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The deviance entries are $-2\ell$ for these fitted models. The completed values areThe likelihood-ratio test compares a model with one age coefficient against its restriction ${\beta }_1=0$. Its small p-value, approximately $0.000529$, supports a positive age association under the assumed Gaussian linear mixed model. Refitting with maximum likelihood estimation is essential here: restricted maximum likelihood values from models with different fixed-effect design matrices cannot be compared by this likelihood-ratio test.

Allow each subject to have a separate baseline and slope through a correlated random-intercept and random-slope model:The subject random effects are independent of all measurement errors, and subjects are independent. The within-person covariance between times $s,t$ is ${\tau }_0^2+(s+t)\rho {\tau }_0{\tau }_1+st{\tau }_1^2$, with an additional ${\sigma }^2$ when the same reading is used twice.

Prefer the model with a random slope. The maximum likelihood estimation refits improve twice the log-likelihood by $227.9604$ while adding two covariance statistical parameters. Both the Akaike information criterion ($5165.779$ to $4941.819$) and Bayesian information criterion ($5183.367$ to $4968.200$) strongly favour it. The printed nominal likelihood-ratio test is overwhelming. The usual reference chi-squared distribution with two statistical degrees of freedom is not an exact regular calibration, since zero slope variance is a boundary and the intercept–slope correlation is then unidentified; a design-specific parametric bootstrap could calibrate it. This qualification does not undermine the substantial descriptive improvement shown by both information criteria.

The preferred fit estimates population mean baseline strength ${\hat{\beta }}_0=61.09286$ kg and weekly gain ${\hat{\beta }}_1=2.83143$ kg/week. The between-person baseline standard deviation is ${\hat{\tau }}_0=15.785582$ kg, and the between-person slope standard deviation is ${\hat{\tau }}_1=2.738666$ kg/week. Their estimated correlation $\hat{\rho }=0.117$ is weakly positive, giving random-effect covariance about $5.058$ kg${}^2$/week; its uncertainty is not supplied. The measurement-error standard deviation is $\hat{\sigma }=9.923280$ kg. The printed $-0.038$ instead describes the correlation between the estimated fixed effects, not between the subject random effects. These statistical parameter estimates come from restricted maximum likelihood; the model comparison uses the separate maximum likelihood estimation fits.

The population mean fitted trajectory is $61.09286+2.83143t$ kg. HenceUsing the reported slope standard error, an approximate 95% confidence interval for the population mean gain is $28.3143\pm 1.96(2.984464)=(22.46,34.16)$ kg; a Student t confidence interval with 499 statistical degrees of freedom is almost identical.

Successful individuals can improve far more than the average. Their latent ten-week gains have fitted normal distributionA clear estimate for an upper-performing group uses a between-person slope quantile: the 95th percentile is $28.3143+1.645(27.38666)\simeq 73.4$ kg, and the 97.5th percentile is about $82.0$ kg. The upper 5% of fitted underlying gains begin around 73 kg. These are person-to-person performance quantiles, not confidence intervals for the population mean. Identifying the best observed trainee would require that person's data or fitted subject random effects; the aggregate output cannot identify a literal maximum. If performance means the observed difference of endpoint readings, add the measurement-error variance $2{\sigma }^2$ to the latent gain variance.

Assume initially that the design points are distinct and ordered on $[a,b]$. The cubic smoothing spline minimizesover functions with an absolutely continuous first derivative and square-integrable second derivative. Dividing the residual term by $n$ simply changes the scaling assigned to $\lambda$. The minimum roughness property of the natural cubic spline interpolant reduces the problem to natural cubic splines with knots at the design points: among functions with any prescribed fitted values, that interpolant has the smallest integrated squared curvature. The minimizer is therefore a natural cubic smoothing spline, with natural second-derivative boundary conditions and linear tails when extended.

Choose a full basis $B_1,\dots ,B_n$ for this natural-spline space. Put $B_{ij}=B_j(X_i)$ and ${\Omega }_{jk}={\int }_a^b{B}_j^{\prime \prime }(t)B_k^{\prime \prime }(t)dt$. Writing $g(t)={\sum }_j{c}_j{B}_j(t)$ changes the objective toDifferentiation gives $(B^{T}B+\lambda \Omega )\hat{c}=B^{T}Y$. Although the curvature penalty has an affine nullspace, the full basis at distinct design points makes the combined matrix positive definite. HenceEquivalently, use the cardinal basis that interpolates the observations, making $B=I$ and $S_{\lambda }=(I+\lambda \Omega {)}^{-1}$. These are smoothing matrices, symmetric but generally not idempotent. Their effective degrees of freedom are $\mathrm{tr}(S_{\lambda })$. As $\lambda \downarrow 0$ the fit interpolates; as $\lambda \uparrow \infty$ it approaches ordinary least squares on the affine functions. With replicated predictors, use a design matrix for distinct knots and observation weights; the basis form remains valid when identifiable.

Useful choices include Leave-one-out cross-validation, generalized cross-validation, and estimation of smoothness by restricted maximum likelihood through a mixed-model representation. For fixed $\lambda$, the leave-one-out residual identity for a linear smoother givesMinimize these over a suitable range. Choose smoothing by predictive performance or a variance-component likelihood, not by arbitrarily forcing a visually appealing curve.

The restricted maximum likelihood procedure estimates covariance parameters from error contrasts that remove the unknown fixed effects. Let $X$ have rank $p$ and choose an $n\times (n-p)$ full-rank matrix $A$ with $A^{T}X=0$. Then $A^{T}Y\sim N(0,A^{T}V(\vartheta )A)$ has a likelihood involving the variance parameters $\vartheta$ but not $\beta$. Maximizing that likelihood is restricted maximum likelihood. An equivalent restricted likelihood from orthogonal error contrasts, up to terms independent of $\vartheta$, iswhereAfter estimating $\vartheta$, use generalized least squares for $\hat{\beta }=(X^T{\hat{V}}^{-1}X{)}^{-1}{X}^T{\hat{V}}^{-1}Y$ and the conditional modes from part (b). In an independent-error normal linear model, this covariance procedure reduces to estimating ${\sigma }^2$ by $\mathrm{RSS}/(n-p)$ instead of $\mathrm{RSS}/n$.

The two models being compared have different fixed-effect spaces, so their error contrasts, dimensions, and restricted likelihoods differ. Their REML values are not likelihoods of the same transformed data and must not be used directly for this fixed-effect likelihood-ratio test. Refit both with ordinary maximum likelihood, integrating out the random effects but retaining the original response vector, and maximize each model's marginal likelihood.

The null hypothesis is ${\beta }_1=0$, leaving the random slope variance free; the alternative permits a nonzero population stirring effect. The supplied test has $2({\ell }_1-{\ell }_0)=7.9588$, one extra fixed coefficient, and approximate ${\chi }_1^2$ p-value $0.004786$. Retain the fixed stirring-rate effect at 5%. A mean-zero random slope cannot substitute for an estimated nonzero population slope. The asymptotic calibration assumes regular nuisance covariance parameters and should be interpreted cautiously with only three furnaces; simulation can provide a better finite-sample calibration.

The marginal Akaike information criterion is $\mathrm{AIC}=-2\ell ({\hat{\vartheta }}_{\mathrm{ML}})+2k$, where $k$ counts estimated population parameters. Here they are ${\beta }_0,{\beta }_1,{\sigma }^2,{\tau }^2$, so $k=4$. The realized incubator slopes have been integrated out of the likelihood function; they are not four additional free population coefficients. From the marginal Gaussian log-likelihood, the expression isAll hats here denote the ordinary maximum likelihood estimation fit.

The displayed value $14041.1$ is instead a restricted maximum likelihood criterion. Thus it cannot simply be substituted for the ordinary maximum-likelihood deviance. The logLik method defaults to the fitting convention. If one applies AIC(fly.model) directly to the displayed REML object, the default restricted log-likelihood and the same parameter count give the software's restricted-likelihood-based value $14041.1+8=14049.1$. This number should be labelled as such; it is not the ordinary marginal AIC derived above. To obtain the latter, refit and calculateThe output does not contain that numerical answer. In particular, restricted criteria must not be used to compare models with different fixed-effect designs. A conditional AIC targeting predictions for existing groups is yet another criterion and does not follow by counting each latent slope as an ordinary parameter.

Let $X$ have rows $(1,y_i)$ and let ${\Sigma }_{\vartheta }$ be the spatial covariance matrix with $\vartheta =({\tau }^2,{\sigma }^2,a)$. Conditional on chosen covariance parameters, the best linear unbiased estimator of the drift coefficients is the generalized least squares estimatorThe printed procedure first estimates the linear drift from depth ~ y, constructs a binned residual empirical semivariogram, fits a Gaussian semivariogram to it, and then uses the fitted covariance in generalized least squares trend estimation and universal kriging. The missing fit could be supplied aswhere those arguments are initial values, not the reported final estimates. Such semivariogram fitting typically minimizes a weighted sum of squared discrepancies between binned empirical values and model values; it is not automatically a joint Gaussian likelihood maximization. One can iterate: form residuals using the current drift, refit the covariance model, recompute the generalized least squares drift, and repeat until changes are small. The displayed commands themselves show a single sequence, not evidence that such iteration occurred.

A likelihood-based alternative estimates the two blocks coherently fromSubstitute $\hat{\beta }(\vartheta )$ to obtain a profile log-likelihood, maximize over ${\tau }^2,{\sigma }^2\ge 0$ and $a>0$ with a positive-definite matrix ${\Sigma }_{\vartheta }$, and recover the drift coefficients from the optimizing covariance. Restricted maximum likelihood adds the design determinant term $\log \det (X^T{\Sigma }_{\vartheta }^{-1}X)$ and uses $n-2$ in place of $n$ in the normalizing term, up to a fixed-design constant. It can reduce bias from estimating the drift before the covariance. A zero fitted nugget is a legitimate boundary estimate, not proof that measurement error is absent. Estimate drift using covariance-weighted regression, and spatial dependence from drift-adjusted variation, with the two stages or likelihood explicitly distinguished.

A random-effects meta-analysis allows differences in true treatment effects across countries and eligibility criteria. For trial $i=1,\dots ,6$, let $y_i$ be its estimated log odds ratio and $v_i$ its estimated within-trial variance. A usual approximate statistical model isindependently across trials, with $b_i$ independent of sampling errors. Here $\mu$ is the mean true log odds ratio in the population of comparable trials, and ${\tau }^2\ge 0$ is between-trial heterogeneity, not additional sampling error. Therefore $y_i\sim N(\mu ,v_i+{\tau }^2)$, and for a fitted heterogeneity value,One can estimate ${\tau }^2$ by restricted maximum likelihood or another justified method; $({\sum }_i{w}_i{)}^{-1}$ is a plug-in conditional variance and does not fully account for estimating heterogeneity. With only six studies that uncertainty matters. Different eligibility rules motivate this random effect but do not by themselves establish exchangeability or remove bias; known effect modifiers may warrant stratification or regression.

Use leave-one-study-out influence analysis: fit all six trials, then omit Cohen 1989 and refit both $\mu$ and ${\tau }^2$. Report $\hat{\mu }-{\hat{\mu }}_{(-C)}$, the corresponding change in the odds ratio, and changes in the confidence interval and heterogeneity. As a diagnostic with heterogeneity held fixed, writing $W={\sum }_i{w}_i$ givesThe fitted Cohen weight would be $(0.15+{\hat{\tau }}^2{)}^{-1}$ and $y_C=-1.95$. A precise but discordant trial can have large influence; refitting assesses additional influence through heterogeneity. The other five trials' data are absent, so a numerical six-trial influence assessment is not identifiable from the displayed table.

Let $Z_{ir}=1_{\{\text{observation }i\text{ belongs to rat }r\}}$. After integrating out the random intercepts,The fixed-effect design matrix has four independent columns, so the given $A$ has dimensions $176\times 172$, with $A^{T}A=I_{172}$ and $A^{T}X=0$. Consequently the error contrasts $U=A^{T}Y$ have a multivariate normal distribution with mean zero and covariance matrix $W=A^{T}VA$.

The restricted likelihood from orthogonal error contrasts is their density. Equivalently, the estimates maximizeThis is restricted maximum likelihood, not maximization over individual rat effects. The unknown $\beta$ disappears because $A^{T}X=0$. Replacing $A$ by $AQ$ for an orthogonal $Q$ rotates $U$ and conjugates $W$, preserving the determinant and quadratic form; hence the objective is independent of the chosen orthonormal basis. The software's integrated REML log-likelihood can differ by an additive constant depending only on $X$, which has no effect on these variance estimates.

There are two defects. The mixed fit supplies a restricted maximum likelihood, whereas the ordinary fit supplies an ordinary log-likelihood, so their difference is not a likelihood-ratio test statistic. Also, $H_0:{\tau }^2=0$ lies on the boundary of ${\tau }^2\ge 0$; the usual Wilks theorem does not give a ${\chi }_1^2$ null law.

A valid approach first refits the mixed model by ordinary maximum likelihood estimation, setting REML to false, and fits the same fixed effects under $H_0$. For $V={\tau }^{2}Z{Z}^T+{\sigma }^{2}I$, maximizeover $\beta ,{\sigma }^2>0,{\tau }^2\ge 0$, and separately over $\beta ,{\sigma }^2>0$ with ${\tau }^2=0$. Set $T=2({\hat{\ell }}_1-{\hat{\ell }}_0)\ge 0$.

For finite-sample calibration, use the location-scale invariant simulation test for a Gaussian variance component. With the actual $X,Z$ fixed, simulate $B$ independent vectors $Y^{(b)}\sim N(0,I_{176})$, refit both models by ordinary maximum likelihood estimation to each, and calculate $T_b$ in exactly the same way. Under $H_0$, $Y=X\beta +\sigma z$. Translating by a vector in the column space of $X$ and multiplying by a positive scalar preserves the statistic: both maximized log-likelihoods acquire the same scale constant. Thus this simulation has the correct null law without knowing $\beta$ or $\sigma$. A conservative Monte Carlo p-value isIn the usual regular limit with increasing independent groups, a variance-component likelihood-ratio test at a boundary instead uses $\frac{1}{2}{\delta }_0+\frac{1}{2}{\chi }_1^2$: for $T>0$, its approximate tail probability is $\frac{1}{2}\mathrm{Pr}({\chi }_1^2\ge T)$, and at $T=0$ the nonrandomized p-value is one. This approximation is not an exact guarantee for sixteen rats. Alternatively one can compare consistently defined restricted likelihoods with the same $X$ and simulate their restricted-ratio null distribution, as in the RLRsim documentation.

For $Y\sim N(X\beta ,V_{\theta })$ and a full-column-rank design matrix $X\in {\mathbb{R}}^{n\times p}$, take $A\in {\mathbb{R}}^{n\times (n-p)}$ with $A^{T}A=I$ and $A^{T}X=0$. Then $A^{T}Y\sim N(0,A^T{V}_{\theta }A)$, so restricted maximum likelihood maximizesChanging the orthonormal basis by an orthogonal matrix leaves this expression unchanged.