Successful scaling in social franchising: The case of Impact Hub

Social entrepreneurs increasingly use franchising to scale social value. Tracey and Jarvis (2007) described how social franchising is similar to commercial franchising, but also noted critical challenges arising from dual social and commercial goals. We investigate a social franchisor that overcame these challenges and describe how the social mission became the source of innovation for its business model. We show that the social mission fostered a shared identity that motivated and guided the search for adaptations to the franchise model. In particular, the shared mission-driven identity created pressure toward (1) decentralized decision-making, (2) shared governance, and (3) a new role for the franchisor as orchestrator of collaborative knowledge sharing among franchisees. Findings should help social franchisors avoid common pitfalls and suggest future research questions for social entrepreneurship and franchising scholars

CXC chemokines exhibit bactericidal activity against multidrug-resistant gram-negative pathogens

The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A. Colistin-resistant K. pneumoniae isolates affected by genetic mutation of the PmrA/PmrB two-component system, a chromosomally encoded regulator of lipopolysaccharide modification, and containing 4-amino-4-deoxy-l-arabinose-modified lipid A were also found to be susceptible to chemokine-mediated antimicrobial activity. However, loss of PhoP/PhoQ autoregulatory control, caused by disruption of the gene encoding the negative regulator MgrB, limited the bactericidal effects of CXCL9 and CXCL10 in a variable, strain-specific manner. Cumulatively, these findings provide mechanistic insight into chemokine-mediated antimicrobial activity, highlight disparities amongst determinants of colistin resistance, and suggest that chemokine-mediated bactericidal effects merit additional investigation as a therapeutic avenue for treating infections caused by multidrug-resistant pathogens

Computer-Aided Imaging Analysis of Probe-Based Confocal Laser Endomicroscopy With Molecular Labeling and Gene Expression Identifies Markers of Response to Biological Therapy in IBD Patients: The Endo-Omics Study

Abstract Background We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response. Methods Twenty-nine patients (15 with Crohn’s disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4β7 therapy. Biopsies were taken for fluorescein isothiocyanate–labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort. Results In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn’s disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7). Conclusions Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF–responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders

CXC chemokines exhibit bactericidal activity against multidrug-resistant gram-negative pathogens

The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A. Colistin-resistant K. pneumoniae isolates affected by genetic mutation of the PmrA/PmrB two-component system, a chromosomally encoded regulator of lipopolysaccharide modification, and containing 4-amino-4-deoxy-l-arabinose-modified lipid A were also found to be susceptible to chemokine-mediated antimicrobial activity. However, loss of PhoP/PhoQ autoregulatory control, caused by disruption of the gene encoding the negative regulator MgrB, limited the bactericidal effects of CXCL9 and CXCL10 in a variable, strain-specific manner. Cumulatively, these findings provide mechanistic insight into chemokine-mediated antimicrobial activity, highlight disparities amongst determinants of colistin resistance, and suggest that chemokine-mediated bactericidal effects merit additional investigation as a therapeutic avenue for treating infections caused by multidrug-resistant pathogens

Entrepreneurship at the Base of the Pyramid: The Moderating Role of Person-Facilitator Fit and Poverty Alleviation

Facilitating entrepreneurship through micro-credit, micro-franchise, and micro-consignment potentially helps to alleviate desperate poverty. However, the effectiveness of these facilitators have varied from positive outcomes of poverty alleviation to negative outcomes of increased debt. Therefore, we seek to understand: how and why are different facilitators of entrepreneurial activity at the Base of the Pyramid (BOP) relatively more effective at alleviating poverty? Building on the foundation of person-entrepreneurship fit, we introduce the construct of person-facilitator fit and develop propositions about how and why the fit between entrepreneurs and the different facilitators of entrepreneurship may influence poverty alleviation. Specifically, using a remediation perspective, we explicate how the demands-abilities and needs-supplies fit between an entrepreneur and the different facilitators of micro-credit, micro-franchise and micro-consignment moderates the likelihood of poverty alleviation and how person-facilitator fit moderates the magnitude of poverty alleviation over time. We offer theoretical and practical implications of our framework for different perspectives (remediation, reform, and revolution) on entrepreneurship and poverty alleviation

Source of magmas that generated eruptive products at Mt. Somma-Vesuvius and Campi Flegrei based on melt inclusions

Definizione e discussione sulle sorgenti magmatiche attraverso lo studio delle melt inclusions del Vesuvio e dei campi Flegre

Magmatic evolution recorded in trace and volatile element variations in melt inclusion of the Grey Porri Tuffs, Salina, southern Italy

Descrizione e discussione sull'evoluzione magmatica registrata attraverso la variazione di elementi volatili nei melts dei Tufi Grigi del Vulcano Porri dell'Isola di Salina, Isole Eolie, Itali