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In the analysis, the investigators decided to focus on the soil, air, and blood Mn levels for exposure measurements, and to focus on hand-cye coordination (by Pursuit Aiming Test) and motor coordination (by Luria Test) for outcome measurements They considered age, gender, SES and study site as potential confounders. Q1. Summarize the distribution of measured exposure (soil, air. blood Mn), outcome scores (total correct dots from Pursuit Aiming Test and Luria score), as well as other relevant characteristics (age, gender, SES. study site, obesity) in Table Note that the lab technician labeled any soil Mn level >1200 Oppm as lab error and should be removed from analysis Hint: For continuous variables, report mean and SD if normally distributed, and report median and 25th/75th percentiles if not normally distributed For categorical variable, report number of observations and percentage In addition to Table 1. answer the following questions: 1a) Are the exposure measurements and outcome measurements normally distributed? Which of them are skewed and what is the direction of skewness? 1b) For exposure measurements that are not normally distributed does log transformation help with normalizing the data? Assess by histograms, Q-Q plots, and normality tests. Q2. Examine the associations between Mn exposure and motor function outcomes, using univariate linear regression and multivariate linear regression adjusting for age, gender, SES. and study site. Consider treating the exposure as both continuous (log transformation only if needed) and quartiles. Summarize the quantitative results in Table (for Pursuit Aiming Test) and Table (for Luria Test). See sample table on Page 5 Hint: When treating the exposure variable as continuous, researchers sometimes still proceed to evaluate the associations using parametric methods (such as linear regression) even if the distribution of predictors is not completely normal after data transformation (but within reasonable acceptable range based on other alternative criteria). For this assignment, please proceed the analysis even when log -transformation does not fully help with normalizing the data Page Table (Insert title) Univariate analysis Multivariate analysis' Exposure beta s.e p-value beta s.e p-value Mn As continuous** As quartiles quartile 2nd quartile 3rd quartile 4th quartile Mo As continuous** As quartiles quartile 2nd quartile 3rd quartile 4th quartile Blood Mn As continuous** As quartiles 2nd quart 3rd quartile 4th quartile Multivariate analysis adjusted for age, gender, SES. and study site. ** Hint: Please note whether the variable was in original scale or log --Transformed scale. Q3. Summarize your interpretation of the results in Table 2 and Table 3 above: 3a) Write Results section as seen in journal articles which summarizes the observed quantitative results If the results are similar for univariate analysis (crude association) and multivariate analysis (adjusted association), focus on multivariate analysis results For models treating exposure variable as continuous, interpret the associations by each 1-unit increase for original scale, and by 10% increase for log- transformedscale. For models treating exposure variable as quartiles, discuss whether the results suggest exposure- response relationship (whether the change in outcome becomes larger as exposure becomes higher) 3b) Write abrief Conclusion paragraph within 3 sentences: as seen in the last part of the Abstract in journal articles. What is the main message you learned from these results? Page Q4. Based on your findings from Questions 1-3, answer the following questions. 4a) Were the association with motor function outcomes consistent when considering soil Mn and air Mn? If not, explain why you think the results may be different. (Hint: think about whether there is: possibility of exposure misclassification and how would this affect the observed associations, what is the timing of exposure that each measured exposure metric reflects, etc.) 4b) In addition to age, gender, SES, and study site that were adjusted in the analysis, the investigators have also considered other factors as potential confounders of the association between Mn exposure and motor function. These include: (i) experience of playing video games, (ii) occupation that requires hand dexterity, and (iii) alcohol consumption. Do you think these are possible confounders? Ifso, explain what the direction of confounding and why If not, explain your reason. Q5. The investigators were also interested in examining whether obesity may modify the association between Mn exposure and motor function measurements. Table 4is the results of obesity-stratified analysis that the investigators reported for soil Mn and Pursuit Airning Test Table 4. Association between soil Mn (log -transformed) and number of correct dots in Pursuit Aiming Test: stratified by obesity status Univariate analysis Multivariate analysis Stratification beta p-value beta s.e. p-value Non-obesity 31.40 2.26 <.0001 3182 3.01 <.0001 Obesity -42.07 4.28 <.0001 -41.18 5.67 <.0001 a Multivariate analysis adjusted for age, gender, SES. and study site Based on Table do you think there is suggestion of effect modification by obesity on the association between soil Mn and hand-ey coordination? Explain why or why not. and state your conclusion Q6. Replicate the analysis in Table 4,but looking at Luria Test score as the outcome instead of Pursuit Aiming Test. Summarize these results in Table (using the same format as Table 4) and briefly discuss the findings.

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