Symptom control and quality of life in lux-lung 3 : a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations

Purpose Patient-reported symptoms and health-related quality of life (QoL) benefits were investigated in a randomized, phase III trial of afatinib or cisplatin/pemetrexed. Patients and Methods Three hundred forty-five patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma were randomly assigned 2:1 to afatinib 40 mg per day or up to six cycles of cisplatin/pemetrexed. Lung cancer symptoms and health-related QoL were assessed every 21 days until progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Lung Cancer-13 questionnaires. Analyses of cough, dyspnea, and pain were preplanned, including percentage of patients who improved on therapy, time to deterioration of symptoms, and change in symptoms over time. Results Questionnaire compliance was high. Compared with chemotherapy, afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; 95% CI, 0.41 to 0.87; P = .007) and dyspnea (HR, 0.68; 95% CI, 0.50 to 0.93; P = .015), but not pain (HR, 0.83; 95% CI, 0.62 to 1.10; P = .19). More patients on afatinib (64%) versus chemotherapy (50%) experienced improvements in dyspnea scores (P lt; .010). Differences in mean scores over time significantly favored afatinib over chemotherapy for cough (P lt; .001) and dyspnea (P = .001). Afatinib showed significantly better mean scores over time in global health status/QoL (P = .015) and physical (P = .001), role (P = .004), and cognitive (P lt; .007) functioning compared with chemotherapy. Fatigue and nausea were worse with chemotherapy, whereas diarrhea, dysphagia, and sore mouth were worse with afatinib (all P = .01). Conclusion In patients with lung adenocarcinoma with EGFR mutations, first-line afatinib was associated with better control of cough and dyspnea compared with chemotherapy, although diarrhea, dysphagia, and sore mouth were worse. Global health status/QoL was also improved over time with afatinib compared with chemotherapy.

Theatre and beyond : the application of theatre directing to other contexts

At a time when theatre practitioners and companies are concerned with dwindling audience numbers, funding and interest (so what’s new?), what this paper discusses is less about theatre ‘changing direction’ and more about ‘changing theatre Direction’. A subtle semantic shift perhaps but one which has proven enormously useful over 25 years as a professional creator, director, performer, designer and teacher for stage, screen – and other contexts. Applying theatrical skills to apparently unrelated contexts is not new, however it bears re-examining. My own experience as a ‘directorial specialist’ in mime and movement confirms the fundamental theatricality in all human communication – whether stage, screen, auditorium or meeting room – I would argue that there is no professional context completely devoid of some measure of ‘performance’. And if you’re going to do performance, however minutely, subtly and in whatever context, at least make it the best performance you can by ‘directing it’. This paper examines the adaptation of theatre direction to other contexts and discusses:- • which other contexts • directing non-performers • what theatre direction provides

What’s Mime got to do with it?

What has Mime got to do with Corporate Communication? As a professional Mime artist on both stage and screen for more than 25 years, the author has been adapting and applying the techniques of Mime to the corporate communication context over a number of years, coaching corporate CEO’s, Executives and Managers, representing both public and private sector corporations and organisations. This unusual inter-contextual skill transfer is the subject of both a book and series of VODCasts by the author (currently in the final stages of completion), which form part of the author’s Doctoral Research and from which this paper is substantially drawn. The author’s professional background is multi-disciplinary – encompassing theatre, television, media, music, tertiary education and corporate training contexts. It is also inter-disciplinary – concerned with the commonality of different artistic mediums and forms and how, where and why these professional disciplines: intersect; interact, and inform each other – and therefore how they support each other - rather than losing creative/professional opportunities because of areas where they might conflict. This paper examines in particular the physicality of presentation and communication – beyond ‘generic’ body-language analysis. It involves the analysis, manipulation and stylisation of human physicality to support and enhance individual inter-professional communication, and how mime performance skills specifically, inform that process. This paper discusses:- • how mime skills clarify and enhance inter-professional communication. • what adaptations need to be applied in that context • getting a ‘performance’ from ‘non-performers’

Blind Collaboration

This paper examines the creation, development and implementation of an artistic process termed by the author ‘Blind Collaboration’. The process involves musicians collaborating on an album of contemporary music where they, the collaborators, do not see or hear each other nor record in the same studio at the same time as their fellow musicians. The notion of musicians recording separately or indeed remotely is not new, however what is new is the ‘blind’ aspect of the process. Each musician is completely unaware of any others’ contributions, and is therefore uninfluenced by what the others might play. None of the musicians hears the overall result until the final mix. The principal focus of this case study lies in the analysis of specific aspects and outcomes of the creative/artistic process - how it evolved, how it was managed, how it was influenced by the particular artists involved and how the Blind Collaboration process ultimately shaped the final musical work.

Association of MMP-2 activation potential with metastatic progression in human breast cancer cell lines independent of MMP-2 production

Background: Expression of matrix metalloproteinase-2 (MMP-2), the 72-kd type IV collagenase/gelatinase, by cancer cells has been implicated in metastasis through cancer cell invasion of basement membranes mediated by degradation of collagen IV. However, the abundance of this latent proenzyme in normal tissues and fluids suggests that MMP-2 proenzyme utilization is limited by its physiological activation rather than expression alone. We previously reported activation of this proenzyme by normal and malignant fibroblastoid cells cultured on collagen I (vitrogen) gels. Purpose: Our purposes in this study were 1) to determine whether MMP-2 activation is restricted to the more invasive human breast cancer cell lines and 2) to localize the activating mechanism. Methods: Zymography was used to monitor MMP-2 activation through detection of latent MMP-2 (72 kd) and mature species of smaller molecular weight (59 or 62 kd). Human breast cancer cell lines cultured on plastic, vitrogen, and other matrices were thus screened for MMP- 2 activation. Collagen I-cultured cells were exposed to cycloheximide, a protein synthesis inhibitor, or to protease inhibitors to determine the nature of the MMP-2-activating mechanism. Triton X-114 (TX-114) detergent extracts from cells cultured on collagen I or plastic were incubated with latent MMP-2 and analyzed by zymography to localize the MMP-2 activator. Results: MMP-2 activation was only induced by collagen I culture in the more aggressive, highly invasive estrogen receptor-negative, vimentin-positive human breast cancer cell lines (Hs578T, MDA-MB-436, BT549, MDA-MB-231, MDA- MB-435, MCF-7(ADR)) and was independent of MMP-2 production. MMP-2 activation was detected in cells cultured on collagen I gels but not in those cultured on gelatin gels, Matrigel, or thin layers of collagen I or IV, gelatin, or fibronectin. Collagen-induced activation was specific for the enzyme species MMP-2, since MMP-9, the 92-kd type IV collagenase/gelatinase, was not activatable under similar conditions. MMP-2 activation was inhibited by cycloheximide and was sensitive to a metalloproteinase inhibitor but not to aspartyl, serine, or cysteinyl protease inhibitors. MMP-2 activation was detected in the hydrophobic, plasma membrane-enriched, TX-114 extracts from invasive collagen I-cultured cells. Conclusion: Collagen I-induced MMP-2 activation is restricted to highly invasive estrogen receptor-negative, vimentin-positive human breast cancer cell lines, is independent of MMP-2 production, and is associated with metastatic potential. Our findings are consistent with plasma membrane localization of the activator. Implications: The MMP-2 activation mechanism may represent a new target for diagnosis, prognosis, and treatment of human breast cancer.

The 'gourmet' sausage factory: Keeping it human

Whilst tertiary institutions continue to invest heavily in the technological aspects of online Teaching & Learning (T&L), there does not appear to have been a commensurate investment in the “human” aspects of the use of the technology. Despite the broad recognition that teaching and learning materials need to be adapted for and to the onscreen medium, little attention appears to have been paid thus far to the actual people who are delivering it – who equally need to “adapt themselves” to that medium, in order to maximise the benefit of the technology by maximising the human communication skills of those using the online medium – as distinct from the technical skills required to drive and deliver the bits and bytes. The REdelivery Initiative was a direct response to that notion. This paper details – by way of a narrative of one of the workshop participants – that part of the process involving the professional development of academics specifically in and specifically for the digital, online, T&L context, in order to both illuminate and maximise the potential and opportunities afforded by the technology.

Molecular analysis of asymptomatic bacteriuria escherichia coli strain VR50 reveals adaptation to the urinary tract by gene acquisition

Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli responsible for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. To understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. Our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder.

Experimental measurement of the mechanical properties of carotid atherothrombotic plaque fibrous cap

Eleven carotid atherothrombotic plaque samples were harvested from patients. Three samples that were highly calcified were discarded, while eight yielded results. The elastic properties of the material were estimated by fitting the measured indentation response to finite element simulations. The methodology was refined and its accuracy quantified using a synthetic rubber. The neo-Hookean form of the material model gave a good fit to the measured response of the tissue. The inferred shear modulus μ was found to be in the range 7-100 kPa, with a median value of 11 kPa. A review of published materials data showed a wide range of material properties for human atherothrombotic tissue. The effects of anisotropy and time dependency in these published results were highlighted. The present measurements were comparable to the static radial compression tests of Lee et al, 1991 [Structure-dependent dynamic behaviour of fibrous caps from human atherosclerotic plaques. Circulation 83, 1764-1770].

Effect of iodine doping on surface and optical properties of polyterpenol thin films

This study presents the effect of iodine doping on optical and surface properties of polyterpenol thin films deposited from non-synthetic precursor by means of plasma polymerisation. Spectroscopic ellipsometry studies showed iodine doping reduced the optical band gap from 2.82 eV to 1.50 eV for pristine and doped samples respectively. Higher levels of doping notably reduced the transparency of films, an issue if material is considered for applications that require high transparency. Contact angle studies demonstrated higher hydrophilicity for films deposited at increased doping levels, results confirmed by XPS Spectroscopy and FTIR. Doping had no significant effect on the surface profile or roughness of the film.