Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dataset”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,585 records · Page 88Linked to original sources
PubMed1999

Causal inference in a clinical trial: a comparative example.

Recently there has been much interest in methods for analyzing clinical trials of treatments that are subject to noncompliance. In this paper I study a small, simple dataset from a clinical trial of immunosuppressive therapy in the treatment of multiple sclerosis. I apply and compare a range of methods: the as-randomized (intention-to-treat) analysis, the as-treated analysis, estimates based on a nonignorable selection model, and Rubin's causal model. The results differ substantially even in this small dataset that exhibits modest noncompliance. For this reason, data analysts should be clear about which parameters are of greatest importance in the analysis of a clinical trial.

Azathioprine↗
PubMed2003

Modelling multivariate biomechanical measurements of the spine during a rowing exercise.

OBJECTIVE: To investigate the ability of statistical techniques to detect systematic changes in rowing technique during a rowing session and to discriminate between rowers of different abilities with and without back pain. DESIGN: Statistical techniques were applied to kinematic datasets of elite level rowers, in order to construct an empirical model of the rowing stroke. BACKGROUND: The size and complexity of datasets generated by biomechanical kinematics evaluations has led to opportunities for analysing pathology whilst introducing substantial challenges for statistical analysis. METHODS: Spinal motion and load output of 18 International and National standard competitive rowers were monitored during ergometer rowing sessions. International rower data were used to construct an empirical model of this activity. Linear stroke models were derived using principal components and a generalized cross-validation procedure. Performance characteristics of the identified models were calculated for all rowing groups. The stroke model was applied to distinguishing pattern variations within and between rowers. A multivariate logistic regression analysis was carried out to examine the relationship between stroke model parameters on the incidence of low back pain. RESULTS: 90% of the variability in the data was explained by the first three principal component variables. Stroke models with three basis functions were selected for each variable. The models performed well on the National rowers, providing validation of the models. A 2-variable model showed a significant difference between the rowing stroke characteristics of rowers with and without low back pain (P<0.01). CONCLUSIONS: A parsimonious collection of empirical models effectively describes motion and load characteristics of ergometer rowing. Patterns in rowing technique are found to be strongly associated with the incidence lower back pain. RELEVANCE: Empirical statistical models can be used to track changes in rowing technique, and discriminate between different rowing groups. This may impact rowing training, and rehabilitation.

Biomechanical Phenomena↗
PubMed2003

Spatial and temporal analysis of second-generation anticoagulant rodenticide residues in polecats (Mustela putorius) from throughout their range in Britain, 1992-1999.

Polecats (Mustela putorius) in Britain are currently expanding their range eastwards from Wales to reoccupy central and eastern areas of England. Second-generation anticoagulant rodenticides (SGARs), to which polecats are exposed by eating contaminated prey, are used more extensively in these central and eastern regions, leading to fears of increased exposure, and possible resultant mortality. We measured bromadiolone, difenacoum, flocoumafen and brodifacoum concentrations in the livers of 50 polecats from areas that included newly recolonised habitats and found that at least one SGAR was detected in the livers of 13 out of 37 (35.1%) male and 5 out of 13 (38.5%) female polecats. Difenacoum and bromadiolone were detected most frequently. We then combined these data with measurements on another 50 individuals from earlier studies to create a dataset for 100 polecats collected throughout the 1990s from across the whole of their current range. Using this dataset, we determined if there was any evidence that contamination in polecats had increased during the 1990s and whether animals from England were more contaminated than those from Wales, as might be expected given regional differences in the patterns of SGAR use. Overall, 31 of the 100 polecats analysed to date contained SGAR residues. The incidence was a little higher (40%) in animals that died between January and June and this probably better reflects the overall proportion of animals that are sub-lethally exposed. There was no statistically significant change during the 1990s in the proportion of polecats exposed to SGARs nor any evidence that greater use of SGARs in England resulted in more contamination of polecats. Contrary to expectation, the proportion of animals that contained difenacoum was marginally higher in Wales than elsewhere.

4-Hydroxycoumarins↗
PubMed2004

Tinker, tailor, soldier, patient: work attributes and depression disparities among young adults.

Prior studies have consistently found the occurrence of depression to be higher among persons with lower socio-economic status (SES), but causal mechanisms for this relationship are often not well understood. For example, while depression has been shown to increase during spells of unemployment, little work has been done on job attributes that may be related to depression among employed people early in their careers. This study links the 1992 wave of the National Longitudinal Survey of Youth 1979 cohort-which included Depression symptom scores on the Center for Epidemiologic Studies Depression (CES-D) instrument-to the US Department of Labor's new occupational characteristics O*Net dataset. The resulting dataset includes information regarding depression, SES, and specific attributes of jobs held by the young adult respondents. Job attributes included measures of social status, interpersonal stressors, and physical conditions. Multivariate analysis revealed that for young men, higher job status is associated with lower CES-D scores. Higher scores on the opposition scale, which measures the extent to which employees are obliged to take a position opposed to others, is associated with higher CES-D scores. For young women, physically uncomfortable or dangerous jobs are associated with more depressive symptoms. Results are stratified by race/ethnicity. For Black men, unlike for White men or Latinos, job security is associated with fewer depressive symptoms; and for Latino men, but not for Black or White men, physically uncomfortable or dangerous jobs are associated with more depressive symptoms. For Black women, job status is associated with fewer depressive symptoms. We conclude that part of the SES-depression relationship may arise from the psychosocial aspects of jobs, which we have found to be significantly and meaningfully associated with depressive symptoms among employed young adults.

Adolescent↗
PubMed1997

Predicting survival from out-of-hospital cardiac arrest: a multivariate analysis.

From 954 attempts to resuscitate patients from out-of-hospital cardiac arrest two datasets were derived, namely 861 cases of cardiac arrest and 906 cases of either cardiac or primary respiratory arrest. For each dataset, multivariate analysis was performed by fitting a number of explanatory variables with respect to the outcomes of admission to hospital and discharge home in logistic regression models. There were numerous interactions between these variables. Being conscious at the time of the arrival of the ambulance crew and subsequently having cardiac arrest strongly predicted survival, as did both the presence of a witness to the arrest and the initiation of cardiopulmonary resuscitation (CPR) by a bystander; this latter effect was a marker for early CPR. The strongest predictor of a poor outcome was delay to CPR or delay to advanced cardiac life support.

Age Distribution↗
PubMed2003

Assessing soil biodiversity across Great Britain: national trends in the occurrence of heterotrophic bacteria and invertebrates in soil.

An assessment of the biodiversity of soils was a component of the Countryside Survey 2000 (CS2000). This was the first integrated survey of soil biota and chemical properties at a national scale. A total of 1052 soil samples were collected across Great Britain during CS2000 and analysed for a range of soil microbial and invertebrate characteristics resulting in the production of a series of robust datasets. A principal objective was to use these datasets to investigate relationships between soil biota and environmental factors such as geographical location, vegetation, land use, land cover, soil type and pollutant levels as first stages in characterising the inherent biodiversity of British soils and investigating the potential of soil biodiversity as indicators of soil health at a regional or national scale. Preliminary results for culturable heterotrophic, invertebrate taxa, Acari, Collembola and Oribatid mites are presented here to illustrate the nature of the data collected and the patterns of soil biodiversity in relation to large-scale regional, vegetation and soil characteristics across the British countryside.

Animals↗
PubMed2002

Selection of a representative set of chemical accidents from a complex data matrix for the development of environment-accident index.

Chemical accidents often lead to negative consequences for the environment. Preparedness and proper actions are, therefore, essential components in order to minimise environmental effects. To assist and facilitate this work, a proposed planning tool, the environment-accident index (EAI), was formulated by Scott [J. Hazard. Mater. 61 (1998) 305]. As a result of a first validation of the index, based on 21 chemical accidents, the database was complemented with 42 additional accidents covering a broader spectrum of chemicals. The additional accidents were collected by means of an inquiry and their environmental consequences are, so far, unknown. The collected data had an overrepresentation of accidents involving petroleum products (69%). Because of the overrepresentation of this group of chemicals in the material, the data was skewed with respect to chemical properties. Since the model should be valid for a variety of chemical accidents, a method was needed which enabled a proper and unbiased selection of a representative subset of accidents to be used in development and validation of the model. For this purpose, the possibility to use multivariate data analysis in combination with statistical design was investigated. The result showed the feasibility of this method in the selection of a representative subset from a complex and skewed large dataset. Within the new dataset, 53% were accidents involving petroleum products and 47% involved other chemicals. The selected accidents will be used in further work to evaluate the environmental consequences, for model development and model validation.

Accidents↗
PubMedDate not supplied

Efficient sampling for three-dimensional atom probe microscopy data.

The best calculation of concentration profiles, isoconcentration surfaces or Gibbsian interfacial excesses from three-dimensional atom-probe microscopy data requires a compromise between spatial positioning error and statistical sampling error. For example, sampling from larger spatial regions decreases the statistical error, but increases the error in spatial positioning. Finding the appropriate balance for a particular calculation can be tricky, especially when the three-dimensional nature of the data presents an infinite number of degrees of freedom in defining surfaces, and when the statistical error is changing from one region of a sample to another due to differences in collection efficiency or atomic density. We present some strategies for approaching these problems, focusing on efficient algorithms for generating different spatial samplings. We present a unique double-splat algorithm, in which an initial, fine-grained sampling is taken to convert the data to a regular grid, followed by a second, variable width splat, to spread the effective sampling distance to any value desired. The first sampling is time consuming for a large dataset, but needs only be performed once. The second splat is done on a regular grid, so it is efficient, and can be repeated as many times as necessary to find the correct balance of statistical and positioning error. The net effect is equivalent to a Gaussian spreading of each data point, without the necessity of calculating Gaussian coefficients for millions of data points. We show examples of isoconcentration surfaces calculated under different circumstances from the same dataset.

Journal Article↗
PubMed2003

Performance of different radiotherapy workload models.

PURPOSE: The purpose of this study was to evaluate the performance of different radiotherapy workload models using a prospectively collected dataset of patient and treatment information from a single center. METHODS AND MATERIALS: Information about all individual radiotherapy treatments was collected for 2 weeks from the three linear accelerators (linacs) in our department. This information included diagnosis code, treatment site, treatment unit, treatment time, fields per fraction, technique, beam type, blocks, wedges, junctions, port films, and Eastern Cooperative Oncology Group (ECOG) performance status. We evaluated the accuracy and precision of the original and revised basic treatment equivalent (BTE) model, the simple and complex Addenbrooke models, the equivalent simple treatment visit (ESTV) model, fields per hour, and two local standards of workload measurement. RESULTS: Data were collected for 2 weeks in June 2001. During this time, 151 patients were treated with 857 fractions. The revised BTE model performed better than the other models with a mean [observed -predicted] of 2.62 (2.44-2.80). It estimated 88.0% of treatment times within 5 min, which is similar to the previously reported accuracy of the model. CONCLUSION: The revised BTE model had similar accuracy and precision for data collected in our center as it did for the original dataset and performed the best of the models assessed. This model would have uses for patient scheduling, and describing workloads and case complexity.

Appointments and Schedules↗
PubMed1998

Validation and predictive power of Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90-06.

PURPOSE: The recursive partitioning analysis (RPA) classes for malignant glioma patients were previously established using data on over 1500 patients entered on Radiation Therapy Oncology Group (RTOG) clinical trials. The purpose of the current analysis was to validate the RPA classes with a new dataset (RTOG 90-06), determine the predictive power of the RPA classes, and establish the usefulness of the database norms for the RPA classes. PATIENTS AND METHODS: There are six RPA classes for malignant glioma patients that comprise distinct groups of patients with significantly different survival outcome. RTOG 90-06 is a randomized Phase III study of 712 patients accrued from 1990 to 1994. The minimum potential follow-up is 18 months. The treatment arms were combined for the purpose of this analysis. There were 84, 13, 105, 240, 150, and 23 patients in the RPA Classes I-VI from RTOG 90-06, respectively. RESULTS: The median survival times (MST) and 2-year survival rates for the six RPA classes in RTOG 90-06 are compared to those previously published. The MST and 2-year survival rates for the RTOG RPA classes were within 95% confidence intervals of the 90-06 estimates for Classes I, III, IV, and V. The RPA classes explained 43% of the variation (squared error loss). By comparison, a Cox model explains 30% of the variation. The RPA classes within RTOG 90-06 are statistically distinct with all comparisons exceeding 0.0001, except those involving Class II. A survival analysis from a prior RTOG study indicated that 72.0 Gy had superior outcome to literature controls; analysis of this data by RPA classes indicates the survival results were not superior to the RTOG database norms. CONCLUSION: The validity of the model is verified by the reliability of the RPA classes to define distinct groups with respect to survival. Further evidence is given by prediction of MST and 2-year survival for all classes except Class II. The RPA classes explained a good portion of the variation in survival outcome in the data. Lack of correlation in RPA Class II between datasets may be an artifact of the small sample size or an indication that this class is not distinct. The validation of the RPA classes attests to their usefulness as historical controls for the comparison of future Phase II results.

Dose Fractionation, Radiation↗
PubMed1999

Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: a quantitative dosimetric study.

PURPOSE: To analyze the failure patterns for patients with high-grade astrocytomas treated with high-dose conformal radiotherapy (CRT) using a quantitative technique to calculate the dose received by the CT- or MR-defined recurrence volume and to assess whether the final target volume margin used in the present dose escalation study requires redefinition before further escalation. METHODS AND MATERIALS: Between 4/89 and 10/95, 71 patients with high-grade supratentorial astrocytomas were entered in a phase I/II dose escalation study using 3-D treatment planning and conformal radiotherapy. All patients were treated to either 70 or 80 Gy in conventional daily fractions of 1.8-2.0 Gy. The clinical and planning target volumes (CTV, PTV) consisted of successively smaller volumes with the final PTV defined as the enhancing lesion plus 0.5 cm margin. As of 10/95, 47 patients have CT or MR evidence of disease recurrence/progression. Of the 47 patients, 36 scans obtained at the time of recurrence were entered into the 3-D radiation therapy treatment planning system. After definition of the recurrent tumor volumes, the recurrence scan dataset was registered with the pretreatment CT dataset so that the actual dose received by the recurrent tumor volumes during treatment could be accurately calculated and then analyzed dosimetrically using dose-volume histograms. Recurrences were divided into several categories: 1) "central," in which 95% or more of the recurrent tumor volume (Vrecur) was within D95, the region treated to high dose (95% of the prescription dose); 2) "in-field," in which 80% or more of Vrecur was within the D95 isodose surface; 3) "marginal," when between 20 and 80% of Vrecur was inside the D95 surface; 4) "outside," in which less than 20% of Vrecur was inside the D95 surface. RESULTS: In 29 of 36 patients, a solitary lesion was seen on recurrence scans. Of the 29 solitary recurrences, 26 were central, 3 were marginal, and none were outside. Multiple recurrent lesions were seen in seven patients: three patients had multiple central and/or in-field lesions only, three patients had central and/or in-field lesions with additional small marginal or outside lesions, and one patent had 6 outside and one central lesion. Since total recurrence volume was used in the final analysis, 6 of the 7 patients with multiple recurrent lesions were classified into centra/in-field category. CONCLUSION: Analysis of the 36 evaluable patients has shown that 32 of 36 patients (89%) failed with central or in-field recurrences, 3/36 (8%) had a significant marginal component to the recurrence, whereas only 1/36 (3%) could be clearly labeled as failing mainly outside the high-dose region. Seven patients had multiple recurrences, but only 1 of 7 had large-volume recurrences outside the high-dose region. This study shows that the great majority of patient recurrences that occur after high-dose (70 or 80 Gy) conformal irradiation are centrally located: only 1/36 patients (with 7 recurrent lesions) had more than 50% of the recurrence volume outside the region previously treated to high dose. Further dose escalation to 90 Gy (and beyond) thus seems reasonable, based on the same target volume definition criteria

Adult↗
PubMed2000

Radiation pneumonitis after breast cancer irradiation: analysis of the complication probability using the relative seriality model.

BACKGROUND: Toxicity of the respiratory system is quite common after radiotherapy of thoracic tumors; breast cancer patients represent one of the groups for which there is also a long expected survival. The quantification of lung tissue response to irradiation is important in designing treatments associated with a minimum of complications and maximum tumor control. METHODS: The study population consisted of 68 patients who received irradiation for breast cancer at Stage II. Radiation pneumonitis was retrospectively assessed on the basis of clinical symptoms and radiological findings. For each patient, a measure of the exposure (i.e., the lung dose-volume histogram [DVH]) and a measure of the outcome was available. Based on these data, a maximum likelihood fitting to the relative seriality model was performed. The uncertainties of the model parameters were calculated and their impact on the dose-response curve was studied. The optimum parameter set was then applied to 5 other patient groups treated for breast cancer, and the normal tissue complication probability (NTCP) was calculated. Each group was individuated by the radiotherapy treatment technique used; the dose distribution in the lung was described by a mean DVH and the incidence of radiation pneumonitis in each group was known. Lung radiosensitivity was assumed to be homogeneous through all of the calculations. RESULTS: The relative seriality model could describe the dataset. The volume effect was found to be relevant in the description of radiation pneumonitis. Age was found to be associated with increased risk of radiation pneumonitis. Two distinct dose-response curves were obtained by splitting the group according to age. The impact of the parameter uncertainties on the dose-response curve was quite large. The parameter set determined could be used predictively on 3 of the 5 patient groups. CONCLUSION: The complication data could be modeled with the relative seriality model. However, further independent datasets, classified according to the same endpoint, must be analyzed before introducing NTCP modeling in clinical practice.

Age Factors↗
PubMed2000

Regrowth delay analysis of irradiated tumors in the curative dose region.

PURPOSE: To develop a method to analyze regrowth delay times, including cured tumors. METHODS AND MATERIALS: Regrowth delay measured in the in vitro squamous cell carcinoma megacolony system following fractionated irradiation was analyzed using two different approaches. A conventional regrowth delay analysis based on means or medians of dose groups was contrasted with a one-step procedure using the inverse of individual regrowth delay times, where cured tumors are represented by an infinite delay time. Two data sets with different proportions of cured tumors were compared in this way. In addition, for both approaches, confidence limits were also generated by the bootstrap technique. RESULTS: The parameter estimated was the alpha/beta ratio. The inverse analysis yielded similar results as the conventional analysis, but with much smaller confidence limits. When the dataset was stripped by stepwise removal of lower dose groups with no cures, the estimates of the alpha/beta ratio remained definitely more robust in inverse analysis. Results of the bootstrap procedure confirmed the accuracy of the calculated confidence intervals. CONCLUSION: Regrowth delay analysis using reciprocal regrowth delay times is a useful tool, especially when the data shows large variations, or a substantial fraction of the dataset falls into the curative dose region.

Animals↗
PubMed2000

Covariation of GC content and the silent site substitution rate in rodents: implications for methodology and for the evolution of isochores.

Many attempts to test selectionist and neutralist models employ estimates of synonymous (Ks) and non-synonymous (Ka) substitution rates of orthologous genes. For example, a stronger Ka-Ks correlation than expected under neutrality has been argued to indicate a role for selection and the absence of a Ks-GC4 correlation has been argued to be inconsistent with neutral models for isochore evolution. However, both of these results, we have shown previously, are sensitive to the method by which Ka and Ks are estimated. Using a maximum likelihood (ML) estimator (GY94) we found a positive correlation between Ks and GC4 and only a weak correlation between Ka and Ks, lower than expected under neutral expectations. This ML method is computationally slow. Recently, a new ad hoc approximation of this ML method has been provided (YN00). This is effectively an extension of Li's protocol but that also allows for codon usage bias. This method is computationally near-instantaneous and therefore potentially of great utility for analysis of large datasets. Here we ask whether this method might have such applicability. To this end we ask whether it too recovers the two unusual results. We report that when the ML and earlier ad hoc methods disagree, YN00 recovers the results described by the ML methods, i.e. a positive correlation between GC4 and Ks and only a weak correlation between Ks and Ka. If the ML method can be trusted, then YN00 can also be considered an adequately reliable method for analysis of large datasets. Assuming this to be so we also analyze further the patterns. We show, for example, that the positive correlation between GC4 and Ks is probably in part a mutational bias, there being more methyl induced CpG-->TpG mutations in GC rich regions. As regards the evolution of isochores, it seems inappropriate to use the claimed lack of a correlation between GC and Ks as definitive evidence either against or for any model. If the positive correlation is real then, we argue, this is hard to reconcile with the biased gene conversion model for isochore formation as this predicts a negative correlation.

Animals↗
PubMed2002

Playing chicken (Gallus gallus): methodological inconsistencies of molecular divergence date estimates due to secondary calibration points.

For any given taxonomic divergence event, one may find in the literature a wide range of time estimates. Many factors contribute to the variation in molecular date estimates for the same evolutionary event. High on the list is the choice of calibration points for converting genetic distances into evolutionary rates and, subsequently, into dates of divergence. In this study, we investigate one critical source of error in estimating divergence times, i.e. the use of secondary calibration points, which are divergence time estimates that have been derived from one molecular dataset on the basis of a primary external calibration point, and which are used again independently of the original external calibration point on a second dataset. Unless particular care is exercised, this practice leads to internal inconsistencies, and the inferred dates of divergence are by necessity unreliable. We present a consistency test for assessing the reliability of divergence time estimates based on secondary calibration points. As a case study, we examine recent estimates of divergence times among phyla and kingdoms based on multiple nuclear protein-coding genes, and show that they fail the consistency test.

Amino Acid Substitution↗
PubMed2003

Superiority of 3D wavelet-packet denoising in MR microscopy.

Three dimensional Magnetic Resonance Imaging (MRI) datasets are becoming increasingly important in clinical and research applications because of their inherent signal to noise (SNR) advantages, high resolution and isotropic voxels. Despite SNR advantages, some 3D acquisitions may be SNR-limited, particularly in MR microscopy. Historically, both classic filtering and wavelet-based denoising techniques have been performed on a slice-by-slice basis. In principle, adaptive techniques such as best- basis wavelet-packet denoising might offer inherent advantages when performed in 3D, instead of 2D, by tracking through plane "structure" and suppressing noise "pseudostructure." This hypothesis was tested in 10 volumetric MR microscopy datasets from several different MR microscopy atlas projects. 3D wavelet-packet denoised images consistently yielded lower minimum mean-square error and subjectively perceived noise power than corresponding 2D denoised images using otherwise identical algorithms and parameters. MR microscopy researchers preferred the denoised images to the unprocessed images for their atlas projects.

Animals↗
PubMed2000

A QSAR model for the eye irritation of cationic surfactants.

A QSAR model for the eye irritation of cationic surfactants has been constructed using a dataset consisting of the maximum average scores (MAS-accordance to Draize) for 29 in vivo rabbit eye irritation tests on 19 different cationic surfactants. The parameters used were logP (log [octanol/water partition coefficient]) and molecular volume (to model the partition of the surfactants into the membranes of the eye), logCMC (log critical micelle concentration-a measure of the reactivity of the surfactants with the eye) together with surfactant concentration. The model was constructed using neural network analysis. MAS showed strongly positive, non-linear correlations with surfactant concentration and logCMC and a strongly negative, non-linear correlation with logP. The Pearson correlation between the actual and predicted values of MAS was 0.838 showing that around 70% (r(2)=0.702) of the variance in the dataset is explained by the model. This value is consistent with levels of biological variability reported historically for the Draize rabbit eye test. The relationship provides a potentially useful prediction model for the eye irritation potential of new or untested cationic surfactants with physicochemical properties lying within the parameter space of the model.

Animals↗
PubMedDate not supplied

Chemical testing strategies for predicting health hazards to children.

The United States Environmental Protection Agency has proposed the development of a Children's Health Test Program under the Toxic Substances Control Act. The Environmental Protection Agency's proposal for the children's health test battery has 12 different assays including general toxicity, genotoxicity, carcinogenicity, neurotoxicity, and developmental and reproductive toxicity. The current Environmental Protection Agency testing proposal is an "all or nothing" test battery. An alternative and preferable approach would be to use a science-based, tiered testing scheme. It is proposed that the Screening Information Dataset program, currently used by the Organization for Economic Co-operation and Development (OECD) for the Screening Information Dataset-High Production Volume test battery, or equivalent, be considered for the first step. Step 1 would include acute and repeat dose toxicity testing, developmental toxicity testing (first species OECD 414 or OECD 422), reproductive toxicity screening (OECD 415 or 422), and genetic toxicity testing. For this step, the rat would be the initial and only species tested unless the mouse was used for in vivo genetic toxicity. Step 2 of the proposed children's health test battery would include developmental testing (second species OECD 414) or special mode of action studies performed for those chemicals that proved to be developmental toxicants in Step 1. Those chemicals that tested positive as reproductive toxicants in Step 1 would be tested in a two-generation reproduction study (OECD 416) or a special mode of action study. Steps 1 and 2 provide information on whether oncogenicity or developmental neurotoxicity testing is useful. Step 3 would include chronic toxicity/oncogenicity testing for those chemicals that tested positive for genetic toxicity in Step 1, and positive for developmental concerns in Step 2. In this step, chemicals would also be tested for developmental neurotoxicity if they showed evidence of neuropathy, behavioral effects, or neurotoxic potential in earlier studies. This stepwise approach would conserve resources and answer scientific questions in a logical, orderly, timely, and cost-effective manner.

Animals↗