134 research outputs found
Postfeminism, men, masculinities and work: a research agenda for gender and organization studies scholars
Mobilizing the concept of postfeminism as a sensibility, this article invites organization and gender scholars to examine how postfeminist masculinities are discursively constituted and performed by men within contemporary work contexts. Acknowledging that women are interpellated within postfeminist discourses as empowered and autonomous subjects whose lives are shaped by individual choice, this article explores the implications for men, in particular how men variously perform postfeminist masculinities and the implications for addressing gendered inequalities within the workplace. Developing a research agenda, this article outlines three research trajectories: 1) problematizing a gender binary in which women are depicted as empowered at work and men in a state of crisis; 2) interrogating signs of ‘new’ postfeminist masculinities coded as inclusive in the workplace and; 3) examining how different types of men perform postfeminist masculinities at work. This article concludes by providing examples of research questions to generate future organizational scholarship in these areas
Brief Report: Clinical Response, Toxicity, and Resistance Mechanisms to Osimertinib Plus MET Inhibitors in Patients With EGFR-Mutant MET-Amplified NSCLC
INTRODUCTION:MET amplification is a known resistance mechanism to EGFR tyrosine kinase inhibitor (TKI) treatment in EGFR-mutant NSCLC. Dual EGFR-MET inhibition has been reported with success in overcoming such resistance and inducing clinical benefit. Resistance mechanisms to dual EGFR-MET inhibition require further investigation and characterization.
METHODS: Patients with NSCLC with both MET amplification and EGFR mutation who have received crizotinib, capmatinib, savolitinib, or tepotinib plus osimertinib (OSI) after progression on OSI at MD Anderson Cancer Center were included in this study. Molecular profiling was completed by means of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). Radiological response was assessed on the basis of Response Evaluation Criteria in Solid Tumors version 1.1.
RESULTS: From March 2016 to March 2022, 23 treatments with dual MET inhibitor and osi were identified with a total of 20 patients included. Three patients received capmatinib plus OSI after progression on crizotinib plus OSI. Median age was 64 (38–89) years old and 75% were female. MET amplification was detected by FISH in 14 patients in the tissue, NGS in 10 patients, and circulating tumor DNA in three patients. Median MET gene copy number was 13.6 (6.4–20). Overall response rate was 34.8% (eight of 23). In assessable patients, tumor shrinkage was observed in 82.4% (14 of 17). Median time on treatment was 27 months. Two of three patients responded to capmatinib plus OSI after progression on crizotinib plus OSI. Dual EGFR-MET inhibition was overall well tolerated. Two patients on crizotinib plus OSI and one pt on capmatinib plus OSI discontinued therapy due to pneumonitis. One pt discontinued crizotinib plus OSI due to gastrointestinal toxicity. Six patients were still on double TKI treatment. At disease progression to dual EGFR-MET inhibition, FISH and NGS on tumor and plasma were completed in six patients. Notable resistance mechanisms observed include acquired MET D1246H (n = 1), acquired EGFR C797S (n = 2), FGFR2 fusion (n = 1, concurrent with C797S), and EGFR G796S (n = 1, concurrent with C797S). Four patients lost MET amplification.
CONCLUSIONS: Dual EGFR and MET inhibition yielded high clinical response rate after progression on OSI. Resistance mechanisms to EGFR-MET double TKI inhibition include MET secondary mutation, EGFR secondary mutation, or loss of MET amplification
Bifidobacterium breve UCC2003 induces a distinct global transcriptomic programme in neonatal murine intestinal epithelial cells
The underlying health-driving mechanisms of Bifidobacterium during early life are not well understood, particularly how this microbiota member may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). We investigated the impact of Bifidobacterium breve UCC2003 on the transcriptome of neonatal murine IECs. Small IECs from two-week-old neonatal mice administered B. breve UCC2003 or PBS (control) were subjected to global RNA-Seq, and differentially expressed genes, pathways and affected cell types determined. We observed extensive regulation of the IEC transcriptome with ∼4,000 genes significantly up-regulated, including key genes linked with epithelial barrier function. Enrichment of cell differentiation pathways were observed, along with an overrepresentation of stem cell marker genes, indicating an increase in the regenerative potential of the epithelial layer. In conclusion, B. breve UCC2003 plays a central role in driving intestinal epithelium homeostatic development during early life and suggests future avenues for next-stage clinical studies
The Role of Health Kiosks in 2009: Literature and Informant Review
Kiosks can provide patients with access to health systems in public locations, but with increasing home Internet access their usefulness is questioned. A literature and informant review identified kiosks used for taking medical histories, health promotion, self assessment, consumer feedback, patient registration, patient access to records, and remote consultations. Sited correctly with good interfaces, kiosks can be used by all demographics but many ‘projects’ have failed to become routine practice. A role remains for: (a) integrated kiosks as part of patient ‘flow’, (b) opportunistic kiosks to catch people’s attention. Both require clear ‘ownership’ to succeed
A transient presence: black visitors and sojourners in Imperial Germany, 1884-1914
The onset of German colonial rule in Africa brought increasing numbers of Black men and women to Germany. Pre-1914 the vast majority of these Africans can best be described as visitors or sojourners and the Black population as a whole was a transient one. This makes recovering their presence in the archival record exceptionally difficult and it is not surprising that the existing historiography almost exclusively focuses on individual biographies of well documented lives. Through utilising a number of newly digitised archival materials, particularly the Hamburg Passenger Lists, this article draws upon a database with information on 1092 individuals from sub-Saharan Africa who spent time in Germany over the period 1884-1914 in order to add considerable bread and depth to our understanding of the Black presence as a whole. It provides increasing empirical detail about the make-up and character of this fluid population - where visitors came from, why they came to Germany, their age on arrival - as well as more accurate detail on the temporal and, to a lesser extent, spatial distribution of visitors
Directionally accelerated detection of an unknown second reactor with antineutrinos for mid-field nonproliferation monitoring
When monitoring a reactor site for nuclear nonproliferation purposes, the presence of an unknown or hidden nuclear reactor could be obscured by the activities of a known reactor of much greater power nearby. Thus when monitoring reactor activities by the observation of antineutrino emissions, one must discriminate known background reactor fluxes from possible unknown reactor signals under investigation. To quantify this discrimination, we find the confidence to reject the (null) hypothesis of a single proximal reactor, by exploiting directional antineutrino signals in the presence of a second, unknown reactor. In particular, we simulate the inverse beta decay (IBD) response of a detector filled with a 1 kT fiducial mass of Gadolinium-doped liquid scintillator in mineral oil. We base the detector geometry on that of WATCHMAN, an upcoming antineutrino monitoring experiment soon to be deployed at the Boulby mine in the United Kingdom whose design and deployment will be detailed in a forthcoming white paper. From this simulation, we construct an analytical model of the IBD event distribution for the case of one 4 GWt±2% reactor 25 km away from the detector site, and for an additional, unknown, 35 MWt reactor 3 to 5 km away. The effects of natural-background rejection cuts are approximated. Applying the model, we predict 3σ confidence to detect the presence of an unknown reactor within five weeks, at standoffs of 3 km or nearer. For more distant unknown reactors, the 3σ detection time increases significantly. However, the relative significance of directional sensitivity also increases, providing up to an eight week speedup to detect an unknown reactor at 5 km away. Therefore, directionally sensitive antineutrino monitoring can accelerate the mid-field detection of unknown reactors whose operation might otherwise be masked by more powerful reactors in the vicinity
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