Using In Vitro High‐Throughput Screening Data for Predicting Benzo[k]Fluoranthene Human Health Hazards

Today there are more than 80,000 chemicals in commerce and the environment. The potential human health risks are unknown for the vast majority of these chemicals as they lack human health risk assessments, toxicity reference values, and risk screening values. We aim to use computational toxicology and quantitative high‐throughput screening (qHTS) technologies to fill these data gaps, and begin to prioritize these chemicals for additional assessment. In this pilot, we demonstrate how we were able to identify that benzo[k]fluoranthene may induce DNA damage and steatosis using qHTS data and two separate adverse outcome pathways (AOPs). We also demonstrate how bootstrap natural spline‐based meta‐regression can be used to integrate data across multiple assay replicates to generate a concentration–response curve. We used this analysis to calculate an in vitro point of departure of 0.751 μM and risk‐specific in vitro concentrations of 0.29 μM and 0.28 μM for 1:1,000 and 1:10,000 risk, respectively, for DNA damage. Based on the available evidence, and considering that only a single HSD17B4 assay is available, we have low overall confidence in the steatosis hazard identification. This case study suggests that coupling qHTS assays with AOPs and ontologies will facilitate hazard identification. Combining this with quantitative evidence integration methods, such as bootstrap meta‐regression, may allow risk assessors to identify points of departure and risk‐specific internal/in vitro concentrations. These results are sufficient to prioritize the chemicals; however, in the longer term we will need to estimate external doses for risk screening purposes, such as through margin of exposure methods.     

Charisma as signal: An evolutionary perspective on charismatic leadership

We present an evolutionary perspective on charismatic leadership, arguing that charisma has evolved as a credible signal of a person's ability to solve a coordination challenge requiring urgent collective action from group members. We suggest that a better understanding of charisma's evolutionary and biological origins and functions can provide a broader perspective in which to situate current debates surrounding the utility and validity of charismatic leadership as a construct in the social sciences. We outline several key challenges which have shaped our followership psychology, and argue that the benefits of successful coordination in ancestral environments has led to the evolution of context-dependent psychological mechanisms which are especially attuned to cues and signals of outstanding personal leadership qualities. We elaborate on several implications of this signaling hypothesis of charismatic leadership, including opportunities for deception (dishonest signaling) and for large-scale coordination.     

The age of exploration and exploitation: Younger-looking leaders endorsed for change and older-looking leaders endorsed for stability

The current contribution extends theorizing on leadership and the exploration–exploitation dilemma using an evolutionary perspective. A theoretical connection is made between the exploration–exploitation dilemma and age-biased leadership preferences for exploratory change versus stable exploitation. For the majority of human evolution our species was semi- or entirely nomadic and the trade-off between exploration versus exploitation had substantial physical- and experience-based requirements which align with leadership opportunities as moderated by age. Thus, given the consistency and importance of correctly assigning leadership for the exploration–exploitation dilemma, human evolution has likely selected for age-biased leadership endorsement. Across three experiments we find that younger-looking leaders are endorsed for times of exploratory change and older-looking leaders for stable exploitation. Further, our results indicated that older leaders are endorsed for leading conservative exploitation of nonrenewable resources and younger leaders for exploration of renewable alternatives (i.e., green leadership). The results introduce an age-biased leadership endorsement hypothesis.     

The Effect of Product Development Restructuring on Shareholder Value

This article examines the effect of product development restructuring (PDR) on shareholder value. The results are based on a sample of 165 announcements made during 2002–2011. PDR announcements are associated with an economically and statistically significant positive stock market reaction. Over a two‐day period (the day of the announcement and the day preceding the announcement), the mean (median) market reaction is 1.63% (0.87%). The market reaction is generally positive regardless of the PDR purpose or action. Although the market reaction is more positive for higher R&D intensity firms, it is not directly affected by the firm's prior financial performance or whether the firm's primary PDR objective is to increase revenues or cut costs. However, the interaction between the firm's prior financial performance and its primary PDR objective is significant. For firms that are financial outperformers, the market reaction is more positive if the firm's primary PDR objective is to increase revenues. For financial underperformers, the market reaction is more positive if the firm's primary PDR objective is to cut costs.     

China, Globalisation and Health Biotechnology Innovation: Venture Capital and the Adaptive State

This paper explores the changing approach of the Chinese state to health biotechnology innovation and, in particular, the position of venture capital within that process. How has the Chinese state dealt with the opportunities and threats posed by globalisation in this field, what status has it attached to the role of venture capital in innovation and what are the implications of these actions for the role of the state? In addressing these questions, the paper begins by examining the global context of the venture capital and innovation relationship, the varied nature of VC organisation, the business models that inform the VC approach to health biotechnology innovation and the implications of these factors for the role of the state. Secondly, it explores the nature and impact of state intervention in China on the VC contribution to innovation, the particular character of the Chinese VC industry and its economic environment and the capacity of the VC sector to contribute to China’s position as a global player in health technology innovation. The paper concludes by reviewing the insights this case study provides into the problematic character of state adaptation in China to the challenges of globalisation.     

Towards more productive industrial relations

The author suggests that a critical factor in bringing about an overall improvement in the UK's economic performance is an improvement in Industrial Relations—with the aim of achieving levels of productivity which match the best in the world. The article asks how this is to be done; what has gone wrong; and, more importantly, what can be done to improve the situation in the future.     

Planning and health care—The approach in a reorganized NHS

From April 1974, National Health Service authorities have been merged to provide integrated and comprehensive services. The reorganization policies place considerable emphasis on the need for management and planning but planning for health services is not well developed. Ambiguous operational objectives and obscured criteria for effectiveness are not the most promising basis for planning. Nevertheless, a commendable beginning is to be made on planning comprehensively through a systematic annual review of Government health service policies and planning and programming procedures for health authorities. The outlines of the system are described and the prospects for success and further development are considered.     

TOR pathway: linking nutrient sensing to life span

Recent studies point to an emerging role for the TOR (target of rapamycin) pathway in the regulation of life span. In this Perspective, we discuss the possibility that this pathway is an important modulator of nutrient-dependent changes in life span. Additionally, we discuss the interactions between the TOR and insulin-like signaling pathways as well as the key downstream processes that TOR regulates.