Children of the 1950s
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The ‘Children of the 1950s’ study began in 1962 when researchers surveyed all the primary school children in Aberdeen aged 7-12 years. At the time they were interested in investigating the occurrence and causes of learning disabilities in a distinct population.

Now, over 50 years later, scientists are using the data collected along with information collected via a postal questionnaire. Their aim is to investigate the factors in infancy and childhood which can shape health and disease in adult life. New research suggests size at birth, growth in childhood and social circumstances can all have an effect. If we can understand some of the causes of ill health, it may help us to produce preventative measures for the future.

Tracing the study members

Questionnaire response

Ensuring the data is valid

Heart disease

Pregnancy

Intelligence

Across the generations

Schooling

Mental health

1. Tracing the study members

We attempted to trace 12,150 of the children in the original school survey in 1962 who were born in Aberdeen. By March 2004 we had found over 97% of the population of whom 477 were deceased and 288 were known to have emigrated from the UK. Of those still found to be living in the UK, 81% still lived in Scotland while 73% were in Grampian region.

By looking at the data collected in the 1960s and comparing who had moved away and who had not, we found that children who were taller, from higher social classes and those who did better at school tests were more likely to have moved away from Grampian.

2. Response to the questionnaire

We mailed more than 11,000 study members of whom over 7,000 (64%) completed and returned the questionnaire. This is a good rate of response compared to other similar postal research surveys. We were keen to have as big a response as possible as if any section of the population are not represented this could affect the way we view our results. Encouragingly for the study researchers, 95% of those who responded to the questionnaire were willing to take part in future surveys.

We found that slightly more women than men responded. Those who had better primary school test results were more likely to return the questionnaire, as were those who had fewer siblings, were taller, heavier and those whose father was in a non-manual occupation at the time of their birth.

3. Ensuring the data is valid

An important part of our work is to ensure the data we are using is valid. We therefore looked at how the answers in the questionnaire relating to father’s occupation matched up with answers given in the original study in 1962. We found a degree of difference between the two that was enough to affect the interpretation of results. We could therefore suggest that in similar studies, data collected where participants recall past events should be used with caution.

4. Heart disease

Coronary heart disease and stroke are amongst the biggest killers in Scotland today. We were therefore keen to look at their prevalence in this population and any possible explanations as to why some people are more likely to suffer than others.

First of all we found that social class at birth was associated with lifestyle behaviours in adult life such as smoking, binge drinking and being overweight. These factors are known to be risk factors for heart disease. Those in the higher social classes were on average less likely to have these ‘risky’ behaviours. There is evidence from the data that levels of education may be an important factor here.

Those study members who had a father in a higher social class according to occupation were less likely to suffer from heart disease than those in the lower classes. Coronary heart disease and stroke were also more prevalent in those with a lower weight at birth. This has been shown in other similar studies of previous generation, but it is interesting that we have found it to be the case in more recent times. Interestingly, we did not find any association between being obese or overweight at primary school age and increased risk of heart disease in adult life. It may be that if weight had been measured later in childhood or in adolescence an increase in risk would have been apparent.

5. Pregnancy

Differences in temperature during the pregnancies of the mothers of the ‘Children of the 1950s’ affected birth weight of their offspring. The explanation for this is unclear as yet, but this is of interest if weather patterns are changing to more extreme conditions as is suspected.

Raised blood pressure in pregnancy is one of the most common complications, but the causes are not known. We examined the links between poor social circumstances in childhood and this condition. Results indicate that women who lived in poorer childhood circumstances as children were at greater risk of a severe from of high blood pressure known as pre-eclampsia. Unfortunately information on smoking in pregnancy was limited. Ideally we would like to have factored this into our results.

6. Intelligence

It is known that intelligence in childhood is an indicator for state of health in later adult life. If we knew what factors determine IQ in early life, it may help us to understand how it is related to health. These factors may be social and biological. In this study we found that height in childhood, growth before birth, characteristics of the mother and, especially, father’s social class could be related to IQ as measured by performance in school tests at age 7,9 and 11 years.

Season of birth also appeared to have a small effect on how children in this study performed in school tests. This effect was found to be due to the differences in the age at school entry as this depends on the time of year you were born.

7. Across the generations

By linking the female members of the study to the birth records of their own children we have shown that the size at birth of the offspring is related to that of their mother. This is separate from the mother’s growth and circumstances throughout her own life.

8. Schooling

One of the questions researchers wanted to ask was ‘Can the school you attend influence your later health’. While there was a difference between the average health of those attending different schools, this seemed to be due to the composition of the school intake of pupils rather than a direct influence by the school.

9. Mental health

Low birth weight not due to prematurity was related to adult psychological health in this study. It may be that this is due to impaired development of the brain during growth in fetal life. More research is required to find a possible mechanism.

We hope to keep you updated on future findings. If you have any further questions please contact the study co-ordinator Heather Clark at the University of Aberdeen: phone 01224 438443 or write children1950s@abdn.ac.uk

Beyond Test Scores: How being top of your class affects educational attainments and socio-emotional development

University of Essex

Making comparisons between individuals and objects is the way we experience the world as humans. That inevitably leads to create rankings. In the context of a primary school, students will likely be able to rank themselves and their peers based on observed grades in a certain subject. Teachers will have an even better perspective on how their pupils rank, as they observe the entire distribution of grades within a class. The existence of a “rank effect” has been documented by the literature: . However, little attention was paid to the impact on the development of social and emotional skills. In this project we would like to investigate whether ranking by ability at the class or grade level in the early years of primary school has long lasting effect on children’s outcomes, including later educational attainment but also behaviour and emotional skills.

Multidisciplinary Ecosystem to study Lifecourse Determinants and Prevention of Burdensome Mid-life Multimorbidity

University of Southampton

A growing number of people are living with multiple long-term health conditions like diabetes, heart disease or dementia. We call this multi-morbidity. Many things throughout a person’s life influence the chances of developing health conditions. People from more disadvantaged backgrounds and/or certain ethnicities are more likely to develop multi-morbidity and to develop it earlier. The order that people develop conditions also varies.

We aim to understand the way people develop early multi-morbidity over their lifetime and the things that influence that, including broader experiences. By ‘early’ we mean before age 65. This will identify key time points in a person’s life where prevention efforts should be targeted or strengthened to reduce the risk of that person developing burdensome multi-morbidity.

Long-term effect of separation from best friends

H Kawarazaki, University College London

Using the data from the Aberdeen Children of the Nineteen-Fifties (ACONF), this study examines the long-term effects of attending an elite school. Since childhood environment may affect various statuses in adulthood, we look at health, socioeconomic, and socioemotional outcomes. In addition, many students experience separation from their best friends at primary schools when they proceeded to secondary schools. Therefore, we also examine the long-term effect of this type of separation.

Association between childhood epilepsy and socioeconomic status in adulthood

P Mazzone, University of Edinburgh

The proposed study will use data from the Aberdeen Children of the Nineteen-Fifties (ACONF) to investigate the association between childhood epilepsy and socioeconomic deprivation in adulthood. We will compare our findings to other population-based studies to better understand how changes in education and social support, and how better diagnostic and treatment options since the 1950s have shaped education, health, and deprivation outcomes in children with epilepsy in Scotland.

Guide and Scout participation in childhood and influence on cognitive ability, social mobility and mental health in adulthood

Dr Lynne Forrest, University of Edinburgh

This study examines whether being a member of the Guides, Scouts or Boys Brigade in childhood influences mental health in adulthood, using the Aberdeen Child of the 1950s birth cohort. We also want to look at whether being a member enhances intelligence and social mobility.

Growing up in Aberdeen

Professor C Wallace, University of Aberdeen

This study aims to find out people’s experiences of growing up in Aberdeen. Through face to face interviews, it will help us to understand how the lives of people from your generation were affected by the social and economic changes that have taken place, including the rebuilding of residential areas, the changing educational system, the impact of the oil industry and decline of the fishing industries and other factors.

Multimorbidity

Dr M Johnston, University of Aberdeen

Multimorbidity, the co-existence of two or more health conditions, is a growing Public Health challenge due to the ageing of our population and a rise in the number of long term conditions. It is associated with poorer outcomes and the increased use of health and social care services. If interventions are to be developed and services better targeted, there is a need to investigate the prevalence of multimorbidity and the early and later life factors associated with its development and resilience to its effects.

STRADL

Professor A Murray, University of Aberdeen

Professor A McIntosh, University of Aberdeen

Clinical depression is a chronic worldwide health problem affecting millions of people and approximately 13 per cent of the UK population. Researchers say that although it is a chronic and recurrent problem for many sufferers, little is known about what makes people vulnerable or resilient to the condition. By studying groupings of people both with and without depression in this way researchers hope to be able to identify its causes and mechanisms, which can be used in the quest for diagnostic tests and new therapies.

The investigators will test whether the subgroups of depressed individuals correspond to different diseases using tests of memory and intelligence (cognition) as well as brain imaging. website

Benzodiazepines and Z-drugs Prescribing Patterns over Time among the Aberdeen Children of the Nineteen Fifties Cohort

M Khezrian, University of Aberdeen

Long-term benzodiazepines (BZD) and Z-drugs prescribing is a concern worldwide due to the risks associated with these medicines. Guidelines recommend that they should be prescribed only for severe anxiety/insomnia and that prescribing should be limited to the lowest possible dose for the shortest possible time period (up to four weeks). Despite guidelines, in Scotland the sustained level of prescribing over the last decade suggests long-term use. A large amount of the BZD and Z-drugs prescribing occurred in those aged 40-69. Understanding BZD and Z-drugs prescribing patterns and whether particular patient characteristics (such as socioeconomic status and circumstances, social mobility, having several chronic conditions) are related to long-term prescribing might allow us to prevent long-term use.

Experience of social mobility

K Adamczyk, University of Aberdeen

We are taught from a young age to aim high, to reach for the stars, to want more, more than our parents, more than the generations before us, to climb the social ladder. But as we surge forward, as we grapple for university places and promotions, what are we leaving behind? And from our ladder in the stars, if we look back, what do we see?

This study employs a mixed-methods approach to examine how individuals understand, experience and evaluate social mobility and the effect of social mobility trajectories on health and wellbeing. Through statistical analysis of survey data and life-history interviews, this research aims to illuminate how people experience life-course transitions, occupational and otherwise, in times of social change.

How strongly is family socioeconomic status associated with children’s cognitive and scholastic performance during the years of attending primary school?

Professor von Stum, University of York

Family background is one of the key factors influences children’s differences in cognitive and scholastic performance.

Previous studies have shown that children from more advantaged family backgrounds tend to perform better in cognitive tests and school exams than children from impoverished family homes. However, the strength of the association between family background and children’s performance in cognitive tests and school exams during the years of attending primary school in the ACONF sample is yet unknown. For this project, we will estimate this association to compare its strength to that reported for other samples from Britain.

Three comprehensive descriptions of the study have been published:

Batty G D, Morton S M B, Campbell D, Clark H, Davey Smith G, Hall M, Macintyre S, Leon D A.

The Aberdeen Children of the 1950s cohort study: background, methods and follow-up information as a new resource for the study of life course and intergenerational influences on health. Pediatric and Perinatal Epidemiology 2004; 18: 221-239 PubMed

Leon D A, Lawlor D A, Clark H, Macintyre S

Cohort profile: the Aberdeen Children of the 1950s study. International Journal of Epidemiology. 2006 :35:549-552. PubMed

Illsley R and Wilson F

The Aberdeen Child Development Survey. In Prospective longitudinal research: an empirical basis for the primary prevention of psychosocial disorders, Mednick and Baert, eds., Oxford University Press, 1981

Publications

Mazzone PP, Weir CJ, Bhattacharya S, Chin RFM.

Socioeconomic status in adulthood of children with and without a history of seizures: A retrospective cohort study. Epilepsy Behaviour 2024: doi: 10.1016/j.yebeh.2024.109705

Bashir MT, McNeil C, Rasul U, Murray A.

Haemoglobin Concentration and Cognitive Ability in the Aberdeen Children of the 1950s. Cureus 2022: https://doi.org/10.7759/cureus.21806

Berrie L, Adair L, Williamson L, Dibben C.

Youth organizations, social mobility and health in middle age: evidence from a Scottish 1950s prospective cohort study. Eur J Public Health 2022: doi: 10.1093/eurpub/ckac144

Warrilow A, Der G, Cooper S, Minnis H.

Childhood neurodevelopmental markers and risk of premature mortality: Follow-up to age 60-65 years in the Aberdeen Children of the 1950s study. PLOS One 2021: https://doi.org/10.1371/journal.pone.0255649

Beange, I., Kirkham, E. J., Fletcher-Watson, S., Iveson, M. H., Lawrie, S. M., Batty, G. D., Boardman, J. P., Deary, I. J., Black, C., Porteous, D. J., & McIntosh, A. M. (2020). Using a knowledge exchange event to assess study participants’ attitudes to research in a rapidly evolving research context. Wellcome Open Research, 5, 1–21. https://doi.org/10.12688/wellcomeopenres.15651.1

Johnston MC, Black C, Mercer SW, Prescott GJ, Crilly M.

Prevalence of secondary care multimorbidity in mid-life and its association with premature mortality in a large longitudinal cohort. BMJ Open 2020: 10; e033622 doi.10.1136/bmjopen-2019-033622

de Vries CF, Staff RT, Waiter GD, Sokunbi MO Sandu AL, Murray AD.

Motion during acquisition is associated with fMRI brain entropy. IEEE Journal of Biomedical and Health Informatics 2020: 24;586-593 doi: 10.1109/JBHI.2019.2907189

Butler J, Black C, Craig P, Dibben C, Dundas R, Hilton Boom M, Johnston M, Popham F. The long-term health effects of attending a selective school: a natural experiment. BMC Medicine 2020 18, 77 https://doi.org/10.1186/s12916-020-01536-7

Johnston MC, Black C, Mercer SW, Prescott GJ, Crilly M.

Impact of educational attainment on the association between social class at birth and multimorbidity in middle age in the Aberdeen Children of the 1950s cohort study. BMJ Open 2019: 9; e024048 doi.10.1136/bmjopen-2018-024048

Stuart J.

Predicting risky health behaviours 35 years later. Are parents or teacher's reports of childhood behaviour problems a better judge of outcomes? Addictive behaviours 2018: 84; 255-262 doi.org/10.1016/j.addbeh.2018.04.023

Clark D, Del Bono E.

The long-run effects of attending an elite school: evidence from the United Kingdom. American Economic Journal: Applied Economics 2016: 8 (1); 150-176 DOI: 10.1257/app.20130505

Bhattacharya S, McNeill G, Raja EA, Allan K, Clark H, Reynolds RM, Norman JE, Hannaford PC.

Maternal gestational weight gain and offspring's risk of cardiovascular disease and mortality.

Heart 2016:102;1456-1463 doi:10.1136/heartjnl-2015-308709

Stuart J, Jose PE.

Is bullying bad for your health? The consequences of bullying, perpetration and victimization in childhood on health behaviours in adulthood.

Journal of Conflict, Aggression and Peace Research 2014:5-5 Link

Dundas R, Leyland A, Macintyre S.

Early life school, neighbourhood and family influences on adult health: a multilevel, cross-classified analysis of the Aberdeen Children of the 1950s study.

Am J Epidemiol 2014 PubMed

Morton SM, De Stavola BL, Leon DA.

Intergenerational determinants of offspring at birth: a life course and graphical analysis using the Aberdeen Children of the 1950s study (ACONF).

Int J Epidemiol 2014: 43(3); 749-759 DOI:10.1093/ije/dyu028PubMed

von Stumm S, Deary IJ, Hagger-Johnson G.

Life-course pathways to psychological distress: a cohort study.

BMJ Open 2013;3:e002772 PubMed

Almquist YM.

Childhood friendships and adult health: findings from the Aberdeen Children of the 1950s Cohort study.

Eur J Public Health. 2012;22:378-83 PubMed

von Stumm, Batty GD, Deary IJ.

Marital status and reproduction: Associations with intelligence and adult social class in the Aberdeen Children of the 1950s study.

Intelligence. 2011;39:161-167 doi.org/10.1016/j.intell.2011.02.007

Almquist Y.

The school class as a social network and contextual effects on childhood and adult health: Findings from the Aberdeen Children of the 1950s cohort study.

Social Networks. 2011;33:281-291 Link

Hagger-Johnson G, Batty GD, Deary IJ, von Stumm S.

Childhood socioeconomic status and adult health: comparative formative and reflective models in the Aberdeen Children of the 1950s Study (prospective cohort study).

J Epidemiol Community Health. 2011;65:1024-1029. PubMed

von Stumm S, Deary IJ, Kivimäki M, Jokela M, Clark H, Batty GD.

Childhood behaviour problems and health at midlife: 35-year follow-up of a Scottish birth cohort.

J Child Psychol Psychiatry. 2011; 52:992-1001 Pubmed

von Stumm S, Macintyre S Batty GD, Clark H, Deary IJ.

Intelligence, social class of origin, childhood behaviour disturbance and education as predictors of status attainment in midlife in men: The Aberdeen Children of the 1950s study.

Intelligence. 2010;38:202-211 Link

Leon DA, Lawlor DA, Clark H, Batty GD, Macintyre S.

The association of childhood intelligence with mortality risk from adolescence to middle age: Findings from the Aberdeen Children of the 1950s cohort study.

Intelligence. 2009;37:520-528 Link

Henderson M, Hoptof M, Leon DA.

Childhood temperament and long-term sickness absence in adult life.

Br J Psychiatry. 2009;194(3):220-3. PubMed

Whincup PH et al.

Birth weight and risk of type 2 diabetes: a systematic review.

JAMA 2008;300(24):2886-97. PubMed

Lawlor DA, David Batty G, Clark H, McIntyre S, Leon DA.

Association of childhood intelligence with risk of coronary heart disease and stroke: findings from the Aberdeen Children of the 1950s cohort study.

Eur J Epidemiol. 2008;23(10):695-706. Epub 2008 Aug 15. PubMed

Ostberg V, Modin B.

Status relations in school and their relevance for health in a life course perspective: Findings from the Aberdeen children of the 1950's cohort study.

Soc Sci Med. 2008 Feb;66(4):835-48. Epub 2007 Dec 26. PubMed

Lawlor DA, Morton S. Batty GD, Macintyre S, Clark H, Davey Smith G.

Obstetrician-assessed maternal health at pregnancy predicts offspring future health.

PLoS ONE. 2007 Aug 1;2:e666. PubMed

Batty GD, Deary IF, Macintyre S.

Childhood IQ in relation to risk factors for premature mortality in middle-aged persons: the Aberdeen Children of the 1950s study.

J Epidemiol Community Health. 2007 Mar;61(3):241-7.PubMed

Lawlor DA, Clark H, Leon DA.

Associations between childhood intelligence and hospital admissions for unintentional injuries in adulthood: the Aberdeen Children of the 1950s cohort study.

Am J Public Health. 2007 Feb;97(2):291-7. Epub 2006 Dec 28.PubMed

Lawlor DA, Davey Smith G, Clark H, Leon DA.

The association of birthweight, gestational age and childhood BMI with type 2 diabetes: findings from the Aberdeen Children of the 1950s cohort.

Diabetologia. 2006 Nov;49(11):2614-7. Epub 2006 Sep 21 PubMed<

Batty GD, Deary IJ, Macintyre S.

Childhood IQ and life course socioeconomic position in relation to alcohol induced hangovers in adulthood: the Aberdeen Children of the 1950s study.

J Epidemiol Community Health. 2006 Oct;60(10):872-4 PubMed

Lawlor DA, Clark H, Ronalds G, Leon DA.

Season of birth and childhood intelligence: Findings from the Aberdeen Children of the 1950s cohort study.

Br J Educ Psychol. 2006 Sep;76(pt 3):481-499 PubMed

Lawlor DA, Ronalds G, Macintyre S, Clark H, Leon DA.

Family Socioeconomic Position at Birth and Future Cardiovascular Disease Risk: Findings From the Aberdeen Children of the 1950s Cohort Study.

Am J Public Health. 2006 Jul;96(7):1271-7. Epub 2006 May 30 PubMed

Illsley R.

Commentary: Development of the Aberdeen children of the 1950s study.

Int J Epidemiol. 2006 Jun;35(3):554-5. Epub 2006 May 9 . PubMed

Lawlor DA, Clark H, Smith GD, Leon DA.

Intrauterine growth and intelligence within sibling pairs: findings from the Aberdeen children of the 1950s cohort.

Pediatrics. 2006 May;117(5):e894-902 . PubMed

Nitsch D, Morton S, DeStavlova BL, Clark H, Leon DA.

How good is probabilistic record linkage to reconstruct reproductive histories? Results from the Aberdeen Children of the 1950s study.

BMC Med Res Methodol. 2006 Mar 22;6:15 . PubMed

Lawlor DA, Clark H, Davey Smith G, Leon DA.

Childhood intelligence, educational attainment and adult body mass index: findings from a prospective cohort and within sibling-pairs analysis.

International Journal of Obesity 2006, Mar 21. PubMed

Leon DA, Lawlor DA, Clark H, Macintyre S.

Cohort profile: the Aberdeen Children of the 1950s study.

Int J Epidemiol. 2006 Jun;35(3):549-52. Epub 2006 Feb 1 PubMed

De Stavola BL, Nitsch D, dos Santos Silva I, McCormack V, Hardy R, Mann V, Cole TJ, Morton S, Leon DA.

Statistical issues in life course epidemiology.

Am J Epidemiol. 2006 Jan 1;163(1):84-96. Epub 2005 Nov 23 PubMed

Ronalds GA, Stavola BL, Leon DA.

The cognitive cost of being a twin: evidence from comparisons within families in the Aberdeen children of the 1950s cohort study.

BMJ.Dec 3;331(7528):1306. Epub 2005 Nov 18. PubMed

Dundas R, Leyland AH, Macintyre S, Leon DA

Does the primary school attended influence self-reported health or its risk factors in later life? Aberdeen Children of the 1950s Study.

Int J Epidemiol. 2005 Nov 12; PubMed

Kuh D, Butterworth S, Kok H, Richards M, Hardy R, Wadsworth MEJ, Leon D.

Childhood cognitive ability and age at menopause: evidence from two cohort studies.

Menopause 2005;12:475-82. PubMed

Pierce MB, Leon DA.

Age at menarche and adult BMI in the Aberdeen Children of the 1950s Cohort Study.

Am J Clin Nutr. 2005 Oct;82(4):733-9. PubMed

Batty GD, Lawlor DA, Macintyre S, Clark H, Leon DA

Accuracy of adults' recall of childhood social class: findings from the Aberdeen children of the 1950s study.

Journal of Epidemiology and Community Health. 2005 Oct;59(10):898-903. PubMed

Lawlor DA, Ronalds G, Clark H, Smith GD, Leon DA

Birth weight is inversely associated with incident coronary heart disease and stroke among individuals born in the 1950s: findings from the Aberdeen Children of the 1950s prospective cohort study.

Circulation. 2005 Sep 6;112(10):1414-8. Epub 2005 Aug 29. PubMed

Cooper R, Lawlor DA, Hardy R, Ebrahim S, Leon DA, Wadsworth ME, Kuh D.

Socio-economic position across the life course and hysterectomy in three British cohorts: a cross-cohort comparative study.

British Journal of Obstetrics & Gynaecology. 2005 Aug;112(8):1126-33. PubMed

Lawlor DA, Batty GD, Morton SM, Deary IJ, Macintyre S, Ronalds G, Leon DA.

Early life predictors of childhood intelligence: evidence from the Aberdeen children of the 1950s study.

Journal of Epidemiology and Community Health. 2005 Aug;59(8):656-63. PubMed

Wiles NJ, Peters TJ, Leon DA, Lewis G.

Birth weight and psychological distress at age 45-51 years: results from the Aberdeen Children of the 1950s cohort study.

British Journal of Psychiatry. 2005 Jul;187:21-8. PubMed

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Childhood socioeconomic position, educational attainment, and adult cardiovascular risk factors: the aberdeen children of the 1950s cohort study.

American Journal of Public Health. 2005 Jul;95(7):1245-51. PubMed

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Lawlor D, Leon, D, Smith, G. The association of ambient outdoor temperature throughout pregnancy and offspring birthweight: Findings from the Aberdeen Children of the 1950s cohort. British Journal of Obstetrics and Gynaecology, 2005: 112(5); 647-657 DOI:10.1111/j.1471-0528.2004.00488.x

Lawlor D, Morton S, Nitsch D, Leon D. Association between childhood and adulthood socioeconomic position and pregnancy induced hypertension: Results from the Aberdeen Children of the 1950s cohort study. Journal of Epidemiology and Community Health 2005: 59(1); 49-55. DOI:10.1136/jech.2004.020560

Nishiwaki Y, Clark H, Morton SM, Leon DA. (2005). Early life factors, childhood cognition and postal questionnaire response rate in middle age: The Aberdeen Children of the 1950s study. BMC Medical Research Methodology. 2005:5;16 DOI:10.1186/1471-2288-5-16

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