A cohort of 839 young girls at the ages of 14 and 15 years was screened for total antibodies to herpes simplex virus (HSV) and, if positive, for specific antibodies to HSV-2, by means of a sensitive, enzyme-linked immunosorbent assay (ELISA). The cohort was followed from 1972-1987. Blood samples were obtained on six occasions during these 16 years. In total, 2270 blood samples were taken. The number of sero-converting girls was studied in relation to calendar time. Two methods were constructed for the statistical analyses. The first of these gave an estimate of the sero-prevalence at different points in time. This analysis showed that the sero-prevalence which was 23% against HSV-1 in 1972 had increased to 36% in 1976. At the end of the study in 1987, 50% of the cohort had sero-converted against HSV-1. The proportion of girls who had sero-converted against HSV-2 was 0.4% in the 14-15-year-olds and had reached 22% by the end of the study. The second statistical method used all the available information implicit in the observations so as to obtain a maximum-likelihood (ML) estimate of the prevalence. The ML estimates were slightly more precise, but the two estimates did not differ significantly. The observations were further analysed by the Mantel-Haenszel test in order to see if there was any dependence between positivity to HSV-1 and HSV-2 respectively but none was found.
Since Dr. Fogh-Andersen's legendary 1942 thesis, the Danish facial cleft population has been one of the most extensively studied in terms of epidemiology and genetic-epidemiology. The etiology of cleft lip and/or palate (CLP) is still largely an enigma, and different results concerning environmental and genetic risk factors are obtained in different countries and regions. This may be due to etiological heterogeneity between settings. Therefore, an in-depth studied area with an ethnically homogeneous population, such as Denmark, has provided one of the best opportunities for progress in CLP etiological research. The present review summarizes epidemiological and genetic-epidemiological studies conducted in the 20th century Danish facial cleft population. Furthermore, analyses of sex differences, time trends and seasonality for more than 7000 CLP cases born in Denmark in the period 1936 to 1987 are presented. The review also points toward the excellent opportunities for continued etiological CLP research in Denmark in the 21st century using already established resources and an on-going prospective cohort study of 100,000 pregnant women.
Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.
Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear.
We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy.
We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K).
We found differential DNA methylation at epigenome-wide statistical significance (p-value
We evaluated whether the association between low education and greater risk of dementia is explained by genetic influences, using three different types of analyses. The HARMONY study (Swedish for "health" (Hälsa), "genes" (ARv), "environment" (Miljö), "and" (Och), and "new" (NY)) includes members of the Swedish Twin Registry who were aged 65 and older and alive in 1998, and who were screened and clinically assessed for dementia. There were 394 cases with dementia and 7786 unrelated controls. Analyses included co-twin control, tests for association between education and a measured genotype, and bivariate twin modeling. Low education was a significant risk factor for dementia both in case-control analyses (odds ratio=1.77, 95% confidence interval 1.38 to 2.28) and co-twin control analyses with monozygotic twin pairs (odds ratio=3.17, 95% confidence interval 1.26 to 7.93). Apolipoprotein E genotype was not associated with education and did not account for the relationship between education and dementia. Bivariate twin modeling showed that the association between education and dementia was not mediated by genetic influences in common between education and dementia. The association was mediated by shared environmental influences that were related to both dementia and to education. Low education is confirmed as a risk factor for dementia. Findings from three different analytic approaches showed that genetic influences did not explain this association.
The burden of celiac disease (CD) is increasingly recognized as a global problem. However, whether this situation depends on genetics or environmental factors is uncertain. The authors examined these aspects in Sweden, a country in which the risk of CD is generally considered to be high. If environmental factors are relevant, CD risk in second-generation immigrant children should be related to maternal length of stay in Sweden before delivery.
Linking the Swedish Medical Birth Registry to other national registries, the authors investigated all singleton children (n = 792,401) born in Sweden between 1987 and 1993. They studied the risk of CD in children before age 6 as a function of the mother's geographical region of birth and length of stay in Sweden before delivery using Cox regression models.
In children whose mothers immigrated to Sweden from a country outside of Europe, a maternal length of stay in Sweden of more than 5 years increased the hazard ratio (HR) of CD (1.73, 95% confidence interval (CI) 1.06-2.81). The authors observed a similar result among children born to mothers from a Nordic country outside of Sweden (HR 1.57, 95% CI 0.89-2.75), but a non-conclusive protective effect was observed in second-generation immigrant children from a non-Nordic European country (HR 0.65, 95% CI 0.39-1.09).
The risk of CD among second-generation immigrants seems to be conditioned by maternal length of stay in Sweden before delivery, suggesting that environmental factors contribute to the variation in CD risk observed across populations.
Acrylamide, a probable human carcinogen, is formed in several foods during high-temperature processing. So far, epidemiological studies have not shown any association between human cancer risk and dietary exposure to acrylamide. The purpose of this study was to conduct a nested case control study within a prospective cohort study on the association between breast cancer and exposure to acrylamide using biomarkers. N-terminal hemoglobin adduct levels of acrylamide and its genotoxic metabolite, glycidamide in red blood cells were analyzed (by LC/MS/MS) as biomarkers of exposure on 374 breast cancer cases and 374 controls from a cohort of postmenopausal women. The adduct levels of acrylamide and glycidamide were similar in cases and controls, with smokers having much higher levels (approximately 3 times) than nonsmokers. No association was seen between acrylamide-hemoglobin levels and breast cancer risk neither unadjusted nor adjusted for the potential confounders HRT duration, parity, BMI, alcohol intake and education. After adjustment for smoking behavior, however, a positive association was seen between acrylamide-hemoglobin levels and estrogen receptor positive breast cancer with an estimated incidence rate ratio (95% CI) of 2.7 (1.1-6.6) per 10-fold increase in acrylamide-hemoglobin level. A weak association between glycidamide hemoglobin levels and incidence of estrogen receptor positive breast cancer was also found, this association, however, entirely disappeared when acrylamide and glycidamide hemoglobin levels were mutually adjusted.
Population aging increases the need for knowledge on positive aspects of aging, and contributions of older people to their own wellbeing and that of others. We defined active aging as an individual's striving for elements of wellbeing with activities as per their goals, abilities and opportunities. This study examines associations of health, health behaviors, health literacy and functional abilities, environmental and social support with active aging and wellbeing. We will develop and validate assessment methods for physical activity and physical resilience suitable for research on older people, and examine their associations with active aging and wellbeing. We will examine cohort effects on functional phenotypes underlying active aging and disability.
For this population-based study, we plan to recruit 1000 participants aged 75, 80 or 85 years living in central Finland, by drawing personal details from the population register. Participants are interviewed on active aging, wellbeing, disability, environmental and social support, mobility, health behavior and health literacy. Physical activity and heart rate are monitored for 7 days with wearable sensors. Functional tests include hearing, vision, muscle strength, reaction time, exercise tolerance, mobility, and cognitive performance. Clinical examination by a nurse and physician includes an electrocardiogram, tests of blood pressure, orthostatic regulation, arterial stiffness, and lung function, as well as a review of chronic and acute conditions and prescribed medications. C-reactive protein, small blood count, cholesterol and vitamin D are analyzed from blood samples. Associations of factors potentially underlying active aging and wellbeing will be studied using multivariate methods. Cohort effects will be studied by comparing test results of physical and cognitive functioning with results of a cohort examined in 1989-90.
The current study will renew research on positive gerontology through the novel approach to active aging and by suggesting new biomarkers of resilience and active aging. Therefore, high interdisciplinary impact is expected. This cross-sectional study will not provide knowledge on temporal order of events or causality, but an innovative cross-sectional dataset provides opportunities for emergence of novel creative hypotheses and theories.
The Inuit population of Nunavik (Canada) is exposed to immunotoxic organochlorines (OCs) mainly through the consumption of fish and marine mammal fat. We investigated the effect of perinatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) on the incidence of acute infections in Inuit infants. We reviewed the medical charts of a cohort of 199 Inuit infants during the first 12 months of life and evaluated the incidence rates of upper and lower respiratory tract infections (URTI and LRTIs, respectively), otitis media, and gastrointestinal (GI) infections. Maternal plasma during delivery and infant plasma at 7 months of age were sampled and assayed for PCBs and DDE. Compared to rates for infants in the first quartile of exposure to PCBs (least exposed), adjusted rate ratios for infants in higher quartiles ranged between 1.09 and 1.32 for URTIs, 0.99 and 1.39 for otitis, 1.52 and 1.89 for GI infections, and 1.16 and 1.68 for LRTIs during the first 6 months of follow-up. For all infections combined, the rate ratios ranged from 1.17 to 1.27. The effect size was similar for DDE exposure but was lower for the full 12-month follow-up. Globally, most rate ratios were > 1.0, but few were statistically significant (p
Human development reportedly includes critical and sensitive periods during which environmental stressors can affect traits that persist throughout life. Controversy remains over which of these periods provides an opportunity for such stressors to affect health and longevity. The elaboration of reproductive biology and its behavioral sequelae during adolescence suggests such a sensitive period, particularly among males. We test the hypothesis that life expectancy at age 20 among males exposed to life-threatening stressors during early adolescence will fall below that among other males. We apply time-series methods to cohort mortality data in France between 1816 and 1919, England and Wales between 1841 and 1919, and Sweden between 1861 and 1919. Our results indicate an inverse association between cohort death rates at ages 10-14 and cohort life expectancy at age 20. Our findings imply that better-informed and more strategic management of the stressors encountered by early adolescents may improve population health.
Neck pain is very common but the occurrence of bothersome neck pain is not well described. Therefore our objective was to report on the prevalence and incidence of, as well as the rate of recovery from, bothersome neck pain in men and women of different ages in the general population.
We used data from a recently conducted population-based cohort study, comprising 23,794 individuals in Stockholm County, Sweden. Study participants were surveyed with a self-administered questionnaire in 2002/2003 and 2007, and information on episodes of neck pain was gathered at baseline and at follow-up. We then measured bothersome neck pain in 2005 and 2006 retrospectively in 2007 using the follow-up questionnaire.
The one-year prevalence of bothersome neck pain for at least seven consecutive days was 25% (95% confidence interval (CI): 24-25) among women and 16% (95% CI: 15-16) among men, peaking in individuals aged 30-59 years. The one-year incidence proportion of bothersome neck pain was 7% (95% CI: 6-7) among women, and 4% (95% CI: 4-5) among men. Women recovered more infrequently than men. The one-year incidence proportion of recovery (of at least one year duration) was 11% (95% CI: 10-12) among women and 14% (95% CI: 12-16) among men.
Bothersome neck pain is most common in middle-aged individuals. Women are more likely than men to have and to develop bothersome neck pain, and less likely to recover from such pain. Younger men and women have a higher incidence, but recover more often from bothersome neck pain than older individuals.
Airborne particulate matter from primarily geologic, non-industrial sources at levels below National Ambient Air Quality Standards is associated with outpatient visits for asthma and quick-relief medication prescriptions among children less than 20 years old enrolled in Medicaid in Anchorage, Alaska.
In Anchorage, Alaska, particulates with aerodynamic diameter or = 34 micro g/m(3). A significant 18.1% increase (RR: 1.181, 95% CI: 1.010-1.381) in the rate of quick-relief medication prescriptions occurred during days with PM(10) of 34-60 micro g/m(3), and a 28.8% increase (RR: 1.288, 95% CI: 1.026-1.619) occurred during days with PM(10) > or = 61 micro g/m(3). Similar results for outpatient asthma visits and quick-relief medication occurred in weekly models. There were no significant associations with PM(2.5) in either daily or weekly models. These subtle but statistically significant associations suggest that non-industrial, geologic sources of PM(10) may have measurable health effects at levels below current national standards.
It has been suggested that children that are exposed to a stressful environment at home have an increased susceptibility for air pollution-related asthma. The aim here was to investigate the association between air pollution exposure and asthma, and effect modification by mental health and by socio-economic status (as markers of a stressful environment). All individuals under 18 years of age in four Swedish counties during 2007 to 2010 (1.2 million people) were included. The outcome was defined as dispensing at least two asthma medications during follow up. We linked data on NO2 from an empirical land use regression to data from national registers on outcome and potential confounders. Data was analyzed with logistic regression. There was an odds ratio (OR) of 1.02 (95% Confidence Interval (CI: 1.01-1.03) for asthma associated with a 10 µg·m-3 increase in NO2. The association only seemed to be present in areas where NO2 was higher than 15 µg·m-3 with an OR of 1.09 (95% CI: 1.07-1.12), and the association seemed stronger in children with parents with a high education, OR = 1.05 (95% CI: 1.02-1.09) and OR = 1.04 (95% CI: 1.01-1.07) in children to mothers and father with a high education, respectively. The association did not seem to depend on medication history of psychiatric disorders. There was weak evidence for the association between air pollution and asthma to be stronger in neighborhoods with higher education levels. In conclusion, air pollution was associated with dispensed asthma medications, especially in areas with comparatively higher levels of air pollution, and in children to parents with high education. We did not observe support for our hypothesis that stressors linked to socio-economy or mental health problems would increase susceptibility to the effects of air pollution on the development of asthma.
Vehicle engine exhaust includes ultrafine particles with a large surface area and containing absorbed polycyclic aromatic hydrocarbons, transition metals and other substances. Ultrafine particles and soluble chemicals can be transported from the airways to other organs, such as the liver, kidneys, and brain. Our aim was to investigate whether air pollution from traffic is associated with risk for other cancers than lung cancer.
We followed up 54,304 participants in the Danish Diet Cancer and Health cohort for 20 selected cancers in the Danish Cancer Registry, from enrolment in 1993-1997 until 2006, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used modeled concentration of nitrogen oxides (NO(x)) and amount of traffic at the residence as indicators of traffic-related air pollution and used Cox models to estimate incidence rate ratios (IRRs) after adjustment for potential confounders.
NO(x) at the residence was significantly associated with risks for cervical cancer (IRR, 2.45; 95% confidence interval [CI], 1.01;5.93, per 100 µg/m(3) NO(x)) and brain cancer (IRR, 2.28; 95% CI, 1.25;4.19, per 100 µg/m(3) NO(x)).
This hypothesis-generating study indicates that traffic-related air pollution might increase the risks for cervical and brain cancer, which should be tested in future studies.
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Limited research has examined the association between physical activity, health-related fitness, and disease outcomes in breast cancer survivors. Here, we present the rationale and design of the Alberta Moving Beyond Breast Cancer (AMBER) Study, a prospective cohort study designed specifically to examine the role of physical activity and health-related fitness in breast cancer survivorship from the time of diagnosis and for the balance of life. The AMBER Study will examine the role of physical activity and health-related fitness in facilitating treatment completion, alleviating treatment side effects, hastening recovery after treatments, improving long term quality of life, and reducing the risks of disease recurrence, other chronic diseases, and premature death.
The AMBER Study will enroll 1500 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a 5 year period. Assessments will be made at baseline (within 90 days of surgery), 1 year, and 3 years consisting of objective and self-reported measurements of physical activity, health-related fitness, blood collection, lymphedema, patient-reported outcomes, and determinants of physical activity. A final assessment at 5 years will measure patient-reported data only. The cohort members will be followed for an additional 5 years for disease outcomes.
The AMBER cohort will answer key questions related to physical activity and health-related fitness in breast cancer survivors including: (1) the independent and interactive associations of physical activity and health-related fitness with disease outcomes (e.g., recurrence, breast cancer-specific mortality, overall survival), treatment completion rates, symptoms and side effects (e.g., pain, lymphedema, fatigue, neuropathy), quality of life, and psychosocial functioning (e.g., anxiety, depression, self-esteem, happiness), (2) the determinants of physical activity and health-related fitness including demographic, medical, social cognitive, and environmental variables, (3) the mediators of any observed associations between physical activity, health-related fitness, and health outcomes including biological, functional, and psychosocial, and (4) the moderators of any observed associations including demographic, medical, and biological/disease factors. Taken together, these data will provide a comprehensive inquiry into the outcomes, determinants, mechanisms, and moderators of physical activity and health-related fitness in breast cancer survivors.
BACKGROUND: Two contradictory hypotheses have been proposed to explain the relationship between allergic conditions and malignancies, the immune surveillance hypothesis and the antigenic stimulation hypothesis. The former advocates that allergic conditions may be protective against development of cancer, whereas the latter proposes an increased risk. This relationship has been studied in several case-control studies, but only in a few cohort studies. METHODS: The association between allergic conditions and risk of developing leukemia, Hodgkin's disease, non-Hodgkin's lymphoma and myeloma was investigated in a cohort of 16,539 Swedish twins born 1886-1925. Prospectively collected, self-reported information about allergic conditions such as asthma, hay fever or eczema was obtained through questionnaires administered in 1967. The cohort was followed 1969-99 and cancer incidence was ascertained from the Swedish Cancer Registry. RESULTS: Hives and asthma tended to increase the risk of leukemia (relative risk [RR] = 2.1, 95% Confidence Interval [CI] 1.0-4.5 and RR = 1.6, 95% CI 0.8-3.5, respectively). There was also an indication of an increased risk of non-Hodgkin's lymphoma associated with eczema during childhood (RR = 2.3, 95% CI 1.0-5.3). CONCLUSION: In contrast to most previous studies, our results do not indicate a protective effect of allergic conditions on the risk of developing hematological malignancies. Rather, they suggest that allergic conditions might increase the risk of some hematological malignancies.
The theory that natural selection has conserved mechanisms by which women subjected to environmental stressors abort frail male fetuses implies that climate change may affect sex ratio at birth and male longevity. Using time series methods, we find that cold ambient temperatures during gestation predict lower secondary sex ratios and longer life span of males in annual birth cohorts composed of Danes, Finns, Norwegians, and Swedes born between 1878 (earliest year with complete life tables) and 1914 (last birth cohort for which male life span can be estimated). We conclude that ambient temperature affects the characteristics of human populations by influencing who survives gestation, a heretofore unrecognized effect of climate on humanity.
The aim of this study was to assess the influence of social environmental factors on school performance and behavioural problems among 14-year-old children who had been exposed to amphetamine during foetal life. The study group comprised a cohort of 65 children who had suffered intrauterine exposure to amphetamine due to maternal drug abuse. This group has been followed since birth and examined at regular intervals. Information regarding the academic performance of the children was gathered from the school authorities. The psychosocial environment of the children was determined through interviews and through information obtained from the social authorities. Of the 64 children who attended a school within the state school system, 10 (15%) were a year behind for their age. The mean grades were significantly lower than those of their classmates. Behavioural problems were mentioned in the social authority documentation of one-third of the children, regardless of whether the child was placed in a foster home or was residing with the biological mother. A positive significant correlation was found between maternal age and the outcome of the children, as well as between therapy during pregnancy and outcome, whilst several environmental factors, particularly during the child's first four years, correlate negatively to outcome. Psychosocial factors early in life influence the outcome at 14 years. The positive effect of intervention during pregnancy illustrates the importance of early identification preferable during pregnancy.
There is a need to better define phenotypes of asthma. However, many studies have data available only on asthma and atopy, so they are often used to define ‘atopic’ and ‘non-atopic’ asthma. We discuss and illustrate the problems of analyzing such outcomes. We used the 31 year follow-up of the Northern Finland Birth Cohort 1966 (n=5,429). ‘Atopic asthma’ and ‘non-atopic asthma’ were defined based on presence or absence of atopy (any skin prick test =3 mm) at age 31. Gender and ownership of cat in childhood were used as risk factors. Simple calculations on hypothetical datasets were used to support the conclusions. ‘Atopic asthma’ and ‘non-atopic asthma’, are not well separated disease entities. The association of a risk factor with ‘atopic asthma’ and ‘non-atopic asthma’ is determined both by its association with asthma and with atopy. E.g. if a risk factor is not associated with asthma, but is protective for atopy, this will produce a protective association with ‘atopic asthma’, but an opposite association with ‘non-atopic asthma’. This is the result from the typical analysis, which uses all non-asthmatics as the comparison group. Valid results, unconfounded by atopy, can be gained by comparing asthmatics to nonasthmatics separately among atopics and non-atopics, i.e. by doing the analysis stratified by atopy. If data only on asthma and atopy are available, asthma and atopy should be analyzed at first as separate outcomes. If atopic and nonatopic asthma are used as additional outcomes, valid results can be gained by stratifying the analysis by atopy.
To identify and describe work related serious injuries among sawmill workers in British Columbia, Canada using hospital discharge records, and compare the agreement and capturing patterns of the work related indicators available in the hospital discharge records.
Hospital discharge records were extracted from 1989 to 1998 for a cohort of sawmill workers. Work related injuries were identified from these records using International Classification of Disease (ICD-9) external cause of injury codes, which have a fifth digit, and sometimes a fourth digit, indicating place of occurrence, and the responsibility of payment schedule, which identifies workers' compensation as being responsible for payment.
The most frequent causes of work related hospitalisations were falls, machinery related, overexertion, struck against, cutting or piercing, and struck by falling objects. Almost all cases of machinery related, struck by falling object, and caught in or between injuries were found to be work related. Overall, there was good agreement between the two indicators (ICD-9 code and payment schedule) for identifying work relatedness of injury hospitalisations (kappa = 0.75, p
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To investigate whether high rates of chromosomal aberrations (CAs), sister chromatid exchange (SCE), or micronuclei(MN) in peripheral lymphocytes indicate an increased risk for subsequent cancer, a prospective cohort study of 2,969 subjects cytogenetically examined between 1970 and 1988 in four Swedish, two Finnish, and two Norwegian laboratories was initiated. To standardize for the interlaboratory variation, the results of the three cytogenetic endpoints were trichotomized for each laboratory into "low" (1st to 33rd percentile), "medium" (34th to 66th percentile), and "high" (67th to 100th percentile]. Thirty-four cancers had been diagnosed in the cohort during the observation period (1970 to 1985). The point-estimates of the standardized morbidity ratio (SMR) in the three CA strata were 90, 92, and 180, respectively. This trend for a positive association was not statistically significant (p = 0.06). There was no significant trend between SMR and the trichotomized rates of SCE. In the subcohort examined for MN only two cases of cancer had been diagnosed until now. If subjects with "high" frequencies of CA or SCE have a two-fold (or greater) risk of developing cancer as compared with individuals who have "medium" or "low" frequencies, we estimate that there is a likelihood of 80% and 70%, respectively, that this will be detectable as significant (p less than or equal to 0.05) differences after a further follow-up period of 5 years. Weaker associations between cancer risk and the cytogenetic endpoints would not be possible to evaluate until even later follow-ups.