Glycosyl transferase GT2 genes mediate the biosynthesis of an unusual (1,3;1,4)-ß-glucan exopolysaccharide in the bacterium Sarcina ventriculi.

Linear, unbranched (1,3;1,4)-ß-glucans (mixed-linkage glucans or MLGs) are commonly found in the cell walls of grasses, but have also been detected in basal land plants, algae, fungi and bacteria. Here we show that two family GT2 glycosyltransferases from the Gram-positive bacterium Sarcina ventriculi are capable of synthesizing MLGs. Immunotransmission electron microscopy demonstrates that MLG is secreted as an exopolysaccharide, where it may play a role in organizing individual cells into packets that are characteristic of Sarcina species. Heterologous expression of these two genes shows that they are capable of producing MLGs in planta, including an MLG that is chemically identical to the MLG secreted from S. ventriculi cells but which has regularly spaced (1,3)-ß-linkages in a structure not reported previously for MLGs. The tandemly arranged, paralogous pair of genes are designated SvBmlgs1 and SvBmlgs2. The data indicate that MLG synthases have evolved different enzymic mechanisms for the incorporation of (1,3)-ß- and (1,4)-ß-glucosyl residues into a single polysaccharide chain. Amino acid variants associated with the evolutionary switch from (1,4)-ß-glucan (cellulose) to MLG synthesis have been identified in the active site regions of the enzymes. The presence of MLG synthesis in bacteria could prove valuable for large-scale production of MLG for medical, food and beverage applications.

Palaeontological evidence for an Oligocene divergence between Old World monkeys and apes.

Apes and Old World monkeys are prominent components of modern African and Asian ecosystems, yet the earliest phases of their evolutionary history have remained largely undocumented. The absence of crown catarrhine fossils older than ∼20 million years (Myr) has stood in stark contrast to molecular divergence estimates of ∼25-30 Myr for the split between Cercopithecoidea (Old World monkeys) and Hominoidea (apes), implying long ghost lineages for both clades. Here we describe the oldest known fossil 'ape', represented by a partial mandible preserving dental features that place it with 'nyanzapithecine' stem hominoids. Additionally, we report the oldest stem member of the Old World monkey clade, represented by a lower third molar. Both specimens were recovered from a precisely dated 25.2-Myr-old stratum in the Rukwa Rift, a segment of the western branch of the East African Rift in Tanzania. These finds extend the fossil record of apes and Old World monkeys well into the Oligocene epoch of Africa, suggesting a possible link between diversification of crown catarrhines and changes in the African landscape brought about by previously unrecognized tectonic activity in the East African rift system.

Embryology of Early Jurassic dinosaur from China with evidence of preserved organic remains.

Fossil dinosaur embryos are surprisingly rare, being almost entirely restricted to Upper Cretaceous strata that record the late stages of non-avian dinosaur evolution. Notable exceptions are the oldest known embryos from the Early Jurassic South African sauropodomorph Massospondylus and Late Jurassic embryos of a theropod from Portugal. The fact that dinosaur embryos are rare and typically enclosed in eggshells limits their availability for tissue and cellular level investigations of development. Consequently, little is known about growth patterns in dinosaur embryos, even though post-hatching ontogeny has been studied in several taxa. Here we report the discovery of an embryonic dinosaur bone bed from the Lower Jurassic of China, the oldest such occurrence in the fossil record. The embryos are similar in geological age to those of Massospondylus and are also assignable to a sauropodomorph dinosaur, probably Lufengosaurus. The preservation of numerous disarticulated skeletal elements and eggshells in this monotaxic bone bed, representing different stages of incubation and therefore derived from different nests, provides opportunities for new investigations of dinosaur embryology in a clade noted for gigantism. For example, comparisons among embryonic femora of different sizes and developmental stages reveal a consistently rapid rate of growth throughout development, possibly indicating that short incubation times were characteristic of sauropodomorphs. In addition, asymmetric radial growth of the femoral shaft and rapid expansion of the fourth trochanter suggest that embryonic muscle activation played an important role in the pre-hatching ontogeny of these dinosaurs. This discovery also provides the oldest evidence of in situ preservation of complex organic remains in a terrestrial vertebrate.

Residential Agricultural Pesticide Exposures and Risks of Spontaneous Preterm Birth.

BACKGROUND: Pesticides exposures are aspects of the human exposome that have not been sufficiently studied for their contribution to risk for preterm birth. We investigated risks of spontaneous preterm birth from potential residential exposures to 543 individual chemicals and 69 physicochemical groupings that were applied in the San Joaquin Valley of California during the study period, 1998-2011. METHODS: The study population was derived from birth certificate data linked with Office of Statewide Health Planning and Development maternal and infant hospital discharge data. After exclusions, the analytic study base included 197,461 term control births and 27,913 preterm case births. Preterm cases were more narrowly defined as 20-23 weeks (n = 515), 24-27 weeks (n = 1,792), 28-31 weeks (n = 3,098), or 32-36 weeks (n = 22,508). RESULTS: The frequency of any (versus none) pesticide exposure was uniformly lower in each preterm case group relative to the frequency in term controls, irrespective of gestational month of exposure. All odds ratios were below 1.0 for these any versus no exposure comparisons. The majority of odds ratios were below 1.0, many of them statistically precise, for preterm birth and exposures to specific chemical groups or chemicals. CONCLUSIONS: This study showed a general lack of increased risk of preterm birth associated with a range of agriculture pesticide exposures near women's residences.

Residential agricultural pesticide exposures and risks of preeclampsia.

We investigated risks of preeclampsia phenotypes from potential residential pesticide exposures, including 543 individual chemicals and 69 physicochemical groupings that were applied in the San Joaquin Valley of California during the study period, 1998-2011. The study population was derived from birth certificate data linked with Office of Statewide Health Planning and Development maternal and infant hospital discharge data. The following numbers of women with preeclampsia phenotypes were identified: 1045 with superimposed (pre-existing hypertension with preeclampsia) preeclampsia (265 with gestational weeks 20-31 and 780 with gestational weeks 32-36); 3471 with severe preeclampsia (824 with gestational weeks 20-31 and 2647 with gestational weeks 32-36); and 2780 with mild preeclampsia (207 with gestational weeks 20-31 and 2573 with gestational weeks 32-36). The reference population for these groups was 197,461 women who did not have diabetes (gestational or pre-existing), did not have any hypertensive disorder, and who delivered at 37 weeks or later. The frequency of any exposure was lower or about the same in each preeclampsia case group (further delineated by gestational age), and month time period, relative to the frequency in reference population controls. Nearly all odds ratios were below 1.0 for these any vs no exposure comparisons. This study showed a general lack of increased risks between a range of agriculture pesticide exposures near women's residences and various preeclampsia phenotypes.

Estimating the Proportion of Childhood Cancer Cases and Costs Attributable to the Environment in California.

OBJECTIVES: To estimate the proportion of cases and costs of the most common cancers among children aged 0 to 14 years (leukemia, lymphoma, and brain or central nervous system tumors) that were attributable to preventable environmental pollution in California in 2013. METHODS: We conducted a literature review to identify preventable environmental hazards associated with childhood cancer. We combined risk estimates with California-specific exposure prevalence estimates to calculate hazard-specific environmental attributable fractions (EAFs). We combined hazard-specific EAFs to estimate EAFs for each cancer and calculated an overall EAF. Estimated economic costs included annual (indirect and direct medical) and lifetime costs. RESULTS: Hazards associated with childhood cancer risks included tobacco smoke, residential exposures, and parental occupational exposures. Estimated EAFs for leukemia, lymphoma, and brain or central nervous system cancer were 21.3% (range = 11.7%-30.9%), 16.1% (range = 15.0%-17.2%), and 2.0% (range = 1.7%-2.2%), respectively. The combined EAF was 15.1% (range = 9.4%-20.7%), representing $18.6 million (range = $11.6 to $25.5 million) in annual costs and $31 million in lifetime costs. CONCLUSIONS: Reducing environmental hazards and exposures in California could substantially reduce the human burden of childhood cancer and result in significant annual and lifetime savings.

Analysis of multiple-variable missing-not-at-random survey data for child lead surveillance using NHANES.

BACKGROUND: Although ongoing, multi-topic surveys form the basis of public health surveillance in many countries, their utility for specific subject matter areas can be limited by high proportions of missing data. For example, the National Health and Examination Survey is the main resource for surveillance of elevated blood lead levels (EBLLs) in US children, but key predictor variables are missing for as many as 35% of respondents. METHODS: Using a Bayesian framework, we formulate a t-distributed Heckman selection model applicable to the case of multiple missing-not-at-random variables in the context of a complex survey design. We demonstrate the utility of the results by calculating prevalence estimates for lead levels exceeding 2.5, 5.0, and 10.0 µg/dL among children 1 to 5 years of age for a variety of time points and geographies by applying the coefficients to data from the American Community Survey from the US Census. RESULTS: We present a protocol for estimating posterior distributions of parameters using Gibbs and grid sampling steps. Stark disparities in the prevalence of EBLL by race/ethnicity, age of housing, and poverty are readily quantified, and three- to five-fold differences in predicted prevalence across geographies within the US are presented. CONCLUSIONS: We are able to conduct multivariate analyses of EBLLs that incorporate the crucial variable age of housing, analyses that have not been previously available using these data. This represents an expansion of the utility of National Health and Examination Survey that is likely to be relevant to many similar ongoing, multi-topic health surveillance efforts. Copyright © 2016 John Wiley & Sons, Ltd.

The evolution of mammal-like crocodyliforms in the Cretaceous Period of Gondwana.

Fossil crocodyliforms discovered in recent years have revealed a level of morphological and ecological diversity not exhibited by extant members of the group. This diversity is particularly notable among taxa of the Cretaceous Period (144-65 million years ago) recovered from former Gondwanan landmasses. Here we report the discovery of a new species of Cretaceous notosuchian crocodyliform from the Rukwa Rift Basin of southwestern Tanzania. This small-bodied form deviates significantly from more typical crocodyliform craniodental morphologies, having a short, broad skull, robust lower jaw, and a dentition with relatively few teeth that nonetheless show marked heterodonty. The presence of morphologically complex, complementary upper and lower molariform teeth suggests a degree of crown-crown contact during jaw adduction that is unmatched among known crocodyliforms, paralleling the level of occlusal complexity seen in mammals and their extinct relatives. The presence of another small-bodied mammal-like crocodyliform in the Cretaceous of Gondwana indicates that notosuchians probably filled niches and inhabited ecomorphospace that were otherwise occupied by mammals on northern continents.

Oldest known dinosaurian nesting site and reproductive biology of the Early Jurassic sauropodomorph Massospondylus.

The extensive Early Jurassic continental strata of southern Africa have yielded an exceptional record of dinosaurs that includes scores of partial to complete skeletons of the sauropodomorph Massospondylus, ranging from embryos to large adults. In 1976 an incomplete egg clutch including in ovo embryos of this dinosaur, the oldest known example in the fossil record, was collected from a road-cut talus, but its exact provenance was uncertain. An excavation program at the site started in 2006 has yielded multiple in situ egg clutches, documenting the oldest known dinosaurian nesting site, predating other similar sites by more than 100 million years. The presence of numerous clutches of eggs, some of which contain embryonic remains, in at least four distinct horizons within a small area, provides the earliest known evidence of complex reproductive behavior including site fidelity and colonial nesting in a terrestrial vertebrate. Thus, fossil and sedimentological evidence from this nesting site provides empirical data on reproductive strategies in early dinosaurs. A temporally calibrated optimization of dinosaurian reproductive biology not only demonstrates the primary significance of the Massospondylus nesting site, but also provides additional insights into the initial stages of the evolutionary history of dinosaurs, including evidence that deposition of eggs in a tightly organized single layer in a nest evolved independently from brooding.

Residential agricultural pesticide exposures and risk of neural tube defects and orofacial clefts among offspring in the San Joaquin Valley of California.

We examined whether early gestational exposures to pesticides were associated with an increased risk of anencephaly, spina bifida, cleft lip with or without cleft palate (CLP), or cleft palate only. We used population-based data along with detailed information from maternal interviews. Exposure estimates were based on residential proximity to agricultural pesticide applications during early pregnancy. The study population derived from the San Joaquin Valley, California (1997-2006). Analyses included 73 cases with anencephaly, 123 with spina bifida, 277 with CLP, and 117 with cleft palate only in addition to 785 controls. A total of 38% of the subjects were exposed to 52 chemical groups and 257 specific chemicals. There were relatively few elevated odds ratios with 95% confidence intervals that excluded 1 after adjustment for relevant covariates. Those chemical groups included petroleum derivatives for anencephaly, hydroxybenzonitrile herbicides for spina bifida, and 2,6-dinitroaniline herbicides and dithiocarbamates-methyl isothiocyanate for CLP. The specific chemicals included 2,4-D dimethylamine salt, methomyl, imidacloprid, and α-(para-nonylphenyl)-ω-hydroxypoly(oxyethylene) phosphate ester for anencephaly; the herbicide bromoxynil octanoate for spina bifida; and trifluralin and maneb for CLP. Adjusted odds ratios ranged from 1.6 to 5.1. Given that such odds ratios might have arisen by chance because of the number of comparisons, our study showed a general lack of association between a range of agricultural pesticide exposures and risks of selected birth defects.

Bayesian modeling of time-dependent vulnerability to environmental hazards: an example using autism and pesticide data.

BACKGROUND: Flexible modeling of time-dependent effects is required when vulnerability to hazards can be expected to vary over time, but the nature of this temporal dependency cannot be specified in advance. We present an analytic approach requiring minimal a priori assumptions about temporal parameters and producing measures of uncertainty for these parameters. METHODS: As a demonstration, we employ data describing autism spectrum disorders and applications of organochlorine pesticides in proximity to maternal residence before, during, and after pregnancy. We formulate a Bayesian model specifying temporal vulnerability as a flexible step function and constrain the dose-response relationship to be linear. We separately pooled information regarding hazard frequency and magnitude among cases and controls and used it as inputs for a Metropolis-within-Gibbs algorithm. To assess statistical significance, we conduct Monte Carlo simulations based on parameters calculated in the Gibbs portion of the algorithm. RESULTS: This method delineated two discrete periods of association between hazard and outcome. The first corresponded to a previously noted period of vulnerability with the added information of wide credible intervals, suggesting a high degree of uncertainty with respect to timing. Parameters for the second, previously unobserved period displayed slightly higher precision. Assessment of model fit favored the simultaneous inclusion of both these periods, and both periods appeared statistically significant on the basis of posterior distributions of specific parameters using Monte Carlo simulations. CONCLUSIONS: This method enabled a fuller accounting of time-dependent associations between hazards and outcomes without specifying temporal structure in advance.

Guidelines for the mapping of cancer registry data: results from a breast cancer expert panel study.

CONTEXT: Small area (eg, subcounty) cancer mapping is one of the analytic services most commonly requested of cancer registries and local public health agencies, and difficulties in providing it have been noted to undermine public confidence. Although a great many statistical protocols have been published to enable this practice, none of them are in common use to generate information for the general public. OBJECTIVES: To evaluate the utility of subcounty breast cancer mapping and articulate guidelines and a possible protocol for its implementation by cancer registries and local public health agencies. METHODS: We convened an Expert Advisory Group of breast cancer stakeholders from around California to elicit values, priorities, and preferred characteristics of protocols for proactive subcounty breast cancer mapping. Upon formulating a protocol, we applied it to 9 years of data (2000-2008) describing invasive breast cancer in California for evaluation by the Expert Advisory Group. RESULTS: Maps with subcounty resolution were seen to provide important information with a wide range of applications. Priorities included the avoidance of false-positive findings, scientific credibility, and the provision of information elucidating social and environmental characteristics. A protocol using Kulldorff's Scan Statistic along with postanalytic steps for refining results was elaborated; when applied to the data, 4 discrete regions with elevated rates of invasive breast cancer were identified and described. CONCLUSIONS: Expert Advisory Group priorities were readily translatable into a scientifically rigorous protocol that protected confidentiality and avoided statistically unstable rate estimates. The resulting maps enabled participants to visualize geographically defined populations falling within and crossing county boundaries. These findings support the enactment of policies for the routine and proactive analysis of breast cancer surveillance data to provide subcounty information.

Iyuku raathi, a new iguanodontian dinosaur from the Early Cretaceous Kirkwood Formation, South Africa.

We name and describe a new iguanodontian dinosaur from the Early Creteceous Kirkwood Formation, Eastern Cape Province, South Africa. This dinosaur is one of only two ornithopod dinosaurs known from the Cretaceous of southern Africa, and is unique in being represented primarily by hatchling to young juvenile individuals as demonstrated by bone histological analysis. All of the juvenile material of this new taxon comes from a single, laterally-restricted bonebed and specimens were primarily recovered as partial to complete single elements, although rare articulated materials and one partial skeleton were found. Sedimentology of the bonebed suggests that this horizon heralds a change in environment upsection to a drier and more seasonal climate. This accumulation of bones is interpreted as seasonal mortality from a nesting site or nesting grounds and may be linked to this environmental shift.

Calibrating the zenith of dinosaur diversity in the Campanian of the Western Interior Basin by CA-ID-TIMS U-Pb geochronology.

The spectacular fossil fauna and flora preserved in the Upper Cretaceous terrestrial strata of North America's Western Interior Basin record an exceptional peak in the diversification of fossil vertebrates in the Campanian, which has been termed the 'zenith of dinosaur diversity'. The wide latitudinal distribution of rocks and fossils that represent this episode, spanning from northern Mexico to the northern slopes of Alaska, provides a unique opportunity to gain insights into dinosaur paleoecology and to address outstanding questions regarding faunal provinciality in connection to paleogeography and climate. Whereas reliable basin-wide correlations are fundamental to investigations of this sort, three decades of radioisotope geochronology of various vintages and limited compatibility has complicated correlation of distant fossil-bearing successions and given rise to contradictory paleobiogeographic and evolutionary hypotheses. Here we present new U-Pb geochronology by the CA-ID-TIMS method for 16 stratigraphically well constrained bentonite beds, ranging in age from 82.419 ± 0.074 Ma to 73.496 ± 0.039 Ma (2σ internal uncertainties), and the resulting Bayesian age models for six key fossil-bearing formations over a 1600 km latitudinal distance from northwest New Mexico, USA to southern Alberta, Canada. Our high-resolution chronostratigraphic framework for the upper Campanian of the Western Interior Basin reveals that despite their contrasting depositional settings and basin evolution histories, significant age overlap exists between the main fossil-bearing intervals of the Kaiparowits Formation (southern Utah), Judith River Formation (central Montana), Two Medicine Formation (western Montana) and Dinosaur Park Formation (southern Alberta). Pending more extensive paleontologic collecting that would allow more rigorous faunal analyses, our results support a first-order connection between paleoecologic and fossil diversities and help overcome the chronostratigraphic ambiguities that have impeded the testing of proposed models of latitudinal provinciality of dinosaur taxa during the Campanian.

Geology and taphonomy of a unique tyrannosaurid bonebed from the upper Campanian Kaiparowits Formation of southern Utah: implications for tyrannosaurid gregariousness.

Tyrannosaurids are hypothesized to be gregarious, possibly parasocial carnivores engaging in cooperative hunting and extended parental care. A tyrannosaurid (cf. Teratophoneus curriei) bonebed in the late Campanian age Kaiparowits Formation of southern Utah, nicknamed the Rainbows and Unicorns Quarry (RUQ), provides the first opportunity to investigate possible tyrannosaurid gregariousness in a taxon unique to southern Laramidia. Analyses of the site's sedimentology, fauna, flora, stable isotopes, rare earth elements (REE), charcoal content and taphonomy suggest a complex history starting with the deaths and transport of tyrannosaurids into a peri-fluvial, low-energy lacustrine setting. Isotopic and REE analyses of the fossil material yields a relatively homogeneous signature indicating the assemblage was derived from the same source and represents a fauna living in a single ecospace. Subsequent drying of the lake and fluctuating water tables simultaneously overprinted the bones with pedogenic carbonate and structurally weakened them through wet-dry cycling. Abundant charcoal recovered from the primary bone layer indicate a low temperature fire played a role in the site history, possibly triggering an avulsion that exhumed and reburied skeletal material on the margin of a new channel with minimal transport. Possible causes of mortality and concentration of the tyrannosaurids include cyanobacterial toxicosis, fire, and flooding, the latter being the preferred hypothesis. Comparisons of the RUQ site with other North American tyrannosaur bonebeds (Dry Island-Alberta; Daspletosaurus horneri-Montana) suggest all formed through similar processes. Combined with ichnological evidence, these tyrannosaur mass-burial sites could be part of an emerging pattern throughout Laramidia reflecting innate tyrannosaurid behavior such as habitual gregariousness.

Spatially continuous local rate modeling for communication in public health: a practical approach.

A primary function of Environmental Public Health Tracking is the communication of spatial trends of diseases. Traditional (choropleth) approaches to disease mapping}?> have difficulty conveying intuitive understandings of the spatial continuity of disease risk, rate calculations in rural areas, and degrees of statistical significance. A spatial loess function can be utilized to depict continuous variations in preterm birth risk for the state of California on the basis of a 3-year birth cohort. Results from this function were graphically depicted and incorporated into a Web mapping service to maximize public accessibility. The function was evaluated as a tool for communication by considering its intuitive interpretation and comparing information derived from the function with that, which would be derived from a choropleth map using the same data. In general, the loess function was able to generate risk information for a variety of both urban and rural settings. Although richer in detail, this information was mostly consistent with that which would come from choropleth maps. Occasionally, information from the loess function stood in contradiction to the choropleth mapping procedure; however; we enumerate these occasions and discuss ways to maximize the consistency of the loess function with intuitive understandings of disease risk.

Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley.

BACKGROUND: Ambient levels of pesticides ("pesticide drift") are detectable at residences near agricultural field sites. OBJECTIVE: Our goal was to evaluate the hypothesis that maternal residence near agricultural pesticide applications during key periods of gestation could be associated with the development of autism spectrum disorders (ASD) in children. METHODS: We identified 465 children with ASD born during 1996-1998 using the California Department of Developmental Services electronic files, and matched them by maternal date of last menstrual period to 6,975 live-born, normal-birth-weight, term infants as controls. We determined proximity to pesticide applications using California Department of Pesticide Regulation records refined using Department of Water Resources land use polygons. A staged analytic design applying a priori criteria to the results of conditional logistic regressions was employed to exclude associations likely due to multiple testing error. RESULTS: Of 249 unique hypotheses, four that described organochlorine pesticide applications--specifically those of dicofol and endosulfan--occurring during the period immediately before and concurrent with central nervous system embryogenesis (clinical weeks 1 through 8) met a priori criteria and were unlikely to be a result of multiple testing. Multivariate a posteriori models comparing children of mothers living within 500 m of field sites with the highest nonzero quartile of organochlorine poundage to those with mothers not living near field sites suggested an odds ratio for ASD of 6.1 (95% confidence interval, 2.4-15.3). ASD risk increased with the poundage of organochlorine applied and decreased with distance from field sites. CONCLUSIONS: The association between residential proximity to organochlorine pesticide applications during gestation and ASD among children should be further studied.

The outdoor air quality flag program in central California: a school-based educational intervention to potentially help reduce children's exposure to environmental asthma triggers.

This paper describes a novel school-based, visual environmental public health educational intervention intended to help reduce the exposure of children-and adults-to outdoor air pollution, including known environmental asthma triggers like ozone and particles. The overarching goal was to enhance the learning, recreational, and work environments of students and staff. The specific purpose of the Asthma-Friendly Outdoor (Ambient) Air Quality Flag Program was to establish an education and communication tool for Central California communities that would accomplish two things: (1) Establish permanent local policy change to existing operating procedures in school districts and schools to help reduce the exposure of students, teachers, staff, and nearby communities to outdoor environmental asthma triggers and (2) provide education on air quality and potential health effects of exposure to air pollutants. Data on the program from its initial years are presented. To date, the following important lessons have been learned: (1) Science-based, simple, visual, low-cost school-based educational interventions to help reduce human exposure to outdoor environmental asthma triggers (i.e., ozone, particles, and pollens) can work in socioeconomically and ethnically diverse urban and rural or agricultural communities, and (2) local health and environmental justice groups such as asthma coalitions can successfully lead school-based environmental interventions to help improve children's quality of life.

Assessing Child Lead Poisoning Case Ascertainment in the US, 1999-2010.

OBJECTIVES: To compare prevalence estimates for blood lead level ≥10.0 µg/dL (elevated blood lead level [EBLL]) with numbers reported to the Centers for Disease Control and Prevention (CDC) for children 12 months to 5 years of age from 1999 to 2010 on a state-by-state basis. METHODS: State-specific prevalence estimates were generated based on the continuous NHANES according to newly available statistical protocols. Counts of case reports were based on the 39 states (including the District of Columbia) reporting to the CDC Childhood Lead Poisoning Prevention Program during the study period. Analyses were conducted both including and excluding states and years of nonreporting to the CDC. RESULTS: Approximately 1.2 million cases of EBLL are believed to have occurred in this period, but 607 000 (50%) were reported to the CDC. Including only states and years for which reporting was complete, the reporting rate was 64%. Pediatric care providers in 23 of 39 reporting states identified fewer than half of their children with EBLL. Although the greatest numbers of reported cases were from the Northeast and Midwest, the greatest numbers based on prevalence estimates occurred in the South. In southern and western states engaged in reporting, roughly 3 times as many children with EBLL were missed than were diagnosed. CONCLUSIONS: Based on the best available estimates, undertesting of blood lead levels by pediatric care providers appears to be endemic in many states.