An evaluation of the antimetabolites of purines and pyrimidines, and their use as chemotherapeutic agents in oncology is presented. Application of these inhibitor drugs, although potent anti-cancer ...and anti-viral substances, are limited due to their toxicity to healthy tissue as well as tumors.
Drawing from social/political influence, leader–member exchange (LMX), and social comparison theories, the present two-study investigation examines three levels of LMX differentiation (i.e., ...individual-level, meso-level, and group-level LMX differentiation) and further tests a model of the joint effects of political skill and LMX differentiation on LMX, relative LMX, and employee work outcomes. In Study 1, we used data from 231 employees and found support for the interactive effect of political skill and individual perceptions of LMX differentiation on LMX quality. We also found partial support for the moderating role of individual-level LMX differentiation on the indirect effects of political skill on self-rated task performance and job satisfaction via LMX. In Study 2, we used data from 185 supervisor–subordinate dyads and examined both meso-level and group-level LMX differentiation via a multilevel moderated mediation model. Results supported the moderating role of group-level LMX differentiation and group mean LMX on the indirect effects of political skill on supervisor-rated task performance and contextual performance/citizenship behavior as well as job satisfaction via relative LMX. Overall, the results suggest that politically skilled employees reap the benefits of LMX differentiation, as they enjoy higher absolute LMX and relative (i.e., to their peers) LMX quality.
This review provides a brief background on the extraction of uranium from seawater as well as recent work by the United States Department of Energy on this project. The world's oceans contain uranium ...at 3 parts per billion, and despite this low concentration, there has been historical interest in harvesting it, mainly in Japan in the 1980s and the United States in this decade. Improvements in materials, chemistry, and deployment methods have all been made, with the ultimate goal of lower cost. This has been partially realized, dropping from approximately $2000 per kg U
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extracted in 1984 to $500 per kg today, although this is not yet competitive with terrestrial uranium. This technology may become cost-competitive if the cost of land-based uranium rises, especially if seawater extraction technology is improved further. The coordination chemistry aspects of the project are described in more detail, exploring the functional groups that are present on typical polymer sorbents as well as small-molecule analogues of these ligands. Selectivity for uranium over other metals, particularly vanadium, remains problematic, and techniques to both quantify binding strength and selectivity in order to overcome this issue are essential for future cost improvements.
There has been historical interest in harvesting uranium from seawater for nuclear energy over the past few decades, with the goal of lower extraction cost to become competitive with land-based uranium. This review provides a brief background on the extraction of uranium from seawater and on recent work from groups supported by the United States Department of Energy on this project.
•We conduct a systematic literature review of the destructive leadership literature.•We meta-analytically examine results from 418 studies of destructive leadership.•We provide definitions of ...different styles of destructive leadership.•We build the solid empirical foundation necessary to advance knowledge in this area.•We identify actionable opportunities for future research to advance this literature.
The destructive leadership literature has grown remarkably in recent years. Although the field has generated an impressive body of knowledge, we still have an incomplete understanding of destructive leadership. We conduct a systematic literature review of destructive leadership research so we can create a solid foundation for knowledge production and theory development within this literature. Further, we draw from 418 empirical samples of data (k = 418, N = 123,511) to conduct random-effects meta-analyses that estimate the magnitude and direction of relationships within destructive leadership’s nomological network. Ultimately, our study leverages and integrates the many insights from the destructive leadership literature to advance knowledge, facilitate nuanced theory development, generate useful directions for future research, and create evidence-based recommendations for policy and practice.
Dimethyl fumarate (DMF) is a first-line prodrug for the treatment of relapsing-remitting multiple sclerosis (RRMS) that is completely metabolized to monomethyl fumarate (MMF), the active metabolite, ...before reaching the systemic circulation. Its metabolism has been proposed to be due to ubiquitous esterases in the intestines and other tissues, but the specific enzymes involved are unknown. We hypothesized based on its structure and extensive presystemic metabolism that DMF would be a carboxylesterase substrate subject to interaction with alcohol. We sought to determine the enzymes(s) responsible for the extensive presystemic metabolism of DMF to MMF and the effect of alcohol on its disposition by conducting metabolic incubation studies in human recombinant carboxylesterase-1 (CES1), carboxylesterase-2 (CES2) and human intestinal microsomes (HIM), and by performing a follow-up study in an in vivo mouse model. The in vitro incubation studies demonstrated that DMF was only metabolized to MMF by CES1. Consistent with the incubation studies, the mouse pharmacokinetic study demonstrated that alcohol decreased the maximum concentration and area-under-the-curve of MMF in the plasma and the brain after dosing with DMF. We conclude that alcohol may markedly decrease exposure to the active MMF metabolite in the plasma and brain potentially decreasing the effectiveness of DMF in the treatment of RRMS.
•Adolescence characterised by experience of strong emotions that influence behaviour.•Emotions were found to impact upon the driving behaviour of adolescent drivers.•Driving context, driver ...characteristics, and social influences important.•Interventions need to consider adolescent-heterogeneity and driving-related factors.
The intractable global road safety problem of the overrepresentation of young drivers in road crashes, despite a plethora of intervention, suggests that innovative approaches to understanding – and thus intervening in – road crash risks is required. The current research recognises that young drivers frequently are adolescents, and that adolescence is characterised by rapid physical, psychological, cognitive, and social development, each of which interacts with, contributes to, and is impacted upon by a wealth of negative, neutral and positive moods and emotions. The literature regarding relevant to adolescent drivers and emotions between 1 January 2005 and 30 September 2015 will be synthesise, in addition to posing future research questions regarding adolescents, emotions, and driving behaviour.
One hundred and three peer-reviewed articles were identified, and these were summarised within emotions and the adolescent (44 papers); emotions, the adolescent, and driving risks (23 papers); emotions, the adolescent, and risky driving behaviour (30 papers); and emotions, the adolescent, and road safety interventions (6 papers). The findings were synthesised within the context of the characteristics of the adolescent driver, their emotions, the driving context and their driving behaviour, including a pictorial representation of two temporal models depicting the sequence via which emotions can impact upon adolescent driving behaviour (Path A in which the adolescent driver experiences emotions after entering the car; Path B in which the adolescent experiences emotions before entering the car).
The relatively recent proliferation of literature pertaining to adolescents, emotions, and their driving behaviour suggests that the breadth of research questions posed in relation to the domains of the adolescent driver, their emotions, the driving context, and their driving behaviour are timely. Indeed, recent applications of systems thinking within road safety, including young driver road safety specifically, maintain that a holistic approach to the understanding of who plays what role in this system that currently contributes to crash risks, and conversely can play a role in effective and efficient intervention, is essential before the real world realisation of a safe road system. Addressing these research questions are fundamental to sustaining progress on the path to young driver road crash prevention through a safe young driver road safety system.
The prevailing perspective in the organizational politics literature is that political skill facilitates heightened employee performance. Indeed, meta-analytic results have consistently found a ...positive relationship between political skill and both task and contextual performance. However, the literature has neglected the possibility of a contingent relationship between political skill and employee performance, despite arguments that organizations are political arenas in which employees also need political will. This is problematic because although politics are described as an ever-present facet of organizations, the extent to which work environments are politicized varies (Pfeffer, 1981), and such contexts can either constrain or enhance organizational behavior (Johns, 2006, 2018). Therefore, underpinned by the multiplicative framework of performance (i.e., P = f(M × A × C); Hirschfeld et al., 2004), we argue that the effects of political skill on employee task and contextual performance are contingent upon employee political will and the degree to which the work context is politicized. Results from a sample of working adults and their supervisors provided support for our hypothesis. Namely, political skill and political will interacted to predict heightened levels of task performance and citizenship behavior within more political contexts, but not within less political contexts. The contributions of this study to the politics literature are discussed commensurate with this study's associated strengths and limitations.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ
Although much research has examined human resource management (HRM), managers’ roles in HRM seem to have been ancillary to this area of research. That is, HRM theory and research largely has advanced ...with a focus on policies, practices, systems, and their implementation and effectiveness, with less attention focused on the managers responsible for the design, adoption, enactment, and implementation of HRM strategy and practice. The purpose of this review is to examine extant research to determine the state of knowledge of the role of managers across organizational hierarchy in HRM. Thus, we review empirical literature for studies that include aspects of the impact lower-to-middle managers, human resource managers, top management teams, CEOs, and boards of directors have on HRM content, process, and outcomes. On the basis of the findings of this systematic, multilevel review, we discuss avenues for future research at each specific manager’s level, as well as general opportunities and challenges for research on managers’ roles in HRM across all hierarchical levels.
We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen and examined potential correlates of endoxifen concentration levels in serum including ...cytochrome P450 2D6 (CYP2D6) metabolizer phenotype and body mass index (BMI). Concentration levels of tamoxifen, endoxifen, 4‐hydroxytamoxifen (4OH‐tamoxifen), and N‐desmethyltamoxifen (ND‐tamoxifen) were measured from samples taken from 1,370 patients with estrogen receptor (ER)‐positive breast cancer who were participating in the Women's Healthy Eating and Living (WHEL) Study. We tested these concentration levels for possible associations with breast cancer outcomes and found that breast cancer outcomes were not associated with the concentration levels of tamoxifen, 4‐hydroxytamoxifen, and ND‐tamoxifen. For endoxifen, a threshold was identified, with women in the upper four quintiles of endoxifen concentration appearing to have a 26% lower recurrence rate than women in the bottom quintile (hazard ratio (HR) = 0.74; 95% confidence interval (CI), (0.55–1.00)). The predictors of this higher‐risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and lower tamoxifen concentrations as compared with the mean for the cohort as a whole. This study suggests that there is a minimal concentration threshold above which endoxifen is effective against the recurrence of breast cancer and that ~80% of tamoxifen takers attain this threshold.
Clinical Pharmacology & Therapeutics (2011) 89 5, 718–725. doi:10.1038/clpt.2011.32
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