56 results on '"Lawrence L. Wu"'
Search Results
2. Sexual Abstinence in the United States: Cohort Trends in Abstaining from Sex While Never Married for U.S. Women Born 1938 to 1983
- Author
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Lawrence L. Wu, Steven P. Martin, Paula England, and Nicholas D. E. Mark
- Subjects
Social Sciences ,Sociology (General) ,HM401-1281 - Abstract
In this data visualization, the authors document trends in abstaining from sex while never married for U.S. women born 1938–1939 to 1982–1983. Using data from the six most recent National Surveys of Family Growth, the authors’ estimates suggest that for women born in the late 1930s and early 1940s, 48 percent to 58 percent reported abstaining from sex while never married. Abstinence then declined rapidly among women born in the late 1940s through the early 1960s, leveling off at between 9 percent and 12 percent for more recent birth cohorts. Thus, for U.S. women born between the mid-1960s and the early 1980s, roughly one in nine abstained from sex while never married.
- Published
- 2020
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3. The Decoupling of Sex and Marriage: Cohort Trends in Who Did and Did Not Delay Sex until Marriage for U.S. Women Born 1938–1985
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Lawrence L. Wu, Steven P. Martin, and Paula England
- Subjects
Cohort Analyses ,Competing Risks ,Marriage ,Sexual Revolution ,Sexuality ,Sociology (General) ,HM401-1281 - Abstract
In this study, we examine cohort trends in who did and did not delay sex until marriage for U.S. women born between 1938 and 1985 using Cycles 3–7 of the National Survey of Family Growth. We find that roughly half of women born in the late 1930s and early 1940s were already sexually active prior to marriage. Especially rapid increases in not delaying sex until marriage occurred for women born between 1942–43 and 1954–55, with subsequent cohorts experiencing less rapid increases and with premarital sex reaching a plateau of roughly 85 to 90 percent for those born after 1962. Our continuous-time competing-risk models illustrate the methodological dangers of using single-decrement procedures for questions such as who did and did not delay sex until marriage. More generally, our findings suggest that the decoupling of sex and marriage was underway well before the so-called "sexual revolution" of the late 1960s and early 1970s.
- Published
- 2017
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4. Reexamining trends in premarital sex in the United States
- Author
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Lawrence L. Wu, Steven Martin, and Paula England
- Subjects
cohort trends ,competing risks ,premarital sex ,single- vs. multiple-decrement analyses ,United States ,Demography. Population. Vital events ,HB848-3697 - Abstract
Background: In a heavily cited paper, Finer (2007) asserted that by age 30, 82Š of US women born 1939-1948 engaged in premarital sex, increasing to 94Š for those born 1969-1978. Using the same data, our age 30 estimates are 55Š and 87Š for women born 1939-1948 and 1969-1978. Our analyses thus document strikingly different levels and trends. Methods: We replicate Finer's single-decrement Kaplan-Meier estimates of premarital sex using Cycles 3-6 of the National Survey of Family Growth, the same data as analyzed by him. We then contrast such single-decrement estimates for both premarital sex and first marriage with estimates of the simple percentages in three states: an origin state in which women begin life as never-married virgins and two destination states for first sex and for first marriage, depending on which occurs first. These analyses provide an empirical illustration of the fact that single-decrement estimates cannot be interpreted as simple percentages for demographic processes involving multiple decrements. Results: Our cohort estimates document increases in the percent of US women who had premarital sex by age 25, rising from 53Š to 75Š, 83Š, and 87Š for those born 1939-1948, 1949-1958, 1959-1968, and 1969-1978, respectively. Contribution: Our cohort analyses reveal sharp increases in premarital sex for US women born between 1939 and 1968, with increases most rapid for those born in the 1940s and 1950s. Our findings also reemphasize a standard lesson from formal demography - that single-decrement life table estimates cannot be interpreted as simple percentages for a multiple-decrement demographic process.
- Published
- 2018
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5. Premarital conceptions, postconception ('shotgun') marriages, and premarital first births: Education gradients in U.S. cohorts of white and black women born 1925-1959
- Author
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Paula England, Emily Fitzgibbons Shafer, and Lawrence L. Wu
- Subjects
education ,nonmarital fertility ,premarital fertility ,social class ,Demography. Population. Vital events ,HB848-3697 - Abstract
BACKGROUND In the U.S. today, premarital first births occur disproportionately to women with low education and income. We lack studies of whether this education gradient was present in cohorts born earlier. OBJECTIVE We examine education differences in the proportion of U.S. white and black women who: (a) experienced a premarital conception taken to term resulting in a first birth, and (b) had a premarital first birth by age 35. Among those experiencing a premarital conception, we examine the association between education and whether women married before the birth. We examine these patterns for birth cohorts born between 1925 and 1959. METHODS We use the 1980, 1985, 1990, and 1995 June Fertility Supplements from the U.S. Current Population Survey to examine cohorts of women born between 1925 and 1959. The survey asked women the dates of their first marriage and their first birth, allowing us to determine premarital conceptions taken to term, and whether the resulting first births occurred within or outside of first marriage. We present descriptive information on the proportion of black and white women in each cohort who experienced the events of interest by age 35. RESULTS For all cohorts, women with low education were generally more likely than their more educated counterparts to experience premarital conceptions and premarital first births. For blacks, but not whites, who experienced a premarital conception that was taken to term, those with more education were more likely to marry before the birth. CONCLUSIONS In the U.S., the concentration of premarital conceptions and premarital first births among less educated women was present for cohorts extending back to those born in 1925.
- Published
- 2012
6. Hazard Versus Linear Probability Difference-in-Differences Estimators for Demographic Processes
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Lawrence L. Wu and Fangqi Wen
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Models, Statistical ,Humans ,Computer Simulation ,Demography ,Probability - Abstract
This study examines the properties of the linear probability difference-in-differences estimator when the data are in fact generated by a single-decrement, continuous-time hazard process. We focus on the textbook case of two groups and two periods in which the control and treatment groups are observed before and after treatment. We provide formal derivations and illustrate matters concretely by reexamining economic studies that have relied on the linear probability difference-in-differences estimator when attempting to obtain estimates of the causal effect of unilateral and no-fault divorce. In particular, we show that the increasing then decreasing pattern of effects found by Wolfers (2006) can be generated by a time-invariant effect of treatment in a proportional hazard setting. We conclude that often implicit assumptions about how the data are generated are an important and necessary component of causal identification.
- Published
- 2022
7. Synchronous gubernacular canals with compound odontoma associated with a calcifying odontogenic cyst and transmigrated canine: An extremely rare event
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Zaid H. Khoury, Jeffery B. Price, John K Brooks, Linh T. Tran, John R. Basile, and Lawrence L. Wu
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Pathology ,medicine.medical_specialty ,business.industry ,Enucleation ,Ghost cell ,Compound Odontoma ,030206 dentistry ,medicine.disease ,Epithelium ,Dentigerous cyst ,Fibrous connective tissue ,03 medical and health sciences ,Calcifying odontogenic cyst ,0302 clinical medicine ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,medicine ,Dentistry (miscellaneous) ,business ,030217 neurology & neurosurgery - Abstract
This article reports the novel incidental concurrences of multiple oral lesions in a 13-year-old boy. Radiographically, an over-retained primary canine was seen with a subjacent mixed radiopacity and transmigrated permanent canine with a suspected dentigerous cyst (each with gubernacular canals). Treatment consisted of enucleation and removal of the impacted canine. The histopathologic findings were compound odontoma containing multiple tooth-like structures and calcifying odontogenic cyst with epithelium containing ghost cells, calcifications and subjacent fibrous connective tissue wall. All cases of odontomas should undergo microscopic assessment for diagnosis and ascertainment of associated pathosis.
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- 2020
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8. More comprehensive sex education reduced teen births: Quasi-experimental evidence
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Nicholas D. E. Mark and Lawrence L. Wu
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Young Adult ,Multidisciplinary ,Contraception ,Adolescent ,Pregnancy ,Sexual Behavior ,Pregnancy in Adolescence ,Humans ,Female ,Sex Education ,Models, Theoretical ,Birth Rate ,United States - Abstract
Women in the United States are much more likely to become mothers as teens than those in other rich countries. Teen births are particularly likely to be reported as unintended, leading to debate over whether better information on sex and contraception might lead to reductions in teen births. We contribute to this debate by providing causal evidence at the population level. Our causal identification strategy exploits county-level variation in the timing and receipt of federal funding for more comprehensive sex education and data on age-specific teen birth rates at the county level constructed from birth certificate natality data covering all births in the United States. Our results show that federal funding for more comprehensive sex education reduced county-level teen birth rates by more than 3%. Our findings thus complement the mixed evidence to date from randomized control trials on teen pregnancies and births by providing population-level causal evidence that federal funding for more comprehensive sex education led to reductions in teen births.
- Published
- 2021
9. Reexamining trends in premarital sex in the United States
- Author
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Steven P. Martin, Lawrence L. Wu, and Paula England
- Subjects
030505 public health ,single- vs. multiple-decrement analyses ,Competing risks ,premarital sex ,01 natural sciences ,United States ,010104 statistics & probability ,03 medical and health sciences ,lcsh:HB848-3697 ,Premarital sex ,lcsh:Demography. Population. Vital events ,cohort trends ,0101 mathematics ,0305 other medical science ,Psychology ,competing risks ,Demography - Abstract
Background: In a heavily cited paper, Finer (2007) asserted that by age 30, 82Š of US women born 1939-1948 engaged in premarital sex, increasing to 94Š for those born 1969-1978. Using the same data, our age 30 estimates are 55Š and 87Š for women born 1939-1948 and 1969-1978. Our analyses thus document strikingly different levels and trends. Methods: We replicate Finer's single-decrement Kaplan-Meier estimates of premarital sex using Cycles 3-6 of the National Survey of Family Growth, the same data as analyzed by him. We then contrast such single-decrement estimates for both premarital sex and first marriage with estimates of the simple percentages in three states: an origin state in which women begin life as never-married virgins and two destination states for first sex and for first marriage, depending on which occurs first. These analyses provide an empirical illustration of the fact that single-decrement estimates cannot be interpreted as simple percentages for demographic processes involving multiple decrements. Results: Our cohort estimates document increases in the percent of US women who had premarital sex by age 25, rising from 53Š to 75Š, 83Š, and 87Š for those born 1939-1948, 1949-1958, 1959-1968, and 1969-1978, respectively. Contribution: Our cohort analyses reveal sharp increases in premarital sex for US women born between 1939 and 1968, with increases most rapid for those born in the 1940s and 1950s. Our findings also reemphasize a standard lesson from formal demography - that single-decrement life table estimates cannot be interpreted as simple percentages for a multiple-decrement demographic process.
- Published
- 2018
- Full Text
- View/download PDF
10. Sexual Abstinence in the United States: Cohort Trends in Abstaining from Sex While Never Married for U.S. Women Born 1938 to 1983
- Author
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Paula England, Steven P. Martin, Nicholas D.E. Mark, and Lawrence L. Wu
- Subjects
lcsh:Social Sciences ,lcsh:H ,Sexual abstinence ,lcsh:Sociology (General) ,NEVER MARRIED ,Cohort ,Premarital sex ,lcsh:HM401-1281 ,General Social Sciences ,Psychology ,Demography - Abstract
In this data visualization, the authors document trends in abstaining from sex while never married for U.S. women born 1938–1939 to 1982–1983. Using data from the six most recent National Surveys of Family Growth, the authors’ estimates suggest that for women born in the late 1930s and early 1940s, 48 percent to 58 percent reported abstaining from sex while never married. Abstinence then declined rapidly among women born in the late 1940s through the early 1960s, leveling off at between 9 percent and 12 percent for more recent birth cohorts. Thus, for U.S. women born between the mid-1960s and the early 1980s, roughly one in nine abstained from sex while never married.
- Published
- 2020
11. Premarital first births: The influence of the timing of sexual onset versus post-onset risks in the United States
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Steven P. Martin and Lawrence L. Wu
- Subjects
Adult ,History ,Time Factors ,Adolescent ,Sexual Behavior ,media_common.quotation_subject ,Article ,First birth ,Young Adult ,Risk-Taking ,Pregnancy ,Risk Factors ,medicine ,Humans ,Longitudinal Studies ,Marriage ,Young adult ,Sexual Abstinence ,Demography ,media_common ,Age Factors ,Abstinence ,medicine.disease ,United States ,Disadvantaged ,Birth order ,Sexual intercourse ,Sexual abstinence ,Female ,Birth Order ,Psychology - Abstract
Motivated by long-standing debates between abstinence proponents and sceptics, we examine how socio-economic factors influence premarital first births via: (i) age at first sexual intercourse and (ii) the risk of a premarital first birth following the onset of sexual activity. Factors associated with an earlier age at first intercourse will imply more premarital first births owing to increased exposure to risk, but many of these same factors will also be associated with higher risks of a premarital first birth following onset. Our analyses confirm previous findings that women from disadvantaged backgrounds are younger at first intercourse and have higher premarital first-birth risks than women from more advantaged backgrounds. However, differences in onset timing have a strikingly smaller influence on premarital first-birth probabilities than do differences in post-onset risks. Our findings thus suggest that premarital first births result primarily from differences in post-onset risk behaviours as opposed to differences in onset timing.
- Published
- 2015
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12. Recent Demographic Trends and the Family
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Lawrence L. Wu
- Subjects
Population ageing ,Exceptionalism ,Sub-replacement fertility ,Political science ,Development economics ,American exceptionalism ,Demographic transition ,Population growth ,World population ,Socioeconomics ,Family life - Abstract
For demographers, perhaps the most stunning set of changes in the family to have emerged over the last century are changes that drove what appeared to have been exploding populations, both in the world at large as well as in individual countries, to changes that now raise the distinct possibility of future population decline in a non-negligible number of nations. These changes are in turn intimately connected to profound changes in family life and most particularly in fertility—trends in how many women, on average, remain childless over their lifetimes, and for those women who become mothers, how many births they will have. What is especially intriguing is “American exceptionalism”—that the United States appears to have been largely immune, at least to date, from demographic trends that are so pronounced and potentially worrisome in so many other advanced industrialized nations. I review what lies behind the shift from exploding populations to the possibility of population decline in at least some parts of the world, and then speculate on what may be the likely sources of why the United States has been an exception to these trends. This then leads me to highly speculative remarks about why two specific groups very often seen in a negative light—immigrants and women who give birth outside of formal marriage—have played an important role in American demographic exceptionalism, and why these groups may likewise continue to be a major factor in why the future of the United States may be far rosier than that of other advanced industrialized nations. However, I caution that this optimistic scenario depends crucially on realizing the social, economic, and demographic potential of these subpopulations. In this essay, I review what demographers regard as perhaps the most striking family trend to have emerged over the last century—a shift from what appeared to be exploding populations, both in the world at large as well as in individual nations, because too many were having too many children, to the emergence in a growing number of nations of what appears to be a shift in which too many are having too few children. Why might we care about these issues? On one hand, Americans tend to regard the issue of who chooses to remain childless, or how many children are born to those who become parents, as very private matters, to be decided by a pregnant woman or the prospective parents. But we also have a collective interest in children because they constitute the future of any society, and this in turn means that we might worry if too many have too few children. What is especially intriguing is “American exceptionalism,” that the United States appears to be largely immune to what is so pronounced and potentially worrisome in a growing number of nations. So how can it be that worries about an exploding world population have turned into worries about too many having too few children? The correct answer, in my view, is that it remains the case that in some nations, too many are having too many children, with these nations continuing to have far too rapid population growth. There is thus a broad consensus among social scientists that these countries would benefit were rapid population growth to be curbed. But in other nations, there have been emerging trends that look as if too many are having too few children; thus, there has been a growing concern, which I share, that these countries would benefit were these trends to be curbed. In this essay, I review what lies behind the shift from exploding populations to the possibility of population decline. I then discuss what are the likely sources of why the United States has been an exception to trends seen in so many other developed nations of the world. This discussion then leads to highly speculative remarks on my part regarding the future of US, which in my view is likely to be substantially more promising than for most other highly industrialized nations. However, I also note that this optimistic scenario depends crucially on realizing the “demographic potential” of subpopulations that have often been viewed as problematic. This leads me to conclude that these issues will pose difficult but critically important challenges in the coming decades. Keywords: demographic potential; dynamics of population change; fertility change; first demographic transition; immigration; Malthus; nonmarital fertility; population aging; sub-replacement fertility
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- 2015
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13. Premarital conceptions, postconception ('shotgun') marriages, and premarital first births
- Author
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Emily Fitzgibbons Shafer, Lawrence L. Wu, and Paula England
- Subjects
education.field_of_study ,White (horse) ,business.industry ,media_common.quotation_subject ,05 social sciences ,Population ,Fertility ,Abortion ,medicine.disease ,Social class ,Miscarriage ,Cohabitation ,5. Gender equality ,050902 family studies ,0502 economics and business ,Cohort ,medicine ,050207 economics ,0509 other social sciences ,education ,business ,Demography ,media_common - Abstract
BACKGROUND In the U.S. today, premarital first births occur disproportionately to women with low education and income. We lack studies of whether this education gradient was present in cohorts born earlier. OBJECTIVE We examine education differences in the proportion of U.S. white and black women who: (a) experienced a premarital conception taken to term resulting in a first birth, and (b) had a premarital first birth by age 35. Among those experiencing a premarital conception, we examine the association between education and whether women married before the birth. We examine these patterns for birth cohorts born between 1925 and 1959. METHODS We use the 1980, 1985, 1990, and 1995 June Fertility Supplements from the U.S. Current Population Survey to examine cohorts of women born between 1925 and 1959. The survey asked women the dates of their first marriage and their first birth, allowing us to determine premarital conceptions taken to term, and whether the resulting first births occurred within or outside of first marriage. We present descriptive information on the proportion of black and white women in each cohort who experienced the events of interest by age 35. RESULTS For all cohorts, women with low education were generally more likely than their more educated counterparts to experience premarital conceptions and premarital first births. For blacks, but not whites, who experienced a premarital conception that was taken to term, those with more education were more likely to marry before the birth. CONCLUSIONS In the U.S., the concentration of premarital conceptions and premarital first births among less educated women was present for cohorts extending back to those born in 1925. 1. Introduction It is well known that, in the U.S., nonmarital births have increased for both whites and blacks (Bachu 1999; Wu 2008; Ventura 2009), and that, in recent decades, women who have nonmarital births are disproportionately of low education and income (Upchurch et al. 2002; Ellwood and Jencks 2004). This paper examines whether the relationship between education and having a premarital conception or first birth existed for earlier U.S. birth cohorts. 2. Data and methods We pool data from the retrospective marital and fertility histories from the June 1980, 1985, 1990, and 1995 U.S. Current Population Surveys (CPS). These June CPS fertility and marital supplements were administered to married women aged 15 or older and never-married women aged 18 or older. We use these data to identify the date (to the nearest month) of first births and first marriages. We assume that all conceptions occurred nine months prior to the birth, and employ a definition of a premaritally conceived but postmarital first birth as a first birth occurring less than seven months after a first marriage.4 This in effect assumes that first births that occur seven or eight months after a first marriage are premature births conceived within marriage. This procedure clearly introduces some classification errors, but provides a standard operational definition of a premarital conception for those conceptions taken to term. Because these data contain no information on pregnancies ending in miscarriage or abortion, our analyses are limited to conceptions taken to term. A further limitation of these data is that they lack information on cohabitation. However, the vast majority of premarital conceptions taken to term and resulting in a first birth to women born between 1925 and 1959 occurred in periods when abortion and cohabitation were relatively uncommon. Unweighted estimates are presented throughout. We limit our analysis to first marriages and first births. For the birth cohorts we examine, about three out of four premarital conceptions taken to term involved first births, and about nine out of ten marriages occurring between a premarital conception and a first birth were first marriages (results not shown). …
- Published
- 2012
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14. 6. Effects of Exposure on Prevalence and Cumulative Relative Risk: Direct and Indirect Effects in a Recursive Hazard Model
- Author
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Lawrence L. Wu and Steven P. Martin
- Subjects
education.field_of_study ,Sociology and Political Science ,business.industry ,Proportional hazards model ,Population ,Affect (psychology) ,Hazard ,Relative risk ,Statistics ,Cohort ,Covariate ,Medicine ,business ,education ,Parametric statistics - Abstract
This paper outlines decomposition methods for assessing how exposure affects prevalence and cumulative relative risk. Let x denote a vector of exogenous covariates and suppose that a single dimension of time t governs two event processes T1 and T2. If the occurrence of the event T1 determines entry into the risk of the event T2, then subgroup variation in T1 will affect the prevalence T2, even if subgroups in the population are otherwise identical. Although researchers often acknowledge this phenomenon, the literature has not provided procedures to assess the magnitude of an exposure effect of T1 on the prevalence of T2. We derive decompositions that assess how variation in exposure generated by direct and indirect effects of the covariates x affect measures of absolute and relative prevalence of T2. We employ a parametric but highly flexible specification for baseline hazard for the T1 and T2 processes and use the resulting parametric proportional hazard model to illustrate the direct and indirect effects of family structure when T1 is age at first sexual intercourse and T2 is age at a premarital first birth for data on a cohort of non-hispanic white U.S. women.
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- 2009
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15. No trend in the intergenerational transmission of divorce
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Jui-Chung fnAllen Li and Lawrence L. Wu
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Adult ,Male ,Logistic regression ,law.invention ,Divorce ,Risk Factors ,law ,Economics ,Humans ,Proportional Hazards Models ,Demography ,Intergenerational transmission ,Models, Statistical ,Marital Status ,Proportional hazards model ,Articles ,United States ,General Social Survey ,Logistic Models ,Transmission (mechanics) ,Social Class ,Intergenerational Relations ,Educational Status ,Regression Analysis ,Female - Abstract
Previous studies on trends in the intergenerational transmission of divorce have produced mixed findings, with two studies (McLanahan and Bumpass 1988; Teachman 2002) reporting no trend in divorce transmission and one study (Wolfinger 1999) finding that divorce transmission has weakened substantially. Using a stratified Cox proportional hazard model, we analyze data from the National Survey of Families and Households and find no evidence for any trend in divorce transmission. To reconcile apparent differences in results, we note that the General Social Survey data used by Wolfinger lack information on marital duration, permitting analysis only for whether respondents have divorced by interview. As a result, an apparent decline in divorce transmission could be due to inadequate adjustments for the longer exposures to risk by earlier marriage cohorts, yielding a higher probability of divorce by interview for earlier cohorts relative to more recent cohorts even if divorce risks are identical across all marriage cohorts. We confirm this possibility by using a series of discrete-time hazard logistic regressions to investigate the sensitivity of estimates of trends in divorce transmission to different adjustments for exposure to risk. We conclude that there has been no trend in the intergenerational transmission of divorce.
- Published
- 2008
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16. Cohort estimates of nonmarital fertility for U.S. Women
- Author
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Lawrence L. Wu
- Subjects
Adult ,Adolescent ,media_common.quotation_subject ,Population ,Ethnic group ,Marital separation ,Fertility ,White People ,Nonmarital fertility ,Residence Characteristics ,Humans ,Life Tables ,education ,Retrospective Studies ,Demography ,media_common ,Family Characteristics ,education.field_of_study ,Marital Status ,Data Collection ,Retrospective cohort study ,Articles ,Middle Aged ,United States ,Black or African American ,Vital Statistics ,Geography ,Cohort ,Marital status ,Female - Abstract
Historical trends in U.S. nonmarital fertility have been compiled almost exclusively from vital statistics on births. This paper complements this historical record by providing cohort estimates of nonmarital fertility for cohorts of U.S. women spanning approximately 50 years of cohort experience. Life table estimates using retrospective marital and fertility histories in the June 1980, 1985, 1990, and 1995 Current Population Surveys reveal nonnegligible levels of nonmarital fertility historically. For women born between 1925 and 1929, nearly 1 in 10 had at least one nonmarital birth by age 30. For women born between 1965 and 1969, more than 1 of 4 had one or more nonmarital births by age 30, with roughly 1 of 5 white, 3 of 5 black, and 1 in 3 Hispanic women having at least one nonmarital birth by age 30. Life table estimates reveal a twofold increase between ages 20 and 30 in the percentage of women with at least one child outside of formal marriage for all cohorts of white and Hispanic women, and an increase of roughly two-thirds for all cohorts of black women. I also document qualitative differences in nonmarital fertility by race/ethnicity, with the percentage of nonmarital births following a divorce or marital separation for white women approximately twice that for black or Hispanic women. Finally, I introduce a new measure, the cohort nonmarital fertility ratio (CNMFR), which provides a cohort complement to the standard period nonmarital fertility ratio. Conservative estimates reveal a roughly threefold increase in the CNMFR for women born from 1925-1929 to 1950-1954 for both whites and blacks, despite substantially higher levels of nonmarital fertility among black women. Overall, these findings reveal surprisingly high levels of nonmarital fertility for women born since the 1920s and confirm that nonmarital fertility has become an increasingly substantial component of overall U.S. fertility
- Published
- 2008
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17. Book Review: Nonparametric Simple Regression: Smoothing Scatterplots. By John Fox. Volume 130, Quantitative Applications in the Social Sciences. Thousand Oaks, CA: Sage, 2000. 83 pp. $14.95; Local Regression and Likelihood. By Clive Loader. New York: Springer, 1999. 290 pp. $79.95
- Author
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Lawrence L. Wu
- Subjects
Loader ,Sociology and Political Science ,Statistics ,Nonparametric statistics ,Local regression ,Simple linear regression ,Psychology ,Social Sciences (miscellaneous) ,Smoothing ,Volume (compression) - Published
- 2003
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18. Questions in Time: Investigating the Structure and Dynamics of Unfolding Classroom Discourse
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Lawrence L. Wu, Susie Zeiser, Martin Nystrand, Adam Gamoran, and Daniel A. Long
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Structure (mathematical logic) ,Linguistics and Language ,Dialogic ,Dynamics (music) ,Communication ,Discourse analysis ,Contrast (statistics) ,Academic achievement ,Affect (linguistics) ,Interpersonal communication ,Psychology ,Language and Linguistics ,Linguistics - Abstract
In the 1st-ever use of event-history analysis to investigate discourse processes quantitatively, this study recasts understanding of discourse in terms of the (a) antecedents and (b) consequences of discourse participant "moves" as they (c) affect the inertia of the discourse and accordingly structure unfolding discourse processes. The method is used to compute the probabilities of the effects of particular discourse moves on subsequent discourse patterns and to measure and systematically contrast static (macrosocial) and dynamic (microsocial) conditions prompting and sustaining dialogic discourse. Theoretically, the authors draw on Russian scholar Mikhail Bakhtin's epistemological distinctions between monologic and dialogic discourse to identify pedagogically rich sequences of teacher-student interaction as dialogic spells and discussion, which the authors' previous work has shown to contribute to achievement. Empirically, the authors examine data collected in hundreds of observations of more than 200 8t...
- Published
- 2003
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19. Fertility of Single and Cohabiting Women
- Author
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Lawrence L. Wu
- Subjects
Economic growth ,Cohabitation ,Nonmarital fertility ,Empirical research ,media_common.quotation_subject ,Current theory ,Fertility ,Demographic economics ,Sociology ,Single mothers ,Socioeconomic status ,Disadvantage ,media_common - Abstract
This article provides an overview of current theory and empirical research on the fertility of single or cohabiting parents, with particular emphasis on research in the fields of demography, economics, history, and sociology. Topics covered include: historical shifts in usage concerning the terms employed to refer to these behaviors; measurement issues that arise in the study of nonmarital fertility; demographic trends; functionalist, historical, and policy literatures; empirical research to date on the socioeconomic determinants, including within-country and cross-national variation in the association between nonmarital fertility and socioeconomically disadvantage; consequences for women and children; and the continuing conceptual and theoretical challenges posed by the study of nonmarital fertility.
- Published
- 2015
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20. Race Differences in Family Experience and Early Sexual Initiation: Dynamic Models of Family Structure and Family Change
- Author
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Elizabeth Thomson and Lawrence L. Wu
- Subjects
Sexually transmitted disease ,Sexual intercourse ,Arts and Humanities (miscellaneous) ,Family structure/dynamics ,Single-Parent Family ,Anthropology ,Sociology of the family ,Human sexuality ,Psychology ,Nuclear family ,Social Sciences (miscellaneous) ,Family life ,Developmental psychology - Abstract
We examine the effects of family structure on age at first sexual intercourse before marriage for a recent cohort of women. Previous research on the linkage between family structure and sexual initiation has employed relatively crude measures of family structure-typically a snapshot of the respondent's family structure at age 14. We use retrospective parent histories from the 1979-1987 National Longitudinal Survey of Youth to construct dynamic measures of family structure, using information on the number and types of parents in the respondent's household between birth and age 18. We use these measures in proportional hazard models to test the effects of prolonged exposure to a single-mother family, prolonged absence of a biological father, parental presence during adolescence, and family turbulence. For White women, age-specific rates of first sexual intercourse are significantly and positively associated with the number of family transitions; for Black women, age-specific rates are significantly and positively associated with having resided in a mother-only or father-only family during adolescence. Net of other effects of family structure, we find no significant effects for White or Black women of being born out of wedlock, prolonged exposure to a single-mother family, or prolonged absence of a biological father. Our results for White women are consistent with a turbulence hypothesis, whereas for Black women our results suggest the importance of family structure during adolescence. For neither White nor Black women are our results consistent with hypotheses positing earlier initiation of sexual activity for women with prolonged exposure to a single-mother or fatherabsent family. Key Words: family structure dynamics, father abuse, premarital sexual initiation, racial and ethnic differences, single mothers. Numerous studies have found that sexual activity occurs earlier for adolescents who experienced a parental divorce or who have an absent father relative to those who resided with both biological parents (Billy, Brewster, & Grady, 1994; Booth, Brinkerhoff, & White, 1984; Brewster, 1994; Flewelling & Bauman, 1990; Hogan & Kitagawa, 1985; Inazu & Fox, 1980; Newcomer & Udry, 1984; Thornton & Camburn, 1987; Trent & South, 1992; Weinstein & Thornton, 1989; Whitbeck, Simons, & Goldberg, 1996). This empirical association is important because of the increasing prevalence of single-parent families and because early sexual activity may increase the risk of contraceptive nonuse, sexually transmitted disease, teen pregnancy, teen motherhood, and out-of-wedlock childbearing. Despite substantial empirical research, the mechanisms linking family structure to the initiation of sexual activity are not well understood. One difficulty has been the reliance of much previous research on relatively crude measures of family structure-typically a child's family structure at age 14. Such snapshot measures say little about what aspect of family structure influences adolescent behavior, in part because they conflate differences in an adolescent's family trajectory that are, we argue, important in explaining the timing of first intercourse. In addition, snapshot measures ignore the increasingly fluid nature of family life accompanying increases in nonmarital childbearing, divorce, and remarriage. We use data from the National Longitudinal Survey of Youth (NLSY) to examine age-specific rates of first sexual intercourse before first marriage for a nationally representative sample of women who entered adolescence during the late 1970s and early 1980s. We exploit detailed family histories available in the NLSY to estimate the effects of the number of family transitions, exposure to specific types of families, and family structure during adolescence. These results help shed light on how parental socialization, parental supervision during adolescence, and family turbulence may have affected the timing of sexual initiation for this cohort of women. …
- Published
- 2001
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21. Some Comments on 'Sequence Analysis and Optimal Matching Methods in Sociology: Review and Prospect'
- Author
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Lawrence L. Wu
- Subjects
0504 sociology ,Sociology and Political Science ,Professional career ,Research methodology ,05 social sciences ,050602 political science & public administration ,050401 social sciences methods ,Ethnology ,Sociology ,Humanities ,Social Sciences (miscellaneous) ,0506 political science - Abstract
Apres un rappel methodologique de l'analyse sequentielle, l'A. expose les forces et les faiblesses de cette technique. Il emet un jugement critique sur les avis de Abbott et Tsay a propos de l'application de l'analyse sequentielle aux carrieres professionnelles. En particulier, l'A. met l'accent sur la question de l'asymetrie des relations unissant les differentes sequences composant une carriere professionnelle. Ce probleme souleve la question des couts en jeu dans les transitions entre les sequences. L'A. defend la methode de l'analyse historique evenementielle et expose en quoi son avis diverge de celui d'Abbott et Tsay
- Published
- 2000
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22. Cohort trends in premarital first births: what role for the retreat from marriage?
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Paula England, Lawrence L. Wu, and Emily Fitzgibbons Shafer
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Male ,Pregnancy ,Illegitimacy ,business.industry ,media_common.quotation_subject ,Sexual Behavior ,Statistics as Topic ,Fertility ,medicine.disease ,United States ,Article ,First birth ,Cohort Studies ,Cohort ,medicine ,Premarital sex ,Humans ,Female ,Birth Order ,Marriage ,business ,Demography ,media_common - Abstract
We examine cohort trends in premarital first births for U.S. women born between 1920 and 1964. The rise in premarital first births is often argued to be a consequence of the retreat from marriage, with later ages at first marriage resulting in more years of exposure to the risk of a premarital first birth. However, cohort trends in premarital first births may also reflect trends in premarital sexual activity, premarital conceptions, and how premarital conceptions are resolved. We decompose observed cohort trends in premarital first births into components reflecting cohort trends in (1) the age-specific risk of a premarital conception taken to term; (2) the age-specific risk of first marriages not preceded by such a conception, which will influence women’s years of exposure to the risk of a premarital conception; and (3) whether a premarital conception is resolved by entering a first marriage before the resulting first birth (a “shotgun marriage”). For women born between 1920–1924 and 1945–1949, increases in premarital first births were primarily attributable to increases in premarital conceptions. For women born between 1945–1949 and 1960–1964, increases in premarital first births were primarily attributable to declines in responding to premarital conceptions by marrying before the birth. Trends in premarital first births were affected only modestly by the retreat from marriages not preceded by conceptions—a finding that holds for both whites and blacks. These results cast doubt on hypotheses concerning “marriageable” men and instead suggest that increases in premarital first births resulted initially from increases in premarital sex and then later from decreases in responding to a conception by marrying before a first birth.
- Published
- 2013
23. Race and Unemployment: Labor Market Experiences of Black and White Men, 1968-1988
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Lawrence L. Wu, Marta Tienda, and Franklin D. Wilson
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Organizational Behavior and Human Resource Management ,White (horse) ,Sociology and Political Science ,Earnings ,media_common.quotation_subject ,05 social sciences ,0211 other engineering and technologies ,Ethnic group ,021107 urban & regional planning ,Gender studies ,02 engineering and technology ,Educational attainment ,0502 economics and business ,Unemployment ,Labor market segmentation ,Position (finance) ,Demographic economics ,Sociology ,Salary ,050207 economics ,media_common - Abstract
This article addresses two questions: First, why is Black unemployment persistently higher than White unemployment? Second, how can this fact be reconciled with narrowing Black/White differentials in educational attainment, occupational position, and earnings? We show that the persistent racial gap in unemployment is due to differential access to employment opportunities by region, occupational placement, labor market segmentation by race, and labor market discrimination. Our findings showing that the racial gap in unemployment is greatest for college-educated men and are consistent with the view that Blacks still encounter barriers to employment in the labor market.
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- 1995
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24. Event History Analysis
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Lawrence L. Wu
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education.field_of_study ,Proportional hazards model ,media_common.quotation_subject ,Population ,Social change ,Omitted-variable bias ,Genealogy ,Econometric model ,Cohabitation ,Unemployment ,Life course approach ,Sociology ,education ,Demography ,media_common - Abstract
VOLUME 1 Overviews Event History Models for Life Course Analysis - Lawrence Wu Nonparametric Estimation: Theory Nonparametric Estimation from Incomplete Observations - E.L. Kaplan and Paul Meier Theory and Applications of Hazard Plotting for Censored Failure Data - Wayne Nelson Nonparametric Inference for a Family of Counting Processes - Odd Aalen A Flaw in Actuarial Exposed-to-Risk Theory - Jan Hoem Issues in Smoothing Empirical Hazards - Lawrence Wu Nonparametric Estimation: Applications The Incidence of Divorce within Cohorts of American Marriages Contracted since the Civil War - Samuel Preston and John McDonald Slipping Into and Out of Poverty: The Dynamics of Spells - Mary Jo Bane and David Ellwood Trends in Cohabitation and Implications for Children's Family Contexts - Larry Bumpass and Hsien-Hen Lu Cohort Estimates of Nonmarital Fertility - Lawrence Wu The Cox Model: Theory Regression Models and Life Tables - D. R. Cox Understanding Cox's Regression Model: A Martingale Approach - Richard Gill The Cox Model: Applications Unemployment over the Life Cycle: Racial Differences and the Effect of Changing Economic Conditions - Thomas DiPrete Entry into Marriage and Parenthood by Young Men and Women: The Influence of Family Background - Robert Michael and Nancy Brandon Tuma Parametric Models: Theory On the Nature of the Function Expressive of the Law of Human Mortality - Benjamin Gompertz The Distribution by Age of the Frequency of First Marriage - Ansley Coale and Donald McNeil The Process of Entry into First Marriage - Gudmund Hernes A Comparison of the 'Sickle Function' with Alternative Stochastic Models of Divorce Rates - Andreas Diekmann and Peter Mitter VOLUME 2 Parametric Models: Applications The Divergence of Black and White Marriage Patterns - Neil Bennett, David Bloom and Patricia Craig Social Inheritance of Divorce in Postwar Germany - Andreas Diekman and Henriette Engelhardt Legal Environments and Organizational Governance: The Expansion of Due Process in the American Workplace - Lauren Edelman Contextual Effects in the Classroom: The Impact of Ability Groups on Student Attention - Diane Felmlee and Donna Eder The Liability of Newness: Age Dependence in Organizational Death Rates - John Freeman, Glenn Carroll and Michael Hannan Income and Independence Effects on Marital Dissolution: Results from the Seattle and Denver Income-Maintenance Experiments - Michael Hannan, Nancy Brandon Tuma and Lyle Groeneveld Diverging Fertility Among U.S. Women Who Delay Childbearing - Steven Martin Rewards, Resources and the Rate of Mobility: A Nonstationary Multivariate Stochastic Model - Nancy Brandon Tuma Work as a Turning Point in the Life Course of Criminals: A Duration Model of Age, Employment, and Recidivism - Christopher Uggen Time-Varying Covariates: Applications Social Change, the Social Organization of Families and Fertility Limitation - William Axinn and Scott Yabiku Principles of Cohesion in Cohabitation and Marriage - Julie Brines and Kara Joyner An Event History Analysis of Racial Rioting in the 1960s - Daniel Myers Questions in Time: Investigating the Structure and Dynamics of Unfolding Classroom Discourse - Martin Nystrand, Lawrence Wu, Adam Gamoran, Susie Zeiser and Daniel Long Family Structure and the Risk of a Premarital Birth - Lawrence Wu and Brian Martinson Effects of Family Instability, Income and Income Instability on the Risk of a Premarital Birth - Lawrence Wu VOLUME 3 Discrete-Time Models: Theory Discrete-Time Methods for the Analysis of Event Histories - Paul Allison Change and Stability in Educational Stratification - Robert Mare Discrete-Time Models: Applications Mothers, Children, and Cohabitation: The Intergenerational Effects of Attitudes and Behavior - William Axinn and Arland Thornton Two Decades of Family Change: The Shifting Economic Foundations of Marriage - Megan Sweeney No Trend in the Intergenerational Transmission of Divorce - Jui-Chung Allen Li and Lawrence Wu Another Look at the Stratification of Educational Transitions: The Logistic Response Model with Partial Proportionality Constraints - Robert Hauser and Megan Andrew Unobserved Heterogeneity: Theory Heterogeneity's Ruses: Some Surprising Effects of Selection on Population Dynamics - James Vaupel and Anatoli Yashin A Method for Minimizing the Impact of Distributional Assumptions in Econometric Models for Duration Data - James Heckman and Burton Singer Heterogeneity, Omitted Variable Bias and Duration Dependence - Gary Chamberlain Simultaneous Equations for Hazards: Marriage Duration and Fertility Timing - Lee Lillard Kindred Lifetimes: Frailty Models in Population Genetics - J.W. Vaupel Unobserved Heterogeneity: Applications Interrelated Family-Building Behaviors: Cohabitation, Marriage, and Nonmarital Conception - Michael Brien, Lee Lillard and Linda Waite Does Unemployment Cause Future Unemployment? Definitions, Questions, and Answers from a Continuous Time Model of Heterogeneity and State Dependence - James Heckman and George Borjas New Evidence on the Timing and Spacing of Births - James Heckman, V. Joseph Hotz and James Walker VOLUME 4 Competing Risks: Theory A Nonidentifiability Aspect of the Problem of Competing Risks - A Tsiatis The Identifiability of the Competing Risks Model - James Heckman and Bo Honore Competing Risks: Applications Drug Use and Other Determinants of Premarital Pregnancy and Its Outcome: A Dynamic Analysis of Competing Events - Kazuo Yamaguchi and Denise Kandel Social Capital and International Migration: A Test Using Information on Family Networks - Alberto Palloni, Douglas Massey, Miguel Ceballos, Kristin Espinosa and Michael Spittel Nonproportionalmodels Local Hazard Models - Lawrence Wu and Nancy Brandon Tuma Log-Multiplicative Models for Discrete-Time Discrete-Covariate Event History Data - Yu Xie An Approach to Nonparametric Regression for Life History Data using Local Linear Fitting - Gang Li and Hani Doss Trajectories of Fetal Loss in the Czech Republic - Elwood Carlson, Jan Hoem and Jitka Rychtarikova Left Truncation and Left Censoring On the Treatment of Interrupted Spells and Initial Conditions in Event History Analysis - Alfred Hamerle The Distribution of Single Spell Duration Data - Geert Ridder Models for Clustered, Sequential, and Diffusion Processes Estimating a Multivariate Proportional Hazards Model for Clustered Data Using the EM Algorithm, with an Application to Child Survival in Guatemala - Guang Guo and German Rodriguez Multivariate Survivorship Analysis Using Two Cross-Sectional Samples - Mark Hill A Nested Frailty Model for Survival Data, With an Application to the Study of Child Survival in Northeast Brazil - Narayan Sastry Spatial and Temporal Heterogeneity in Diffusion - David Strang and Nancy Brandon Tuma Effects of Exposure on Prevalence and Cumulative Risk: Direct and Indirect Effects in a Recursive Hazard Model - Lawrence Wu and Steven Martin
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- 2012
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25. EFFECTS OF EXPOSURE ON PREVALENCE AND CUMULATIVE RELATIVE RISK: DIRECT AND INDIRECT EFFECTS IN A RECURSIVE HAZARD MODEL
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Lawrence L, Wu and Steven P, Martin
- Subjects
Article - Abstract
This paper outlines decomposition methods for assessing how exposure affects prevalence and cumulative relative risk. Let x denote a vector of exogenous covariates and suppose that a single dimension of time t governs two event processes T(1) and T(2). If the occurrence of the event T(1) determines entry into the risk of the event T(2), then subgroup variation in T(1) will affect the prevalence T(2), even if subgroups in the population are otherwise identical. Although researchers often acknowledge this phenomenon, the literature has not provided procedures to assess the magnitude of an exposure effect of T(1) on the prevalence of T(2). We derive decompositions that assess how variation in exposure generated by direct and indirect effects of the covariates x affect measures of absolute and relative prevalence of T(2). We employ a parametric but highly flexible specification for baseline hazard for the T(1) and T(2) processes and use the resulting parametric proportional hazard model to illustrate the direct and indirect effects of family structure when T(1) is age at first sexual intercourse and T(2) is age at a premarital first birth for data on a cohort of nonhispanic white U.S. women.
- Published
- 2010
26. Parent Histories
- Author
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Brian C. Martinson and Lawrence L. Wu
- Subjects
education.field_of_study ,Family structure ,05 social sciences ,Population ,050401 social sciences methods ,Early life ,0504 sociology ,050902 family studies ,Data quality ,Respondent ,Snapshot (computer storage) ,0509 other social sciences ,Family history ,education ,Psychology ,Developed country ,Social Sciences (miscellaneous) ,Demography - Abstract
Most studies that examine the effects of family structure have employed relatively crude measures, typically a snapshot of family intactness at age 14. In this article, we use data from the National Survey of Families and Households to examine (a) how one might better construct measures of family structure that reflect change during early life and (b) what analytical and empirical opportunities are available when the data provide a more complete parent history. We draw four conclusions. First, a substantial fraction of children have extremely diverse parental situations, even though the majority of children live in intact families. Snapshot measures understate greatly the dynamic complexities of a respondent's parental situation. Second, the parent histories of respondents provide a rich but complicated set of longitudinal data and the complexity of these data makes it infeasible to adopt a data-driven approach to summarize family structure over the early lives of children. It is therefore useful to adopt a more theoretical approach in identifying salient dimensions of a respondent's parent history. Third, existing theoretical perspectives conceptualize the influences of parents in markedly different ways. These contrasting views, in turn, imply quite distinct empirical measures. Finally, more informative measures of family structure may allow one to adjudicate between alternative hypotheses of family structure in ways not possible with snapshot measures.
- Published
- 1992
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27. Assessing Bias and Fit of Global and Local Hazard Models
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Nancy Brandon Tuma and Lawrence L. Wu
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Hazard (logic) ,education.field_of_study ,Diagnostic methods ,Sociology and Political Science ,Computer science ,Age at first marriage ,05 social sciences ,Gompertz function ,Hazard ratio ,Population ,Nonparametric statistics ,Event history ,050401 social sciences methods ,0506 political science ,0504 sociology ,Statistics ,050602 political science & public administration ,Econometrics ,education ,Social Sciences (miscellaneous) - Abstract
This article assesses the bias and fit of a hazard rate model by comparing predicted and nonparametric estimates of survivor probabilities. These comparisons also generate several diagnostic displays for event history data. We illustrate these diagnostic methods for several global and local hazard models using data on age at first marriage for women from the June 1980 Current Population Survey. Our results suggest that a nonproportional local Gompertz model performs better than other models we examined.
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- 1991
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28. Event History Models for Life Course Analysis
- Author
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Lawrence L. Wu
- Subjects
Social group ,Duration (philosophy) ,Transition (fiction) ,Life course approach ,Hogan ,Single mothers ,Psychology ,Social psychology ,Structural holes ,Focus (linguistics) - Abstract
The questions posed by life course researchers often differ in fundamental ways from those posed by sociologists, developmental psychologists, or economists (Elder, 1998; Mayer & Tuma, 1990). For example, life course researchers often focus analytic attention on transitions marking adolescence or early adulthood and the roles and statuses accompanying such transitions (Hogan & Astone, 1986; Modell, Furstenberg, & Hershberg, 1976; Shanahan, 2000). Prototypical questions along these lines include whether certain social groups experience a more rapid transition to adulthood or whether the timing of such transitions (or the duration spent in selected life course statuses) has changed for successive cohorts (Winsborough, 1980). As Mayer and Tuma (1990) note, work in this vein often implicitly conceives of social structure as arising out of individual experiences of varying duration, as opposed to alternative perspectives that see social structure in terms of collectivities of persons with particular fixed attributes (Blau, 1977), as generated from relational networks (and resulting “structural holes”) among individual actors (White, Boorman, & Breiger, 1976) or from the aggregate behavior of rational actors (Becker, 1991).
- Published
- 2007
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29. Stability of Marital and Cohabiting Unions Following a First Birth
- Author
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Lawrence L. Wu and Kelly Musick
- Subjects
union dissolution ,Cohabitation ,social sciences ,Management, Monitoring, Policy and Law ,behavioral disciplines and activities ,Parental separation ,First birth ,childbearing ,National Survey of Family Growth ,Economics ,Childbirth ,union stability ,marriage ,Demography - Abstract
In a recent paper, Manning, Smock, and Majumdar (2004) examine the stability of marital and cohabiting unions from the perspective of children and find that children born to cohabiting parents are more likely to experience a parental separation than children born to married parents. They find, further, that subsequent marriage among cohabiting parents is associated with increases in the stability of these families, particularly among whites. We rely on the same data, the 1995 National Survey of Family Growth, to extend their findings. We focus on family stability from the perspective of the couple, estimating the risks of union dissolution following a first birth. Our empirical results complement Manning et al.'s by modeling four distinct trajectories of cohabitation and marriage around the time of the first birth and comparing the dissolution risks associated with each. We focus particular attention on comparing the stability of cohabiting couples who marry before a first birth and those who marry after a first birth. For these couples, we find that the ordering of cohabitation, marriage, and childbirth is not associated with union stability, and we interpret this to suggest that many cohabiting couples jointly plan marriage and childbirth.
- Published
- 2006
30. Historical Roots of Family Diversity
- Author
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Jui-Chung Allen Li and Lawrence L. Wu
- Subjects
Ecology ,media_common.quotation_subject ,Sociology ,Diversity (politics) ,media_common - Published
- 2005
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31. Composition and decomposition in nonmarital fertility
- Author
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Lawrence L. Wu
- Subjects
education.field_of_study ,Nonmarital fertility ,media_common.quotation_subject ,Population ,Economics ,Marital status ,Fertility ,education ,Demography ,media_common - Abstract
Ermisch (2009) criticized Gray, Stockard, and Stone (2006), arguing that they incorrectly tested a model positing a nonlinear relationship between the nonmarital fertility ratio and the proportion of unmarried women. I identify a different problem, which is that even if this model were to hold for a particular population, it would not in general hold for subgroups of this population; likewise, were it to hold for subgroups, it would not hold for aggregations of these subgroups.
- Published
- 2009
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32. Comparing Data Quality of Fertility and First Sexual Intercourse Histories
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Steven P. Martin, Daniel A. Long, and Lawrence L. Wu
- Subjects
Organizational Behavior and Human Resource Management ,Economics and Econometrics ,Strategy and Management ,media_common.quotation_subject ,Fertility ,Survey methodology ,Sexual intercourse ,Management of Technology and Innovation ,Data quality ,Statistics ,National Survey of Family Growth ,Respondent ,Survey data collection ,National Longitudinal Surveys ,Psychology ,Demography ,media_common - Abstract
This paper evaluates the data quality of two demographic variables in light of hypotheses on respondent recall from the literature on survey methodology. An emerging consensus in this literature is that recall of the timing of an event declines with recall duration unless the dating of an event is frequently "rehearsed." We provide empirical evidence consistent with this hypothesis by assessing the quality of demographic data on two event history variables as supplied by female respondents. A first outcome concerns the interval between a first and second birth. We assess examine birth intervals using birth registration data from the Vital Statistics on Natality (VSN) and individual-level survey data from the 1990 June Current Population Survey (CPS), the 1979-93 waves of the National Longitudinal Survey of Youth (NLSY), and the 1988 National Survey of Family Growth (NSFG). Overall, we find relatively little variation in the quality of birth interval data across these four surveys, with onie exception-CPS data in which responses have been allocated. A second demographic variable is age at first sexual intercourse. We engage in several analyses of this variable. First, we use NLSY data to analyze discrepan
- Published
- 2001
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33. Effects of Family Instability, Income, and Income Instability on the Risk of a Premarital Birth
- Author
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Lawrence L. Wu
- Subjects
education.field_of_study ,Sociology and Political Science ,Poverty ,Permanent income hypothesis ,Population ,Economics ,National Longitudinal Surveys ,Family income ,Social class ,education ,Developed country ,Socioeconomic status ,Demography - Abstract
In this study I contrast hypotheses about the effects of family structure on premarital birth risks with three income hypotheses: (1) a low income hypothesis--that the risk of a premarital birth is higher for women from disadvantaged economic backgrounds because they possess fewer or less attractive economic opportunities; (2) a permanent income and transitory income hypothesis--that uncertainties generated by unexpected fluctuations in family income increase premarital birth risks net of absolute income levels; and (3) an income level and income change hypothesis--that downward trends in family income reflect worsening socioeconomic opportunities that increase premarital birth risks net of absolute income levels. I use prospective income and retrospective parental histories in the [U.S.] National Longitudinal Survey of Youth to determine if the effect of family instability...is an artifact of low unstable or declining income in the family of origin. (EXCERPT)
- Published
- 1996
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34. Family Structure and the Risk of a Premarital Birth
- Author
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Lawrence L. Wu and Brian C. Martinson
- Subjects
education.field_of_study ,Sociology and Political Science ,media_common.quotation_subject ,Population ,Socialization ,Fertility ,Child development ,Developmental psychology ,Marital status ,Psychology ,education ,Construct (philosophy) ,Developed country ,Social control ,media_common - Abstract
The authors examine three hypotheses regarding the impact of a womans family characteristics between birth and age 19 on her chances of having a premarital birth. "We construct dynamic measures of family structure using parent-history data from the [U.S.] National Survey of Families and Households. We use these data to examine the relative importance of family events during childhood changes in family structure during childhood and adolescence and durations spent in the modal family structures experienced by respondents while growing up. Our results suggest that these dynamic measures capture both theoretically and empirically distinct dimensions of family experience and that distinguishing between these dimensions provides sufficient analytical leverage to test the socialization social control and instability and change hypotheses." (EXCERPT)
- Published
- 1993
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35. Local Hazard Models
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Nancy Brandon Tuma and Lawrence L. Wu
- Subjects
Hazard (logic) ,education.field_of_study ,Sociology and Political Science ,Population ,Hazard ratio ,Gompertz function ,Nonparametric statistics ,Covariate ,Statistics ,Econometrics ,Piecewise ,education ,Parametric statistics ,Mathematics - Abstract
We introduce a class of local hazard models that maintain parametric assumptions locally rather than globally. These models allow estimation of a flexible baseline hazard rate and nonproportional covariate effects. Recently developed local likelihood methods which generalize maximum likelihood methods can be used to estimate these models. We illustrate these techniques by estimating two local hazard models of first marriage--a local exponential model and a local Gompertz model--from data in the June 1980 [U.S.] Current Population Survey. We also compare results of the local hazard models with those of Coxs model an exponential model a piecewise exponential model and a piecewise Gompertz model. Estimates for the local exponential and local Gompertz models agree closely with nonparametric estimates for various subgroups. Moreover results of the local models provide interesting substantive insights into the process of first marriage that are not easily obtained from global models. (EXCERPT)
- Published
- 1990
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36. Robust M-Estimation of Location and Regression
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Lawrence L. Wu
- Subjects
Estimation ,Sociology and Political Science ,Statistics ,Regression analysis ,Regression ,Mathematics - Published
- 1985
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37. Issues in Smoothing Empirical Hazard Rates
- Author
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Lawrence L. Wu
- Subjects
Hazard (logic) ,education.field_of_study ,Sociology and Political Science ,Computer science ,Population ,Hazard ratio ,Estimator ,Demographic analysis ,Statistics ,Econometrics ,Log-linear model ,education ,Smoothing ,Parametric statistics - Abstract
This chapter presents a smooth estimator of the hazard rate using a variable-span running loglinear specification that allows investigators to maintain only mild assumptions about the functional forms of population heterogeneity and time inhomogeneity in the rate. This estimator is useful both in exploratory data analyses (EDA) and in checking parametric assumptions. Examples drawn from data on the transition to first marriage for women in the U.S. show that several common parametric assumptions are violated in these data and illustrate that the smoothed hazard estimator can yield important insights not easily obtained from more conventional methods. (EXCERPT)
- Published
- 1989
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38. Understanding Toscanini: How He Became an American Culture-God and Helped Create a New Audience for Old Music
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Michele Lamont, Lawrence L. Wu, and Joseph Horowitz
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Sociology and Political Science - Published
- 1989
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39. Local Blockmodel Algebras for Analyzing Social Networks
- Author
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Lawrence L. Wu
- Subjects
Sociology and Political Science ,Sociology ,Social relation ,Epistemology ,Theme (narrative) - Abstract
Roles and ways of thinking about roles have been a major concern of sociologists. One common approach to roles conceptualizes and analyzes them within networks of multiple social relations (see, for example, Radcliffe-Brown, 1940; Barnes, 1954; Nadel, 1957; Mayer, 1966; Kapferer, 1969; Mitchell, 1969; Bott, 1971; Boissevain, 1973; Laumann and Pappi, 1976). A recurrent theme throughout this literature is that the fundamental variables of interest are not particular characteristics of individuals but rather the social relations that connect
- Published
- 1983
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40. Evaluating the Scope of Services and Monetary Impact of Charity Medical Clinics in North Texas.
- Author
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Mills LG, Newsom B, Lewis A, Pottorff A, Wallace Wu A, Castro E, Morgan K, Wu L, Tran BP, Lake K, Guirguis M, Wagner JM, Gimpel N, and Kindratt TB
- Subjects
- Humans, Texas, Cross-Sectional Studies, Female, Male, Adult, Medically Uninsured statistics & numerical data, Middle Aged, Health Services Accessibility economics, United States, Child, Adolescent, Young Adult, Charities economics
- Abstract
Introduction/objectives: The cost of medical services is a major barrier to healthcare accessibility for underserved populations in the United States. Community charity medical clinics help address this disparity by providing free or reduced-cost care for the medically underinsured; however, their economic and public health contributions are unknown. The objective of this study was to evaluate the scope of services and monetary impact of 4 community charity medical clinics in North Texas, with one of the largest medically underinsured populations in the United States., Methods: A cross-sectional study was conducted using electronic health records from 4 clinics serving adults and children in North Texas. Encounters from June 1 to December 31, 2018 completed by with sufficient documentation to assign a level of service were reviewed. There were 3942 encounters identified and 2148 (54.5%) audited. Centers for Medicare and Medicaid Services Evaluation and Management Standards were used to identify level of service provided for each encounter, and their subsequent value was determined based on CMS fee-for-service schedules at the time service was provided. Common conditions managed during these encounters were identified using ICD-10 codes documented with each encounter., Results: The most prevalent diagnoses encountered were hypertension, diabetes, hyperlipidemia, and major depressive disorder. We estimate the total value of services and medications provided for 1 year is between $840 278.30 to $845 737.41., Conclusions: The charity clinics in North Texas provide a significant economic impact through a high level of charity care and a broad scope of services for a vulnerable patient population. The results may be used in the development and implementation of future services to meet the needs of the medically underinsured., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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41. COVID-19 Vaccination Concerns and Reasons for Acceptance Among US Health Care Personnel.
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Oberleitner LMS, Lucia VC, Navin MC, Ozdych M, M Afonso N, Kennedy RH, Keil H, Wu L, and Mathew TA
- Subjects
- Attitude of Health Personnel, COVID-19 Vaccines, Health Personnel, Humans, Vaccination, COVID-19 epidemiology, COVID-19 prevention & control, Influenza Vaccines, Influenza, Human prevention & control
- Abstract
Objectives: Because health care personnel (HCP) are potentially at increased risk of contracting COVID-19, high vaccination rates in this population are essential. The objective of this study was to assess vaccination status, barriers to vaccination, reasons for vaccine acceptance, and concerns about COVID-19 vaccination among HCP., Methods: We conducted an anonymous online survey at a large US health care system from April 9 through May 4, 2021, to assess COVID-19 vaccination status and endorsement of reasons for acceptance and concerns related to vaccination (based on selections from a provided list)., Results: A total of 4603 HCP (12.2% response rate) completed the survey, 3947 (85.7%) had received at least 1 dose of a COVID-19 vaccine at the time of the survey, and 550 (11.9%) reported no plans to receive the vaccine. Unvaccinated HCP were 30 times more likely than vaccinated HCP to endorse religious or personal beliefs as a vaccine concern (odds ratio = 30.95; 95% CI, 21.06-45.48) and 15 times more likely to believe that personal vaccination is not needed if enough others are vaccinated (odds ratio = 14.99; 95% CI, 10.84-20.72). The more reasons endorsed for vaccination (ß = 0.60; P < .001), the higher the likelihood of having received the vaccine. However, the number of concerns about COVID-19 vaccine was not related to vaccination status (ß = 1.01; P = .64)., Conclusions: Our findings suggest that reasons for vaccination acceptance and concerns about vaccination need to be considered to better understand behavioral choices related to COVID-19 vaccination among HCP, because these beliefs may affect vaccination advocacy, responses to vaccine mandates, and promotion of COVID-19 vaccine boosters.
- Published
- 2022
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42. COVID-19 Vaccine Hesitancy Among Healthcare Personnel Who Generally Accept Vaccines.
- Author
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Navin MC, Oberleitner LM, Lucia VC, Ozdych M, Afonso N, Kennedy RH, Keil H, Wu L, and Mathew TA
- Subjects
- COVID-19 Vaccines therapeutic use, Cross-Sectional Studies, Female, Humans, Vaccination psychology, Vaccination Hesitancy, COVID-19 prevention & control, Vaccines
- Abstract
To identify psychological antecedents of COVID-19 vaccine hesitancy among healthcare personnel (HCP). We surveyed 4603 HCP to assess psychological antecedents of their vaccination decisions (the '5 Cs') for vaccines in general and for COVID-19 vaccines. Most HCP accept vaccines, but many expressed hesitancy about COVID-19 vaccines for the psychological antecedents of vaccination: confidence (vaccines are effective), complacency (vaccines are unnecessary), constraints (difficult to access), calculation (risks/benefits), collective responsibility (need for vaccination when others vaccinate). HCP who were hesitant only about COVID-19 vaccines differed from HCP who were consistently hesitant: those with lower confidence were more likely to be younger and women, higher constraints were more likely to have clinical positions, higher complacency were more likely to have recently cared for COVID-19 patients, and lesser collective responsibility were more likely to be non-white. These results can inform interventions to encourage uptake of COVID-19 vaccines in HCP., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2022
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43. Design of Fe,N co-doped multi-walled carbon nanotubes for efficient oxygen reduction.
- Author
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Du P, Bao Y, Guo C, Wu L, Pan J, Zhao C, Ma FX, Lu J, and Li YY
- Abstract
Unique Fe and N co-doped multi-walled carbon nanotubes are designed to efficiently catalyze the oxygen reduction reaction (ORR). The preparation processes involve surface functionalization, subsequent wet impregnation and final thermal fixation of Fe-Nx species. The catalyst achieved outstanding alkaline ORR performance with a very positive half-wave potential (∼0.91 V). Theoretical calculations show that the carbon layer below the active Fe-Nx sites is beneficial to the ORR.
- Published
- 2020
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- View/download PDF
44. Rare copy number variants in over 100,000 European ancestry subjects reveal multiple disease associations.
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Li YR, Glessner JT, Coe BP, Li J, Mohebnasab M, Chang X, Connolly J, Kao C, Wei Z, Bradfield J, Kim C, Hou C, Khan M, Mentch F, Qiu H, Bakay M, Cardinale C, Lemma M, Abrams D, Bridglall-Jhingoor A, Behr M, Harrison S, Otieno G, Thomas A, Wang F, Chiavacci R, Wu L, Hadley D, Goldmuntz E, Elia J, Maris J, Grundmeier R, Devoto M, Keating B, March M, Pellagrino R, Grant SFA, Sleiman PMA, Li M, Eichler EE, and Hakonarson H
- Subjects
- Comparative Genomic Hybridization, Databases, Genetic, Genetic Loci, Genetic Predisposition to Disease ethnology, Genome-Wide Association Study, Humans, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, DNA Copy Number Variations, Genetic Predisposition to Disease genetics, Genome, Human genetics, White People genetics
- Abstract
Copy number variants (CNVs) are suggested to have a widespread impact on the human genome and phenotypes. To understand the role of CNVs across human diseases, we examine the CNV genomic landscape of 100,028 unrelated individuals of European ancestry, using SNP and CGH array datasets. We observe an average CNV burden of ~650 kb, identifying a total of 11,314 deletion, 5625 duplication, and 2746 homozygous deletion CNV regions (CNVRs). In all, 13.7% are unreported, 58.6% overlap with at least one gene, and 32.8% interrupt coding exons. These CNVRs are significantly more likely to overlap OMIM genes (2.94-fold), GWAS loci (1.52-fold), and non-coding RNAs (1.44-fold), compared with random distribution (P < 1 × 10
-3 ). We uncover CNV associations with four major disease categories, including autoimmune, cardio-metabolic, oncologic, and neurological/psychiatric diseases, and identify several drug-repurposing opportunities. Our results demonstrate robust frequency definition for large-scale rare variant association studies, identify CNVs associated with major disease categories, and illustrate the pleiotropic impact of CNVs in human disease.- Published
- 2020
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45. Tumor-associated B-cells induce tumor heterogeneity and therapy resistance.
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Somasundaram R, Zhang G, Fukunaga-Kalabis M, Perego M, Krepler C, Xu X, Wagner C, Hristova D, Zhang J, Tian T, Wei Z, Liu Q, Garg K, Griss J, Hards R, Maurer M, Hafner C, Mayerhöfer M, Karanikas G, Jalili A, Bauer-Pohl V, Weihsengruber F, Rappersberger K, Koller J, Lang R, Hudgens C, Chen G, Tetzlaff M, Wu L, Frederick DT, Scolyer RA, Long GV, Damle M, Ellingsworth C, Grinman L, Choi H, Gavin BJ, Dunagin M, Raj A, Scholler N, Gross L, Beqiri M, Bennett K, Watson I, Schaider H, Davies MA, Wargo J, Czerniecki BJ, Schuchter L, Herlyn D, Flaherty K, Herlyn M, and Wagner SN
- Subjects
- Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Cell Survival, Cisplatin therapeutic use, Fibroblast Growth Factor 2 metabolism, Humans, In Vitro Techniques, Melanoma genetics, Paclitaxel therapeutic use, Pilot Projects, Proto-Oncogene Proteins B-raf genetics, Receptor, Fibroblast Growth Factor, Type 3 metabolism, Skin Neoplasms genetics, Tumor Microenvironment, Antineoplastic Agents therapeutic use, B-Lymphocytes metabolism, Drug Resistance, Neoplasm, Insulin-Like Growth Factor I metabolism, Lymphocytes, Tumor-Infiltrating metabolism, Melanoma drug therapy, Protein Kinase Inhibitors therapeutic use, Skin Neoplasms drug therapy
- Abstract
In melanoma, therapies with inhibitors to oncogenic BRAF
V600E are highly effective but responses are often short-lived due to the emergence of drug-resistant tumor subpopulations. We describe here a mechanism of acquired drug resistance through the tumor microenvironment, which is mediated by human tumor-associated B cells. Human melanoma cells constitutively produce the growth factor FGF-2, which activates tumor-infiltrating B cells to produce the growth factor IGF-1. B-cell-derived IGF-1 is critical for resistance of melanomas to BRAF and MEK inhibitors due to emergence of heterogeneous subpopulations and activation of FGFR-3. Consistently, resistance of melanomas to BRAF and/or MEK inhibitors is associated with increased CD20 and IGF-1 transcript levels in tumors and IGF-1 expression in tumor-associated B cells. Furthermore, first clinical data from a pilot trial in therapy-resistant metastatic melanoma patients show anti-tumor activity through B-cell depletion by anti-CD20 antibody. Our findings establish a mechanism of acquired therapy resistance through tumor-associated B cells with important clinical implications.Resistance to BRAFV600E inhibitors often occurs in melanoma patients. Here, the authors describe a potential mechanism of acquired drug resistance mediated by tumor-associated B cells-derived IGF-1.- Published
- 2017
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46. Oncogenic RAS Regulates Long Noncoding RNA Orilnc1 in Human Cancer.
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Zhang D, Zhang G, Hu X, Wu L, Feng Y, He S, Zhang Y, Hu Z, Yang L, Tian T, Xu W, Wei Z, Lu Y, Flaherty KT, Zhong X, Mills GB, Gimotty PA, Xu X, Herlyn M, and Zhang L
- Subjects
- Animals, Cell Line, Tumor, Cell Proliferation, Female, Heterografts, High-Throughput Nucleotide Sequencing methods, Humans, Mice, Mice, Nude, Signal Transduction, Genes, ras, Neoplasms genetics, RNA, Long Noncoding genetics
- Abstract
RAS and its downstream cascades transmit cellular signals, resulting in increased transcription of genes involved in cell growth and division. Protein-coding gene targets of RAS signaling have been characterized extensively, but long noncoding RNAs (lncRNA) regulated by these processes have not. Using a custom-designed lncRNA microarray, we identified the lncRNA Orilnc1 as a genetic target of RAS that is critical for RAS oncogenicity. Orilnc1 expression was regulated by RAS-RAF-MEK-ERK signaling via the transcription factor AP1. Orilnc1 was highly expressed in BRAF-mutant cancers, such as melanoma. Silencing of Orilnc1 blocked tumor cell proliferation and growth in vitro and in vivo In addition, Orilnc1 blockade reduced expression of cyclin E1 and induced G
1 -S cell-cycle arrest in tumor cells. Taken together, our results identify Orilnc1 as a novel, nonprotein mediator of RAS/RAF activation that may serve as a therapeutic target in RAS/RAF-driven cancers. Cancer Res; 77(14); 3745-57. ©2017 AACR ., (©2017 American Association for Cancer Research.)- Published
- 2017
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47. PERK Is a Haploinsufficient Tumor Suppressor: Gene Dose Determines Tumor-Suppressive Versus Tumor Promoting Properties of PERK in Melanoma.
- Author
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Pytel D, Gao Y, Mackiewicz K, Katlinskaya YV, Staschke KA, Paredes MC, Yoshida A, Qie S, Zhang G, Chajewski OS, Wu L, Majsterek I, Herlyn M, Fuchs SY, and Diehl JA
- Subjects
- Apoptosis drug effects, Apoptosis genetics, Cell Cycle Checkpoints, Cell Line, Tumor, Cell Transformation, Neoplastic drug effects, Endoplasmic Reticulum genetics, Endoplasmic Reticulum pathology, Gene Dosage genetics, Haploinsufficiency genetics, Humans, Melanoma drug therapy, Melanoma pathology, Mutation, Signal Transduction drug effects, Signal Transduction genetics, Small Molecule Libraries administration & dosage, Tumor Suppressor Proteins biosynthesis, Unfolded Protein Response genetics, eIF-2 Kinase antagonists & inhibitors, eIF-2 Kinase biosynthesis, Melanoma genetics, Proto-Oncogene Proteins B-raf genetics, Tumor Suppressor Proteins genetics, eIF-2 Kinase genetics
- Abstract
The unfolded protein response (UPR) regulates cell fate following exposure of cells to endoplasmic reticulum stresses. PERK, a UPR protein kinase, regulates protein synthesis and while linked with cell survival, exhibits activities associated with both tumor progression and tumor suppression. For example, while cells lacking PERK are sensitive to UPR-dependent cell death, acute activation of PERK triggers both apoptosis and cell cycle arrest, which would be expected to contribute tumor suppressive activity. We have evaluated these activities in the BRAF-dependent melanoma and provide evidence revealing a complex role for PERK in melanoma where a 50% reduction is permissive for BrafV600E-dependent transformation, while complete inhibition is tumor suppressive. Consistently, PERK mutants identified in human melanoma are hypomorphic with dominant inhibitory function. Strikingly, we demonstrate that small molecule PERK inhibitors exhibit single agent efficacy against BrafV600E-dependent tumors highlighting the clinical value of targeting PERK., Competing Interests: KAS and MCGP are employed by Eli Lilly.
- Published
- 2016
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48. Oncogenic BRAF-Mediated Melanoma Cell Invasion.
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Lu H, Liu S, Zhang G, Kwong LN, Zhu Y, Miller JP, Hu Y, Zhong W, Zeng J, Wu L, Krepler C, Sproesser K, Xiao M, Xu W, Karakousis GC, Schuchter LM, Field J, Zhang PJ, Herlyn M, Xu X, and Guo W
- Subjects
- Actins metabolism, Animals, Cell Line, Tumor, Cell Movement genetics, Cell Surface Extensions metabolism, Cortactin metabolism, Extracellular Matrix metabolism, Extracellular Signal-Regulated MAP Kinases metabolism, Genetic Engineering, Humans, Mice, Neoplasm Invasiveness, Phosphorylation, Proto-Oncogene Proteins B-raf metabolism, Vesicular Transport Proteins metabolism, Melanoma genetics, Melanoma pathology, Oncogenes, Proto-Oncogene Proteins B-raf genetics, Skin Neoplasms genetics, Skin Neoplasms pathology
- Abstract
Melanoma patients with oncogenic BRAF(V600E) mutation have poor prognoses. While the role of BRAF(V600E) in tumorigenesis is well established, its involvement in metastasis that is clinically observed in melanoma patients remains a topic of debate. Here, we show that BRAF(V600E) melanoma cells have extensive invasion activity as assayed by the generation of F-actin and cortactin foci that mediate membrane protrusion, and degradation of the extracellular matrix (ECM). Inhibition of BRAF(V600E) blocks melanoma cell invasion. In a BRAF(V600E)-driven murine melanoma model or in patients' tumor biopsies, cortactin foci decrease upon inhibitor treatment. In addition, genome-wide expression analysis shows that a number of invadopodia-related genes are downregulated after BRAF(V600E) inhibition. Mechanistically, BRAF(V600E) induces phosphorylation of cortactin and the exocyst subunit Exo70 through ERK, which regulates actin dynamics and matrix metalloprotease secretion, respectively. Our results provide support for the role of BRAF(V600E) in metastasis and suggest that inhibiting invasion is a potential therapeutic strategy against melanoma., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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49. Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors.
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Zhang G, Frederick DT, Wu L, Wei Z, Krepler C, Srinivasan S, Chae YC, Xu X, Choi H, Dimwamwa E, Ope O, Shannan B, Basu D, Zhang D, Guha M, Xiao M, Randell S, Sproesser K, Xu W, Liu J, Karakousis GC, Schuchter LM, Gangadhar TC, Amaravadi RK, Gu M, Xu C, Ghosh A, Xu W, Tian T, Zhang J, Zha S, Liu Q, Brafford P, Weeraratna A, Davies MA, Wargo JA, Avadhani NG, Lu Y, Mills GB, Altieri DC, Flaherty KT, and Herlyn M
- Subjects
- Animals, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Extracellular Signal-Regulated MAP Kinases genetics, Extracellular Signal-Regulated MAP Kinases metabolism, Female, HSP90 Heat-Shock Proteins antagonists & inhibitors, HSP90 Heat-Shock Proteins genetics, HSP90 Heat-Shock Proteins metabolism, Humans, Male, Melanoma genetics, Melanoma metabolism, Melanoma pathology, Mice, Mitochondria genetics, Mitochondria pathology, Mitochondrial Proteins genetics, Mitochondrial Proteins metabolism, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Transcription Factors genetics, Transcription Factors metabolism, Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors, Guanidines pharmacology, Lactams, Macrocyclic pharmacology, Melanoma drug therapy, Mitochondria metabolism, Mitochondrial Dynamics drug effects, Neoplasm Proteins antagonists & inhibitors, Protein Kinase Inhibitors pharmacology
- Abstract
Targeting multiple components of the MAPK pathway can prolong the survival of patients with BRAFV600E melanoma. This approach is not curative, as some BRAF-mutated melanoma cells are intrinsically resistant to MAPK inhibitors (MAPKi). At the systemic level, our knowledge of how signaling pathways underlie drug resistance needs to be further expanded. Here, we have shown that intrinsically resistant BRAF-mutated melanoma cells with a low basal level of mitochondrial biogenesis depend on this process to survive MAPKi. Intrinsically resistant cells exploited an integrated stress response, exhibited an increase in mitochondrial DNA content, and required oxidative phosphorylation to meet their bioenergetic needs. We determined that intrinsically resistant cells rely on the genes encoding TFAM, which controls mitochondrial genome replication and transcription, and TRAP1, which regulates mitochondrial protein folding. Therefore, we targeted mitochondrial biogenesis with a mitochondrium-targeted, small-molecule HSP90 inhibitor (Gamitrinib), which eradicated intrinsically resistant cells and augmented the efficacy of MAPKi by inducing mitochondrial dysfunction and inhibiting tumor bioenergetics. A subset of tumor biopsies from patients with disease progression despite MAPKi treatment showed increased mitochondrial biogenesis and tumor bioenergetics. A subset of acquired drug-resistant melanoma cell lines was sensitive to Gamitrinib. Our study establishes mitochondrial biogenesis, coupled with aberrant tumor bioenergetics, as a potential therapy escape mechanism and paves the way for a rationale-based combinatorial strategy to improve the efficacy of MAPKi.
- Published
- 2016
- Full Text
- View/download PDF
50. Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 kinase inhibitor (BMS-540215).
- Author
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Cai ZW, Zhang Y, Borzilleri RM, Qian L, Barbosa S, Wei D, Zheng X, Wu L, Fan J, Shi Z, Wautlet BS, Mortillo S, Jeyaseelan R Sr, Kukral DW, Kamath A, Marathe P, D'Arienzo C, Derbin G, Barrish JC, Robl JA, Hunt JT, Lombardo LJ, Fargnoli J, and Bhide RS
- Subjects
- Administration, Oral, Alanine analogs & derivatives, Animals, Biological Availability, Cell Proliferation drug effects, Clinical Trials, Phase II as Topic, Drug Design, Drug Evaluation, Preclinical, Humans, Intestines drug effects, Liver drug effects, Mice, Microsomes drug effects, Molecular Structure, Prodrugs chemical synthesis, Prodrugs chemistry, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors chemistry, Pyrroles chemical synthesis, Pyrroles chemistry, Solubility, Stereoisomerism, Triazines chemical synthesis, Triazines chemistry, Water chemistry, Xenograft Model Antitumor Assays, Carcinoma drug therapy, Lung Neoplasms drug therapy, Prodrugs pharmacology, Protein Kinase Inhibitors pharmacology, Pyrroles pharmacology, Receptor, Fibroblast Growth Factor, Type 1 antagonists & inhibitors, Triazines pharmacology, Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors
- Abstract
A series of amino acid ester prodrugs of the dual VEGFR-2/FGFR-1 kinase inhibitor 1 (BMS-540215) was prepared in an effort to improve the aqueous solubility and oral bioavailability of the parent compound. These prodrugs were evaluated for their ability to liberate parent drug 1 in in vitro and in vivo systems. The l-alanine prodrug 8 (also known as brivanib alaninate/BMS-582664) was selected as a development candidate and is presently in phase II clinical trials.
- Published
- 2008
- Full Text
- View/download PDF
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