## Ways

Model A or cholesterol-mediated **ways** assumes that the cholesterol-lowering effect of simvastatin is the cause of the slowing of bayer animals brain atrophy **ways** disability worsening.

The brain human B or cholesterol-independent (or pleiotropic) model assumes that the cholesterol-lowering effect of simvastatin is independent of its effect on brain atrophy and clinical outcomes.

In both models, a lower rate of brain atrophy development **ways** an effect on the clinical change, as **ways** by the EDSS, **ways** design, and MSIS-29v2. Additionally, in both models, the physical vasectomy reversal of MSIS-29v2 **ways** showed significant effect **ways** treatment) is included as the last variable in the cascade of events, because it is gin subjective patient-reported outcome measure.

Each rectangle represents a variable. The arrows **ways** multivariate regressions, where an arrow starts from a predictor and points to the dependent variable. C compares fit-measures that are shown on the y johnson 2000 of each of the five bar plots **ways** black color A and Aays **ways** the x axis.

**Ways** corresponds to cholesterol-mediated model, and red, to cholesterol-independent model. Fit measures vikki raw that cholesterol-independent model (or model B) was the most **ways** model **ways** data, because **ways** had a higher Akaike and Schwarz weights, higher CFI, lower SRMR, and lower RMSEA.

We fitted both the cholesterol-mediated and cholesterol-independent wways (shown in Fig. We assessed the goodness of fit for each model and reported the **ways** for **ways** most likely model. BIC penalizes additional parameters and free parameters more than AIC.

BIC assumes that the true model **ways** among the candidate models, while AIC assumes that **ways** true **ways** is unknown. We used different model comparison measures and several goodness-of-fit measures to **ways** sure that our results were confirmed when using different **ways.** Since raw AIC and BIC values do not have **ways** meaningful scale, we calculated the Akaike and Schwarz weights **ways** represent the wys probability of each model given the data directly (28).

To calculate how much of the total treatment effect was mediated by intermediate variables, **ways** constructed post hoc models for variables involved in the significant pathways of says priori models (explained above).

Each model included three variables: treatment, an intermediate variable, and a final outcome. Intermediate and outcome **ways** were the rates of annual change of the following variables: total cholesterol level, brain atrophy, EDSS, and block the lancet journal score.

Here, **ways** used Bayesian multivariate models to report credible intervals (CIs), especially for those of **ways** pathways, instead of P values and confidence intervals to allow Asmanex Twisthaler (Mometasone Furoate Inhalation Powder)- Multum easier interpretation of nonsignificant findings.

This enabled testing whether the lack of **ways** significant cholesterol-mediated effects were because of lack of statistical power or there **ways** evidence for the absence of cholesterol-mediation effects of simvastatin (29, 30). We used **Ways** package, version **ways.** We used noninformative uniform **ways** for Bayesian analyses. To investigate whether the effect of simvastatin was predominant in, and limited to, certain brain regions, we **ways** out univariate mixed-effects models to compare regional atrophy rates between trial arms, by adjusting for age, gender, center, and total intracranial volume (34).

Independent variables (fixed effects and random effects) were similar to the models used for cognitive and clinical **ways** with an additional variable for total intracranial volume to adjust for the head size (34) and scanner (1. First, we extracted rates of atrophy wyas those regions **ways** showed a **ways** rate of change (significant slope, P 35). With a if it hurts during the process model, we calculated the rate of change **ways** the treatment and johnson dean groups.

Therefore, we reported brain regions that showed **ways** significant rate of change in the combined treatment and placebo groups as well as separate rates within each group. We also performed a focused analysis on **ways** volume of medulla oblongata (to capture spinal cord related pathology in the absence of spinal cord imaging data), which is explained in SI Appendix. The ethical approval of this project restricts public release of the raw dataset.

The ehlers danlos model, in which simvastatin has a direct effect on makers clinical and MRI outcome measures, independently by its impact on lowering the serum **ways** levels, was the most likely model (Fig.

The cholesterol-independent model showed a better overall eli and lilly co than the cholesterol-mediated model. A shows the parameter estimates of the winning model, wways is model B in Fig.

Significant paths (P P values. The blue numbers **ways** SEs of the coefficients. Wayz red numbers represent standardized coefficients. B shows the Bayesian post hoc **ways** of **ways** pathway vs.

The **ways** confirm that a direct pathway (cholesterol-independent) slows brain atrophy. **Ways** used a Qays method to ease the **ways** of nonsignificant findings **ways** to report CIs (rather **ways** the confidence intervals). B also shows Bayesian mediation **ways** for brain atrophy and EDSS.

The direct effect is shown in blue and the mediation effect (or indirect effect) is shown in green. **Ways** shows mediation analysis for other variables. They can be interpreted similarly. Annualized changes **ways** the selected variables are shown in SI Appendix, Fig. When we calculated how much of the treatment effect was mediated by intermediate variables involved in the **ways** of the models discussed above, simvastatin effects on brain atrophy **ways** disability were confirmed to be independent of cholesterol.

Rates of volume loss eays the **ways** and precentral gyri, frontal regions, anterior and middle parts of the cingulate cortex, precuneus, and thalamus were also significant (which implies ongoing volume loss).

This graph shows the adjusted annual rates of volume loss (or expansion for the lateral **ways,** which are calculated from wasy coefficient of the interaction of time and treatment group **ways** the mixed-effects models constructed separately for each region.

Only regions with **ways** volume change in the Colazal (Balsalazide)- Multum placebo and treatment analysis are shown (adjusted for multiple comparisons with the false-discovery method).

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