Dairy Sci, March 1, 2007; 90(3): 1281 - 1288. [Abstract] [Full Text] [PDF]

				E. Wall, M. P. Coffey, and S. Brotherstone The Relationship Between Body Energy Traits and Production and Fitness Traits in First-Lactation Dairy Cows J Dairy Sci, March 1, 2007; 90(3): 1527 - 1537. [Abstract] [Full Text] [PDF]

				M. A. Mirando The National Research Initiative Competitive Grants Program in animal reproduction: Changes in priorities and scope relevant to United States animal agriculture J Anim Sci, March 1, 2007; 85(13_suppl): E11 - E15. [Abstract] [Full Text] [PDF]

				J. M. DeJarnette, C. G. Sattler, C. E. Marshall, and R. L. Nebel Voluntary Waiting Period Management Practices in Dairy Herds Participating in a Progeny Test Program J Dairy Sci, February 1, 2007; 90(2): 1073 - 1079. [Abstract] [Full Text] [PDF]

				P. Melendez and P. Pinedo The Association Between Reproductive Performance and Milk Yield in Chilean Holstein Cattle J Dairy Sci, January 1, 2007; 90(1): 184 - 192. [Abstract] [Full Text] [PDF]

				K.-J. Petersson, B. Berglund, E. Strandberg, H. Gustafsson, A. P. F. Flint, J. A. Woolliams, and M. D. Royal Genetic Analysis of Postpartum Measures of Luteal Activity in Dairy Cows J Dairy Sci, January 1, 2007; 90(1): 427 - 434. [Abstract] [Full Text] [PDF]

				D. Z. Caraviello, K. A. Weigel, M. Craven, D. Gianola, N. B. Cook, K. V. Nordlund, P. M. Fricke, and M. C. Wiltbank Analysis of Reproductive Performance of Lactating Cows on Large Dairy Farms Using Machine Learning Algorithms J Dairy Sci, December 1, 2006; 89(12): 4703 - 4722. [Abstract] [Full Text] [PDF]

				B. J. Heins, L. B. Hansen, and A. J. Seykora Fertility and Survival of Pure Holsteins Versus Crossbreds of Holstein with Normande, Montbeliarde, and Scandinavian Red J Dairy Sci, December 1, 2006; 89(12): 4944 - 4951. [Abstract] [Full Text] [PDF]

				D. H. Townson Immune cell-endothelial cell interactions in the bovine corpus luteum Integr. Comp. Biol., December 1, 2006; 46(6): 1055 - 1059. [Abstract] [Full Text] [PDF]

				H. Han, K. J Austin, L. A Rempel, and T. R Hansen Low blood ISG15 mRNA and progesterone levels are predictive of non-pregnant dairy cows. J. Endocrinol., November 1, 2006; 191(2): 505 - 512. [Abstract] [Full Text] [PDF]

				C. A. Blevins, J. E. Shirley, and J. S. Stevenson Milking frequency, estradiol cypionate, and somatotropin influence lactation and reproduction in dairy cows. J Dairy Sci, November 1, 2006; 89(11): 4176 - 4187. [Abstract] [Full Text] [PDF]

				M. G. G. Chagunda, N. C. Friggens, M. D. Rasmussen, and T. Larsen A model for detection of individual cow mastitis based on an indicator measured in milk. J Dairy Sci, August 1, 2006; 89(8): 2980 - 2998. [Abstract] [Full Text] [PDF]

				J. M. Cornwell, M. L. McGilliard, R. Kasimanickam, and R. L. Nebel Effect of sire fertility and timing of artificial insemination in a Presynch + Ovsynch protocol on first-service pregnancy rates. J Dairy Sci, July 1, 2006; 89(7): 2473 - 2478. [Abstract] [Full Text] [PDF]

				K.-J. Petersson, H. Gustafsson, E. Strandberg, and B. Berglund Atypical progesterone profiles and fertility in Swedish dairy cows. J Dairy Sci, July 1, 2006; 89(7): 2529 - 2538. [Abstract] [Full Text] [PDF]

				J. S. Stevenson, J. R. Pursley, H. A. Garverick, P. M. Fricke, D. J. Kesler, J. S. Ottobre, and M. C. Wiltbank Treatment of cycling and noncycling lactating dairy cows with progesterone during Ovsynch. J Dairy Sci, July 1, 2006; 89(7): 2567 - 2578. [Abstract] [Full Text] [PDF]

				M. A. Mirando and D. L. Hamernik Funding Priorities in Animal Reproduction at the United States Department of Agriculture's Cooperative State Research, Education, and Extension Service Biol Reprod, March 1, 2006; 74(3): 459 - 462. [Abstract] [Full Text] [PDF]

				D. R. Stein, D. T. Allen, E. B. Perry, J. C. Bruner, K. W. Gates, T. G. Rehberger, K. Mertz, D. Jones, and L. J. Spicer Effects of Feeding Propionibacteria to Dairy Cows on Milk Yield, Milk Components, and Reproduction J Dairy Sci, January 1, 2006; 89(1): 111 - 125. [Abstract] [Full Text] [PDF]

				E. Hare, H. D. Norman, and J. R. Wright Trends in Calving Ages and Calving Intervals for Dairy Cattle Breeds in the United States J Dairy Sci, January 1, 2006; 89(1): 365 - 370. [Abstract] [Full Text] [PDF]

				J L M R Leroy, T Vanholder, B Mateusen, A Christophe, G Opsomer, A de Kruif, G Genicot, and A Van Soom Non-esterified fatty acids in follicular fluid of dairy cows and their effect on developmental capacity of bovine oocytes in vitro Reproduction, October 1, 2005; 130(4): 485 - 495. [Abstract] [Full Text] [PDF]

				A. de Vries and C. A. Risco Trends and Seasonality of Reproductive Performance in Florida and Georgia Dairy Herds from 1976 to 2002 J Dairy Sci, September 1, 2005; 88(9): 3155 - 3165. [Abstract] [Full Text] [PDF]

				M. A. Portaluppi and J. S. Stevenson Pregnancy Rates in Lactating Dairy Cows After Presynchronization of Estrous Cycles and Variations of the Ovsynch Protocol J Dairy Sci, March 1, 2005; 88(3): 914 - 921. [Abstract] [Full Text] [PDF]

				J. S. Stevenson and A. P. Phatak Inseminations at Estrus Induced by Presynchronization Before Application of Synchronized Estrus and Ovulation J Dairy Sci, January 1, 2005; 88(1): 399 - 405. [Abstract] [Full Text] [PDF]

				R. L. A. Cerri, J. E. P. Santos, S. O. Juchem, K. N. Galvao, and R. C. Chebel Timed Artificial Insemination with Estradiol Cypionate or Insemination at Estrus in High-Producing Dairy Cows J Dairy Sci, November 1, 2004; 87(11): 3704 - 3715. [Abstract] [Full Text] [PDF]

				M. Sakaguchi, Y. Sasamoto, T. Suzuki, Y. Takahashi, and Y. Yamada Postpartum Ovarian Follicular Dynamics and Estrous Activity in Lactating Dairy Cows J Dairy Sci, July 1, 2004; 87(7): 2114 - 2121. [Abstract] [Full Text] [PDF]

				H. Groenendaal, D. T. Galligan, and H. A. Mulder An Economic Spreadsheet Model to Determine Optimal Breeding and Replacement Decisions for Dairy Cattle J Dairy Sci, July 1, 2004; 87(7): 2146 - 2157. [Abstract] [Full Text] [PDF]

				P. M. VanRaden, A. H. Sanders, M. E. Tooker, R. H. Miller, H. D. Norman, M. T. Kuhn, and G. R. Wiggans Development of a National Genetic Evaluation for Cow Fertility J Dairy Sci, July 1, 2004; 87(7): 2285 - 2292. [Abstract] [Full Text] [PDF]

				J. S. Clay, B. T. McDaniel, and C. H. Brown Variances of and Correlations Among Progeny Tests for Reproductive Traits of Cows Sired by AI Bulls J Dairy Sci, July 1, 2004; 87(7): 2307 - 2313. [Abstract] [Full Text] [PDF]

				J. M. DeJarnette, C. E. Marshall, R. W. Lenz, D. R. Monke, W. H. Ayars, and C. G. Sattler Sustaining the Fertility of Artificially Inseminated Dairy Cattle: The Role of the Artificial Insemination Industry J Dairy Sci, July 1, 2004; 87(13_suppl): E93 - 104. [Abstract] [Full Text] [PDF]

				A Meikle, M Kulcsar, Y Chilliard, H Febel, C Delavaud, D Cavestany, and P Chilibroste Effects of parity and body condition at parturition on endocrine and reproductive parameters of the cow Reproduction, June 1, 2004; 127(6): 727 - 737. [Abstract] [Full Text] [PDF]

				J. E. P. Santos, S. O. Juchem, R. L. A. Cerri, K. N. Galvao, R. C. Chebel, W. W. Thatcher, C. S. Dei, and C. R. Bilby Effect of bST and Reproductive Management on Reproductive Performance of Holstein Dairy Cows J Dairy Sci, April 1, 2004; 87(4): 868 - 881. [Abstract] [Full Text] [PDF]

				S. Z. El-Zarkouny, J. A. Cartmill, B. A. Hensley, and J. S. Stevenson Pregnancy in Dairy Cows After Synchronized Ovulation Regimens With or Without Presynchronization and Progesterone J Dairy Sci, April 1, 2004; 87(4): 1024 - 1037. [Abstract] [Full Text] [PDF]

				F. M. Rhodes, S. McDougall, C. R. Burke, G. A. Verkerk, and K. L. Macmillan Invited Review: Treatment of Cows with an Extended Postpartum Anestrous Interval J Dairy Sci, June 1, 2003; 86(6): 1876 - 1894. [Abstract] [Full Text] [PDF]

				J. R. Chenault, J. F. Boucher, K. J. Dame, J. A. Meyer, and S. L. Wood-Follis Intravaginal Progesterone Insert to Synchronize Return to Estrus of Previously Inseminated Dairy Cows J Dairy Sci, June 1, 2003; 86(6): 2039 - 2049. [Abstract] [Full Text] [PDF]

				R. Sartori, R. Sartor-Bergfelt, S. A. Mertens, J. N. Guenther, J. J. Parrish, and M. C. Wiltbank Fertilization and Early Embryonic Development in Heifers and Lactating Cows in Summer and Lactating and Dry Cows in Winter J Dairy Sci, November 1, 2002; 85(11): 2803 - 2812. [Abstract] [Full Text] [PDF]

				S. Sangsritavong, D. K. Combs, R. Sartori, L. E. Armentano, and M. C. Wiltbank High Feed Intake Increases Liver Blood Flow and Metabolism of Progesterone and Estradiol-17{beta} in Dairy Cattle J Dairy Sci, November 1, 2002; 85(11): 2831 - 2842. [Abstract] [Full Text] [PDF]