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Purpose The purpose of this study is to investigate the link between downsizing cues and market performance prior to and after a major crisis. We use a recent exogenous shock – the COVID-19 pandemic – to test hypotheses on the nature of the relationship between downsizing cues and market performance within two distinct groups: pre and post-crisis. We purport that the sudden increase in uncertainty brought about by a major crisis widens information asymmetry between firms and their shareholders, and that top managers sending downsizing cues to the market with high levels of authenticity may be more likely to trigger positive market reactions. Design/methodology/approach The authors rely on computer-assisted text analysis (CATA) methodology, event-study methodology and a data set of 952 pre- and post-crisis earnings conference calls held by 476 S&P 500 firms to test the hypotheses in this study. Findings The authors find that downsizing cues have no effect on market performance in the pre-crisis group, but are negatively related to market performance in the post-crisis group. The authors also find that authenticity cues positively mitigate the relationship between downsizing cues and market performance relationship in the post-crisis group. Originality/value This empirical study extends our knowledge of the influence of a major crisis on the relationship between downsizing and market performance by leveraging the revelatory power of an exogenous environmental shock. The authors also explore the role played by managerial authenticity and find that the market is more inclined to accept post-crisis downsizing efforts when top managers are perceived as authentic.

Tubulin-binding vascular-disrupting agents (VDA) are currently in clinical trials for cancer therapy but the factors that influence tumor susceptibility to these agents are poorly understood. We evaluated the consequences of modifying tumor vascular morphology and function on vascular and therapeutic response to combretastatin-A4 3-O-phosphate (CA-4-P), which was chosen as a model VDA. Mouse fibrosarcoma cell lines that are capable of expressing all vascular endothelial growth factor (VEGF) isoforms (control) or only single isoforms of VEGF (VEGF120, VEGF164, or VEGF188) were developed under endogenous VEGF promoter control. Once tumors were established, VEGF isoform expression did not affect growth or blood flow rate. However, VEGF188 was uniquely associated with tumor vascular maturity, resistance to hemorrhage, and resistance to CA-4-P. Pericyte staining was much greater in VEGF188 and control tumors than in VEGF120 and VEGF164 tumors. Vascular volume was highest in VEGF120 and control tumors (CD31 staining) but total vascular length was highest in VEGF188 tumors, reflecting very narrow vessels forming complex vascular networks. I.v. administered 40 kDa FITC-dextran leaked slowly from the vasculature of VEGF188 tumors compared with VEGF120 tumors. Intravital microscopy measurements of vascular length and RBC velocity showed that CA-4-P produced significantly more vascular damage in VEGF120 and VEGF164 tumors than in VEGF188 and control tumors. Importantly, this translated into a similar differential in therapeutic response, as determined by tumor growth delay. Results imply differences in signaling pathways between VEGF isoforms and suggest that VEGF isoforms might be useful in vascular-disrupting cancer therapy to predict tumor susceptibility to VDAs. [Cancer Res 2008;68(7):2301–11]

Supplementary Figure 3 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Table 1 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Figure 4 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Figure 5 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Figure 2 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Figures, Table and Movie Legend from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Figure 1 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Movie from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

PurposePast research has generally purported that market orientation (MO) leads to superior firm performance, despite emerging evidence suggesting that the highest levels of MO are not always rewarded. Drawing on resource-based view and MO literature, the authors posit that too much MO may be as detrimental as too little for firms seeking to achieve better performance, and that moderate MO capabilities may be the most beneficial. Furthermore, the authors propose and test for organizational confidence as a first potential moderator of the MO-performance inverted U-shaped link.Design/methodology/approachThe authors use Computer-Assisted-Text-Analysis (CATA) methodology assess constructs from annual reports matched with a 5-year longitudinal dataset of 2,245 firm-year observations drawn from the S&P 500.FindingsThe results not only support the presence of an inverted U-shaped link between MO and firm performance, but also identify organizational confidence as an important moderator of this newly uncovered curvilinear relationship.Practical implicationsWhen it comes to the effect of MO on firm performance, there can be indeed be “too much of a good thing,” and managers should be aware of the trade-offs that come attached with overcommitting to a MO strategy.Originality/valueThe authors contribute to extant research on the MO–performance link by moving beyond simple linear relationships and identifying an inverted U-shaped relationship between MO and firm performance. This newly found curvilinear relationship may explain and reconcile prior contradicting findings on the benefits of MO. Organizational confidence is also found to trigger a shape-flip of the MO–performance link, thereby suggesting a new boundary condition.

Triple-negative breast cancer (TNBC) remains the most lethal breast cancer subtype with poor response rates to the current chemotherapies and a lack of additional effective treatment options. We have identified deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) as a critical gatekeeper that protects tumour DNA from the genotoxic misincorporation of uracil during treatment with standard chemotherapeutic agents commonly used in the FEC regimen. dUTPase catalyses the hydrolytic dephosphorylation of deoxyuridine triphosphate (dUTP) to deoxyuridine monophosphate (dUMP), providing dUMP for thymidylate synthase as part of the thymidylate biosynthesis pathway and maintaining low intracellular dUTP concentrations. This is crucial as DNA polymerase cannot distinguish between dUTP and deoxythymidylate triphosphate (dTTP), leading to dUTP misincorporation into DNA. Targeting dUTPase and inducing uracil misincorporation during the repair of DNA damage induced by fluoropyrimidines or anthracyclines represents an effective strategy to induce cell lethality. dUTPase inhibition significantly sensitised TNBC cell lines to fluoropyrimidines and anthracyclines through imbalanced nucleotide pools and increased DNA damage leading to decreased proliferation and increased cell death. These results suggest that repair of treatment-mediated DNA damage requires dUTPase to prevent uracil misincorporation and that inhibition of dUTPase is a promising strategy to enhance the efficacy of TNBC chemotherapy.

PurposeThis paper aims to investigate whether cues of morality can mitigate stock sell-offs in the face of earnings uncertainty prior to earnings conference calls and draws on moral foundations theory to study the effect of universal moral cues (harm/care and fairness/reciprocity rhetoric) and primarily conservative moral cues (ingroup/loyalty, authority/respect and purity/sanctity rhetoric) on market performance.Design/methodology/approachThe study relies on a longitudinal data set of 1,920 firm-quarter observations corresponding to calls held by firms listed on the S&P 500 in 2015 and relies on computer-assisted-text-analysis and event-study methodology to test hypotheses.FindingsThe results suggest that cues of universal moral foundations have a mitigating effect on stock sell-offs and are able to create firm value; while cues primarily conservative moral foundations are not found to have an effect on market performance.Originality/valueThis investigation highlights why earnings conference calls may serve as a valuable tool for communicating a firm’s moral inclination and why universal morality may appeal to a wider range of shareholders than primarily conservative morality.

This article examines the phenomenon of dynamic capabilities in international new ventures (INVs) from emerging markets. While this research stream is gaining traction, the literature is fragmented as to how INVs from emerging markets develop dynamic capabilities to overcome resource constraints and legitimacy issues. The authors highlight the importance of a comprehensive international entrepreneurial culture (IEC) to better understand how these INVs develop dynamic capabilities and foster international performance. This study draws on organisational learning and the knowledge-based view (KBV) to examine the role of IEC in shaping dynamic capabilities and international performance under various levels of market turbulence. To conduct our analyses, this study uses a sample of INVs from India – a key emerging market. The results indicate that IEC shapes dynamic capabilities and both support superior international performance. The findings also confirm the utility of IEC towards dynamic capabilities and international performance when operating in turbulent markets.