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Single nucleotide polymorphisms (SNPs) in genes on chromosome 17q12-q21 are associated with childhood-onset asthma and rhinovirus-induced wheeze. There are few mechanistic data linking chromosome 17q12-q21 to wheezing illness. We investigated whether 17q12-q21 risk alleles were associated with impaired interferon responses to rhinovirus. In a population-based birth cohort of European ancestry, we stimulated peripheral blood mononuclear cells with rhinovirus A1 (RV-A1) and rhinovirus A16 (RV-A16) and measured IFN and IFN-induced C-X-C motif chemokine ligand 10 (aka IP10) responses in supernatants. We investigated associations between virus-induced cytokines and 6 SNPs in 17q12-q21. Bayesian profile regression was applied to identify clusters of individuals with different immune response profiles and genetic variants. Five SNPs (in high linkage disequilibrium, r 2 ≥ 0.8) were significantly associated with RV-A1–induced IFN-β (rs9303277, P =.010; rs11557467, P =.012; rs2290400, P =.006; rs7216389, P =.008; rs8079416, P =.005). A reduction in RV-A1–induced IFN-β was observed among individuals with asthma risk alleles. There were no significant associations for RV-A1–induced IFN-α or CXCL10, or for any RV-A16–induced IFN/CXCL10. Bayesian profile regression analysis identified 3 clusters that differed in IFN-β induction to RV-A1 (low, medium, high). The typical genetic profile of the cluster associated with low RV-A1–induced IFN-β responses was characterized by a very high probability of being homozygous for the asthma risk allele for all SNPs. Children with persistent wheeze were almost 3 times more likely to be in clusters with reduced/average RV-A1–induced IFN-β responses than in the high immune response cluster. Polymorphisms on chromosome 17q12-q21 are associated with rhinovirus-induced IFN-β, suggesting a novel mechanism—impaired IFN-β induction—links 17q12-q21 risk alleles with asthma/wheeze. [ABSTRACT FROM AUTHOR]

The Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother-child cohorts have provided a foundation of 25 years of research on the origins, prevention, and natural history of childhood asthma and related disorders. COPSAC's approach is characterized by clinical translational research with longitudinal deep phenotyping and exposure assessments from pregnancy, in combination with multi-omic data layers and embedded randomized controlled trials. One trial showed that fish oil supplementation during pregnancy prevented childhood asthma and identified pregnant women with the highest benefits from supplementation, thereby creating the potential for personalized prevention. COPSAC revealed that airway colonization with pathogenic bacteria in early life is associated with an increased risk of asthma. Further, airway bacteria were shown to be a trigger of acute asthma-like symptoms, with benefit from antibiotic treatment. COPSAC identified an immature gut microbiome in early life as a risk factor for asthma and allergy and further demonstrated that asthma can be predicted by infant lung function. At a molecular level, COPSAC has identified novel susceptibility genes, early immune deviations, and metabolomic alterations associated with childhood asthma. Thus, the COPSAC research program has enhanced our understanding of the processes causing childhood asthma and has suggested means of personalized prevention and treatment. [ABSTRACT FROM AUTHOR]

Distribution of environmental hazards and vulnerability to their effects vary across socioeconomic groups. Our objective was to analyse the relationship between child socioeconomic position (SEP) at birth and the external exposome at pre-school age (0–4 years). This study included more than 60,000 children from eight cohorts in eleven European cities (Oslo, Copenhagen, Bristol, Bradford, Rotterdam, Nancy, Poitiers, Gipuzkoa, Sabadell, Valencia and Turin). SEP was measured through maternal education and a standardised indicator of household income. Three child exposome domains were investigated: behavioral, diet and urban environment. We fitted separate logistic regression model for each exposome variable - dichotomised using the city-specific median - on SEP (medium/low vs high) adjusting for maternal age, country of birth and parity. Analyses were carried out separately in each study-area. Low-SEP children had, consistently across study-areas, lower Odds Ratios (ORs) of breastfeeding, consumption of eggs, fish, fruit, vegetables and higher ORs of TV screen time, pet ownership, exposure to second-hand smoke, consumption of dairy, potatoes, sweet beverages, savory biscuits and crisps, fats and carbohydrates. For example, maternal education-breastfeeding OR (95% Confidence Interval (CI)) ranged from 0.18 (0.14–0.24) in Bristol to 0.73 (0.58–0.90) in Oslo. SEP was also strongly associated with the urban environment with marked between-city heterogeneity. For example, income-PM 2.5 OR (95%CI) ranged from 0.69 (0.47–1.02) in Sabadell to 2.44 (2.16–2.72) in Oslo. Already at pre-school age, children with lower SEP have consistently poorer diets and behaviours, which might influence their future health and wellbeing. SEP-urban environment relationships are strongly context-dependent. • Harmonised data on 61378 children from eight cohorts in eleven European cities. • Two indicators of socioeconomic position (SEP): household income and maternal education. • Low SEP children had consistently poor diet and unhealthy behaviours at preschool age. • SEP-urban environment relationships are strongly context-dependent. • The preschool age period is a window of opportunity to mitigate SEP inequalities. [ABSTRACT FROM AUTHOR]

Social factors have a profound impact on child health – they are the "causes of the causes", creating social gradients and inequalities in almost all morbidities. The social determinants of health are complex and intertwined, and in the UK child health inequalities are entrenched and intractable. We describe how longitudinal research on children's health and life course trajectories gives us insights into the ways in which the social determinants interact to affect children, and how these insights can shape policy and practice to improve child health. We also touch on three major contemporary issues in child health: adverse childhood experiences, the Covid-19 pandemic and climate change. We explore how paediatricians can engage with the social determinants of child health and be agents for change, and share examples of innovative practice. [ABSTRACT FROM AUTHOR]

Background: Birth cohort studies are a valuable source of information about potential risk factors for childhood asthma. To better understand similarities and variations in findings between birth cohort studies, the methodologies used to measure asthma require consideration.Objective: To review and appraise the definitions of "asthma" used in birth cohort studies.Methods: A literature search, conducted in December 2017 in the MEDLINE database and birth cohort repositories, identified 1721 citations published since 1990. Information extracted included: study name, year of publication, sample size, sample age, prevalence of asthma (%), study region, source of information about asthma, measured outcome, and asthma case definition. A meta-analysis evaluated whether asthma prevalence in cohorts from Europe and North America varied by the studies' definition of asthma and by their data sources.Results: The final review included 67 birth cohorts, of which 48 (72%) were from Europe, 14 (21%) from North America, 3 (5%) from Oceania, 1 (1%) from Asia and 1 (1%) from South America. We identified three measured outcomes: "asthma ever", "current asthma", and "asthma" without further specification. Definitions of "asthma ever" were primarily based upon an affirmative parental response to the question whether the child had ever been diagnosed with asthma by a physician. The most frequently used definition of "current asthma" was "asthma ever" and either asthma symptoms or asthma medications in the last 12 months. This definition of "current asthma" was used in 16 cohorts. There was no statistically significant difference in the pooled asthma prevalence in European and North American cohorts that used questionnaire alone versus other data sources to classify asthma.Conclusion: There is substantial heterogeneity in childhood asthma definitions in birth cohort studies. Standardisation of asthma case definitions will improve the comparability and utility of future cohort studies and enable meta-analyses. [ABSTRACT FROM AUTHOR]

Background: Though high rates of co-occurring cannabis use and depression are well-documented, data regarding the association between cannabis use and dysthymia is scarce. The aim of this cross-sectional study was to explore clinical correlations of cannabis use among individuals with dysthymia, as well as the changes in the association between cannabis use and dysthymia across six decades of birth cohorts.Methods: Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III; 2012-2013; N = 36,309). Participants were divided into six birth cohorts (1940s-1990s), based on their decade of birth, and individuals with dysthymia were further categorized by 3 levels of lifetime cannabis use: non-users, non-CUD users, and CUD-users. We compared rates of co-occurring psychiatric and substance use disorders among cannabis users vs non-users and conducted logistic regression analyses in order to determine the odds of dysthymia among cannabis users across six decades.Results: Rates of several psychiatric disorders, such as personality disorders, and substance use disorders were higher among individuals with dysthymia who used cannabis compared to those who did not. The interaction between cannabis use (without a CUD) and birth cohort was associated with a decrease in the odds of dysthymia (OR=0.90, 95% CI 0.84-0.97) and remained significant after controlling for confounding variables. Similar changes over time were not demonstrated for CUD users.Limitations: Likelihood for recall bias and misclassification based on cross-sectional nature of the study and on respondents' self-reports of symptoms throughout their lifetime.Conclusions and Implications: Our study's findings demonstrate that the association between cannabis use (but not CUDs) and dysthymia has weakened over time. These findings highlight the need for further research examining changes over time in the relationship between cannabis use and associated psychiatric disorders. [ABSTRACT FROM AUTHOR]

Previous studies documented inconsistent findings of cohort differences in attitudes toward migrants. Some research has shown that younger people tend to be more welcoming toward migrants compared to older people; however, other research has shown the opposite. This suggests that the way different generations perceive migrants may depend on the specific local contexts in which they live. In this paper, we compared attitudes toward migrants in Hong Kong and Shanghai under the "one country, two systems" framework, using comparable data from the Hong Kong Panel Study of Social Dynamics and Shanghai Urban Neighborhood Survey. We found a sharp contrast in the attitudes toward migrants between Hong Kong and Shanghai. Compared to older people, young people in Shanghai were more friendly to migrants, yet young people in Hong Kong were more resistant to migrants. Our study identified disparities of generational gaps in attitudes toward migrants of the same ethnicity within one country. The relatively more positive attitudes toward migrants of younger cohorts (compared to people born before 1960) in Shanghai could be explained by educational level and life satisfaction. The relatively more negative attitudes toward migrants in Hong Kong could be explained by identity. Our empirical analyses suggest that local contexts matter in explaining generational gaps in attitudes toward migrants. [ABSTRACT FROM AUTHOR]

Objectives Our study aimed to describe the temporal changes in self-rated health status (SRH) from 1997 to 2012 in adults aged 25 to 84 residing in Switzerland, with a view to identifying groups at risk for declining health. Study design Secondary analysis of population-based cross-sectional health surveys. Methods Data were collected from the cross-sectional, population-based, five-year Swiss Health Survey, from 1997, 2002, 2007 and 2012. A total of 63,861 individuals' data were included. Multilevel mixed-effect logistic regression analysis was employed to estimate the probability of very good and good health within the framework of a hierarchical cross-classified age-period-cohort model (HAPC), adjusting for education level, gender, civil status, smoking status and body mass index. Results Individuals with higher education were substantially more likely than those with primary education to report good SRH (OR = 2.12; 95% CI = 1.93–2.33 for secondary education and OR = 3.79; 95% CI = 3.39–4.23 for tertiary education). The education effect depended on birth cohort and age: higher proportions of good SRH were reported by secondary (8%–17%) and tertiary (10%–22%) compared with primary educated individuals from the 1940 birth cohort onward; the proportion of secondary/tertiary (compared to primary) educated people reporting good SRH increased with age (by 10/11% at 45–50 years and 25/36% at 80–84 years). Gender health equality was achieved by the 1955 (primary educated) and 1960 (secondary educated) birth cohorts, while these women overtook men in reporting good SRH from the 1975 birth cohort onward. Tertiary educated younger women were significantly less likely to report good SRH than men but parity was achieved at around pension age. Similarly, gender inequality in those with primary and secondary education reduced in the younger ages to not be significant at around age 55, with women overtaking men from age 65. Conclusions Younger birth cohorts with lower education levels appear most vulnerable in terms of their SRH. The education effect cumulatively increases when attaining incrementally higher education levels. While women report lower health than men, gender inequality in SRH has declined and even reversed over time and is substantially linked to differences in educational status. Swiss public health strategies should particularly target the younger adults with only primary school education of both genders; for women, to combat health burdens in their early life, and men, to mitigate issues in their later life. [ABSTRACT FROM AUTHOR]

Objectives: A robust literature documents generational trends in drug use. We examined the implications of changing national drug use patterns on drug injection histories of diverse people who inject drugs (PWID).Methods: Drug use histories were collected from 776 active PWID in 2011-13. Using descriptive statistics, we examine drug use initiation by year and birth cohort (BC) differences in drug first injected. A multivariate linear regression model of time to injection initiation ([TTII] (year of first injection minus year of first illicit drug use) was developed to explore BC differences.Results: The first drug injected by BC changed in tandem with national drug use trends with heroin declining from 77% for the pre-1960's BC to 58% for the 1960's BC before increasing to 71% for the 1990's BC. Multivariate linear regression modeling found that shorter TTII was associated with the 1980's/1990's BC (-3.50 years; 95% Confidence Interval [CI]=-0.79, -6.21) as compared to the 1970's BC. Longer TTII was associated with being female (1.65 years; 95% CI=0.40, 2.90), African American (1.69 years; 95% CI=0.43, 2.95), any substance use treatment prior to injection (4.22 years; 95% CI=2.65, 5.79), and prior non-injection use of drug that was first injected (3.29 years; 95% CI=2.19, 4.40).Conclusion: National drug trends appear to influence injection drug use patterns. The prescription opiate drug era is associated with shorter TTII. Culturally competent, demographically and generationally-targeted prevention strategies to combat transitions to drug injection are needed to prevent or shorten upstream increases in risky drug use practices on a national level. [ABSTRACT FROM AUTHOR]

The Developmental Origins of Health and Disease (DOHaD) scientific field investigates the influence of early life environmental stressors on later life health outcomes. Environmental chemical exposures are a particular focus area within this field. Although the DOHaD hypothesis originated in the 1990s, the data evaluating this hypothesis in environmental epidemiology has not been comprehensively summarized. We conducted a scoping literature review to describe the human evidence for the DOHaD hypothesis and to identify, 1) where there may be reasonable data to draw conclusions, and 2) areas warranting further research. Using PubMed and Web of Science we identified 425 publications through 2014 that met our criteria for evaluating the DOHaD hypothesis in environmental epidemiology. These publications covered 60 different chemicals. The majority of publications focused on neurological/cognitive outcomes, followed by cancer, and respiratory outcomes. We note areas ready for more detailed review, those requiring more data and ideas for future directions. [ABSTRACT FROM AUTHOR]

We are facing a major challenge in bridging the gap between identifying subtypes of asthma to understand causal mechanisms and translating this knowledge into personalized prevention and management strategies. In recent years, “big data” has been sold as a panacea for generating hypotheses and driving new frontiers of health care; the idea that the data must and will speak for themselves is fast becoming a new dogma. One of the dangers of ready accessibility of health care data and computational tools for data analysis is that the process of data mining can become uncoupled from the scientific process of clinical interpretation, understanding the provenance of the data, and external validation. Although advances in computational methods can be valuable for using unexpected structure in data to generate hypotheses, there remains a need for testing hypotheses and interpreting results with scientific rigor. We argue for combining data- and hypothesis-driven methods in a careful synergy, and the importance of carefully characterized birth and patient cohorts with genetic, phenotypic, biological, and molecular data in this process cannot be overemphasized. The main challenge on the road ahead is to harness bigger health care data in ways that produce meaningful clinical interpretation and to translate this into better diagnoses and properly personalized prevention and treatment plans. There is a pressing need for cross-disciplinary research with an integrative approach to data science, whereby basic scientists, clinicians, data analysts, and epidemiologists work together to understand the heterogeneity of asthma. [ABSTRACT FROM AUTHOR]

Background Dioxins and dioxin-like compounds are endocrine disrupting chemicals (EDCs). Experimental studies suggest perinatal exposure to EDCs results in later obesity. However, the few epidemiological investigations on dioxins are inconclusive. We investigated perinatal exposure to dioxins and dioxin-like compounds, infant growth and body mass index (BMI) in childhood. Methods We pooled data from 3 European birth cohorts (Belgian, Norwegian, Slovak) with exposure assessment in cord blood or breast milk. Two cohorts had dioxin-like toxicity assessed using dioxin-responsive chemical-activated luciferase expression (DR-CALUX) bioassay and one cohort had measured concentrations of dioxins, furans and dioxin-like polychlorinated biphenols with CALUX relative potency values applied. Growth was cohort- and sex-specific change in weight-for-age z-score between birth and 24 months (N = 367). BMI was calculated at around 7 years (median 7.17, interquartile range [IQR] 7.00–7.37 years, N = 251), and overweight defined according to international standards for children equivalent to adult BMI > 25 kg/m 2 (Cole and Lobstein, 2012). We fitted multivariate models using generalized estimating equations, and tested effect modification by sex, breastfeeding and cohort. Results per 10 pg CALUX TEQ/g lipid increase in exposure. Results Dioxin exposure was highest in the Belgian and lowest in the Norwegian cohort; median (IQR) of the pooled sample 13 (12.0) pg CALUX TEQ/g lipid. Perinatal exposure to dioxins and dioxin-like compounds appeared associated with increased growth between 0 and 24 months (adjusted estimate for change in z-score: β = 0.07, 95% CI: − 0.01, 0.14). At 7 years, dioxins exposure was associated with a statistically significant increase in BMI in girls (adjusted estimate for BMI units β = 0.49, 95% CI: 0.07, 0.91) but not in boys (β = − 0.03, 95% CI: − 0.55, 0.49) ( p -interaction = 0.044). Furthermore, girls had a 54% (− 6%, 151%) increased risk of overweight at 7 years ( p -interaction = 0.023). Conclusion Perinatal exposure to dioxin and dioxin-like compounds was associated with increased early infant growth, and increased BMI in school age girls. Studies in larger sample sizes are required to confirm these sex-specific effects. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl acids (PFAAs) are ubiquitous chemicals extremely resistant and widespread throughout the environment, frequently being detected in human blood samples. Animal studies have revealed that exposure to PFAAs results in immunotoxicity. However, the association between PFAAs, especially long-chain PFAAs, and allergies in humans is not well established. We examined whether prenatal exposure to PFAAs is associated with allergic diseases among 4-year-old children in a large-scale prospective birth cohort in Hokkaido, Japan. In total, 1558 mother–child pairs were included in this study and prenatal levels of eleven PFAAs were measured in maternal plasma samples obtained between 28 and 32 weeks of pregnancy by using ultra-performance liquid chromatography-tandem mass spectrometry. Participant demographic and characteristic information were obtained from self-administered pre- and postnatal questionnaires and medical birth records. Infant allergies were assessed using the Japanese version of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three questionnaire, which was administered 4 years post-delivery. Symptoms included eczema, wheezing and rhinoconjunctivitis with a prevalence of 19.0%, 18.7%, and 5.4%, respectively. Associations of PFAA quartiles with allergic outcomes were examined using logistic models. Adjusted odds ratios (ORs) in the 4th quartile vs. 1st quartile (Q4 vs. Q1) for total allergic diseases (including at least one allergic outcome) significantly decreased for perfluorododecanoic acid (PFDoDa) (Q4 vs. Q1 OR: 0.621; 95% confidence interval (CI): 0.454, 0.847) and perfluorotridecanoic acid (PFTrDA) (Q4 vs. Q1 OR: 0.712; 95% CI: 0.524, 0.966) in all children. We obtained similar results when examining the association between PFAAs and eczema. The adjusted OR (Q4 vs. Q1) for wheezing in relation to higher maternal PFHxS levels was 0.728 (95% CI: 0.497, 1.06) in all children. In conclusion, prenatal exposure to long-chain PFAAs, such as PFDoDa and PFTrDA may have an immunosuppressive effect on allergic diseases in 4-year-old children. [ABSTRACT FROM AUTHOR]

Introduction Environmental exposures have been linked to length of gestation but the question as to during which weeks of gestation pregnancies are most susceptible still remains little explored. We estimated the effect of maximum apparent temperature and air pollution levels on risk of birth by week of gestation. Methods We analyzed two cohorts of singleton live births in Rome (2001–2010) and Barcelona (2007–2012). Maximum apparent temperature (MAT), PM 10 , O 3 and NO 2 were analyzed in the warm period (1st April–31st October). Gestational week-specific hazard ratios of giving birth associated to a 1-unit increase in exposure were estimated fitting Cox regression models adjusted for seasonality, and demographic and clinical characteristics of the mother. Results We observed 78,633 births (5.5% preterm) in Rome and 27,255 (4.5% preterm) in Barcelona. The highest hazard ratios for 1 °C increase in MAT were in the 22nd–26th weeks of gestation, 1.071, (95% CI 1.052–1.091) in Rome and 1.071 (95% CI 1.036–1.106) in Barcelona, and decreased to 1.032 (95% CI 1.026–1.038) and 1.033 (95% CI 1.020–1.045) at the 36th week of gestation, respectively. Similar associations and trends were observed for PM 10 and NO 2 after adjusting for MAT. O 3 showed similar trends but weaker associations. Conclusions We found, consistently in Rome and Barcelona, an increased risk of delivery for a unit increase in MAT, PM 10 , NO 2 and O 3 , especially in the second half of the second trimester, thus effectively increasing the risk of preterm and particularly early preterm birth. Results may help to increase awareness of these risks among public-health regulators and clinicians, leading to better preventive strategies. [ABSTRACT FROM AUTHOR]

Resilience is an important psychological resource that helps individuals successfully adapt to trauma, adversity, and stress. Rapid economic growth and increasing social problems constitute the basic features of social change in China. Considering that resilience is a psychological resource in dynamic adaptation, it may be affected by social change. College life is a major period of transition from school academic to social life. College students face more potential challenges from physical and psychological changes and need more resilience resources. The dynamic trends of college students' resilience with social changes and its relationship with macroenvironmental factors are worth exploring. Therefore, cross-temporal meta-analysis was employed to investigate resilience changes from 2007 to 2020. One hundred forty-four studies (N = 87,017) that used the Connor-Davidson resilience scale (CD-RISC) were analysed. Additionally, direct and lag correlation analyses were conducted to investigate the relationship between resilience and the macrosocial environment. Over the past 13 years, research has found that resilience has decreased by 12.7 points (d = −0.97). Macrosocial indicators, such as economic conditions, social connectedness, and overall threat, are important predictors of declining resilience. [ABSTRACT FROM AUTHOR]

This review addresses predictors of remission or persistence of wheezing and asthma from early childhood through adulthood. Early childhood wheezing is common, but predicting who will remit or have persistent childhood asthma remains difficult. By adding parental history of asthma and selected infant biomarkers to the history of recurrent wheezing, the Asthma Predictive Index and its subsequent modifications provide better predictions of persistence than simply the observation of recurrent wheeze. Sensitization, especially to multiple allergens, increases the likelihood of development of classic childhood asthma. Remission is more likely in male subjects and those with milder disease (less frequent and less severe symptoms), less atopic sensitization, a lesser degree of airway hyperresponsiveness, and no concomitant allergic disease. Conversely, persistence is linked strongly to allergic sensitization, greater frequency and severity of symptoms, abnormal lung function, and a greater degree of airway hyperresponsiveness. A genetic risk score might predict persistence more accurately than family history. Remission of established adult asthma is substantially less common than remission during childhood and adolescence. Loss of lung function can begin early in life and tracks through childhood and adolescence. Despite therapy which controls symptoms and exacerbations, the outcomes of asthma appear largely resistant to pharmacologic therapy. [ABSTRACT FROM AUTHOR]

Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts. [Copyright &y& Elsevier]

Abstract: There are emerging concerns about potential effects on child health and development of early-life exposure to substances such as brominated flame retardants (BFRs), perfluorinated compounds (PFCs), phthalates and phenols (including bisphenol A (BPA)); pregnancy and birth cohort studies are ideally designed to study such concerns prospectively. As part of the ENRIECO project, we evaluated existing human biomonitoring data for these substances in European birth cohorts and develop recommendations for more harmonized methods that will enable combination and comparison of cohort data in the future. The ENRIECO inventory shows that 20 European birth cohorts have measured or are measuring BFRs (N =10), PFCs (N =11), phthalates (N =16) or phenols (N =8). Generally, samples were collected prenatally or at birth and measurements involved few subjects in each cohort (a few hundred maximum). Biological matrices, timing, and analytical methods of the measurements varied between cohorts. Few cohorts have measured at multiple time points or in children. In European cohorts, levels of BFRs were very low and at least 10-fold lower than in US; levels of PFCs and phthalates have decreased over the last decade since the phasing out of certain of these compounds; concentrations of phenols are comparable to those in the US. Although there is little published data in the cohorts now, many measurements are ongoing and we recommend that cohorts start working towards combined and comparison studies. Specific recommendations for use of existing data include the development of conversion models for the different media used for measurement of persistent chemicals, and inter-laboratory comparisons and calibrations. Recommendations for further data collection include more evaluation of exposure to these chemicals in children; repeated measurements of non-persistent chemicals; validation and harmonisation of questionnaires; and the development of mechanisms for fast European birth cohort response for the detection and prioritisation of new chemicals of concern. [Copyright &y& Elsevier]

Abstract: Background: It has been suggested that African-American males, born in the 1970s, initiated the practice of smoking blunts during the rise of the hip-hop subculture in the 1990s. The objective of this study was to determine if other racial/ethnic groups from more recent birth cohorts adopted the practice as well. Methods: Data from seven cross-sectional surveys, the 2004–2010 National Surveys on Drug Use and Health, were aggregated for constructing six five-year birth cohorts (n =297,478), starting with the 1970–1974 cohort. Age-stratified regression models were then developed to test the effect of the interaction between race/ethnicity and birth cohort on the past-year use of blunts. Results: Fewer differences in the prevalence of past-year blunt smoking were observed between African-Americans and other racial/ethnic groups from more recent birth cohorts. Statistically significant interaction terms in age-stratified models indicated that relative to African-Americans, the odds ratios of blunt smoking were greater in Caucasians and Hispanics born in the1980s compared to those born in the late 1970s. These results were replicated when the sample was limited to past-year cannabis users (n =61,038). Conclusions: African-Americans, who likely initiated blunt smoking as adolescents/young adults in the 1990s, continued the practice into adulthood. As characterized by other drug eras, the drug became popular over time and expanded into other demographic groups. The additional exposure to tobacco should alert tobacco-control advocates about blunt smokers’ risk of developing nicotine dependence. [Copyright &y& Elsevier]

Abstract: North-western Italy has a long history of domestic influx, however little is known on how migrant mortality compares to mortality at the local level. While geographic mortality gradients may play a role, conceptualizations developed for international migration may also be relevant. Using this theoretical framework, the study investigated immigrant-native differentials in the north-western city of Turin through a 34-year follow-up that was facilitated by the Turin Longitudinal Study. The study population comprised inhabitants of age 30–74 years at the 1971 census. Survival trajectories were modelled through the Gompertz distribution and were examined for nativity status, birthplace, length of stay and age at arrival (the last two variables were combined). All estimates were adjusted for socio-economic factors. Overall, the risk of dying for internal migrants was lower, compared to locals, and consistent with geographic gradients. However, this pattern hid significant differences mediated by both age at arrival and length of stay. The advantage appeared to be exclusive to young and adult migrants, despite differentials narrowing over time. Immigrants who arrived after age 44 suffered instead a progressively greater excess risk, compared to natives, as residence increased. The dissipation of the health advantage found in internal migrants, along with poor health outcomes amongst people older at arrival, raises concern about immigrants from developing countries who need to endure a more demanding journey and adjustment to the new environment. The study indicated, through lengthy longitudinal data, that immigrant-native differentials were best explained by the stratified variable ‘length of stay by age at arrival’ and this should inform future studies. [Copyright &y& Elsevier]

Abstract: A huge cross-section literature, written by economists and others, argues that human well-being is U-shaped through the life cycle. In many cases this U-shape is robust (with a well-known exception the pattern evident in some U.S. data sets if few independent variables are included). However, a lively debate is currently ongoing about its true shape. This paper discusses the identification problem of age, time, and cohort effects. It suggests a simple way to interpret estimates of age variables in a first-difference framework. Building on methodology, the paper shows that no extra assumptions are needed in order to identify the second derivative of well-being to age, i.e. to estimate the changes in the actual age and well-being relationship. An empirical application, using a large German data set, finds that human well-being is convex in age until after midlife, which is approximately consistent with a U-shaped pattern through life, and not with the concave relationship sometimes found in U.S. studies. [Copyright &y& Elsevier]

Background: An increase in IgE antibody levels to inhalant allergens is associated with an increased likelihood of wheezing. The role of allergen-specific IgG and IgG4 in relation to wheezing is yet to be determined. Objective: We sought to investigate whether Fel d 1–specific IgG and IgG4 antibodies modify the association between cat allergen–specific IgE and childhood wheezing. Methods: We used data from 2 population-based birth cohorts (United Kingdom [UK], n = 473; Australia, n = 1336). Current wheeze was defined as wheezing in the previous 12 months at age 5 (UK) and 14 (Australia) years. We determined cat allergen–specific IgE (whole extract) and IgG and IgG4 antibody (purified rFel d 1) levels and used logistic regression to estimate the relationship between wheeze and the quantitative allergen antibody levels. Results: In the univariate analysis risk of wheezing increased significantly with increasing cat-specific IgE levels (UK: odds ratio [OR], 1.56; 95% CI, 1.28-1.90; Australia: OR, 1.29; 95% CI, 1.19-1.40). rFel d 1–specific IgG or IgG4 had no significant effect on wheeze in either population. However, a different pattern of the relationship between antibody levels and wheezing emerged in the multivariate analysis. In the UK cat-specific IgE increased the risk of wheeze (OR, 2.01; 95% CI, 1.29-3.12; P = .002), whereas rFel d 1–specific IgG decreased the risk (OR, 0.46; 95% CI, 0.21-0.99; P = .05). This finding was replicated in Australia (IgE: OR, 1.46; 95% CI, 1.28-1.68; P < .001; IgG: OR, 0.66; 95% CI, 0.44-0.99; P = .049). There was no significant association between IgG4 antibody levels and wheezing in either population. Conclusions: rFel d 1–specific IgG but not IgG4 antibody levels significantly modify the association between cat-specific IgE and childhood wheezing, with the risk of symptoms decreasing with increasing IgG levels. [ABSTRACT FROM AUTHOR]

Abstract: Many studies have cited the importance of secular changes or “period effects” as causes of the U.S. obesity epidemic. Unfortunately, relatively little attention has been devoted to the possible influence of cohort-related mechanisms. To address this current gap in the scientific literature, this investigation utilized the responses from 1.7 million participants in the 1976–2002 National Health Interview Surveys to determine how birth cohorts may have contributed to the rapid increase in the prevalence of obesity. Results from hierarchical age-period-cohort (HAPC) models confirmed that period effects are principally responsible for the U.S. obesity epidemic. However, HAPC models also demonstrated that birth cohort membership is influential. Independent of age and period effects, the predicted probability of obesity at age 25 increased by 30% for cohorts born between 1955 and 1975. Our results also showed that age, period and cohort effects varied by race/gender and educational attainment. For instance, increases in the predicted probabilities of obesity were particularly sharp for recent cohorts of Black females. Our investigation successfully demonstrated that both secular change and birth cohort membership have independently contributed to elevated odds of obesity among recent generations of Americans, suggesting that cohort-specific strategies may be needed to combat disconcertingly high rates of obesity in the U.S. [Copyright &y& Elsevier]

Abstract: Objectives: To examine the associations of age at menarche, timing of first birth and parity with hysterectomy rates; to investigate whether these associations were independent of each other and other potential confounders and varied by reason for hysterectomy. Methods: Women from the Medical Research Council National Survey of Health and Development, a cohort followed prospectively since birth in March 1946 across England, Scotland and Wales, were studied. Survival analyses were used to assess the relationships between reproductive characteristics and hysterectomy. Results: Age at menarche was inversely associated with hysterectomy rates (adjusted Hazard Ratio for hysterectomy associated with a 1 year increase in menarche=0.85 (95% CI: 0.77–0.95)). Parity was also associated with hysterectomy; women with ≥3 children experienced higher rates of hysterectomy than women with 1–2 children, who themselves experienced higher rates than nulliparous women. The associations of parity and age at menarche with hysterectomy were independent of each other and potential confounders. The association between age at menarche and hysterectomy was stronger for hysterectomies performed for fibroids than for other reasons. Conclusions: Our findings suggest that age at menarche is most likely acting to influence hysterectomy risk through its association with lifetime oestrogen exposure whereas parity is most likely acting through an effect on decision-making processes. This highlights the importance of considering both biological and social pathways to hysterectomy and confirms that medical need is not the only factor which needs to be considered when making treatment decisions for gynaecological problems. [Copyright &y& Elsevier]

Purpose: The aim was to follow the time trends of mortality from ulcerative colitis and compare them with those of gastric and duodenal ulcer. Methods: Mortality data from 21 different countries between 1941 and 2004 were analyzed. The age-specific death rates of each individual country, as well as the average age-specific rates of all countries, were plotted against the periods of birth and death. Results: The average trends of mortality from ulcerative colitis, gastric and duodenal ulcer reveal distinctive and unique birth-cohort patterns of all three diseases. Similar to both types of peptic ulcer, the risk of developing ulcerative colitis started to rise in successive generations born during the second half of the 19th century. It peaked shortly before the turn of the century and has continued to decline since then. The rise and fall in the occurrence of ulcerative colitis preceded those of both ulcer types. Conclusion: The birth-cohort pattern indicates that exposure to the relevant risk factors of ulcerative colitis occurs during early life. As the model of H. pylori and its associated birth-cohort patterns of gastric and duodenal ulcer suggest, an enteric infection provides a possible explanation for such temporal trends of ulcerative colitis as well. [Copyright &y& Elsevier]

Abstract: The focus of this contribution is on the changing patterns of offending among young people (aged 16–20 years) over time. Using six ‘birth cohorts’ aged 16–20 in the late 1960s, early 1970s, late 1970s, early 1980s, late 1980s, early 1990s and late 1990s, the study shows that crime participation – in terms of the proportions ever convicted – declined for both males and females. There has also been an overall shift from more ‘specialist’ criminal behaviour to more ‘versatile’ behaviour. While the gap between male and female offending is narrowing, the differences remain large. Although fewer young people are coming before the courts, the changing case mix has probably influenced the perception that offending is getting worse. As those committing ‘lesser’ offences are being dealt with by other means, there are higher proportions of young people coming before the courts who exhibit greater versatility and more violence. [Copyright &y& Elsevier]

Purpose: The aim of the study is to determine period and birth-cohort effects in the early initiation of phencyclidine (PCP) use in drug users in New York City (NYC). Methods: We analyzed data collected from two surveys of street-recruited drug users in NYC. We used survival analysis and proportional hazards modeling to assess period and birth-cohort effects on risk for early initiation of PCP use. Results: Of 787 participants, 292 (37.1%) had used PCP by the age of 23 years. Before 1987, there was a greater risk for initiation of PCP use through the age of 23 years (hazard ratio [HR] = 34.77; 95% confidence interval [CI], 21.45–56.36). Proportional hazards modeling showed that those born in the 1971 to 1975 birth cohort compared with those born in 1976 to 1980 had a lower risk for initiation of PCP use through age 23 years (HR = 0.58; 95% CI, 0.37–0.91). Other significant predictors of PCP use by age 23 included white race and having been in a juvenile detention center. Conclusions: There are period and birth-cohort differences in the likelihood of early initiation of PCP use. Changes in drug culture and social norms may influence the likelihood of initiation of PCP use. This may have implications for interventions aimed at slowing the nationwide increase in use of PCP. [Copyright &y& Elsevier]

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Based on interview data from 10,841 Danish women aged 20 to 29 years, determinants for non-use of contraception at first intercourse (NU) were studied. One-fourth of the women (n = 2704) reported NU, whereas condoms and oral contraceptives were used by, respectively, 59% and 15%. NU decreased with the birth year of the first male partner (OR = 3.6; 95% CI: 2.8–4.8 for ≤1954 vs. 1968–1974) mainly in favor of condom use. Other determinants were the birth cohort of the woman (OR = 1.4; 95% CI: 1.0–1.9 for 1961–1962 vs. 1970–1972) and the calendar year of the first intercourse (OR = 1.4; 95% CI: 1.2–1.7 for 1985–1986 vs. 1987–1992), both initially in favor of oral contraception and later in favor of condom use, whereas young age at first intercourse was associated with a high prevalence of NU (OR = 1.8; 95% CI: 1.4–2.1 for ≤14 years vs. ≥17 years) at the expense of both oral contraception and condom use. Finally, NU was found to predict high-risk sexual behavior in terms of subsequent multiple sex partners, non-use of condoms, and induced abortion. [Copyright &y& Elsevier]

Background: Variation in the Toll-like receptor 2 gene (TLR2/–16934) is associated with allergic diseases among farmers'' children but not among children not living on farms. Objective: To test the hypothesis that the same genetic variant conferring protection in the farming environment is associated with reduced risk of developing allergic phenotypes among urban children attending day care in early life. Methods: In 2 population-based birth cohorts (Manchester, United Kingdom, Manchester Asthma and Allergy Study [MAAS]; Tucson, Ariz, Tucson Infant Immune Study [IIS]), participants were recruited prenatally and followed prospectively (MAAS: 3, 5, 8 and 11 years; IIS: 1, 2, 3 and 5 years). We assessed allergic sensitization and atopic wheezing at each follow-up. Results: A total of 727 children participated in Manchester and 263 in Tucson. We found no significant associations between TLR2/–16934 and sensitization and atopic wheeze in either cohort. However, a different pattern emerged when we explored the interaction between TLR2/–16934 and day care attendance on these outcomes. We found a significant interaction between day care and TLR2/–16934 on the development of sensitization in the longitudinal model in MAAS in that children carrying the T allele who attended day care were less likely to be sensitized than those who did not attend day care, whereas among AA homozygotes, the association tended to be in the opposite direction. In a longitudinal model in IIS, we found a significant interaction between day care attendance and TLR2/–16934 on the development atopic wheezing. Significant interactions between TLR2/–16934 and day care were maintained when adjusting for socioeconomic status. Conclusion: The effect of day care on sensitization and atopic wheezing may differ among children with different variants of the TLR2 gene. [Copyright &y& Elsevier]

Summary: Although genetic component of asthma has been well recognised, genetics alone cannot explain the rise in asthma prevalence. This increase is likely a consequence of environmental factors increasing the risk in genetically susceptible individuals. As wheezing illness usually begins within months of birth, prospective birth cohorts with detailed measures of environmental exposures and objective measures of disease are essential to study gene-environment interactions in the development of different wheeze phenotypes. Such studies will enable identification of children at increased risk of disease because of a genetic predisposition when exposed to a particular environmental factor. Tailor-made evidence-based strategies for prevention of asthma and atopic sensitization applicable to individuals at risk (rather than the whole population) will then be developed to reduce the risk of asthma and allergy development. [Copyright &y& Elsevier]