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Background: The Early Markers for Autism (EMA) study is a population-based case–control study designed to learn more about early biologic processes involved in ASD. Methods: Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n = 629) and intellectual disability without ASD (ID, n = 230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n = 599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions. Results: EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels. Limitations: Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced. Conclusions: Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures. [ABSTRACT FROM AUTHOR]

The Study to Explore Early Development (SEED) is a multi-site case-control study designed to explore the relationship between autism spectrum disorder (ASD) phenotypes and etiologies. The goals of this paper are to (1) describe the SEED algorithm that uses the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) to classify children with ASD, (2) examine psychometric properties of different ASD classification methods, including the SEED method that incorporates rules for resolving ADI-R and ADOS discordance, and (3) determine whether restricted interests and repetitive behaviors were noted for children who had instrument discordance resolved using ADI-R social and communication scores. Results support the utility of SEED criteria when well-defined groups of children are an important clinical or research outcome. [ABSTRACT FROM AUTHOR]

Objective: To describe the implementation of a test-negative design case-control study in California during the Coronavirus Disease 2019 (COVID-19) pandemic. Study design: Test-negative case-control study Methods: Between February 24, 2021 ‐ February 24, 2022, a team of 34 interviewers called 38,470 Californians, enrolling 1,885 that tested positive for SARS-CoV-2 (cases) and 1,871 testing negative for SARS-CoV-2 (controls) for 20-minute telephone survey. We estimated adjusted odds ratios for answering the phone and consenting to participate using mixed effects logistic regression. We used a web-based anonymous survey to compile interviewer experiences. Results: Cases had 1.29-fold (95% CI: 1.24–1.35) higher adjusted odds of answering the phone and 1.69-fold (1.56–1.83) higher adjusted odds of consenting to participate compared to controls. Calls placed from 4pm to 6pm had the highest adjusted odds of being answered. Some interviewers experienced mental wellness challenges interacting with participants with physical (e.g., food, shelter, etc.) and emotional (e.g., grief counseling) needs, and enduring verbal harassment from individuals called. Conclusions: Calls placed during afternoon hours may optimize response rate when enrolling controls to a case-control study during a public health emergency response. Proactive check-ins and continual collection of interviewer experience(s) and may help maintain mental wellbeing of investigation workforce. Remaining adaptive to the dynamic needs of the investigation team is critical to a successful study, especially in emergent public health crises, like that represented by the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Given the potential for retraumatization among survivors of sexual violence engaged in research, we aimed to provide pertinent knowledge and exemplification of the integration of trauma-informed practice to research with survivors. Grounded in trauma-informed care, we discuss the need for trauma-informed research, drawing upon experiences and data from a longitudinal case-control study on sexual violence. Through trauma-informed research settings, we can improve research experiences for survivors of sexual violence, as demonstrated by positive experiences of participants in The THRIVE Study. By meeting the needs of survivors, researchers can increase participation while maximizing the research quality and advancement of research. [ABSTRACT FROM AUTHOR]

Background: Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. Methods: This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. Results: Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81–10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04–1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06–1.22). Conclusions: We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation. [ABSTRACT FROM AUTHOR]

To determine occupational risk factors for coccidioidomycosis among adult Hispanic outdoor agricultural workers in California, USA, we conducted a case-control study of workers seen at the Kern County medical facility and referred to the public health laboratory for coccidioidomycosis serologic testing. Participants completed an interviewer-administered health and work questionnaire. Among 203 participants (110 case-patients with positive and 93 controls with negative serologic results), approximately half were women, and more than three quarters were born in Mexico. Associated with coccidioidomycosis were self-reported dust exposure and work with root and bulb vegetable crops. A protective factor was leaf removal, an activity associated with grape cultivation. We conclude that subjective dust exposure and work with root and bulb vegetable crops are associated with increased risk for coccidioidomycosis among Hispanic farm workers. The agricultural industry should evaluate and promote dust-reduction measures, including wetting soil and freshly harvested products. [ABSTRACT FROM AUTHOR]

Anesthesia workspaces are integral components in the chains of many intraoperative bacterial transmission events resulting in surgical site infections (SSI). Matched cohort designs can be used to compare SSI rates among operating rooms (ORs) with or without capital equipment purchases (e.g., new anesthesia machines). Patients receiving care in intervention ORs (i.e., with installed capital equipment) are matched with similar patients receiving care in ORs lacking the intervention. We evaluate statistical power of an alternative design for clinical trials in which, instead, SSI incidences are compared directly among ORs (i.e., the ORs form the clusters) at single hospitals (e.g., the 5 ORs with bactericidal lights vs. the 5 other ORs). Data used for parameter estimates were SSI for 24 categories of procedures among 338 hospitals in the State of California, 2015. Estimated statistical power was ≅8.4% for detecting a reduction in the incidence of SSI from 3.6% to 2.4% over 1 year with 5 intervention ORs and 5 control ORs. For ≅80% statistical power, >20 such hospitals would be needed to complete a study in 1 year. Matched paired cluster designs pair similar ORs (e.g., 2 cardiac ORs, 1 to intervention and 1 to control). With 5 pairs, statistical power would be even less than the estimated 8.4%. Cluster designs (i.e., analyses by OR) are not suitable for comparing SSI among ORs at single hospitals. Even though matched cohort designs are non-randomized and thus have lesser validity, matching patients by their risk factors for SSI is more practical. [ABSTRACT FROM AUTHOR]

The article presents information on a summary of a case control medical research published in the journal, which evaluates the effectiveness of pertussis vaccines in adolescents and adults. The study illustrates that the effect of acellular pertussis vaccines is abated eventually when given in childhood. This study included participants including both cases and controls from Kaiser Permanente Northern California, a healthcare delivery system.

Background: There is evidence that tibial slope may play a role in revision risk after anterior cruciate ligament reconstruction (ACLR); however, prior studies are inconsistent. Purpose: To determine (1) whether there is a difference in lateral tibial posterior slope (LTPS) or medial tibial posterior slope (MTPS) between patients undergoing revised ACLR and those not requiring revision and (2) whether the medial-to-lateral slope difference is different between these 2 groups. Study Design: Case-control study; Level of evidence, 3. Methods: We conducted a matched case-control study (2006-2015). Cases were patients aged ≤21 years who underwent revision surgery after primary unilateral ACLR; controls were patients aged ≤21 years without revision who were identified from the same source population. Controls were matched to cases by age, sex, body mass index, race, graft type, femoral fixation device, and post-ACLR follow-up time. Tibial slope measurements were made by a single blinded reviewer using magnetic resonance imaging. The Wilcoxon signed rank test and McNemar test were used for continuous and categorical variables, respectively. Results: No difference was observed between revised and nonrevised ACLR groups for LTPS (median: 6° vs 6°, P =.973) or MTPS (median: 4° vs 5°, P =.281). Furthermore, no difference was found for medial-to-lateral slope difference (median: −1 vs −1, P =.289). A greater proportion of patients with revised ACLR had an LTPS ≥12° (7.6% vs 3.8%) and ≥13° (4.7% vs 1.3%); however, this was not statistically significant after accounting for multiple testing. Conclusion: We failed to observe an association between revision ACLR surgery and LTPS, MTPS, or medial-to-lateral slope difference. However, there was a greater proportion of patients in the revision ACLR group with an LTPS ≥12°, suggesting that a minority of patients who have more extreme values of LTPS have a higher revision risk after primary ACLR. A future cohort study evaluating the angle that best differentiates patients at highest risk for revision is needed. [ABSTRACT FROM AUTHOR]

Purpose: Hypertension in pregnancy has been associated with decreased future risk of breast cancer in many but not all studies. In the Marin Women's Study, pregnancy-induced hypertension was shown to interact with the T allele of a functional IGF1R gene variant, rs2016347, to result in lower breast density, as well as decreased breast cancer risk. Our objective was to explore these findings in a larger sample of women from the California Teachers Study (CTS).Methods: The CTS cohort consists of over 130,000 female educators. DNA was available from a nested case-control study, which included 2,030 non-Hispanic white women who developed breast cancer and 1,552 controls. The current study included all participants from the case-control group with a self-reported history of preeclampsia (80 cases/57 controls).Results: Comparing TT to GG genotypes revealed adjusted odds ratios of 0.38 (CI 0.13, 1.14) for all invasive breast cancers, 0.26 (CI 0.07, 0.89) for hormone receptor-positive (HR+) breast cancers, 0.15 (CI 0.04, 0.56) for those with age at first birth (AFB) < 30, and 0.10 (CI 0.02, 0.49) for those with AFB < 30 and HR+ breast cancers. Trend analysis yielded p values of 0.09, 0.03, 0.005, and 0.004 respectively, suggesting a biological effect for each T allele.Conclusion: Study findings indicate that the T allele of IGF1R variant rs2016347 is associated with a significant reduction in breast cancer risk in women with a history of preeclampsia, most marked for HR+ breast cancer and in women with AFB < 30. [ABSTRACT FROM AUTHOR]

Purpose: Studies have reported an increased risk of childhood leukemia associated with exposure to magnetic fields. We conducted a large records-based case-control study of childhood leukemia risk and exposure to magnetic fields from power lines in California.Methods: The study included 5,788 childhood leukemia cases (born in and diagnosed in California 1986-2008) matched to population-based controls on age and sex. We calculated magnetic fields at birth addresses using geographic information systems, aerial imagery, historical information on load and phasing, and site visits.Results: Based on unconditional logistic regression controlling for age, sex, race/ethnicity, and socioeconomic status using subjects geocoded to a basic standard of accuracy, we report a slight risk deficit in two intermediate exposure groups and a small excess risk in the highest exposure group (odds ratio of 1.50 (95% confidence interval [0.70, 3.23])). Subgroup and sensitivity analyses as well as matched analyses gave similar results. All estimates had wide confidence intervals.Conclusion: Our large, statewide, record-based case-control study of childhood leukemia in California does not in itself provide clear evidence of risk associated with greater exposure to magnetic fields from power lines, but could be viewed as consistent with previous findings of increased risk. [ABSTRACT FROM AUTHOR]

Previous studies on maternal nutrition and childhood leukaemia risk have focused on the role of specific nutrients such as folate and have not considered broader measures of diet quality, which may better capture intake of diverse nutrients known to impact fetal development. We examined the relationship between maternal diet quality before pregnancy, as summarised by a diet quality index, and risk of childhood acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in a case–control study in California. Dietary intake in the year before pregnancy was assessed using FFQ in 681 ALL cases, 103 AML cases and 1076 matched controls. Conditional logistic regression was used to estimate OR and 95 % CI for diet quality continuous score and quartiles (Q1–Q4). Higher maternal diet quality score was associated with reduced risk of ALL (OR 0·66; 95 % CI 0·47, 0·93 for Q4 v. Q1) and possibly AML (OR 0·42; 95 % CI 0·15, 1·15 for Q4 v. Q1). No single index component appeared to account for the association. The association of maternal diet quality with risk of ALL was stronger in children diagnosed under the age of 5 years and in children of women who did not report using vitamin supplements before pregnancy. These findings suggest that the joint effects of many dietary components may be important in influencing childhood leukaemia risk. [ABSTRACT FROM AUTHOR]

BACKGROUND: Preterm birth (PTB) has been associated with exposure to air pollution, but it is unclear whether effects might vary among air pollution sources and components. OBJECTIVES: We studied the relationships between PTB and exposure to different components of air pollution, including gases and particulate matter (PM) by size fraction, chemical composition, and sources. METHODS: Fine and ultrafine PM (respectively, PM2.5 and PM0.1) by source and composition were modeled across California over 2000-2008. Measured PM2.5, nitrogen dioxide, and ozone concentrations were spatially interpolated using empirical Bayesian kriging. Primary traffic emissions at fine scale were modeled using CALINE4 and traffic indices. Data on maternal characteristics, pregnancies, and birth outcomes were obtained from birth certificates. Associations between PTB (n = 442,314) and air pollution exposures defined according to the maternal residence at birth were examined using a nested matched case-control approach. Analyses were adjusted for maternal age, race/ethnicity, education and neighborhood income. RESULTS: Adjusted odds ratios for PTB in association with interquartile range (IQR) increases in average exposure during pregnancy were 1.133 (95% CI: 1.118, 1.148) for total PM2.5, 1.096 (95% CI: 1.085, 1.108) for ozone, and 1.079 (95% CI: 1.065, 1.093) for nitrogen dioxide. For primary PM, the strongest associations per IQR by source were estimated for onroad gasoline (9-11% increase), followed by onroad diesel (6-8%) and commercial meat cooking (4-7%). For PM2.5 composition, the strongest positive associations per IQR were estimated for nitrate, ammonium, and secondary organic aerosols (11-14%), followed by elemental and organic carbon (2-4%). Associations with local traffic emissions were positive only when analyses were restricted to births with residences geocoded at the tax parcel level. CONCLUSIONS: In our statewide nested case-control study population, exposures to both primary and secondary pollutants were associated with an increase in PTB. [ABSTRACT FROM AUTHOR]

Objectives Despite being encouraged to take pre-natal supplements, suboptimal micronutrient intake is common in pregnancy, especially among Hispanic women. In this study, we assessed whether initiation and timing of pre-natal vitamin use influences the risk of preterm birth. Methods Women who gave birth to singletons in 2003 in Los Angeles County, California, were enrolled into a population-based case-control study. Focusing on non-Hispanic white and Hispanic women, associations between timing of pre-natal supplement use and preterm birth were assessed using logistic regression. Results Among Hispanic mothers, the odds of preterm birth increased the later a woman initiated pre-natal supplement use in pregnancy. The magnitude of this association was larger in US-born compared to foreign-born Hispanic women. Conclusions These findings suggest that nativity may modify the relationship between pre-natal supplement use and preterm birth possibly due to underlying differences in diet composition of Hispanic women by place of birth. [ABSTRACT FROM AUTHOR]

Purpose: Folate, vitamins B12 and B6, riboflavin, and methionine are critical nutrients for the one-carbon metabolism cycle involved in DNA synthesis and epigenetic processes. We examined the association between maternal intake of these nutrients before pregnancy and risk of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in a matched case-control study.Methods: Maternal dietary intake and vitamin supplement use in the year before pregnancy was assessed by food frequency questionnaire for 681 ALL cases, 103 AML cases, and 1076 controls. Principal component analysis was used to construct a variable representing combined nutrient intake, and conditional logistic regression estimated the odds ratio (OR) and 95% confidence interval (CI) for the association of ALL and AML with the principal component and each nutrient.Results: Higher maternal intake of one-carbon metabolism nutrients from food and supplements combined was associated with reduced risk of ALL (OR for one-unit change in the principal component = 0.91, CI 0.84-0.99) and possibly AML (OR for the principal component = 0.83, CI 0.66-1.04). When analyzed separately, intake of supplements high in these nutrients was associated with a reduced risk of ALL in children of Hispanic women only.Conclusions: In conclusion, these data suggest that higher maternal intake of one-carbon metabolism nutrients may reduce risk of childhood leukemia. [ABSTRACT FROM AUTHOR]

We conducted a nested case-control study including 407 cases and 2,075 frequency matched controls to investigate the association between maternal infections during pregnancy and risk of autism spectrum disorders (ASD). Cases, controls, and maternal infections were ascertained from Kaiser Permanente Northern California clinical databases. No overall association between diagnoses of any maternal infection during pregnancy and ASD was observed [adjusted odds ratio (OR) = 1.15, 95 % confidence interval (CI) 0.92-1.43]. However, women with infections diagnosed during a hospital admission (OR = 1.48, 95 % CI 1.07-2.04), particularly bacterial infections (OR = 1.58, 95 % CI 1.06-2.37), were at increased risk of delivering a child with ASD. Multiple infections during pregnancy were associated with ASD (OR = 1.36, 95 % CI 1.05-1.78). [ABSTRACT FROM AUTHOR]

Objectives:Hispanics are the fastest growing ethnic/racial group of the older adult population in the United States, yet little is known about positive mental health in this group. We examined differences in life satisfaction between demographically matched groups of older Hispanics and non-Hispanic Whites, and sought to identify specific factors associated with these differences Methods:Participants included 126 community-dwelling English-speaking Hispanics aged 50 and older, and 126 age-, gender-, and education-matched non-Hispanic Whites. Participants completed standardized measures of life satisfaction and postulated correlates, including physical, cognitive, emotional and social functioning, as well as positive psychological traits and religiosity/spirituality. Results:Hispanics reported greater life satisfaction than non-Hispanic Whites (p< 0.001). Ethnic groups were comparable on most postulated correlates of life satisfaction, except that Hispanics had lower levels of cognitive performance, and higher levels of daily spiritual experiences, private religious practices and compassion (ps< 0.001). Among these factors, spiritual experiences, religious practices, and compassion were significantly associated with life satisfaction in the overall sample. Multivariable analyses testing the influence of these three factors on the association between ethnicity and life satisfaction showed that higher spirituality among Hispanics accounted for ethnic differences in life satisfaction. Conclusion:English-speaking Hispanics aged 50 and older appeared to be more satisfied with their lives than their non-Hispanic White counterparts, and these differences were primarily driven by higher spirituality among Hispanics. Future studies should examine positive mental health among various Hispanic subgroups, including Spanish speakers, as an important step toward development of culturally sensitive prevention and intervention programs aimed at promoting positive mental health. [ABSTRACT FROM PUBLISHER]

Background We conducted a large registry-based study in California to investigate the association between race/ethnicity and childhood leukaemia focusing on two subtypes: acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Methods We obtained information on 5788 cases and 5788 controls by linking California cancer and birth registries. We evaluated relative risk of childhood leukaemia by race and ethnicity of the child and their parents using conditional logistic regression, with adjustment for potential confounders. Results Compared with Whites, Black children had lower risk of ALL (OR=0.54, 95% CI 0.45 to 0.66) as well as children of Black/Asian parents (OR=0.31, 95% CI 0.10 to 0.94). Asian race was associated with increased risk of AML with OR=1.643, 95% CI 1.10 to 2.46 for Asian vs Whites; and OR=1.67, 95% CI 1.04 to 2.70 for Asian/Asian vs White/White. Hispanic ethnicity was associated with increased risk of ALL (OR=1.37, 95% CI 1.22 to 1.52). A gradient in risk of ALL was observed while comparing Hispanic children with both parents Hispanic, one parent Hispanic and non-Hispanic children (p Value for trend <0.0001). The highest risk of ALL was observed for children with a combination of Hispanic ethnicity and White race compared with non-Hispanic whites (OR=1.27, 95% CI 1.12 to 1.44). The lowest risk was observed for non-Hispanic blacks (OR=0.46, 95% CI 0.36 to 0.60). Associations for total childhood leukaemia were similar to ALL. Conclusions Our results confirm that there are ethnic and racial differences in the incidence of childhood leukaemia. These differences indicate that some genetic and/or environmental/cultural factors are involved in aetiology of childhood leukaemia. [ABSTRACT FROM AUTHOR]

Thyroid hormones are critical for normal brain development. This study examined autism spectrum disorders (ASD) and thyroid stimulating hormone (TSH) levels measured in mid-pregnancy maternal serum and infant blood after birth. Three groups of children born in Orange County, CA in 2000-2001were identified: ASD (n = 78), developmental delay (n = 45), and general population controls (GP) (n = 149). Samples were retrieved from prenatal and newborn screening specimen archives. Adjusted logistic regression models showed inverse associations between ASD and log transformed TSH levels in maternal serum samples (ASD vs. GP: OR [95 % CI] 0.33 [0.12-0.91], Early Onset ASD vs. GP: 0.31 [0.10-0.98]). Results for thyroid levels in newborn blood samples were similar though not significant (ASD vs. GP: 0.61 [0.18-2.04]). [ABSTRACT FROM AUTHOR]

Objectives. We examined variations in having a usual source of care (USC) among non-Hispanic White and Asian American adults in California. Methods. Data were from the 2005 and 2009 California Health Interview Survey. Using a modified Anderson model, we used multiple logistic regression to compare odds of having a USC between non-Hispanic White (n = 38 554) and Asian American adults (n = 7566) and to examine associations with acculturation factors (English proficiency, length of residence, residence in a racially concordant neighborhood) and key enabling (employment, income, insurance) and predisposing (education) factors. Results. Race-related disparities between Asian Americans and non-Hispanic Whites in having a USC were no longer significant after accounting for acculturation factors. Limited English proficiency and short time in the United States (< 5 years) were significantly associated with not having a USC for both races. Increasing levels of education and insurance were not associated with better access among Asian Americans. Conclusions. Key differences exist in how Asian American and non- Hispanic White adults access care. Acculturation factors are key drivers of disparities and should be included in access-to-care models with Asians. Insurance and education are differentially significant for Asian Americans and non-Hispanic Whites. [ABSTRACT FROM AUTHOR]

We conducted a large epidemiologic case-control study in California to examine the association between childhood cancer risk and distance from the home address at birth to the nearest high-voltage overhead transmission line as a replication of the study of Draper et al. in the United Kingdom. We present a detailed description of the study design, methods of case ascertainment, control selection, exposure assessment and data analysis plan. A total of 5788 childhood leukemia cases and 3308 childhood central nervous system cancer cases (included for comparison) and matched controls were available for analysis. Birth and diagnosis addresses of cases and birth addresses of controls were geocoded. Distance from the home to nearby overhead transmission lines was ascertained on the basis of the electric power companies' geographic information system (GIS) databases, additional Google Earth aerial evaluation and site visits to selected residences. We evaluated distances to power lines up to 2000 m and included consideration of lower voltages (60-69 kV). Distance measures based on GIS and Google Earth evaluation showed close agreement (Pearson correlation >0.99). Our three-tiered approach to exposure assessment allowed us to achieve high specificity, which is crucial for studies of rare diseases with low exposure prevalence. [ABSTRACT FROM AUTHOR]

Background: Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism. Objectives: We evaluated whether residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Methods: The CHARGE study is a population-based case–control study of ASD, DD, and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997–2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25‑km, 1.5‑km, and 1.75‑km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316). Results: Approximately one-third of CHARGE study mothers lived, during pregnancy, within 1.5 km (just under 1 mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for third-trimester exposures (OR = 2.0; 95% CI: 1.1, 3.6), and second-trimester chlorpyrifos applications (OR = 3.3; 95% CI: 1.5, 7.4). Children of mothers residing near pyrethroid insecticide applications just before conception or during third trimester were at greater risk for both ASD and DD, with ORs ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified. Conclusions: This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, particularly organophosphates, and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates. [ABSTRACT FROM AUTHOR]

We investigated whether there is an association between increased risk for autism spectrum disorders (ASD) and selective serotonin reuptake inhibitors (SSRIs) used during pregnancy. This study used Denmark's health and population registers to obtain information regarding prescription drugs, ASD diagnosis, and health and socioeconomic status. There were 1.5 % of cases and 0.7 % of controls exposed to SSRIs during the pregnancy period, and higher effect estimates observed with longer use. We found evidence that in utero exposure to SSRIs increases a child's risk associated with ASD. These results, while adding to the limited knowledge on prenatal pharmacological exposures as potential ASD risk factors, need to be balanced against the benefits of indicated medication use by pregnant mothers. [ABSTRACT FROM AUTHOR]

Previous studies of memory in autism spectrum conditions (ASC) have consistently shown that persons with ASC have reduced memories for social information, relative to a spared memory for non-social facts. The current study aims to reproduce these findings, while examining the possible causes leading to this difference. Participants' memory for trait-words was tested after they had viewed the words in three study contexts: visuo-motor, letter-detection, and social judgment. While participants with ASC showed a levels-of-processing effect, such that their memory for words viewed in the social judgment context was greater than their memory for words viewed in the letter-detection context, their memory for socially-processed words was reduced relative to comparison participants. This interaction effect could not be explained by a speed/accuracy trade-off, nor could it be explained solely by differences in encoding. These results suggest that social memory deficits in ASC arise from difficulties both in orienting towards and encoding social content, as well as retaining and retrieving it. Implications for theory and clinical practice are discussed. [ABSTRACT FROM AUTHOR]

The current study tested fine discrimination of upright and inverted faces and objects in adolescents with Autism Spectrum Disorder (ASD) as compared to age- and IQ-matched controls. Discrimination sensitivity was tested using morphed faces and morphed objects, and all stimuli were equated in low-level visual characteristics (luminance, contrast, spatial frequency make-up). Participants with ASD exhibited slight, non-significant impairments in discrimination sensitivity for faces, yet significantly enhanced discrimination sensitivity for objects. The ASD group also showed a protracted development of face and object inversion effects. Finally, for ASD participants, face sensitivity improved with increasing IQ while object sensitivity improved with age. By contrast, for controls, face sensitivity improved with age, but neither face nor object sensitivity was influenced by IQ. These findings suggest that individuals with ASD follow a qualitatively different path in the development of face and object processing abilities. [ABSTRACT FROM AUTHOR]

Early return to work after childbirth has been increasing among working mothers in the US. We assessed the relationship between access to employer-offered maternity leave (EOML) (both paid and unpaid) and uptake and duration of maternity leave following childbirth in a socio-economically diverse sample of full-time working women. We focus on California, a state that has long provided more generous maternity leave benefits than those offered by federal maternity leave policies through the State Disability Insurance program. The sample included 691 mothers who gave birth in Southern California in 2002-2003. Using weighted logistic regression, we examined the EOML-maternity leave duration relationship, controlling for whether the leave was paid, as well as other occupational, personality and health-related covariates. Compared with mothers who were offered more than 12 weeks of maternity leave, mothers with <6 weeks of EOML and those offered 6-12 weeks had five times higher odds of returning to work within 12 weeks; those offered no leave had six times higher odds of an early return. These relationships were similar after controlling for whether the leave was paid and after controlling for other occupational and health characteristics. Access to and duration of employer-offered maternity leave significantly determine timing of return to work following childbirth, potentially affecting work-family balance. Policy makers should recognize the pivotal role of employers in offering job security during and after maternity leave and consider widening the eligibility criteria of the Family and Medical Leave Act. [ABSTRACT FROM AUTHOR]

Linear growth from birth to 2 years of children enrolled in the World Health Organization Multicentre Growth Reference Study was similar despite substantial parental height differences among the six study sites. Within-site variability in child length attributable to parental height was estimated by repeated measures analysis of variance using generalized linear models. This approach was also used to examine relationships among selected traits (e.g. breastfeeding duration and child morbidity) and linear growth between 6 and 24 months of age. Differences in intergenerational adult heights were evaluated within sites by comparing mid-parental heights (average of the mother's and father's heights) to the children's predicted adult height. Mid-parental height consistently accounted for greater proportions of observed variability in attained child length than did either paternal or maternal height alone. The proportion of variability explained by mid-parental height ranged from 11% in Ghana to 21% in India. The average proportion of between-child variability accounted for by mid-parental height was 16% and the analogous within-child estimate was 6%. In the Norwegian and US samples, no significant differences were observed between mid-parental and children's predicted adult heights. For the other sites, predicted adult heights exceeded mid-parental heights by 6.2-7.8 cm. To the extent that adult height is predicted by height at age 2 years, these results support the expectation that significant community-wide advances in stature are attainable within one generation when care and nutrition approximate international recommendations, notwithstanding adverse conditions likely experienced by the previous generation. [ABSTRACT FROM AUTHOR]

Concerns persist about a possible link between infertility and risk of autism spectrum disorders (ASD). Interpretation of existing studies is limited by racial/ethnic homogeneity of study populations and other factors. Using a case-control design, we evaluated infertility history and treatment documented in medical records of members of Kaiser Permanente Northern California. Among singletons (349 cases, 1,847 controls), we found no evidence to support an increase in risk of ASD associated with infertility. Among multiple births (21 cases, 54 controls), we found an increased risk associated with infertility history and with infertility evaluations and treatment around the time of index pregnancy conception; however, small sample size and lack of detailed data on treatments preclude firm interpretation of results for multiple births. [ABSTRACT FROM AUTHOR]

Association studies among admixed populations pose many challenges including confounding of genetic effects due to population substructure and heterogeneity due to different patterns of linkage disequilibrium (LD). We use simulations to investigate controlling for confounding by indicators of global ancestry and the impact of including a covariate for local ancestry. In addition, we investigate the use of an interaction term between a single-nucleotide polymorphism (SNP) and local ancestry to capture heterogeneity in SNP effects. Although adjustment for global ancestry can control for confounding, additional adjustment for local ancestry may increase power when the induced admixture LD is in the opposite direction as the LD in the ancestral population. However, if the induced LD is in the same direction, there is the potential for reduced power because of overadjustment. Furthermore, the inclusion of a SNP by local ancestry interaction term can increase power when there is substantial differential LD between ancestry populations. We examine these approaches in genome-wide data using the University of Southern California's Children's Health Study investigating asthma risk. The analysis highlights rs10519951 (P = 8.5 × 10−7), a SNP lacking any evidence of association from a conventional analysis (P = 0.5). [ABSTRACT FROM AUTHOR]

Objective:To examine the risk and etiology of preterm delivery in women with polycystic ovary syndrome (PCOS).Study Design:Retrospective cohort study comparing preterm delivery rate among non-diabetic PCOS and non-PCOS women with singleton pregnancy. Multivariable logistic regression was used to identify predictors of preterm delivery among PCOS women.Result:Among 908 PCOS women with singleton pregnancy, 12.9% delivered preterm compared with 7.4% among non-PCOS women (P<0.01). Causes of preterm delivery among PCOS women included preterm labor (41%), cervical insufficiency (11%), hypertensive complications (20%), preterm premature rupture of membranes (15%), fetal-placental concerns (9%) and intrauterine fetal demise (5%). Maternal age, race/ethnicity and nulliparity were significant predictors of preterm delivery in PCOS, whereas body mass index and fertility medications were not.Conclusion:A higher proportion of PCOS women delivered preterm (12.9%) compared with non-PCOS women, with the majority of cases due to spontaneous preterm birth. Future studies should explore etiologies and strategies to improve pregnancy outcomes in PCOS. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the time-course of processing of lexical items in auditorily presented canonical (subject-verb- object) constructions in young, neurologically unimpaired control participants and participants with left-hemisphere damage and agrammatic aphasia. Method: A cross modal picture priming (CMPP) paradigm was used to test 114 control participants and 8 participants with agrammatic aphasia for priming of a lexical item (direct object noun) immediately after it is initially encountered in the ongoing auditory stream and at 3 additional time points at 400-ms intervals. Results: The control participants demonstrated immediate activation of the lexical item, followed by a rapid loss (decay). The participants with aphasia demonstrated delayed activation of the lexical item. Conclusion: This evidence supports the hypothesis of a delay in lexical activation in people with agrammatic aphasia. The delay in lexical activation feeds syntactic processing too slowly, contributing to comprehension deficits in people with agrammatic aphasia. [ABSTRACT FROM AUTHOR]

Whereas preterm birth has consistently been associated with low maternal pre-pregnancy weight, the relationship with high pre-pregnancy weight has been inconsistent. We quantified the pre-pregnancy BMI-preterm delivery (PTD) relationship using traditional BMI categories (underweight, normal weight, overweight and obese) as well as continuous BMI. Eligible women participated in California's statewide prenatal screening program, worked during pregnancy, and delivered a live singleton birth in Southern California in 2002-2003. The final analytic sample included 354 cases delivering at <37 weeks, as identified by clinical estimate of gestational age from screening records, and 710 term normal-birthweight controls. Multivariable logistic regression models using categorical BMI levels and continuous BMI were compared. In categorical analyses, PTD was significantly associated with pre-pregnancy underweight only. Nonparametric local regression revealed a V-shaped relationship between continuous BMI and PTD, with minimum risk at the high end of normal, around 24 kg/m. The odds ratio (OR) for PTD associated with low BMI within the normal range (19 kg/m) was 2.84 (95%CI = 1.61-5.01); ORs for higher BMI in the overweight (29 kg/m) and obese (34 kg/m) ranges were 1.42 (95%CI = 1.10-1.84) and 2.01 (95% CI = 1.20-3.39) respectively, relative to 24 kg/m). BMI categories obscured the preterm delivery risk associated with low-normal, overweight, and obese BMI. We found that higher BMI up to around 24 kg/m is increasingly protective of preterm delivery, beyond which a higher body mass index becomes detrimental. Current NHLBI/WHO BMI categories may be inadequate for identifying women at higher risk for PTD. [ABSTRACT FROM AUTHOR]

In a population-based case-control study in California's intensely agricultural Central Valley (2005–2006), the authors investigated relations between environmental pesticide/fungicide exposure and prostate cancer. Cases (n = 173) were obtained from a population-based cancer registry, and controls (n = 162) were obtained from Medicare listings and tax assessor mailings. Past ambient exposures to pesticides/fungicides were derived from residential history and independently recorded pesticide and land-use data, using a novel geographic information systems approach. In comparison with unexposed persons, increased risks of prostate cancer were observed among persons exposed to compounds which may have prostate-specific biologic effects (methyl bromide (odds ratio = 1.62, 95% confidence interval: 1.02, 2.59) and a group of organochlorines (odds ratio = 1.64, 95% confidence interval: 1.02, 2.63)) but not among those exposed to other compounds that were included as controls (simazine, maneb, and paraquat dichloride). The authors assessed the possibility of selection bias due to less-than-100% enrollment of eligible cases and controls (a critical methodological concern in studies of this kind) and determined that there was little evidence of bias affecting the estimated effect size. This study provides evidence of an association between prostate cancer and ambient pesticide exposures in and around homes in intensely agricultural areas. The associations appear specific to compounds with a plausible biologic role in prostate carcinogenesis. [ABSTRACT FROM PUBLISHER]

The study investigated how children with heavy prenatal alcohol exposure regulate movement speed and accuracy during goal-directed movements. 16 children ages 7 to 17 years with confirmed histories of heavy in utero alcohol exposure, and 21 nonalcohol-exposed control children completed a series of reciprocal tapping movements between two spatial targets. 5 different targets sets were presented, representing a range of task difficulty between 2 and 6 bits of information. Estimates of percent error rate, movement time, slope, and linear fit of the resulting curve confirmed that for goal-directed, reciprocal tapping responses, performance of the group with prenatal alcohol exposure was described by a linear function, as predicted by Fitts' law, by sacrificing movement accuracy. The index of performance was the same for the two groups: it initially increased, then leveled off for more difficult movements. [ABSTRACT FROM AUTHOR]

In genome-wide association studies, inherited risk of glioma has been demonstrated for rare familial syndromes and with common variants from 3–5 chromosomal regions. To assess the degree of familial aggregation of glioma, the authors performed a pooled analysis of data from 2 large glioma case-control studies in the United States (MD Anderson Cancer Center, Houston, Texas (1994–2006) and University of California, San Francisco (1991–2004)) and from the Swedish Cancer Registry (1958–2006) to measure excess cases of cancer among first-degree relatives of glioma probands. This analysis included 20,377 probands with glioma and 52,714 first-degree relatives. No overall increase was found in the expected number of cancers among family members; however, there were 77% more gliomas than expected. There were also significantly more sarcoma and melanoma cases than expected, which is supported by evidence in the literature, whereas there were significantly fewer-than-expected cases of leukemia, non-Hodgkin lymphoma, and bladder, lung, pancreatic, prostate, and uterine cancers. This large pooled analysis provided sufficient numbers of related family members to examine the genetic mechanisms involved in the aggregation of glioma with other cancers in these families. However, misclassification due to unvalidated cancers among family members could account for the differences seen by study site. [ABSTRACT FROM PUBLISHER]

Background and Aim: Intestinal and extra-intestinal complications are associated with inflammatory bowel disease (IBD) but their exact incidence is not well known. In order to improve our understanding of their incidence and impact, we assessed the complications associated with ulcerative colitis (UC) and Crohn's disease (CD) in a population-based study in Medicaid patients.Methods: We utilized a retrospective cohort design and identified cases of UC and CD using Medi-Cal, the Medicaid program for the State of California. The disease cohort was age- and gender-matched to four controls each and the intestinal and extra-intestinal complications of CD and UC (analyzed separately) were studied over a period of 5 years following the initial diagnosis.Results: For UC, the total number of intestinal complications, per 100 cases, was 92 observed compared to 21 expected; the total number of extra-intestinal complications was 42 observed compared to 30 expected. For CD, the number of intestinal complications was 81 observed compared to 20 expected and for extra-intestinal complications, 37 observed compared to 26 expected (all p < 0.001). For both UC and CD, bleeding was the most frequently seen intestinal complication, while the most common extra-intestinal complication was osteoporosis.Conclusions: IBD is associated with several intestinal and extra-intestinal complications of variable incidence and risk. Success of therapeutic regimens should be measured by decreases in incidence, risks, and costs of these complications, in addition to the usual impact on disease activity. [ABSTRACT FROM AUTHOR]

Background: It has been demonstrated that Agent Orange exposure increases the risk of developing several soft tissue malignancies. Federally funded studies, now nearly a decade old, indicated that there was only a weak association between exposure and the subsequent development of prostate cancer. Because Vietnam War veterans are now entering their 60s, the authors reexamined this association by measuring the relative risk of prostate cancer among a cohort of men who were stratified as either exposed or unexposed to Agent Orange between the years 1962 and 1971 and who were followed during the interval between 1998 and 2006. Methods: All Vietnam War era veterans who receive their care in the Northern California Veteran Affairs Health System were stratified as either exposed (n=6214) or unexposed (n=6930) to Agent Orange. Strata-specific incidence rates of prostate cancer (International Classification of Diseases, 9th Revision code 185.0) were calculated. Differences in patient and disease characteristics (age, race, smoking history, family history, body mass index, finasteride exposure, prebiopsy prostate-specific antigen (PSA) level, clinical and pathologic stage, and Gleason score) were assessed with chi-square tests, t tests, a Cox proportional hazards model, and multivariate logistic regression. Results: Twice as many exposed men were identified with prostate cancer (239 vs 124 unexposed men, respectively; odds ratio [OR], 2.19; 95% confidence interval [95% CI], 1.75-2.75). This increased risk also was observed in a Cox proportional hazards model from the time of exposure to diagnosis (hazards ratio [HR], 2.87; 95% CI, 2.31-3.57). The mean time from exposure to diagnosis was 407 months. Agent Orange-exposed men were diagnosed at a younger age (59.7 years; 95% CI, 58.9-60.5 years) compared with unexposed men (62.2 years; 95% CI, 60.8-63.6 years), had a 2-fold increase in the proportion of Gleason scores 8 through 10 (21.8%; 95% CI, 16.5%-27%) compared with unexposed men (10.5%; 95% CI, 5%-15.9%), and were more likely to have metastatic disease at presentation than men who were not exposed (13.4%; 95% CI, 9%-17.7%) than unexposed men (4%; 95% CI, 0.5%-7.5%). In univariate analysis, distribution by race, smoking history, body mass index, finasteride exposure, clinical stage, and mean prebiopsy PSA were not statistically different. In a multivariate logistic regression model, Agent Orange was the most important predictor not only of developing prostate cancer but also of high-grade and metastatic disease on presentation. Conclusions: Individuals who were exposed to Agent Orange had an increased incidence of prostate cancer; developed the disease at a younger age, and had a more aggressive variant than their unexposed counterparts. Consideration should be made to classify this group of individuals as 'high risk,' just like men of African-American heritage and men with a family history of prostate cancer. [ABSTRACT FROM AUTHOR]

A cohort of 197 Medicaid-insured patients presenting for treatment in Kaiser Permanente's outpatient chemical dependency treatment program were observed the year prior to their program intake visit and followed for 3 years afterwards, to compare their medical costs and utilization to demographically matched commercially insured patients entering the same programs. The Medicaid-insured patients on average incurred medical costs 60% higher than non-Medicaid patients during the 12-month preintake period ($5402 vs $3377). [corrected] During the 3 years subsequently, however, both groups of chemical dependency patients displayed significant declines in medical costs, averaging 30% from the baseline period to the third year of follow-up. Cost trends reflected declines in use of hospital days, emergency department visits, and nonemergent outpatient visits. These results may help address concerns among Medicaid managed care providers and payers by giving a more realistic account of the long-term costs of this group of high-utilizing enrollees. [ABSTRACT FROM AUTHOR]

Evidence from epidemiologic and experimental studies suggests that use of nonsteroidal antiinflammatory drugs (NSAIDs) reduces risk of colon and breast cancer. The association between use of aspirin and other NSAIDs and risk of adult glioblastoma multiforme (GBM) was evaluated among 236 incident GBM cases and 401 population-based controls frequency-matched on age, gender, and ethnicity from the San Francisco Bay Area Adult Glioma Study. Cases (or proxies) and controls were interviewed in person between May 1997 and August 2000. Cases with self-reported GBM reported less use of at least 600 pills of all types of NSAIDs combined during the 10-year prediagnostic period than did controls (odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.3, 0.8). Findings were consistent for aspirin (OR = 0.51, 95% CI: 0.3, 0.8), ibuprofen (OR = 0.41, 95% CI: 0.2, 0.8), and naproxen/other NSAIDs (OR = 0.34, 95% CI: 0.1, 0.8). GBM cases also reported less use of acetaminophen than did controls (OR = 0.51, 95% CI: 0.3, 1.0). Eliminating participants who initiated NSAID use within 2 years of diagnosis yielded similar results. These findings show an inverse association between NSAID use and GBM. Further studies are warranted to determine whether NSAIDs might be effective in the inhibition of GBM development or progression. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of parental occupations in the etiology of childhood brain tumors (CBT).Methods: Population-based case-control studies were conducted concurrently in seven countries under the coordination of the International Agency for Research on Cancer, gathering 1,218 cases and 2,223 controls. We report here the findings related to parental occupations during the 5-year period before the child's birth. Risk estimates related to a number of paternal and maternal occupations were obtained by unconditional logistic regression adjusted for age, sex, year of birth, and center, for all types of CBT combined and for the subgroups of astroglial, primitive neuroectodermal tumors (PNET), and other glial tumors.Results: An increased risk in relation with agricultural work was seen for all CBT combined and for other glial tumors. Increased risks for all tumors and PNET were seen for paternal occupation as an electrician; the same pattern held for maternal occupation when children under 5 were selected. Paternal occupation as a driver or mechanic, and maternal work in an environment related to motor-vehicles were associated with an increased risk for all CBT and astroglial tumors. More case mothers compared to control mothers were employed in the textile industry.Conclusion: Our study reinforces previous findings relative to the role of parental work in agriculture, electricity, or motor-vehicle related occupations and maternal work in the textile industry. It does not confirm previous associations with work environments including aerospace, the chemical industry, or the food industry, or with maternal occupation as a hairdresser, a nurse, or a sewing machinist, and paternal occupation as a welder. [ABSTRACT FROM AUTHOR]

Objectives: Sigmoidoscopy screening and fecal occult blood (FOB) tests have been demonstrated as effective ways to reduce mortality from colorectal cancer. However, most studies of colorectal cancer screening and cancer mortality have not taken into consideration lifestyle factors that could account for the observed associations. The purpose of this study was to determine the association between screening and incidence of colon cancer, taking into consideration important lifestyle factors.Methods: We estimated the association between screening and colon cancer after taking into consideration health and lifestyle factors using data obtained as part of population-based case-control study of incident colon cancers.Results: Sigmoidoscopy screening, especially as part of a checkup, was protective against incident colon cancer in both men (OR 0.56, 95% CI 0.44-0.77) and women (OR 0.53, 95% CI 0.33-0.77) after adjusting for other risk factors for colon cancer. For men, associations were stronger for distal tumors (OR 0.48, 95% CI 0.31-0.71) than for proximal tumors (OR 0.67, 95% CI 0.45-1.11). We did not observe significant associations between FOB test and colon cancer. Differences in characteristics between those who were screened and not screened were also observed. Men were more likely to report having a sigmoidoscopy as part of a checkup than were women, as were people with higher levels of education. People who reported having a sigmoidoscopy as part of a checkup also reported eating diets lower in fat and higher in fiber, folate, and vegetables. Men were more likely to report higher levels of physical activity, and women were more likely to report taking hormone replacement therapy (HRT) if they also reported a sigmoidoscopy. Both men and women who reported a sigmoidoscopy for screening purposes were more likely to have a family history of colorectal cancer.Conclusions: These data provide additional support for the benefits of having a screening sigmoidoscopy. The associations between screening sigmoidoscopy and colon cancer do not appear to be the result of lifestyle factors. [ABSTRACT FROM AUTHOR]

The often observed association between red meat and colorectal cancer could be due in part to mutagens, such as heterocyclic amines (HCA), that are present in cooked meat. HCAs are highly mutagenic and cause intestinal tumors in animals. The hypothesis that HCAs are also carcinogenic to humans remains to be substantiated in epidemiologic studies. We determined the associations of meat preparation and frequency of intake (proxy variables for HCA exposure, since HCA concentration depends on the type of meat and the way it is cooked) with the prevalence of distal colorectal adenomas in a sigmoidoscopy-based case-control study of 488 matched pairs of subjects from two California (United States) Kaiser Permanente Medical Centers. A more than twofold difference in adenoma prevalence between subjects at extreme ends of estimated HCA intake was observed. For subjects who ate red meat more than once per week, fried it more than 10 percent of the time, and ate it with a darkly browned surface, compared with subjects who ate red meat one time or less per week, fried it 10 or less percent of the time, and ate it with a lightly browned surface, the odds ratio was 2.2 (95 percent confidence interval = 1.1-4.3). Adenoma prevalence also increased with frequency of frying red meat (P trend = 0.004). These results are consistent with a carcinogenic effect of HCA. [ABSTRACT FROM AUTHOR]