Imagining alternative and better worlds:Isabel Fletcher talks with Adele E. Clarke

In this interview, Adele Clarke and Isabel Fletcher discuss the different routes that led Clarke to science and technology studies (STS), the field’s increasing engagement with biomedical topics, and her perspectives on its character today. Clarke describes how women’s health activism and teaching feminist critiques of bioscience/biomedicine led her to participate in academic networks now known as feminist STS and trans-national reproduction studies. She reflects on the importance of inter-/trans-disciplinary collaboration in her work, but also raises concerns that the rapid expansion of the field has resulted in inadequate training for newcomers in the “theory-method packages” of STS, and hence poor quality scholarship. For her, the future of STS lies in approaches analyzing the complex intersections between technoscience, gender, race, (post)coloniality, and indigenous knowledges, and in its expansion beyond Europe and North America, to Asia, Central and South America, and Africa. In her following reflection, Isabel Fletcher considers the importance of inter/trans-disciplinarity for STS and highlights the role a politically engaged STS can play in imagining alternative and better worlds

Engaging Complexities: Working Against Simplification as an Agenda for Qualitative Research Today. Adele Clarke in Conversation With Reiner Keller

En 2005, Adele CLARKE publicó su libro sobre "Análisis situacional", bien recibida elaboración de la metodología de teoría fundamentada. El análisis situacional (AS) combina las tradiciones más viejas así como las más recientes de la sociología pragmática, especialmente las de la Escuela de Chicago y la teoría de mundos/arenas sociales de Anselm STRAUSS, con la perspectiva de FOUCAULT sobre el discurso, el pensamiento feminista y la epistemología post-positivista. En esta entrevista con Reiner KELLER, ella explica los fundamentos teóricos y las motivaciones académicas de este enfoque y describe las estrategias analíticas concretas propuestas por el AS. En el momento oportuno, ella narra sus experiencias pasadas, desde sus primeros encuentros con la investigación cualitativa hasta las influencias más recientes desde los estudios feministas y de ciencias y tecnología. CLARKE también aclara donde se coloca el AS dentro del campo más amplio de las metodologías cualitativas y aborda cuestiones relativas a la contribución del AS para el análisis de cambios sociales complejos. El AS está diseñado para ofrecer una heurística analítica capaz de confrontar estas complejidades con un conjunto amplio de estrategias para hacer investigación cualitativa.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs140212Im Jahr 2005 veröffentlichte Adele CLARKE unter dem Titel "Situational Analysis" (dt. "Situationsanalyse") eine viel beachtete Weiterführung der Grounded-Theory-Methodologie. Darin verbindet sie ältere und jüngere Traditionen der pragmatistischen Soziologie, insbesondere der Chicago School und des Social World/Arena-Ansatzes von Anselm STRAUSS mit diskursorientierten Perspektiven FOUCAULTs, feministischen Positionen und postpositivistischer Epistemologie. Im Interview mit Reiner KELLER erläutert sie die theoretischen Grundlagen und wissenschaftlichen Motivationen, die diesem Ansatz zu Grunde liegen, sowie die darin vorgeschlagenen konkreten Analysestrategien. Dabei spannt sie einen weiten Bogen von ihren ersten Kontakten mit qualitativer Forschung bis hin zu jüngeren Einflüssen aus der feministischen Forschung sowie der Wissenschafts- und Technologieforschung. Zugleich thematisiert sie die Verortung der Situationsanalyse im Feld der qualitativen Methodologien und diskutiert die Frage nach deren Bedeutung in der Analyse komplexer aktueller gesellschaftlicher Entwicklungen. Ziel der Situationsanalyse ist die Bereitstellung einer Analyseheuristik, die dieser Komplexität mit entschieden erweiterten qualitativen Forschungsstrategien begegnet.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs140212In 2005, Adele CLARKE first published her book on "Situational Analysis," a well-received elaboration of grounded theory methodology. Situational analysis (SA) combines older as well as more recent traditions of pragmatist sociology, especially those of the Chicago School and social worlds/arenas theory by Anselm STRAUSS, with FOUCAULT's perspective on discourse, feminist thinking, and post-positivist epistemology. In this interview with Reiner KELLER, she explains the theoretical foundations and academic motivations of this approach, and describes the concrete analytical strategies proposed by SA. In due course, she recounts her past experiences, from her very first encounters with qualitative research up to more recent influences from feminist studies and science & technology studies. CLARKE also clarifies where SA is positioned within the broader field of qualitative methodologies, and discusses questions regarding the contribution of SA to the analysis of complex social change. SA is designed to offer an analytical heuristic able to confront these complexities with a considerably expanded set of strategies for doing qualitative research.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs14021

Engaging Complexities: Working Against Simplification as an Agenda for Qualitative Research Today. Adele Clarke in Conversation With Reiner Keller

En 2005, Adele CLARKE publicó su libro sobre "Análisis situacional", bien recibida elaboración de la metodología de teoría fundamentada. El análisis situacional (AS) combina las tradiciones más viejas así como las más recientes de la sociología pragmática, especialmente las de la Escuela de Chicago y la teoría de mundos/arenas sociales de Anselm STRAUSS, con la perspectiva de FOUCAULT sobre el discurso, el pensamiento feminista y la epistemología post-positivista. En esta entrevista con Reiner KELLER, ella explica los fundamentos teóricos y las motivaciones académicas de este enfoque y describe las estrategias analíticas concretas propuestas por el AS. En el momento oportuno, ella narra sus experiencias pasadas, desde sus primeros encuentros con la investigación cualitativa hasta las influencias más recientes desde los estudios feministas y de ciencias y tecnología. CLARKE también aclara donde se coloca el AS dentro del campo más amplio de las metodologías cualitativas y aborda cuestiones relativas a la contribución del AS para el análisis de cambios sociales complejos. El AS está diseñado para ofrecer una heurística analítica capaz de confrontar estas complejidades con un conjunto amplio de estrategias para hacer investigación cualitativa.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs140212Im Jahr 2005 veröffentlichte Adele CLARKE unter dem Titel "Situational Analysis" (dt. "Situationsanalyse") eine viel beachtete Weiterführung der Grounded-Theory-Methodologie. Darin verbindet sie ältere und jüngere Traditionen der pragmatistischen Soziologie, insbesondere der Chicago School und des Social World/Arena-Ansatzes von Anselm STRAUSS mit diskursorientierten Perspektiven FOUCAULTs, feministischen Positionen und postpositivistischer Epistemologie. Im Interview mit Reiner KELLER erläutert sie die theoretischen Grundlagen und wissenschaftlichen Motivationen, die diesem Ansatz zu Grunde liegen, sowie die darin vorgeschlagenen konkreten Analysestrategien. Dabei spannt sie einen weiten Bogen von ihren ersten Kontakten mit qualitativer Forschung bis hin zu jüngeren Einflüssen aus der feministischen Forschung sowie der Wissenschafts- und Technologieforschung. Zugleich thematisiert sie die Verortung der Situationsanalyse im Feld der qualitativen Methodologien und diskutiert die Frage nach deren Bedeutung in der Analyse komplexer aktueller gesellschaftlicher Entwicklungen. Ziel der Situationsanalyse ist die Bereitstellung einer Analyseheuristik, die dieser Komplexität mit entschieden erweiterten qualitativen Forschungsstrategien begegnet.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs140212In 2005, Adele CLARKE first published her book on "Situational Analysis," a well-received elaboration of grounded theory methodology. Situational analysis (SA) combines older as well as more recent traditions of pragmatist sociology, especially those of the Chicago School and social worlds/arenas theory by Anselm STRAUSS, with FOUCAULT's perspective on discourse, feminist thinking, and post-positivist epistemology. In this interview with Reiner KELLER, she explains the theoretical foundations and academic motivations of this approach, and describes the concrete analytical strategies proposed by SA. In due course, she recounts her past experiences, from her very first encounters with qualitative research up to more recent influences from feminist studies and science & technology studies. CLARKE also clarifies where SA is positioned within the broader field of qualitative methodologies, and discusses questions regarding the contribution of SA to the analysis of complex social change. SA is designed to offer an analytical heuristic able to confront these complexities with a considerably expanded set of strategies for doing qualitative research.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs14021

PRMT5 is a critical regulator of breast cancer stem cell function via Histone Methylation and FOXP1 expression

Breast cancer progression, treatment resistance, and relapse are thought to originate from a small population of tumor cells, breast cancer stem cells (BCSCs). Identification of factors critical for BCSC function is therefore vital for the development of therapies. Here, we identify the argininemethyltransferase PRMT5 as a key in vitro and in vivo regulator of BCSC proliferation and self-renewal and establish FOXP1, a winged helix/forkhead transcription factor, as a critical effector of PRMT5-induced BCSC function. Mechanistically, PRMT5 recruitment to the FOXP1 promoter facilitates H3R2me2s, SET1 recruitment, H3K4me3, and gene expression. Our findings are clinically significant, as PRMT5 depletion within established tumor xenografts or treatment of patient- derived BCSCs with a pre-clinical PRMT5 inhibitor substantially reduces BCSC numbers. Together, our findings highlight the importance of PRMT5 in BCSC maintenance and suggest that small-molecule inhibitors of PRMT5 or downstream targets could be an effective strategy eliminating this cancer-causing population

Life, time, and the organism:Temporal registers in the construction of life forms

In this paper, we articulate how time and temporalities are involved in the making of living things. For these purposes, we draw on an instructive episode concerning Norfolk Horn sheep. We attend to historical debates over the nature of the breed, whether it is extinct or not, and whether presently living exemplars are faithful copies of those that came before. We argue that there are features to these debates that are important to understanding contemporary configurations of life, time and the organism, especially as these are articulated within the field of synthetic biology. In particular, we highlight how organisms are configured within different material and semiotic assemblages that are always structured temporally. While we identify three distinct structures, namely the historical, phyletic and molecular registers, we do not regard the list as exhaustive. We also highlight how these structures are related to the care and value invested in the organisms at issue. Finally, because we are interested ultimately in ways of producing time, our subject matter requires us to think about historiographical practice reflexively. This draws us into dialogue with other scholars interested in time, not just historians, but also philosophers and sociologists, and into conversations with them about time as always multiple and never an inert background

Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy

Peer reviewe

Measurements of the Higgs boson production and decay rates and coupling strengths using pp collision data at √S=7 and 8 TeV in the ATLAS experiment

Combined analyses of the Higgs boson production and decay rates as well as its coupling strengths to vector bosons and fermions are presented. The combinations include the results of the analyses of the H -> gamma gamma, ZZ*, WW*, Z gamma, b (b) over bar, tau tau and mu mu decay modes, and the constraints on the associated production with a pair of top quarks and on the off-shell coupling strengths of the Higgs boson. The results are based on the LHC proton-proton collision datasets, with integrated luminosities of up to 4.7 fb(-1) at root s = 7 TeV and 20.3 fb(-1) at root s = 8 TeV, recorded by the ATLAS detector in 2011 and 2012. Combining all production modes and decay channels, the measured signal yield, normalised to the Standard Model expectation, is 1.18(-0.14)(+0.15). The observed Higgs boson production and decay rates are interpreted in a leading-order coupling framework, exploring a wide range of benchmark coupling models both with and without assumptions on the Higgs boson width and on the Standard Model particle content in loop processes. The data are found to be compatible with the Standard Model expectations for a Higgs boson at a mass of 125.36 GeV for all models considered

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Risk and protective factors for structural brain ageing in the eighth decade of life

Individuals differ markedly in brain structure, and in how this structure degenerates during ageing. In a large sample of human participants (baseline n = 731 at age 73 years; follow-up n = 488 at age 76 years), we estimated the magnitude of mean change and variability in changes in MRI measures of brain macrostructure (grey matter, white matter, and white matter hyperintensity volumes) and microstructure (fractional anisotropy and mean diffusivity from diffusion tensor MRI). All indices showed significant average change with age, with considerable heterogeneity in those changes. We then tested eleven socioeconomic, physical, health, cognitive, allostatic (inflammatory and metabolic), and genetic variables for their value in predicting these differences in changes. Many of these variables were significantly correlated with baseline brain structure, but few could account for significant portions of the heterogeneity in subsequent brain change. Physical fitness was an exception, being correlated both with brain level and changes. The results suggest that only a subset of correlates of brain structure are also predictive of differences in brain ageing