M P Little

Summary

Affiliation: Imperial College
Country: UK

Publications

  1. ncbi request reprint Projection of cancer risks from the Japanese atomic bomb survivors to the England and Wales population taking into account uncertainty in risk parameters
    M P Little
    Department of Epidemiology and Public Health, Imperial College School of Medicine, London, UK
    Radiat Environ Biophys 39:241-52. 2000
  2. pmc Systematic review of worldwide variations of the prevalence of wheezing symptoms in children
    Swatee P Patel
    School of Health and Social Care, University of Greenwich, Southwood Site, Avery Hill Road, London SE9 2UG, UK
    Environ Health 7:57. 2008
  3. pmc Cancer models, genomic instability and somatic cellular Darwinian evolution
    Mark P Little
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College Faculty of Medicine, London, UK
    Biol Direct 5:19; discussion 19. 2010
  4. ncbi request reprint A systematic review of epidemiological associations between low and moderate doses of ionizing radiation and late cardiovascular effects, and their possible mechanisms
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London W2 1PG, United Kingdom
    Radiat Res 169:99-109. 2008
  5. pmc Systems biological and mechanistic modelling of radiation-induced cancer
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London W2 1PG, UK
    Radiat Environ Biophys 47:39-47. 2008
  6. ncbi request reprint Systematic review of experimental studies on the relative biological effectiveness of tritium
    M P Little
    Department of Epidemiology and Public Health, Imperial College, London W2 1PG, UK
    Radiat Environ Biophys 47:71-93. 2008
  7. ncbi request reprint Are cancer risks associated with exposures to ionising radiation from internal emitters greater than those in the Japanese A-bomb survivors?
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College London, Faculty of Medicine, St Mary s Campus, Norfolk Place, London, UK
    Radiat Environ Biophys 46:299-310. 2007
  8. ncbi request reprint Factors associated with fall in neonatal intubation rates in the United Kingdom--prospective study
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, St Mary s Campus, and Paediatric Department, St Mary s Hospital, London, UK
    BJOG 114:156-64. 2007
  9. ncbi request reprint A multi-compartment cell repopulation model allowing for inter-compartmental migration following radiation exposure, applied to leukaemia
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London W2 1PG, UK
    J Theor Biol 245:83-97. 2007
  10. ncbi request reprint Stochastic modelling of colon cancer: is there a role for genomic instability?
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London W2 1PG, UK
    Carcinogenesis 28:479-87. 2007

Detail Information

Publications56

  1. ncbi request reprint Projection of cancer risks from the Japanese atomic bomb survivors to the England and Wales population taking into account uncertainty in risk parameters
    M P Little
    Department of Epidemiology and Public Health, Imperial College School of Medicine, London, UK
    Radiat Environ Biophys 39:241-52. 2000
    ..Overall, cancer risks predicted by Bayesian Markov Chain Monte Carlo methods are similar to those derived by classical likelihood-based methods and which form the basis of established estimates of radiation-induced cancer risk...
  2. pmc Systematic review of worldwide variations of the prevalence of wheezing symptoms in children
    Swatee P Patel
    School of Health and Social Care, University of Greenwich, Southwood Site, Avery Hill Road, London SE9 2UG, UK
    Environ Health 7:57. 2008
    ..Considerable variation in the prevalence of childhood asthma and its symptoms (wheezing) has been observed in previous studies and there is evidence that the prevalence has been increasing over time...
  3. pmc Cancer models, genomic instability and somatic cellular Darwinian evolution
    Mark P Little
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College Faculty of Medicine, London, UK
    Biol Direct 5:19; discussion 19. 2010
    ..Biosci. 2003:183;111-134; Little et al. J. Theoret. Biol. 2008:254;229-238)...
  4. ncbi request reprint A systematic review of epidemiological associations between low and moderate doses of ionizing radiation and late cardiovascular effects, and their possible mechanisms
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London W2 1PG, United Kingdom
    Radiat Res 169:99-109. 2008
    ..Further epidemiological and biological evidence will allow a firmer conclusion to be drawn...
  5. pmc Systems biological and mechanistic modelling of radiation-induced cancer
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London W2 1PG, UK
    Radiat Environ Biophys 47:39-47. 2008
    ....
  6. ncbi request reprint Systematic review of experimental studies on the relative biological effectiveness of tritium
    M P Little
    Department of Epidemiology and Public Health, Imperial College, London W2 1PG, UK
    Radiat Environ Biophys 47:71-93. 2008
    ..17 (95% CI 0.96, 1.39). Again, problems with the design, in particular the range of doses used in some of these studies, mean that these RBE values should also probably not be interpreted as RBE(max)...
  7. ncbi request reprint Are cancer risks associated with exposures to ionising radiation from internal emitters greater than those in the Japanese A-bomb survivors?
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College London, Faculty of Medicine, St Mary s Campus, Norfolk Place, London, UK
    Radiat Environ Biophys 46:299-310. 2007
    ....
  8. ncbi request reprint Factors associated with fall in neonatal intubation rates in the United Kingdom--prospective study
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, St Mary s Campus, and Paediatric Department, St Mary s Hospital, London, UK
    BJOG 114:156-64. 2007
    ..To investigate the trend of neonatal resuscitation by intubation or mask ventilation over time and to assess its association with changes in prevalence of caesarean section and use of general anaesthesia in labour...
  9. ncbi request reprint A multi-compartment cell repopulation model allowing for inter-compartmental migration following radiation exposure, applied to leukaemia
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London W2 1PG, UK
    J Theor Biol 245:83-97. 2007
    ..In general, mutant cell numbers are highly overdispersed, with variance much greater than the mean...
  10. ncbi request reprint Stochastic modelling of colon cancer: is there a role for genomic instability?
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London W2 1PG, UK
    Carcinogenesis 28:479-87. 2007
    ....
  11. ncbi request reprint Hemoglobin concentration in pregnancy and perinatal mortality: a London-based cohort study
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College London, Faculty of Medicine, St Mary s Campus, Norfolk Place, United Kingdom
    Am J Obstet Gynecol 193:220-6. 2005
    ..The objective of the study was to determine the association between maternal hemoglobin concentration during pregnancy and perinatal mortality...
  12. ncbi request reprint A model for radiation-induced bystander effects, with allowance for spatial position and the effects of cell turnover
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, Norfolk Place, London W2 1PG, UK
    J Theor Biol 232:329-38. 2005
    ..It is shown that the generally intractable solution of the full stochastic system can be considerably simplified by assumption of pairwise conditional dependence that varies exponentially over time...
  13. doi request reprint Systematic review of epidemiological studies of exposure to tritium
    M P Little
    Department of Epidemiology and Public Health, Imperial College, London, UK
    J Radiol Prot 28:9-32. 2008
    ..Although the studies presently reported are uninformative on risks from tritium, a number of the occupationally exposed cohorts would be potentially informative, particularly if data were suitably combined...
  14. doi request reprint New models for evaluation of radiation-induced lifetime cancer risk and its uncertainty employed in the UNSCEAR 2006 report
    M P Little
    Department of Epidemiology and Public Health, Imperial College, London, UK
    Radiat Res 169:660-76. 2008
    ..Linear-quadratic-exponential models predict lower risks (at least at low test doses) and appear to fit as well, although for other (theoretical) reasons we favor the simpler linear-quadratic models...
  15. pmc Parameter identifiability and redundancy: theoretical considerations
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London, United Kingdom
    PLoS ONE 5:e8915. 2010
    ..Before data is analysed it is critical to determine which model parameters are identifiable or redundant to avoid ill-defined and poorly convergent regression...
  16. pmc Do non-targeted effects increase or decrease low dose risk in relation to the linear-non-threshold (LNT) model?
    M P Little
    Department of Epidemiology and Biostatistics, Imperial College School of Public Health, Faculty of Medicine, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Mutat Res 687:17-27. 2010
    ..If there is to be modification by low doses of ionizing radiation of cardiovascular disease through this mechanism, a role for non-DNA-targeted effects cannot be excluded...
  17. pmc Parameter identifiability and redundancy in a general class of stochastic carcinogenesis models
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College, London, UK
    PLoS ONE 4:e8520. 2009
    ..Math Biosci 1979 47 55-77), the generalized multistage model of Little (Biometrics 1995 51 1278-1291), and a recently developed cancer model of Nowak et al. (PNAS 2002 99 16226-16231)...
  18. doi request reprint Updated estimates of the proportion of childhood leukaemia incidence in Great Britain that may be caused by natural background ionising radiation
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College, London W2 1PG, UK
    J Radiol Prot 29:467-82. 2009
    ..The slightly lower attributable proportions compared with those previously derived by Wakeford et al (Leukaemia 2009 23 770-6) are largely due to the lower doses (and in particular lower high LET doses) for the first year of life...
  19. pmc Review and meta-analysis of epidemiological associations between low/moderate doses of ionizing radiation and circulatory disease risks, and their possible mechanisms
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, Norfolk Place, London, W2 1PG, UK
    Radiat Environ Biophys 49:139-53. 2010
    ..Although the predictions of the model are consistent with the epidemiological data, the experimental predictions made have yet to be tested. Further epidemiological and biological evidence will allow a firmer conclusion to be drawn...
  20. doi request reprint Heterogeneity of variation of relative risk by age at exposure in the Japanese atomic bomb survivors
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College, London, UK
    Radiat Environ Biophys 48:253-62. 2009
    ..Stratification by solid cancer type slightly weakens the evidence for quadratic variation in relative risk by age at exposure (P = 0.060)...
  21. doi request reprint Cancer and non-cancer effects in Japanese atomic bomb survivors
    M P Little
    Department of Epidemiology and Public Health, Imperial College, London W2 1PG, UK
    J Radiol Prot 29:A43-59. 2009
    ..Further epidemiological and biological evidence will allow a firmer conclusion to be drawn...
  22. doi request reprint Leukaemia following childhood radiation exposure in the Japanese atomic bomb survivors and in medically exposed groups
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Radiat Prot Dosimetry 132:156-65. 2008
    ..The effects of cell sterilisation can largely explain the discrepancy between the Japanese and the medical series...
  23. doi request reprint A stochastic carcinogenesis model incorporating multiple types of genomic instability fitted to colon cancer data
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London W21PG, UK
    J Theor Biol 254:229-38. 2008
    ..Given the good fit of the model to this large dataset, it is unlikely that further information on presence of genomic instability or of types of genomic instability can be extracted from age-incidence data by extensions of this model...
  24. ncbi request reprint The bystander effect model of Brenner and Sachs fitted to lung cancer data in 11 cohorts of underground miners, and equivalence of fit of a linear relative risk model with adjustment for attained age and age at exposure
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    J Radiol Prot 24:243-55. 2004
    ..In particular, both models are capable of describing the observed inverse dose rate effect in this data set...
  25. ncbi request reprint Risks associated with ionizing radiation
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, St Mary s Campus, London, UK
    Br Med Bull 68:259-75. 2003
    ..Risks among occupationally exposed groups such as nuclear workforces and underground miners are generally consistent with those observed in the Japanese atomic bomb survivors...
  26. ncbi request reprint Association between microfilarial load and excess mortality in onchocerciasis: an epidemiological study
    M P Little
    Department of Epidemiology and Public Health, Imperial College London, London, UK
    Lancet 363:1514-21. 2004
    ..Excess mortality has been noted among people with onchocerciasis, but it is not clear whether this effect is entirely due to blindness, or mediated by some more direct effects of the infection...
  27. ncbi request reprint A stochastic carcinogenesis model incorporating genomic instability fitted to colon cancer data
    M P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London, UK
    Math Biosci 183:111-34. 2003
    ....
  28. ncbi request reprint Threshold and other departures from linear-quadratic curvature in the non-cancer mortality dose-response curve in the Japanese atomic bomb survivors
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London W2 1PG, UK
    Radiat Environ Biophys 43:67-75. 2004
    ..Again, increasing the size of the errors resulted in wider confidence intervals on the power of dose, without marked effect on the central estimates. In general these findings remain true for various non-cancer disease subtypes...
  29. ncbi request reprint Potential funding crisis for the Radiation Effects Research Foundation
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, London W2 1PG, UK
    Lancet 364:557-8. 2004
  30. pmc A model of cardiovascular disease giving a plausible mechanism for the effect of fractionated low-dose ionizing radiation exposure
    Mark P Little
    Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom
    PLoS Comput Biol 5:e1000539. 2009
    ..The analysis of the present paper suggests that linear extrapolation would be appropriate for this endpoint...
  31. ncbi request reprint Incidence of blindness during the Onchocerciasis control programme in western Africa, 1971-2002
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College London, Faculty of Medicine, St Mary s Campus, London, United Kingdom
    J Infect Dis 189:1932-41. 2004
    ..Infection with Onchocerca volvulus is associated with the prevalence of severe visual impairment and blindness. However, longitudinal studies of the incidence of blindness caused by onchocerciasis are scarce...
  32. ncbi request reprint Flexible dose-response models for Japanese atomic bomb survivor data: Bayesian estimation and prediction of cancer risk
    James Bennett
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, St Mary s Campus, Norfolk Place, London, W2 1PG, UK
    Radiat Environ Biophys 43:233-45. 2004
    ..Overall, cancer incidence risks predicted by Bayesian Markov Chain Monte Carlo methods are similar to those derived by classical likelihood-based methods and which form the basis of established estimates of radiation-induced cancer risk...
  33. ncbi request reprint Absence of evidence for differences in the dose-response for cancer and non-cancer endpoints by acute injury status in the Japanese atomic-bomb survivors
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Int J Radiat Biol 78:1001-10. 2002
    ..To ascertain possible evidence for radiosensitive subgroups in the Japanese atomic-bomb survivors...
  34. ncbi request reprint Comparisons of lung tumour mortality risk in the Japanese A-bomb survivors and in the Colorado Plateau uranium miners: support for the ICRP lung model
    M P Little
    Department of Epidemiology and Public Health, Imperial College of Science, Technology and Medicine, St Mary s Campus, Norfolk Place, London, W2 1PG, UK
    Int J Radiat Biol 78:145-63. 2002
    ..To estimate the ratio of risks for exposure to radon progeny relative to low-LET radiation based on human lung cancer data, taking account of possible time and age variations in radiation-induced lung cancer risk...
  35. ncbi request reprint The bystander effect in experimental systems and compatibility with radon-induced lung cancer in humans
    M P Little
    Department of Epidemiology and Public Health, Imperial College of Science, Technology and Medicine, London, UK
    J Radiol Prot 22:A27-31. 2002
    ..Other experimental data relating to the bystander effect after alpha-particle exposure are surveyed; some of these data are more compatible with the epidemiological data...
  36. ncbi request reprint The proportion of thyroid cancers in the Japanese atomic bomb survivors associated with natural background radiation
    M P Little
    Department of Epidemiology and Public Health, Imperial College of Science, Technology and Medicine, London, UK
    J Radiol Prot 22:279-91. 2002
    ..5% for those over the age of 60, assuming that the absolute risk model applies. There is a similar increase in this percentage, if to a rather lower level (from 0.2 to 10.2%), assuming that the relative risk model applies...
  37. ncbi request reprint Comparison of the risks of cancer incidence and mortality following radiation therapy for benign and malignant disease with the cancer risks observed in the Japanese A-bomb survivors
    M P Little
    Department of Epidemiology and Public Health, Imperial College School of Medicine, Norfolk Place, London, UK
    Int J Radiat Biol 77:431-64. 2001
    ....
  38. ncbi request reprint Derivation of low-dose extrapolation factors from analysis of curvature in the cancer incidence dose response in Japanese atomic bomb survivors
    M P Little
    Department of Epidemiology and Public Health, Imperial College School of Medicine, London, UK
    Int J Radiat Biol 76:939-53. 2000
    ..To assess the degree of overestimation in low-dose cancer risk when models linear in dose are fitted to cancer data...
  39. ncbi request reprint A comparison of the degree of curvature in the cancer incidence dose-response in Japanese atomic bomb survivors with that in chromosome aberrations measured in vitro
    M P Little
    Department of Epidemiology and Public Health, Imperial College School of Medicine, St Mary s Campus, London, UK
    Int J Radiat Biol 76:1365-75. 2000
    ..To compare the degree of curvature in the dose-response for chromosome aberrations and for radiation-induced cancer...
  40. ncbi request reprint Cancer after exposure to radiation in the course of treatment for benign and malignant disease
    M P Little
    Department of Epidemiology and Public Health, Imperial College School of Medicine, London, UK
    Lancet Oncol 2:212-20. 2001
    ..This increase in risk has to be balanced against the generally high spontaneous cancer risk in these individuals and the benefits accruing from radiotherapy...
  41. doi request reprint The statistical power of epidemiological studies analyzing the relationship between exposure to ionizing radiation and cancer, with special reference to childhood leukemia and natural background radiation
    M P Little
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College Faculty of Medicine, London W2 1PG, United Kingdom
    Radiat Res 174:387-402. 2010
    ..Sufficiently large studies should be capable of detecting the predicted risk attributable to natural background radiation...
  42. ncbi request reprint The bystander effect in C3H 10T cells and radon-induced lung cancer
    M P Little
    Department of Epidemiology and Public Health, Imperial College of Science, Technology and Medicine, St Mary s Campus, Norfolk Place, London W2 1PG, United Kingdom
    Radiat Res 156:695-9. 2001
    ..As a consequence, the bystander effect observed in the experimental C3H 10T(1/2) cell system probably does not play a large part in the process of radon-induced lung carcinogenesis in humans...
  43. ncbi request reprint Modelling lung tumour risk in radon-exposed uranium miners using generalizations of the two-mutation model of Moolgavkar, Venzon and Knudson
    Mark P Little
    Department of Epidemiology and Public Health, Imperial College of Science, Technology and Medicine, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Int J Radiat Biol 78:49-68. 2002
    ..To model radon-induced lung cancer in uranium miners using a quasi-biological model of carcinogenesis...
  44. pmc Maternal blood pressure in pregnancy, birth weight, and perinatal mortality in first births: prospective study
    Philip J Steer
    Academic Department of Obstetrics and Gynaecology, Imperial College London, Faculty of Medicine, Chelsea and Westminster Hospital, London SW10 9NH
    BMJ 329:1312. 2004
    ..To investigate the relation of diastolic blood pressure in pregnancy with birth weight and perinatal mortality...
  45. ncbi request reprint Change in salt intake affects blood pressure of chimpanzees: implications for human populations
    Paul Elliott
    Department of Epidemiology and Public Health, Imperial College London, Faculty of Medicine, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Circulation 116:1563-8. 2007
    ..Effects of more modest alterations to sodium intakes in chimpanzees, akin to current efforts to lower sodium intakes in the human population, are unknown...
  46. pmc River blindness: a success story under threat?
    Maria Gloria Basanez
    Department of Infectious Disease Epidemiology, Imperial College of Science, Technology and Medicine, London, United Kingdom
    PLoS Med 3:e371. 2006
  47. ncbi request reprint Transmission intensity and the patterns of Onchocerca volvulus infection in human communities
    Maria Gloria Basanez
    Department of Infectious Disease Epidemiology, Imperial College School of Medicine, St Mary s Campus, London, United Kingdom
    Am J Trop Med Hyg 67:669-79. 2002
    ..ochraceum than in those where the vector is S. damnosum. A role for focal vector control in Mexico and Guatemala, in addition to nodulectomy and ivermectin, is suggested...
  48. pmc Human infection patterns and heterogeneous exposure in river blindness
    Joao A N Filipe
    Department of Infectious Disease Epidemiology, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom
    Proc Natl Acad Sci U S A 102:15265-70. 2005
    ..The basic reproductive number, R0, ranges from 5 to 8, which is slightly above estimates for other helminth parasites but well below previously presented values...
  49. ncbi request reprint Childhood cancer after low-level intrauterine exposure to radiation
    Richard Wakeford
    BNFL, Risley, Warrington, Cheshire, UK
    J Radiol Prot 22:A123-7. 2002
    ..Nonetheless, the evidence does suggest that the risk is not zero at doses of the order of 10 mSv...
  50. pmc Comment on "Use of A-bomb survivor studies as a basis for nuclear worker compensation"
    Mark P Little
    Environ Health Perspect 111:A267-8. 2003
  51. ncbi request reprint Radiation: a dose of the bomb
    Mark P Little
    Nature 424:495-6. 2003
  52. ncbi request reprint Radiation-induced leukemia at doses relevant to radiation therapy: modeling mechanisms and estimating risks
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th St, New York, NY 10032, USA
    J Natl Cancer Inst 98:1794-806. 2006
    ..This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks...
  53. ncbi request reprint Risks of non-cancer disease incidence and mortality in the Japanese atomic bomb survivors
    Mark P Little
    J Radiol Prot 24:327-8. 2004
  54. ncbi request reprint Funding crisis at the Radiation Effects Research Foundation
    Mark P Little
    J Radiol Prot 24:195-7. 2004
  55. ncbi request reprint Does gestation vary by ethnic group? A London-based study of over 122,000 pregnancies with spontaneous onset of labour
    Roshni R Patel
    Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, University of London, Keppel St, London WC1E 7HT, UK
    Int J Epidemiol 33:107-13. 2004
    ..Evidence exists that normal gestational length varies with ethnicity. This UK-based study compares gestational length amongst a cohort of white European, Black and Asian women...
  56. pmc Early growth and adult respiratory function in men and women followed from the fetal period to adulthood
    Dexter Canoy
    Department of Public Health Science and General Practice, University of Oulu, Finland
    Thorax 62:396-402. 2007
    ..A study was undertaken to determine the association between early growth and adult respiratory function...