Engineered Knottin Peptide Enables Noninvasive Optical Imaging of Intracranial Medulloblastoma

Central nervous system tumors carry grave clinical prognoses due to limited effectiveness of surgical resection, radiation, and chemotherapy. Thus, improved strategies for brain tumor visualization and targeted treatment are critically needed. We demonstrate that mouse cerebellar medulloblastoma (MB) can be targeted and illuminated with a fluorescent, engineered cystine knot (knottin) peptide that binds with high affinity to α β , α β , and α β integrin receptors. This integrin-binding knottin peptide, denoted EETI 2.5F, was evaluated as a molecular imaging probe in both orthotopic and genetic models of MB. Following tail vein injection, fluorescence arising from dye-conjugated EETI 2.5F was localized to the tumor compared with the normal surrounding brain tissue, as measured by optical imaging. The imaging signal intensity correlated with tumor volume. Due to its unique ability to bind to α β integrin, EETI 2.5F showed superior in vivo and ex vivo brain tumor imaging contrast compared with other engineered integrin-binding knottin peptides and with c(RGDfK), a well-studied integrin-binding peptidomimetic. Next, EETI 2.5F was fused to an antibody fragment crystallizable (Fc) domain (EETI 2.5F-Fc) to determine if a larger integrin-binding protein could also target intracranial brain tumors. EETI 2.5F-Fc, conjugated to a fluorescent dye, illuminated MB following i.v. injection and was able to distribute throughout the tumor parenchyma. In contrast, brain tumor imaging signals were not detected in mice injected with EETI 2.5F proteins containing a scrambled integrin-binding sequence, demonstrating the importance of target specificity. These results highlight the potential of using EETI 2.5F and EETI 2.5-Fc as targeted molecular probes for brain tumor imaging

Human Resources and the Resource Based View of the Firm

The resource-based view (RBV) of the firm has influenced the field of strategic human resource management (SHRM) in a number of ways. This paper explores the impact of the RBV on the theoretical and empirical development of SHRM. It explores how the fields of strategy and SHRM are beginning to converge around a number of issues, and proposes a number of implications of this convergence

Accounting, Soci(et)al Risks, and Public Reason: Governmental Risk Discourses About the ILVA Steel Plant in Taranto (Italy)

The case of the ILVA steel plant in Taranto represents an example of con- trasting, incommensurable sustainability issues, explored in terms of “social” and “societal” risks (Asenova et al. in Managing the risks of public spending cuts in Scotland, 2013; Redistribution of social and societal risk: the impact on individuals, their networks and communities, 2015) [Asenova et al. (2015) refer to social risks as the risks of unemployment, and to societal risks as environmental and health risks.]. The case of ILVA has received significant attention for the great amount of dangerous pollutants spread in the environment, as well as the evidence of higher illness and mortality rates in the districts nearest to the plant. In July 2012, the Italian Judiciary halted activity in the steel plant. Four months after, the Italian Government declared the steel plant site as a “Strategic National Interest Site”, and allowed the company to restart its activity. Drawing on governmentality (Foucault in Questions of method, 1991), the paper aims to explore the role of accounting—here broadly intended as calculative practices (Miller in Soc Res 68:379–396, 2001)—in moulding ministerial discourse to support decisions when the governance of contrasting risks is needed to safeguard public interest. Supported by discourse analysis of governmental speech, the research shows that the Italian Government based its decision on various experts’ risk appraisals: accounting shaped governmental discourse by giving more visibility and relevance to “social” risks (i.e. unemployment, economic development, produc- tivity and competitiveness risks), while silencing “societal” ones (i.e. environmental and health risks). Focusing on a case of incommensurable contrasting issues, the findings contribute to show that accounting concurrently plays a significant role in government decisions legitimizing the business continuity through the creation of a specific risk discourse

Progressive Focusing and Trustworthiness in Qualitative Research: The Enabling Role of Computer-Assisted Qualitative Data Analysis Software (CAQDAS)

* The business and management community increasingly recognises that qualitative research is a ‘messy’, non-linear and often unpredictable undertaking. Yet, a considerable proportion of the qualitative research published in top journals is still presented as the result of a linear, predictable research process, thus wrongly suggesting deductive reasoning. * In this paper, we focus on a particular type of ‘messiness’ where during fieldwork, the research context is revealed to be more complex than anticipated, forcing the researcher to gradually refine/shift their focus to reflect ‘what really matters’. We adopt Stake’s notion of progressive focusing for this gradual approach. * Progressive focusing is well-suited to qualitative research in international business requiring complex iteration between theory and data, and the truthful yet coherent presentation of the research process. We propose that this dual challenge of complexity and trustworthiness may be addressed by using computer-assisted qualitative data analysis software (CAQDAS). * We present conceptual considerations and guidelines and offer a view on a ‘messy’, non-linear doctoral research project conducted using a progressive focusing approach, to demonstrate how CAQDAS can help to develop and re-negotiate insights from theory and interview data, as well as enhance trustworthiness, transparency and publication potential

The blameworthiness of health and safety rule violations

Man-made disasters usually lead to the tightening of safety regulations, because rule breaking is seen as a major cause of them. This reaction is based on the presumptions that the safety rules are good and that the rule-breakers are wrong. The reasons the personnel of a coke factory gave for breaking rules raise doubt about the tenability of these presumptions. It is unlikely that this result would have been achieved on the basis of a disaster evaluation or High-Reliability Theory. In both approaches, knowledge of the consequences of human conduct hinders an unprejudiced judgement about the blameworthiness of rule breaking

Organizing risk: organization and management theory for the risk society

Risk has become a crucial part of organizing, affecting a wide range of organizations in all sectors. We identify, review and integrate diverse literatures relevant to organizing risk, building on an existing framework that describes how risk is organized in three ‘modes’ – prospectively, in real-time, and retrospectively. We then identify three critical issues in the existing literature: its fragmented nature; its neglect of the tensions associated with each of the modes; and its tendency to assume that the meaning of an object in relation to risk is singular and stable. We provide a series of new insights with regard to each of these issues. First, we develop the concept of a risk cycle that shows how organizations engage with all three modes and transition between them over time. Second, we explain why the tensions have been largely ignored and show how studies using a risk work perspective can provide further insights into them. Third, we develop the concept of risk translation to highlight the ways in the meanings of risks can be transformed and to identify the political consequences of such translations. We conclude the paper with a research agenda to elaborate these insights and ideas further

Behavior in behavioral strategy : capturing, measuring, analyzing

Measuring behavior requires research methods that can capture observed outcomes and expose underlying processes and mechanisms. In this chapter, we present a toolbox of instruments and techniques we designed experimental tasks to simulate decision environments and capture behavior. We deployed protocol analysis and text analysis to examine the underlying cognitive processes. In combination, these can simultaneously grasp antecedents, outcomes, processes, and mechanisms. We applied them to collect rich behavioral data on two key topics in strategic management: the exploration–exploitation trade-off and strategic risk-taking. This mix of methods is particularly useful in describing actual behavior as it is, not as it should be, replacing assumptions with data and offering a finer-grained perspective of strategic decision-making

Blue Food Demand Across Geographic and Temporal Scales

Numerous studies have focused on the need to expand production of ‘blue foods’, defined as aquatic foods captured or cultivated in marine and freshwater systems, to meet rising population- and income-driven demand. Here we analyze the roles of economic, demographic, and geographic factors and preferences in shaping blue food demand, using secondary data from FAO and The World Bank, parameters from published models, and case studies at national to sub-national scales. Our results show a weak cross-sectional relationship between per capita income and consumption globally when using an aggregate fish metric. Disaggregation by fish species group reveals distinct geographic patterns; for example, high consumption of freshwater fish in China and pelagic fish in Ghana and Peru where these fish are widely available, affordable, and traditionally eaten. We project a near doubling of global fish demand by mid-century assuming continued growth in aquaculture production and constant real prices for fish. Our study concludes that nutritional and environmental consequences of rising demand will depend on substitution among fish groups and other animal source foods in national diets

How does ethical leadership trickle down? Test of an integrative dual-process model

Although the trickle-down effect of ethical leadership has been documented in the literature, its underlying mechanism still remains largely unclear. To address this gap, we develop a cross-level dual-process model to explain how the effect occurs. Drawing on social learning theory, we hypothesize that the ethical leadership of high-level managers could cascade to middle-level supervisors via its impact on middle-level supervisors’ two ethical expectations. Using a sample of 69 middle-level supervisors and 381 subordinates across 69 sub-branches from a large banking firm in China, we found that middle-level supervisors’ ethical efficacy expectation and unethical behavior–punishment expectation (as one form of ethical outcome expectations) accounted for the trickle-down effect. The explanatory role of middle-level supervisors’ ethical behavior–reward expectation (as the other form of ethical outcome expectations), however, was not supported. The theoretical and practical implications are discussed