Ecosystems—communities of interdependent yet hierarchically independent heterogeneous participants who collectively generate an ecosystem value proposition—often emerge through collective action, ...where ecosystem participants interact with each other and the external environment. When such organizational forms are emerging, they require legitimacy to overcome the “liability of newness.” Adopting a collective action lens and taking a legitimacy-as-process approach, we propose a process model of ecosystem collective action, where an orchestrator, complementors, users, and external actors together drive ecosystem legitimacy. We identify three key legitimation processes—discursive legitimation, performative legitimation, and ecosystem identity construction—and demonstrate how these three processes together facilitate the emergence of ecosystem legitimacy and reduce the liability of newness of emerging ecosystems.
Research Summary: Entrepreneurial ecosystems command increasing attention from policy makers, academics, and practitioners, yet the phenomenon itself remains under‐theorized. Specifically, the ...conceptual similarities and differences of entrepreneurial ecosystems relative to, for instance, clusters, “knowledge clusters,” regional systems of innovation, and “innovative milieus” remain unclear. Drawing on research on industrial districts and agglomerations, clusters, and systems of innovation, we suggest that entrepreneurial ecosystems differ from traditional clusters by their emphasis on the exploitation of digital affordances; by their organization around entrepreneurial opportunity discovery and pursuit; by their emphasis on business model innovation; by voluntary horizontal knowledge spillovers; and by cluster‐external locus of entrepreneurial opportunities. We highlight how these distinctive characteristics set entrepreneurial ecosystems apart from other cluster types, propose a structural model of entrepreneurial ecosystems, summarize the articles in this special issue, and suggest promising avenues for future research.
Managerial Summary: Entrepreneurial ecosystems command increasing attention from policy makers, academics, and practitioners. We suggest that entrepreneurial ecosystems differ from traditional clusters by their emphasis on the exploitation of digital affordances; by their organization around entrepreneurial opportunity discovery and pursuit; by their emphasis on business model innovation; by voluntary horizontal knowledge spillovers; and by cluster‐external locus of entrepreneurial opportunities. We highlight how these distinctive characteristics set entrepreneurial ecosystems apart from regional cluster phenomena discussed in received economic geography and innovation literatures. We suggest policy makers need to adopt novel approaches to stimulate entrepreneurial ecosystems that differ from those in place to develop industrial clusters or support already established small‐ and medium‐sized companies.
Vibrational spectroscopy is an essential tool in chemical analyses, biological assays, and studies of functional materials. Over the past decade, various coherent nonlinear vibrational spectroscopic ...techniques have been developed and enabled researchers to study time-correlations of the fluctuating frequencies that are directly related to solute-solvent dynamics, dynamical changes in molecular conformations and local electrostatic environments, chemical and biochemical reactions, protein structural dynamics and functions, characteristic processes of functional materials, and so on. In order to gain incisive and quantitative information on the local electrostatic environment, molecular conformation, protein structure and interprotein contacts, ligand binding kinetics, and electric and optical properties of functional materials, a variety of vibrational probes have been developed and site-specifically incorporated into molecular, biological, and material systems for time-resolved vibrational spectroscopic investigation. However, still, an all-encompassing theory that describes the vibrational solvatochromism, electrochromism, and dynamic fluctuation of vibrational frequencies has not been completely established mainly due to the intrinsic complexity of intermolecular interactions in condensed phases. In particular, the amount of data obtained from the linear and nonlinear vibrational spectroscopic experiments has been rapidly increasing, but the lack of a quantitative method to interpret these measurements has been one major obstacle in broadening the applications of these methods. Among various theoretical models, one of the most successful approaches is a semiempirical model generally referred to as the vibrational spectroscopic map that is based on a rigorous theory of intermolecular interactions. Recently, genetic algorithm, neural network, and machine learning approaches have been applied to the development of vibrational solvatochromism theory. In this review, we provide comprehensive descriptions of the theoretical foundation and various examples showing its extraordinary successes in the interpretations of experimental observations. In addition, a brief introduction to a newly created repository Web site (http://frequencymap.org) for vibrational spectroscopic maps is presented. We anticipate that a combination of the vibrational frequency map approach and state-of-the-art multidimensional vibrational spectroscopy will be one of the most fruitful ways to study the structure and dynamics of chemical, biological, and functional molecular systems in the future.
Based on a longitudinal case study, this paper presents an ecosystem‐level process model of the interlocking key activities of the business model disruptor, other ecosystem participants (customers, ...partners, media, analysts), and the incumbent. Together these constitute a strategic process of ecosystem evolution from incumbent‐centred to disruptor‐centred. We identify the phenomenon of a ‘disruptor's gambit’, where the disruptor reveals its intentions early on through effective framing, followed by rapid adaptation of its business model to satisfy ecosystem needs. These processes generate a virtuous framing‐adaptation cycle, where feed‐forward and feedback enable rapid response to customers and partners, while engaging them as force multipliers during new ecosystem creation. Our findings suggest that framing constitutes a dynamic strategic process enabling disruptors to reduce uncertainty, dislodge powerful incumbents, and shape new ecosystems through business model innovation.
Large, longitudinal, multi-center MR neuroimaging studies require comprehensive quality assurance (QA) protocols for assessing the general quality of the compiled data, indicating potential ...malfunctions in the scanning equipment, and evaluating inter-site differences that need to be accounted for in subsequent analyses.
We describe the implementation of a QA protocol for functional magnet resonance imaging (fMRI) data based on the regular measurement of an MRI phantom and an extensive variety of currently published QA statistics. The protocol is implemented in the MACS (Marburg-Münster Affective Disorders Cohort Study, http://for2107.de/), a two-center research consortium studying the neurobiological foundations of affective disorders. Between February 2015 and October 2016, 1214 phantom measurements have been acquired using a standard fMRI protocol. Using 444 healthy control subjects which have been measured between 2014 and 2016 in the cohort, we investigate the extent of between-site differences in contrast to the dependence on subject-specific covariates (age and sex) for structural MRI, fMRI, and diffusion tensor imaging (DTI) data.
We show that most of the presented QA statistics differ severely not only between the two scanners used for the cohort but also between experimental settings (e.g. hardware and software changes), demonstrate that some of these statistics depend on external variables (e.g. time of day, temperature), highlight their strong dependence on proper handling of the MRI phantom, and show how the use of a phantom holder may balance this dependence. Site effects, however, do not only exist for the phantom data, but also for human MRI data. Using T1-weighted structural images, we show that total intracranial (TIV), grey matter (GMV), and white matter (WMV) volumes significantly differ between the MR scanners, showing large effect sizes. Voxel-based morphometry (VBM) analyses show that these structural differences observed between scanners are most pronounced in the bilateral basal ganglia, thalamus, and posterior regions. Using DTI data, we also show that fractional anisotropy (FA) differs between sites in almost all regions assessed. When pooling data from multiple centers, our data show that it is a necessity to account not only for inter-site differences but also for hardware and software changes of the scanning equipment. Also, the strong dependence of the QA statistics on the reliable placement of the MRI phantom shows that the use of a phantom holder is recommended to reduce the variance of the QA statistics and thus to increase the probability of detecting potential scanner malfunctions.
•Quality assurance (QA) protocol for large, longitudinal, multi-center MR neuroimaging studies.•Dependence of QA statistics on MR-scanner type, hardware and software changes and external variables (e.g., time of day, temperature).•Consequences of phantom data variations for human MRI data.•Dependence of MR phantom placement on QA statistics.
B cells are important in the pathogenesis of many, and perhaps all, immune-mediated diseases. Each B cell expresses a single B cell receptor (BCR)
, and the diverse range of BCRs expressed by the ...total B cell population of an individual is termed the 'BCR repertoire'. Our understanding of the BCR repertoire in the context of immune-mediated diseases is incomplete, and defining this could provide new insights into pathogenesis and therapy. Here, we compared the BCR repertoire in systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Crohn's disease, Behçet's disease, eosinophilic granulomatosis with polyangiitis, and immunoglobulin A (IgA) vasculitis by analysing BCR clonality, use of immunoglobulin heavy-chain variable region (IGHV) genes and-in particular-isotype use. An increase in clonality in systemic lupus erythematosus and Crohn's disease that was dominated by the IgA isotype, together with skewed use of the IGHV genes in these and other diseases, suggested a microbial contribution to pathogenesis. Different immunosuppressive treatments had specific and distinct effects on the repertoire; B cells that persisted after treatment with rituximab were predominately isotype-switched and clonally expanded, whereas the inverse was true for B cells that persisted after treatment with mycophenolate mofetil. Our comparative analysis of the BCR repertoire in immune-mediated disease reveals a complex B cell architecture, providing a platform for understanding pathological mechanisms and designing treatment strategies.
RET fusions are present in 1%-2% of non-small-cell lung cancer (NSCLC). Pralsetinib, a highly potent, oral, central nervous system-penetrant, selective RET inhibitor, previously demonstrated clinical ...activity in patients with RET fusion–positive NSCLC in the phase I/II ARROW study, including among treatment-naive patients. We report an updated analysis from the ARROW study.
ARROW is a multi-cohort, open-label, phase I/II study. Eligible patients were ≥18 years of age with locally advanced or metastatic solid tumours and an Eastern Cooperative Oncology Group performance status of 0-2 (later 0-1). Patients initiated pralsetinib at the recommended phase II dose of 400 mg once daily until disease progression, intolerance, consent withdrawal, or investigator’s decision. The co-primary endpoints (phase II) were overall response rate (ORR) by blinded independent central review and safety.
Between 17 March 2017 and 6 November 2020 (data cut-off), 281 patients with RET fusion–positive NSCLC were enrolled. The ORR was 72% 54/75; 95% confidence interval (CI) 60% to 82% for treatment-naive patients and 59% (80/136; 95% CI 50% to 67%) for patients with prior platinum-based chemotherapy (enrolment cut-off for efficacy analysis: 22 May 2020); median duration of response was not reached for treatment-naive patients and 22.3 months for prior platinum-based chemotherapy patients. Tumour shrinkage was observed in all treatment-naive patients and in 97% of patients with prior platinum-based chemotherapy; median progression-free survival was 13.0 and 16.5 months, respectively. In patients with measurable intracranial metastases, the intracranial response rate was 70% (7/10; 95% CI 35% to 93%); all had received prior systemic treatment. In treatment-naive patients with RET fusion–positive NSCLC who initiated pralsetinib by the data cut-off (n = 116), the most common grade 3-4 treatment-related adverse events (TRAEs) were neutropenia (18%), hypertension (10%), increased blood creatine phosphokinase (9%), and lymphopenia (9%). Overall, 7% (20/281) discontinued due to TRAEs.
Pralsetinib treatment produced robust efficacy and was generally well tolerated in treatment-naive patients with advanced RET fusion–positive NSCLC. Results from the confirmatory phase III AcceleRET Lung study (NCT04222972) of pralsetinib versus standard of care in the first-line setting are pending.
•Pralsetinib produced an ORR of 72% in treatment-naive patients with RET fusion–positive NSCLC.•Pralsetinib was generally well tolerated and there were no new safety signals.•The confirmatory phase III AcceleRET Lung study (NCT04222972) of pralsetinib versus standard of care in the first-line setting is ongoing
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