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Purpose This purpose of this study is to develop actionable marketing insights regarding why consumers might elect to purchase vintage products. A concept called consumer pastness is introduced, developed and defined to achieve this end. Consumer pastness demonstrably affected consumers’ perceptions of vintage products’ scarcity and consumers’ propensity to purchase vintage items. When applied inside marketing contexts, consumer pastness may also explain how and why consumers distinguish vintage products that are “of the past” from new and second-hand products. The data suggest that when consumers perceive products are characterized by higher consumer pastness the products will be perceived as scarcer, more desirable and more valuable than new or second-hand versions of the same item. Design/methodology/approach A scale was developed to capture three dimensions that comprise consumer pastness and then a pilot study and two experiments were conducted to test the research propositions. Findings Study propositions were confirmed. Consumers perceive vintage products as scarcer and more desirable than other types of products. Originality/value A novel and useful concept is introduced to the marketing literature inside this study. To the best of the authors’ knowledge, this study is the first to investigate and develop theoretical insights regarding how and why consumers perceive vintage products differently from new and second-hand products. The investigations reported below are also the first to develop practical insights regarding how management might respond to these insights about the role consumer pastness plays.

Video research methods provide a powerful yet accessible way for researchers to observe and theorize entrepreneurial phenomena by analyzing entrepreneurship "in motion." Despite the growing uptake of video data in entrepreneurship research, there is no available overview or analysis of current uses of video research methods, which makes it difficult for interested researchers to grasp its value and possibilities. Our systematic review of 142 entrepreneurship research articles published in leading journals reveals three dominant video research methods: (a) videography of entrepreneurship "in the wild" (such as pitching and other naturally occurring practices); (b) video content analysis using entrepreneur-generated videos (such as crowdfunding and archival videos); and (c) video elicitation in "manufactured" contexts (such as interviews and focus groups, experiments and interventions). Building on these studies, we put forward a research agenda for video-based entrepreneurship research that capitalizes on the unique affordances of video to understand the interactional, embodied, material, and emotional nature of entrepreneurial practice.

This article reviews the literature on non-profit volunteering to argue that the concept of ‘work calling’ is critical to broadening our understanding of volunteer motivation and retention. As an emerging concept, work calling is generally used to explain how individuals satisfy their calling by doing meaningful work. This concept is introduced to the issue of volunteer motivation and retention to detail why volunteers decide to join non-profit organisations and then willingly stay longer. Current theories explain volunteer motivation and retention by focusing on individual factors (commitment and job satisfaction) and organisational factors (management practices, volunteer tasks and organisational reputation). This article integrates work calling with these theories and thus contributes two important insights: (a) volunteers may choose to engage in meaningful work and, therefore, experience self-satisfaction and meaningful life by volunteering; and (b) work calling improves current theories of volunteering motivation and retention at both the individual and organisational levels.

PurposeDespite the gains that have been made by adopting contemporary theories of practice in entrepreneurship studies, the field still lacks a comprehensive practice theory of entrepreneurial learning. In this article, we develop a practice theory of entrepreneurial learning by elaborating on the relations between practicing, knowing and learning.Design/methodology/approachUsing a video ethnography of a two-day “Startup Weekend for Refugees” event in Amsterdam, our aim is to further theorise the relational, material and embodied nature of entrepreneurial learning through analysing video fragments of naturally occurring practices.FindingsOur findings demonstrate that entrepreneurial learning transpires through, and is emergent from, practices and their relations. On the one hand, practitioners learn to competently participate in various practices by sensing, observing and experimenting with the meaning of others' gestures and utterances. On the other, the learning of new opportunities for value creation emerges as practitioners connect various practices to one another through translation.Originality/valueThis article contributes by illustrating and explaining real-time instances of learning to develop a practice theory of entrepreneurial learning. This contributes to the literature by detailing the relations between learning, knowing and practising entrepreneurship, which leads to a novel alternative to existing individual- and organisational-level learning theories.

Entrepreneurship has long been recognized as a key socioeconomic activity that is essential for regional economic development. Entrepreneurship research in developing countries often uses macro level or meso level analyses of large surveys to examine institutional constraints and enablers of entrepreneurial activities, which can mask fascinating insights on day to day practices.This book reveals insider perspectives of the everyday struggles of Tanzanian and Zambian entrepreneurs by distinguishing institutional constraints and enablers, and sustainability practices as responses to those opportunities and barriers. The book contributes to existing literature by providing entrepreneurs from sub-Saharan Africa the opportunity to illustrate how their institutional context influences their sustainability practices at the micro level. Written for scholars of Business and Entrepreneurship, this book showcases how entrepreneurs use creative and bricolage methods to implement sustainability practices that contribute to social and environmental well-being.

The compact linear accelerator for research and applications (CLARA) is an ultrabright electron beam test facility being developed at STFC Daresbury Laboratory. The ultimate aim of CLARA is to test advanced free electron laser (FEL) schemes that can later be implemented on existing and future short-wavelength FELs. In addition, CLARA is a unique facility to provide a high-quality electron beam to test novel concepts and ideas in a wide range of disciplines and to function as a technology demonstrator for a future United Kingdom x-ray FEL facility. CLARA is being built in three phases; the first phase, or front end (FE), comprises an S-band rf photoinjector, a linac, and an S-bend merging with the existing versatile electron linear accelerator beam line; the second phase will complete the acceleration to full beam energy of 250 MeV and also incorporate a separate beam line for use of electrons at 250 MeV; and the third phase will include the FEL section. The CLARA FE was commissioned during 2018, and the facility was later made available for user experiments. Significant advancements have been made in developing high-level software and a simulation framework for start-to-end simulations. The high-level software has been successfully used for unmanned rf conditioning and for characterization of the electron beam. This paper describes the design of the CLARA FE, performance of technical systems, high-level software developments, preliminary results of measured beam parameters, and plans for improvements and upgrades. © 2020 authors. Published by the American Physical Society.

In this article, we contend that entrepreneurship studies would greatly benefit from engagement with contemporary theorizations of practice. The practice tradition conceives of the process of entrepreneuring as the enactment and entanglement of multiple practices. Appreciating entrepreneurial phenomena as the enactment and entanglement of practices orients researchers to an ontological understanding of entrepreneuring as relational, material and processual. Therefore, practice theories direct scholars towards observing and explaining the real-time practices of entrepreneuring practitioners. Articles in this special issue on ‘entrepreneurship-as-practice’ are discussed and suggestions for future research and scholarship that utilize contemporary theorizations of practice are offered.

The study of future-making – how practitioners make and enact imagined futures – has become a cornerstone for understanding the temporal dynamics of organization, strategy and entrepreneurship. This article investigates the texture of practical knowledge that enables entrepreneuring practitioners to jointly address the challenges inherent to future-making. We conduct a video ethnography of a business modelling programme producing 79 hours of audio-visual recordings. Using multimodal conversation analysis, we unpack different forms of practical knowledge that simultaneously binds practitioners in a web of mutual expectations and establishes modes of thinking and acting for the creation of imagined futures. This contributes to existing studies by demonstrating that the discursive, embodied and material dimensions of future-making are fundamentally entangled within textures of practical knowledge. Consequently, we shift the mode of theorizing towards non-representationalism, which opens up new frontiers for future research to observe, participate and reflect with practitioners on the textures of practical knowledge constitutive of future-making in different circumstances and contexts.

Heeding calls to generate a creative synthesis between business history and organisation studies, this article analyses the emergence, institutionalisation and digitalisation of record pooling practices through the lens of institutional work. By developing an ‘analytically structured history’, this article contributes to the field of business history by demonstrating the value of practice and boundary work as organising categories. Practice and boundary work capture the continuous, recursive relations between structure and agency when constructing narrative explanations. It also contributes to neo-institutionalist history by demonstrating the embeddedness of institutional work – the everyday motivations and actions to revise practices and boundaries are shown to be intimately shaped by the conditions and affordances of historically-situated technologies.

Little is known of the effect of entrepreneurs’ happiness on living standards in the world’s developing countries. This study explores (1) the causal relationship of entrepreneurs’ happiness and living standards; and (2) examines the interaction effects of socio-demographics (i.e. gender, age and education) and happiness on living standards in a developing context: Zambia. Following a qualitative pre-study with local experts, we develop a quantitative survey study including a unique sample of 170 entrepreneurs in Zambia. The analyses show that the entrepreneurs are relatively happy and an increasing level of happiness is related to an increasing standard of living. Moreover, the entrepreneurs’ happiness moderated by age (i.e. being older and happy) and education (i.e. being better-educated and happy) is a strong positive determinant of their living standard. The entrepreneurs’ awareness of the factors conducive to being happy, as well as the practitioners focussing on the social conditions of happiness, is instrumental.

Understanding experiences of and responses to anxiety is foundational to developing robust theories of entrepreneurial behavior. Using open-ended, vignette and graphical elicitation interviews with 77 entrepreneurs, we inductively investigate the experience of and coping responses to anxiety during the entrepreneurship process. We develop a comprehensive and dynamic goal-striving model to explain experiencing and coping with entrepreneurial anxiety by integrating empirical findings with appraisal and control theories. In doing so, we theorize that entrepreneurial anxiety is endogenous to a cyclical conception of goal-striving, such that various sources of anxiety make sense only in consideration of the goals, standards or values to which they pertain. In this regard, entrepreneurs’ coping responses influence four different points of an iterative goal-striving cycle—an insight that moves beyond problematic static and binary coping classifications.

PurposeEntrepreneurship research in the context of developing countries has typically investigated the ways in which culture, politics or economic institutions prohibit or enable entrepreneurial activities using macro-level surveys and deductive designs. In contrast, the purpose of this paper is to take a micro-institutional perspective to study these three institutions influencing entrepreneurial activities in such a context.Design/methodology/approachThe analysis is based on inductive, qualitative field data from a challenging institutional environment, Tanzania. This includes two focus groups, one with experts and one with entrepreneurs; and 24 individual interviews with entrepreneurs.FindingsEntrepreneurial activities in Tanzania are not constrained only by bureaucracy and arbitrary enforcement, access to capital, competition and consumer spending, but also by language barriers, negative media portrayals and gender disparity. In their favour, recent trade policy, opening up of borders and changing gender relations, has led to more opportunities, but just as important are traditional festivals, marital gift-giving and familial support. Entrepreneurs respond to institutional constraints in many creative ways, including undertaking entrepreneurial strategies, developing inner strength, joining associations, giving back to communities and skilfully managing relations with authorities.Originality/valueThe fine-grained discussion of the findings of this study specifically contributes to theory by illustrating the constraining and enabling role of under-represented institutions, such as festivals and marriages, as well as entrepreneurial creative responses that define everyday entrepreneurial life in a developing country.

With this special issue we aim at furthering the entrepreneurship as practice perspective by grounding the broader and contemporary ‘practice turn’ in social science (Schatzki, Knorr-Cetina, and vo...

Well-being is a concept which can connect together a number of important ideas that have a strong resonance for professional education and practice across the human services. This can critically include considerations of illness, crisis, and loss. Such acute moments in individuals’ lives can be examined through their precipitating events, coping mechanisms, and responses. This article explores some of the dimensions of well-being and how they facilitate a greater understanding of illness, crisis, and loss. These deliberations are then exemplified through a focus on alcohol and other drug use.

Entrepreneurship is widely recognized to play a crucial role in transitioning societies towards sustainability, yet sustainable ventures often have difficulty in attracting talented management employees that are necessary to scale their sustainable opportunities. This study examined 19 qualitative interviews with three interview groups (human resource managers of sustainable ventures, recently hired employees at sustainable ventures, and management professionals looking for employment opportunities) to explain the impediments of attracting management talent and what competitive advantages sustainable ventures may have in the labour market. We discuss how these findings have theoretical and practical implications for scholars and sustainable entrepreneurs by drawing out a number of ways that sustainable ventures may attract management professionals.

Sustainable ventures often lack legitimacy (perceived to be desirable and appropriate) because various stakeholder groups use contradictory institutions (rules and norms) to make their judgements, which leads to there being fewer resources available and higher failure rates. Using an institutional theory framework and a multi-case research design with 15 biofuel ventures operating in the Netherlands, this study asks how sustainable entrepreneurs attempt to gain legitimacy in these circumstances. Analysis reveals that the entrepreneurs use a combination of rhetorical, reconciliatory and institutional change strategies to obtain legitimacy from different stakeholder groups. These findings further our understanding of sustainable entrepreneurial behavior by revealing how and why different legitimation strategies are used in complex institutional environments.

Dying, death, and bereavement do not occur in a social vacuum. How individuals and groups experience these phenomena will be largely influenced by the social context in which they occur. To develop an adequate understanding of dying, death, and bereavement we therefore need to incorporate a sociological perspective into our analysis. This article examines why a sociological perspective is necessary and explores various ways in which sociology can be of practical value in both intellectual and professional contexts. A case study comparing psychological and sociological perspectives is offered by way of illustration.

Scholars adopting a relational ontology of organisational creativity have shifted attention away from a preoccupation with individual minds towards that which is enacted, emergent, shared, unpredictable and contingent. This article follows suit, yet breaks new ground by reconsidering how the mind plays an active role in unfolding creative interactions by building a bridge between literature on organisational creativity, aesthetics and philosophy of imagination. I draw on English Romanticism to craft a theoretical model of organisational creativity as an aesthetic and relational process of shared imagining. This model demonstrates how organisational members use primary and secondary modes of imagination and creative expression to develop, materialise and share perceptions and images of possible futures. By elaborating on their interplay, this article contributes to literature by theorising an active and generative role of mind that does not have the ontological shortcomings of leading theories. In turn, this has a number of implications for literature on entrepreneurship and organisational creativity in terms of situating and embodying creative thinking, explaining the intentionality and motivation for creative actions, overcoming perceptual differences and changing practices and routines.

In response to cellular stress, the p53 tumor suppressor is activated to modulate cell cycle progression, DNA repair, and cell death. The activity of p53 is tightly regulated by MDM2, an E3 ubiquitin ligase that targets p53 for proteasomal degradation. Inhibition of the MDM2-p53 interaction in tumors carrying wild-type p53 can therefore reactivate p53 and elicit an anti-cancer effect. Small molecule inhibitors of the MDM2-p53 interaction remains a promising strategy for cancer therapy and a number of these compounds are in clinical development. An isoindolinone series, identified by the Northern Institute for Cancer Research (NICR), has been used as a starting point for the development of potent MDM2-p53 inhibitors. Structure based drug design was applied during lead optimisation to gain potency whilst also focusing on stabilizing the main metabolically labile position and reducing lipophilicity. This approach led to potent compounds with EC50 Citation Format: Lynsey Fazal, Maria Ahn, Luke Bevan, Ildiko Buck, Juan Castro, Gianni Chessari, Ben Cons, Keisha Hearn, Steven Howard, Chris Johnson, Judith Reeks, Emiliano Tamanini, Neil Thompson, Hugh Walton, Pamela Williams, Ruth H. Bawn, Tim J. Blackburn, Celine Cano, Sarah J. Cully, Bernard Golding, Roger Griffin, Karen Haggerty, Ian Hardcastle, Herbie Newell, Martin Noble, Huw Thomas, Elaine Willmore, Yan Zhao, Steve Wedge. Development of a potent class of small molecule inhibitors of the MDM2-p53 protein-protein interaction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1652.

Non-small cell lung cancer (NSCLC) molecular profiling is a key factor in treatment selection. Although, patients with NSCLC tumors harboring EGFR or ALK mutations can benefit from personalized therapies, there are currently no approved targeted therapies for KRAS mutant tumors which occur in 25% to 30% of patients with NSCLC. The constitutive activation of the MAPK pathway in these tumors provides a rationale for targeting effectors such as MEK1/2 (MEK) or ERK1/2 (ERK). Inhibitor of MEK kinase have been tested clinically in KRAS-mutant NSCLC but results have been disappointing, possibly because compensatory signaling such as the reactivation of ERK is triggered following the inhibition of MEK, leading to cancer cell survival. Therefore, targeting ERK directly represents an attractive therapeutic approach. As previously described, we have developed a novel, potent and selective ERK inhibitor identified by fragment-based drug discovery which has potent activity in vitro and in vivo. Here, we demonstrate the activity of this lead compound in KRAS-mutant NSCLC models. Our novel ERK inhibitor was tested in a panel of 440 human cancer cell lines of which the KRAS NSCLC population was identified as particularly sensitive. 62% of the KRAS-mutant NSCLC cell lines tested, exhibited antiproliferative IC50s ranging from 1 nM to 500 nM. This lead compound also inhibited ERK downstream signaling in KRAS NSCLC models both in vitro and in vivo. Indeed, the phosphorylation level of the ERK substrate, RSK, was strongly decreased in HCC-44 and Calu-6 xenograft tumors 2h after oral administration of the lead compound at 50 mg/kg. Levels of pRSK remained below those of untreated tumors for up to 16h in HCC-44 tumors and 24h in Calu-6 tumors. We also confirmed that, the ERK inhibitor conferred a decrease in phosphorylation of ERK itself in both models. The inhibition of ERK signaling corresponded to significant anti-tumor activity in these models with a daily oral administration of 50 mg/kg compound leading to significant tumor regression in subcutaneous models of HCC-44 (18.3% T/C) and Calu-6 (8.9% T/C) xenograft tumors. This work demonstrates the in vitro and in vivo activity of a novel, highly potent, selective ERK inhibitor in models of KRAS-mutant NSCLC. These data support the further optimisation of this series of compounds for clinical development. Citation Format: Aurelie Courtin, Luke Bevan, Tom Heightman, Birikiti Kidane, Justyna Kucia-Tran, John Lyons, Sandra Muench, Alpesh Shah, Lukas Stanczuk, Neil Thompson, Nicola Wallis, Nicola Wilsher, Joanne Munck. A novel ERK1/2 inhibitor has potent activity in KRAS-mutant non-small cell lung cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5781.

Objective: To pilot a brief cognitive behavioral therapy-based intervention designed to enhance client empowerment and the therapeutic alliance with the aim of reducing clozapine discontinuation. Design: Randomized controlled trial with two conditions: therapy (Alliance Enhancement Therapy [AET]) and control (psychoeducation alone). Assess ments took place at: baseline, twelve weeks and twenty-four weeks (follow-up). The primary outcomes were levels of empowerment, alliance with the clinical team and clozapine discontinuation. Secondary outcomes included insight and other clinical measures. Methods: Treatment-resistant patients who had a diagnosis of schizophrenia, had been registered for clozapine in the previous month and who consented, were independently randomized to active versus control therapy. Results: Thirty-nine patients entered the study. Both groups improved on the main measures with no differential effects of AET intervention. However, patients who attended for more than five sessions showed a differen tial enhancement of working alliance. Conclusions: Although the active therapy showed no general improvement, it did provide some added value over psychoeducation alone when patients attended several sessions. Effective methods of reducing clozapine discontinuation and engaging patients in psychosocial interventions are needed.

Aurora kinases play a key role in regulating mitotic division and are attractive oncology targets. AT9283, a multi-targeted kinase inhibitor with potent activity against Aurora A and B kinases, inhibited growth and survival of multiple solid tumor cell lines and was efficacious in mouse xenograft models. AT9283-treatment resulted in endoreduplication and ablation of serine-10 histone H3 phosphorylation in both cells and tumor samples, confirming that in these models it acts as an Aurora B kinase inhibitor. In vitro studies demonstrated that exposure to AT9283 for one complete cell cycle committed an entire population of p53 checkpoint-compromised cells (HCT116) to multinucleation and death whereas treatment of p53 checkpoint-competent cells (HMEC, A549) for a similar length of time led to a reversible arrest of cells with 4N DNA. Further studies in synchronized cell populations suggested that exposure to AT9283 during mitosis was critical for optimal cytotoxicity. We therefore investigated ways in which these properties might be exploited to optimize the efficacy and therapeutic index of Aurora kinase inhibitors for p53 checkpoint compromised tumors in vivo. Combining Aurora B kinase inhibition with paclitaxel, which arrests cells in mitosis, in a xenograft model resulted in promising efficacy without additional toxicity. These findings have implications for optimizing the efficacy of Aurora kinase inhibitors in clinical practice.

Housing affordability and sustainable development are not polarized ideologies as both are necessary with increasing urbanization. Researchers must bridge the gap between current median house pricing and target affordable house pricing while pursuing sustainability. This paper examines the potential of initial construction cost and ongoing utilities and transport cost reduction, through the integration of sustainable housing design and transit oriented development principles in a commuter energy and building utilities system (CEBUS). It also introduces current research on the development of a dynamic simulation model for CEBUS applications in the Australian property development and construction industry.

Objectives. The authors investigated the effects of cigarette smoking on midlife cognitive performance. Methods. Multiple regression was used to test the association between cigarette smoking and changes in cognitive test scores among male and female members of the British 1946 birth cohort aged between 43 and 53 years. Results. Smoking was associated with faster declines in verbal memory and with slower visual search speeds. These effects were largely accounted for by individuals who smoked more than 20 cigarettes per day and were independent of sex, socioeconomic status, previous (adolescent) cognitive ability, and a range of health indicators. Conclusions. The present results show that heavy smoking is associated with cognitive impairment and decline in midlife. Smokers who survive into later life may be at risk of clinically significant cognitive declines.

The RAS-RAF-MEK-ERK signalling cascade is activated through mutations in RAS or RAF in over 30% of cancers. The successful development of inhibitors of BRAF and MEK kinases has led to effective treatment particularly of melanomas whose tumor growth is driven by activating mutations in BRAF such as V600E. Despite these successes, resistance emerges after several months, leading to increased signaling through ERK1/2. This has prompted the development of direct inhibitors of ERK1/2, several of which are in early clinical trials. The majority of clinical ERK1/2 inhibitors are ATP competitive, blocking ERK1/2 catalytic phosphorylation of downstream substrates such as RSK, but do not modulate phosphorylation of ERK1/2 by MEK. Crystal structural studies performed by us and others on the pERK1/2 modulating inhibitor SCH772984 suggested that it induces a conformational change in the glycine-rich loop of ERK2, which leads to Tyr36 becoming tucked under the loop and creating a new binding pocket. We hypothesized that this binding mode might underlie the ability of SCH772984 to block the phosphorylation of ERK1/2, and initiated a fragment-based approach to develop novel, orally bioavailable inhibitors that elicit a similar conformational change and also modulate the phosphorylation of ERK1/2. Using screening methods including high-throughput X-ray crystallography and biophysical assays, we identified fragments binding to both the hinge and the inducible pocket of ERK2. Progressive rounds of structure-guided fragment optimization and growing led to an understanding of inhibitor structure determinants required to induce the conformational change in ERK2. These efforts, together with iterative optimization in a screening cascade including measurement of pRSK and pERK levels and antiproliferative activity in RAS and BRAF mutant cells, led to the discovery of a novel series of pERK modulating ERK1/2 inhibitors. The lead compound shows low nanomolar potency in biochemical ERK1/2 assays and an excellent kinome selectivity profile. In BRAF and RAS mutant cell lines, the lead shows low nanomolar cell proliferation IC50 values, while sparing cell lines not driven by the MAPK pathway. The lead exhibits robust antitumor activity upon oral dosing in a range of subcutaneous xenograft models including the mutant BRAF colorectal line Colo205, providing a promising basis for further optimization towards clinical pERK1/2 modulating ERK1/2 inhibitors. Citation Format: Tom D. Heightman, Valerio Berdini, Hannah Braithwaite, Ildiko Buck, Megan Cassidy, Juan Castro, Aurélie Courtin, James Day, Charlotte East, Lynsey Fazal, Brent Graham, Charlotte Griffiths-Jones, John Lyons, Vanessa Martins, Sandra Muench, Joanne Munck, David Norton, Marc O'Reilly, Nick Palmer, Puja Pathuri, Mike Reader, David Rees, Sharna Rich, Caroline Richardson, Harpreet Saini, Neil Thompson, Nicola Wallis, Hugh Walton, Nicola Wilsher, Alison Woolford, Chris Murray. Fragment-based discovery of a highly potent, orally bioavailable ERK1/2 inhibitor that modulates the phosphorylation and catalytic activity of ERK1/2 [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B161.

We have previously described the development and initial validation of a telephone administered cognitive test battery (TACT). This report investigates the retest reliability of the TACT battery between telephone administration and face-to-face administration and measures the concurrent validity of the test components against a standard test of cognitive ability, the WAIS-RUK. Data were collected on 27 participants aged 62–63 years. There was a two- to 10-month interval between time 1 (telephone) and time 2 (face-to-face) administration. Intra-class correlation coefficients for telephone versus face-to-face administration of the TACT were satisfactory for all component measures except for ‘object rotation’ and WAIS similarities. There was no evidence of systematic cheating on the telephone-administered test. Tests of concurrent validity showed stronger correlations for the TACT battery components with verbal tests rather than performance tests, as measured by the WAIS-RUK. A few administration difficulties are noted and recommendations for change are outlined. The TACT is a convenient assessment tool with potential for measuring cognitive change in epidemiological studies. Copyright © 2001 Whurr Publishers Ltd.

Traditionally, regulations are seen as harmful for the starting and growing of firms. However, strict environmental regulation can also trigger the discovery and introduction of clean technologies, and this innovation might improve the competitiveness of the firm (the so-called Porter hypothesis). This project focuses on the environmental regulation paradox in the context of new venture growth. The key questions are: 1) to what extent do new ventures perceive environmental regulation to be a bottleneck; and 2) how does environmental regulation affect the growth of clean tech ventures? The characteristics of a panel of new ventures are analyzed during their emergence, and in particular the effect of environmental regulation on the subsequent growth of these new ventures. These analyses are also performed on a subsample of firms that is especially liable to environmental regulations, namely clean tech ventures. The empirical evidence shows the paradox of environmental regulation for clean tech ventures: they more often perceive this to be a bottleneck, but environmental regulation also seems to drive their growth. Our interpretation of the environmental regulation paradox is that environmental regulation should be treated as a barrier to growth: entrepreneurs that aim to expand their business in markets that are sensitive to environmental regulation face these regulations as a bottleneck for their activities, but this necessary evil informs them how to successfully expand in these markets giving them a competitive edge over other less well informed firms. Without this hurdle they would probably not be sufficiently informed about the possibilities and impossibilities in these markets. This especially counts for clean tech ventures, but also for the group of non-clean tech ventures that is active on markets liable to environmental regulations. This interpretation does justice to the initial Porter hypothesis - environmental regulation can trigger innovation that may partially or more than fully offset the costs of complying with them – as environmental regulation is both perceived as a cost, but in the end seems to more than fully offset these costs indicated by the growth inducing effect of environmental regulation.

In this paper we argue that insights in the actor level of sustainability transitions are a necessary next step in the study of sustainability transitions. The paper outlines a first step towards a more systematic analysis of actor strategies in sustainability transitions by linking strategies described in the sustainable entrepreneurship literature to the technological innovation systems literature. The focus is thereby on nascent entrepreneurs and entrepreneurial incumbent firms which both play a crucial role in developing and commercializing the technologies needed in a transition to sustainability. Our analysis points to two avenues for further research: the role of legitimacy strategies in sustainability transitions and the role of cooperative versus competitive strategies in sustainability transitions.

The understanding of pathways into care is necessary to plan services and identify health care needs of patients. We set out to study these pathways into care in south Asian and white elderly patients coming into contact with secondary care psychiatric services. All inpatients, day patients and community assessments of patients over 65 being referred for the first time or after a gap of one year were invited to take part in the study over a 6 month period and those willing were interviewed. Pathways to care encounter, GP satisfaction, Past Psychiatric History Schedule and menul illness beliefs were studied. Only the pathways and GP satisfaction are presented here. Of 117 patients, 71 were white and 46 south Asians. South Asians were more likely to ask for help but had longer delays in contacting psychiatric services. They were also more dissatisfied with their GPs. A complex interaction of interpersonal and intrapersonal factors influences pathways into help-seeking.

While numerous academic studies sufficiently bond the emergence of (radical) innovations to macroeconomic growth (Plosser (1989); Freeman and Perez (1988); Mansfield (1983); Mensch (1979); Jovanovic and Lach (1997); Giedeman and Simons (2006)), the competitive mechanisms that influence small firm innovation activity are under-theorized and empirically under-represented (see Heger (2004)). Moreover, policy-maker tend to assume a “one-size-fits-all” stimulus agenda can be implemented nation-wide to enhance innovation activity in small firms, i.e. suggesting that supportive policies for the macroeconomic climate will have the same effect on all industries, while in reality, firm and industry innovativeness results in different effects from the macro-economy. Therefore, our main research question asks to what extent and how do macroeconomic dynamics affect product innovations. We take a quantitative approach by examining innovation survey responses from small and medium sized enterprises (SMEs) from 1999-2009 in the Netherlands. Methodologically, we utilize logistic regressions on the pooled cross-section dataset to examine statistically significant effects at an aggregate, innovativeness, and sector level using macroeconomic indicators such as Real GDP, domestic consumption, unemployment rates, and long-term interest rates. Findings suggest that innovativeness of firms and industries results in varying significant effects from the macroeconomic condition. Policy should account for sector specifics and innovativeness when considering future innovation stimulus objectives.Length

Background: Kinase inhibitors have been used successfully in the clinic, but relapse is common due to the emergence of resistance. Inhibition of HSP90 leads to the depletion of oncogenic ‘client’ proteins and the simultaneous inhibition of many signalling pathways. As such, the use of HSP90 inhibitors to overcome resistance has been widely investigated. Onalespib (AT13387) is a potent, second generation HSP90 inhibitor, which has been studied in many preclinical models of kinase inhibitor resistance. Recent findings indicate that an upfront combination of onalespib and either vemurafenib or crizotinib, in models of mutant BRAF melanoma or ALK-translocated non-small cell lung cancer (NSCLC), can delay the emergence of resistance to these therapies. Here we have extended this work to a combination of onalespib and erlotinib in an EGFR-driven NSCLC model. Methods: Mice bearing HCC827 tumor xenografts were dosed with either 12.5 mg/kg erlotinib po qd, or a combination of 12.5 mg/kg erlotinib and 55 mg/kg onalespib ip qw for 52 weeks. Results: Initially both the erlotinib single-agent and onalespib/erlotinib combination treatments significantly inhibited tumor growth of the EGFR-driven NSCLC HCC827 xenograft model; all tumors in the monotherapy and combination groups regressed rapidly and achieved complete response (CR) (median times to CR were 79 and 56 days for monotherapy and combination treatments respectively). However, after 20 weeks of continuous treatment, tumor relapse was observed in one of the xenografts dosed with erlotinib only and this was followed by regrowth of a further 2 tumors in this group over the 52-week study period, with these tumors reaching 50% of the original tumor volumes by 26 and 46 weeks. Of the remaining tumors, 5 out of 6 were detectable at the end of the study. In comparison, tumor growth remained inhibited in the group treated with the erlotinib/onalespib combination; no tumors were observed to regrow over the course of the study and none (of 9) were palpable when treatments were terminated. This suggests that while treatment with monotherapy erlotinib in this model leads to relapse, as seen in the clinic, combination treatment with onalespib can delay the emergence of resistance. Conclusions: These data demonstrate that an upfront combination of onalespib and erlotinib can delay the emergence of resistance in an EGFR-driven xenograft model, suggesting there is therapeutic potential for an upfront erlotinib/onalespib combination in the clinic. Onalespib is currently being tested in a Phase 2 clinical trial in combination with crizotinib in ALK-positive NSCLC. The preclinical data presented here, alongside our previous data on combinations of onalespib with vemurafenib or crizotinib, suggest that the concept of using an HSP90 inhibitor combination upfront in the clinic to delay resistance could be extended to further targeted therapies. Citation Format: Aurélie Courtin, Tomoko Smyth, Keisha Hearn, John Lyons, Neil Thompson, Nicola G. Wallis. The HSP90 inhibitor, onalespib (AT13387), delays the emergence of resistance to erlotinib in an EGFR-driven xenograft model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2688. doi:10.1158/1538-7445.AM2015-2688