The Acute Effects of 5 Fluorouracil on Skeletal Muscle Resident and Infiltrating Immune Cells in Mice

5 fluorouracil (5FU) has been a first-choice chemotherapy drug for several cancer types (e.g., colon, breast, head, and neck); however, its efficacy is diminished by patient acquired resistance and pervasive side effects. Leukopenia is a hallmark of 5FU; however, the impact of 5FU-induced leukopenia on healthy tissue is only becoming unearthed. Recently, skeletal muscle has been shown to be impacted by 5FU in clinical and preclinical settings and weakness and fatigue remain among the most consistent complaints in cancer patients undergoing chemotherapy. Monocytes, or more specifically macrophages, are the predominate immune cell in skeletal muscle which regulate turnover and homeostasis through removal of damaged or old materials as well as coordinate skeletal muscle repair and remodeling. Whether 5FU-induced leukopenia extends beyond circulation to impact resident and infiltrating skeletal muscle immune cells has not been examined. The purpose of the study was to examine the acute effects of 5FU on resident and infiltrating skeletal muscle monocytes and inflammatory mediators. Male C57BL/6 mice were given a physiologically translatable dose (35 mg/kg) of 5FU, or PBS, i.p. once daily for 5 days to recapitulate 1 dosing cycle. Our results demonstrate that 5FU reduced circulating leukocytes, erythrocytes, and thrombocytes while inducing significant body weight loss (\u3e5%). Flow cytometry analysis of the skeletal muscle indicated a reduction in total CD45+ immune cells with a corresponding decrease in total CD45+CD11b+ monocytes. There was a strong relationship between circulating leukocytes and skeletal muscle CD45+ immune cells. Skeletal muscle Ly6cHigh activated monocytes and M1-like macrophages were reduced with 5FU treatment while total M2-like CD206+CD11c- macrophages were unchanged. Interestingly, 5FU reduced bone marrow CD45+ immune cells and CD45+CD11b+ monocytes. Our results demonstrate that 5FU induced body weight loss and decreased skeletal muscle CD45+ immune cells in association with a reduction in infiltrating Ly6cHigh monocytes. Interestingly, the loss of skeletal muscle immune cells occurred with bone marrow cell cycle arrest. Together our results highlight that skeletal muscle is sensitive to 5FU’s off-target effects which disrupts both circulating and skeletal muscle immune cells

Advertising, earnings prediction and market value: An analysis of persistent UK advertisers

YesThis paper examines whether major media advertising expenditures help in predicting future earnings. We consider the role of media advertising in firms’ marketing efforts and posit that persistent advertisers are more likely to benefit from advertising activities in creating long‐lived intangible assets. Employing a sample of persistent UK advertisers over the period 1997–2013, we find that advertising expenditures are significantly positively associated with firms’ future earnings and market value. We also report size and sector‐based differences in the association between advertising and firms’ future earnings. Our additional analysis provides support for the arguments that despite the recent rise in digital advertising budgets, traditional advertising media are still effective in positively influencing firms’ performance. Overall, the results of this study are consistent with the view that advertising expenditures produce intangible assets, at least for firms in certain sectors. These findings have implications for marketers in providing evidence of the value generated by firms’ advertising budgets, for investors in validating the relevance of advertising information in influencing future earnings, and for accounting regulators in relation to the provision of useful insights for any future deliberations on financial reporting policies for advertising expenditures

The Informativeness of Micro and Macro Information During Economic Crisis and Non-crisis Periods

We investigate whether the informativeness of reported profitability and macroeconomic expectations differs between non-crisis and crisis economic periods by analyzing data for five European Union countries over the period 2005-2011. We find, first, macroeconomic expectations: a) are useful in predicting future profitability only in non-crisis periods, and b) are not useful in predicting stock returns in either period. Second, reported profitability: a) is useful in predicting future profitability in both crisis and non-crisis periods but less so in crisis periods, and b) is useful in predicting returns only in crisis periods. The cash flow component of profitability drives these results while the accrual component appears to be uninformative. Third, expected profitability, implied by the interaction between current profitability and macroeconomic expectations, is informative in predicting future profitability in both crisis and non-crisis periods and is efficiently priced only for high profitability firms during non-crisis periods

Do Accounting Earnings or Free Cash Flows Provide a Better Estimate of Capital Gain Rates of Return on Stocks?

There are two widely accepted approaches used to estimate the market value of a firm's equity (Vs). The accounting approach assumes the estimated Vs is based on the discounted value of a firm's future net income stream (NI). A finance model assumes that the value of a firm's stock (Vs) is related to the performance of its discounted future free cash flows to equity (FCFE). The motivation of this paper is to discover whether the accounting earnings approach or the finance FCFE approach provides a better explanation for estimating the capital gain rates of return on American and Japanese equities. Three sets of hypotheses were developed and regression analysis was used to test the hypothesized relationships. Financial data from a large sample of American and Japanese companies provided the information for testing the hypotheses. The regression results found a strong statistical relationship existed between net earrnings and capital gain rates of return for both American and Japanese companies. However, the Fama-MacBeth t value was only significant for the Japanese data, which cast doubt on the predictability of the net earnings approach based on American data. The study found the free cash flow to equity measure was not closely related to the capital gain rates of return for either the American or Japanese companies. However, a strong relationship was discovered to exits between the capital gain rates of return and the cash flow associated with operations, interest and financing for the American companies. Cash flows related to net investment and working captial were not consistently related to the capital gain returns for American and Japanese companies.