Nonlinear semigroups for nonlocal conservation laws

We investigate a class of nonlocal conservation laws in several space dimensions, where the continuum average of weighted nonlocal interactions are considered over a finite horizon. We establish well-posedness for a broad class of flux functions and initial data via semigroup theory in Banach spaces and, in particular, via the celebrated Crandall–Liggett Theorem. We also show that the unique mild solution satisfies a Kružkov-type nonlocal entropy inequality. Similarly to the local case, we demonstrate an efficient way of proving various desirable qualitative properties of the unique solution

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Kinetic discretization of one-dimensional nonlocal flow models

We show that one-dimensional nonlocal flow models in PDE form with Lighthill-Whitham-Richards flux supplemented with appropriate in- and out-flow terms can be spatially discretized with a finite volume scheme to obtain formally kinetic models with physically meaningful reaction graph structure. This allows the utilization of the theory of chemical reaction networks, as demonstrated here via the stability analysis of a flow model with circular topology. We further propose an explicit time discretization and a Courant-Friedrichs-Lewy condition ensuring many advantageous properties of the scheme. Additional characteristics, including monotonicity and the total variation diminishing property are also discussed. Copyright (C) 2022 The Authors

Bi-exponential diffusion signal decay in normal appearing white matter of multiple sclerosis.

PURPOSE Our aim was to characterize bi-exponential diffusion signal changes in normal appearing white matter of multiple sclerosis (MS) patients. METHODS Diffusion parameters were measured using mono-exponential (0-1000 s/mm(2)) and bi-exponential (0-5000 s/mm(2)) approaches from 14 relapsing-remitting subtype of MS patients and 14 age- and sex-matched controls after acquiring diffusion-weighted images on a 3T MRI system. The results were analyzed using parametric or nonparametric tests and multiple linear regression models. RESULTS Mono-exponential apparent diffusion coefficient (ADC) slightly increased in controls (P=.09), but decreased significantly in MS as a function of age, nonetheless an elevated ADC was observed with increasing lesion number in patients. Bi-exponential analyses showed that the increased ADC is the result of decreased relative volume fraction of slow diffusing component (f(s)). However, the fast and slow diffusion components (ADC(f), ADC(s)) did not change as a function of either age in controls or lesion number and age in MS patients. CONCLUSIONS These data demonstrated that the myelin content of the white matter affects diffusion in relapsing-remitting subtype of multiple sclerosis that is possibly a consequence of the shift between different water fractions