Preface |
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ix | |
Acknowledgments |
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xi | |
About the Companion Website |
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xiii | |
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1 An Introduction to Toxicity Experiments |
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1 | (18) |
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1.1 Nature and Purpose of Toxicity Experiments |
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1 | (6) |
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1.2 Regulatory Context for Toxicity Experiments |
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7 | (1) |
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1.3 Experimental Design Basics |
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8 | (4) |
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1.4 Hierarchy of Models for Simple Toxicity Experiments |
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12 | (1) |
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1.5 Biological vs. Statistical Significance |
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13 | (2) |
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1.6 Historical Control Information |
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15 | (1) |
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1.7 Sources of Variation and Uncertainty |
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15 | (1) |
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1.8 Models with More Complex Structure |
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16 | (1) |
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1.9 Multiple Tools to Meet a Variety of Needs or Simple Approaches to Capture Broad Strokes? |
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16 | (3) |
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2 Statistical Analysis Basics |
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19 | (28) |
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19 | (1) |
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19 | (5) |
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2.3 Probability Distributions |
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24 | (5) |
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2.4 Assessing Data for Meeting Model Requirements |
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29 | (1) |
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30 | (1) |
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2.6 Visual Examination of Data |
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30 | (2) |
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32 | (2) |
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34 | (1) |
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35 | (2) |
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37 | (1) |
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2.11 Experiments with Multiple Controls |
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38 | (9) |
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41 | (6) |
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3 Analysis of Continuous Data: NOECs |
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47 | (42) |
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47 | (1) |
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47 | (6) |
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3.3 Preliminary Assessment of the Data to Select the Proper Method of Analysis |
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53 | (9) |
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3.4 Pairwise Tests When Data do not Meet Normality or Variance Homogeneity Requirements |
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62 | (5) |
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67 | (8) |
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3.6 Protocol for NOEC Determination of Continuous Response |
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75 | (1) |
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3.7 Inclusion of Random Effects |
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75 | (1) |
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3.8 Alternative Error Structures |
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76 | (1) |
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3.9 Power Analyses of Models |
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77 | (12) |
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81 | (8) |
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4 Analysis of Continuous Data: Regression |
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89 | (34) |
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89 | (3) |
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4.2 Models in Common Use to Describe Ecotoxicity Dose-Response Data |
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92 | (3) |
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4.3 Model Fitting and Estimation of Parameters |
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95 | (9) |
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104 | (8) |
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4.5 Summary of Model Assessment Tools for Continuous Responses |
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112 | (11) |
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114 | (9) |
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5 Analysis of Continuous Data with Additional Factors |
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123 | (34) |
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123 | (1) |
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5.2 Analysis of Covariance |
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123 | (12) |
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5.3 Experiments with Multiple Factors |
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135 | (22) |
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154 | (3) |
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6 Analysis of Quantal Data: NOECs |
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157 | (24) |
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157 | (1) |
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157 | (3) |
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6.3 Model Assessment for Quantal Data |
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160 | (2) |
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6.4 Pairwise Models that Accommodate Overdispersion |
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162 | (3) |
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6.5 Trend Tests for Quantal Response |
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165 | (3) |
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6.6 Power Comparisons of Tests for Quantal Responses |
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168 | (4) |
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6.7 Zero-Inflated Binomial Responses |
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172 | (3) |
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6.8 Survival- or Age-Adjusted Incidence Rates |
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175 | (6) |
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179 | (2) |
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7 Analysis of Quantal Data: Regression Models |
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181 | (38) |
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181 | (1) |
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181 | (7) |
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188 | (1) |
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188 | (2) |
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7.5 Abbott's Formula and Normalization to the Control |
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190 | (7) |
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7.6 Proportions Treated as Continuous Responses |
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197 | (1) |
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198 | (1) |
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7.8 Including Time-Varying Responses in Models |
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199 | (5) |
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7.9 Up-and-Down Methods to Estimate LC50 |
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204 | (2) |
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7.10 Methods for ECx Estimation When there is Little or no Partial Mortality |
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206 | (13) |
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215 | (4) |
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8 Analysis of Count Data: NOEC and Regression |
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219 | (24) |
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8.1 Reproduction and Other Nonquantal Count Data |
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219 | (1) |
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8.2 Transformations to Continuous |
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219 | (4) |
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223 | (5) |
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8.4 Analysis of Other Types of Count Data |
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228 | (15) |
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237 | (6) |
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9 Analysis of Ordinal Data |
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243 | (16) |
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243 | (1) |
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9.2 Pathology Severity Scores |
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243 | (6) |
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249 | (10) |
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255 | (4) |
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259 | (16) |
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259 | (2) |
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10.2 Kaplan-Meier Product-Limit Estimator |
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261 | (5) |
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10.3 Cox Regression Proportional Hazards Estimator |
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266 | (2) |
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10.4 Survival Analysis of Grouped Data |
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268 | (7) |
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271 | (4) |
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275 | (18) |
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275 | (1) |
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275 | (1) |
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11.3 Development of International Standardized Test Guidelines |
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276 | (3) |
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11.4 Strategic Approach to International Chemicals Management (SAICM) |
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279 | (1) |
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11.5 The United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) |
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279 | (1) |
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11.6 Statistical Methods in OECD Ecotoxicity Test Guidelines |
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279 | (1) |
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11.7 Regulatory Testing: Structures and Approaches |
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279 | (8) |
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287 | (4) |
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11.9 Nonguideline Studies |
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291 | (2) |
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12 Species Sensitivity Distributions |
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293 | (16) |
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293 | (1) |
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12.2 Number, Choice, and Type of Species Endpoints to Include |
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294 | (1) |
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12.3 Choice and Evaluation of Distribution to Fit |
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294 | (6) |
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12.4 Variability and Uncertainty |
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300 | (7) |
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12.5 Incorporating Censored Data in an SSD 302 Exercises |
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307 | (2) |
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13 Studies with Greater Complexity |
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309 | (36) |
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309 | (1) |
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13.2 Mesocosm and Mcrocosm Experiments |
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310 | (6) |
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13.3 Microplate Experiments |
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316 | (5) |
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13.4 Errors-in-Variables Regression |
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321 | (2) |
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13.5 Analysis of Mixtures of Chemicals |
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323 | (3) |
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13.6 Benchmark Dose Models |
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326 | (1) |
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327 | (2) |
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13.8 Minimum Safe Dose and Maximum Unsafe Dose |
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329 | (2) |
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13.9 Toxicokinetics and Toxicodynamics |
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331 | (14) |
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343 | (2) |
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345 | (2) |
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Appendix 2 Mathematical Framework |
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347 | (16) |
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A2.1 Basic Probability Concepts |
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347 | (1) |
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A2.2 Distribution Functions |
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348 | (2) |
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A2.3 Method of Maximum Likelihood |
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350 | (2) |
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A2.4 Bayesian Methodology |
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352 | (2) |
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A2.5 Analysis of Toxicity Experiments |
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354 | (4) |
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A2.6 Newton's Optimization Method |
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358 | (1) |
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359 | (1) |
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360 | (3) |
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363 | (8) |
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Table A3.1 Studentized Maximum Distribution |
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364 | (1) |
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Table A3.2 Studentized Maximum Modulus Distribution |
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365 | (1) |
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Table A3.3 Linear and Quadratic Contrast Coefficients |
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366 | (1) |
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Table A3.4 Williams' Test ta,k for α = 0.05 |
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367 | (4) |
References |
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371 | (14) |
Author Index |
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385 | (4) |
Subject Index |
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389 | |