The generation of creative ideas and their manifestation as new products (NPs) are fundamental innovation activities of product innovation teams. Despite the importance of generating creative ideas ...at the fuzzy front end of the product innovation process, our understanding of antecedents and consequences of creativity of product innovation teams is limited. Drawing on Shane and Ulrich's organization design perspective of innovation, this study aims at examining the intermediary role of creativity as a critical link between team dynamics and product competitive advantage. In this study, the authors focus on NP and marketing program (MP) creativity in product innovation teams. They develop and empirically test a model that examines how internal and external team dynamics influence NP and MP creativity, and how NP and MP creativity affect product competitive advantage as a strategic innovation outcome. The study uses 206 matched responses from senior managers and product team leaders in high‐tech manufacturing firms in the United States to avoid common‐method bias. The authors use maximum likelihood estimation in a structural equation model to empirically test the proposed model. They find that two separate dimensions of creativity—novelty and meaningfulness—are differentially affected by team dynamics. For example, NP novelty as a result of divergent process is predominantly influenced by external team factors such as market‐based reward system and planning process formalization. On the other hand, NP meaningfulness as a result of convergent process is dominantly influenced by internal team factors such as social cohesion and superordinate identity. In addition, MP novelty is determined by social cohesion, superordinate identity, planning process formalization, and encouragement to take risks, while MP meaningfulness is influenced by social cohesion and planning process formalization. Our findings also suggest that NP novelty and meaningfulness, but not MP novelty and meaningfulness, play important intermediary roles in determining product competitive advantage. This study contributes to narrowing the important gap in the literature by examining the effect of team dynamics on creativity and by linking creativity to strategic innovation outcomes. Our study suggests that a firm's ability to manage team dynamics toward generating creative NPs and MPs constitutes a dynamic capability that can provide a competitive advantage over the competition.
The ability to generate and market creative ideas in new products (NPs) and related marketing programs (MPs) in response to changing market needs is key to the success of a firm. This research ...examines the mediating role of NP and MP creativity between market orientation and NP success. The authors investigate (1) whether market orientation facilitates or inhibits creativity, (2) whether creativity influences NP performance, and (3) how to define and measure creativity in the NP development and launch contexts. They use a two-stage sampling frame to collect 312 sets of responses from managers and NP team leaders and thereby address the potential for common method bias in measures of creativity and NP performance. The findings indicate that NP and MP creativity mediates the relationship between market orientation and NP success. The authors also show that the meaningfulness dimension, rather than the novelty dimension, of creativity is of greater importance in explaining the link between market orientation and NP success. The empirical results provide significant theoretical and managerial implications for NP strategy.
The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we ...discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution.
Clinical Pharmacology & Therapeutics (2013); 93 3, 252–259. doi:10.1038/clpt.2012.237
The molecular chaperone Hsp90 is not only of major current interest in fundamental biological research but also recognised as an exciting new target for the treatment of cancer and other diseases. In ...addition to playing an important role in response to proteotoxic heat shock and others stresses, Hsp90 is also critical for maintaining normal cellular homeostasis. Hsp90 is responsible for ensuring the conformational stability, shape and function of a selected range of key proteins, including many kinases and transcription factors. Furthermore, recent studies show that Hsp90 plays a key role in development and evolution. Hsp90 is overexpressed in cancer cells and is thought to be involved in dealing with the cellular stress associated with malignancy, as well as being essential for a range of key oncogenic proteins, including ErbB2, Raf-1, Akt/PKB, mutant p53 and many others. A major attraction of Hsp90 inhibitors is their potential to inhibit a range of ‘mission critical’ cancer pathways, thereby blocking all of the ‘hallmark traits’ of malignancy and exhibiting broad-spectrum antitumour activity. The first-in-class Hsp90 inhibitor 17AAG has entered clinical trials with promising early results and a range of other agents is under investigation and preclinical development. This article reviews the current status and future prospects for the exploitation of Hsp90 as a new molecular target for cancer treatment.
It is well established that people with irritable bowel syndrome (IBS) have higher levels of anxiety and depression compared with controls. However, the role of these as risk factors is less clearly ...established. The aims of this systematic review were to investigate: (1) whether anxiety and/or depression predict IBS onset; (2) the size of the relative risk (RR) of anxiety versus depression in IBS onset. Subgroup analyses explored if methodological factors affected the overall findings.
Prospective cohort or case-control studies were included if they: (1) focused on the development of IBS in population-based or gastroenteritis cohorts; (2) explored the effects of anxiety and/or depression at baseline as predictors of IBS onset at a future point. In all, 11 studies were included of which eight recruited participants with a gastrointestinal infection. Meta-analyses were conducted.
The risk of developing IBS was double for anxiety cases at baseline compared with those who were not RR 2.38, 95% confidence interval (CI) 1.58-3.60. Similar results were found for depression (RR 2.06, 95% CI 1.44-2.96). Anxiety and depression seemed to play a stronger role in IBS onset in individuals with a gastrointestinal infection although this could be attributed to other differences in methodology, such as use of diagnostic interviews rather than self-report.
The findings suggest that self-reported anxiety and depression provide a twofold risk for IBS onset. There is less support for the role of anxiety or depressive disorder diagnosed using clinical interview. These findings may have implications for the development of interventions focused on IBS prevention and treatment.
Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of ...animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on the welfare and use of animals in cancer research. All experiments should incorporate the 3Rs: replacement, reduction and refinement. Focusing on animal welfare, we present recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models (e.g., genetically engineered, orthotopic and metastatic); therapy (including drugs and radiation); imaging (covering techniques, anaesthesia and restraint); humane endpoints (including tumour burden and site); and publication of best practice.
The common marmoset (Callithrix jacchus) is uniquely suited for longitudinal studies of cognitive aging, due to a relatively short lifespan, sophisticated cognitive abilities, and patterns of brain ...aging that resemble those of humans. We examined cognitive function and fine motor skills in male and female marmosets (mean age ∼5 at study entry) followed longitudinally for 2 years. Each year, monkeys were tested on a reversal learning task with three pairs of stimuli (n = 18, 9 females) and a fine motor task requiring them to grasp small rewards from two staircases (Hill and Valley test, n = 12, 6 females). There was little evidence for a decline in cognitive flexibility between the two time points, in part because of practice effects. However, independent of year of testing, females took longer than males to reach criterion in the reversals, indicating impaired cognitive flexibility. Motivation was unlikely to contribute to this effect, as males refused a greater percentage of trials than females in the reversals. With regards to motor function, females were significantly faster than males in the Hill and Valley task. From Year 1 to Year 2, a slight slowing of motor function was observed in both sexes, but accuracy decreased significantly in males only. This study (1) demonstrates that marmosets exhibit sex differences in cognitive flexibility and fine motor function that resemble those described in humans; (2) that changes in fine motor function can already be detected at middle‐age; and (3) that males may experience greater age‐related changes in fine motor skills than females. Additional data points will determine whether these sex and age differences persist over time.
Sex differences in cognition and motor function as marmosets age.
There is extensive evidence from the molecular and genomic analysis of human cancers that the PI 3-kinase (phosphoinositide 3-kinase)-Akt/PKB (protein kinase B) pathway is deregulated in malignant ...progression. Furthermore, the causal involvement of PI 3-kinase is supported by gene-knockout mouse models. Prototype inhibitors show evidence of anticancer activity in vitro and in vivo animal models. The recent development of isoform-selective inhibitors shows considerable promise for cancer treatment.
Most firms struggle with the challenge of managing their key customer accounts. There is a significant gap between the importance of this organizational design problem in practice and the research ...attention paid to it. Sound academic research on key account management (KAM) is limited and fragmented. Drawing on research on KAM and team selling, the authors develop an integrative conceptualization of KAM and define key constructs in four areas: (1) activities, (2) actors, (3) resources, and (4) approach formalization. Adopting a configurational perspective to organizational research, the authors then use numerical taxonomy to empirically identify eight prototypical KAM approaches on the basis of a cross-industry, cross-national study. The results show significant performance differences among the approaches. Overall, the article builds a bridge between marketing organization research and relationship marketing research.
The cochaperone CDC37 promotes the association of HSP90 with the protein kinase subset of client proteins to maintain their stability and signalling functions. HSP90 inhibitors induce depletion of ...clients, which include several oncogenic kinases. We hypothesized that the targeting of CDC37 using siRNAs would compromise the maturation of these clients and increase the sensitivity of cancer cells to HSP90 inhibitors. Here, we show that silencing of CDC37 in human colon cancer cells diminished the association of kinase clients with HSP90 and reduced levels of the clients ERBB2, CRAF, CDK4 and CDK6, as well as phosphorylated AKT. CDC37 silencing promoted the proteasome-mediated degradation of kinase clients, suggesting a degradation pathway independent from HSP90 binding. Decreased cell signalling through kinase clients was also demonstrated by reduced phosphorylation of downstream substrates and colon cancer cell proliferation was subsequently reduced by the inhibition of the G1/S-phase transition. Furthermore, combining CDC37 silencing with the HSP90 inhibitor 17-AAG induced more extensive and sustained depletion of kinase clients and potentiated cell cycle arrest and apoptosis. These results support an essential role for CDC37 in concert with HSP90 in maintaining oncogenic protein kinase clients and endorse the therapeutic potential of targeting CDC37 in cancer.
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