Mathematical modeling of adipocyte size distributions: Identifiability and parameter estimation from rat data.

Fat cells, called adipocytes, are designed to regulate energy homeostasis by storing energy in the form of lipids. Adipocyte size distribution is assumed to play a role in the development of obesity-related diseases. These cells that do not have a characteristic size, indeed a bimodal size distribution is observed in adipose tissue. We propose a model based on a partial differential equation to describe adipocyte size distribution. The model includes a description of the lipid fluxes and the cell size fluctuations and using a formulation of a stationary solution fast computation of bimodal distribution is achieved. We investigate the parameter identifiability and estimate parameter values with CMA-ES algorithm. We first validate the procedure on synthetic data, then we estimate parameter values with experimental data of 32 rats. We discuss the estimated parameter values and their variability within the population, as well as the relation between estimated values and their biological significance. Finally, a sensitivity analysis is performed to specify the influence of parameters on cell size distribution and explain the differences between the model and the measurements. The proposed framework enables the characterization of adipocyte size distribution with four parameters and can be easily adapted to measurements of cell size distribution in different health conditions.

A Lifshitz-Slyozov type model for adipocyte size dynamics: limit from Becker-Döring system and numerical simulation.

Biological data show that the size distribution of adipose cells follows a bimodal distribution. In this work, we introduce a Lifshitz-Slyozov type model, based on a transport partial differential equation, for the dynamics of the size distribution of adipose cells. We prove a new convergence result from the related Becker-Döring model, a system composed of several ordinary differential equations, toward mild solutions of the Lifshitz-Slyozov model using distribution tail techniques. Then, this result allows us to propose a new advective-diffusive model, the second-order diffusive Lifshitz-Slyozov model, which is expected to better fit the experimental data. Numerical simulations of the solutions to the diffusive Lifshitz-Slyozov model are performed using a well-balanced scheme and compared to solutions to the transport model. Those simulations show that both bimodal and unimodal profiles can be reached asymptotically depending on several parameters. We put in evidence that the asymptotic profile for the second-order system does not depend on initial conditions, unlike for the transport Lifshitz-Slyozov model.

Scientists' views about attribution of global warming.

Results are presented from a survey held among 1868 scientists studying various aspects of climate change, including physical climate, climate impacts, and mitigation. The survey was unique in its size, broadness and level of detail. Consistent with other research, we found that, as the level of expertise in climate science grew, so too did the level of agreement on anthropogenic causation. 90% of respondents with more than 10 climate-related peer-reviewed publications (about half of all respondents), explicitly agreed with anthropogenic greenhouse gases (GHGs) being the dominant driver of recent global warming. The respondents' quantitative estimate of the GHG contribution appeared to strongly depend on their judgment or knowledge of the cooling effect of aerosols. The phrasing of the IPCC attribution statement in its fourth assessment report (AR4)-providing a lower limit for the isolated GHG contribution-may have led to an underestimation of the GHG influence on recent warming. The phrasing was improved in AR5. We also report on the respondents' views on other factors contributing to global warming; of these Land Use and Land Cover Change (LULCC) was considered the most important. Respondents who characterized human influence on climate as insignificant, reported having had the most frequent media coverage regarding their views on climate change.

Survival and response to pulmonary vasodilator therapies in patients with chronic obstructive pulmonary disease and pulmonary vascular phenotype.

BACKGROUND: The aim of the study was to describe and investigate the effect of pulmonary arterial hypertension (PAH) therapies in a cohort of patients with severe precapillary pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD; PH-COPD), and to assess factors predictive of treatment response and mortality. MATERIAL AND METHODS: We retrospectively included patients with severe incident PH-COPD who received PAH therapy and underwent RHC at diagnosis and on treatment. RESULTS: From 2015 to 2022, 35 severe PH-COPD patients, with clinical features of pulmonary vascular phenotype, were included. Seventeen (48.5%) patients were treated with combined PAH therapy. PAH therapy led to a significant improvement in hemodynamics (PVR -3.5 Wood Units (-39.3%); p < 0.0001), and in the simplified four-strata risk-assessment score, which improved by at least one category in 21 (60%) patients. This effect was more pronounced in patients on dual therapy. Kaplan-Meier estimated survival rates at 1, 3 and 5 years were 94%, 65% and 42% respectively. Univariate analysis showed a significant reduction in survival in patients with a higher simplified risk score at follow-up (Hazard ratio (HR) 2.88 [1.16-7.15]; p = 0.02). Hypoxemia <50 mmHg was correlated to mortality in multivariate analysis (HR 4.33 [1.08-17.42]; p = 0.04). CONCLUSIONS: Our study confirms the poor prognosis of patients with COPD and a pulmonary vascular phenotype and the potential interest of combined PAH therapy in this population, with good tolerability and greater clinical and hemodynamic improvement than monotherapy. Using the simplified risk score during follow-up could be of interest in this population.