Trends in the Concentration and Distribution of Health Care Expenditures in the US, 2001-2018.

Importance: The concentration of health care expenditures has important implications for managing risk pools, drug benefit design, and care management.

Objective: To examine trends in the concentration of health care spending in different population groups and expenditure categories in the US between 2001 and 2018.

Design, Setting, And Participants: This study is a cross-sectional analysis of Medical Expenditure Panel Surveys (MEPS) collected between 2001 and 2018.

An integrative toy model of cell flattening, spreading, and ruffling.

Background: The processes of cell spreading and crawling are frequently associated with mysterious waves and ruffling cycles of the leading edge.

Objective: To develop a physical model that can account for these phenomena based on a few simple and plausible rules governing adhesion, contractility, polymerization of cytoskeleton, and membrane tension.

Methods: Extension of a continuum mechanical model of phagocytosis [J Cell Sci.

Target-specific mechanics of phagocytosis: protrusive neutrophil response to zymosan differs from the uptake of antibody-tagged pathogens.

The physical mechanisms that control target-specific responses of human neutrophils to distinct immune threats are poorly understood. Using dual-micropipette manipulation, we have quantified and compared the time courses of neutrophil phagocytosis of two different targets: zymosan (a prominent model of fungal infection), and antibody-coated (Fc) particles. Our single-live-cell/single-target approach exposes surprising differences between these two forms of phagocytosis.

Protrusive push versus enveloping embrace: computational model of phagocytosis predicts key regulatory role of cytoskeletal membrane anchors.

Encounters between human neutrophils and zymosan elicit an initially protrusive cell response that is distinct from the thin lamella embracing antibody-coated targets. Recent experiments have led us to hypothesize that this behavior has its mechanistic roots in the modulation of interactions between membrane and cytoskeleton. To test and refine this hypothesis, we confront our experimental results with predictions of a computer model of leukocyte mechanical behavior, and establish the minimum set of mechanistic variations of this computational framework that reproduces the differences between zymosan and antibody phagocytosis.

Cytopede: a three-dimensional tool for modeling cell motility on a flat surface.

When cultured on flat surfaces, fibroblasts and many other cells spread to form thin lamellar sheets. Motion then occurs by extension of the sheet at the leading edge and retraction at the trailing edge. Comprehensive quantitative models of these phenomena have so far been lacking and to address this need, we have designed a three-dimensional code called Cytopede specialized for the simulation of the mechanical and signaling behavior of plated cells.

Analysis of actin FLAP dynamics in the leading lamella.

Background: The transport of labeled G-actin from the mid-lamella region to the leading edge in a highly motile malignant rat fibroblast line has been studied using fluorescence localization after photobleaching or FLAP, and the transit times recorded in these experiments were so fast that simple diffusion was deemed an insufficient explanation (see Zicha et al., Science, v. 300, pp.

Form and function in cell motility: from fibroblasts to keratocytes.

It is plain enough that a horse is made for running, but similar statements about motile cells are not so obvious. Here the basis for structure-function relations in cell motility is explored by application of a new computational technique that allows realistic three-dimensional simulations of cells migrating on flat substrata. With this approach, some cyber cells spontaneously display the classic irregular protrusion cycles and handmirror morphology of a crawling fibroblast, and others the steady gliding motility and crescent morphology of a fish keratocyte.

Baseline mechanical characterization of J774 macrophages.

Macrophage cell lines like J774 cells are ideal model systems for establishing the biophysical foundations of autonomous deformation and motility of immune cells. To aid comparative studies on these and other types of motile cells, we report measurements of the cortical tension and cytoplasmic viscosity of J774 macrophages using micropipette aspiration. Passive J774 cells cultured in suspension exhibited a cortical resting tension of approximately 0.

Mechanics of neutrophil phagocytosis: experiments and quantitative models.

To quantitatively characterize the mechanical processes that drive phagocytosis, we observed the FcgammaR-driven engulfment of antibody-coated beads of diameters 3 mum to 11 mum by initially spherical neutrophils. In particular, the time course of cell morphology, of bead motion and of cortical tension were determined. Here, we introduce a number of mechanistic models for phagocytosis and test their validity by comparing the experimental data with finite element computations for multiple bead sizes.

Mechanics of neutrophil phagocytosis: behavior of the cortical tension.

The mechanical implementation of phagocytosis requires a well-coordinated deployment of cytoplasm and membrane during the creation of a phagosome. We follow the time course of this process in initially round passive neutrophils presented with antibody-coated beads of radii 1.1 to 5.

The mechanics of neutrophils: synthetic modeling of three experiments.

Much experimental data exist on the mechanical properties of neutrophils, but so far, they have mostly been approached within the framework of liquid droplet models. This has two main drawbacks: 1), It treats the cytoplasm as a single phase when in reality, it is a composite of cytosol and cytoskeleton; and 2), It does not address the problem of active neutrophil deformation and force generation. To fill these lacunae, we develop here a comprehensive continuum-mechanical paradigm of the neutrophil that includes proper treatment of the membrane, cytosol, and cytoskeleton components.