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Introduction: The cell cycle cyclin-dependent kinases (CDKs) play a critical role in controlling the transition between cell cycle phases, as well as cellular transcription. Aberrant CDK activation...

Lego Serious Play was founded within the Lego Corporation in the mid-90s as a response to an unusual problem why a company that sold creativity by the kilo was struggling for market share, profit and new thinking. Built from the ground up as a make-or-break proposition, the LSP process is an industry strength business solution designed to create conducive conditions for problem recognition, knowledge creation, and shared understanding. Based on these condition, and the 2010 open source licence of the protocol, this paper outlines the Lego Serious Play process, the history and origin of the method, and the seven principles underpinning its operation. The paper then outlines the adaptation of the LSP method from industry to academy, to showcase how to bring the technique into the classroom. Educators can use the step by step guide to construct a classroom activity that draws on Lego Serious Play to further promote key graduate outcomes of communication, creativity and shared understanding.

© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Purpose: Articles 19, 26 and 27 of the Universal Declaration of Human Rights and Articles 4, 9 and 21 of the Convention on the Rights of Persons with Disabilities promote the human rights of communication, education, use of technology and access to information. Social media is an important form of online communication, and Twitter increases users’ visibility, influence and reach online. The aim of this sociotechnical research was to determine the impact of teaching three people who use Augmentative and Alternative Communication (AAC) to use Twitter. Method: Three participants were trained in ways of using Twitter strategically. Data collected from participants’ Twitter profiles were examined to determine the impact of training on Twitter follower count, frequency of tweeting, tweet content and the development of social networks. Data were also examined using (1) KH Coder software analysis and visualisation of co-occurring networks in the text data, based on word frequencies; and (2) Gephi software analysis to show the Twitter network for each participant. Result: Two participants showed an improvement in Twitter skills and strategies. Conclusions: Twitter can be used to improve social connectedness of people who use AAC, and should not be overlooked in relation to communication rights.

Summary The CDK4/6 inhibitor, palbociclib (PAL), significantly improves progression-free survival in HR+/HER2− breast cancer when combined with anti-hormonals. We sought to discover PAL resistance mechanisms in preclinical models and through analysis of clinical transcriptome specimens, which coalesced on induction of MYC oncogene and Cyclin E/CDK2 activity. We propose that targeting the G1 kinases CDK2, CDK4, and CDK6 with a small-molecule overcomes resistance to CDK4/6 inhibition. We describe the pharmacodynamics and efficacy of PF-06873600 (PF3600), a pyridopyrimidine with potent inhibition of CDK2/4/6 activity and efficacy in multiple in vivo tumor models. Together with the clinical analysis, MYC activity predicts (PF3600) efficacy across multiple cell lineages. Finally, we find that CDK2/4/6 inhibition does not compromise tumor-specific immune checkpoint blockade responses in syngeneic models. We anticipate that (PF3600), currently in phase 1 clinical trials, offers a therapeutic option to cancer patients in whom CDK4/6 inhibition is insufficient to alter disease progression.

SummaryPalbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6 and used as a first-line treatment for patients with estrogen receptor positive breast cancer. It has been shown that patients have improved progression-free survival when treated in combination with fulvestrant, an estrogen receptor antagonist. However, the mechanisms for this survival advantage are not known. We sought to analyze metabolic and transcriptomic changes in MCF-7 adenocarcinoma breast cancer cells following single and combined treatments to determine if selective metabolic pathways are targeted during combination therapy. Our results showed that individually, the drugs caused metabolic disruption to the same metabolic pathways, however fulvestrant additionally attenuated the pentose phosphate pathway and the production of important coenzymes. A comprehensive effect was observed when the drugs were applied together, confirming the combinatory therapy′s synergism in the cell model. This study highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.Highlights○First study employing multi-omics to investigate combined therapy on breast cancer cells○Fulvestrant attenuates the pentose phosphate pathway and coenzyme production○Synergism of palbociclib and fulvestrant was confirmed in vitro○Altered key pathways have been identifiedeTOC BlurbJohnson et al. applied an innovative multi-omics approach to decipher metabolic pathways affected by single versus combination dosing of palbociclib and fulvestrant in estrogen receptor positive breast cancer. Key metabolites and genes were correlated within metabolic pathways and shown to be involved in the drugs′ synergism.

Purpose: Endocrine therapy, using tamoxifen or an aromatase inhibitor, remains first-line therapy for the management of estrogen receptor (ESR1)–positive breast cancer. However, ESR1 mutations or other ligand-independent ESR1 activation mechanisms limit the duration of response. The clinical efficacy of fulvestrant, a selective estrogen receptor downregulator (SERD) that competitively inhibits agonist binding to ESR1 and triggers receptor downregulation, has confirmed that ESR1 frequently remains engaged in endocrine therapy–resistant cancers. We evaluated the activity of a new class of selective estrogen receptor modulators (SERM)/SERD hybrids (SSH) that downregulate ESR1 in relevant models of endocrine-resistant breast cancer. Building on the observation that concurrent inhibition of ESR1 and the cyclin-dependent kinases 4 and 6 (CDK4/6) significantly increased progression-free survival in advanced patients, we explored the activity of different SERD– or SSH–CDK4/6 inhibitor combinations in models of endocrine therapy–resistant ESR1+ breast cancer. Experimental Design: SERDs, SSHs, and the CDK4/6 inhibitor palbociclib were evaluated as single agents or in combination in established cellular and animal models of endocrine therapy–resistant ESR1+ breast cancer. Results: The combination of palbociclib with a SERD or an SSH was shown to effectively inhibit the growth of MCF7 cell or ESR1-mutant patient-derived tumor xenografts. In tamoxifen-resistant MCF7 xenografts, the palbociclib/SERD or SSH combination resulted in an increased duration of response as compared with either drug alone. Conclusions: A SERD– or SSH–palbociclib combination has therapeutic potential in breast tumors resistant to endocrine therapies or those expressing ESR1 mutations. Clin Cancer Res; 21(22); 5121–30. ©2015 AACR. See related commentary by DeMichele and Chodosh, p. 4999

Purpose: The aim of this study was to investigate the Twitter experiences of adults with severe communication disabilities who use augmentative and alternative communication (AAC) to inform Twitter training and further research on the use of Twitter in populations with communication disabilities. Method: This mixed methods research included five adults with severe communication disabilities who use AAC. It combined (a) quantitative analysis of Twitter networks and (b) manual coding of tweets with (c) narrative interviews with participants on their Twitter experiences and results. Results: The five participants who used AAC and Twitter were diverse in their patterns and experiences of using Twitter. Twitter networks reflected interaction with a close-knit network of people rather than with the broader publics on Twitter. Conversational, Broadcast and Pass Along tweets featured most prominently, with limited use of News or Social Presence tweets. Tweets appeared mostly within each participant's micro- or meso-structural layers of Twitter. Conclusions: People who use AAC report positive experiences in using Twitter. Obtaining help in Twitter, and engaging in hashtag communities facilitated higher frequency of tweets and establishment of Twitter networks. Results reflected an inter-connection of participant Twitter networks that might form part of a larger as yet unexplored emergent community of people who use AAC in Twitter.Implications for RehabilitationTwitter can be used as an important vehicle for conversation and a forum for people with communication disabilities to exchange information and participate socially in online communities.It is important that information and resources relating to the effective use of Twitter for a range of purposes are made available to people with communication disabilities who wish to take up or maintain use of Twitter.People with communication disabilities might benefit from support in using Twitter to meet their goals relating to participation in online forums and information exchange. Practitioners need to consider how their own social media skills might impact on service delivery and supporting these goals.

In this reply to Lilienfeld, Marshall, Todd, and Shane (2015) we provide a social marketing perspective on ways that facilitated communication (FC) is presented and discussed on social media platforms, in the field of augmentative and alternative communication (AAC). The growth in uptake and use of FC in recent years has occurred in the context of rapid growth in mobile technologies and AAC integrated with social media and online learning. Social media have been used to disseminate both materials that are supportive of FC and materials that provide scientific evidence of facilitator influence over authorship in FC. In order to illustrate how social media are being used to spread information about FC, we present a limited scan of two social media sites—TwitterTM and YouTubeTM—for information about FC. In this paper we discuss barriers to evidence and facilitators for FC in social media and consider the role that social marketing might play in relation to FC. Clinical implications for using social m...

© 2017 International Society for Augmentative and Alternative Communication. Augmentative and alternative communication (AAC) social media research is relatively new, and is built on a foundation of research on use of the Internet and social media by people with communication disabilities. Although the field is expanding to include a range of people who use AAC, there are limitations and gaps in research that will need to be addressed in order to keep pace with the rapid evolution of social media connectivity in assistive communication technologies. In this paper, we consider the aims, scope, and methodologies of AAC social media research, with a focus on social network sites. Lack of detailed attention to specific social network sites and little use of social media data limits the extent to which findings can be confirmed. Increased use of social media data across a range of platforms, including Instagram and YouTube, would provide important insights into the lives of people who use AAC and the ways in which they and their supporters use social media. New directions for AAC social media research are presented in line with those discussed at the social media research symposium at the International Society for Augmentative and Alternative Communication in Toronto, Canada, on August 12, 2016.

In this chapter we propose a review of the influence of halal certification on consumer perceptions of food quality. As one of the few systematic studies that examines the influence of the halal sign in advertising as a quality assurance marker, this research investigates the use and effectiveness of consumers’ perceptions of halal certification as a quality assurance mark in the context of the Malaysian multicultural society. Malaysia is moving to become a global hub for halal certification and production.

Social marketing is based on the adaptation of the contemporary commercial marketing theory and practice as a means of guiding and aiding social change campaigns. This paper draws on recent developments in commercial marketing theory and prior work in social marketing definitions to create a new definition of social marketing which integrates the commercial definitions of the American Marketing Association (AMA) and Chartered Instituted of Marketing (CIM) with established social marketing definitions from the past thirty years of social marketing conceptual development. The development of the definition is supported through the use of qualitative research technique of text mining which uncovered a core series of principles consistent to the historical definitions of social marketing. Finally, the new definition also introduces clarification of several key subcomponent elements as part of an expanded definition of social marketing.

Success in social marketing is rarely clear cut and even more rarely believed to have been achieved. Social marketing practitioners are under increasing scrutiny to benchmark efficiencies of social change programs to achieve ‘success’ outcomes. Using road safety as a case study, this paper addresses the complex nature of success within a social marketing context. First, we discuss the conundrum facing road safety in articulating ‘success’ when at policy level success is quantified objectively, yet at a community level perceptions of system failure are equated with individual death. Methodologically we apply comparative empirical approaches to examine perceptual versus objective road safety outcomes. The paper concludes with a discussion and proposal of alternate strategies for measuring programmatic success, and raise issues concerning the longevity of developing competitive and sustainable benchmarks.

Political marketing theory has developed and evolved in conjunction with advancements in political science and commercial marketing. Commercial marketing has been increasingly interested in developing marketing mechanisms which allows it to satisfy the core customer groups while also meeting the broader needs of the community and other stakeholders. Political marketing has the opportunity to build a marketing framework that focuses on delivering value to a core target market (voters, supporters) and addressing the needs of society at large. The paper outlines a new definition of political marketing to meet the challenges of addressing the needs of the political marketplace, political party stakeholders, and the broader social agenda.

PurposeThe paper aims to describe the application of two key service quality frameworks for improving the delivery of postgraduate research supervision. The services quality frameworks are used to identify key areas of overlap between services marketing practice and postgraduate supervision that can be used by the supervisor to improve research supervision outcomes for the student.Design/methodology/approachThe paper is a conceptual and theoretical examination of the two streams of literature that proposes a supervision gap model based on the services gap literature, and the application of services delivery frameworks of co‐creation and service quality.FindingsServices marketing literature can inform the process of designing and delivering postgraduate research supervision by clarifying student supervisor roles, setting parameters and using quality assurance frameworks for supervision delivery. The five services quality indicators can be used to examine overlooked areas of supervision delivery, and the co‐creation approach of services marketing can be used to empower student design and engaged in the quality of the supervision experience.Research limitations/implicationsAs a conceptual paper based on developing a theoretical structure for applying services marketing theory into the research supervision context, the paper is limited to suggesting potential applications. Further research studies will be necessary to test the field implementation of the approach.Practical implicationsThe practical implications of the paper include implementation suggestions for applying the supervisor gaps for assessing areas of potential breakdown in the supervision arrangement.Originality/valueThe paper draws on two diverse areas of theoretical work to integrate the experience, knowledge and frameworks of commercial services marketing into the postgraduate research supervision literature.

Social change through the use of social marketing has often grappled with the principle of “social good”. Building on the tradition of Klein and Laczniak (2009, 2012) in applying Catholic Social Teaching (CST) to commercial marketing, this paper outlines the points of similarity and divergence of contemporary social marketing frameworks with CST. As social marketing theory and practice moves away from its marketing parent discipline roots, this paper argues that CST with its focus on human dignity, subsidiary and the common good provides an increasingly relevant and compatible framework with which to evaluate ethical issues emerging in the social marketing domain. There is potential for social marketers to draw on the intellectual work underpinning CST to inform social marketing practice in engaging in the delivery of social benefit independent of the religious tradition.

Social marketing has been a discipline founded on the open and robust exchange of ideas regarding the nature of social change, the adaptation and adoption of commercial marketing, and the ethics of influencing behavior for beneficial outcomes. As a practical discipline, with a strong theoretical and philosophical framework, it also relies on the open communication between academic and practitioner to ensure those researching and those implementing are speaking the same social marketing language. In early 2006, the international social marketing mailing list (SOC-MKT) was subject to a short, albeit critical, debate on the ethics and nature of social marketing, the social marketing tool kit, and the role of social marketers. This article reports on the summary and implications of the debate among academics, practitioners, and founders of the social marketing discipline.

The paper reports on the core challenges faced by the nonprofit, political and social marketing disciplinary areas and suggests a series of research agendas to develop theory and practice to meet these challenges. � Social marketing’s research agenda involves the continued adaptation of the new developments in commercial marketing, whilst building a base of social marketing theory and best practice benchmarks that can be used to identify, clarify and classify the boundaries of social marketing against social change techniques. � Nonprofit marketing is pursuing the dual research agenda of developing the theory and practice of social entrepreneurship whilst seeking deeper consumer-based research to understand motivations for charitable behaviour and gift giving. � Political Marketing’s research agenda looks for an increase in the level of background research, core data and market research to use as a basis for developing more advanced theoretical and practical models. In addition, as political marketing is being transferred internationally between a range of political and electoral systems, there is a need for comparative research into both the relevance and effectiveness of these techniques to isolate nation independent and nation dependent political marketing strategies and campaigns.

To review the literature relating to use of social media by people with a traumatic brain injury (TBI), specifically its use for social engagement, information exchange or rehabilitation.A systematic review with a qualitative meta-synthesis of content themes was conducted. In June 2014, 10 databases were searched for relevant, peer-reviewed research studies in English that related to both TBI and social media.Sixteen studies met the inclusion criteria, with Facebook™ and Twitter™ being the most common social media represented in the included studies. Content analysis identified three major categories of meaning in relation to social media and TBI: (1) risks and benefits; (2) barriers and facilitators; and (3) purposes of use of social media. A greater emphasis was evident regarding potential risks and apparent barriers to social media use, with little focus on facilitators of successful use by people with TBI.Research to date reveals a range of benefits to the use of social media by people with TBI however there is little empirical research investigating its use. Further research focusing on ways to remove the barriers and increase facilitators for the use of social media by people with TBI is needed.

Phosphorylation of the retinoblastoma protein (Rb) by cyclin-dependent kinases 4 and 6 (CDK4/6) is a critical checkpoint for G1/S cell cycle progression and commitment to cellular proliferation. Human malignancies often subvert these control mechanisms through a range of genetic and biochemical adaptations. Accordingly, tumors that depend on CDK4/6 activity for proliferation and survival are particularly sensitive to inhibition of this pathway by palbociclib (Ibrance™), a highly selective inhibitor of CDK4/6 kinase activities. Treatment regimen of palbociclib with letrozole significantly improved progression-free survival in a randomized phase 2 study of women with advanced estrogen receptor-positive (ER+), HER2-negative breast cancer. Likewise, in ER+ breast cancer models palbociclib and estrogen antagonists combine for greater anti-proliferative activity, increased hallmarks of cellular senescence and prolonged durability of response following drug removal. Dual inhibition of CDK4/6 and ER signaling demonstrated robust anti-tumor activity in xenograft studies. The addition of Palbociclib to other targeted therapeutics elicits improved activity in pre-clinical models of several non-breast indications and these effects also manifest through modulation of cellular proliferation, senescence and growth arrest. Data will be presented on the molecular basis of combination benefit with Palbociclib in ER+ breast and other oncology indications. Citation Format: Stephen Dann, John Chionis, Liu Choating, Enhong Chen, Ping Wei, Koleen Eisele, David J. Shields, Paul A. Rejto, Todd VanArsdale. Mechanistic basis of Palbociclib combinatorial activity in ER+ breast cancer and non-breast indications. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Cancer Cell Cycle - Tumor Progression and Therapeutic Response; Feb 28-Mar 2, 2016; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(11_Suppl):Abstract nr A08.

Phosphorylation of the retinoblastoma protein (Rb) by cyclin-dependent kinases 4 and 6 (CDK4/6) is a critical checkpoint for G1/S cell cycle progression and commitment to cellular proliferation. Human malignancies often subvert these control mechanisms through a range of genetic and biochemical adaptations. Accordingly, tumors that depend on CDK4/6 activity for proliferation and survival are particularly sensitive to inhibition of this pathway by palbociclib (IbranceTM), a highly selective inhibitor of CDK4/6 kinase activities. Treatment regimen of palbociclib with letrozole significantly improved progression-free survival in a randomized phase 2 study of women with advanced estrogen receptor-positive (ER+), HER2-negative breast cancer. Likewise, in ER+ breast cancer models palbociclib and estrogen antagonists combine for greater anti-proliferative activity, increased hallmarks of cellular senescence and prolonged durability of response following drug removal. Dual inhibition of CDK4/6 and ER signaling demonstrated robust anti-tumor activity in xenograft studies. The addition of Palbociclib to other targeted therapeutics elicits improved activity in pre-clinical models of several non-breast indications and these effects also manifest through modulation of cellular proliferation, senescence and growth arrest. Data will be presented on the molecular basis of combination benefit with Palbociclib in ER+ breast and other oncology indications. Citation Format: Stephen Dann, Jing Yuan, John Chionis, Chaoting Liu, Tao Xie, Nathan V. Lee, Enhong Chen, Ping Wei, Paul A. Rejto, David J. Shields, Todd VanArsdale. Mechanistic basis of Palbociclib combinatorial activity in ER+ breast cancer and non-breast indications. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2740.

Space is the final frontier for e-marketing. Advances in storage space, digital data transmission, and infrastructure development have created a near limitless marketspace that exists over the contemporary physical marketplaces, and as an independent market of ideas, data, experience, and content. This chapter overviews a series of key issues in the use of the new “space” for e-novation with attention given to the rise of user generated content through prosumer activity. This chapter is based on exploring how companies and individuals are currently co-creating value in the dynamic marketplace of the new collaborative platforms, and how these new concepts such as the “home shopping channel”, digital rights management, and user generated distribution channels can factor in the future success on and offline for marketing.

This paper delivers a new Twitter content classification framework based sixteen existing Twitter studies and a grounded theory analysis of a personal Twitter history. It expands the existing understanding of Twitter as a multifunction tool for personal, profession, commercial and phatic communications with a split level classification scheme that offers broad categorization and specific sub categories for deeper insight into the real world application of the service.