Exploring the topology of the plausible: Fs/QCA counterfactual analysis and the plausible fit of unobserved organizational configurations

The main aim of this contribution is to expand the dominant rationale of organizational design research by including solutions and possibilities not observed in reality. We believe that the counterfactual approach to configurations responds to an open call in organization theory and strategy to move the modelling of fit towards a more robust and theory-based specification. With this new approach we propose to rediscover the roots of organization design as a distinct normative discipline that ‘should stand approximately in relation to the basic social sciences as engineering stands with respect to physical sciences or medicine to the biological’. At a more general level, our view implies an expansion of the dominant meaning of the concept of ‘relevance’ in management research. While we agree with Gulati (2007: 780) that we as scholars should probe ‘more deeply into the problems and other issues that managers care about’, we also believe that relevance does not necessarily mean that researchers have to use an ex-post rationality by studying only empirically frequent phenomena. In contrast, we think that any management esearcher should bring with her or himself a fragment of the spirit of the great Greek philosopher Anaximander (c. 610–c. 546 BC), who foresaw the concept of the infinite universe without the support of any empirical observation and against the predominant wisdom of the time. Not by chance, Karl Popper (1998) onsidered Anaximander’s intuitions among the most vivid demonstrations of the power of human thought and logic

Knowledge, attitudes and behaviors regarding influenza vaccination among Hygiene and Preventive Medicine residents in Calabria and Sicily.

Vaccinating health care workers is considered to be one of the most important steps in preventing the transmission of the influenza virus to vulnerable patients. Public Health physicians are the main promoters and executors of influenza vaccination campaigns for both healthcare workers and the general population. The objective of the present survey was to analyze the knowledge, attitudes and practices regarding influenza vaccination among Hygiene and Preventive Medicine Residents. 64% of the participants had not been vaccinated against the influenza virus in the past 5 years, and 29% had been vaccinated only occasionally , with only 7.2% of the study popu-lation having been vaccinated every year. 20.3% of those surveyed were vaccinated in the 2010/2011 season. The best strategy to increase vaccination rates among health care workers according to the study participants was the participation of future public health operators to multidisciplinary training (34.8%). the main factors associated with influenza vaccination compliance were having been vaccinated in the previous season for 2011/2012 (OR [95%]: 41.14 [7.56 - 223.87]) and having received the vaccination always or occasionally during the previous 5 years for both 2010/2011 (p-value <0.0001) and 2011/2012 (p-value <0.0001). The findings of this study suggest that future public health physicians with a history of refusing influenza vaccination in previous years usually tend to maintain their beliefs over time. Changing this trend among Hygiene and Preventive Medicine residents is the real challenge for the future, and it can be achieved through organization of multidisciplinary training, improvement of university education and increasing the involvement of Hygiene and Preventive Medicine residents in influenza vaccination campaigns both for the gen-eral population and health care workers

Performative Work: Bridging Performativity and Institutional Theory in the Responsible Investment Field

Callon’s performativity thesis has illuminated how economic theories and calculative devices shape markets, but has been challenged for its neglect of the organizational, institutional and political context. Our seven-year qualitative study of a large financial data company found that the company’s initial attempt to change the responsible investment field through a performative approach failed because of the constraints posed by field practices and organizational norms on the design of the calculative device. However, the company was subsequently able to put in place another form of performativity by attending to the normative and regulative associations of the device. We theorize this route to performativity by proposing the concept of performative work, which designates the necessary institutional work to enable translation and the subsequent adoption of the device. We conclude by considering the implications of performative work for the performativity and the institutional work literatures

Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA

Intratumoral heterogeneity contributes to cancer drug resistance, but the underlying mechanisms are not understood. Single-cell analyses of patient-derived models and clinical samples from glioblastoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate that tumor cells reversibly up-regulate or suppress mutant EGFR expression, conferring distinct cellular phenotypes to reach an optimal equilibrium for growth. Resistance to EGFR TKIs is shown to occur by elimination of mutant EGFR from extrachromosomal DNA. After drug withdrawal, reemergence of clonal EGFR mutations on extrachromosomal DNA follows. These results indicate a highly specific, dynamic, and adaptive route by which cancers can evade therapies that target oncogenes maintained on extrachromosomal DNA

Dental Hygienists\u27 Knowledge of HIV, Attitudes Towards People with HIV and Willingness to Conduct Rapid HIV Testing

This study was aimed to determine the dental hygienists\u27 knowledge of HIV, attitudes towards people living with HIV and willingness to conduct rapid HIV testing

Regulation of the Epstein-Barr virus DNA polymerase gene.

The gene (pol) encoding the Epstein-Barr virus (EBV) DNA polymerase is a member of the "early" class of viral genes which are expressed shortly after activation of latent virus infection. First, mRNA from the EBV-producing cell line, B95-8, treated with 12-O-tetradecanoylphorbol-13-acetate and sodium butyrate to induce lytic replication and expression of this gene was analyzed. Northern (RNA) analysis revealed a message of 3.7 kb found only in induced cells. 5' mapping of pol mRNA by S1 nuclease and primer extension analyses indicates that transcription initiates at tightly clustered sites within a G + C-rich region 126 bp upstream of the open reading frame. The same initiation region was identified in two other EBV-infected cell lines, P3HR1 and Raji, after induction. Second, a 1.29-kb genomic fragment containing this region, when cloned upstream of the chloramphenicol acetyltransferase reporter gene, demonstrated promoter activity in lymphoid cells cotransfected with pEBV-RZ, a genomic expression construct that includes genes for the EBV immediate-early transactivator proteins, BZLF-1 and BRLF-1. Within the upstream 1.29-kb sequence, two regions of 140 bp and 101 bp appear to be needed for promoter activity. These results demonstrate that unlike most EBV genes studied thus far, the pol gene contains multiple transcriptional start sites. The upstream regulatory region of the promoter for the pol gene does not contain canonical promoter elements such as TATA and CAAT boxes and, furthermore, is not constitutively active but requires transactivation by two or more viral proteins

Single-cell analysis tools for drug discovery and development

The genetic, functional or compositional heterogeneity of healthy and diseased tissues presents major challenges in drug discovery and development. Such heterogeneity hinders the design of accurate disease models and can confound the interpretation of biomarker levels and of patient responses to specific therapies. The complex nature of virtually all tissues has motivated the development of tools for single-cell genomic, transcriptomic and multiplex proteomic analyses. Here, we review these tools and assess their advantages and limitations. Emerging applications of single cell analysis tools in drug discovery and development, particularly in the field of oncology, are discussed