<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">OALibJ</journal-id><journal-title-group><journal-title>Open Access Library Journal</journal-title></journal-title-group><issn pub-type="epub">2333-9705</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/oalib.1102086</article-id><article-id pub-id-type="publisher-id">OALibJ-68746</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biomedical&amp;Life Sciences</subject><subject> Business&amp;Economics</subject><subject> Chemistry&amp;Materials Science</subject><subject> Computer Science&amp;Communications</subject><subject> Earth&amp;Environmental Sciences</subject><subject> Engineering</subject><subject> Medicine&amp;Healthcare</subject><subject> Physics&amp;Mathematics</subject><subject> Social Sciences&amp;Humanities</subject></subj-group></article-categories><title-group><article-title>
 
 
  The Effects of Covariance Structures on Modelling of Longitudinal Data
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Yin</surname><given-names>Chen</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Yu</surname><given-names>Fei</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Jianxin</surname><given-names>Pan</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib></contrib-group><aff id="aff2"><addr-line>School of Statistics and Mathematics, Yunnan University of Finance and Economics, Kunming, China</addr-line></aff><aff id="aff3"><addr-line>School of Mathematics, University of Manchester, Manchester, UK</addr-line></aff><aff id="aff1"><addr-line>School of Insurance, University of International Business and Economics, Beijing, China</addr-line></aff><author-notes><corresp id="cor1">* E-mail:<email>chenyin@uibe.edu.cn(YC)</email>;</corresp></author-notes><pub-date pub-type="epub"><day>30</day><month>10</month><year>2015</year></pub-date><volume>02</volume><issue>10</issue><fpage>1</fpage><lpage>10</lpage><history><date date-type="received"><day>20</day>	<month>September</month>	<year>2015</year></date><date date-type="rev-recd"><day>accepted</day>	<month>24</month>	<year>October</year>	</date><date date-type="accepted"><day>28</day>	<month>October</month>	<year>2015</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
   
   Extending the general linear model to the linear mixed model takes into account the within-subject correlation between observations with introduction of random effects. Fixed covariance structures of random error and random effect are assumed in linear mixed models. However, a potential risk of model selection still exists. That is, if the specified structure is not appropriate to real data, we cannot make correct statistical inferences. Joint modelling method removes all specifications about covariance structures and comes over the above risk. It simply models covariance structures just like modelling the mean structures in the general linear model. Our conclusions include: a) The estimators of fixed effects parameters are similar, that is, the expected mean values of response variables are similar. b) The standard deviations from different models are obviously different, which indicates that the width of confidence interval is evidently different. c) Through comparing the AIC or BIC value, we conclude that the data-driven mean-covariance regression model can fit data much better and result in more precise and reliable statistical inferences. 
  
 
</p></abstract><kwd-group><kwd>Linear Mixed Models</kwd><kwd> Correlated Random Effects</kwd><kwd> Mean-Covariance Modeling</kwd><kwd> Longitudinal Data</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>After the within subject correlation is taken into account in general linear models, the random errors are not assumed independent. Linear mixed models are setting up to solve this problems. Previous literature work on linear models and linear mixed models has mainly focused on setting up a list of possible covariance matrix structures of random errors and random effects. However, a potential vital risk still exists. If no one structure in list can fit data properly, even the best one in that list may distort statistical inference. Misspecification of covariance structures can lead to a great loss of efficiency of the parameter estimates (Wang and Carey, 2003, [<xref ref-type="bibr" rid="scirp.68746-ref1">1</xref>] ).</p><p>Joint modelling (Pourahmadi, (1999), [<xref ref-type="bibr" rid="scirp.68746-ref2">2</xref>] ) is a data-driven methodology for modelling the variance-covariance matrix similar to the general linear model framework for mean modelling. The main idea of joint modelling is considering mean and variance components in equally important level, modelling the mean, variance and correlation of response variables in three submodels, building three design matrices for mean, variance and correlation respectively, and estimating three parameters vectors for these three submodels simultaneously. The advantage of these method is to reduce the high dimensionality of computation for the covariance matrix. Modified Cholesky decomposition of the inverse of covariance matrix, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x6.png" xlink:type="simple"/></inline-formula>, guarantees that <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x7.png" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x8.png" xlink:type="simple"/></inline-formula> must be positive definite. The resulting parameters estimates are obtained and compared to those obtained using the above approaches. Assumed structures and joint modelling are compared and discussed further in terms of their ability to accurately estimate both regression coefficients and variance components.</p><p>In this paper, we aim to model covariance structures of random errors in the linear models in Section 2, model covariance structures of random errors and random effects in linear mixed models in Section 3 and model mean and covariance simultaneously based on modified Cholesky decomposition (Pourahmadi, (2000), [<xref ref-type="bibr" rid="scirp.68746-ref3">3</xref>] ) in Section 4. Cattle data published by Kenward in 1987 [<xref ref-type="bibr" rid="scirp.68746-ref4">4</xref>] were analyzed using the above three models in Section 5. The core conclusion is that real data analysis confirms the superiority of joint modelling of mean-covariance. Further discussions are followed in Section 6.</p></sec><sec id="s2"><title>2. General Linear Models with Correlated Errors</title><p>The linear regression model assumes that the response variables and the explanatory variables are related through</p><disp-formula id="scirp.68746-formula972"><label>(1)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x9.png"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.68746-formula973"><graphic  xlink:href="http://html.scirp.org/file/68746x10.png"  xlink:type="simple"/></disp-formula><p>where, for the <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x11.png" xlink:type="simple"/></inline-formula> subject of of m subjects, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x12.png" xlink:type="simple"/></inline-formula>is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x13.png" xlink:type="simple"/></inline-formula> responses, X<sub>i</sub> is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x14.png" xlink:type="simple"/></inline-formula> design matrix, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x15.png" xlink:type="simple"/></inline-formula>is a <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x16.png" xlink:type="simple"/></inline-formula> fixed effect, random error <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x17.png" xlink:type="simple"/></inline-formula> is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x18.png" xlink:type="simple"/></inline-formula> random vector and assumed as normal distributed with mean zero and covariance matrix identity structure, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x19.png" xlink:type="simple"/></inline-formula>is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x20.png" xlink:type="simple"/></inline-formula> identity matrix. Under Gauss assumption, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x21.png" xlink:type="simple"/></inline-formula>,</p><p>However, response in real data may be not independent. The inferences of the regression parameters of primary interest take account of the likely correlation in the data. So linear models with correlated errors is considered,</p><disp-formula id="scirp.68746-formula974"><label>(2)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x22.png"  xlink:type="simple"/></disp-formula><p>Under this assumption, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x23.png" xlink:type="simple"/></inline-formula>, where<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x23.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x24.png" xlink:type="simple"/></inline-formula>.</p><sec id="s2_1"><title>2.1. Random Errors in AR(1) Covariance Structure</title><p>In this model, for the <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x25.png" xlink:type="simple"/></inline-formula> subject, the <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x25.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x26.png" xlink:type="simple"/></inline-formula> element <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x25.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x26.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x27.png" xlink:type="simple"/></inline-formula> in <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x25.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x26.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x27.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x28.png" xlink:type="simple"/></inline-formula> has the form</p><disp-formula id="scirp.68746-formula975"><label>(3)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x29.png"  xlink:type="simple"/></disp-formula><p>The correlation between a pair of measurements on the same subject decays towards zero as the time separation between the measurements increases. The rate of decay is faster for larger values of<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x30.png" xlink:type="simple"/></inline-formula>. Note that if the observation times, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x30.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x31.png" xlink:type="simple"/></inline-formula>, are equally spaced, say <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x30.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x31.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x32.png" xlink:type="simple"/></inline-formula> for all j, then Equation (3) is expressible as</p><disp-formula id="scirp.68746-formula976"><label>(4)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x33.png"  xlink:type="simple"/></disp-formula><p>where <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x34.png" xlink:type="simple"/></inline-formula> is the correlation between successive observations on the same subject.</p><p>A justification of (4) is to represent the random variables <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x35.png" xlink:type="simple"/></inline-formula> as</p><disp-formula id="scirp.68746-formula977"><label>(5)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x36.png"  xlink:type="simple"/></disp-formula><p>with</p><disp-formula id="scirp.68746-formula978"><label>(6)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x37.png"  xlink:type="simple"/></disp-formula><p>and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x38.png" xlink:type="simple"/></inline-formula> are mutually independent <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x38.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x39.png" xlink:type="simple"/></inline-formula> random variables, to give <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x38.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x39.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x40.png" xlink:type="simple"/></inline-formula> as required. In view of (5) and (6), the exponential correlation model is sometimes called the first order auto- regressive model, because (6) is the standard definition of a discrete-time first-order autoregressive process. By substituting <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x38.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x39.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x40.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x41.png" xlink:type="simple"/></inline-formula> into (6), we obtain the conditional distribution of<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x38.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x39.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x40.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x41.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x42.png" xlink:type="simple"/></inline-formula>, given the preceding response, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x38.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x39.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x40.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x41.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x42.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x43.png" xlink:type="simple"/></inline-formula>, as</p><disp-formula id="scirp.68746-formula979"><label>(7)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x44.png"  xlink:type="simple"/></disp-formula><p>This form treats both the explanatory variables and prior response as explicit predictors of the current outcome. So we can get the analytical form of<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x45.png" xlink:type="simple"/></inline-formula>:</p><disp-formula id="scirp.68746-formula980"><label>(8)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x46.png"  xlink:type="simple"/></disp-formula></sec><sec id="s2_2"><title>2.2. Log Likelihood</title><p>The log of the likelihood is</p><disp-formula id="scirp.68746-formula981"><label>(9)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x47.png"  xlink:type="simple"/></disp-formula><p>for given<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x48.png" xlink:type="simple"/></inline-formula>, the maximum likelihood estimator for <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x48.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x49.png" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x48.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x49.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x50.png" xlink:type="simple"/></inline-formula> is, namely,</p><disp-formula id="scirp.68746-formula982"><label>(10)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x51.png"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.68746-formula983"><label>(11)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x52.png"  xlink:type="simple"/></disp-formula><p>where <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x53.png" xlink:type="simple"/></inline-formula></p></sec><sec id="s2_3"><title>2.3. AIC Criterion</title><p>AIC and BIC Criterion are defined as before:</p><disp-formula id="scirp.68746-formula984"><label>(12)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x54.png"  xlink:type="simple"/></disp-formula><p>where <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x55.png" xlink:type="simple"/></inline-formula> is the maximum likelihood, K the number of parameters to be estimated in the model, and N the sample size. High-order terms are ignored here.</p></sec></sec><sec id="s3"><title>3. Linear Mixed Models and Restricted Maximum Likelihood Estimation (REML)</title><p>The distributional assumption about <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x56.png" xlink:type="simple"/></inline-formula> in Model (2) may be too restrictive. For example, when data are collected over time on an individual such as in repeated measurements data, it is more likely that observed measurements have a high correlation within individual. The linear mixed model extends the general linear model by allowing a more flexible specification of the covariance matrix of<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x56.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x57.png" xlink:type="simple"/></inline-formula>. In other word, it allows for both correlation and heterogenous variances, although we still assume normality.</p><p>Laird and Ware (1982) [<xref ref-type="bibr" rid="scirp.68746-ref5">5</xref>] provided the following description of a linear mixed model</p><disp-formula id="scirp.68746-formula985"><label>(13)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x58.png"  xlink:type="simple"/></disp-formula><p>where, for the <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula> subject of of m subjects, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula>is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula> responses, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula>is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula> design matrix, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula>is a <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula> fixed effect. <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x66.png" xlink:type="simple"/></inline-formula>is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x66.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x67.png" xlink:type="simple"/></inline-formula> design matrix, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x66.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x67.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x68.png" xlink:type="simple"/></inline-formula>is a <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x66.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x67.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x68.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x69.png" xlink:type="simple"/></inline-formula> random effect, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x66.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x67.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x68.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x69.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x70.png" xlink:type="simple"/></inline-formula>, random effects are independent between subjects. Random error <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x66.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x67.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x68.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x69.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x70.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x71.png" xlink:type="simple"/></inline-formula> is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x66.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x67.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x68.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x69.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x70.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x71.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x72.png" xlink:type="simple"/></inline-formula> random vector and assumed as normal distributed with mean zero and covariance matrix identity structure <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x66.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x67.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x68.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x69.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x70.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x71.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x72.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x73.png" xlink:type="simple"/></inline-formula> , <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x66.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x67.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x68.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x69.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x70.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x71.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x72.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x73.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x74.png" xlink:type="simple"/></inline-formula>is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x66.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x67.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x68.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x69.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x70.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x71.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x72.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x73.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x74.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x75.png" xlink:type="simple"/></inline-formula> identity matrix.<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x59.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x60.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x61.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x62.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x63.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x64.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x65.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x66.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x67.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x68.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x69.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x70.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x71.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x72.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x73.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x74.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x75.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x76.png" xlink:type="simple"/></inline-formula>, random errors are independent between subjects.</p><p>The model also can be written in</p><disp-formula id="scirp.68746-formula986"><label>(14)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x77.png"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.68746-formula987"><label>(15)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x78.png"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.68746-formula988"><label>(16)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x79.png"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.68746-formula989"><label>(17)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x80.png"  xlink:type="simple"/></disp-formula><p>where Y is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x81.png" xlink:type="simple"/></inline-formula> responses, X is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x81.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x82.png" xlink:type="simple"/></inline-formula> design matrix, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x81.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x82.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x83.png" xlink:type="simple"/></inline-formula>is a <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x81.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x82.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x83.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x84.png" xlink:type="simple"/></inline-formula> fixed effect, Z is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x81.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x82.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x83.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x84.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x85.png" xlink:type="simple"/></inline-formula> design matrix, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x81.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x82.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x83.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x84.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x85.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x86.png" xlink:type="simple"/></inline-formula>is a <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x81.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x82.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x83.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x84.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x85.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x86.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x87.png" xlink:type="simple"/></inline-formula> random effect, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x81.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x82.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x83.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x84.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x85.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x86.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x87.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x88.png" xlink:type="simple"/></inline-formula>is an <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x81.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x82.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x83.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x84.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x85.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x86.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x87.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x88.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x89.png" xlink:type="simple"/></inline-formula> random error.</p><p>The method of restricted maximum likelihood, or REML estimation, was introduced by Patterson and Thompson (1971) [<xref ref-type="bibr" rid="scirp.68746-ref6">6</xref>] as a way of estimating variance components in a general linear model. The objection to the standard maximum likelihood procedure is that it produces biased estimators. In REML, the degree of freedom of fixed effects are taken into account implicitly, unlike in the ML where they are not. That is why the ML estimator are biased.</p><p>REML is an alternative maximum likelihood procedure which involves applying the ML idea to linear combinations of y. Denote <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x90.png" xlink:type="simple"/></inline-formula> and B the <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x90.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x91.png" xlink:type="simple"/></inline-formula> matrix defined by the requirements that <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x90.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x91.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x92.png" xlink:type="simple"/></inline-formula> and<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x90.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x91.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x92.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x93.png" xlink:type="simple"/></inline-formula>, where I denote the <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x90.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x91.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x92.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x93.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x94.png" xlink:type="simple"/></inline-formula> identity matrix. Finally, let<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x90.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x91.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x92.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x93.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x94.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x95.png" xlink:type="simple"/></inline-formula>.</p><p>For fixed<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x96.png" xlink:type="simple"/></inline-formula>, where <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x96.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x97.png" xlink:type="simple"/></inline-formula> is variance components parameters, defined as in Section 2, the maximum likelihood estimator for <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x96.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x97.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x98.png" xlink:type="simple"/></inline-formula> is</p><disp-formula id="scirp.68746-formula990"><label>(18)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x99.png"  xlink:type="simple"/></disp-formula><p>Also, the respective pdf of Y and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x100.png" xlink:type="simple"/></inline-formula> are</p><disp-formula id="scirp.68746-formula991"><label>(19)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x101.png"  xlink:type="simple"/></disp-formula><p>and</p><disp-formula id="scirp.68746-formula992"><label>(20)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x102.png"  xlink:type="simple"/></disp-formula><p>Furthermore, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x103.png" xlink:type="simple"/></inline-formula>and Z and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x103.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x104.png" xlink:type="simple"/></inline-formula> are independent, whatever the value of<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x103.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x104.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x105.png" xlink:type="simple"/></inline-formula>, as we now show.</p><p>Firstly, we prove<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x106.png" xlink:type="simple"/></inline-formula>,</p><disp-formula id="scirp.68746-formula993"><graphic  xlink:href="http://html.scirp.org/file/68746x107.png"  xlink:type="simple"/></disp-formula><p>since<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x108.png" xlink:type="simple"/></inline-formula>. But since<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x108.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x109.png" xlink:type="simple"/></inline-formula>, this gives</p><disp-formula id="scirp.68746-formula994"><graphic  xlink:href="http://html.scirp.org/file/68746x110.png"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.68746-formula995"><graphic  xlink:href="http://html.scirp.org/file/68746x111.png"  xlink:type="simple"/></disp-formula><p>Hence <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x112.png" xlink:type="simple"/></inline-formula> as required.</p><p>Secondly, we prove <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x113.png" xlink:type="simple"/></inline-formula></p><disp-formula id="scirp.68746-formula996"><graphic  xlink:href="http://html.scirp.org/file/68746x114.png"  xlink:type="simple"/></disp-formula><p>Now, substituting <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x115.png" xlink:type="simple"/></inline-formula> into this last expression gives</p><disp-formula id="scirp.68746-formula997"><graphic  xlink:href="http://html.scirp.org/file/68746x116.png"  xlink:type="simple"/></disp-formula><p>Also,</p><disp-formula id="scirp.68746-formula998"><graphic  xlink:href="http://html.scirp.org/file/68746x117.png"  xlink:type="simple"/></disp-formula><p>and</p><disp-formula id="scirp.68746-formula999"><graphic  xlink:href="http://html.scirp.org/file/68746x118.png"  xlink:type="simple"/></disp-formula><p>Where <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x119.png" xlink:type="simple"/></inline-formula> as in the proof that<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x119.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x120.png" xlink:type="simple"/></inline-formula>.</p><p>It follows that<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x121.png" xlink:type="simple"/></inline-formula>. Finally, in the multivariate Gaussian setting, zero covariance is equivalent to independence. It follows that the algebraic form of the (singular) multivariate Gaussian pdf</p><p>of Z, expressed in term of Y, is proportional to the ratio<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x122.png" xlink:type="simple"/></inline-formula>. To obtain the explicit form of this ratio, we use</p><p>the following standard result for the general linear mixed model that</p><disp-formula id="scirp.68746-formula1000"><graphic  xlink:href="http://html.scirp.org/file/68746x123.png"  xlink:type="simple"/></disp-formula><p>Then, the pdf of <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x124.png" xlink:type="simple"/></inline-formula> is proportional to</p><disp-formula id="scirp.68746-formula1001"><label>(21)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x125.png"  xlink:type="simple"/></disp-formula><p>where the omitted constant of proportionality is the Jacobian of the transformation from Y to<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x126.png" xlink:type="simple"/></inline-formula>. Harville</p><p>(1974) [<xref ref-type="bibr" rid="scirp.68746-ref7">7</xref>] shows that the Jacobian reduces to<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x127.png" xlink:type="simple"/></inline-formula>, which does not depend on any of the parameters in the</p><p>model and can therefore be ignored for making inferences about <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x128.png" xlink:type="simple"/></inline-formula> and<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x128.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x129.png" xlink:type="simple"/></inline-formula>. Note that the right hand side of (21) is independent of A, and the same result would therefore hold for any Z such that <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x128.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x129.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x130.png" xlink:type="simple"/></inline-formula> and<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x128.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x129.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x130.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x131.png" xlink:type="simple"/></inline-formula>.</p><p>The practical implication of (21) is that the REML estimator, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x132.png" xlink:type="simple"/></inline-formula>, maximizes the log likelihood</p><disp-formula id="scirp.68746-formula1002"><graphic  xlink:href="http://html.scirp.org/file/68746x133.png"  xlink:type="simple"/></disp-formula><p>whereas the maximum likelihood estimator, MLE, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x134.png" xlink:type="simple"/></inline-formula>maximizes</p><disp-formula id="scirp.68746-formula1003"><graphic  xlink:href="http://html.scirp.org/file/68746x135.png"  xlink:type="simple"/></disp-formula></sec><sec id="s4"><title>4. Joint Mean-Covariance Model for Longitudinal Data</title><p>Response variables <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x136.png" xlink:type="simple"/></inline-formula> was assumed Gaussian distribution</p><disp-formula id="scirp.68746-formula1004"><graphic  xlink:href="http://html.scirp.org/file/68746x137.png"  xlink:type="simple"/></disp-formula><sec id="s4_1"><title>4.1. Modified Cholesky Decomposition for Longitudinal Data</title><p>The subject-specific covariance matrices <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x138.png" xlink:type="simple"/></inline-formula> can be composed into</p><disp-formula id="scirp.68746-formula1005"><graphic  xlink:href="http://html.scirp.org/file/68746x139.png"  xlink:type="simple"/></disp-formula><p>where <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x140.png" xlink:type="simple"/></inline-formula> is a lower triangular matrix with 1’s as diagonal entries and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x140.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x141.png" xlink:type="simple"/></inline-formula> is a diagonal matrix with positive diagonal entries.</p><p>Denote</p><disp-formula id="scirp.68746-formula1006"><graphic  xlink:href="http://html.scirp.org/file/68746x142.png"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.68746-formula1007"><graphic  xlink:href="http://html.scirp.org/file/68746x143.png"  xlink:type="simple"/></disp-formula><p><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x144.png" xlink:type="simple"/></inline-formula>and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x144.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x145.png" xlink:type="simple"/></inline-formula> have clear statistical interpretations:</p><p>a) <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x146.png" xlink:type="simple"/></inline-formula>are autoregressive coefficients in the autoregression models</p><disp-formula id="scirp.68746-formula1008"><graphic  xlink:href="http://html.scirp.org/file/68746x147.png"  xlink:type="simple"/></disp-formula><p>b) <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x148.png" xlink:type="simple"/></inline-formula>are the innovation variances</p><disp-formula id="scirp.68746-formula1009"><graphic  xlink:href="http://html.scirp.org/file/68746x149.png"  xlink:type="simple"/></disp-formula><p>where <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x150.png" xlink:type="simple"/></inline-formula> and<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x150.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x151.png" xlink:type="simple"/></inline-formula>.</p></sec><sec id="s4_2"><title>4.2. Mean-Covariance Regression Model for Longitudinal Data</title><p>The unconstrained parameters<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x152.png" xlink:type="simple"/></inline-formula>, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x152.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x153.png" xlink:type="simple"/></inline-formula>and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x152.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x153.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x154.png" xlink:type="simple"/></inline-formula> can be modelled in terms of regression models</p><disp-formula id="scirp.68746-formula1010"><label>(22)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x155.png"  xlink:type="simple"/></disp-formula><p>where<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x156.png" xlink:type="simple"/></inline-formula>, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x156.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x157.png" xlink:type="simple"/></inline-formula>and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x156.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x157.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x158.png" xlink:type="simple"/></inline-formula> are p-, q- and d-dimensional parameter vectors, associated with the covariates<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x156.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x157.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x158.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x159.png" xlink:type="simple"/></inline-formula>, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x156.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x157.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x158.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x159.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x160.png" xlink:type="simple"/></inline-formula>and<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x156.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x157.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x158.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x159.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x160.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x161.png" xlink:type="simple"/></inline-formula>, respectively (Pourahmadi, 1999, [<xref ref-type="bibr" rid="scirp.68746-ref2">2</xref>] ).</p><p>For growth curve data, such as the cattle data which we want to analyse, the covariates may take the forms:</p><disp-formula id="scirp.68746-formula1011"><graphic  xlink:href="http://html.scirp.org/file/68746x162.png"  xlink:type="simple"/></disp-formula><p>where the superscript “()” stands for the orthogonalization vector.</p><p>Linear mean-covariance model for growth curve data is</p><disp-formula id="scirp.68746-formula1012"><label>(23)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x163.png"  xlink:type="simple"/></disp-formula><p>where<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x164.png" xlink:type="simple"/></inline-formula>, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x164.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x165.png" xlink:type="simple"/></inline-formula>, and<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x164.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x165.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x166.png" xlink:type="simple"/></inline-formula>.</p></sec><sec id="s4_3"><title>4.3. Advantages of Joint Mean-Covariance Model</title><p>First, mean-covariance regression models have compact form and clear interpretations, so that they can be understood easily.</p><p>Second, the numerical linear algebra method can reduce the high dimensional <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x167.png" xlink:type="simple"/></inline-formula> parameters in <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x167.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x168.png" xlink:type="simple"/></inline-formula></p><p>into <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x169.png" xlink:type="simple"/></inline-formula> dimensional parameters in terms of <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x169.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x170.png" xlink:type="simple"/></inline-formula> and<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x169.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x170.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x171.png" xlink:type="simple"/></inline-formula>. This approach can decrease the computational time to a great extent.</p><p>Third, modified Cholesky decomposition of <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x172.png" xlink:type="simple"/></inline-formula> can guarantee that <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x172.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x173.png" xlink:type="simple"/></inline-formula> is positive definite.</p><p>Fourth, this model can be used commonly. For special cases, this approach can also be valid with certain constraints placed on <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x174.png" xlink:type="simple"/></inline-formula> and<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x174.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x175.png" xlink:type="simple"/></inline-formula>. For example, AR(1) structure</p><disp-formula id="scirp.68746-formula1013"><graphic  xlink:href="http://html.scirp.org/file/68746x176.png"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.68746-formula1014"><graphic  xlink:href="http://html.scirp.org/file/68746x177.png"  xlink:type="simple"/></disp-formula><disp-formula id="scirp.68746-formula1015"><graphic  xlink:href="http://html.scirp.org/file/68746x178.png"  xlink:type="simple"/></disp-formula></sec><sec id="s4_4"><title>4.4. Maximum Likelihood Estimation for Joint Modelling</title><p>For clarity and simplicity of presentation, we only consider standard multivariate data or balanced longitudinal data (Diggle and Kenward, 1994) [<xref ref-type="bibr" rid="scirp.68746-ref8">8</xref>] . For<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula>, we assure that <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula> are independent <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula>-dimension vectors, where <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x182.png" xlink:type="simple"/></inline-formula> stand for the <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x182.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x183.png" xlink:type="simple"/></inline-formula> repeated measurements on the <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x182.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x183.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x184.png" xlink:type="simple"/></inline-formula> subject,<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x182.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x183.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x184.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x185.png" xlink:type="simple"/></inline-formula>. <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x182.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x183.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x184.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x185.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x186.png" xlink:type="simple"/></inline-formula>is <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x182.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x183.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x184.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x185.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x186.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x187.png" xlink:type="simple"/></inline-formula> design matrix and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x182.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x183.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x184.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x185.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x186.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x187.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x188.png" xlink:type="simple"/></inline-formula> is <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x182.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x183.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x184.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x185.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x186.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x187.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x188.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x189.png" xlink:type="simple"/></inline-formula> vector of mean parameters. We assume that the components <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x182.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x183.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x184.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x185.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x186.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x187.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x188.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x189.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x190.png" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x182.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x183.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x184.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x185.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x186.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x187.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x188.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x189.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x190.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x191.png" xlink:type="simple"/></inline-formula> of the covariance matrix<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x179.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x180.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x181.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x182.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x183.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x184.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x185.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x186.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x187.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x188.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x189.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x190.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x191.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x192.png" xlink:type="simple"/></inline-formula>, are modelled as (22), so that the likelihood function has three representations corresponding to the three submodels in (22).</p><p>Log-likelihood function is</p><disp-formula id="scirp.68746-formula1016"><label>(24)</label><graphic position="anchor" xlink:href="http://html.scirp.org/file/68746x193.png"  xlink:type="simple"/></disp-formula></sec><sec id="s4_5"><title>4.5. Algorithm for Calculating Parameters</title><p>Step 1. Select an initial value <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x194.png" xlink:type="simple"/></inline-formula> for<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x194.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x195.png" xlink:type="simple"/></inline-formula>.</p><p>Step 2. Compute <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x196.png" xlink:type="simple"/></inline-formula> and its factors <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x196.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x197.png" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x196.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x197.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x198.png" xlink:type="simple"/></inline-formula> to be used as initial values for T and D in the next step.</p><p>Step 3. For the inner loop, compute <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x199.png" xlink:type="simple"/></inline-formula> by solving the last two equations above using Newton-Raphson method. At convergence, compute <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x199.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x200.png" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x199.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x200.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x201.png" xlink:type="simple"/></inline-formula> and form<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x199.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x200.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x201.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x202.png" xlink:type="simple"/></inline-formula>.</p><p>Step 4. Update <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x203.png" xlink:type="simple"/></inline-formula> using</p><disp-formula id="scirp.68746-formula1017"><graphic  xlink:href="http://html.scirp.org/file/68746x204.png"  xlink:type="simple"/></disp-formula><p>Step 5. Stop the process if<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x205.png" xlink:type="simple"/></inline-formula>. Take <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x205.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x206.png" xlink:type="simple"/></inline-formula> as an estimate of <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x205.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x206.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x207.png" xlink:type="simple"/></inline-formula> and form the estimate<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x205.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x206.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x207.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x208.png" xlink:type="simple"/></inline-formula>. Otherwise, repeat Steps 2 - 4 replacing <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x205.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x206.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x207.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x208.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x209.png" xlink:type="simple"/></inline-formula> by<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x205.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x206.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x207.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x208.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x209.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x210.png" xlink:type="simple"/></inline-formula>.</p></sec></sec><sec id="s5"><title>5. Cattle Data Analysis</title><p>Kenward (1987) [<xref ref-type="bibr" rid="scirp.68746-ref4">4</xref>] reported a set of data on cattle’s growth. 60 cattle were randomly allocated into two groups, each of which would hold 30 animals. The animals were put out to pasture at the start of the grazing season, and the members of each group received one of two different treatments, A and B say, respectively. The weight (response) of each animal was then recorded 11 times to the nearest kilogram over a 133-day period. The first 10 measurements were made at two-week intervals and the final measurement was made after one-week interval.</p><p>We extract the best structure in different models from different models and put them in the <xref ref-type="table" rid="table1">Table 1</xref>. The second column gives the result for classical linear model with identical matrix of random errors in Section 2. The third column shows the result for linear model with AR(1) structure covariance matrix of random errors in linear model in Section 2. The fourth column represent the Model (13) (AR(1) structure for random effect and AR(1) structure for random error) in Section 3. The last column lists the joint modelling of mean-covariance regression in Section 4.</p></sec><sec id="s6"><title>6. Conclusions and Discussions</title><p>The main conclusions of this paper include:</p><p>a) The estimated mean value for the response variable and the estimators of fixed effects parameters are similar whatever the covariance structure is chosen.</p><p>b) The standard deviation of fixed effects parameters estimates is relatively different, which indicates the confidence intervals depend on the specification of covariance structure.</p><p>c) As a model selection criterion, AIC or BIC value is very important. The smaller the AIC or BIC value is, the better the model is. We conclude that the joint mean-covariance regression model is the best model for analysing cattle data. Note that in all of these models, the sample size in AIC or BIC value is 660.</p><p>Apart from the above three conclusions, we can see some other hiding connotations. In the first column of <xref ref-type="table" rid="table1">Table 1</xref>, we assume all measurements are independent, and then the maximum marginal log-likelihood value is −2782.644. When extending this model and assuming some correlations in successive measurements within individual, for example, the first order autoregressive model AR(1), the result shown in the second column becomes much better. The maximum marginal log-likelihood value increase from −2782.644 to −2289.697.</p><table-wrap id="table1" ><label><xref ref-type="table" rid="table1">Table 1</xref></label><caption><title> Comparison among the best structures in different models</title></caption><table><tbody><thead><tr><th align="center" valign="middle" ></th><th align="center" valign="middle" >Classical Linear Model</th><th align="center" valign="middle" >General Linear Model With AR(1)</th><th align="center" valign="middle" >LMM AR(1) (random effect) AR(1) (random error) REML</th><th align="center" valign="middle" >Linear Joint Model</th></tr></thead><tr><td align="center" valign="middle"  rowspan="11"  ><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x211.png" xlink:type="simple"/></inline-formula></td><td align="center" valign="middle" >222.4591</td><td align="center" valign="middle" >225.2165</td><td align="center" valign="middle" >225.2492</td><td align="center" valign="middle" >219.2690</td></tr><tr><td align="center" valign="middle" >233.6470</td><td align="center" valign="middle" >233.9385</td><td align="center" valign="middle" >234.0066</td><td align="center" valign="middle" >230.8766</td></tr><tr><td align="center" valign="middle" >247.0486</td><td align="center" valign="middle" >245.8849</td><td align="center" valign="middle" >245.9751</td><td align="center" valign="middle" >244.5267</td></tr><tr><td align="center" valign="middle" >261.7197</td><td align="center" valign="middle" >259.9175</td><td align="center" valign="middle" >260.0181</td><td align="center" valign="middle" >259.3281</td></tr><tr><td align="center" valign="middle" >276.7159</td><td align="center" valign="middle" >274.8982</td><td align="center" valign="middle" >274.9988</td><td align="center" valign="middle" >274.3896</td></tr><tr><td align="center" valign="middle" >291.0929</td><td align="center" valign="middle" >289.6890</td><td align="center" valign="middle" >289.7807</td><td align="center" valign="middle" >288.8202</td></tr><tr><td align="center" valign="middle" >303.9065</td><td align="center" valign="middle" >303.1519</td><td align="center" valign="middle" >303.2270</td><td align="center" valign="middle" >301.7286</td></tr><tr><td align="center" valign="middle" >314.2123</td><td align="center" valign="middle" >314.1488</td><td align="center" valign="middle" >314.2012</td><td align="center" valign="middle" >312.2236</td></tr><tr><td align="center" valign="middle" >321.0661</td><td align="center" valign="middle" >321.5416</td><td align="center" valign="middle" >321.5666</td><td align="center" valign="middle" >319.4143</td></tr><tr><td align="center" valign="middle" >323.5234</td><td align="center" valign="middle" >324.1923</td><td align="center" valign="middle" >324.1864</td><td align="center" valign="middle" >322.4093</td></tr><tr><td align="center" valign="middle" >322.8083</td><td align="center" valign="middle" >323.3837</td><td align="center" valign="middle" >323.3616</td><td align="center" valign="middle" >320.3175</td></tr><tr><td align="center" valign="middle"  rowspan="4"  ><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x212.png" xlink:type="simple"/></inline-formula></td><td align="center" valign="middle" >283.47273</td><td align="center" valign="middle" >283.26935</td><td align="center" valign="middle" >283.3247</td><td align="center" valign="middle" >281.20939</td></tr><tr><td align="center" valign="middle" >116.57233</td><td align="center" valign="middle" >116.54085</td><td align="center" valign="middle" >116.4581</td><td align="center" valign="middle" >117.19641</td></tr><tr><td align="center" valign="middle" >−18.32619</td><td align="center" valign="middle" >−14.58151</td><td align="center" valign="middle" >−14.68762</td><td align="center" valign="middle" >−22.29320</td></tr><tr><td align="center" valign="middle" >−10.52633</td><td align="center" valign="middle" >−12.68589</td><td align="center" valign="middle" >−12.67034</td><td align="center" valign="middle" >−11.67378</td></tr><tr><td align="center" valign="middle"  rowspan="4"  >Std of <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x213.png" xlink:type="simple"/></inline-formula></td><td align="center" valign="middle" >0.6403</td><td align="center" valign="middle" >0.1093</td><td align="center" valign="middle" >1.6366</td><td align="center" valign="middle" >1.8487</td></tr><tr><td align="center" valign="middle" >2.1235</td><td align="center" valign="middle" >0.1630</td><td align="center" valign="middle" >2.6177</td><td align="center" valign="middle" >2.5327</td></tr><tr><td align="center" valign="middle" >2.1235</td><td align="center" valign="middle" >0.0933</td><td align="center" valign="middle" >1.6960</td><td align="center" valign="middle" >1.4091</td></tr><tr><td align="center" valign="middle" >2.1235</td><td align="center" valign="middle" >0.0665</td><td align="center" valign="middle" >1.3390</td><td align="center" valign="middle" >0.9784</td></tr><tr><td align="center" valign="middle" ><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x214.png" xlink:type="simple"/></inline-formula></td><td align="center" valign="middle" >−2782.644</td><td align="center" valign="middle" >−2289.697</td><td align="center" valign="middle" >−2273.92</td><td align="center" valign="middle" >−2251.517</td></tr><tr><td align="center" valign="middle" >AIC</td><td align="center" valign="middle" >5575.288</td><td align="center" valign="middle" >4591.395</td><td align="center" valign="middle" >4563.841</td><td align="center" valign="middle" >4527.033</td></tr><tr><td align="center" valign="middle" >BIC</td><td align="center" valign="middle" >5597.749</td><td align="center" valign="middle" >4618.348</td><td align="center" valign="middle" >4599.779</td><td align="center" valign="middle" >4580.94</td></tr></tbody></table></table-wrap><p>Simultaneously, AIC value reduces from 5575.288 to 4591.395 and BIC from 5597.749 to 4618.348. Obviously, these two values reduce remarkably. Large reduction implies that the correlation between successive observations should not be ignored. It also implies that the joint mean-covariance model provides correct information from the increasing of log likelihood or from changes of AIC and BIC value.</p><p>What’s more, we expect that if the structure of variance is AR(2), the result will be better than AR(1) structure. This part of work can be done as further work.</p><p>When we separate the variance-covariance matrix for each animal, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x215.png" xlink:type="simple"/></inline-formula>, into two parts, <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x215.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x216.png" xlink:type="simple"/></inline-formula>for random effect between subjects and <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x215.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x216.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x217.png" xlink:type="simple"/></inline-formula> for random error within subject. The maximum log-likelihood value increases very little (from −2289.697 to −2273.92) compared to the last increase from column 2 to column 3. If <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x215.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x216.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x217.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x218.png" xlink:type="simple"/></inline-formula> is not AR(1) structure, for example, we try identity and identity for<inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x215.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x216.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x217.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x218.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x219.png" xlink:type="simple"/></inline-formula>, the log-likelihood value in the linear mixed model is not better than that in general linear model, which indicates that the AR(1) structure for <inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x215.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x216.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x217.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x218.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x219.png" xlink:type="simple"/></inline-formula><inline-formula><inline-graphic xlink:href="http://html.scirp.org/file/68746x220.png" xlink:type="simple"/></inline-formula> is more appropriate than other specifications.</p><p>Another further work on the cattle data analysis that may be carried out is to assume that different groups of animals may have different covariance structures, unlike in this dissertation where we assume the same covariance structure applied in both groups of animals. Other modelling methods, for example, nonlinear regression model might be also used to analyse cattle data.</p></sec><sec id="s7"><title>Acknowledgements</title><p>We thank the editors and the reviewers for their comments. This research is funded by the National Social Science Foundation No. 12CGL077, National Science Foundation granted No. 71201029, No. 71303045 and No. 11561071. This support is greatly appreciated.</p></sec><sec id="s8"><title>Cite this paper</title><p>Yin Chen,Yu Fei,Jianxin Pan, (2015) The Effects of Covariance Structures on Modelling of Longitudinal Data. Open Access Library Journal,02,1-10. doi: 10.4236/oalib.1102086</p></sec><sec id="s9"><title>NOTES</title></sec></body><back><ref-list><title>References</title><ref id="scirp.68746-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Wang, Y.G. and Carey, V. (2003) Working Correlation Structure Misspecification, Estimation and Covariate Design: Implications for Generalised Estimating Equations Performance. Biometrika, 90, 29-41. http://dx.doi.org/10.1093/biomet/90.1.29</mixed-citation></ref><ref id="scirp.68746-ref2"><label>2</label><mixed-citation publication-type="other" xlink:type="simple">Pourahmadi, M. (1999) Joint Mean-Covariance Models with Applications to Longitudinal Data: Unconstrained Parameterization. Biometrika, 86, 677-690. http://dx.doi.org/10.1093/biomet/86.3.677</mixed-citation></ref><ref id="scirp.68746-ref3"><label>3</label><mixed-citation publication-type="other" xlink:type="simple">Pourahmadi, M. (2000) Maximum Likelihood Estimation of Generalised Linear Models for Multivariate Normal Covariance Matrix. Biometrika, 87, 425-435. http://dx.doi.org/10.1093/biomet/87.2.425</mixed-citation></ref><ref id="scirp.68746-ref4"><label>4</label><mixed-citation publication-type="other" xlink:type="simple">Kenward, M.G. (1987) A Method for Comparing Profiles of Repeated Measurements. Applied Statistics, 36, 296-308. http://dx.doi.org/10.2307/2347788</mixed-citation></ref><ref id="scirp.68746-ref5"><label>5</label><mixed-citation publication-type="other" xlink:type="simple">Laird, N.M. and Ware, J.J. (1982) Random-Effects Models for Longitudinal Data. Biometrics, 38, 963-974. http://dx.doi.org/10.2307/2529876</mixed-citation></ref><ref id="scirp.68746-ref6"><label>6</label><mixed-citation publication-type="other" xlink:type="simple">Patterson, H.D. and Thompson, R. (1971) Recovery of Interblock Information When Block Sizes Are Unequal. Biometrika, 58, 545-554. http://dx.doi.org/10.1093/biomet/58.3.545</mixed-citation></ref><ref id="scirp.68746-ref7"><label>7</label><mixed-citation publication-type="other" xlink:type="simple">Harville, D. (1974) Bayesian Inference for Variance Components Using Only Error Constrasts. Biometrika, 61, 383-385. http://dx.doi.org/10.1093/biomet/61.2.383</mixed-citation></ref><ref id="scirp.68746-ref8"><label>8</label><mixed-citation publication-type="other" xlink:type="simple">Diggle, P.J. and Kenward, M.G. (1994) Informative Drop-Out in Longitudinal Data Analysis. Applied Statistics, 43, 49-93. http://dx.doi.org/10.2307/2986113</mixed-citation></ref></ref-list></back></article>