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Changes in U.S. textbooks indicate that U.S. first-grade students in the Common Core era were exposed to a wider variety of word problem types than students in previous generations were. We compared the performance of U.S. first graders in the Common Core era with that of previous generations in solving 11 types of additive word problems to investigate a decades-long debate—whether certain types of word problems are inherently more difficult than others or whether relative difficulty is influenced by exposure. We found that overall patterns of relative difficulty persist; however, U.S. first graders in the Common Core era outperformed their historical counterparts when solving the types of problems that rarely appeared in textbooks used in the 1980s.

PDF file - 59K, The description of studies included in this pooled analysis

Background: Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer (CRC). What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association.Methods: We conducted a pooled analysis of eight studies, including 6,796 CRC cases and 7,770 controls, to evaluate the association between cigarette smoking history and CRC risk and to investigate potential effect modification by other risk factors.Results: Current smokers [OR, 1.26; 95% confidence interval (CI), 1.11–1.43] and former smokers (OR, 1.18; 95% CI, 1.09–1.27), relative to never smokers, showed higher risks of CRC. Former smokers remained at higher CRC risk, relative to never smokers, for up to about 25 years after quitting. The impact of time since quitting varied by cancer subsite: The excess risk due to smoking decreased immediately after quitting for proximal colon and rectal cancer but not until about 20 years post-quitting for distal colon cancer. Furthermore, we observed borderline statistically significant additive interactions between smoking status and body mass index [BMI; relative excess risk due to interaction (RERI]), 0.15; 95% CI, −0.01 to 0.31; P = 0.06] and significant additive interaction between smoking status and fruit consumption (RERI, 0.16; 95% CI, 0.01–0.30; P = 0.04).Conclusion: CRC risk remained increased for about 25 years after quitting smoking, and the pattern of decline in risk varied by cancer subsite. BMI and fruit intake modified the risk associated with smoking.Impact: These results contribute to a better understanding of the mechanisms through which smoking impacts CRC etiology. Cancer Epidemiol Biomarkers Prev; 21(11); 1974–85. ©2012 AACR.

PDF file - 68K, The description of smoking variables included in this analysis

BRAFV600E mutation is a driver mutation in the serrated pathway to colorectal cancers. BRAFV600E drives tumorigenesis through constitutive downstream extracellular signal-regulated kinase (ERK) activation, but high-intensity ERK activation can also trigger tumor suppression. Whether and how oncogenic ERK signaling can be intrinsically adjusted to a “just-right” level optimal for tumorigenesis remains undetermined. In this study, we found that FAK (Focal adhesion kinase) expression was reduced in BRAFV600E-mutant adenomas/polyps in mice and patients. In Vill-Cre;BRAFV600E/+;Fakfl/fl mice, Fak deletion maximized BRAFV600E’s oncogenic activity and increased cecal tumor incidence to 100%. Mechanistically, our results showed that Fak loss, without jeopardizing BRAFV600E-induced ERK pathway transcriptional output, reduced EGFR (epidermal growth factor receptor)-dependent ERK phosphorylation. Reduction in ERK phosphorylation resulted in increased mRNA expression and stability of Lgr4, promoting intestinal stemness and cecal tumor formation. Together, our findings show that a “just-right” ERK signaling optimal for BRAFV600E-induced cecal tumor formation can be achieved via Fak loss-mediated downregulation of ERK phosphorylation.

From a population perspective, the trajectories of both the total fertility at successive time periods and the total fertility of successive birth cohorts are derived from the same array of age-specific fertility rates. This analysis uses the assumption of constant age-specific fertility proportions to derive new explicit relationships between period and cohort fertility. In short, period total fertility is approximately equal to the total fertility of the cohort born a generation earlier, with a modest additive adjustment. A simple relationship also links both period and cohort total fertility to ACF, the average fertility of the childbearing cohorts in a given year. Assuming that fertility levels follow a cubic curve, cohort values from the derived relationships are then compared to observed cohort fertility values for the United States in 1917–2019. Despite substantial violations of the constant proportional fertility assumption, the calculated values deviate from the observed values by an average of only 7–8%. Short-term projections suggest that U.S. cohort fertility will continue to decline.

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and East Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions, and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Cross-tissue analyses indicated that over a third of effector genes most likely act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis, and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article.

Cross-product ratios (αs), which are structurally analogous to odds ratios, are statistically sound and demographically meaningful measures. Assuming constant cross-product ratios in the elements of a matrix of multistate transition probabilities provides a new basis both for calculating probabilities from minimal data and for modeling populations with changing demographic rates. Constant-α estimation parallels log linear modeling, in which the αs are the fixed interactions, and the main effects are calculated from relevant data. Procedures are presented showing how an N state model’s matrix of transition probabilities can be found from the constant αs and (1) the state composition of adjacent populations, (2) (N – 1) known probabilities, (3) (N – 1) known transfer rates, or (4) (2N – 1) known numbers of transfers. The scope and flexibility of constant-α models makes them applicable to a broad range of demographic subjects, including marital/union status, political affiliation, residential status, and labor force status. Here, an application is provided to the important but understudied topic of poverty status. Census data, separately for men and women, provide age-specific numbers of persons in three poverty statuses for the years 2009 and 2014. Using an estimated transition matrix that furnishes a set of cross-product ratios, the constant-α approach allows the calculation of male and female poverty status life tables for the 2009–2014 period. The results describe the time spent in each poverty state and the transitions between states over the entire life course.

The prevalence of multipartner fertility (W) depends on both the level of fertility (TFR) and the likelihood (s) that a woman has a birth of parity 2 or higher by a different partner. The relationship between those factors is analyzed, and the joint variability of W with TFR and s is shown for a range of contemporary values. Similar calculations are made for the fraction of children with a maternal half sibling. Index S is then proposed as a measure that can approximate the probability that a woman has a birth by a different partner based on the TFR and the observed prevalence of multipartner fertility or children with half siblings.

As fertility in much of the developed world remains far below replacement level, it is appropriate to look closely at trends and patterns in childlessness. The rationale for doing so is reinforced by a multidimensional scaling analysis of 80 countries, which finds that contemporary fertility patterns are largely determined by two factors: the overall level and the proportion childless. Parity status life tables for 24 low fertility nations for periods since 2000 show that 15 of them have period parity progression rates implying that over 20% of women will never have any children. Commonly used figures on proportions at parity zero in cohorts completing their reproductive years have understated the level of childlessness inherent in recent data by ignoring the behavior of younger cohorts. Still, even those cohort data reveal an upward trend in childlessness. The likelihood of a resurgence in childlessness is bolstered by steady increases in the mean ages at first birth observed in all 24 study populations. Looking ahead, high proportions childless can be consistent with stable, egalitarian unions, as children now bring few resources to parents while making great demands upon them.

The retreat from marriage and the rapid rise in cohabitation are examined using data from the National Survey of Families and Households. A multistate approach is used to follow the experience of U.S. females born between 1928-1967. In recent cohorts both the average duration of a 1st cohabitation and the likelihood that a 1st cohabitation leads to marriage declined. Moreover the probability of ever marrying is greater for women who never cohabited than for women who did. Those findings suggest that cohabitation is not simply a prelude to marriage but rather another kind of relationship. It is well-suited to our era of individualism as it emphasizes autonomy and downplays commitment. While accommodating a dual career lifestyle cohabitation also offers advantages to men at all socioeconomic levels. (authors)

Demographic analyses of fertility customarily focus on age-specific birth rates, implicitly assuming that, at every age, fertility is the same for women of every parity. This chapter looks at the implications of that common assumption, and finds that they are far-reaching. From a set of age-specific birth rates, one can determine the likelihood that sibships of any size and gender composition arise in a cohort. Calculations for several fertility levels and a variety of sibship constellations are given. Further, overall cohort experience can be divided into subcohorts based on their ultimate number of children, and those subcohorts can be further broken down into the pathways by which that ultimate parity is reached. Such an analysis allows a detailed examination of fertility timing and birth spacing. Illustrative calculations indicate that higher parity subcohorts have children of every birth order earlier and move to higher parities faster than lower parity subcohorts. Because of the sequential nature of fertility, parity homogeneity casts a long shadow.

Demographers have long been interested in parity, the number of children a person has ever produced. Explicit recognition of parity opens the door to analyzing the kinship network. This chapter first examines kinship ties in models that vary both the level of fertility and the pattern of parity progression in order to quantify the influence of parity progression on the number of kin. We then re-examine the American experience over the 1917 to 2005–2010 period to see how fertility levels, family sizes, and number of kin have changed over time. The end of the Baby Boom in the mid-1960s marked a watershed, a Sibsize Transition, ending the era of large families and reshaping the American kinship network.

In multistate populations, the rates of interstate transfer cannot generally be determined from the size and composition of the populations at the beginning and end of a time interval. With N living states, the population data give only N equations to determine the N 2 possible rates. Here, the QERT (quadratic estimation of rates of transfer) approach is advanced that allows the transfer rates to be estimated when the products of selected pairs of rates can be assumed constant. The solution can be written in closed form and, for N living states, involves no more than N−1 quadratic equations. Compared to the leading alternative approaches, QERT provides very similar numerical estimates, while yielding the underlying behavioral rates, having flexible input requirements, accommodating all structural zeros, and reproducing the exact solution when interstate transfers are strictly hierarchical. The QERT approach is applied to construct labor force life tables for U.S. men and women for 2005–2010. The results show that labor force participation differences between men and women have continued to narrow, and that the QERT approach can generate robust worklife estimates. QERT thus provides new opportunities for demographic analysis in the absence of direct data on behavioral rates.

The lack of vital statistics data on American marriage and divorce has made it difficult to follow post-1995 changes in marriage behavior. Here, a new approach, Rate Estimation from Adjacent Populations (REAP), is used in conjunction with vital statistics mortality data and recently released divorce data from the American Community Survey to construct marital status life tables that reflect the lifetime implications of observed or inferred rates of marriage, divorce, and mortality. Methodologically, the chapter sets forth the features of the REAP approach. Substantively, the analysis shows that the retreat from marriage is continuing, but unevenly. The probability that a woman ever marries has fallen to 80 %, and the average age at first marriage has risen, slightly, to 27 years. At the same time, the probability of divorce appears to be holding steady at about 43–46 %. The results suggest that the great transformation of the American family has not yet run its course.

Recent work from our lab showed that in a colon cancer prevention trial of a tumor antigen MUC1 vaccine in patients with premalignant colon adenomas, those who did not make anti-MUC1 IgG, had higher pre-vaccination levels of circulating MDSC compared to vaccine responders. This was the first observation of increased MDSC in premalignancy. MDSC in premalignancy have not been compared to MDSC in cancer and our hypothesis is that there might be differences in the composition of various MDSC subpopulation and their immunosuppressive functions due to the shorter time of exposure to disease and differences in the disease microenvironment. We are testing this hypothesis on two cohorts of patient samples, premalignant and malignant colon and pancreas. In both cohorts we saw an increase in MDSC in premalignant and malignant disease over healthy controls. The colon premalignant group could be divided into MDSChighAnti-MUC1 IgGlow and MDSClowAnti-MUC1 IgGhigh confirming our previous observations that MDSC are impeding anti-MUC1 immune response in premalignancy as well therefore potentially facilitating progression to cancer. The pancreas cohort also showed increase in MDSC in patients with pancreatic cysts (IPMN), precursors to pancreatic cancer, as well as their suppression of anti-tumor immunity. Furthermore, we found increased levels of PGE2 and its metabolite in patients’ serum from both cohorts, which is closely related to MDSC proliferation and mechanism of suppression. While we do not see much difference in the MDSC phenotype and subpopulation composition, the immunosuppressive capacity of tumor MDSC appears to be greater. We are currently testing this observation in vitro in T cell suppression assays.

Multistate life table models, which follow persons through more than one living state, have found increasing use in demographic analyses. Multistate stable populations, however, are infrequently used because the constant rate assumption is quite strong and such populations can take centuries to approach stability. Dynamic models, that is models where the rates can change over time, are examined to derive a new solution for the size and composition of a multistate population in terms of the sequence of underlying population projection matrices (PPMs). Constraints on the subordinate eigenvalues and the subordinate eigenvectors of the time-varying PPMs produce a model population that grows according to the dominant eigenvalues of each time-specific PPM and has a state composition that depends only on the most recent PPM. The two living state model is examined in detail, relationships between the PPM elements and the size and composition of the model are explored, and two illustrative applications of the mode...

We investigated the effect of the September 11, 2001 terrorist attack on marital stability. Previous research showed rates of divorce changed in opposite directions following natural disaster versus terrorist disaster. Using a prospective, longitudinal design and time series analysis, we examined rates of divorces filed by month, with respect to the World Trade Center attack in New York City (NYC). To examine whether effects radiated beyond NYC according to geographic proximity or psychological proximity, we examined four other counties of varying distance from NYC. Results showed geographic and psychological proximity effects. Following a major manmade disaster characterized by death, divorce rates decreased in NYC and Bergen County, NJ, geographically proximal locales, and in Los Angeles and Philadelphia, psychologically proximal locales.

Social background has historically been recognized as a major factor influencing family behavior, though recent work has largely emphasized racial/ethnic influences. Here we use 1994 - 1995 and 2001 - 2002 Add Health data to examine the cohabitation, first marriage, and first birth experience of young women. In a multistate life table context, hypothetical cohorts specified in terms of race and mother's education are followed, from age 11 to age 24, as they move through 6 family-related statuses. The results indicate that, for both Black and White women, a higher level of maternal education is generally associated with less cohabitation, less marriage, fewer first births, and a higher percentage of women who experience none of those transitions before age 24. Racial and social background differences are conceptually and empirically distinct. Because mother's education is associated with substantially different trajectories of early family behavior for both Blacks and Whites, we argue that social background merits increased attention in research on contemporary American family patterns. Key Words: cohabitation, first birth, first marriage, multistate life tables, race, socioeconomic status. Since 1960, profound changes in family behavior have occurred in the United States and many other Western countries. Often described as the "Second Demographic Transition," those changes include an emphasis on individual freedom, sharp increases in cohabitation and premarital sexual behavior, delays in marriage and childbearing, and a rise in nonmarital childbearing (Lesfhaeghe, 1995). In 1960, U.S. rates implied that 94% of women would ever marry, with an average age at first marriage of 20.4 years (Schoen & Nelson, 1974). In 1995, comparable rates implied that 88% of women would ever marry, with an average age at first marriage of 26.6 (Schoen & Standish, 2001). Cohabitation was rather uncommon in 1960, but in the 1990s most first unions were cohabitations, rather than marriages (Bumpass & Lu, 2000). Only 5% - 6% of all births were to unmarried women in the 1960s, but in the 1990s 32% - 33% of all births were out of wedlock (Ventura & Bachrach, 2000). Here we explore recent patterns in early family behavior, that is, the cohabitation, first birth, first marriage, and first marital dissolution behavior of Black and White women up to age 24. (To facilitate the presentation, we use the terms "Whites" and "Blacks" to refer, respectively, to non-Hispanic Whites and non-Hispanic Blacks.) The emphasis on racial differences in much recent work has led to a relative neglect of socioeconomic factors. Our focus is on differences in family behavior by mother's educational level within the Black and White groups. Using a longitudinal perspective, we provide new measurements of the influence of social background on a broad range of early family transitions. Sociodemographic Differentials in Family Behavior The social and demographic changes associated with the Second Demographic Transition are continuing, and the rapidity of recent change in marriage and cohabitation means that what we know quickly becomes outdated (Raley, 2000). Moreover, as family patterns have changed, differences by socioeconomic background and by race have continued to evolve. Marriage occurs substantially later among Blacks than among Whites (Landale & Oropesa, 2007). The marriage rates of Black women have declined much more steeply than those of White women (Raley, 2000). Nonmarital fertility differentials by race have been substantial. In 2000, the percentage of nonmarital births was 22% among Whites and 69% among Blacks (Bramlett & Mosher, 2002). At the same time, half of nonmarital births to Whites arose from cohabiting unions, while only a fifth of Black nonmarital births did (Bumpass & Lu, 2000; Ventura & Bachrach, 2000). Cohabitation is the most common initial family-related event for Whites, but not for Blacks, whose most common first event is a birth (Schoen, Landale, & Daniels, 2007). …

Recently it has been demonstrated that after selenium (Se) supplementation in autoimmune thyroiditis (AIT) patients, there was a significant decrease of thyroid peroxidase (TPO) autoantibody (TPOAb) levels. The aim of our study was to evaluate the immunological benefit of Se administration in unselected AIT patients and thus address the question whether Se administration should generally be recommended for AIT patients.Thirty-six consecutive AIT patients (aged 19-85 years) were included in the present study. In addition to their levothyroxine (LT(4)) treatment, 18 patients received 200 microg (2.53 micromol) sodium selenite per day orally for the time span of 3 months, whereas 18 patients received placebo. All patients had measurement of thyroid hormones, thyrotropin (TSH), autoantibodies (thyroglobulin antibodies [TgAb] and TPOAb), Se levels, and intracellular cytokine detection in CD4(+) and CD8(+) T cells of peripheral blood mononuclear cells (PBMC) by flow cytometry before and after Se or placebo administration.No significant difference in the TPOAb levels was found after Se administration (524 +/- 452 vs. 505 +/- 464 IU/mL; p0.05). Furthermore, we found no significant differences in the CD4(+) or CD8(+) cytokine pattern (IFN-gamma, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-alpha, TNF-beta) in patients before and after Se administration, in patients before and after placebo administration and between Se group and placebo group before and after Se vs. placebo administration.We demonstrate that Se administration in our AIT patient's cohort does not induce significant immunological changes, either in terms of cytokine production patterns of peripheral T lymphocytes or of TPOAb levels. Our data suggest that AIT patients with moderate disease activity (in terms of TPOAb and cytokine production patterns) may not (equally) benefit as patients with high disease activity.