Model structure of compartmental model.

<p>The same structural model was used for all individuals and in both the mixed effects and the STS model. Model constraints, <i>k</i>_2,1 = <i>k</i>_1,2, <i>k</i>_3,4 = 0.1 <i>k</i>_4,3, <i>k</i>_9,8 = <i>k</i>_7,5 and <i>k</i>_0,9 = <i>k</i>_0,7 were used. Compartment 1 represents the free leucine in the plasma, compartments 3 and 4 represents leucine recycling in non-hepatic tissue and compartment 2 is the intrahepatic leucine that feeds the apoB synthesis compartment represented as a delay (D₁-D₇). Newly synthesized apoB enters the plasma as VLDL₁ (large particles, compartment 5) or VLDL₂ (small particles, compartment 8). VLDL₂ may also be produced through conversion of VLDL₁ via compartment 6. Particles may leave the system through compartments 6, 7, 9 or 10.</p

Residual plots of enrichment data using all data.

<p>The residuals (model fit minus measurement data) for the three enrichment data sets (A and B, plasma leucine; C and D, VLDL₁; E and F VLDL₂) were plotted for the two methods (STS and NLME) and the two groups (A, C and E, Control; B, D and F, type 2 diabetes mellitus (DM2)). Both methods produced good fits to the data. The NLME approach used a sequential procedure; the plasma leucine were fitted first and the VLDL₁ and VLDL₂ curves were fitted using the leucine results. This may explain the worse fit for the plasma leucine in the STS approach. Lines, mean of mixed effects approach (red) and STS approach (black); Areas, mean ± SD for mixed effects approach (red) and STS approach (black).</p

Sample size analysis.

<p>P-values for the difference between the groups were first calculated using all data, significant differences and the means and variances were considered as true. Desired sample sizes with study power of 80% were first estimated directly, using the estimated means and variances. The comparisons between healthy control subjects and DM2 patients were also repeated with both the mixed effects model and the STS model in re-sampled groups of 4, 6, 8, 10 and 12 subjects. For each group size the analysis was repeated 30 times. The minimum number of individuals needed to correctly identify a true difference at least 80% was considered as the minimal sample size. FCR, fractional catabolic rate; FTR, fractional transfer rate; FDCR, fractional direct catabolic rate; SR, secretion rate; indSR, in-direct secretion rate (ie flux from VLDL₁), DSR, direct secretion rate.</p><p>Sample size analysis.</p

Long-term trends in the prevalence of patients hospitalized with ischemic stroke from 1995 to 2010 in Sweden

<div><p>Objective</p><p>The prevalence of stroke is expected to increase partly because of prolonged life expectancy in the general population. The objective of this study was to investigate trends in the prevalence of patients hospitalized with ischemic stroke (IS) in Sweden from 1995–2010.</p><p>Methods</p><p>The Swedish inpatient and cause-specific death registries were used to estimate the absolute numbers and prevalence of patients who were hospitalized with and survived an IS from 1995–2010.</p><p>Results</p><p>The overall number of IS increased from 129,418 in 1995 to 148,778 in 2010. In 1995, the prevalence of IS was 189 patients per 10,000 population. An increase in overall prevalence was observed until 2000, and then it remained stable, followed by a decline with an annual percentage change of (APC) -0.8% (95% CI -1.0 to 0.6) and with a final prevalence of 199 patients per 10,000 population in 2010. The prevalence of IS in people aged <45 years increased from 6.4 in 1995 to 7.6 patients per 10,000 population in 2010, with an APC of 2.1% (95% CI 0.9 to 3.4) from 1995–1998 and 0.7% (95% CI 0.6–0.9) from 1998–2010. Among those aged 45–54 years, the prevalence rose through the mid to late 1990s, followed by a slight decrease (APC: -0.7%, 95% CI-1.1 to -0.4) until 2006 and then remained stable with a prevalence of 43.8 patients per 10,000 population in 2010. Among ≥85 years, there was a minor decrease (APC: -0.3%, 95% CI -0.5 to -0.1) in overall prevalence after 2002 from 1481 to 1453 patients per 10,000 population in 2010.</p><p>Conclusion</p><p>The overall prevalence of IS increased until 2000, but then remained stable followed by a slight decline. However, the prevalence of IS in the young increased through the study period. The absolute number of IS survivors has markedly increased, mainly because of demographic changes.</p></div

Jointpoint analysis of trends in prevalence of ischemic stroke among men and women in Sweden from 1995–2010.

<p>Jointpoint analysis of trends in prevalence of ischemic stroke among men and women in Sweden from 1995–2010.</p

Relative change in the prevalence of IS divided by age groups in A) all patients, B) in men, and C) in women.

<p>Relative change in the prevalence of IS divided by age groups in A) all patients, B) in men, and C) in women.</p

Intracellular ROS correlates with macrophage content and extracellular ROS with smooth muscle cell content in advanced atherosclerotic lesions Female <i>Apoe</i>^<i>-/-</i> mice were fed Western diet to induce advanced atherosclerotic lesions in the aortic arch.

<p>(<i>A)</i> Intracellular and extracellular ROS were analyzed in the aortic arch (red area) <i>(B)</i> Smooth muscle cell and macrophage content was quantified in the aortic arch by analyzing sections from 4 different levels. <i>(C)</i> Section stained for macrophages (CD68: blue) and smooth muscle cells (α-actin: red). <i>(D and E)</i> Smooth muscle cell content in lesions correlated with extracellular <i>(E)</i> but not intracellular ROS <i>(D)</i>. <i>(F and G)</i> Macrophage content in lesions correlated with intracellular <i>(F)</i> but not extracellular ROS <i>(G)</i>. Linear regression (n = 25). NS (non significant).</p

Prevalence of patients hospitalized with ischemic stroke in the total population divided by age groups, sex and calendar year from 1995–2010.

<p>Prevalence of patients hospitalized with ischemic stroke in the total population divided by age groups, sex and calendar year from 1995–2010.</p

Atorvastatin does not affect extent of atherosclerosis, lesion cell composition or lesion inflammation Female <i>Apoe</i>^<i>-/-</i> mice were first fed Western diet to induce advanced lesions in the aortic arch.

<p>Then, mice were treated with vehicle (DMSO) or oral atorvastatin (100 mg/kg per day) for 5 days. <i>(A)</i> Atorvastatin did not affect lesion area in the aorta. <i>(B)</i> Atorvastatin did not affect lesion cell composition. <i>(C)</i> Atorvastatin did not affect mRNA levels of inflammatory mediators. n = 6 in each group. Student’s t-test.</p

Atorvastatin reduces intracellular and extracellular ROS levels within the atherosclerotic aortic arch.

<p>Female <i>Apoe</i>^<i>-/-</i> mice were fed Western diet to induce advanced atherosclerotic lesions in the aortic arch. Then, mice were treated with vehicle (DMSO) or oral atorvastatin (100 mg/kg per day) for 5 days. <i>(A)</i> ROS levels were analyzed in the aortic arch (red areas). <i>(B–D)</i> Atorvastatin treatment reduced intracellular <i>(B and C)</i> and extracellular ROS levels <i>(D)</i>. <i>(E and F)</i> Plasma cholesterol <i>(E)</i> and triglycerides <i>(F)</i> was reduced by atorvastatin and, to larger extent, by lipid lowering by diet. n = 6 in each group. **p<0.01 vs vehicle, *p<0.05 vs vehicle. One sample t-test (C and D). ANOVA with Dunnet’s test for multiple comparisons (E and F).</p