Skip to main content Accessibility help

Strength of nonhuman primate studies of developmental programming: review of sample sizes, challenges, and steps for future work

  • Hillary F. Huber (a1), Susan L. Jenkins (a1), Cun Li (a1) (a2) and Peter W. Nathanielsz (a1) (a2)


Nonhuman primate (NHP) studies are crucial to biomedical research. NHPs are the species most similar to humans in lifespan, body size, and hormonal profiles. Planning research requires statistical power evaluation, which is difficult to perform when lacking directly relevant preliminary data. This is especially true for NHP developmental programming studies, which are scarce. We review the sample sizes reported, challenges, areas needing further work, and goals of NHP maternal nutritional programming studies. The literature search included 27 keywords, for example, maternal obesity, intrauterine growth restriction, maternal high-fat diet, and maternal nutrient reduction. Only fetal and postnatal offspring studies involving tissue collection or imaging were included. Twenty-eight studies investigated maternal over-nutrition and 33 under-nutrition; 23 involved macaques and 38 baboons. Analysis by sex was performed in 19; minimum group size ranged from 1 to 8 (mean 4.7 ± 0.52, median 4, mode 3) and maximum group size from 3 to 16 (8.3 ± 0.93, 8, 8). Sexes were pooled in 42 studies; minimum group size ranged from 2 to 16 (mean 5.3 ± 0.35, median 6, mode 6) and maximum group size from 4 to 26 (10.2 ± 0.92, 8, 8). A typical study with sex-based analyses had group size minimum 4 and maximum 8 per sex. Among studies with sexes pooled, minimum group size averaged 6 and maximum 8. All studies reported some significant differences between groups. Therefore, studies with group sizes 3–8 can detect significance between groups. To address deficiencies in the literature, goals include increasing age range, more frequently considering sex as a biological variable, expanding topics, replicating studies, exploring intergenerational effects, and examining interventions.


Corresponding author

Address for correspondence: Hillary F. Huber, Texas Pregnancy & Life-Course Health Research Center, Herff Building 13, Texas Biomedical Research Institute, P.O. Box 760549, San Antonio, TX 78245-0549, USA. Email:


Hide All

Institution at which work was performed: Southwest National Primate Research Center, San Antonio, TX, USA.



Hide All
1. Sullivan, EL, Rivera, HM, True, CA, et al. Maternal and postnatal high-fat diet consumption programs energy balance and hypothalamic melanocortin signaling in nonhuman primate offspring. Am J Physiol Regul Integr Comp Physiol. 2017; 313(2), R169R179.
2. Cox, LA, Li, C, Glenn, JP, et al. Expression of the placental transcriptome in maternal nutrient reduction in baboons is dependent on fetal sex. J Nutr. 2013; 143(11), 16981708.
3. Gandhi, K, Li, C, German, N, et al. Effect of maternal high-fat diet on key components of the placental and hepatic endocannabinoid system. Am J Physiol Endocrinol Metab. 2017; 314(4), E322E333.
4. Guo, C, Li, C, Myatt, L, Nathanielsz, PW, Sun, K. Sexually dimorphic effects of maternal nutrient reduction on expression of genes regulating cortisol metabolism in fetal baboon adipose and liver tissues. Diabetes. 2013; 62(4), 11751185.
5. McCurdy, CE, Schenk, S, Hetrick, B, et al. Maternal obesity reduces oxidative capacity in fetal skeletal muscle of Japanese macaques. JCI Insight. 2016; 1(16), e86612.
6. Muralimanoharan, S, Li, C, Nakayasu, ES, et al. Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction. J Mol Cell Cardiol. 2017; 108, 181193.
7. Pereira, SP, Oliveira, PJ, Tavares, LC, et al. Effects of moderate global maternal nutrient reduction on fetal baboon renal mitochondrial gene expression at 0.9 gestation. Am J Physiol Renal Physiol. 2015; 308(11), F1217F1228.
8. Tchoukalova, YD, Krishnapuram, R, White, UA, et al. Fetal baboon sex-specific outcomes in adipocyte differentiation at 0.9 gestation in response to moderate maternal nutrient reduction. Int J Obes (Lond). 2014; 38(2), 224230.
9. Franke, K, Clarke, GD, Dahnke, R, et al. Premature brain aging in baboons resulting from moderate fetal undernutrition. Front Aging Neurosci. 2017; 9, 92.
10. Huber, HF, Considine, MM, Jenkins, S, Li, C, Nathanielsz, PW. Reproductive cycling in adult baboons (Papio species) that were intrauterine growth restricted at birth implies normal fertility but increased psychosocial stress. J Med Primatol. 2018; 47(6), 427429.
11. Kuo, AH, Li, C, Li, J, Huber, HF, Nathanielsz, PW, Clarke, GD. Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing. J Physiol (Lond). 2017; 595(4), 10931110.
12. Kuo, AH, Li, C, Huber, HF, Schwab, M, Nathanielsz, PW, Clarke, GD. Maternal nutrient restriction during pregnancy and lactation leads to impaired right ventricular function in young adult baboons. J Physiol. 2017; 595(13), 42454260.
13. Kuo, AH, Li, C, Huber, HF, Clarke, GD, Nathanielsz, PW. Intrauterine growth restriction results in persistent vascular mismatch in adulthood. J Physiol (Lond). 2018; 596(23), 57775790.
14. Kuo, AH, Li, J, Li, C, Huber, HF, Nathanielsz, PW, Clarke, GD. Poor perinatal growth impairs baboon aortic windkessel function. J Dev Orig Health Dis. 2018; 9(2), 137142.
15. Kuo, AH, Li, C, Mattern, V, et al. Sex-dimorphic acceleration of pericardial, subcutaneous, and plasma lipid increase in offspring of poorly nourished baboons. Int J Obes. 2018; 42(5), 10921096.
16. Salmon, AB, Dorigatti, J, Huber, HF, Li, C, Nathanielsz, PW. Maternal nutrient restriction in baboon programs later-life cellular growth and respiration of cultured skin fibroblasts: a potential model for the study of aging-programming interactions. Geroscience. 2018; 40(3), 269278.
17. Thompson, JR, Valleau, JC, Barling, AN, et al. Exposure to a high-fat diet during early development programs behavior and impairs the central serotonergic system in juvenile non-human primates. Front Endocrinol (Lausanne). 2017; 8, 164.
18. Grant, WF, Nicol, LE, Thorn, SR, Grove, KL, Friedman, JE, Marks, DL. Perinatal exposure to a high-fat diet is associated with reduced hepatic sympathetic innervation in one-year old male Japanese macaques. PLoS One. 2012; 7(10), e48119.
19. Sullivan, EL, Grayson, B, Takahashi, D, et al. Chronic consumption of a high-fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety-like behavior in nonhuman primate offspring. J Neurosci. 2010; 30(10), 38263830.
20. Aagaard-Tillery, KM, Grove, K, Bishop, J, et al. Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome. J Mol Endocrinol. 2008; 41(2), 91102.
21. Abu Shehab, M, Damerill, I, Shen, T, et al. Liver mTOR controls IGF-I bioavailability by regulation of protein kinase CK2 and IGFBP-1 phosphorylation in fetal growth restriction. Endocrinology. 2014; 155(4), 13271339.
22. Antonow-Schlorke, I, Schwab, M, Cox, LA, et al. Vulnerability of the fetal primate brain to moderate reduction in maternal global nutrient availability. PNAS. 2011; 108(7), 30113016.
23. Cox, LA, Nijland, MJ, Gilbert, JS, et al. Effect of 30 per cent maternal nutrient restriction from 0.16 to 0.5 gestation on fetal baboon kidney gene expression. J Physiol. 2006; 572(1), 6785.
24. Cox, J, Williams, S, Grove, K, Lane, RH, Aagaard-Tillery, KM. A maternal high-fat diet is accompanied by alterations in the fetal primate metabolome. Am J Obstet Gynecol. 2009; 201(3), 281.e1–9.
25. DuBois, BN, O’Tierney-Ginn, P, Pearson, J, Friedman, JE, Thornburg, K, Cherala, G. Maternal obesity alters feto-placental cytochrome P4501A1 activity. Placenta. 2012; 33(12), 10451051.
26. Farley, D, Tejero, ME, Comuzzie, AG, et al. Feto-placental adaptations to maternal obesity in the baboon. Placenta. 2009; 30(9), 752760.
27. Frias, AE, Morgan, TK, Evans, AE, et al. Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition. Endocrinology. 2011; 152(6), 24562464.
28. Grant, WF, Gillingham, MB, Batra, AK, et al. Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates. PLoS One. 2011; 6(2), e17261.
29. Grayson, BE, Levasseur, PR, Williams, SM, Smith, MS, Marks, DL, Grove, KL. Changes in melanocortin expression and inflammatory pathways in fetal offspring of nonhuman primates fed a high-fat diet. Endocrinology. 2010; 151(4), 16221632.
30. Hellmuth, C, Uhl, O, Kirchberg, FF, et al. Influence of moderate maternal nutrition restriction on the fetal baboon metabolome at 0.5 and 0.9 gestation. Nutr Metab Cardiovasc Dis. 2016; 26(9), 786796.
31. Kamat, A, Nijland, MJ, McDonald, TJ, Cox, LA, Nathanielsz, PW, Li, C. Moderate global reduction in maternal nutrition has differential stage of gestation specific effects on β1- and β2-adrenergic receptors in the fetal baboon liver. Reprod Sci. 2011; 18(4), 398405.
32. Kavitha, JV, Rosario, FJ, Nijland, MJ, et al. Down-regulation of placental mTOR, insulin/IGF-I signaling, and nutrient transporters in response to maternal nutrient restriction in the baboon. FASEB J. 2014; 28(3), 12941305.
33. Li, C, Levitz, M, Hubbard, GB, et al. The IGF axis in baboon pregnancy: placental and systemic responses to feeding 70% global ad libitum diet. Placenta. 2007; 28(11–12), 12001210.
34. Li, C, Schlabritz-Loutsevitch, NE, Hubbard, GB, et al. Effects of maternal global nutrient restriction on fetal baboon hepatic insulin-like growth factor system genes and gene products. Endocrinology. 2009; 150(10), 46344642.
35. Li, C, Ramahi, E, Nijland, MJ, et al. Up-regulation of the fetal baboon hypothalamo-pituitary-adrenal axis in intrauterine growth restriction: coincidence with hypothalamic glucocorticoid receptor insensitivity and leptin receptor down-regulation. Endocrinology. 2013; 154(7), 23652373.
36. Li, C, McDonald, TJ, Wu, G, Nijland, MJ, Nathanielsz, PW. Intrauterine growth restriction alters term fetal baboon hypothalamic appetitive peptide balance. J Endocrinol. 2013; 217(3), 275282.
37. Maloyan, A, Muralimanoharan, S, Huffman, S, et al. Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity. Physiol Genomics. 2013; 45(19), 889900.
38. McDonald, TJ, Wu, G, Nijland, MJ, Jenkins, SL, Nathanielsz, PW, Jansson, T. Effect of 30 % nutrient restriction in the first half of gestation on maternal and fetal baboon serum amino acid concentrations. Br J Nutr. 2013; 109(08), 13821388.
39. Nathanielsz, PW, Yan, J, Green, R, et al. Maternal obesity disrupts the methionine cycle in baboon pregnancy. Physiol Rep. 2015; 3(11), e12564.
40. Nijland, MJ, Schlabritz-Loutsevitch, NE, Hubbard, GB, Nathanielsz, PW, Cox, LA. Non-human primate fetal kidney transcriptome analysis indicates mammalian target of rapamycin (mTOR) is a central nutrient-responsive pathway. J Physiol. 2007; 579(3), 643656.
41. Roberts, VHJ, Pound, LD, Thorn, SR, et al. Beneficial and cautionary outcomes of resveratrol supplementation in pregnant nonhuman primates. FASEB J. 2014; 28(6), 24662477.
42. Suter, MA, Sangi-Haghpeykar, H, Showalter, L, et al. Maternal high-fat diet modulates the fetal thyroid axis and thyroid gene expression in a nonhuman primate model. Mol Endocrinol. 2012; 26(12), 20712080.
43. Suter, MA, Chen, A, Burdine, MS, et al. A maternal high-fat diet modulates fetal SIRT1 histone and protein deacetylase activity in nonhuman primates. FASEB J. 2012; 26(12), 51065114.
44. Li, C, Shu, Z-J, Lee, S, et al. Effects of maternal nutrient restriction, intrauterine growth restriction, and glucocorticoid exposure on phosphoenolpyruvate carboxykinase-1 expression in fetal baboon hepatocytes in vitro. J Med Primatol. 2013; 42(4), 211219.
45. McCurdy, CE, Bishop, JM, Williams, SM, et al. Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. J Clin Invest. 2009; 119(2), 323335.
46. Unterberger, A, Szyf, M, Nathanielsz, PW, Cox, LA. Organ and gestational age effects of maternal nutrient restriction on global methylation in fetal baboons. J Med Primatol. 2009; 38(4), 219227.
47. Ye, W, Xie, L, Li, C, Nathanielsz, PW, Thompson, BJ. Impaired development of fetal serotonergic neurons in intrauterine growth restricted baboons. J Med Primatol. 2014; 43(4), 284287.
48. Pantham, P, Rosario, FJ, Weintraub, ST, et al. Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in maternal nutrient restricted baboons. Biol Reprod. 2016; 95(5), 98.
49. Puppala, S, Li, C, Glenn, JP, et al. Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation. J Physiol (Lond). 2018; 596(23), 58235837.
50. Nijland, MJ, Mitsuya, K, Li, C, et al. Epigenetic modification of fetal baboon hepatic phosphoenolpyruvate carboxykinase following exposure to moderately reduced nutrient availability. J Physiol. 2010; 588(8), 13491359.
51. Xie, L, Antonow-Schlorke, I, Schwab, M, McDonald, TJ, Nathanielsz, PW, Li, C. The frontal cortex IGF system is down regulated in the term, intrauterine growth restricted fetal baboon. Growth Horm IGF Res. 2013; 23(5), 187192.
52. Fan, L, Lindsley, SR, Comstock, SM, et al. Maternal high-fat diet impacts endothelial function in nonhuman primate offspring. Int J Obes (Lond). 2013; 37(2), 254.
53. Ma, J, Prince, AL, Bader, D, et al. High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model. Nat Commun. 2014; 5, 3889.
54. Suter, MA, Takahashi, D, Grove, KL, Aagaard, KM. Postweaning exposure to a high-fat diet is associated with alterations to the hepatic histone code in Japanese macaques. Pediatr Res. 2013; 74(3), 252258.
55. Pace, RM, Prince, AL, Ma, J, et al. Modulations in the offspring gut microbiome are refractory to postnatal synbiotic supplementation among juvenile primates. BMC Microbiol. 2018; 18(1), 28.
56. Rivera, HM, Kievit, P, Kirigiti, MA, et al. Maternal high-fat diet and obesity impact palatable food intake and dopamine signaling in nonhuman primate offspring. Obesity. 2015; 23(11), 21572164.
57. Choi, J, Li, C, McDonald, TJ, Comuzzie, A, Mattern, V, Nathanielsz, PW. Emergence of insulin resistance in juvenile baboon offspring of mothers exposed to moderate maternal nutrient reduction. Am J Physiol Regul Integr Comp Physiol. 2011; 301(3), R757R762.
58. Comstock, SM, Pound, LD, Bishop, JM, et al. High-fat diet consumption during pregnancy and the early post-natal period leads to decreased α cell plasticity in the nonhuman primate. Mol Metab. 2012; 2(1), 1022.
59. Suter, M, Bocock, P, Showalter, L, et al. Epigenomics: maternal high-fat diet exposure in utero disrupts peripheral circadian gene expression in nonhuman primates. FASEB J. 2011; 25(2), 714726.
60. Li, C, Jenkins, SL, Mattern, V, et al. Effect of moderate, 30 percent global maternal nutrient reduction on fetal and postnatal baboon phenotype. J Med Primatol. 2017; 46(6), 293303.
61. Pound, LD, Comstock, SM, Grove, KL. Consumption of a Western-style diet during pregnancy impairs offspring islet vascularization in a Japanese macaque model. Am J Physiol Endocrinol Metab. 2014; 307(1), E115E123.
62. Dwan, K, Gamble, C, Williamson, PR, Kirkham, JJ, Reporting Bias Group. Systematic review of the empirical evidence of study publication bias and outcome reporting bias – an updated review. PLoS ONE. 2013; 8(7), e66844.
63. Paterson, JD. Coming to America: acclimation in macaque body structures and Bergmann’s rule. Int J Primatol. 1996; 17(4), 585611.
64. Coelho, AM. Baboon dimorphism: growth in weight, length and adiposity from birth to 8 years of age. In Nonhuman Primate Models for Human Growth and Development (ed. Watts, ES), 1985; pp. 125159. Alan R. Liss, New York.
65. Bronikowski, AM, Alberts, SC, Altmann, J, Packer, C, Carey, KD, Tatar, M. The aging baboon: comparative demography in a non-human primate. PNAS. 2002; 99(14), 95919595.
66. Pavelka, MS, Fedigan, LM. Reproductive termination in female Japanese monkeys: a comparative life history perspective. Am J Phys Anthropol. 1999; 109(4), 455464.
67. Harvey, PH, Clutton-Brock, TH. Life history variation in primates. Evolution. 1985; 39(3), 559581.
68. Schlabritz-Loutsevitch, NE, Howell, K, Rice, K, et al. Development of a system for individual feeding of baboons maintained in an outdoor group social environment. J Med Primatol. 2004; 33(3), 117126.
69. Huber, HF, Kuo, AH, Li, C, et al. Antenatal synthetic glucocorticoid exposure at human therapeutic equivalent doses predisposes middle-age male offspring baboons to an obese phenotype that emerges with aging. Reprod Sci. 2019; 26(5), 591599.
70. Kuo, AH, Huber, HF, Li, C, Li, J, Nathanielsz, PW, Clarke, GD. Accelerated right heart aging in IUGR offspring of undernourished pregnant baboons. Reprod Sci. 2016; 23(Suppl. 1), 147A.
71. Bertram, C, Khan, O, Ohri, S, Phillips, DI, Matthews, SG, Hanson, MA. Transgenerational effects of prenatal nutrient restriction on cardiovascular and hypothalamic-pituitary-adrenal function. J Physiol (Lond). 2008; 586(8), 22172229.
72. Aiken, CE, Ozanne, SE. Transgenerational developmental programming. Hum Reprod Update. 2014; 20(1), 6375.
73. Radford, EJ, Ito, M, Shi, H, et al. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Science. 2014; 345(6198), 1255903.
74. Reyes-Castro, LA, Rodríguez-González, GL, Chavira, R, et al. Paternal line multigenerational passage of altered risk assessment behavior in female but not male rat offspring of mothers fed a low protein diet. Physiol Behav. 2015; 140, 8995.
75. Burdge, GC, Slater-Jefferies, J, Torrens, C, Phillips, ES, Hanson, MA, Lillycrop, KA. Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Br J Nutr. 2007; 97(3), 435439.
76. Pankey, CL, Walton, MW, Odhiambo, JF, et al. Intergenerational impact of maternal overnutrition and obesity throughout pregnancy in sheep on metabolic syndrome in grandsons and granddaughters. Domest Anim Endocrinol. 2017; 60, 6774.
77. Shasa, DR, Odhiambo, JF, Long, NM, Tuersunjiang, N, Nathanielsz, PW, Ford, SP. Multigenerational impact of maternal overnutrition/obesity in the sheep on the neonatal leptin surge in granddaughters. Int J Obes (Lond). 2015; 39(4), 695701.
78. Zambrano, E, Nathanielsz, PW. Mechanisms by which maternal obesity programs offspring for obesity: evidence from animal studies. Nutr Rev. 2013; 71(Suppl. 1), S42S54.
79. Aiken, CE, Ozanne, SE. Sex differences in developmental programming models. Reproduction. 2013; 145(1), R1R13.
80. Sandman, CA, Glynn, LM, Davis, EP. Is there a viability-vulnerability tradeoff? Sex differences in fetal programming. J Psychosom Res. 2013; 75(4), 327335.
81. Dasinger, JH, Alexander, BT. Gender differences in developmental programming of cardiovascular diseases. Clin Sci. 2016; 130(5), 337348.
82. Gilbert, JS, Nijland, MJ. Sex differences in the developmental origins of hypertension and cardiorenal disease. Am J Physiol Regul Integr Comp Physiol. 2008; 295(6), R1941R1952.
83. Ojeda, NB, Intapad, S, Alexander, BT. Sex differences in the developmental programming of hypertension. Acta Physiol (Oxf). 2014; 210(2), 307316.
84. Dearden, L, Bouret, SG, Ozanne, SE. Sex and gender differences in developmental programming of metabolism. Mol Metab. 2018; 15, 819.
85. Huber, HF, Bartlett, TQ, Smith, BK, Li, C, Jenkins, SL, Nathanielsz, PW. Birth sex ratio in baboon mothers fed ad lib, reduced or obesogenic diet. Reprod Sci. 2016; 23(1 Suppl), 236A.
86. Clutton-Brock, TH, Albon, SD, Guinness, FE. Parental investment and sex differences in juvenile mortality in birds and mammals. Nature. 1985; 313(5998), 131133.
87. van Schaik, CP, Hrdy, SB. Intensity of local resource competition shapes the relationship between maternal rank and sex ratios at birth in cercopithecine primates. Am Nat. 1991; 138(6), 15551562.
88. Silk, JB, Brown, GR. Local resource competition and local resource enhancement shape primate birth sex ratios. Proc R Soc B. 2008; 275(1644), 17611765.
89. Vega, CC, Reyes-Castro, LA, Rodríguez-González, GL, et al. Resveratrol partially prevents oxidative stress and metabolic dysfunction in pregnant rats fed a low protein diet and their offspring. J Physiol (Lond). 2016; 594(5), 14831499.
90. Zou, T, Chen, D, Yang, Q, et al. Resveratrol supplementation of high-fat diet-fed pregnant mice promotes brown and beige adipocyte development and prevents obesity in male offspring. J Physiol (Lond). 2016; 595(5), 15471562.
91. Vega, CC, Reyes-Castro, LA, Bautista, CJ, Larrea, F, Nathanielsz, PW, Zambrano, E. Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism. Int J Obes (Lond). 2015; 39(4), 712719.
92. Santos, M, Rodríguez-González, GL, Ibáñez, C, Vega, CC, Nathanielsz, PW, Zambrano, E. Adult exercise effects on oxidative stress and reproductive programming in male offspring of obese rats. Am J Physiol Regul Integr Comp Physiol. 2015; 308(3), R219R225.
93. Tarry-Adkins, JL, Fernandez-Twinn, DS, Madsen, R, et al. Coenzyme Q10 prevents insulin signaling dysregulation and inflammation prior to development of insulin resistance in male offspring of a rat model of poor maternal nutrition and accelerated postnatal growth. Endocrinology. 2015; 156(10), 35283537.
94. Tarry-Adkins, JL, Fernandez-Twinn, DS, Hargreaves, IP, et al. Coenzyme Q10 prevents hepatic fibrosis, inflammation, and oxidative stress in a male rat model of poor maternal nutrition and accelerated postnatal growth. Am J Clin Nutr. 2016; 103(2), 579588.
95. Rabadán-Diehl, C, Nathanielsz, P. From mice to men: research models of developmental programming. J Dev Orig Health Dis. 2013; 4(01), 39.


Strength of nonhuman primate studies of developmental programming: review of sample sizes, challenges, and steps for future work

  • Hillary F. Huber (a1), Susan L. Jenkins (a1), Cun Li (a1) (a2) and Peter W. Nathanielsz (a1) (a2)


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed