Latest Research News
There have been a number of studies in the past few years showing how poverty affects brain development and function. One of these showed specifically that children of high and low socioeconomic status showed differences in brain wave patterns associated with an auditory selective attention task. This was thought to indicate that the groups were using different mechanisms to carry out the task, with the lower SES children employing extra resources to attend to irrelevant information.
In a follow-up study, 28 young adolescents (12-14 years) from two schools in neighborhoods of different socioeconomic status answered questions about their emotional and motivational state at various points during the day, and provided saliva samples to enable monitoring of cortisol levels. At one point in the afternoon, they also had their brainwaves monitored while they carried out an auditory selective attention task (hearing different sounds played simultaneously into both ears, they were required to press a button as fast as possible when they heard one particular sound).
While performance on the task was the same for both groups, there were, once again, differences in the brain wave patterns. Higher SES children exhibited far larger theta waves in the frontal lobes in response to sounds they attended to than to compared to those they should have ignored, while lower SES children showed much larger theta waves to the unattended sounds than for the attended sounds.
While the lower SES children had higher cortisol levels throughout the school day, like the higher SES children, they showed little change around the task, suggesting neither group was particularly stressed by the task. Both groups also showed similar levels of boredom and motivation.
What the findings suggest is that lower SES children have to exert more cognitive control to avoid attending to irrelevant stimuli than higher SES children — perhaps because they live in more threatening environments.
(2012). Frontal EEG/ERP correlates of attentional processes, cortisol and motivational states in adolescents from lower and higher socioeconomic status.
Frontiers in Human Neuroscience. 6,
Full text available at http://www.frontiersin.org/human_neuroscience/10.3389/fnhum.2012.00306/a...
Benefits of high quality child care persist 30 years later
Back in the 1970s, some 111 infants from low-income families, of whom 98% were African-American, took part in an early childhood education program called the Abecedarian Project. From infancy until they entered kindergarten, the children attended a full-time child care facility that operated year-round. The program provided educational activities designed to support their language, cognitive, social and emotional development.
The latest data from that project, following up the participants at age 30, has found that these people had significantly more years of education than peers who were part of a control group (13.5 years vs 12.3), and were four times more likely to have earned college degrees (23% vs 6%).
They were also significantly more likely to have been consistently employed (75% had worked full time for at least 16 of the previous 24 months, compared to 53% of the control group) and less likely to have used public assistance (only 4% received benefits for at least 10% of the previous seven years, compared to 20% of the control group). However, income-to-needs ratios (income taken into account household size) didn’t vary significantly between the groups (mainly because of the wide variability; on the face of it, the means are very different, but the standard deviation is huge), and neither did criminal involvement (27% vs 28%).
See their website for more about this project.
Evidence that more time at school raises IQ
It would be interesting to see what the IQs of those groups are, particularly given that maternal IQ was around 85 for both treatment and control groups. A recent report analyzed the results of a natural experiment that occurred in Norway when compulsory schooling was increased from seven to nine years in the 1960s, meaning that students couldn’t leave until 16 rather than 14. Because all men eligible for the draft were given an IQ test at age 19, statisticians were able to look back and see what effect the increased schooling had on IQ.
They found that it had a substantial effect, with each additional year raising the average IQ by 3.7 points.
While we can’t be sure how far these results extend to other circumstances, they are clear evidence that it is possible to improve IQ through education.
Why children of higher-income parents start school with an advantage
Of course the driving idea behind improved child-care in the early years is all about the importance of getting off to a good start, and you’d expect that providing such care to children would have a greater long-term effect on IQ than simply extending time at school. Most such interventions have looked at the most deprived strata of society. An overlooked area is that of low to middle income families, who are far from having the risk factors of less fortunate families.
A British study involving 15,000 five-year-olds has found that, at the start of school, children from low to middle income families are five months behind children from higher income families in terms of vocabulary skills and have more behavior problems (they were also 8 months ahead of their lowest income peers in vocabulary).
Low-middle income (LMI) households are defined by the Resolution Foundation (who funded this research) as members of the working-age population in income deciles 2-5 who receive less than one-fifth of their gross household income from means-tested benefits (see their website for more detail on this).
Now the difference in home environment between LMI and higher income households is often not that great — particularly when you consider that it is often a difference rooted in timing. LMI households are more common in this group of families with children under five, because the parents are usually at an early stage of life. So what brings about this measurable difference in language and behavior development?
This is a tricky thing to derive from the data, and the findings must be taken with a grain of salt. And as always, interpretation is even trickier. But with this caveat, let’s see what we have. Let’s look at demographics first.
The first thing is the importance of parental education. Income plus education accounted for some 70-80% of the differences in development, with education more important for language development and income more important for behavior development. Maternal age then accounted for a further 10%. Parents in the higher-income group tended to be older and have better education (e.g., 18% of LMI mothers were under 25 at the child’s birth, compared to 6% of higher-income mothers; 30% of LMI parents had a degree compared to 67% of higher-income parents).
Interestingly, family size was equally important for language development (10%), but much less important for behavior development (in fact this was a little better in larger families). Differences in ethnicity, language, or immigration status accounted for only a small fraction of the vocabulary gap, and none of the behavior gap.
Now for the more interesting but much trickier analysis of environmental variables. The most important factor was home learning environment, accounting for around 20% of the difference. Here the researchers point to higher-income parents providing more stimulation. For example, higher-income parents were more likely to read to their 3-year-olds every day (75% vs 62%; 48% for the lowest-income group), to take them to the library at least once a month (42% vs 35% vs 26%), to take their 5-year-old to a play or concert (86% vs 75% vs 60%), to a museum/gallery (67% vs 48% vs 36%), to a sporting activity at least once a week (76% vs 57% vs 35%). Higher-income parents were also much less likely to allow their 3-year-olds to watch more than 3 hours of TV a day (7% vs 17% vs 25%). (I know the thrust of this research is the comparison between LMI and higher income, but I’ve thrown in the lowest-income figures to help provide context.)
Interestingly, the most important factor for vocabulary learning was being taken to a museum/gallery at age 5 (but remember, these correlations could go either way: it might well be that parents are more likely to take an articulate 5-year-old to such a place), with the second most important factor being reading to 3-year-old every day. These two factors accounted for most of the effects of home environment. For behavior, the most important factor was regular sport, followed by being to a play/concert, and being taken to a museum/gallery. Watching more than 3 hours of TV at age 3 did have a significant effect on both vocabulary and behavior development (a negative effect on vocabulary and a positive effect on behavior), while the same amount of TV at age 5 did not.
Differences in parenting style explained 10% of the vocabulary gap and 14% of the behavior gap, although such differences were generally small. The biggest contributors to the vocabulary gap were mother-child interaction score at age 3 and regular bedtimes at age 3. The biggest contributors to the behavior gap were regular bedtimes at age 5, regular mealtimes at age 3, child smacked at least once a month at age 5 (this factor also had a small but significant negative effect on vocabulary), and child put in timeout at least once a month at age 5.
Maternal well-being accounted for over a quarter of the behavior gap, but only a small proportion of the vocabulary gap (2% — almost all of this relates to social support score at 9 months). Half of the maternal well-being component of the behavior gap was down to psychological distress at age 5 (very much larger than the effect of psychological distress at age 3). Similarly, child and maternal health were important for behavior (18% in total), but not for vocabulary.
Material possessions, on the other hand, accounted for some 9% of the vocabulary gap, but none of the behavior gap. The most important factors here were no internet at home at age 5 (22% of LMIs vs 8% of higher-incomes), and no access to a car at age 3 (5% of LMIs had no car vs 1% of higher incomes).
As I’ve intimated, it’s hard to believe we can disentangle individual variables in the environment in an observational study, but the researchers believe the number of variables in the mix (158) and the different time points (many variables are assessed at two or more points) provided a good base for analysis.
(2012). Adult outcomes as a function of an early childhood educational program: An Abecedarian Project follow-up.
Developmental Psychology;Developmental Psychology. No Pagination Specified - No Pagination Specified.
(2012). Schooling in adolescence raises IQ scores.
Proceedings of the National Academy of Sciences. 109(2), 425 - 430.
Washbrook, E., & Waldfogel, J. (2011). On your marks : Measuring the school readiness of children in low-to-middle income families. Resolution Foundation, December 2011.
Quarter of British children performing poorly due to family disadvantage
A British study involving over 18,000 very young children (aged 9 months to 5 years) has found that those exposed to two or more “disadvantages” (28% of the children) were significantly more likely to have impaired intellectual development, expressed in a significantly reduced vocabulary and behavioral problems.
These differences were significant at three, and for the most part tended to widen between ages three or five (cognitive development, hyperactivity, peer problems and prosocial behaviors; the gap didn’t change for emotional problems, and narrowed for conduct problems). However, only the narrowing of the conduct problem gap and the widening of the peer problem gap was statistically significant.
Ten disadvantages were identified: living in overcrowded housing; having a teenage mother; having one or more parents with depression, parent with a physical disability; parent with low basic skills; maternal smoking during pregnancy; excessive alcohol intake; financial stress, unemployment; domestic violence..
Around 41% of the children did not face any of these disadvantages, and 30% faced only one of these disadvantages. Of those facing two or more, half of those (14%) only had two, while 7% of the total group experienced three risk factors, and fewer than 2% had five or more.
There was no dominant combination of risks, but parental depression was the most common factor (19%), followed by parental disability (15%). Violence was present in only 4% of families, and both parents unemployed in only 5.5%. While there was some correlation between various risk factors, these correlations were relatively modest for the most part. The highest correlations were between unemployment and disability; violence and depression; unemployment and overcrowding.
There were ethnic differences in rate: at 48%, Bangladeshi children were most likely to be exposed to multiple disadvantages, followed by Pakistani families (34%), other (including mixed) (33%), black African (31%), black Caribbean (29%), white (28%) and Indian (20%).
There were also differences depending on family income. Among those in the lowest income band (below £10,400 pa) — into which 21% of the families fell, the same proportion as is found nationally — nearly half had at least two risk factors, compared to 27% of those in families above this threshold. Moreover, children in families with multiple risk factors plus low income showed the lowest cognitive development (as measured by vocabulary).
Childhood maltreatment reduces size of hippocampus
In this context, it is interesting to note a recent finding that three key areas of the hippocampus were significantly smaller in adults who had experienced maltreatment in childhood. In this study, brain scans were taken of nearly 200 young adults (18-25), of whom 46% reported no childhood adversity and 16% reported three or more forms of maltreatment. Maltreatment was most commonly physical and verbal abuse from parents, but also included corporal punishment, sexual abuse and witnessing domestic violence.
Reduced volume in specific hippocampus regions (dentate gyrus, cornu ammonis, presubiculum and subiculum) was still evident after such confounding factors as a history of depression or PTSD were taken into account. The findings support the theory that early stress affects the development of subregions in the hippocampus.
While mother’s nurturing grows the hippocampus
Supporting this, another study, involving 92 children aged 7 to 10 who had participated in an earlier study of preschool depression, has found that those children who received a lot of nurturing from their parent (generally mother) developed a larger hippocampus than those who didn’t.
‘Nurturing’ was assessed in a videotaped interaction at the time of the preschool study. In this interaction, the parent performed a task while the child waited for her to finish so they could open an attractive gift. How the parent dealt with this common scenario — the degree to which they helped the child through the stress — was evaluated by independent raters.
Brain scans revealed that children who had been nurtured had a significantly larger hippocampus than those whose mothers were not as nurturing, and (this was the surprising bit), this effect was greater among the healthy, non-depressed children. Among this group, those with a nurturing parent had hippocampi which were on average almost 10% larger than those whose parent had not been as nurturing.
Sabates, R., Dex, S., Sabates, R., & Dex, S. (2012). Multiple risk factors in young children’s development. CLS Cohort Studies Working paper 2012/1.
Full text available at http://www.cls.ioe.ac.uk/news.aspx?itemid=1661&itemTitle=More+than+one+i...
(2012). Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum.
Proceedings of the National Academy of Sciences.
Full text available at http://www.pnas.org/content/early/2012/02/07/1115396109.abstract?sid=f73...
(2012). Maternal support in early childhood predicts larger hippocampal volumes at school age.
Proceedings of the National Academy of Sciences.
The study involved 1,292 children followed from birth, whose cortisol levels were assessed at 7, 15, and 24 months. Three tests related to executive functions were given at age 3. Measures of parenting quality (maternal sensitivity, detachment, intrusiveness, positive regard, negative regard, and animation, during interaction with the child) and household environment (household crowding, safety and noise levels) were assessed during the home visits.
Earlier studies have indicated that a poor environment in and of itself is stressful to children, and is associated with increased cortisol levels. Interestingly, in one Mexican study, preschool children in poor homes participating in a conditional cash transfer scheme showed reduced cortisol levels.
This study found that children in lower-income homes received less positive parenting and had higher levels of cortisol in their first two years than children in slightly better-off homes. Higher levels of cortisol were associated with lower levels of executive function abilities, and to a lesser extent IQ, at 3 years.
African American children were more affected than White children on every measure. Cortisol levels were significantly higher; executive function and IQ significantly lower; ratings of positive parenting significantly lower and ratings of negative parenting significantly higher. Maternal education was significantly lower, poverty greater, homes more crowded and less safe.
The model derived from this data shows executive function negatively predicted by cortisol, while the effect on IQ is marginal. However, both executive function and IQ are predicted by negative parenting, positive parenting, and household risk (although this last variable has a greater effect on IQ than executive function). Neither executive function nor IQ was directly predicted by maternal education, ethnicity, or poverty level. Cortisol level was inversely related to positive parenting, but was not directly related to negative parenting or household risk.
Indirectly (according to this best-fit model), poverty was related to executive function through negative parenting; maternal education was related to executive function through negative parenting and to a lesser extent positive parenting; both poverty and maternal education were related to IQ through positive parenting, negative parenting, and household risk; African American ethnicity was related to executive function through negative parenting and positive parenting, and to IQ through negative parenting, positive parenting, and household risk. Cortisol levels were higher in African American children and this was unrelated to poverty level or maternal education.
Executive function (which includes working memory, inhibitory control, and attention shifting) is vital for self-regulation and central to early academic achievement. A link between cortisol level and executive function has previously been shown in preschool children, as well as adults. The association partly reflects the fact that stress hormone levels affect synaptic plasticity in the prefrontal cortex, where executive functions are carried out. This is not to say that this is the only brain region so affected, but it is an especially sensitive one. Chronic levels of stress alter the stress response systems in ways that impair flexible regulation.
What is important about this study is this association between stress level and cognitive ability at an early age, that the effect of parenting on cortisol is associated with positive aspects rather than negative ones, and that the association between poverty and cognitive ability is mediated by both cortisol and parenting behavior — both positive and negative aspects.
A final word should be made on the subject of the higher cortisol levels in African Americans. Because of the lack of high-income African Americans in the sample (a reflection of the participating communities), it wasn’t possible to directly test whether the effect is accounted for by poverty. So this remains a possibility. It is also possible that there is some genetic difference. But it also might reflect other sources of stress, such as that relating to prejudice and stereotype threat.
Based on mother’s ethnic status, 58% of the families were Caucasian and 42% African American. Two-thirds of the participants had an income-to-need ratio (estimated total household income divided by the 2005 federal poverty threshold adjusted for number of household members) less than 200% of poverty. Just over half of the mothers weren’t married, and most of them (89%) had never been married. The home visits at 7, 15, and 24 months lasted at least an hour, and include a videotaped free play or puzzle completion interaction between mother and child. Cortisol samples were taken prior to an emotion challenge task, and 20 minutes and 40 minutes after peak emotional arousal.
Long-term genetic effects of childhood environment
The long-term effects of getting off to a poor start are deeper than you might believe. A DNA study of forty 45-year-old males in a long-running UK study has found clear differences in gene methylation between those who experienced either very high or very low standards of living as children or adults (methylation of a gene at a significant point in the DNA reduces the activity of the gene). More than twice as many methylation differences were associated with the combined effect of the wealth, housing conditions and occupation of parents (that is, early upbringing) than were associated with the current socio-economic circumstances in adulthood (1252 differences as opposed to 545).
The findings may explain why the health disadvantages known to be associated with low socio-economic position can remain for life, despite later improvement in living conditions. The methylation profiles associated with childhood family living conditions were clustered together in large stretches of DNA, which suggests that a well-defined epigenetic pattern is linked to early socio-economic environment. Adult diseases known to be associated with early life disadvantage include coronary heart disease, type 2 diabetes and respiratory disorders.
(2011). Salivary Cortisol Mediates Effects of Poverty and Parenting on Executive Functions in Early Childhood.
Child Development. no - no.
Fernald, L. C., & Gunnar, M. R. (2009). Poverty-alleviation program participation and salivary cortisol in very low-income children. Social Science and Medicine, 68, 2180–2189.
(2011). Associations with early-life socio-economic position in adult DNA methylation.
International Journal of Epidemiology.
A study involving 750 sets of twins assessed at about 10 months and 2 years, found that at 10 months, there was no difference in how the children from different socioeconomic backgrounds performed on tests of early cognitive ability. However, by 2 years, children from high socioeconomic background scored significantly higher than those from low socioeconomic backgrounds. Among the 2-year-olds from poorer families, there was little difference between fraternal and identical twins, suggesting that genes were not the reason for the similarity in cognitive ability. However, among 2-year-olds from wealthier families, identical twins showed greater similarities in their cognitive performance than fraternal twins — genes accounted for about half of the variation in cognitive changes.
The findings are consistent with other recent research suggesting that individual differences in cognitive ability among children raised in socioeconomically advantaged homes are primarily due to genes, whereas environmental factors are more influential for children from disadvantaged homes.
(2011). Emergence of a Gene × Socioeconomic Status Interaction on Infant Mental Ability Between 10 Months and 2 Years.
Psychological Science. 22(1), 125 - 133.
An Australian study of 3796 14-year-olds has found that those who had been reported as having suffered abuse or neglect (7.9%) scored the equivalent of some three IQ points lower than those who had not been maltreated, after accounting for a large range of socioeconomic and other factors. Abuse and neglect were independent factors: those who suffered both (and 74% of those who suffered neglect also suffered abuse) were doubly affected.
(2011). Child Abuse and Neglect and Cognitive Function at 14 Years of Age: Findings From a Birth Cohort.
Pediatrics. 127(1), 4 - 10.
A study involving 125 women has found the first, direct human evidence that fetuses exposed to elevated levels of the stress hormone cortisol may have trouble paying attention or solving problems at 17 months. But more hopefully, the association only occurred among children showing insecure attachment to their mothers, independent of socioeconomic factors. The findings suggest that a stressful prenatal environment may be effectively counteracted by good parental care. The children will be followed up when they turn 6.
(2010). Maternal Prenatal Cortisol and Infant Cognitive Development: Moderation by Infant-Mother Attachment.
Biological Psychiatry. In Press, Corrected Proof,
A study involving 132 8- and 9-year-old children, some of whom had been adopted into U.S. homes after spending at least a year and three-quarters in institutions in Asia, Latin America, Russia and Eastern Europe, and Africa, while others were adopted by the time they were 8 months old into U.S. homes from foster care in Asia and Latin America, having spent no or very little time in institutional care, has found that those adopted early from foster care didn't differ from children who were raised in their birth families in the United States. However, those adopted from institutional care performed worse on tests measuring visual memory and attention, learning visual information, and impulse control -- but not on tests involving sequencing and planning. The findings suggest that specific aspects of cognitive function may be especially vulnerable to postnatal experience.
(2010). Neurodevelopmental Effects of Early Deprivation in Postinstitutionalized Children.
Child Development. 81(1), 224 - 236.
A study using data on reported homicides in Chicago 1994-2002 and two independent surveys of children and families in Chicago, has revealed that African-American children who were assessed directly after a local homicide occurred scored substantially lower on vocabulary and reading assessments than their peers from the same neighborhood who were assessed at different times. The impact of the homicide faded both with time and distance from the child's home. However, in both datasets, while the results were extremely strong for African Americans, there was no effect of local homicides for Hispanics. Because of the prevalence of homicide in the most violent neighborhoods in cities like Chicago, these results mean that some children spend about one week out of every month functioning at a low level. Whites and other ethnic groups were excluded from the study because they were almost never exposed to local homicides in the samples used.
(2010). The acute effect of local homicides on children's cognitive performance.
Proceedings of the National Academy of Sciences. 107(26), 11733 - 11738.
A study involving 136 healthy institutionalized infants (average age 21 months) from six orphanages in Bucharest, Romania, has found that those randomly assigned to a foster care program showed rapid increases in height and weight (but not head circumference), so that by 12 months, all of them were in the normal range for height, 90% were in the normal range for weight, and 94% were in the normal range of weight for height. Caregiving quality (particularly sensitivity and positive regard for the child, including physical affection) positively correlated with catch-up. Children whose height caught up to normal levels also appeared to improve their cognitive abilities. Each incremental increase of one in standardized height scores between baseline and 42 months was associated with an average increase of 12.6 points in verbal IQ.
(2010). Growth and Associations Between Auxology, Caregiving Environment, and Cognition in Socially Deprived Romanian Children Randomized to Foster vs Ongoing Institutional Care.
Arch Pediatr Adolesc Med. 2010.56 - 2010.56.
Older news items (pre-2010) brought over from the old website
Prefrontal cortex activity in poor children like that of stroke victim
An imaging study of 26 normal 9- and 10-year-olds differing only in socioeconomic status has revealed detectable differences in the response of their prefrontal cortex. While not invariant, those from lower socioeconomic levels were more likely to have low frontal lobe response. This is consistent with earlier studies, but is the first to demonstrate the effect when there is no issue of task complexity (the task was very simple; the measure was how fast the child responded to an unexpected novel picture — the response of many from low socioeconomic backgrounds was similar to the response of adults who have had a portion of their frontal lobe destroyed by a stroke). The effect is thought to be due to growing up in cognitively-impoverished and stressful environments, since these have been found to affect the prefrontal cortex in animal studies. Further research is looking into whether these brain differences can be eliminated by training.
Kishiyama, M.M. et al. 2008. Socioeconomic Disparities Affect Prefrontal Function in Children. Journal of Cognitive Neuroscience
Early life stress can lead to memory loss and cognitive decline in middle age
Age-related cognitive decline is probably a result of both genetic and environmental factors. A rat study has demonstrated that some of these environmental factors may occur in early life. Among the rats, emotional stress in infancy showed no ill effects by the time the rats reached adulthood, but as the rats reached middle age, cognitive deficits started to appear in those rats who had had stressful infancies, and progressed much more rapidly with age than among those who had had nurturing infancies. Middle-aged rats who had been exposed to early life emotional stress showed deterioration in brain-cell communication in the hippocampus.
(2005). Mechanisms of Late-Onset Cognitive Decline after Early-Life Stress.
J. Neurosci.. 25(41), 9328 - 9338.
Varied sensory experience important in childhood
A new baby has far more connections between neurons than necessary; from birth to about age 12 the brain trims 50% of these unnecessary connections while at the same time building new ones through learning and sensory stimulation — in other words, tailoring the brain to its environment. A mouse study has found that without enough sensory stimulation, infant mice lose fewer connections — indicating that connections need to be lost in order for appropriate ones to grow. The findings support the idea that parents should try to expose their children to a variety of sensory experiences.
Mother's work schedule may impact her child's cognitive development
A new study suggests that a mother who works nonstandard hours, such as evenings, nights or rotating shifts, may significantly affect her young child's intellectual development. The study used information from the National Institute of Child Health Development's (NICHD) Study of Early Child Care, which tracked 1,364 children from 10 sites around the country from birth in 1991 through 36 months. Her study focused on 900 children whose mothers had worked in the first three years of their child's life. About half the working mothers worked at nonstandard hours during this time. Even after controlling for the quality of the home environment and child care, maternal depression, and the mother's sensitivity towards her children, researchers found that the children of mothers who worked nonstandard work schedules during their first three years of life performed much worse on cognitive tests, particularly if these schedules began in the 1st year, and particularly for measures of cognitive development at 24 months and expressive language at 36 months. It’s suggested that one reason may be the type of care children receive when their mothers work such hours.
Han, W-J. 2005. Maternal Nonstandard Work Schedules and Child Cognitive Outcomes. Child Development, 76 (1), 137-154.
Growing up in a chaotic home may impair child's cognitive development
An association between disorganized, noisy and cramped homes and lower childhood intelligence has been observed before, but the reasons for the association have never been clear. Now a study of some 8000 3- and 4-year-old twins has perhaps disentangled the variables, and has found that chaos had an influence on cognitive skills independent of socioeconomic status. The findings also suggest that when the environment is more stressful, intelligence is more likely to be constrained by genes.
Petrill, S.A., Pike, A., Price, T. & Plomin, R. 2004. Chaos in the home and socioeconomic status are associated with cognitive development in early childhood: Environmental mediators identified in a genetic design. Intelligence, 32 (5), 445-460.