Transcriptional Profiling of Non-Small Cell Lung Cancer Cells with Activating EGFR Somatic Mutations

Activating somatic mutations in epidermal growth factor receptor (EGFR) confer unique biologic features to non-small cell lung cancer (NSCLC) cells, but the transcriptional mediators of EGFR in this subgroup of NSCLC have not been fully elucidated.Here we used genetic and pharmacologic approaches to elucidate the transcriptomes of NSCLC cell lines. We transcriptionally profiled a panel of EGFR-mutant and -wild-type NSCLC cell lines cultured in the presence or absence of an EGFR tyrosine kinase inhibitor. Hierarchical analysis revealed that the cell lines segregated on the basis of EGFR mutational status (mutant versus wild-type), and expression signatures were identified by supervised analysis that distinguished the cell lines based on mutational status (wild-type versus mutant) and type of mutation (L858R versus Delta746-750). Using an EGFR mutation-specific expression signature as a probe, we mined the gene expression profiles of two independent cohorts of NSCLC patients and found the signature in a subset. EGFR tyrosine kinase inhibitor treatment regulated the expression of multiple genes, and pharmacologic inhibition of the protein products of two of them (PTGS2 and EphA2) inhibited anchorage-independent growth in EGFR-mutant NSCLC cells.We have elucidated genes not previously associated with EGFR-mutant NSCLC, two of which enhanced the clonogenicity of these cells, distinguishing these mediators from others previously shown to maintain cell survival. These findings have potential clinical relevance given the availability of pharmacologic tools to inhibit the protein products of these genes

Speaking and Listening with the Eyes: Gaze Signaling during Dyadic Interactions

Cognitive scientists have long been interested in the role that eye gaze plays in social interactions. Previous research suggests that gaze acts as a signaling mechanism and can be used to control turn-taking behaviour. However, early research on this topic employed methods of analysis that aggregated gaze information across an entire trial (or trials), which masks any temporal dynamics that may exist in social interactions. More recently, attempts have been made to understand the temporal characteristics of social gaze but little research has been conducted in a natural setting with two interacting participants. The present study combines a temporally sensitive analysis technique with modern eye tracking technology to 1) validate the overall results from earlier aggregated analyses and 2) provide insight into the specific moment-to-moment temporal characteristics of turn-taking behaviour in a natural setting. Dyads played two social guessing games (20 Questions and Heads Up) while their eyes were tracked. Our general results are in line with past aggregated data, and using cross-correlational analysis on the specific gaze and speech signals of both participants we found that 1) speakers end their turn with direct gaze at the listener and 2) the listener in turn begins to speak with averted gaze. Convergent with theoretical models of social interaction, our data suggest that eye gaze can be used to signal both the end and the beginning of a speaking turn during a social interaction. The present study offers insight into the temporal dynamics of live dyadic interactions and also provides a new method of analysis for eye gaze data when temporal relationships are of interest

Depression, Rational Identity and the Educational Imperative: Concordance-Finding in Tricky Diagnostic Moments

It is well-documented, within most medical and much health psychology, that many individuals find diagnoses of depression confusing or even objectionable. Within a corpus of research and practical clinical guidance dominated by the social-cognitive paradigm, the explanation for resistance to a depression diagnosis (or advice pertaining to it) within specific interactions is bordering on the canonical; patients misunderstand depression itself, often as an output of an associated social stigma that distorts public knowledge. The best way to overcome corollary resistance in situ is, logically thus, taken to be a clarification of the true (clinical) nature of depression. In this paper, exploring the diagnosis of depression in UK primary care contexts, the social-cognitive position embedded in contemporary medical reasoning around this matter is critically addressed. It is firstly highlighted how, even in a great deal of extant public health research, the link between an individual holding “correct” medical knowledge and being actively compliant with it is far from inevitable. Secondly, and with respect to concerns around direct communication in clinical contexts, a body of research emergent of Discursive Psychology and Conversation Analysis is explored so as to shed light on how non-cognitive concerns (not least those around the local interactional management of a patient’s social identity) that can inform the manner in which ostensibly “tricky” medical talk plays-out in practice, especially in cases where a mental illness is at stake. Finally, observations are drawn together in a formal Discursive Psychological analysis of a small but highly illustrative sample of three cases where a depression diagnosis is initially questioned or disputed by a patient in primary care but, following further in-consultation activity, concordance with the diagnosis is ultimately reached—a specific issue hitherto unaddressed in either DP or CA fields. These cases specifically reveal the coordinative attention of interlocutors to immediate concerns regarding how the patient might maintain a sense of being an everyday and rational witness to their own lives; indeed, the very act of challenging the diagnosis emerges as a means by which a patient can open up conversational space within the consultation to address such issues. While the veracity of the social-cognitive model is not deemed to be without foundation herein, it is concluded that attention to local interactional concerns might firstly be accorded, such that the practical social concerns and skills of practitioners and patients alike might not be overlooked in the endeavour to produce generally applicable theories

Three pillars of sustainability: in search of conceptual origins

The three-pillar conception of (social, economic and environmental) sustainability, commonly represented by three intersecting circles with overall sustainability at the centre, has become ubiquitous. With a view of identifying the genesis and theoretical foundations of this conception, this paper reviews and discusses relevant historical sustainability literature. From this we find that there is no single point of origin of this three-pillar conception, but rather a gradual emergence from various critiques in the early academic literature of the economic status quo from both social and ecological perspectives on the one hand, and the quest to reconcile economic growth as a solution to social and ecological problems on the part of the United Nations on the other. The popular three circles diagram appears to have been first presented by Barbier (Environ Conserv 14:101, doi: 10.1017/s0376892900011449, 1987), albeit purposed towards developing nations with foci which differ from modern interpretations. The conceptualisation of three pillars seems to predate this, however. Nowhere have we found a theoretically rigorous description of the three pillars. This is thought to be in part due to the nature of the sustainability discourse arising from broadly different schools of thought historically. The absence of such a theoretically solid conception frustrates approaches towards a theoretically rigorous operationalisation of ‘sustainability’