Widely implementing evidence-based interventions for fall prevention is essential to decrease the incidence and healthcare costs associated with these injuries.

SUMMARY In response to TNF, NF-κB enters the nucleus and promotes inflammatory and stress-responsive gene transcription. Because NF-κB deregulation is associated with many diseases, one might expect strict control of NF-κB localization. However, nuclear NF-κB levels exhibit considerable cell-to-cell variability, even in unstimulated cells. To resolve this paradox and determine how transcription-inducing signals are encoded, we quantified single-cell NF-κB translocation dynamics and transcriptional responses in the same cells. We show that TNF-induced transcription correlates best with fold-change in nuclear NF-κB, not absolute nuclear NF-κB abundance. Using computational modeling, we find that an incoherent feed-forward loop, from competition for binding to κB motifs, could provide ‘memory’ of pre-ligand state necessary for fold-change detection. Experimentally, we observed three gene-specific patterns of transcription that are recapitulated in our model by modulating competition strength alone. Fold-change detection buffers against stochastic variation in signaling molecules and explains how cells tolerate variability in NF-κB abundance and localization.

The impact of insurer competition on welfare, negotiated provider prices, and premiums in the U.S. private health care industry is theoretically ambiguous. Reduced competition may increase the premiums charged by insurers and their payments made to hospitals. However, it may also strengthen insurers' bargaining leverage when negotiating with hospitals, thereby generating offsetting cost decreases. To understand and measure this trade-off, we estimate a model of employer-insurer and hospital-insurer bargaining over premiums and reimbursements, household demand for insurance, and individual demand for hospitals using detailed California admissions, claims, and enrollment data. We simulate the removal of both large and small insurers from consumers' choice sets. Although consumer welfare decreases and premiums typically increase, we find that premiums can fall upon the removal of a small insurer if an employer imposes effective premium constraints through negotiations with the remaining insurers. We also document substantial heterogeneity in hospital price adjustments upon the removal of an insurer, with renegotiated price increases and decreases of as much as 10% across markets.1 insights are relevant not only when employers change insurance plan menus offered to employees, but also when insurers merge, and when they enter or exit markets.One of this paper's primary contributions is identifying and quantifying the mechanisms by which insurer competition affects negotiated hospital prices in equilibrium. If reducing insurer competition raises premiums via an increase in the remaining insurers' market power, there may be an upward pressure on negotiated prices as hospitals capture part of the increased industry surplus. 4However, there are offsetting effects that arise if insurers consequently have greater bargaining leverage. This can occur if an insurer loses fewer enrollees to a rival insurer upon disagreement with a hospital and if a hospital "recaptures" fewer enrollees through a rival insurer upon disagreement with an insurer. If substantial, these additional effects-variants of countervailing power (Galbraith, 1952)-imply that greater downstream concentration can reduce total hospital payments.Previous papers have examined the relationship between market concentration and medical provider prices, often within a regression framework (c.f. Gaynor and Town, 2012;Gaynor, Ho and Town, 2015). 5 We build on this literature by imposing structure derived from a theoretical model of competition in health care markets in order to uncover heterogeneous responses across firms and markets and conduct counterfactual simulations. Our approach is also related to Gowrisankaran, Nevo and Town (2015) who use a structural model of hospital-insurer bargaining to estimate the impact of hospital mergers on negotiated prices. 6 Our contributions include estimating a model of insurer competition for households in our empirical analysis and incorporating employer bargaining over premiums with insurers. 7 Capturing these interactions is...

In complex organisms, caspase proteases mediate a variety of cell behaviors, including proliferation, differentiation, and programmed cell death/apoptosis. Structural homologs to the caspase family (termed metacaspases) engage apoptosis in singlecell eukaryotes, yet the molecular mechanisms that contribute to nondeath roles are currently undefined. Here, we report an unexpected role for the Saccharomyces cerevisiae metacaspase Yca1 in protein quality control. Quantitative proteomic analysis of Δyca1 cells identified significant alterations to vacuolar catabolism and stress-response proteins in the absence of induced stress. Yca1 protein complexes are enriched for aggregate-remodeling chaperones that colocalize with Yca1-GFP fusions. Finally, deletion and inactivation mutants of Yca1 accrue protein aggregates and autophagic bodies during log-phase growth. Together, our results show that Yca1 contributes to the fitness and adaptability of growing yeast through an aggregate remodeling activity.nonapoptotic caspase activity | quality control | yeast | prion domain