Metabolomics analysis of children with autism, idiopathic-developmental delays, and Down syndrome.

Although developmental delays affect learning, language, and behavior, some evidence suggests the presence of disturbances in metabolism are associated with psychiatric disorders. Here, the plasma metabolic phenotype of children with autism spectrum disorder (ASD, n = 167), idiopathic-developmental delay (i-DD, n = 51), and Down syndrome (DS, n = 31), as compared to typically developed (TD, n = 193) controls was investigated in a subset of children from the case-control Childhood Autism Risk from Genetics and the Environment (CHARGE) Study. Metabolome profiles were obtained using nuclear magnetic resonance spectroscopy and analyzed in an untargeted manner. Forty-nine metabolites were identified and quantified in each sample that included amino acids, organic acids, sugars, and other compounds. Multiple linear regression analysis revealed significant associations between 11 plasma metabolites and neurodevelopmental outcome. Despite the varied origins of these developmental disabilities, we observed similar perturbation in one-carbon metabolism pathways among DS and ASD cases. Similarities were also observed in the DS and i-DD cases in the energy-related tricarboxylic acid cycle. Other metabolites and pathways were uniquely associated with DS or ASD. By comparing metabolic signatures between these conditions, the current study expands on extant literature demonstrating metabolic alterations associated with developmental disabilities and provides a better understanding of overlapping vs specific biological perturbations associated with these disorders

The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism.

Causes and contributing factors for autism are poorly understood. Evidence suggests that prevalence is rising, but the extent to which diagnostic changes and improvements in ascertainment contribute to this increase is unclear. Both genetic and environmental factors are likely to contribute etiologically. Evidence from twin, family, and genetic studies supports a role for an inherited predisposition to the development of autism. Nonetheless, clinical, neuroanatomic, neurophysiologic, and epidemiologic studies suggest that gene penetrance and expression may be influenced, in some cases strongly, by the prenatal and early postnatal environmental milieu. Sporadic studies link autism to xenobiotic chemicals and/or viruses, but few methodologically rigorous investigations have been undertaken. In light of major gaps in understanding of autism, a large case-control investigation of underlying environmental and genetic causes for autism and triggers of regression has been launched. The CHARGE (Childhood Autism Risks from Genetics and Environment) study will address a wide spectrum of chemical and biologic exposures, susceptibility factors, and their interactions. Phenotypic variation among children with autism will be explored, as will similarities and differences with developmental delay. The CHARGE study infrastructure includes detailed developmental assessments, medical information, questionnaire data, and biologic specimens. The CHARGE study is linked to University of California-Davis Center for Children's Environmental Health laboratories in immunology, xenobiotic measurement, cell signaling, genomics, and proteomics. The goals, study design, and data collection protocols are described, as well as preliminary demographic data on study participants and on diagnoses of those recruited through the California Department of Developmental Services Regional Center System

Autism spectrum disorder, flea and tick medication, and adjustments for exposure misclassification: the CHARGE (CHildhood Autism Risks from Genetics and Environment) case–control study

BackgroundThe environmental contribution to autism spectrum disorders (ASD) is largely unknown, but household pesticides are receiving increased attention. We examined associations between ASD and maternally-reported use of imidacloprid, a common flea and tick treatment for pets.MethodsBayesian logistic models were used to estimate the association between ASD and imidacloprid and to correct for potential differential exposure misclassification due to recall in a case control study of ASD.ResultsOur analytic dataset included complete information for 262 typically developing controls and 407 children with ASD. Compared with exposure among controls, the odds of prenatal imidacloprid exposure among children with ASD were slightly higher, with an odds ratio (OR) of 1.3 (95% Credible Interval [CrI] 0.78, 2.2). A susceptibility window analysis yielded higher ORs for exposures during pregnancy than for early life exposures, whereas limiting to frequent users of imidacloprid, the OR increased to 2.0 (95% CI 1.0, 3.9).ConclusionsWithin plausible estimates of sensitivity and specificity, the association could result from exposure misclassification alone. The association between imidacloprid exposure and ASD warrants further investigation, and this work highlights the need for validation studies regarding prenatal exposures in ASD

Phthalate concentrations in house dust in relation to autism spectrum disorder and developmental delay in the CHildhood Autism Risks from Genetics and the Environment (CHARGE) study

Acoustic waves are transmitted into the subsurface ocean will experience scattering (scattering) caused by marine organisms, material distributed in the ocean, the structure is not homogeneous in seawater, as well as reflections from the surface and the seabed. Estimation of fish stocks in the waters wide as in Indonesia have a lot of them are using the acoustic method. The acoustic method has high speed in predicting the size of fish stocks so as to allow acquiring data in real time, accurate and high speed so as to contribute fairly high for the provision of data and information of fishery resources.  Split beam echo sounder comprises two aspects, and a transducer. The first aspect is the high-resolution color display for displaying echogram at some observations and also serves as a controller in the operation of the echo sounder. The second aspect is transceiver consisting of transmitter and receiver. The Echosounder divided beam first inserted into the ES 3800 by SIMRAD beginning of the 1980s and in 1985 was introduced to fishermen in Japan as a tool for catching up. Split beam transducer is divided into four quadrants.  Factors that contribute affect the value of Target Strength (TS) fish Strength target can generally be influenced by three factors: a target factor itself, environmental factors, and factors acoustic instrument. Factors include the size of the target, the anatomy of fish, swim bladder, the behavior of orientation

Cancer and non-cancer health effects from dietary toxic exposure for children and adults in California

BACKGROUND: In the absence of current cumulative dietary exposure assessments, this analysis was conducted to estimate exposure to multiple dietary contaminants for children, who are more vulnerable to toxic exposure than adults. METHODS: We estimated exposure to multiple food contaminants based on dietary data from preschool-age children (2–4 years, n=207), school-age children (5–7 years, n=157), parents of young children (n=446), and older adults (n=149). We compared exposure estimates for eleven toxic compounds (acrylamide, arsenic, lead, mercury, chlorpyrifos, permethrin, endosulfan, dieldrin, chlordane, DDE, and dioxin) based on self-reported food frequency data by age group. To determine if cancer and non-cancer benchmark levels were exceeded, chemical levels in food were derived from publicly available databases including the Total Diet Study. RESULTS: Cancer benchmark levels were exceeded by all children (100%) for arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95% of preschool-age children for acrylamide and by 10% of preschool-age children for mercury. Preschool-age children had significantly higher estimated intakes of 6 of 11 compounds compared to school-age children (p<0.0001 to p=0.02). Based on self-reported dietary data, the greatest exposure to pesticides from foods included in this analysis were tomatoes, peaches, apples, peppers, grapes, lettuce, broccoli, strawberries, spinach, dairy, pears, green beans, and celery. CONCLUSIONS: Dietary strategies to reduce exposure to toxic compounds for which cancer and non-cancer benchmarks are exceeded by children vary by compound. These strategies include consuming organically produced dairy and selected fruits and vegetables to reduce pesticide intake, consuming less animal foods (meat, dairy, and fish) to reduce intake of persistent organic pollutants and metals, and consuming lower quantities of chips, cereal, crackers, and other processed carbohydrate foods to reduce acrylamide intake

Determinants of serum polychlorinated biphenyls and organochlorine pesticides measured in women from the child health and development study cohort, 1963-1967.

We examined predictors of organochlorine concentrations in serum specimens from women who were pregnant in the 1960s and participated in the Child Health and Development Study in the San Francisco Bay Area of California. That study enrolled pregnant women at the Kaiser-Permanente Medical Facilities, conducted interviews, and drew blood specimens; these specimens were centrifuged and the resulting serum specimens were frozen and placed in long-term storage. For the current investigation, organochlorines were measured by dual-column GC-electron capture detection in specimens collected in 1963-1967 from 399 pregnant women during the second and third trimesters. Using multiple linear regression models adjusted for serum lipids, we evaluated factors predicting concentrations of 11 polychlorinated biphenyl (PCB) congeners, their sum, and several pesticides and metabolites. Variables evaluated were age, race, place of birth, date of blood draw, body mass index, occupation, past residence on a farm, parity, and duration of pregnancy at blood draw. Concentrations of highly chlorinated PCBs and the sum of the PCBs increased with age. Concentrations of certain PCB congeners, as well as the sum, were significantly higher among nonwhites and increased with calendar date of blood draw. (italic)p,p(/italic) -DDT and (italic)p,p(/italic) -DDE concentrations were about 50% higher for nonwhites compared with whites and for those born in California or the southeastern United States versus elsewhere in the United States. Higher body mass index was associated with lower concentrations of several PCBs and (italic)p,p(/italic) -DDE but with higher heptachlor epoxide and DDT levels. The increase in use of PCBs during the 1960s is apparently detectable as increasing concentrations in maternal sera between 1963 and 1967. Marked racial and regional differences in serum pesticide levels were likely caused by geographic variation in previous agricultural and vector-control uses. The relationship to body mass index appears to be complex

A procedure to characterize geographic distributions of rare disorders in cohorts

<p>Abstract</p> <p>Background</p> <p>Individual point data can be analyzed against an entire cohort instead of only sampled controls to accurately picture the geographic distribution of populations at risk for low prevalence diseases. Analyzed as individual points, many smaller clusters with high relative risks (RR) and low empirical p values are indistinguishable from a random distribution. When points are aggregated into areal units, small clusters may result in a larger cluster with a low RR or be lost if divided into pieces included in units of larger populations that show no increased prevalence. Previous simulation studies showed lowered validity of spatial scan tests for true clusters with low RR. Using simulations, this study explored the effects of low cluster RR and areal unit size on local area clustering test (LACT) results, proposing a procedure to improve accuracy of cohort spatial analysis for rare events.</p> <p>Results</p> <p>Our simulations demonstrated the relationship of true RR to observed RR and p values with various, randomly located, cluster shapes, areal unit sizes and scanning window shapes in a diverse population distribution. Clusters with RR < 1.7 had elevated observed RRs and high p values.</p> <p>We propose a cluster identification procedure that applies parallel multiple LACTs, one on point data and three on two distinct sets of areal units created with varying population parameters that minimize the range of population sizes among units. By accepting only clusters identified by all LACTs, having a minimum population size, a minimum relative risk and a maximum p value, this procedure improves the specificity achieved by any one of these tests alone on a cohort study of low prevalence data while retaining sensitivity for small clusters. The procedure is demonstrated on two study regions, each with a five-year cohort of births and cases of a rare developmental disorder.</p> <p>Conclusion</p> <p>For truly exploratory research on a rare disorder, false positive clusters can cause costly diverted research efforts. By limiting false positives, this procedure identifies 'crude' clusters that can then be analyzed for known demographic risk factors to focus exploration for geographically-based environmental exposure on areas of otherwise unexplained raised incidence.</p

Comparison of maternal beliefs about causes of autism spectrum disorder and association with utilization of services and treatments

Background: This study aimed to describe parental perceptions of the causes of autism spectrum disorder (ASD) in an ethnically diverse sample and explore whether these perceptions relate to treatment choices. Methods: The sample consisted of White (n=224), Hispanic (n=85) and Asian (n=21) mothers of a child with ASD. A mixed methods approach was used in this secondary analysis focusing on parental perceptions about the causes of ASD and the relationship of these to utilization of services and treatment. Results: Environmental and genetic factors were most often believed to be the cause or one of the causes of ASD by mothers across all ethnic groups studied. Asian mothers were more likely to cite multiple causes. Environmental causes were associated with receiving 20 or more hours of autism related services per week; while belief in environmental exposures and vaccines and medications as causes were associated with complementary-alternative medicine (CAM) use. Conclusion: Our findings suggest that ethnic differences in autism causal beliefs and treatment choices may exist. Future research should be conducted to specifically confirm the findings, to understand parental motivation behind their service and treatment choices; and to gain more insight into the types, usage and sources of CAM treatments. Clinicians can use parental autism causal beliefs in discussions about treatment recommendations