We propose a model of dynamic investment, financing, and risk management for financially constrained firms. The model highlights the central importance of the endogenous marginal value of liquidity (cash and credit line) for corporate decisions. Our three main results are: (1) investment depends on the ratio of marginal q to the marginal value of liquidity, and the relation between investment and marginal q changes with the marginal source of funding; (2) optimal external financing and payout are characterized by an endogenous double-barrier policy for the firm's cashcapital ratio; and (3) liquidity management and derivatives hedging are complementary risk management tools.WHEN FIRMS FACE EXTERNAL financing costs, they must deal with complex and closely intertwined investment, financing, and risk management decisions. How to formalize the interconnections among these margins in a dynamic setting and how to translate the theory into day-to-day risk management and real investment policies remains largely to be determined. Questions such as how corporations should manage their cash holdings, which risks they should hedge and by how much, or the extent to which holding cash is a substitute for financial hedging are not well understood.Our goal in this article is to propose the first elements of a tractable dynamic corporate risk management framework-as illustrated in Figure 1-in which cash inventory, corporate investment, external financing, payout, and dynamic hedging policies are characterized simultaneously for a "financially constrained" firm. We emphasize that risk management is not just about financial hedging; instead, it is tightly connected to liquidity management via * Bolton is at Columbia University, NBER, and CEPR. Chen is at MIT Sloan School of Management and NBER. Wang is at Columbia University, NBER, and Shanghai University of Finance & Economics. We are grateful to Andrew Abel, Peter DeMarzo, Janice Eberly, Andrea Eisfeldt, Mike Faulkender, Michael Fishman, Xavier Gabaix, John Graham, Dirk Hackbarth, Cam Harvey, Christopher Hennessy, Pete Kyle, Yelena Larkin, Robert McDonald, Stewart Myers, Marco Pagano, Gordon Phillips, Robert Pindyck, Adriano Rampini, David Scharfstein, Jiang Wang, Toni Whited, two anonymous referees, and seminar participants at Boston College, Boston University, Columbia Business School, Duke, MIT Sloan, NYU Stern and NYU Economics, University of California at Berkeley, Yale, Maryland, Northwestern, Princeton, Lancaster, Virginia, IMF, Hong Kong University of Science and Technology Finance Symposium, Arizona State University, American Finance Association Meeting, the Caesarea Center 6th Annual Academic Conference, European Summer Symposium on Financial Markets, and Foundation for the Advancement of Research in Financial Economics for their comments. daily operations. By bringing these different aspects of risk management into a unified framework, we show how they interact with and complement each other.The baseline model we propose introduces only the essential building b...

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Depression and anxiety are common comorbidities in breast cancer patients. Whether depression and anxiety are associated with breast cancer progression or mortality is unclear. Herein, based on a systematic literature search, 17 eligible studies involving 282,203 breast cancer patients were included. The results showed that depression was associated with cancer recurrence [1.24 (1.07, 1.43)], all-cause mortality [1.30 (1.23, 1.36)], and cancer-specific mortality [1.29 (1.11, 1.49)]. However, anxiety was associated with recurrence [1.17 (1.02, 1.34)] and all-cause mortality [1.13 (1.07, 1.19)] but not with cancer-specific mortality [1.05 (0.82, 1.35)]. Comorbidity of depression and anxiety is associated with all-cause mortality [1.34 (1.24, 1.45)] and cancer-specific mortality [1.45 (1.11, 1.90)]. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety, being female and of younger age (<60 years), and shorter follow-up duration (≤5 years) were related to a poorer prognosis. Our study highlights the critical role of depression/anxiety as an independent factor in predicting breast cancer recurrence and survival. Further research should focus on a favorable strategy that works best to improve outcomes among breast cancer patients with mental disorders.

Tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and multiple TAM-secreted cytokines have been identified associating with poor clinical outcomes. However, the therapeutic targets existing in the loop between TAMs and cancer cells are still required for further investigation. Here in, cytokine array validated that C-X-C motif chemokine ligand 1 (CXCL1) is the most abundant chemokine secreted by TAMs, and CXCL1 can promote breast cancer migration and invasion ability, as well as epithelial–mesenchymal transition in both mouse and human breast cancer cells. QPCR screening further validated SOX4 as the highest responsive gene following CXCL1 administration. Mechanistic study revealed that CXCL1 binds to SOX4 promoter and activates its transcription via NF-κB pathway. In vivo breast cancer xenografts demonstrated that CXCL1 silencing in TAMs results in a significant reduction in breast cancer growth and metastatic burden. Bioinformatic analysis and clinical investigation finally suggested that high CXCL1 expression is significantly correlated with breast cancer lymph node metastasis, poor overall survival and basal-like subtype. Taken together, our results indicated that TAMs/CXCL1 promotes breast cancer metastasis via NF-κB/SOX4 activation, and CXCL1-based therapy might become a novel strategy for breast cancer metastasis prevention.