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Purpose: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. Methods: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. Results: Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94–1.15), astrocytoma (OR 1.01, 95% CI 0.87–1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93–1.32), or ependymoma (OR 1.06, 95% CI 0.81–1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses. Conclusion: Our data suggest that breastfeeding does not protect against CBT. [ABSTRACT FROM AUTHOR]

Context: Recent epidemiological studies have shown increased risk of diabetes among childhood cancer survivors who received high therapeutic doses of radiation, particularly to the total body or to the abdomen. However, the effect of low-to-moderate dose radiation (<4 Gy) on the risk of diabetes is still unknown. Objectives: To investigate the radiation effect on diabetes incidence among atomic bomb (A-bomb) survivors, and whether the dose response is modified by other factors including city, sex, and age at time of bombing (ATB). Methods: 9131 participants without diabetes at baseline were observed through biennial clinical exams from 1969 to 2015. A Cox proportional hazards model was used to estimate hazard ratios (HR) to evaluate the dose response for diabetes incidence. Results: During the study period, 1417 incident diabetes cases were identified. The overall crude incidence rate was 7.01/103 person-years. Radiation dose was significantly associated with diabetes incidence, with effect modification by city and age ATB. In Hiroshima, at ages 10 and 30 ATB, the HRs at 1 Gy of pancreatic radiation dose were 1.47 (95% CI, 1.31-1.66) and 1.13 (95% CI, 0.97-1.31), respectively. However, no significant radiation dose response was observed at these ages in Nagasaki. The HR for radiation dose was higher among those who were younger ATB and decreased 1% for each additional year of age. Conclusions: Among A-bomb survivors, a radiation association was suggested for incidence of diabetes. Results were inconsistent by city and age ATB, which could indicate potential confounding of the radiation association with diabetes. [ABSTRACT FROM AUTHOR]

For 65 years the interpretation of the statistical association between the risk of cancer in a child and a prior diagnostic X-ray examination of the abdomen of the pregnant mother has been debated. The objections to a direct cause-and-effect explanation of the association vary in their strength, but one of the most notable grounds for controversy is the finding from the first and largest case-control study reporting the association, the Oxford Survey of Childhood Cancers (OSCC), of an almost uniformly raised relative risk (RR) for nearly all of the types of cancer that are most frequent in children. Here we compare the antenatal X-ray associations found in the OSCC for different types of childhood cancer with the results of all other case-control and case-cohort studies appropriately combined in meta-analyses, and we also review the findings of the few cohort studies that have been conducted. From the case-control/case-cohort studies other than the OSCC there are consistent and clear elevations of risk for all types of childhood cancer combined, all leukemia, and all cancers except leukemia combined. This compatibility of the findings of the OSCC with those of the combined other studies is less clear, or effectively absent, when some categories containing smaller numbers of incident cases/deaths are considered, but lack of precision of risk estimates due to sparse data presents inferential challenges, although there is a consistent absence of an association for bone tumors. Further, more recent studies almost certainly address lower intrauterine doses, with an anticipated decrease in estimated risks, which could be misleading when comparisons involve a limited number of studies that are mainly from later years, and a similar problem arises when having to employ all types of antenatal X-ray exposures for a study because data for abdominal exposures are absent. The problem of low statistical power is greater for cohort studies, and this, together with other shortcomings identified in the studies, limits the interpretational value of results. The findings of non-medical intrauterine exposure studies are constrained by sparse data and make a limited contribution to an understanding of the association. Certain aspects of the various studies require a need for caution in interpretation, but overall, the appropriate combination of all case-control/case-cohort studies other than the OSCC lends support to the inference that low-level exposure to radiation in utero proportionally increases the risk of the typical cancers of childhood to around the same level. [ABSTRACT FROM AUTHOR]

Objectives Psychosocial job strain has been associated with a range of adverse health outcomes. The aim of this study was to examine the association between psychosocial job strain and prospective risk of polypharmacy (the prescription of ≥5 medications) and to evaluate whether coping strategies can modify this risk. Methods Cohort study of 9703 working adults [mean age 47.5 (SD 10.8) years; 54% female] who participated in the Swedish Longitudinal Occupational Survey of Health (SLOSH) at baseline in 2006 or 2008. Psychosocial job strain was represented by job demands and control, and measured by the Swedish version of the demand-control questionnaire. The outcome was incidence of polypharmacy over an eight-year follow-up period. Information on dispensed drugs were extracted from the Swedish Prescribed Drug Register. Logistic regression was used to estimate the association of job strain status with polypharmacy, adjusted for a range of confounders. Results During the follow-up, 1409 people developed polypharmacy (incident rate: 20.6/1000 person-years). In comparison to workers with low-strain jobs (high control/low demands), those with high-strain jobs (low control/high demands) had a significantly higher risk of incident polypharmacy (OR 1.40, 95% CI 1.04-1.89). The impact of high-strain jobs on developing polypharmacy remained among those with covert coping strategies (ie, directed inwards or towards others) but not among those with open coping strategies (ie, primarily directed toward the stressor). Conclusions Workers in high-strain jobs may be at an increased risk of polypharmacy. Open coping strategies may reduce the negative impact of psychosocial job strain on risk of polypharmacy. [ABSTRACT FROM AUTHOR]

Purpose: In 2011, the International Commission on Radiological Protection reduced the threshold for the lens effects of low linear energy transfer (LET) radiation. On one hand, the revised threshold of 0.5 Gy is much lower than previously recommended thresholds, but mechanisms behind high radiosensitivity remain incompletely understood. On the other hand, such a threshold is independent of dose rate, in contrast to previously recommended separate thresholds each for single and fractionated/protracted exposures. Such a change was made predicated on epidemiological evidence suggesting that a threshold for fractionated/protracted exposures is not higher than an acute threshold, and that a chronic threshold is uncertain. Thus, the dose rate dependence is still unclear. This paper therefore reviews the current knowledge on the radiosensitivity of the lens and the dose rate dependence of radiation cataractogenesis, and discusses its mechanisms. Conclusions: Mounting biological evidence indicates that the lens cells are not necessarily radiosensitive to cell killing, and the high radiosensitivity of the lens thus appears to be attributable to other mechanisms (e.g., excessive proliferation, abnormal differentiation, a slow repair of DNA double-strand breaks, telomere, senescence, crystallin changes, non-targeted effects and inflammation). Both biological and epidemiological evidence generally supports the lack of dose rate effects. However, there is also biological evidence for the tissue sparing dose rate (or fractionation) effect of low-LET radiation and an enhancing inverse dose fractionation effect of high-LET radiation at a limited range of LET. Emerging epidemiological evidence in chronically exposed individuals implies the inverse dose rate effect. Further biological and epidemiological studies are warranted to gain deeper knowledge on the radiosensitivity of the lens and dose rate dependence of radiation cataractogenesis. [ABSTRACT FROM AUTHOR]

The paper continues the series of publications from the International Nuclear Workers Study cohort that comprises 308,297 workers from France, the United Kingdom and the United States, providing 8.2 million person-years of observation from a combined follow-up period (at earliest 1944 to at latest 2005). These workers' external radiation exposures were primarily to photons, resulting in an estimated average career absorbed dose to the colon of 17.4 milligray. The association between cumulative ionizing radiation dose and cancer mortality was evaluated in general relative risk models that describe modification of the excess relative risk (ERR) per gray (Gy) by time since exposure and age at exposure. Methods analogous to a nested-case control study using conditional logistic regression of sampled risks sets were used. Outcomes included: all solid cancers, lung cancer, leukemias excluding chronic lymphocytic, acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma, Hodgkin lymphoma and non-Hodgkin lymphoma. Significant risk heterogeneity was evident in chronic myeloid leukemia with time since exposure, where we observed increased ERR per Gy estimates shortly after exposure (2-10 year) and again later (20-30 years). We observed delayed effects for acute myeloid leukemia although estimates were not statistically significant. Solid cancer excess risk was restricted to exposure at age 35+ years and also diminished for exposure 30 years prior to attained age. Persistent or late effects suggest additional follow-up may inform on lifetime risks. However, cautious interpretation of results is needed due to analytical limitations and a lack of confirmatory results from other studies. [ABSTRACT FROM AUTHOR]

The number of cancer survivors continues to increase worldwide. Many of these survivors have had children of their own. It is less well-known whether radiation therapy or chemotherapy could affect the risk of stillbirth and neonatal death for these children. To explore this research questions, we identified all women diagnosed with cancer between 1958 and 2012 from the Swedish Cancer Register and they were further linked to the Swedish Medical Birth Register to identify their subsequent child birth between 1973 and 2012. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between stillbirth and neonatal death and maternal cancer diagnosis. As compared to the children without maternal cancer, the risk of stillbirth was significantly higher among children of female cancer survivors born within three years after cancer diagnosis with an OR of 1.92 (95% CI 1.03-3.57). The incidence of neonatal death did not show a significant change. For women with more than one pregnancy after cancer diagnosis, the risk of stillbirth and neonatal death was lower for the second child birth compared to the first child birth. Our study suggested that the risk of stillbirth was negatively associated with the time after cancer diagnosis, providing evidence that the adverse effect associated with cancer treatment may diminish with time. [ABSTRACT FROM AUTHOR]

In cohort mortality studies, there often is interest in associations between an exposure of primary interest and mortality due to a range of different causes. A standard approach to such analyses involves fitting a separate regression model for each type of outcome. However, the statistical precision of some estimated associations may be poor because of sparse data. In this paper, we describe a hierarchical regression model for estimation of parameters describing outcome-specific relative rate functions and associated credible intervals. The proposed model uses background stratification to provide flexible control for the outcome-specific associations of potential confounders, and it employs a hierarchical “shrinkage” approach to stabilize estimates of an exposure’s associations with mortality due to different causes of death. The approach is illustrated in analyses of cancer mortality in 2 cohorts: a cohort of dioxin-exposed US chemical workers and a cohort of radiation-exposed Japanese atomic bomb survivors. Compared with standard regression estimates of associations, hierarchical regression yielded estimates with improved precision that tended to have less extreme values. The hierarchical regression approach also allowed the fitting of models with effect-measure modification. The proposed hierarchical approach can yield estimates of association that are more precise than conventional estimates when one wishes to estimate associations with multiple outcomes. [ABSTRACT FROM AUTHOR]

Introduction: In India there is an increasing trend in hypertension prevalence among the general population. Studies have shown that tribal populations in India are also experiencing this burden. Objective: The aim was to estimate the pooled prevalence of primary hypertension among adult tribal populations of India. Methods: A systematic search was conducted in MEDLINE, IndMed, Web of Science, Google Scholar and major journals for studies published between 1981 and 2011. Two authors independently reviewed the studies, did quality assessment and extracted data in pre-coded spread-sheets. Pooled estimates of prevalence of hypertension were calculated using DerSimonian-Laird random effects model. Subgroup and sensitivity analyses and meta-regression were performed. Results: Twenty studies or 53 subpopulations with 64 674 subjects were included in final review. The pooled estimate of hypertension prevalence was 16.1% (95% CI: 13.5, 19.2). There was significant heterogeneity among the studies (I2 = 99% and Q = 4624.0, df  = 53, p<0.001). Subgroup analyses showed that year of study, acculturation status, special features, and BP measurement techniques significantly influenced prevalence, but after meta-regression analyses, ‘decade of study’ remained the only covariate that significantly and independently influenced prevalence (R2 = 0.57, Q = 119.2, df  = 49, p value <0.001). Conclusion: An increasing trend was found in the prevalence of hypertension in adult tribal populations across three decades. Although acculturation was probably the underlying agent that caused this increase, other unmeasured factors that need further research were also important. Concerned policy makers should focus on the changing health needs of tribal communities. [ABSTRACT FROM AUTHOR]

Objectives. We examined the relationship between genetic ancestry, socioeconomic status (SES), and lung cancer among African Americans and Latinos. Methods. We evaluated SES and genetic ancestry in a Northern California lung cancer case-control study (1998-2003) of African Americans and Latinos. Lung cancer case and control participants were frequency matched on age, gender, and race/ethnicity. We assessed case-control differences in individual admixture proportions using the 2-sample t test and analysis of covariance. Logistic regression models examined associations among genetic ancestry, socioeconomic characteristics, and lung cancer. Results. Decreased Amerindian ancestry was associated with higher education among Latino control participants and greater African ancestry was associated with decreased education among African lung cancer case participants. Education was associated with lung cancer among both Latinos and African Americans, independent of smoking, ancestry, age, and gender. Genetic ancestry was not associated with lung cancer among African Americans. Conclusions. Findings suggest that socioeconomic factors may have a greater impact than genetic ancestry on lung cancer among African Americans. The genetic heterogeneity and recent dynamic migration and acculturation of Latinos complicate recruitment; thus, epidemiological analyses and findings should be interpreted cautiously. [ABSTRACT FROM AUTHOR]

Background: Above-ground and underground nuclear weapon detonation at the Nevada Test Site (1951-1992) has resulted in radioiodine exposure for nearby populations. Although the long-term effect of environmental radioiodine exposure on thyroid disease has been well studied, little is known regarding the effect of childhood radioiodine exposure on subsequent fertility. Objectives: We investigated early childhood thyroid radiation exposure from nuclear testing fallout (supplied predominantly by radioactive isotopes of iodine) and self-reported lifetime incidence of male or female infertility or sterility. Methods: Participants were members of the 1965 Intermountain Fallout Cohort, schoolchildren at the time of exposure who were reexamined during two subsequent study phases to collect dietary and reproductive histories. Thyroid radiation exposure was calculated via an updated dosimetry model. We used multivariable logistic regression with robust sandwich estimators to estimate odds ratios for infertility, adjusted for potential confounders and (in separate models) for a medically confirmed history of thyroid disease. Results: Of 1,389 participants with dosimetry and known fertility history, 274 were classified as infertile, including 30 classified as sterile. Childhood thyroid radiation dose was possibly associated with infertility [adjusted odds ratio (AOR) = 1.17; 95% CI: 0.82, 1.67 and AOR = 1.35; 95% CI: 0.96, 1.90 for the middle and upper tertiles vs. the first tertile of exposure, respectively]. The odds ratios were attenuated (AOR = 1.08; 95% CI: 0.75, 1.55 and AOR = 1.29; 95% CI: 0.91, 1.83 for the middle and upper tertiles, respectively) after adjusting for thyroid disease. There was no association of childhood radiation dose and sterility. Conclusion: Our findings suggest that childhood radioiodine exposure from nuclear testing may be related to subsequent adult infertility. Further research is required to confirm this. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that environmental exposures to pesticides, tobacco, and other xenobiotic chemicals may increase risk of childhood acute lymphoblastic leukemia (ALL). We sought to evaluate the role of genes involved in xenobiotic transport and metabolism in childhood ALL risk, both alone and in conjunction with household chemical exposures previously found to be associated with childhood ALL risk. Methods: We conducted a population-based epidemiologic study of 377 cases and 448 controls in California, utilizing a haplotype-based approach to evaluate 42 xenobiotic transport and metabolism genes in conjunction with data on self-reported household chemical exposures. Results: We identified significant associations of childhood ALL risk with haplotypes of ABCB1, ARNT, CYP2C8, CYP1A2, CYP1B1, and IDH1. In addition, certain haplotypes showed significant joint effects with self-reported household chemical exposures on risk of childhood ALL. Specifically, elevated risks associated with use of paints in the home (ever) and indoor insecticides (pre-birth) were limited to subjects carrying specific haplotypes of CYP2C8 and ABCB1, respectively. Conclusions: Our results provide support for a role of xenobiotic transport and metabolism pathways in risk of childhood ALL and indicate that genes in these pathways may modulate the risk of disease associated with use of common household chemicals. Additional studies are needed to confirm these findings and localize specific causal variants. [ABSTRACT FROM AUTHOR]

Different approaches are necessary when community-based participatory research (CBPR) of environmental illness is initiated after an environmental disaster within a community. Often such events are viewed as golden scientific opportunities to do epidemiological studies. However, the authors believe that in such circumstances, community engagement and empowerment needs to be integrated into the public health service efforts in order for both those and any science to be successful, with special care being taken to address the immediate health needs of the community first, rather than the pressing needs to answer important scientific questions. The authors will demonstrate how they have simultaneously provided valuable public health service, embedded generalizable scientific knowledge, and built a successful foundation for supplemental CBPR through their on-going recovery work after the chlorine gas disaster in Graniteville, South Carolina. [ABSTRACT FROM AUTHOR]

This manuscript provides a comprehensive review of the epidemiologic evidence linking the continuum of adiposity and type 2 diabetes (T2D) with Alzheimer's disease (AD). The mechanisms relating adiposity and T2D to AD may include hyperinsulinemia, advanced products of glycosylation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of AD but the data on this association in old age is conflicting. Several studies have shown that hyperinsulinemia, a consequence of higher adiposity and insulin resistance, is also related to a higher risk of AD. Hyperinsulinemia is a risk factor for T2D, and numerous studies have shown a relation of T2D with higher AD risk. The implication of these associations is that a large proportion of the world population may be at increased risk of AD given the trends for increasing prevalence of overweight, obesity, hyperinsulinemia, and T2D. However these associations may present a unique opportunity for prevention and treatment of AD. Several studies in the prevention and treatment of T2D are currently conducting, or have planned, cognition ancillary studies. In addition, clinical trials using insulin sensitizers in the treatment or prevention of AD are under way. [ABSTRACT FROM AUTHOR]

There are few data on the skeletal health of Hispanic men. We observed differences in vitamin D deficiency and low BMD between Hispanic ethnic subgroups that persisted with adjustment for risk factors. Our data indicate a substantial burden of low BMD and vitamin D deficiency among Hispanic men. Disparities within ethnic groups are generally ignored, but in evolving populations they may have implications for public health. We examined ethnic variation in serum 25-hydroxyvitamin D [25(OH)D] and bone mineral density (BMD) among Hispanic American men. Three hundred and fifty-eight Hispanic males 30 to 79 years of age were studied. Logistic regression models assessed variation in odds of vitamin D deficiency (<20 ng/mL) and low BMD ( T-score<−1) by ethnicity, with and without adjustment for risk factors (age, smoking, occupation, physical activity, body mass index, and sunlight exposure). Vitamin D deficiency was most common among Puerto Rican (26%), compared with Dominican (21%), Central American (11%), and South American (9%) men. Percentages with low BMD were: South American (44%), Puerto Rican (34%), Dominican (29%), and Central American (23%). Adjustment for age and risk factors failed to account for Hispanic subgroup differences in vitamin D deficiency and low BMD. Population estimates indicate a substantial burden of low BMD and vitamin D deficiency among Hispanic men. Our findings underscore the importance of examining the skeletal health of Hispanic subgroups, and suggest that a considerable number of Hispanic men may be at elevated risk of fracture and vitamin D deficiency. [ABSTRACT FROM AUTHOR]

Aims We investigated the association of diabetic retinopathy with the risk of incident cardiovascular disease (CVD) events in a large cohort of Type 2 diabetic adults. Methods Our study cohort comprised 2103 Type 2 diabetic outpatients who were free of diagnosed CVD at baseline. Retinal findings were classified based on fundoscopy (by a single ophthalmologist) to categories of no retinopathy, non-proliferative retinopathy and proliferative/laser-treated retinopathy. Outcomes measures were incident CVD events (i.e. non-fatal myocardial infarction, non-fatal ischaemic stroke, coronary revascularization procedures or cardiovascular death). Results During approximately 7 years of follow-up, 406 participants subsequently developed incident CVD events, whereas 1697 participants remained free of diagnosed CVD. After adjustment for age, body mass index, waist circumference, smoking, lipids, glycated haemoglobin, diabetes duration and medications use, patients with non-proliferative or proliferative/laser-treated retinopathy had a greater risk ( P < 0.001 for all) of incident CVD events than those without retinopathy [hazard ratio 1.61 (95% confidence interval 1.2–2.6) and 3.75 (2.0–7.4) for men, and 1.67 (1.3–2.8) and 3.81 (2.2–7.3) for women, respectively]. After additional adjustment for hypertension and advanced nephropathy (defined as overt proteinuria and/or estimated glomerular filtration rate ≤ 60 ml/min/1.73 m2), the risk of incident CVD remained markedly increased in those with proliferative/laser-treated retinopathy [hazard ratio 2.08 (1.02–3.7) for men and 2.41 (1.05–3.9) for women], but not in those with non-proliferative retinopathy. Conclusions Diabetic retinopathy (especially in its more advanced stages) is associated with an increased CVD incidence independent of other known cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

The prevalence of obesity in adults has been rising continually, as has the prevalence of childhood obesity, and a large number of epidemiological studies have demonstrated a direct relationship between parental obesity and childhood obesity. In this paper, we review the effect of diet, the intrauterine environment, and the genetic inheritance on obesity . We described a study in detail that used experimental animals as a model to investigate the effect of a parental high-fat diet on body-fat accumulation in their offspring. Fertilized eggs were transplanted in that study, and body-fat accumulation in the offspring of the parents fed a high-fat diet was found to be greater than in the offspring of the parents fed a low-fat diet, even when the experimental conditions were the same in the intrauterine and subsequent environment. The results suggested that a parental high-fat diet before intrauterine developmental stage may increase body-fat accumulation in the offspring. We discuss the possibility that parental diet may influence the lifelong health of offspring and epigenetic inheritance may be occurred. [ABSTRACT FROM AUTHOR]

Objective: This article mainly attempts to review the recent human literature on the adverse effects of occupational factors on fertility, developmental effects and genetic changes in the germ line, which lead to genetic malformations or to genetic disease. The secondary study aim is to answer whether occupational exposures are quantitative momentously for 15% involuntarily childless couples, 10–20% spontaneous abortions and 3% birth defects. Methods: A literature survey was conducted for publications on these subjects focusing on the latest publications. PubMed (Medline. ) was used for this literature search. Results: Publication bias and a large amount of confounding factors, which have to be controlled, make the design of human fertility studies difficult. Epidemiologic studies using time to conception techniques have been useful in identifying substances and exposure scenarios with proven toxic effect on fertility. The collected studies suggest that the exposure to the following substances or occupational settings may affect fertility function: lead, organic mercury compounds, manganese, carbon disulfide, 2-bromopropane and dibromochloropropane, welding, professional driving and working with heat. Concerning developmental effects even for methyl mercury, which was in group A of the German MAK list, to date no reliable evidence of the damaging effect on the human fetus under actual work conditions has been obtained. It is also difficult to classify substances according to their mutagenic potential for the germ cell, since no direct evidence of an association between exposure against a physical or chemical pollutant and the occurrence of a hereditary disorder has been found yet. Conclusion: In conclusion there are only a few substances which may affect reproductive function in the workplace without a doubt. The decreasing fertility of women in Western countries can be explained by the increasing female reproduction age, rather than by occupational exposures. Also the rates for spontaneous abortions and birth defects cannot be explained by industrial exposures at the workplace. [ABSTRACT FROM AUTHOR]

Objective To determine the prevalence of neurofibromatosis 1 (NF1) among 6-year-old children in Germany. Setting and Patients A total of 152819 children aged 6 years in 6 German states were screened for NF1 during routine medical examinations at elementary school enrollment in cooperation with local health departments in 2000 and 2001. Main Outcome Measure The prevalence of NF1 among 6-year-old German children was estimated to be 1:2996 (95% confidence interval, 1:2260 to 1:3984). Results Fifty-one NF1 cases were identified and confirmed by evaluation by appropriate medical specialists. Seven other children were found to have multiple café au lait spots without other apparent features of NF1. A minimum estimate of the crude prevalence was 3.0 per 10 000 (95% confidence interval, 2.3-4.0 per 10 000 population). The incidence of NF1 in this population was probably in the range of 30 to 38 cases per 100 000 live births. Conclusion Our study obtained a nearly unbiased birth incidence of NF1 of approximately 1 in 2600 to 1 in 3000 and demonstrates that NF1 can be diagnosed by age 6 years in most cases by routine physical examination with special attention to the disease-associated skin stigmata. [ABSTRACT FROM AUTHOR]

The objectives of the National Survey of American Life (NSAL) are to investigate the nature, severity) and impairment of mental disorders among national samples of the black and non-Hispanic white (n = 1,006) populations in the US. Special emphasis in the study is given to the nature of race and ethnicity within the black population by selecting and interviewing national samples of African-American (N = 3,570), and Afro-Caribbean (N = 1,623) immigrant and second and older generation populations. National multi-stage probability methods were used in generating the samples and race/ethnic matching of interviewers and respondents were used in the largely face-to-face interview, which lasted on average 2 hours and 20 minutes. The Diagnostic and Statistical Manual (DSM) LV World Mental Health Composite Interview (WHO-CIDI) was used to assess a wide range of serious mental disorders, potential risk and resilience factors, and help seeking and service use patterns. This paper provides an overview of the design of the NSAL, sample selection procedures, recruitment and training of the national interviewing team, and some of the special problems faced in interviewing ethnically and racially diverse national samples. Unique features of sample design, including special screening and listing procedures, interviewer training and supervision, and response rate outcomes are described. [ABSTRACT FROM AUTHOR]

Ionizing radiation has been the subject of intense epidemiological investigation. Studies have demonstrated that exposure to moderate-to-high levels can cause most forms of cancer, leukaemia and cancers of the breast, lung and thyroid being particularly sensitive to induction by radiation, especially at young ages at exposure. Predominant among these studies is the Life Span Study of the cohort of survivors of the atomic bombings of Japan in 1945, but substantial evidence is derived from groups exposed for medical reasons, occupationally or environmentally. Notable among these other groups are underground hard rock miners who inhaled radioactive radon gas and its decay products, large numbers of patients irradiated therapeutically and workers who received high doses in the nuclear weapons programme of the former USSR. The degree of carcinogenic risk arising from low levels of exposure is more contentious, but the available evidence points to an increased risk that is approximately proportional to the dose received. Epidemiological investigations of nonionizing radiation have established ultraviolet radiation as a cause of skin cancer. However, the evidence for a carcinogenic effect of other forms of nonionizing radiation, such as those associated with mobile telephones or electricity transmission lines, is not convincing, although the possibility of a link between childhood leukaemia and extremely low-frequency electromagnetic fields cannot be dismissed entirely.Oncogene (2004) 23, 6404-6428. doi:10.1038/sj.onc.1207896 [ABSTRACT FROM AUTHOR]

Major congenital anomalies are diagnosed in 2-4% of births. In this paper we review epidemiological studies that have specifically looked at congenital anomalies as a possible outcome of community exposure to chemical exposures associated with environmental pollution. These include studies of drinking water contaminants (heavy metals and nitrates, chlorinated and aromatic solvents, and chlorination by-products), residence near waste disposal sites and contaminated land, pesticide exposure in agricultural areas, air pollution and industrial pollution sources, food contamination, and disasters involving accidental, negligent or deliberate chemical releases of great magnitude. We conclude that there are relatively few environmental pollution exposures for which we can draw strong conclusions about the potential to cause congenital anomalies and, if so, the chemical constituents implicated, to provide an evidence base for public health and clinical practice. A precautionary approach should be adopted at both community and individual level. In order to prevent congenital anomalies, one must reduce exposure to potential teratogens before pregnancy is recognized (i.e. preconceptionally and in the first few weeks of pregnancy). It is a challenge to develop effective strategies for preconceptional care within the primary care framework. Prenatal service providers and counsellors need to be aware of the uncertainties regarding environmental pollution when addressing parental concerns. [ABSTRACT FROM AUTHOR]

The ongoing debate over the possible beneficial effects of ionising radiation on health, hormesis, is reviewed from different perspectives. Radiation hormesis has not been strictly defined in the scientific literature. It can be understood as a decrease in the risk of cancer due to low-dose irradiation, but other positive health effects may also be encompassed by the concept. The overwhelming majority of the currently available epidemiological data on populations exposed to ionising radiation support the assumption that there is a linear non-threshold dose-response relationship. However, epidemiological data fail to demonstrate detrimental effects of ionising radiation at absorbed doses smaller than 100-200 mSv. Risk estimates for these levels are therefore based on extrapolations from higher doses. Arguments for hormesis are derived only from a number of epidemiological studies, but also from studies in radiation biology. Radiobiological evidence for hormesis is based on radio-adaptive response; this has been convincingly demonstrated in vitro, but some questions remain as to how it affects humans. Furthermore, there is an ecologically based argument for hormesis in that, given the evolutionary prerequisite of best fitness, it follows that humans are best adapted to background levels of ionising radiation and other carcinogenic agents in our environment. A few animal studies have also addressed the hormesis theory, some of which have supported it while others have not. To complete the picture, the results of new radiobiological research indicate the need for a paradigm shift concerning the mechanisms of cancer induction. Such research is a step towards a better understanding of how ionising radiation affects the living cell and the organism, and thus towards a more reliable judgement on how to interpret the present radiobiological evidence for hormesis. [ABSTRACT FROM AUTHOR]

It has been postulated that paternal gonadal exposure would increase the sex ratio by inducing X-chromosomal dominant lethals but that maternal gonadal exposure would decrease the sex ratio by inducing recessive sex-linked lethals. We therefore evaluated the sex ratio (male-to-female ratio) of children born to survivors of childhood cancers in Denmark. Children with cancer were identified from the Danish Cancer Registry from 1943 to 1996 and their offspring from the Central Population Registry. Radiation treatments were determined from records within the Cancer Registry and gonadal radiation exposures were estimated based on the cancer being treated and the likely proximity of the radiation fields to the gonads. Overall, 1100 survivors of childhood cancer became the parents of 2130 children. The sex ratio for male (0.99) and female (1.00) cancer survivors was similar and did not differ significantly from the Danish population (1.06). Radiotherapy did not influence the sex ratio of the children of either male or female survivors, and there was no evidence for dose-related changes over categories of estimated dose to parental gonads. We saw no consistent association between the sex ratio and the interval between cancer diagnosis of the parent and birth of the child. This nationwide study provides no support for the hypothesis that radiation exposure to the gonads results in an inherited genetic effect that would be manifested by a change in the sex ratio of children born after exposure. It may be, however, that sex ratio alterations are not a good or even a valid indicator of possible genetic effects in humans. [ABSTRACT FROM AUTHOR]

Gallbladder cancer is usually associated with gallstone disease, late diagnosis, unsatisfactory treatment, and poor prognosis. We report here the worldwide geographical distribution of gallbladder cancer, review the main etiologic hypotheses, and provide some comments on perspectives for prevention. The highest incidence rate of gallbladder cancer is found among populations of the Andean area, North American Indians, and Mexican Americans. Gallbladder cancer is up to three times higher among women than men in all populations. The highest incidence rates in Europe are found in Poland, the Czech Republic, and Slovakia. Incidence rates in other regions of the world are relatively low. The highest mortality rates are also reported from South America, 3.5-15.5 per 100,000 among Chilean Mapuche Indians, Bolivians, and Chilean Hispanics. Intermediate rates, 3.7 to 9.1 per 100,000, are reported from Peru, Ecuador, Colombia, and Brazil. Mortality rates are low in North America, with the exception of high rates among American Indians in New Mexico (11.3 per 100,000) and among Mexican Americans. The main associated risk factors identified so far include cholelithiasis (especially untreated chronic symptomatic gallstones), obesity, reproductive factors, chronic infections of the gallbladder, and environmental exposure to specific chemicals. These suspected factors likely represent promoters of carcinogenesis. The main limitations of epidemiologic studies on gallbladder cancer are the small sample sizes and specific problems in quantifying exposure to putative risk factors. The natural history of gallbladder disease should be characterized to support the allocation of more resources for early treatment of symptomatic gallbladder disease in high-risk populations. Secondary prevention of gallbladder cancer could be effective if supported by cost-effective studies of prophylactic cholecystectomy among asymptomatic gallstone patients in high-risk areas. [ABSTRACT FROM AUTHOR]

BACKGROUND: Birth weight is positively associated with body mass index (BMI, kg/m²) in later life, but is inversely associated with cardiovascular risk. To understand this paradox, we examined the relationships between birth weight, adult BMI, and estimations of lean and fat tissue in young men. METHODS: From 192 applicants for military service (ages 17-22y, mean BMI 23.2 kg/m²) with known birth weights we measured the circumference and anterior skinfold thickness at midthigh to estimate thigh muscle + bone area and subcutaneous fat area. Linear regression models including birth weight as the independent variable were adjusted for race and adult height. RESULTS: BMI was linearly associated with birth weight (standardized regression coefficient, [SRC] = +0.27; P = 0.0004), as was the thigh muscle + bone area (SRC = +0.22; P = 0.0029), but not the thigh subcutaneous fat area (SRC = +0.13; P = 0.086). The BMI-birth weight association was reduced by 68% when the regression model was further adjusted for thigh muscle + bone area. Separate adjustment for thigh subcutaneous fat, however, reduced the BMI-birth weight association by only 30%. Waist circumference was also associated with birth weight (SRC = +0.24; P = 0.0014), sagittal abdominal diameter was weakly associated (SRC = +0.17; P = 0.028), but waist/thigh ratio and abdominal diameter index were not associated with birth weight. INTERPRETATION: The larger BMI associated with higher birth weight may reflect increments in lean tissue more than increments in fat. Birth weight's influence on lean tissue is observed in the thigh and, among fit young men, perhaps at the waist. Increased muscularity in young men may partly explain the cardiovascular benefit in middle age ascribed to higher birth weight. [ABSTRACT FROM AUTHOR]

Expounds on the role of epidemiology in the detection of harmful effects of radiation. Inaccuracies of data on acute injuries of atomic bomb survivors taken from life span cohort studies; Preferability of using linear extrapolation of the high dose effects observed in atomic bomb survivors.

Objective: The epidemiologic necropsy measures the occurrence of unsuspected disease through the examination of necropsy records of patients who died for other reasons. The estimates of unsuspected disease derived from the epidemiologic necropsy should approximate what actually occurs in the living population.Design/setting: To test this hypothesis, all necropsy records of adult patients at the University of Kansas Medical Center from 1950 to 1984 were examined for the presence of gallstones. Patients with previous cholecystectomy or whose gallstones were diagnosed during life were excluded. The data were stratified by age and race and compared with those of a screening survey from Canada, a surgical series from New York, two screening surveys from Italy, and one from Denmark. The crude necropsy detection rates and the rates from the screening surveys were standardized to the 1970 federal census for Kansas City.Results/conclusions: The standardized occurrence rates were similar and suggest that the epidemiologic necropsy accurately assesses the occurrence of asymptomatic gallstones in the living population, thus strengthening its validity as a research tool. [ABSTRACT FROM AUTHOR]

We investigated offspring sex ratio among 6232 offspring born to 3218 survivors of childhood cancer in relation to therapeutic irradiation, and pooled our data with those from two other large-scale studies giving a total of 9685 offspring. Exposure to high-dose gonadal irradiation was not associated with a significant alteration in offspring sex ratio compared to low doses (men: P=0.58, women: P=0.66). There was also no evidence that the ratio varied with time since cancer diagnosis when comparing survivors treated with radiotherapy vs those without (men: P=0.51; women: P=0.46). This, the largest study to date, finds no evidence that exposure to radiation affects the offspring sex ratio among survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Author(s): Thorkild I. A. Sørensen [sup.1] [sup.2] Author Affiliations: (1) Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Copenhagen, Denmark (2) Department of [...]