Janet Currie

There are many possible pathways between parental education, income, and health, and between child health and education, but only some of them have been explored in the literature. This essay focuses on links between parental socioeconomic status (as measured by education, income, occupation, or in some cases area of residence) and child health, and between child health and adult education or income. Specifically, I ask two questions: What is the evidence regarding whether parental socioeconomic status affects child health? And, what is the evidence relating child health to future educational and labor market outcomes? I show that there is now strong evidence of both links, suggesting that health could play a role in the intergenerational transmission of economic status.

In the epidemiological literature, the fetal origins hypothesis associated with David J. Barker posits that chronic, degenerative conditions of adult health, including heart disease and type 2 diabetes, may be triggered by circumstances decades earlier, particularly, by in utero nutrition. Economists have expanded on this hypothesis, investigating a broader range of fetal shocks and circumstances and have found a wealth of later-life impacts on outcomes including test scores, educational attainment, and income, along with health. In the process, they have provided some of the most credible observational evidence in support of the hypothesis. The magnitude of the impacts is generally large. Thus, the fetal origins hypothesis has not only survived contact with economics, but has flourished.

Journal Article Mother's Education and the Intergenerational Transmission of Human Capital: Evidence from College Openings Get access Janet Currie, Janet Currie Department of Economics, University of California, Los Angeles, and the National Bureau of Economic Research Search for other works by this author on: Oxford Academic Google Scholar Enrico Moretti Enrico Moretti Department of Economics, University of California, Los Angeles, and the National Bureau of Economic Research Search for other works by this author on: Oxford Academic Google Scholar The Quarterly Journal of Economics, Volume 118, Issue 4, November 2003, Pages 1495–1532, https://doi.org/10.1162/003355303322552856 Published: 01 November 2003

This paper discusses early childhood education programs: their goals; effectiveness; optimal timing, targeting, and content; and costs and benefits. Early intervention has significant short- and medium-term benefits: most notably it reduces grade repetition and special education costs, and provides quality child care. The effects are greatest for more disadvantaged children. Some model programs have produced exciting improvements in educational attainment and earnings and have reduced welfare dependency and crime. The jury is still out on the long-term effects of Head Start, but Head Start would pay for itself if it produced a quarter of the long-term gains of model programs.

Specially collected data on adults in the Panel Study of Income Dynamics are used to provide evidence on the longer-term effects of Head Start, an early intervention program for poor preschool-age children. Whites who attended Head Start are, relative to their siblings who did not, significantly more likely to complete high school, attend college, and possibly have higher earnings in their early twenties. African-Americans who participated in Head Start are less likely to have been booked or charged with a crime. There is some evidence of positive spillovers from older Head Start children to their younger siblings.

Journal Article Health Insurance Eligibility, Utilization of Medical Care, and Child Health Get access Janet Currie, Janet Currie University of California at Los Angeles and National Bureau of Economic Research Search for other works by this author on: Oxford Academic Google Scholar Jonathan Gruber Jonathan Gruber Massachusetts Institute of Technology and National Bureau of Economic Research Search for other works by this author on: Oxford Academic Google Scholar The Quarterly Journal of Economics, Volume 111, Issue 2, May 1996, Pages 431–466, https://doi.org/10.2307/2946684 Published: 01 May 1996

This chapter seeks to set out what economists have learned about the effects of early childhood influences on later life outcomes, and about ameliorating the effects of negative influences. We begin with a brief overview of the theory which illustrates that evidence of a causal relationship between a shock in early childhood and a future outcome says little about whether the relationship in question is biological or immutable. We then survey recent work which shows that events before five years old can have large long term impacts on adult outcomes. Child and family characteristics measured at school entry do as much to explain future outcomes as factors that labor economists have more traditionally focused on, such as years of education. Yet while children can be permanently damaged at this age, an important message is that the damage can often be remediated. We provide a brief overview of evidence regarding the effectiveness of different types of policies to provide remediation. We conclude with a list of some of the many outstanding questions for future research.

A key question for health care reform in the United States is whether expanded health insurance eligibility will lead to improvements in health outcomes. We address this question in the context of the dramatic changes in Medicaid eligibility for pregnant women that took place between 1979 and 1992. We build a detailed simulation model of each state's Medicaid policy during this era and use this model to estimate (1) the effect of changes in the rules on the fraction of women eligible for Medicaid coverage in the event of pregnancy and (2) the effect of Medicaid eligibility changes on birth outcomes in aggregate Vital Statistics data. We have three main findings. First, the changes did dramatically increase the Medicaid eligibility of pregnant women, but did so at quite differential rates across the states. Second, the changes lowered the incidence of infant mortality and low birth weight; we estimate that the 30-percentage-point increase in eligibility among 15-44-year-old women was associated with a decrease in infant mortality of 8.5 percent. Third, earlier, targeted changes in Medicaid eligibility, which were restricted to specific low-income groups, had much larger effects on birth out-comes than broader expansions of eligibility to women with higher income levels. We suggest that the source of this difference is the much lower take-up of Medicaid coverage by individuals who became eligible under the broader eligibility changes. Even the targeted changes cost the Medicaid program $840,000 per infant life saved, however, raising important issues of cost effectiveness.

Socioeconomic Status and Child Health: Why Is the Relationship Stronger for Older Children? by Janet Currie and Mark Stabile. Published in volume 93, issue 5, pages 1813-1823 of American Economic Review, December 2003

Child abuse and neglect represent major threats to child health and well-being; however, little is known about consequences for adult economic outcomes. Using a prospective cohort design, court substantiated cases of childhood physical and sexual abuse and neglect during 1967-1971 were matched with nonabused and nonneglected children and followed into adulthood (mean age 41). Outcome measures of economic status and productivity were assessed in 2003-2004 (N 1/4 807). Results indicate that adults with documented histories of childhood abuse and/or neglect have lower levels of education, employment, earnings, and fewer assets as adults, compared to matched control children. There is a 14% gap between individuals with histories of abuse/neglect and controls in the probability of employment in middle age, controlling for background characteristics. Maltreatment appears to affect men and women differently, with larger effects for women than men. These new findings demonstrate that abused and neglected children experience large and enduring economic consequences.

Using data from the National Health and Nutrition Examination Survey, we examine the relationship between nutritional status, poverty, and food insecurity for household members of various ages. Our most striking result is that, while poverty is predictive of poor nutrition among preschool children, food insecurity does not provide any additional predictive power for this age group. Among school age children, neither poverty nor food insecurity is associated with nutritional outcomes, while among adults and the elderly, both food insecurity and poverty are predictive. These results suggest that researchers should be cautious about assuming connections between food insecurity and nutritional outcomes, particularly among children.

That prenatal events can have life-long consequences is now well established. Nevertheless, research on the fetal origins hypothesis is flourishing and has expanded to include the early childhood (postnatal) environment. Why does this literature have a “second act?” We summarize the major themes and contributions driving the empirical literature since our 2011 reviews, and try to interpret the literature in light of an overarching conceptual framework about how human capital is produced early in life. One major finding is that relatively mild shocks in early life can have substantial negative impacts, but that the effects are often heterogeneous reflecting differences in child endowments, budget constraints, and production technologies. Moreover, shocks, investments, and interventions can interact in complex ways that are only beginning to be understood. Many advances in our knowledge are due to increasing accessibility of comprehensive administrative data that allow events in early life to be linked to long-term outcomes. Yet, we still know relatively little about the interval between, and thus about whether it would be feasible to identify and intervene with affected individuals at some point between early life and adulthood. We do know enough, however, to be able to identify some interventions that hold promise for improving child outcomes in early life and throughout the life course. (JEL I12, J13, J16, Q51, Q53)

One in five U.S. youngsters has a mental disorder, but we know little about the effects of these disorders on child outcomes. We examine U.S. and Canadian children with symptoms of Attention Deficit Hyperactivity Disorder (ADHD), the most common child mental health problem. Our innovations include the use of nationally representative samples of children, the use of questions administered to all children rather than focusing only on diagnosed cases, and the use of sibling fixed effects to control for omitted variables. We find large negative effects on test scores and schooling attainment suggesting that mental health conditions are a more important determinant of average outcomes than physical health conditions.

We examine the impact of three "criteria" air pollutants on infant health in New Jersey in the 1990s by combining information about mother's residential location from birth certificates with information from air quality monitors. Our work offers three important innovations. First, we use the exact addresses of mothers to select those closest to air monitors to improve the accuracy of air quality exposure. Second, we include maternal fixed effects to control for unobserved characteristics of mothers. Third, we examine interactions of air pollution with smoking and other risk factors for poor infant health outcomes. We find consistently negative effects of exposure to carbon monoxide (CO), both during and after birth, with effects considerably larger for smokers and older mothers. Since automobiles are the main source of carbon monoxide emissions, our results have important implications for regulation of automobile emissions.

Is the Impact of Health Shocks Cushioned by Socioeconomic Status? The Case of Low Birthweight by Janet Currie and Rosemary Hyson. Published in volume 89, issue 2, pages 245-250 of American Economic Review, May 1999

This chapter provides an overview of the literature linking health, health insurance and labor market outcomes such as wages, earnings, employment, hours, occupational choice, job turnover, retirement, and the structure of employment. The first part of the paper focuses on the relationship between health and labor market outcomes. The empirical literature surveyed suggests that poor health reduces the capacity to work and has substantive effects on wages, labor force participation and job choice. The exact magnitudes, however, are sensitive to both the choice of health measures and to identification assumptions. The second part of the paper considers the link between health insurance and labor market outcomes. The empirical literature here suggests that access to health insurance has important effects on both labor force participation and job choice; the link between health insurance and wages is less clear.

Health at birth is an important predictor of long-term outcomes, including education, income, and disability. Recent evidence suggests that maternal disadvantage leads to worse health at birth through poor health behaviors; exposure to harmful environmental factors; worse access to medical care, including family planning; and worse underlying maternal health. With increasing inequality, those at the bottom of the distribution now face relatively worse economic conditions, but newborn health among the most disadvantaged has actually improved. The most likely explanation is increasing knowledge about determinants of infant health and how to protect it along with public policies that put this knowledge into practice.

The impact of participation in Head Start is investigated using a national sample of children. Comparisons are drawn between siblings to control for selection. Head Start is associated with large and significant gains in test scores among both whites and African-Americans. However, among African-Americans, these gains are quickly lost. Head Start significantly reduces the probability that a white child will repeat a grade but it has no effect on grade repetition among African-American children. Both whites and African-Americans who attend Head Start, or other preschools, gain greater access to preventive health services. Copyright 1995 by American Economic Association.

We use a unique data set of California births to ask whether intergenerational correlations in health contribute to the perpetuation of economic status. We find that if a mother was low birth weight, her child is significantly more likely to be low birth weight, even when we compare mothers who are sisters. Second, the intergenerational transmission of low birth weight is stronger for mothers in high poverty zip codes. Third, low birth weight affects proxies for later socioeconomic status. Fourth, these effects are stronger for women born in high poverty zip codes.

We exploit the introduction of electronic toll collection, (E-ZPass), which greatly reduced both traffic congestion and vehicle emissions near highway toll plazas. We show that the introduction of E-ZPass reduced prematurity and low birth weight among mothers within 2 kilometers (km) of a toll plaza by 10.8 percent and 11.8 percent, respectively, relative to mothers 2–10 km from a toll plaza. There were no immediate changes in the characteristics of mothers or in housing prices near toll plazas that could explain these changes. The results are robust to many changes in specification and suggest that traffic congestion contributes significantly to poor health among infants. (JEL I12, J13, Q51, Q53, R41)

A growing literature documents the links between long-term outcomes and health in the fetal period, infancy, and early childhood. Much of this literature focuses on rich countries, but researchers are increasingly taking advantage of new sources of data and identification to study the long reach of childhood health in developing countries. Health in early life may be a more significant determinant of adult outcomes in these countries because health insults are more frequent, the capacity to remediate is more limited, and multiple shocks may interact. However, the underlying relationships may also be more difficult to measure, given significant mortality selection. We survey recent evidence on the adult correlates of early-life health and the long-term effects of shocks resulting from disease, famine, malnutrition, pollution, and war.

Recent research shows that health at birth is affected by many factors, including maternal education, behaviors, and participation in social programs. In turn, endowments at birth are predictive of adult outcomes, and of the outcomes of future generations. Exposure to environmental pollution is one potential determinant of health at birth that has received increasing attention. A large literature outside of economics advocates for Environmental Justice, and argues that poor and minority families are disproportionately exposed to environmental hazards. I provide new evidence on this question, showing that children born to less educated and minority mothers are more likely to be exposed to pollution in utero and that white, college educated mothers are particularly responsive to changes in environmental amenities. I estimate that differences in exposure to toxic releases may explain 6% of the gap in incidence of low birth weight between infants of white college educated mothers and infants of black high school dropout mothers.

We review theoretical explanations for in-kind transfers in light of the limited empirical evidence. After reviewing the traditional paternalistic arguments, we consider explanations based on imperfect information and self-targeting. We then discuss the large literature on in-kind programs as a way of improving the efficiency of the tax system and a range of other possible explanations, including the “Samaritan's Dilemma,” pecuniary effects, credit constraints, asymmetric information amongst agents, and political economy considerations. Our reading of the evidence suggests that paternalism and interdependent preferences are leading overall explanations for the existence of in-kind transfer programs but that some of the other arguments may apply to specific cases. Political economy considerations must also be part of the story.

Regulatory oversight of toxic emissions from industrial plants and understanding about these emissions' impacts are in their infancy. Applying a research design based on the openings and closings of 1,600 industrial plants to rich data on housing markets and infant health, we find that: toxic air emissions affect air quality only within 1 mile of the plant; plant openings lead to 11 percent declines in housing values within 0.5 mile or a loss of about $4.25 million for these households; and a plant's operation is associated with a roughly 3 percent increase in the probability of low birthweight within 1 mile. (JEL I12, L60, Q52, Q53, Q58, R23, R31)

We examine the effect of air pollution on school absences using administrative data for elementary and middle school children in 39 of the largest school districts in Texas merged with air quality information maintained by the Environmental Protection Agency. We address potentially confounding factors with a difference-in-difference-in-differences strategy that controls for persistent characteristics of schools, years, and attendance periods. Of the pollutants considered, we find that high carbon monoxide (CO) levels, even when below federal air quality standards, significantly increase absences. Our results suggest that the substantial decline in CO levels over the past two decades has yielded economically significant health benefits.

A growing literature suggests that stressful events in pregnancy can have negative effects on birth outcomes. Some of the estimates in this literature may be affected by small samples, omitted variables, endogenous mobility in response to disasters, and errors in the measurement of gestation, as well as by a mechanical correlation between longer gestation and the probability of having been exposed. We use millions of individual birth records to examine the effects of exposure to hurricanes during pregnancy, and the sensitivity of the estimates to these econometric problems. We find that exposure to a hurricane during pregnancy increases the probability of abnormal conditions of the newborn such as being on a ventilator more than 30 min and meconium aspiration syndrome (MAS). Although we are able to reproduce previous estimates of effects on birth weight and gestation, our results suggest that measured effects of stressful events on these outcomes are sensitive to specification and it is preferable to use more sensitive indicators of newborn health.

Background Excessive weight gain during pregnancy seems to increase birthweight and the offspring's risk of obesity later in life. However, this association might be confounded by genetic and other shared effects. We aimed to examine the association between maternal weight gain and birthweight using state-based birth registry data that allowed us to compare several pregnancies in the same mother. Methods In this population-based cohort study, we used vital statistics natality records to examine all known births in Michigan and New Jersey, USA, between Jan 1, 1989, and Dec 31, 2003. From an initial sample of women with more than one singleton birth in the database, we made the following exclusions: gestation less than 37 weeks or 41 weeks or more; maternal diabetes; birthweight less than 500 g or more than 7000 g; and missing data for pregnancy weight gain. We examined how differences in weight gain that occurred during two or more pregnancies for each woman predicted the birthweight of her offspring, using a within-subject design to reduce confounding to a minimum. Findings Our analysis included 513 501 women and their 1 164 750 offspring. We noted a consistent association between pregnancy weight gain and birthweight (β 7·35, 95% CI 7·10–7·59, p<0·0001). Infants of women who gained more than 24 kg during pregnancy were 148·9 g (141·7–156·0) heavier at birth than were infants of women who gained 8–10 kg. The odds ratio of giving birth to an infant weighing more than 4000 g was 2·26 (2·09–2·44) for women who gained more than 24 kg during pregnancy compared with women who gained 8–10 kg. Interpretation Maternal weight gain during pregnancy increases birthweight independently of genetic factors. In view of the apparent association between birthweight and adult weight, obesity prevention efforts targeted at women during pregnancy might be beneficial for offspring. Funding US National Institutes of Health.

We investigate how changes in the supply of fast food restaurants affect weight outcomes of 3 million children and 3 million pregnant women. Among ninth graders, a fast food restaurant within 0.1 miles of a school results in a 5.2 percent increase in obesity rates. Among pregnant women, a fast-food restaurant within 0.5 miles of residence results in a 1.6 percent increase in the probability of gaining over 20 kilos. The implied effects on caloric intake are one order of magnitude larger for children than for mothers, consistent with smaller travel cost for adults. Non-fast food restaurants and future fast-food restaurants are uncorrelated with weight outcomes. (JEL I12, J13, J16, L83)

Journal Article The Concept of Economic Surplus and Its Use in Economic Analysis Get access John Martin Currie, John Martin Currie University of Manchester Search for other works by this author on: Oxford Academic Google Scholar John A. Murphy, John A. Murphy University College, Dublin Search for other works by this author on: Oxford Academic Google Scholar Andrew Schmitz Andrew Schmitz University of California, Berkeley Search for other works by this author on: Oxford Academic Google Scholar The Economic Journal, Volume 81, Issue 324, 1 December 1971, Pages 741–799, https://doi.org/10.2307/2230317 Published: 01 December 1971

The COVID-19 pandemic caused a large decrease in US life expectancy in 2020, but whether a similar decrease occurred in 2021 and whether the relationship between income and life expectancy intensified during the pandemic are unclear.To measure changes in life expectancy in 2020 and 2021 and the relationship between income and life expectancy by race and ethnicity.Retrospective ecological analysis of deaths in California in 2015 to 2021 to calculate state- and census tract-level life expectancy. Tracts were grouped by median household income (MHI), obtained from the American Community Survey, and the slope of the life expectancy-income gradient was compared by year and by racial and ethnic composition.California in 2015 to 2019 (before the COVID-19 pandemic) and 2020 to 2021 (during the COVID-19 pandemic).Life expectancy at birth.California experienced 1 988 606 deaths during 2015 to 2021, including 654 887 in 2020 to 2021. State life expectancy declined from 81.40 years in 2019 to 79.20 years in 2020 and 78.37 years in 2021. MHI data were available for 7962 of 8057 census tracts (98.8%; n = 1 899 065 deaths). Mean MHI ranged from $21 279 to $232 261 between the lowest and highest percentiles. The slope of the relationship between life expectancy and MHI increased significantly, from 0.075 (95% CI, 0.07-0.08) years per percentile in 2019 to 0.103 (95% CI, 0.098-0.108; P < .001) years per percentile in 2020 and 0.107 (95% CI, 0.102-0.112; P < .001) years per percentile in 2021. The gap in life expectancy between the richest and poorest percentiles increased from 11.52 years in 2019 to 14.67 years in 2020 and 15.51 years in 2021. Among Hispanic and non-Hispanic Asian, Black, and White populations, life expectancy declined 5.74 years among the Hispanic population, 3.04 years among the non-Hispanic Asian population, 3.84 years among the non-Hispanic Black population, and 1.90 years among the non-Hispanic White population between 2019 and 2021. The income-life expectancy gradient in these groups increased significantly between 2019 and 2020 (0.038 [95% CI, 0.030-0.045; P < .001] years per percentile among Hispanic individuals; 0.024 [95% CI: 0.005-0.044; P = .02] years per percentile among Asian individuals; 0.015 [95% CI, 0.010-0.020; P < .001] years per percentile among Black individuals; and 0.011 [95% CI, 0.007-0.015; P < .001] years per percentile among White individuals) and between 2019 and 2021 (0.033 [95% CI, 0.026-0.040; P < .001] years per percentile among Hispanic individuals; 0.024 [95% CI, 0.010-0.038; P = .002] years among Asian individuals; 0.024 [95% CI, 0.011-0.037; P = .003] years per percentile among Black individuals; and 0.013 [95% CI, 0.008-0.018; P < .001] years per percentile among White individuals). The increase in the gradient was significantly greater among Hispanic vs White populations in 2020 and 2021 (P < .001 in both years) and among Black vs White populations in 2021 (P = .04).This retrospective analysis of census tract-level income and mortality data in California from 2015 to 2021 demonstrated a decrease in life expectancy in both 2020 and 2021 and an increase in the life expectancy gap by income level relative to the prepandemic period that disproportionately affected some racial and ethnic minority populations. Inferences at the individual level are limited by the ecological nature of the study, and the generalizability of the findings outside of California are unknown.

This project links administrative census microdata to spatially continuous measures of particulate pollution (PM2.5) to first document and then decompose the key drivers of convergence in black-white pollution exposure differences. We use quantile regression to show that a significant portion of the convergence in Black-White exposure is attributable to differential impacts of the Clean Air Act (CAA) in Black and White communities. Areas with larger Black populations saw greater CAA-related declines in PM2.5. We show that the CAA can account for over 60 percent of the racial convergence in PM2.5 pollution exposure in the United States since 2000. (JEL J15, K32, Q51, Q53, Q58)

One goal of federal housing policy is to improve the prospects of children in poor families. This paper examines the effect of public housing participation on housing quality and educational attainment. Using the SIPP, we show that living in projects is associated with more negative outcomes for children, although this appears to be due to unobserved heterogeneity. We control for the endogeneity of project participation using TSIV techniques which combine information on project participation from the CPS with information on outcomes from the Census. We find that project households are less likely to suffer from overcrowding or live in high-density complexes. Project children are less likely to have been held back. Thus, our results run counter to the stereotype that housing projects harm children.

Support for WIC, the Special Supplemental Nutrition Program for Women, Infants, and Children, is based on the belief that "WIC works." This consensus has lately been questioned by researchers who point out that most WIC research fails to properly control for selection into the program. This paper evaluates the selection problem using rich data from the national Pregnancy Risk Assessment Monitoring System. We show that relative to Medicaid mothers, all of whom are eligible for WIC, WIC participants are negatively selected on a wide array of observable dimensions, and yet WIC participation is associated with improved birth outcomes, even after controlling for observables and for a full set of state-year interactions intended to capture unobservables that vary at the state-year level. The positive impacts of WIC are larger among subsets of even more disadvantaged women, such as those who received public assistance last year, single high school dropouts, and teen mothers.

We examine the impact of recent trade reforms. Although employment in the average private sector manufacturing firm was unaffected, there were significant employment losses to exporters and highly affected firms. Parastatals increased employment by hiring low‐paid temporary workers. Many firms did not adjust wages or employment. We examine two possible explanations. First, barriers to labor market mobility could have impeded adjustment. Second, we develop a model of labor demand which allows for imperfect competition and endogenous technological change. Our results suggest that although labor markets were flexible, many firms cut profit margins and raised productivity rather than reducing employment.

The authors sought to determine the effects of cold-weather periods on budgets and nutritional outcomes among poor American families.The Consumer Expenditure Survey was used to track expenditures on food and home fuels, and the Third National Health and Nutrition Examination Survey was used to track calorie consumption, dietary quality, vitamin deficiencies, and anemia.Both poor and richer families increased fuel expenditures in response to unusually cold weather. Poor families reduced food expenditures by roughly the same amount as their increase in fuel expenditures, whereas richer families increased food expenditures.Poor parents and their children spend less on and eat less food during cold-weather budgetary shocks. Existing social programs fail to buffer against these shocks.

Journal Article First Do No Harm? Tort Reform and Birth Outcomes Get access Janet Currie, Janet Currie Columbia University and NBER Search for other works by this author on: Oxford Academic Google Scholar W. Bentley MacLeod W. Bentley MacLeod Columbia University Search for other works by this author on: Oxford Academic Google Scholar The Quarterly Journal of Economics, Volume 123, Issue 2, May 2008, Pages 795–830, https://doi.org/10.1162/qjec.2008.123.2.795 Published: 01 May 2008

The author documents pervasive racial disparities in the health of American children and analyzes how and how much those disparities contribute to racial gaps in school readiness. She explores a broad sample of health problems common to U.S. children, such as attention deficit hyperactivity disorder, asthma, and lead poisoning, as well as maternal health problems and health-related behaviors that affect children's behavioral and cognitive readiness for school.

Poor educational attainment is a persistent problem among US hispanic children, relative to non-hispanics. Many of these children are immigrants and/or come from households that use a minority language in the home. This paper examines the effects of participation in a government sponsored preschool program called Head Start on these children. We find that large and significant benefits accrue to Head Start children when we compare them to siblings who did not participate in the program. On average, Head Start closes at least 1/4 of the gap in test scores between hispanic children and non-hispanic white children, and 2/3 of the gap in the probability of grade repetition. However, we find that the benefits of Head Start are not evenly distributed across sub-groups.

The majority of children in the US and many other high-income nations are now cared for many hours per week by people who are neither their parents nor their school teachers. The role of such pre-school and out-of-school care is potentially two-fold: First, child care makes it feasible for both parents or the only parent in a single-parent family to be employed. Second, early intervention programs and after school programs aim to enhance child development, particularly among disadvantaged children. Corresponding to this distinction, there are two branches of literature to be summarized in this chapter. The first focuses on the market for child care and analyzes factors affecting the supply, demand and quality of care. The second focuses on child outcomes, and asks whether certain types of programs can ameliorate the effects of early disadvantage. The primary goal of this review is to bring the two literatures together in order to suggest ways that both may be enhanced. Accordingly, we provide an overview of the number of children being cared for in different sorts of arrangements; describe theory and evidence about the nature of the private child care market; and discuss theory and evidence about government intervention in the market for child care. Our summary suggests that additional research is needed in order to better characterize interactions between government programs and market-provided child care.

This paper investigates the effects of expanding public health insurance eligibility for older children. Using data from the National Health Interview Surveys from 1986 to 2005, we first show that although income continues to be an important predictor of children's health status, the importance of income for predicting health has fallen for children 9–17 in recent years. We then investigate the extent to which the dramatic expansions in public health insurance coverage for these children in the past decade are responsible for the decline in the importance of income. We find that while eligibility for public health insurance unambiguously improves current utilization of preventive care, it has little effect on current health status. However, we find some evidence that Medicaid eligibility in early childhood has positive effects on future health. This may indicate that adequate medical care early on puts children on a better health trajectory, resulting in better health as they grow.

This study focuses on "network effects" in the utilization of publicly-funded prenatal care using Vital Statistics data from California for 1989–2000. Networks are defined using 5-digit zip codes and a woman's racial or ethnic group. Like others, we find evidence that the use of public programs is highly correlated within groups defined using race/ethnicity and neighborhoods. These correlations persist even when we control for many unobserved characteristics by including zip code-year fixed effects, and when we focus on the interaction between own group behavior and measures of the potential for contacts with other members of the group ("contact availability"). However, the richness of our data allows us to go further and to conduct several tests of one important hypothesis about networks: that the estimated effects represent information sharing within groups. The results cast doubt on the idea that the observed correlations can be interpreted as evidence of information sharing. In particular, we find estimated effects to be as large or larger among women who have previously used the program as among first-time users.

Using panel data on individuals from the National Longitudinal Survey of Youth, we find that employed individuals who were affected by the increases in the federal minimum wage in 1979 and 1980 were about 3 percent less likely to be employed a year later, even after accounting for the fact that workers employed at the minimum wage may differ from their peers in unobserved ways.

We conduct an audit study in which a pair of simulated patients with identical flu-like complaints visits the same physician. Simulated patient A is instructed to ask a question that showcases his/her knowledge of appropriate antibiotic use, whereas patient B is instructed to say nothing beyond describing his/her symptoms. We find that a patient who displays knowledge of appropriate antibiotics use reduces both antibiotic prescription rates and drug expenditures. Such knowledge also increases physicians’ information provision about possible side effects, but has a negative impact on the quality of the physician–patient interactions. Our results suggest that antibiotics abuse in China is not driven by patients actively demanding antibiotics, but is largely a supply-side phenomenon.

Jayanta Bhattacharya, Janet Currie and Steven J. Haider

The authors examine WIC eligibility and participation using the Current Population Survey (CPS), the Survey of Income and Program Participation (SIPP), and state-level administrative data.

We examine the impact of air pollution on infant death in California over the 1990s. Our work offers several innovations: first, most previous studies examine populations subject to far greater levels of pollution. Second, many studies examine a single pollutant in isolation. We examine three “criteria” pollutants in a common framework. Third, we use rich individual-level data and pollution measured at the weekly level. Our most novel finding is a significant effect of CO on infant mortality: we find that reductions in carbon monoxide over the 1990s saved approximately 1000 infant lives in California.

Evidence shows that pollution exposure early in life is detrimental to near-term health, and an increasing body of evidence suggests that early-childhood health influences health and human capital outcomes later in life. This article reviews the economic research that brings these two literatures together. We begin with a conceptual model that highlights the core relationships across the life cycle. We then review the literature concerned with such estimates, focusing particularly on identification strategies to mitigate concerns regarding endogenous exposure. The nascent empirical literature provides both direct and indirect evidence that early-childhood exposure to pollution significantly impacts later-life outcomes. We discuss the potential policy implications of these long-lasting effects and conclude with a number of promising avenues for future research.

A large literature describes relationships between month of birth, birth weight, and gestation. These relationships are hypothesized to reflect the causal impact of seasonal environmental factors. However, recent work casts doubt on this interpretation by showing that mothers with lower socioeconomic status are more likely to give birth in months that are associated with poorer birth outcomes. Seasonality in the numbers of conceptions in different months can also induce a mechanical correlation between preterm birth and month of birth. This paper analyzes the seasonality of health at birth using a large sample of 647,050 groups of US siblings representing 1,435,213 children. By following the same mother over time, we eliminate differences in fixed maternal characteristics as an explanation for seasonal differences in health at birth. We find a sharp trough in gestation length among babies conceived in May, which corresponds to an increase in prematurity of more than 10%. Birth weight conditional on gestation length, however, is found to be strongly hump-shaped over the year, with 8-9 additional g for summer conceptions. We examine several potential mechanisms for explaining seasonality in birth outcomes that have generally been dismissed in the literature on seasonality in rich countries, notably disease prevalence and nutrition. The May trough in gestation length coincides with a higher influenza prevalence in January and February, when these babies are nearing full term, whereas the hump shape in birth weight is associated with a similar pattern in pregnancy weight gain.

Can Mentoring Help Female Assistant Professors? Interim Results from a Randomized Trial by Francine D. Blau, Janet M. Currie, Rachel T. A. Croson and Donna K. Ginther. Published in volume 100, issue 2, pages 348-52 of American Economic Review, May 2010

Low-income children are in worse health than other children are. This paper explores the extent to which insults to health and activity limitations are responsible. In the most recent National Health Interview Survey (NHIS) data, low-income children are more likely than other children to have virtually every measured chronic or acute condition and are more likely to be limited by these conditions. Mental health conditions are particularly common and limiting. But the higher incidence of measured conditions and limits does not explain all of the relationships between income and overall health status, which suggests that unmeasured illnesses and injuries are also involved.

China has high rates of antibiotic abuse and antibiotic resistance but the causes are still a matter for debate. Strong physician financial incentives to prescribe are likely to be an important cause. However, patient demand (or physician beliefs about patient demand) is often cited and may also play a role. We use an audit study to examine the effect of removing financial incentives, and to try to separate out the effects of patient demand. We implement a number of different experimental treatments designed to try to rule out other possible explanations for our findings. Together, our results suggest that financial incentives are the main driver of antibiotic abuse in China, at least in the young and healthy population we draw on in our study.

Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the life cycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population well-being, but also for economic growth and competitiveness in a global economy. In this paper, we first discuss the research on the strength of the link between early-life health and adult outcomes, and then provide an evidence-based review of the effectiveness of existing U.S. policies targeting the early-life environment. We conclude that there is a robust and economically meaningful relationship between early-life conditions and well-being throughout the life cycle, as measured by adult health, educational attainment, labor market attachment, and other indicators of socioeconomic status. However, there is some variation in the degree to which current policies in the United States are effective in improving early-life conditions. Among existing programs, some of the most effective are the Special Supplemental Program for Women, Infants, and Children (WIC), home visiting with nurse practitioners, and high-quality, center-based early-childhood care and education. In contrast, the evidence on other policies such as prenatal care and family leave is more mixed and limited.

This chapter seeks to set out what Economists have learned about the effects of early childhood influences on later life outcomes, and about ameliorating the effects of negative influences.We begin with a brief overview of the theory which illustrates that evidence of a causal relationship between a shock in early childhood and a future outcome says little about whether the relationship in question biological or immutable.We then survey recent work which shows that events before five years old can have large long term impacts on adult outcomes.Child and family characteristics measured at school entry do as much to explain future outcomes as factors that labor economists have more traditionally focused on, such as years of education.Yet while children can be permanently damaged at this age, an important message is that the damage can often be remediated.We provide a brief overview of evidence regarding the effectiveness of different types of policies to provide remediation.We conclude with a list of some of (the many) outstanding questions for future research.

The development of hydraulic fracturing ("fracking") is considered the biggest change to the global energy production system in the last half-century. However, several communities have banned fracking because of unresolved concerns about the impact of this process on human health. To evaluate the potential health impacts of fracking, we analyzed records of more than 1.1 million births in Pennsylvania from 2004 to 2013, comparing infants born to mothers living at different distances from active fracking sites and those born both before and after fracking was initiated at each site. We adjusted for fixed maternal determinants of infant health by comparing siblings who were and were not exposed to fracking sites in utero. We found evidence for negative health effects of in utero exposure to fracking sites within 3 km of a mother's residence, with the largest health impacts seen for in utero exposure within 1 km of fracking sites. Negative health impacts include a greater incidence of low-birth weight babies as well as significant declines in average birth weight and in several other measures of infant health. There is little evidence for health effects at distances beyond 3 km, suggesting that health impacts of fracking are highly local. Informal estimates suggest that about 29,000 of the nearly 4 million annual U.S. births occur within 1 km of an active fracking site and that these births therefore may be at higher risk of poor birth outcomes.

Scholars have been examining the relationship between fertility and unemployment for more than a century. Most studies find that fertility falls with unemployment in the short run, but it is not known whether these negative effects persist, because women simply may postpone childbearing to better economic times. Using more than 140 million US birth records for the period 1975-2010, we analyze both the short- and long-run effects of unemployment on fertility. We follow fixed cohorts of US-born women defined by their own state and year of birth, and relate their fertility to the unemployment rate experienced by each cohort at different ages. We focus on conceptions that result in a live birth. We find that women in their early 20s are most affected by high unemployment rates in the short run and that the negative effects on fertility grow over time. A one percentage point increase in the average unemployment rate experienced between the ages of 20 and 24 reduces the short-run fertility of women in this age range by six conceptions per 1,000 women. When we follow these women to age 40, we find that a one percentage point increase in the unemployment rate experienced at ages 20-24 leads to an overall loss of 14.2 conceptions. This long-run effect is driven largely by women who remain childless and thus do not have either first births or higher-order births.

Research has shown a strong connection between birth weight and future outcomes. We ask how health problems after birth affect outcomes using data from public health insurance records for 50,000 children born between 1979 and 1987 in the Canadian province of Manitoba. We compare children to siblings born an average of three years apart. We find that health problems in early childhood are significant predictors of young adult outcomes. Early physical health problems are linked to outcomes primarily because they predict later health. Early mental health problems have additional predictive power even conditional on future health and health at birth.

Child maltreatment is a major social problem. This paper focuses on measuring the relationship between child maltreatment and crime using data from the National Longitudinal Study of Adolescent Health (Add Health). We focus on crime because it is one of the most costly potential outcomes of maltreatment. Our work addresses two main limitations of the existing literature on child maltreatment. First, we use a large national sample, and investigate different types of maltreatment in a unified framework. Second, we pay careful attention to controlling for possible confounders using a variety of statistical methods that make differing assumptions. The results suggest that maltreatment greatly increases the probability of engaging in crime and that the probability increases with the experience of multiple forms of maltreatment.

Economic downturns lead to lost income and increased poverty. Although high unemployment almost certainly also increases material hardship and government transfers likely decrease hardship, the first relationship is not yet documented and the second is poorly understood. This study uses data from the Fragile Families and Child Wellbeing Study to examine the associations of unemployment, government transfers, and material hardship. The Fragile Families study collected the latest wave of data during the Great Recession, the worst recession since the Great Depression. The data provide a unique opportunity to examine how high unemployment affects the well-being of low-income families. This study finds that the unemployment rate is associated with increased overall material hardship, difficulty paying bills, having utilities disconnected, and increased usage of welfare, food stamps, unemployment insurance, and Medicaid. If not for food stamps, food hardship during the Great Recession might have increased by twice the amount actually observed.

Abstract This paper provides estimates of the effects of in utero exposure to contaminated drinking water on fetal health. To do this, we examine the universe of birth records and drinking water testing results for the state of New Jersey from 1997 to 2007. Our data enable us to compare outcomes across siblings who were potentially exposed to differing levels of harmful contaminants from drinking water while in utero. We find small effects of drinking water contamination on all children, but large and statistically significant effects on birth weight and gestation of infants born to less educated mothers. We also show that those mothers who were most affected by contamination were the least likely to move between births in response to contamination.

Using national data on opioid prescriptions written by physicians from 2006 to 2014, we uncover a striking relationship between opioid prescribing and medical school rank. Even within the same specialty and practice location, physicians who completed their initial training at top medical schools write significantly fewer opioid prescriptions annually than physicians from lower ranked schools. Additional evidence suggests that some of this gradient represents a causal effect of education rather than patient selection across physicians or physician selection across medical schools. Altering physician education may therefore be a useful policy tool in fighting the current epidemic.

We investigate the relationship between foreclosures and hospital visits using data on all foreclosures and all hospital and emergency room visits from four states that were among the hardest hit by the foreclosure crisis. We find that living in a neighborhood with a spike in foreclosures is associated with significant increases in urgent unscheduled visits, including increases in visits for preventable conditions. The estimated relationships cannot be accounted for by increasing unemployment, declines in housing prices, migration, or by people switching from out-patient providers to hospitals.

In this essay, we ask whether the distributions of life expectancy and mortality have become generally more unequal, as many seem to believe, and we report some good news. Focusing on groups of counties ranked by their poverty rates, we show that gains in life expectancy at birth have actually been relatively equally distributed between rich and poor areas. Analysts who have concluded that inequality in life expectancy is increasing have generally focused on life expectancy at age 40 to 50. This observation suggests that it is important to examine trends in mortality for younger and older ages separately. Turning to an analysis of age-specific mortality rates, we show that among adults age 50 and over, mortality has declined more quickly in richer areas than in poorer ones, resulting in increased inequality in mortality. This finding is consistent with previous research on the subject. However, among children, mortality has been falling more quickly in poorer areas with the result that inequality in mortality has fallen substantially over time. We also show that there have been stunning declines in mortality rates for African Americans between 1990 and 2010, especially for black men. Finally we offer some hypotheses about causes for the results we see, including a discussion of differential smoking patterns by age and socioeconomic status.

Many recent studies point to increasing inequality in mortality in the United States over the past 20 years. These studies often use mortality rates in middle and old age. We used poverty level rankings of groups of U.S. counties as a basis for analyzing inequality in mortality for all age groups in 1990, 2000, and 2010. Consistent with previous studies, we found increasing inequality in mortality at older ages. For children and young adults below age 20, however, we found strong mortality improvements that were most pronounced in poorer counties, implying a strong decrease in mortality inequality. These younger cohorts will form the future adult U.S. population, so this research suggests that inequality in old-age mortality is likely to decline.

Mortality is a crucial indicator of well-being, and recent mortality trends have been a subject of public debate in many Western countries. This paper compares mortality inequality in Canada and the United States over the period 1990/91 through 2010/11. In Canada, mortality inequality remained constant among the youngest but increased for men over 24 and women over 14. In contrast, in the United States, mortality inequality fell for children and youth and either modestly increased or held steady at older ages. By 2010/11, the initially higher US rates of infant and child mortality had almost converged to their Canadian counterparts.

Exploiting geological variation and timing in the initiation of hydraulic fracturing, we find that fracking leads to sharp increases in oil and gas recovery and improvements in a wide set of economic indicators. There is also evidence of deterioration in local amenities, which may include increases in crime, noise, and traffic and declines in health. Using a Rosen-Roback-style spatial equilibrium model to infer the net welfare impacts, we estimate that willingness-to-pay (WTP) for allowing fracking equals about $2,500 per household annually (4.9 percent of household income), although WTP is heterogeneous, ranging from more than $10,000 to roughly 0 across 10 shale regions.(JEL D12, K42, L71, Q35, Q51, Q53, R41)

<h3>Importance</h3> The COVID-19 pandemic disrupted medical care, impacting prescribing of opioid analgesics and buprenorphine for opioid use disorder. Understanding these patterns can help address barriers to care. <h3>Objective</h3> To evaluate how prescribing of opioid analgesics and buprenorphine for opioid use disorder changed throughout the COVID-19 pandemic among both new and existing patients. <h3>Design, Setting, and Participants</h3> In this cross-sectional study, use of opioid analgesics and buprenorphine for opioid use disorder from March 18 to September 1, 2020, was projected using a national database of retail prescriptions from January 1, 2018, to March 3, 2020. Actual prescribing was compared with projected levels for all, existing, and new patients. <h3>Exposures</h3> The data include prescriptions to patients independent of insurance status or type and cover 90% of retail prescriptions, 70% of mail-order prescriptions, and 70% of nursing home prescriptions. <h3>Main Outcomes and Measures</h3> Prescriptions for opioid analgesics and buprenorphine for opioid use disorder. Outcomes included total number of prescriptions, total morphine milligram equivalents, mean morphine milligram equivalents per prescription, mean dispensed units per prescription, and number of patients filling prescriptions. <h3>Results</h3> A total of 452 691 261 prescriptions for opioid analgesics and buprenorphine for opioid use disorder were analyzed for 90 420 353 patients (50 921 535 female patients [56%]; mean [SD] age, 49 [20] years). From March 18 to May 19, 2020, 1877 million total morphine milligram equivalents of opioid analgesics were prescribed weekly vs 1843 million projected, a ratio of 102% (95% prediction interval [PI], 94%-111%;<i>P</i> = .71). The weekly number of opioid-naive patients receiving opioids was 370 051 vs 564 929 projected, or 66% of projected (95% PI, 63%-68%;<i>P</i> &lt; .001). Prescribing of buprenorphine was as projected for existing patients, while the number of new patients receiving buprenorphine weekly was 9865 vs 12 008 projected, or 82% (95% PI, 76%-88%;<i>P</i> &lt; .001). From May 20 to September 1, 2020, opioid prescribing for new patients returned to 100% of projected (95% PI, 96%-104%;<i>P</i> = .95), while the number of new patients receiving buprenorphine weekly was 10 436 vs 11 613 projected, or 90% (95% PI, 83%-97%;<i>P</i> = .009). <h3>Conclusions and Relevance</h3> In this cross-sectional study, existing patients receiving opioid analgesics and buprenorphine for opioid use disorder generally maintained access to these medications during the COVID-19 pandemic. Opioid prescriptions for opioid-naive patients decreased briefly and then rebounded, while initiation of buprenorphine remained at a low rate through August 2020. Reductions in treatment entry may be associated with increased overdose deaths.

This cross-sectional study uses data from the Ohio Department of Health to evaluate trends in drug overdose mortality in that state by type of drug and user age during the first 7 months of the COVID-19 epidemic.

This chapter provides an overview of the literature linking health, health insurance and labor market outcomes such as wages, earnings, employment, hours, occupational choice, job turnover, retirement, and the structure of employment. The first part of the paper focuses on the relationship between health and labor market outcomes. The empirical literature surveyed suggests that poor health reduces the capacity to work and has substantive effects on wages, labor force participation and job choice. The exact magnitudes, however, are sensitive to both the choice of health measures and to identification assumptions. The second part of the paper considers the link between health insurance and labor market outcomes. The empirical literature here suggests that access to health insurance has important effects on both labor force participation and job choice; the link between health insurance and wages is less clear.

This paper offers a review of recent literature regarding the take up of social programs in the U.S. and U.K. A few general conclusions are drawn: First, take up is enhanced by automatic or default enrollment and lowered by administrative barriers, although removing individual barriers does not necessarily have much effect, suggesting that one must address the whole bundle.Second, although it may be impossible to devise a definitive test of the "stigma hypothesis", other, more concrete types of transactions costs are probably a good deal more important.Third, although people generally have means-tested programs in the United States in mind when they discuss take up, low take up is also a problem in many non means-tested social insurance programs and in other countries.Historically, economists have paid little attention to rules about eligibility, and virtually no attention to how these rules are enforced or made known to eligibles.Hence, the marginal return to new data about these features of programs is likely to be high in terms of understanding take up.In an era of social experiments, it might also prove useful to consider experimental manipulations of factors thought to influence take up.

Research on Head Start suggests that effects on test scores more quickly for black children than for white children. We use data from the 1988 wave of the National Educational Longitudinal Survey to show that Head Start black children go on to attend schools of worse quality than other black children. We do not see any similar pattern among whites. Moreover, when we stratify by an indicator of school quality, gaps in test scores between Head Start and other children are very similar for blacks and whites. Hence, the effects of Head Start may fade out more rapidly among black students, at least in part because black Head Start children are more likely to subsequently attend inferior schools.

This study uses data from the British National Child Development Survey (NCDS) to examine interactions between socio-economic status (SES), children's test scores, and future wages and employment. We find that children of lower SES have both lower age 16 test scores and higher returns to these test scores in terms of age 33 wages and employment probabilities than high-SES children.We then examine determinants of age 16 scores. Conditional on having had the same age 7 mathematics scores, high-SES children go on to achieve higher age 16 mathematics scores than children of low or middle-SES. They are also much more likely to pass O-levels in English and Mathematics. These differences are either eliminated or greatly reduced when observable measures of school quality are added to the model, suggesting that high-SES children get better age 16 test scores at least in part because they attended better schools.On the other hand, conditional on age 7 scores, low-SES children achieve higher age 16 reading scores than high-SES children and the estimated relationship between the two is not affected by the addition of school quality variables. This observation provides evidence consistent with the conjecture that success in reading may be less dependent on school quality than success in mathematics.

The food stamp program (FSP) is one of the largest transfer programs in the United States, having provided nearly $24 billion in benefits to 27.5 million families in 1994. 1 Participation in the FSP hovered around 20 million persons per year during the 1980s but rose sharply in the early 1990s to a peak of approximately 27.5 million persons in 1994. Participation then began to fall dramatically, declining back to 20 million participants by 1998. About three-fourths of this decline occurred between 1996 and 1998. 2

. . that the labor force status of an individual will be affected by his health is an unassailable proposition [because] a priori reasoning and casual observation tell us it must be so, not because there is a mass of supporting evidence. (Bowen and Finegan, 1969) Despite the near universal finding that health is a significant determinant of work effort, the second major inference drawn from [this] review is that the magnitude of measured health effects varies substantially across studies. (Chirikos, 1993) This chapter provides an overview of some of the literature linking health and labor market behavior. The question is important because for groups as diverse as single mothers and older people, health is thought to be a major determinant of wages, hours, and labor force participation. Thus, an understanding of the effects of health on labor market activity is necessary for evaluations of the cost effectiveness of interventions designed to prevent or cure disease. Moreover, since the relationship between health and the labor market is mediated by social programs, an understanding of this relationship is necessary if we are to assess the effectiveness and solvency of these programs. In countries with aging populations, these questions will only become more pressing over time as more individuals reach the age where health has the greatest impact of labor market outcomes. The two quotations above, one from 1969 and one from 1993, illustrate that a good deal of empirical evidence linking health and labor market activity has sprung up over the last 25 years. Indeed, the literature we review suggests that health has a pervasive effect on most outcomes of interest to labor economists including wages, earnings, labor force participation, hours worked, retirement, job turnover, and benefits packages. But unfortunately there is no consensus about the magnitude of the effects or about their size relative to the effects of other variables. We will, however, be able to shed some light on factors that cause the estimates to disagree. Much of the best work linking health and labor market outcomes focuses on developing countries. This may be because the link between health and work is more obvious in societies in which many prime age adults are under-nourished and in poor health, and also because the theory of efficiency wages provides a natural starting point for investigations of this issue. However several excellent recent surveys of health and labor markets in developing countries already exist (dee Behrman and Deolalikar 1988 and Strauss and Thomas 1998). In order to break newer ground, this survey will have as its primary focus papers written since 1980 using U.S. data, although we will refer to the developing country literature where appropriate.

This paper reports the results of a systematic experimental comparison of the effect of alternative arbitration systems on dispute rates. The key to our experimental design is the use of a common underlying distribution of arbitrator fair awards in the different arbitration systems. This allows us to compare dispute rates across different arbitration procedures where we hold fixed the amount of objective underlying uncertainty about the arbitration awards.There are three main findings. First, dispute rates are inversely related to the monetary costs of disputes. Dispute rates were much lower in cases where arbitration was not available so that the entire pie was lost in the event of dispute. Second, contrary to conventional wisdom, the dispute rate in a final-offer arbitration system is at least as high as the dispute rate in comparable conventional arbitration system. Third, dispute rates are inversely related to the uncertainty costs of disputes. Dispute rates were lower in conventional arbitration treatments where the variance of the arbitration award was higher and imposed greater costs on risk-averse negotiators. Our results can also be interpreted as providing tentative evidence that the negotiators were risk-averse on average.

Most states have adopted administrative measures to encourage the use of prenatal care among medicaid-eligible women. At the same time, declining welfare caseloads have caused many women to lose medicaid. We examine the effects of changes in income eligibility, administrative procedures, and welfare caseloads using data from all birth certificates for 1990–1996. Higher income cutoffs increased use of prenatal care, while decreases in welfare caseloads reduced it. Changes in income cutoffs also reduced fetal deaths. These results suggest that the administrative reforms have not broken the close link between welfare participation and access to medicaid.

Every year, millions of pounds of toxic chemicals thought to be linked to developmental problems in fetuses and young children are released into the air. In this paper we estimate the effect of these releases on the health of newborns. Using data from the Toxic Release Inventory Program and Vital Statistics Natality and Mortality files, we find significant negative effects of prenatal exposure to toxicants on gestation and birth weight. We also find that several developmental chemicals increase the probability of infant death. The effect is quite sizeable: the reported reductions in cadmium, toluene, and epichlorohydrin releases during the 90s could account for about 3.9 percent of the overall decrease in infant mortality. Our results are robust to several specification checks, such as comparing developmental to non-developmental chemicals, and fugitive air releases to stack air releases.

The majority of children in the US and many other high-income nations are now cared for many hours per week by people who are neither their parents nor their school teachers. The role of such pre-school and out-of-school care is potentially two-fold: First, child care makes it feasible for both parents or the only parent in a single-parent family to be employed. Second, early intervention programs and after school programs aim to enhance child development, particularly among disadvantaged children. Corresponding to this distinction, there are two branches of literature to be summarized in this chapter. The first focuses on the market for child care and analyzes factors affecting the supply, demand and quality of care. The second focuses on child outcomes, and asks whether certain types of programs can ameliorate the effects of early disadvantage. The primary goal of this review is to bring the two literatures together in order to suggest ways that both may be enhanced. Accordingly, we provide an overview of the number of children being cared for in different sorts of arrangements; describe theory and evidence about the nature of the private child care market; and discuss theory and evidence about government intervention in the market for child care. Our summary suggests that additional research is needed in order to better characterize interactions between government programs and market-provided child care.

Research has shown a strong connection between birth weight and future outcomes. We ask how health problems after birth affect outcomes using data from public health insurance records for 50,000 children born between 1979 and 1987 in the Canadian province of Manitoba. We compare children to siblings born an average of three years apart. We find that health problems in early childhood are significant predictors of young adult outcomes. Early physical health problems are linked to outcomes primarily because they predict later health. Early mental health problems have additional predictive power even conditional on future health and health at birth.

We are the first to examine the effect of Superfund cleanups on infant health rather than focusing on proximity to a site. We study singleton births to mothers residing within 5km of a Superfund site between 1989-2003 in five large states. Our "difference in differences" approach compares birth outcomes before and after a site clean-up for mothers who live within 2,000 meters of the site and those who live between 2,000- 5,000 meters of a site. We find that proximity to a Superfund site before cleanup is associated with a 20 to 25% increase in the risk of congenital anomalies.

We examine the effects of a policy change in the province of Quebec, Canada which greatly expanded insurance coverage for prescription medications. We show that the change was associated with a sharp increase in the use of stimulant medications commonly prescribed for ADHD in Quebec relative to the rest of Canada. We ask whether this increase in medication use was associated with improvements in emotional functioning or academic outcomes among children with ADHD. We find little evidence of improvement in either the medium or the long run. Our results are silent on the effects on optimal use of medication for ADHD, but suggest that expanding medication in a community setting had little positive benefit and may have had harmful effects given the average way these drugs are used in the community.

We use longitudinal data from the Fragile Families and Child Well-being Study to investigate the impacts of the Great Recession on the health of mothers. We focus on a wide range of physical and mental health outcomes, as well as health behaviors. We find that increases in the unemployment rate decrease self-reported health status and increase smoking and drug use. We also find evidence of heterogeneous impacts. Disadvantaged mothers-African-American, Hispanic, less educated, and unmarried-experience greater deterioration in their health than advantaged mothers-those who are white, married, and college educated.

Child maltreatment is a major social problem. This paper focuses on measuring the relationship between child maltreatment and crime using data from the National Longitudinal Study of Adolescent Health (Add Health). We focus on crime because it is one of the most costly potential outcomes of maltreatment. Our work addresses two main limitations of the existing literature on child maltreatment. First, we use a large national sample, and investigate different types of maltreatment in a unified framework. Second, we pay careful attention to controlling for possible confounders using a variety of statistical methods that make differing assumptions. The results suggest that maltreatment greatly increases the probability of engaging in crime and that the probability increases with the experience of multiple forms of maltreatment.

We construct a unique individual-level dataset linking preschool blood lead levels with third grade test scores for Rhode Island children born 1997–2005. Using two identification strategies, we show for the first time that reductions of lead from even historically low levels have significant positive effects. A one-unit decrease in average blood lead levels reduces the probability of being substantially below proficient in reading (math) by 0.96 (0.79) percentage points on a baseline of 12 (16) percent. Since disadvantaged children have greater exposure to lead, lead poisoning may be one of the causes of continuing disparities in test scores. (JEL I12, I14, I18, I21, I24, J13)

When a patient arrives at the Emergency Room with acute myocardial infarction (AMI), the provider on duty must quickly decide how aggressively the patient should be treated. Using Florida data on all such patients from 1992 to 2014, we decompose practice style into two components: The provider's probability of conducting invasive procedures on the average patient (which we characterize as aggressiveness), and the responsiveness of the choice of procedure to the patient's characteristics. We show that within hospitals and years, patients with more aggressive providers have consistently higher costs and better outcomes. Since all patients benefit from higher utilization of invasive procedures, targeting procedure use to the most appropriate patients benefits these patients at the expense of the less appropriate patients. We also find that the most aggressive and responsive physicians are young, male, and trained in top 20 schools.

Polypharmacy is growing in Canada, along with adverse drug events and drug-related costs. Part of the solution may be deprescribing, the planned and supervised process of dose reduction or stopping of medications that may be causing harm or are no longer providing benefit. Deprescribing can be a complex process, involving the intersection of patients, health care providers, and organizational and policy factors serving as enablers or barriers. This article describes the justification, theoretical foundation, and process for developing a Canadian Deprescribing Network (CaDeN), a network of individuals, organizations, and decision-makers committed to promoting the appropriate use of medications and non-pharmacological approaches to care, especially among older people in Canada. CaDeN will deploy multiple levels of action across multiple stakeholder groups simultaneously in an ecological approach to health system change. CaDeN proposes a unique model that might be applied both in national settings and for different transformational challenges in health care.

Abstract Using a unique data set linking preschool blood lead levels, birth, school, and detention records for 125,000 children born between 1990 and 2004 in Rhode Island, we estimate the impact of lead on school suspension and juvenile detention. Sibling fixed-effect models suggest that omitted variables related to family disadvantage do not bias OLS estimates. However, measurement error does. We use IV methods that exploit local (within-neighborhood), variation in lead exposure deriving from road proximity and the deleading of gasoline. For boys, a 1 unit increase in lead increased the probability of suspension from school by 6% and detention by 57%.

Expert performance is often evaluated assuming that good experts have good outcomes. We examine expertise in medicine and develop a model that allows for two dimensions of physician performance: decision making and procedural skill. Better procedural skill increases the use of intensive procedures for everyone, while better decision making results in a reallocation of procedures from fewer low-risk to high-risk cases. We show that poor diagnosticians can be identified using administrative data and that improving decision making improves birth outcomes by reducing C-section rates at the bottom of the risk distribution and increasing them at the top of the distribution.

Air quality in the United States has improved dramatically over the past 50 years in large part due to the introduction of the Clean Air Act and the creation of the Environmental Protection Agency to enforce it. This article is a reflection on the 50-year anniversary of the formation of the Environmental Protection Agency, describing what economic research says about the ways in which the Clean Air Act has shaped our society—in terms of costs, benefits, and important distributional concerns. We conclude with a discussion of how recent changes to both policy and technology present new opportunities for researchers in this area.

Abstract Child health is increasingly understood to be a critical form of human capital, but only recently have we begun to understand how valuable it is and how its development could be better supported. This article provides an overview of recent work that demonstrates the key role of public insurance in supporting longer term human capital development and points to improvements in child mental health as an especially important mechanism.

The last 40 years have seen huge innovations in computing and in the availability of data. Data derived from millions of administrative records or by using (as we do) new methods of data generation such as text mining are now common. New data often requires new methods, which in turn can inspire new data collection. If history is any guide, some methods will stick and others will prove to be a flash in the pan. However, the larger trends toward demanding greater credibility and transparency from researchers in applied economics and a 'collage' approach to assembling evidence will likely continue.

Although there is a large gap between Black and White American life expectancies, the gap fell 48.9% between 1990 and 2018, mainly due to mortality declines among Black Americans. We examine age-specific mortality trends and racial gaps in life expectancy in high- and low-income US areas and with reference to six European countries. Inequalities in life expectancy are starker in the United States than in Europe. In 1990, White Americans and Europeans in high-income areas had similar overall life expectancy, while life expectancy for White Americans in low-income areas was lower. However, since then, even high-income White Americans have lost ground relative to Europeans. Meanwhile, the gap in life expectancy between Black Americans and Europeans decreased by 8.3%. Black American life expectancy increased more than White American life expectancy in all US areas, but improvements in lower-income areas had the greatest impact on the racial life expectancy gap. The causes that contributed the most to Black Americans' mortality reductions included cancer, homicide, HIV, and causes originating in the fetal or infant period. Life expectancy for both Black and White Americans plateaued or slightly declined after 2012, but this stalling was most evident among Black Americans even prior to the COVID-19 pandemic. If improvements had continued at the 1990 to 2012 rate, the racial gap in life expectancy would have closed by 2036. European life expectancy also stalled after 2014. Still, the comparison with Europe suggests that mortality rates of both Black and White Americans could fall much further across all ages and in both high-income and low-income areas.

Abstract We study the effects of prenatal exposure to violent crime on infant health, using New York City crime records linked to mothers' addresses in birth records data. We address endogeneity of assault exposure with three strategies and find that in utero assault exposure significantly increases the incidence of adverse birth outcomes. We calculate that the annual social cost of assault during pregnancy in the United States is more than $3.8 billion. Since infant health predicts long-term wellbeing and disadvantaged women are disproportionately likely to be domestic abuse victims, violence in utero may be an important channel for intergenerational transmission of inequality.

We examine the impact of air pollution on infant death in California over the 1990s. Our work offers several innovations: First, many previous studies examine populations subject to far greater levels of pollution. In contrast, the experience of California in the 1990s is clearly relevant to current debates over the regulation of pollution. Second, many studies examine a few routinely monitored pollutants in isolation, generally because of data limitations. We examine four criteria pollutants in a common framework. Third, we develop an identification strategy based on within zip code variation in pollution levels that controls for potentially important unobserved characteristics of high pollution areas. Fourth, we use rich individual-level data to investigate effects of pollution on infant mortality, fetal deaths, low birth weight and prematurity in a common framework. We find that the reductions in carbon monoxide (CO) and particulates (PM10) over the 1990s in California saved over 1,000 infant lives. However, we find little consistent evidence of pollution effects on fetal deaths, low birth weight or short gestation.

The majority of children in the U.S. and many other high-income nations are now cared for many hours per week by people who are neither their parents nor their school teachers.The role of such preschool and out of school care is potentially two-fold: First, child care makes it feasible for parents to be employed.Second, early intervention programs and after school programs aim to enhance child development, particularly among disadvantaged children.Corresponding to this distinction, the literature has two branches.The first focuses on the market for child care and analyzes factors affecting the supply, demand, and quality of care.The second focuses on child outcomes and asks whether certain types of programs can ameliorate the effects of early disadvantage.The primary goal of this review is to bring the two literatures together in order to suggest ways that both may be enhanced.Accordingly, we provide an overview of the number of children being cared for in different sorts of arrangements; describe theory and evidence about the nature of the private child care market; and discuss theory and evidence about government intervention in the market for child care.Our summary suggests that additional research is necessary to highlight the ways that government programs and market provided child care interact with each other.

Loss of the RNA-binding protein FMRP (fragile X mental retardation protein) leads to fragile X syndrome, the most common form of inherited mental retardation. Although some of the messenger RNA targets of this protein, including FMR1, have been ascertained, many have yet to be identified. We have found thatXenopus elongation factor 1A (EF-1A) mRNA binds tightly to recombinant human FMRP in vitro. Binding depended on protein determinants located primarily in the C-terminal end of hFMRP, but the hnRNP K homology domain influenced binding as well. When hFMRP was expressed in cultured cells, it dramatically reduced endogenous EF-1A protein expression but had no effect on EF-1A mRNA levels. In contrast, the translation of several other mRNAs, including those coding for dynamin and constitutive heat shock 70 protein, was not affected by the hFMRP expression. Most importantly, EF-1A mRNA and hFMR1 mRNA were coimmunoprecipitated with hFMRP. Finally, in fragile X lymphoblastoid cells in which hFMRP is absent, human EF-1A protein but not its corresponding mRNA is elevated compared with normal lymphoblastoid cells. These data suggest that hFMRP binds to EF-1A mRNA and also strongly argue that FMRP negatively regulates EF-1A expression in vivo. Loss of the RNA-binding protein FMRP (fragile X mental retardation protein) leads to fragile X syndrome, the most common form of inherited mental retardation. Although some of the messenger RNA targets of this protein, including FMR1, have been ascertained, many have yet to be identified. We have found thatXenopus elongation factor 1A (EF-1A) mRNA binds tightly to recombinant human FMRP in vitro. Binding depended on protein determinants located primarily in the C-terminal end of hFMRP, but the hnRNP K homology domain influenced binding as well. When hFMRP was expressed in cultured cells, it dramatically reduced endogenous EF-1A protein expression but had no effect on EF-1A mRNA levels. In contrast, the translation of several other mRNAs, including those coding for dynamin and constitutive heat shock 70 protein, was not affected by the hFMRP expression. Most importantly, EF-1A mRNA and hFMR1 mRNA were coimmunoprecipitated with hFMRP. Finally, in fragile X lymphoblastoid cells in which hFMRP is absent, human EF-1A protein but not its corresponding mRNA is elevated compared with normal lymphoblastoid cells. These data suggest that hFMRP binds to EF-1A mRNA and also strongly argue that FMRP negatively regulates EF-1A expression in vivo. fragile X mental retardation protein agarose gel electrophoretic shift assay coding sequence elongation factor 1A fragile X related proteins 1 and 2, respectively human species designation constitutive heat shock 70 protein hnRNP K homology domain mouse species designation monoclonal antibody rat species designation untranslated region Xenopus species designation The loss of a normal cellular protein, FMRP,1 causes fragile X syndrome, one of the most common forms of mental retardation (MR). FMRP is a RNA-binding protein that contains two hnRNP K-homology (KH) binding domains and an arginine-glycine-rich region that resembles an RGG box (1Sung Y.-J. Denman R. Recent Res. Dev. Biophys. Biochem. 2001; 1: 109-123Google Scholar, 2Kiledjian M. Dreyfuss G. EMBO J. 1992; 11: 2655-2664Crossref PubMed Scopus (506) Google Scholar). Several studies indicate that both the KH2domain and the arginine-glycine-rich region likely play a role in RNA binding (1Sung Y.-J. Denman R. Recent Res. Dev. Biophys. Biochem. 2001; 1: 109-123Google Scholar, 3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar, 4Siomi H. Choi M. Siomi M.C. Nussbaum R.L. Dreyfuss G. Cell. 1994; 77: 33-39Abstract Full Text PDF PubMed Scopus (381) Google Scholar, 5Siomi H. Siomi M.C. Nussbaum R.L. Dreyfuss G. Cell. 1993; 74: 291-298Abstract Full Text PDF PubMed Scopus (556) Google Scholar, 6Darnell J.C. Jensen K. Jin P. Brown V. Warren S. Darnell R.B. Cell. 2001; 107: 489-499Abstract Full Text Full Text PDF PubMed Scopus (779) Google Scholar), the latter interaction being mediated by a G quartet (7Schaeffer C. Bardoni B. Mandel J.L. Ehresmann B. Ehresmann C. Moine H. EMBO J. 2001; 20: 4803-4813Crossref PubMed Scopus (388) Google Scholar). FMRP associates with polyribosomes via a mRNP particle (8Corbin F. Bouillon M. Fortin A. Morin S. Rousseau F. Khandjian E.W. Hum. Mol. Genet. 1997; 6: 1465-1472Crossref PubMed Scopus (204) Google Scholar, 9Feng Y. Absher D. Eberhart D. Brown V. Malter H. Warren S. Mol. Cell. Biol. 1997; 1: 109-118Scopus (406) Google Scholar), and it has been proposed to regulate gene expression post-transcriptionally (5Siomi H. Siomi M.C. Nussbaum R.L. Dreyfuss G. Cell. 1993; 74: 291-298Abstract Full Text PDF PubMed Scopus (556) Google Scholar, 10Ceman S. Brown V. Warren S. Mol. Cell. Biol. 1999; 19: 7925-7932Crossref PubMed Scopus (154) Google Scholar, 11Weiler I.J. Irwin S.A. Klintsova A.Y. Spencer C.M. Brazelton A.D. Miyashiro K. Comery T.A. Patel B. Eberwine J. Greenough W.T. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 5395-5400Crossref PubMed Scopus (541) Google Scholar, 12Ashley Jr., C.T. Wilkinson K.D. Reines D. Warren S.T. Science. 1993; 262: 563-566Crossref PubMed Scopus (614) Google Scholar, 13O'Donnell W.T. Warren S.T. Annu. Rev. Neurosci. 2002; 25: 315-338Crossref PubMed Scopus (391) Google Scholar, 14Inoue S.B. Siomi M.C. Siomi H. J. Med. Invest. 2000; 47: 101-107PubMed Google Scholar). Mammalian FMRPs inhibit mRNA translation in vitro at nanomolar concentrations in both rabbit reticulocyte lysates (15Li Z. Zhang Y. Ku L. Wilkinson K.D. Warren S.T. Feng Y. Nucleic Acids Res. 2001; 29: 2276-2283Crossref PubMed Scopus (372) Google Scholar) and in microinjected Xenopus oocytes (16Laggerbauer B. Ostareck D. Keidel E.-M. Ostareck-Lederer A. Fischer U. Hum. Mol. Genet. 2001; 10: 329-338Crossref PubMed Scopus (471) Google Scholar). These data suggest that translational repression may be an in vivo function of FMRP. Indeed, the Drosophila homolog of FMRP, dFMR1, was found to bind and negatively regulatefutsch mRNA (17Zhang Y.Q. Bailey A.M. Matthies H.J. Renden R.B. Smith M.A. Speese S.D. Rubin G.M. Broadie K. Cell. 2001; 107: 591-603Abstract Full Text Full Text PDF PubMed Scopus (526) Google Scholar). Recent studies have begun to delineate the mRNAs that mammalian FMRPs interact with in vivo. These studies have taken one of two forms. On the one hand, potential FMRP target mRNAs have been identified solely on the basis of their ability to bind to purified recombinant FMRP (15Li Z. Zhang Y. Ku L. Wilkinson K.D. Warren S.T. Feng Y. Nucleic Acids Res. 2001; 29: 2276-2283Crossref PubMed Scopus (372) Google Scholar, 16Laggerbauer B. Ostareck D. Keidel E.-M. Ostareck-Lederer A. Fischer U. Hum. Mol. Genet. 2001; 10: 329-338Crossref PubMed Scopus (471) Google Scholar) or cell-free produced FMRP (1Sung Y.-J. Denman R. Recent Res. Dev. Biophys. Biochem. 2001; 1: 109-123Google Scholar, 3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar). Notwithstanding, it has not been determined whether any of these mRNAs bind to FMRP in vivo. On the other hand, mRNAs, including FMR1 mRNA, which associate with FMRP-containing mRNPs have also been isolated from cultured cells (10Ceman S. Brown V. Warren S. Mol. Cell. Biol. 1999; 19: 7925-7932Crossref PubMed Scopus (154) Google Scholar,18Brown V. Jin P. Ceman S. Darnell J.C. O'Donnell W. Tenenbaum S. Jin X. Feng X. Wilkinson K.D. Keene J. Darnell R.B. Warren S.T. Cell. 2001; 107: 477-489Abstract Full Text Full Text PDF PubMed Scopus (908) Google Scholar). However, although these messages require FMRP in the mRNP for their association, it has not been demonstrated that they bind solely to it. Using the former methodology, we isolated a subset of mRNAs derived from normal adult brain that bind human FMRP (hFMRP) in vitro (3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar). During the course of this investigation we also tested a number of other mRNAs for their ability to interact with hFMRP. One of these mRNAs was Xenopus elongation factor 1A (xEF-1A). In the present paper we demonstrate that xEF-1A mRNA binds to recombinant and cell-free produced hFMRP in vitro. Furthermore, we show that hFMRP inhibits EF-1A mRNA translation in cultured PC12 and COS-7 cells and that the loss of hFMRP in fragile X lymphoblastoid cells derepresses human EF-1A (hEF-1A) mRNA translation. FMRP mAb 2160 and normal mouse serum were purchased from Chemicon. FXR1 (Y-19) mAb and FXR2 (S-16) mAb were obtained from Santa Cruz. Dynamin mAb and EF-1A mAb were purchased from Upstate Biotechnology. Hsp70cP mAb (HSP-820) was obtained fromStressGen. Horseradish peroxidase-conjugated secondary antibodies were purchased from KPL and Santa Cruz. RNA binding buffer 1 contained 50 mmTris-HCl, pH 7.0, 2 mm MgCl2, and 150 mm NaCl. Buffer 2 contained 20 mm Hepes, pH 7.9, 2 mm MgCl2, 70 mmNH4Cl, 0.2% IGEPAL CA630, and 50 mg/ml yeast tRNA. FMRP purification buffer, buffer 3, contained 10 mm Hepes, pH 7.9, 300 mm NaCl, 1% Triton X-100, 1 mmphenylmethylsulfonyl fluoride, 5 mm β-mercaptoethanol, and 20 mm imidazole. TAE buffer contained 40 mmTris acetate and 1 mm EDTA. TMK buffer contained 50 mm Tris-HCl, pH 7.6, 10 mm MgCl2, and 25 mm KCl. pET21A-hFMRP and pET21A-I304N, encoding hFMRP and the corresponding I304N point mutant, were gifts from Dr. Bernhard Laggerbauer, Max Planck Institute for Biochemistry, Germany. Each vector generates full-length FMRP with an N-terminal His tag. pTRI-XEF, encoding Xenopus EF-1A, was obtained from Ambion Laboratories. pAPP-695 and pT7-Control, encoding βAPP695 and a 1.4-kb λ-HindIII/EcoRI RNA, respectively, have been described previously (3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar). pSF2-hFMRP, encoding human FMRP, was a gift from Dr. Ben Oostra, Erasmus University, Rotterdam, The Netherlands. pHA-hFXR1P, encoding human FXR1P, was a gift from Dr. Gideon Dreyfuss, University of Pennsylvania. Full-length and truncated 35S-hFMRPs were prepared by coupled in vitro transcription translation (3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar). Recombinant hFMRPs were expressed in Escherichia coli BL21 from pET21A-FMRP and pET21A-I304N (16Laggerbauer B. Ostareck D. Keidel E.-M. Ostareck-Lederer A. Fischer U. Hum. Mol. Genet. 2001; 10: 329-338Crossref PubMed Scopus (471) Google Scholar, 19Denman R. Sung Y.-J. Biochem. Biophys. Res. Commun. 2002; 292: 1063-1069Crossref PubMed Scopus (21) Google Scholar). Briefly, transformed E. coli BL21 were grown at 37 °C to 1.0A 560 in LB-Amp100 medium. 1 mm isopropyl-1-thio-β-d-galactopyranoside was added, and the cells were grown at 30 °C overnight. Proteins were extracted from cell pellets using B-Per™ supplemented with 300 mm NaCl, 20 mm imidazole, 5 mmβ-mercaptoethanol, 1 mm phenylmethylsulfonyl fluoride, and 1 × Complete™ protease inhibitors and purified on nickel-nitrilotriacetic acid resin, preequilibrated with buffer 3. Bound protein was eluted with buffer 3 plus 230 mmimidazole. hFMRP production (68–70 kDa) was confirmed by Western blotting, and its purity was determined by Coomassie Blue staining. The micro-BCA assay was used to determine protein concentration (20Smith P.K. Krohn R.I. Hermanson G.T. Mallia A.K. Gartner F.H. Provenzano M.D. Fujimoto E.K. Goeke N.M. Olson B.J. Klenk D.C. Anal. Biochem. 1985; 150: 76-85Crossref PubMed Scopus (18512) Google Scholar). RNAs were produced from linearized plasmids by in vitro transcription. The transcripts were purified on QuickSpin™ columns and quantified by UV-visible spectrophotometry at 260 and 280 nm (3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar). Purified recombinant hFMRP was bound to RNA at room temperature. Briefly, the recombinant protein was preincubated for 10 min in buffer 1 supplemented with 0.25 mg/ml tRNA and 0.25 mg/ml ultrapure bovine serum albumin. Subsequently, RNA was added and incubated for an additional 20 min. hFMRP·RNA complexes were then resolved on 1% TAE agarose gels (50–60 V, 50 mA for 1–2 h) and visualized by ethidium bromide staining. Kd values were determined from titrations of recombinant proteins with fixed amounts of in vitro transcribed target RNAs. The percent complex formation was measured from scanned images of the AGESAs using IPLab Gel software (Signal Analytics Corp.) and plotted versus the amount of recombinant protein input into the reaction. A molecular mass of 69,000 Da was used to calculate the molar amount of hFMRP (12Ashley Jr., C.T. Wilkinson K.D. Reines D. Warren S.T. Science. 1993; 262: 563-566Crossref PubMed Scopus (614) Google Scholar). The data were fit using a nonlinear curve-fitting program Kaleidograph software (Synergy Software) (21Setzer D. Hynes S. RNA-Protein Interaction Protocols. 118. Humana Press, Totowa, NJ1999: 115-128Google Scholar). To verify specific complex formation, bands from different regions of a gel shift experiment were excised and boiled for 5 min in SDS buffer (22Tanaka, K. J., and Nishikata, T. (1998) in Technical Tips Online, BioMedNet (bmn.com).Google Scholar). The resulting extracts were blotted and probed with FMRP mAb 2160. 35S-Labeled hFMRP, hFMRPΔRGG, hFMRPΔKH2, and hFMRPΔRNB binding to biotinylated xEF-1A RNA was measured by affinity capture using SoftLink™ resin in buffer 2 (3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar). Nonspecific binding, determined by comparison with reactions without in vitro transcribed RNA or nonbiotinylated xEF-1A RNA, was negligible. RNA binding was quantified using IPLab Gel software. The percent binding was calculated as shown in Equation 1. %binding=boundintensity/(boundintensity +(4×unboundintensity))×100Equation 1 This corrects for load differences between the bound and unbound fractions. For the studies presented in Fig. 2, B andC, in which both full-length and incomplete proteins were produced, only the full-length protein was quantified. The -fold decrease in biotinylated xEF-1A RNA binding between full-length wild-type and full-length truncated hFMRPs was calculated as shown in Equation 2. fold decrease=%bindingfull­length hFMRP/%bindingtruncated hFMRPEquation 2 xEF-1 RNA competition with homoribopolymer resins (poly(rG), and poly(rU)) was carried out with a 10-fold molar excess of xEF-1A RNA over poly(rN), a 2-fold molar excess of soluble poly(rG), or a 2-fold molar excess of soluble poly(rU). Briefly, 35S-hFMRP was incubated in buffer 2 containing 3 μg of poly(rN) resin and either xEF-1A RNA or soluble poly(rN) (1 h, 4 °C). Unbound35S-hFMRP was removed; the resins were then washed with 40 column volumes of buffer 2. Bound 35S-hFMRP was eluted by boiling in SDS buffer. Biotinylated xEF-1A RNA competition with nonbiotinylated target mRNAs was carried out using the SoftLink™ affinity capture protocol described above. A 5-fold molar excess of nonbiotinylated target mRNA over biotinylated xEF-1A mRNA was added to the reaction before adding 35S-hFMRP. Competition was expressed as the ratio of the percentage of biotinylated xEF-1A mRNA bound to hFMRP in the presence of competitor mRNA to the percentage of biotinylated xEF-1A mRNA bound to hFMRP in the absence of competitor mRNA. Undifferentiated PC12 cells were grown at 37 °C in 5% CO2 and maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. COS-7 cells were cultured in RPMI supplemented with 5% fetal calf serum and 2 mm glutamine. Cells (3 × 105/35-mm dish) were transfected with 1 μg of pSF2-hFMRP or with 1 μg of control DNAs (pET21A-hFMRP, pHA-hFXR1P). 24, 48, 72, or 96 h later the cells were harvested and used to prepare total RNA or total proteins (3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar, 23Dolzhanskaya N. Conti J. Schwenk V. Merz G. Denman R.B. Arch. Biochem. Biophys. 2001; 387: 223-232Crossref PubMed Scopus (5) Google Scholar). The transfection efficiency for each experiment varied between 20 and 60%, but within a particular experiment the efficiency was uniform. Fragile X and normal lymphoblastoid cell lines were cultured in RPMI supplemented with 10% fetal bovine serum. Northern blotting was carried out as described previously (23Dolzhanskaya N. Conti J. Schwenk V. Merz G. Denman R.B. Arch. Biochem. Biophys. 2001; 387: 223-232Crossref PubMed Scopus (5) Google Scholar). Probes were prepared by amplifying the first 871 bases of human FMR1 cDNA from pSF2-hFMRP DNA and the entire xEF-1A coding sequence from pTRI-XEF DNA (86.7% identity to rat EF-1A mRNA). cDNAs were random prime labeled with [α-32P]dCTP and desalted on G-50 QuickSpin™ columns before hybridization. Western blotting was performed as described previously (24Denman R. Potempska A. Wolfe G. Ramakrishna N. Miller D.L. Arch. Biochem. Biophys. 1991; 288: 29-38Crossref PubMed Scopus (36) Google Scholar). FMRP mAb 2160 was used at a 1:10,000 dilution; under these conditions the antibody preferentially detects hFMRP, therefore it is not possible to ascertain whether transient transfection results in FMRP overexpression. HSP-820, EF-1A, and dynamin mAbs were used at a 1:5,000 dilution. Blots were blocked for 1 h at room temperature in phosphate-buffered saline supplemented with 3% non-fat dry milk and probed overnight in fresh buffer with the corresponding primary antibody at 4 °C. Blots were developed using LumiGlo. Horseradish peroxidase-conjugated goat anti-mouse secondary antibody was used at a 1:5,000 dilution. FXR1 (Y-19) antibody and FXR2 (S-16) antibodies were used at a 1:100 dilution. Blots were blocked and probed as above and then developed using the manufacturer's washing procedure (www.scbt.com; Research Applications). Horseradish peroxidase-conjugated bovine anti-goat secondary antibody was used at a 1:2,000 dilution. Blots were probed simultaneously with two different antibodies, an internal control antibody such as dynamin or HSP-820 and an antibody directed to the protein of interest. Blots were quantified from scanned images; the ratio of protein to Hsp70cP was used to normalize all data. PC12 cells were transfected with pSF2-hFMRP or pET21A-hFMRP. 48 h post-transfection the cells were scraped in 1.0 ml of diethyl pyrocarbonate-treated 1 × phosphate-buffered saline and pelleted by centrifugation. The pellet was washed twice with ice-cold diethyl pyrocarbonate-treated 1 × phosphate-buffered saline. All subsequent steps were carried out at 4 °C. Pellets were lysed with 100 μl of buffer 1 supplemented with 1% IGEPAL CA630. The lysates (50 μl) were precleared for 3.5 h with 30 μl of protein A/G that was pretreated with 30 μl of normal mouse serum, 10 μl of RNAsin, 20 μl of 50 × Complete protease inhibitors, and 500 μl of buffer 1. The precleared lysates were immunoprecipitated overnight with 30 μl of FMRP mAb 2160-coupled protein A/G beads. After a 10-min 3,000 × g spin, proteins or RNA was extracted from the supernatants and pellets. Supernatant proteins were prepared by adding 3 × SDS sample buffer to the supernatant (250:750 μl ratio). Immunoprecipitated proteins were prepared by adding 300 μl of 1 × SDS sample buffer to each pellet. Total RNA was extracted from the immunoprecipitant using 1 ml of TRI-Reagent™. The final RNA pellet was dissolved in 25 μl of diethyl pyrocarbonate-treated H2O and used to prepared first strand cDNA. cDNAs were amplified using rat-specific EF-1A-specific primers (5′-ATATTATCCCTAACACCTGCC, 5′-GGTCTCAAAATTCTGTGACAG) that amplify a 259-bp fragment from bases 1464 to 1723 of rat EF-1A mRNA, accession no. X61043. FMR1-specific primers (set A: 5′-GGCTAGAAGCTTTCTGGA, 5′-GTGAATGGAGTACCCTAA) were used to amplify a 1,023-bp fragment from bases 945 to 1968 of mouse fmr1 mRNA, accession no. L23971; whereas set B (5′-GGCTAGAAGCTTTCTGGA, 5′-ACGTGGAGGAGGCTTCAAAGGAAA) amplifies a hFMR1-specific 833-bp fragment from bases 831 to 1,644 of human FMR1 mRNA, accession no. NM_002024. Polyribosomes were prepared by pelleting PC12 lysates through 50% sucrose pads (25Denman R.B. Biochem. Biophys. Res. Commun. 1997; 230: 226-231Crossref PubMed Scopus (10) Google Scholar). Briefly, PC12 cells (5 × 107) were transfected with pSF2-hFMRP or pET21A-hFMRP. 24 h later the cells were scraped from the dishes in ice-cold TMK buffer and pelleted. The pellets were lysed in 200 μl of TMK buffer supplemented with 1% IGEPAL CA630. 50-μl aliquots were loaded on 50% sucrose pads containing 500 μl of TMK buffer and centrifuged at 50,000 rpm for 20 h. The resulting polyribosome pellets were washed with 200 μl of TMK buffer and then extracted with 50 μl of 1 × SDS sample buffer. In some cases, the lysates were treated for 5 min at 37 °C with 25 mm EDTA to disrupt the polyribosomes (8Corbin F. Bouillon M. Fortin A. Morin S. Rousseau F. Khandjian E.W. Hum. Mol. Genet. 1997; 6: 1465-1472Crossref PubMed Scopus (204) Google Scholar,25Denman R.B. Biochem. Biophys. Res. Commun. 1997; 230: 226-231Crossref PubMed Scopus (10) Google Scholar, 26Khandjian E.W. Corbin F. Woerly S. Rousseau F. Nat. Genet. 1996; 12: 91-93Crossref PubMed Scopus (207) Google Scholar, 27Siomi M.C. Zhang Y. Siomi H. Dreyfuss G. Mol. Cell. Biol. 1996; 16: 3825-3832Crossref PubMed Scopus (216) Google Scholar). A minimal sequence WGGN1–4WGGN1–4 WGGN1–4 WGGN0–6 was used to assess EF-1A mRNA and individual FMRP-target mRNAs (1Sung Y.-J. Denman R. Recent Res. Dev. Biophys. Biochem. 2001; 1: 109-123Google Scholar, 3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar) for the potential presence of G quartet structures. Candidates containing such sequences were then folded into secondary structure models using Mfold (//bioinfo.math.rpi.edu/) or RNABOB to determine whether a requisite hairpin stem-loop S6NWGGN1–4 WGGN1–4 WGGN1–4WGGN0–6NS6 formed (6Darnell J.C. Jensen K. Jin P. Brown V. Warren S. Darnell R.B. Cell. 2001; 107: 489-499Abstract Full Text Full Text PDF PubMed Scopus (779) Google Scholar). Several studies using FMR1 mRNA have been undertaken to define the RNA motif that FMRP recognizes (3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar,7Schaeffer C. Bardoni B. Mandel J.L. Ehresmann B. Ehresmann C. Moine H. EMBO J. 2001; 20: 4803-4813Crossref PubMed Scopus (388) Google Scholar, 28Brown V. Small K. Lakkis L. Feng Y. Gunter C. Wilkinson K.D. Warren S.T. J. Biol. Chem. 1998; 273: 15521-15527Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar). The results suggest that FMRP may bind to multiple regions of a mRNA (19Denman R. Sung Y.-J. Biochem. Biophys. Res. Commun. 2002; 292: 1063-1069Crossref PubMed Scopus (21) Google Scholar); thus, in assessing FMRP target mRNA binding, an assay that measures interactions of large mRNAs with FMRP is necessary. To do this, we modified a nondenaturing AGESA (30Chung S. Jiang L. Cheng S. Furneaux H. J. Biol. Chem. 1996; 271: 11518-11524Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar) so that unlabeled in vitro transcribed mRNAs and mRNA·protein complexes could be visualized by ethidium bromide staining. Fig. 1 A illustrates results obtained by incubating the 1.9-kb 3′-untranslated region of human FMR1 mRNA (FMR1 3′-UTR) or a 1.4-kb lambda RNA fragment (λ-control RNA) in the presence or absence of purified recombinant human FMRP (hFMRP). As shown in lane 1, FMR1 3′-UTR mRNA migrated as two bands in the absence of hFMRP, indicating that the RNA resides in two conformational states (31Denman R.B. Smedman M. Kung L. Arch. Biochem. Biophys. 1995; 323: 71-78Crossref PubMed Scopus (7) Google Scholar). These two conformers coalesced into a uniquely migrating single band in the presence of hFMRP (lane 2). Although the shift was small, the bands were completely resolved. In contrast, the shift did not occur when the recombinant protein was added to λ-control RNA (lanes 3and 4). This was expected because FMR1 3′-UTR mRNA binds specifically to FMRP (1Sung Y.-J. Denman R. Recent Res. Dev. Biophys. Biochem. 2001; 1: 109-123Google Scholar, 3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar, 7Schaeffer C. Bardoni B. Mandel J.L. Ehresmann B. Ehresmann C. Moine H. EMBO J. 2001; 20: 4803-4813Crossref PubMed Scopus (388) Google Scholar, 28Brown V. Small K. Lakkis L. Feng Y. Gunter C. Wilkinson K.D. Warren S.T. J. Biol. Chem. 1998; 273: 15521-15527Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar), whereas the λ-control RNA does not (1Sung Y.-J. Denman R. Recent Res. Dev. Biophys. Biochem. 2001; 1: 109-123Google Scholar, 3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar). Although these data are consistent with the formation of an hFMRP·FMR1 3′-UTR complex, several control experiments were performed to confirm this observation. To our surprise, another RNA, EF-1A fromXenopus (xEF-1A mRNA, 1.6 kb), displayed the same feature as FMR1 3′-UTR mRNA in AGESA. As shown in Fig.1 B, the two xEF-1A mRNA conformers (lane 1) coalesced into a uniquely migrating single band in the presence of hFMRP (lane 3). This result was recapitulated when we used hFMRP-I304N, containing the KH2 RNA binding domain mutation I304N (lane 4). This mutant was of particular interest because it is associated with exceptionally severe mental retardation (32De Boulle K. Verkerk A.J. Reyniers E. Vits L. Hendrickx J. Van Roy B. Van den Bos F. de Graaff E. Oostra B.A. Willems P.J. Nat. Genet. 1993; 3: 31-35Crossref PubMed Scopus (507) Google Scholar). Because NaCl concentrations above 0.25 m decrease the FMRP affinity for RNA we also examined the effect 0.5 mNaCl had on xEF-1A mRNA binding to hFMRP and hFMRP-I304N. Fig.1 B, lanes 5 and 6, shows that the band shift seen in lanes 3 and 4 was completely abrogated; lesser decreases were observed at lower salt concentrations (lanes 11–15). The RNA mobility shift was also lost when the recombinant proteins were heat denatured at 65 °C for 5 min before adding xEF-1A mRNA (lanes 7 and 8). These data indicate that more than the mere presence of the recombinant hFMRPs is required for the shift. In addition, the fact that 2.5 μg of recombinant bovine serum albumin failed to produce a shift (comparelanes 1 and 2) indicates that the response was not due simply to added native protein. Finally, lanes 9 and10 demonstrate that neither recombinant protein preparation contained large molecular mass nucleic acid, indicating that the shifted bands contained xEF-1A mRNA. We then used AGESA to define further the binding properties of hFMRP and xEF-1A mRNA. Fig. 1 C shows that xEF-1A mRNA binding was saturable with increasing concentrations of hFMRP or hFMRP-I304N. The apparent Kd values for these complexes were 3.0 and 6.1 nm, respectively. These data corroborate the data in Fig. 1 B, suggesting that hFMRP and hFMRP-I304N binding to xEF-1A mRNA is specific. To demonstrate further that the shifted band was an xEF-1A mRNA·hFMRP complex, hFMRP was specifically and uniquely recovered from the putative complex. Here, xEF-1A mRNA was incubated alone or with subsaturating amounts of purified recombinant hFMRP and subsequently resolved by AGESA. Fig. 1 D shows that adding hFMRP resulted in either the loss or decrease in the upper xEF-1A conformers and a concurrent broadening of the lower conformer (comparelanes 1 and 2). Five regions of this gel were then excised and probed for the presence of hFMRP. The right panel of Fig. 1 D shows that only the xEF-1A mRNA-shifted band contained hFMRP (lane 2). Thus, these data demonstrate that recombinant hFMRP and xEF-1A mRNA associatein vitro. FMRP has three RNA binding domains, and there is no a priori basis for knowing whether one or any combination of them interacts with a particular RNA. We have previously used 35S-FMRP truncation mutants in affinity capture assays to show that hFMR1 mRNA binding requires determinants in its KH2 domain (1Sung Y.-J. Denman R. Recent Res. Dev. Biophys. Biochem. 2001; 1: 109-123Google Scholar, 3Sung Y.-J. Conti J. Currie J.R. Brown W.T. Denman R. Biochem. Biophys. Res. Commun. 2000; 275: 973-980Crossref PubMed Scopus (76) Google Scholar). Therefore, we employed this strategy to determine the domains required for binding xEF-1A mRNA. Four different hFMRP forms were assessed: 1) full-length hFMRP, 2) hFMRPΔRGG in which the last 334 amino acids including the arginine-glycine-rich region are deleted, 3) hFMRPΔKH2 in which the arginine-glycine-rich region and the KH2 domain are deleted, and 4) hFMRPΔRNBin which all three RNA binding domains are deleted (Fig.2 A). Fig. 2 B shows that xEF-1A mRNA bound 35S-hFMRP, recapitulating the results of Fig. 1. 35S-hFMRPΔRGG also bound to xEF-1A mRNA, albeit with a 6.5-fold decrease in affinity compared with full-length hFMRP. Removing the KH2 domain (35S-hFMRPΔKH2) reduced the binding further, whereas 35S-hFMRPΔRNB binding was not detectable under the conditions of the assay. Therefore, the C-terminal 334 amino acids of hFMRP play a major role (either

Amyloid beta (Abeta) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer's disease to determine if intraneuronal Abeta immunoreactivity is an early manifestation of Alzheimer-type pathology leading to fibrillar plaque formation and/or neurofibrillary degeneration. The appearance of Abeta immunoreactivity in neurons in infants and stable neuron-type specific Abeta immunoreactivity in a majority of brain structures during late childhood, adulthood, and normal aging does not support this hypothesis. The absence or detection of only traces of reaction with antibodies against 4-13 aa and 8-17 aa of Abeta in neurons indicated that intraneuronal Abeta was mainly a product of alpha- and gamma-secretases (Abeta(17-40/42)). The presence of N-terminally truncated Abeta(17-40) and Abeta(17-42) in the control brains was confirmed by Western blotting and the identity of Abeta(17-40) was confirmed by mass spectrometry. The prevalence of products of alpha- and gamma -secretases in neurons and beta- and gamma-secretases in plaques argues against major contribution of Abeta-immunopositive material detected in neuronal soma to amyloid deposit in plaques. The strongest intraneuronal Abeta(17-42) immunoreactivity was observed in structures with low susceptibility to fibrillar Abeta deposition, neurofibrillary degeneration, and neuronal loss compared to areas more vulnerable to Alzheimer-type pathology. These observations indicate that the intraneuronal Abeta immunoreactivity detected in this study is not a predictor of brain amyloidosis or neurofibrillary degeneration. The constant level of Abeta immunoreactivity in structures free from neuronal pathology during essentially the entire life span suggests that intraneuronal amino-terminally truncated Abeta represents a product of normal neuronal metabolism.

Critics of Head Start contend that many programs spend too much money on programs extraneous to children. On the other hand, Head Start advocates argue that the families of severely disadvantaged children need a broad range of services. Given the available evidence, it has been impossible to assess the validity of these claims. In this study, we match detailed administrative data with data on child outcomes from the National Longitudinal Survey of Youth 1979, including test scores, behavior problems, and grade repetition. We find that former Head Start children have higher reading and vocabulary scores where Head Start spending was higher. Holding per capita expenditures constant, children in programs that devoted higher shares of their budgets to child-specific expenditures have fewer behavior problems and are less likely to have been retained in grade.