Value capture and embeddedness in social-purpose-driven ecosystems : A multiple-case study of European digital healthcare platforms

We aim to answer the question of the effect of a social-purpose-driven ecosystem on value capture from digital health platforms. We call the social-purpose-driven ecosystem a phenomenon which seeks social impact before profits and aims to empower citizens for individual and collective well-being. Thus, capturing value from digital platforms embedded in a social-purpose-driven ecosystem fundamentally differs from profiting from purely commercial digital platforms and poses significant challenges to platform owners and public policy. Previous research has focused mainly on profiting from technological innovations but has yet to consider the contextual role of the social-purpose-driven ecosystem. We applied the Profiting from Innovation (PFI) framework to fill this gap. Furthermore, based on the results of the multiple-case study of five European digital healthcare platforms, we extend the PFI framework. As a result, we define four unique contingencies which enable value capture from digital healthcare platforms embedded in a social-purpose-driven ecosystem: 1) multilayer value creation, (2) multipurpose complementary assets, (3) emerging dominant design, and (4) distributed socio-economic returns mechanisms. The study offers two managerial and policy contributions. First, it calls on platform owners and policymakers to acknowledge the contextual effect of a social-purpose-driven ecosystem. Second, multilayer value creation, multiple complementary assets, dominant design and distributed socio-economic returns mechanisms can positively affect capturing value from digital healthcare platforms.publishedVersionPeer reviewe

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene

Approximately half of the neurons produced during embryogenesis normally die before adulthood. Although target-derived neurotrophic factors are known to be major determinants of programmed cell death--apoptosis--the molecular mechanisms by which trophic factors interfere with cell death regulation are largely unknown. Overexpression of the bcl-2 proto-oncogene in cultured sympathetic neurons has now been shown to prevent apoptosis normally induced by deprivation of nerve growth factor. This finding, together with the previous demonstration of bcl-2 expression in the nervous system, suggests that the Bcl-2 protein may be a major mediator of the effects of neurotrophic factors on neuronal survival

Self-Observation and Peer Feedback as a Faculty Development Approach for Problem-Based Learning Tutors: A Program Evaluation

Problem: Good teaching requires spontaneous, immediate, and appropriate action in response to various situations. It is even more crucial in problem-based learning (PBL) tutorials, as the tutors, while directing students toward the identification and attainment of learning objectives, must stimulate them to contribute to the process and provide them with constructive feedback. PBL tutors in medicine lack opportunities to receive feedback from their peers on their teaching strategies. Moreover, as tutorials provide little or no time to stop and think, more could be learned by reflecting on the experience than from the experience itself. We designed and evaluated a faculty development approach to developing PBL tutors that combined self-reflection and peer feedback processes, both powerful techniques for improving performance in education

High sensitivity of transgenic mice expressing soluble TNFR1 fusion protein to mycobacterial infections: synergistic action of TNF and IFN-gamma in the differentiation of protective granulomas

To investigate the role of tumor necrosis factor (TNF) in protective immune responses to Mycobacterium tuberculosis and M. bovis Bacillus Calmette Guerin (BCG), we have used transgenic mice unable to use TNF because of the expression of high amounts of a soluble TNF receptor (R) type I (sTNFR1) fusion protein, and studied resistance of these mice to infection by lethality assays, evaluation of bacterial recovery and histologic examination. These mice showed a strongly increased sensitivity to M. tuberculosis and BCG infections, with bacterial overgrowth and marked inhibition of macrophage differentiation within granulomas; after M. tuberculosis infection, this resulted in extensive lesions of caseous necrosis in the lung. To explore the respective roles of TNF and interferon (IFN)-gamma in resistance to BCG and granuloma differentiation, controls and sTNFR1-transgenic mice were compared to IFN-gammaR mutant mice and mice double defective in TNF and IFN-gamma activity (obtained by crossing transgenic and mutant mice). The three groups of deficient mice showed a strongly enhanced susceptibility to BCG infection, with the following decreasing order of sensitivity between groups: TNF + IFN-gamma --> TNF --> IFN-gamma-deficient mice. The hepatic granulomas of IFN-gammaR mutant mice were small and contained eosinophils but few differentiated macrophages; compared to those of sTNFR1-transgenic mice, acid-fast bacilli were less numerous within the macrophages. Granulomas of double-deficient mice were strikingly different by their very large size and cellular content, made up large numbers of polymorphonuclears, eosinophils, and cells undergoing apoptosis, but without detectable differentiated macrophages; acid-fast bacilli were spread in the lesions. These studies show the essential role of both TNF and IFN-gamma in the development, during mycobacterial infections, of protective granulomas containing highly differentiated macrophages capable of destroying ingested bacteria, and emphasize that these two cytokines act synergistically in granuloma formation

Low Dose BCG Infection as a Model for Macrophage Activation Maintaining Cell Viability

Mycobacterium bovis BCG, the current vaccine against tuberculosis, is ingested by macrophages promoting the development of effector functions including cell death and microbicidal mechanisms. Despite accumulating reports on M. tuberculosis, mechanisms of BCG/macrophage interaction remain relatively undefined. In vivo, few bacilli are sufficient to establish a mycobacterial infection; however, in vitro studies systematically use high mycobacterium doses. In this study, we analyze macrophage/BCG interactions and microenvironment upon infection with low BCG doses and propose an in vitro model to study cell activation without affecting viability. We show that RAW macrophages infected with BCG at MOI 1 activated higher and sustained levels of proinflammatory cytokines and transcription factors while MOI 0.1 was more efficient for early stimulation of IL-1β, MCP-1, and KC. Both BCG infection doses induced iNOS and NO in a dose-dependent manner and maintained nuclear and mitochondrial structures. Microenvironment generated by MOI 1 induced macrophage proliferation but not MOI 0.1 infection. In conclusion, BCG infection at low dose is an efficient in vitro model to study macrophage/BCG interactions that maintains macrophage viability and mitochondrial structures. This represents a novel model that can be applied to BCG research fields including mycobacterial infections, cancer immunotherapy, and prevention of autoimmunity and allergies

Loss of heterozygosity for the short arm of chromosome 11 (11p15) in human milk epithelial cells immortalized by microinjection of SV40 DNA.

We have developed, by microinjection of SV40 DNA into human milk epithelial cells, a new mammary cell line, Hu-MI, which exhibits the phenotype of luminal cells or so-called "breast cancer precursor cells." This cell line retains the phenotype of primary cells as demonstrated by the expression of keratins 18 and 19 and of polymorphic epithelial mucins. However, the cells do not grow in agar after more than 80 passages, nor do they form tumors in nude mice. Established cells contain 2 copies of SV40 DNA integrated into the cellular genome and up to 14 copies of free SV40 DNA. A deletion of the short arm of chromosome 11 (11p15) including the c-Ha-ras and the beta-globin genes was found in the immortalized cells when the DNA from these cells was compared to the DNA from peripheral blood mononuclear cells obtained from the same donor. In addition, this cell line showed a good transfection efficiency for other DNA sequences using classical transfection and selection techniques with a neomycin resistance gene (pKOneo). Selective microinjection of DNA into tumor precursor cells may prove useful for the study of the molecular mechanisms involved in breast carcinogenesis. The possible significance of the loss of 11p13-15 in malignant progression of breast cancer is discussed