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.

Elucidating the host–pathogen interaction between human colorectal cells and invading Enterovirus 71 using transcriptomics profiling

Enterovirus 71 (EV71) is one of the main etiological agents for Hand, Foot and Mouth Disease (HFMD) and has been shown to be associated with severe clinical manifestation. Currently, there is no antiviral therapeutic for the treatment of HFMD patients owing to a lack of understanding of EV71 pathogenesis. This study seeks to elucidate the transcriptomic changes that result from EV71 infection. Human whole genome microarray was employed to monitor changes in genomic profiles between infected and uninfected cells. The results reveal altered expression of human genes involved in critical pathways including the immune response and the stress response. Together, data from this study provide valuable insights into the host–pathogen interaction between human colorectal cells and EV71.

Enterovirus71 (EV71) utilise host microRNAs to mediate host immune system enhancing survival during infection

Hand, Foot and Mouth Disease (HFMD) is a self-limiting viral disease that mainly affects infants and children. In contrast with other HFMD causing enteroviruses, Enterovirus71 (EV71) has commonly been associated with severe clinical manifestation leading to death. Currently, due to a lack in understanding of EV71 pathogenesis, there is no antiviral therapeutics for the treatment of HFMD patients. Therefore the need to better understand the mechanism of EV71 pathogenesis is warranted. We have previously reported a human colorectal adenocarcinoma cell line (HT29) based model to study the pathogenesis of EV71. Using this system, we showed that knockdown of DGCR8, an essential cofactor for microRNAs biogenesis resulted in a reduction of EV71 replication. We also demonstrated that there are miRNAs changes during EV71 pathogenesis and EV71 utilise host miRNAs to attenuate antiviral pathways during infection. Together, data from this study provide critical information on the role of miRNAs during EV71 infection.

Aha! The return of Alan Partridge

Throughout a long and occasionally distinguished career first as a television sports correspondent, then chat show host (dramatically ended by the accidental homicide of a guest live on air), then rebirth as a radio presenter at North Norfolk Digital, Alan Partridge has navigated the stormy waters of the British media landscape, now achieving mainstream success on the big screen with a starring role in Steve Coogan’s Alpha Papa (Declan Lowney, 2013). A man who in his desperation for a television series of his own once sank so low as to pitch a show called Monkey Tennis to the BBC finally finds his inner hero in a film which, while presenting mainly as comedy, also contains a biting critique of trends in the British media with which all journalists and media practitioners in general will be familiar. Alpha Papa is a nostalgic, elegiac riff on the pleasures and values of local radio the way it used to be, exemplified by North Norfolk Digital’s stable of flawed, but endearing jocks – Wally Banter, Bruno Brooks, Dave Clifton (who in one scene recounts the depths to which he sank as an alcoholic, drug addicted wreck—“I woke up in a skip with someone else’s underpants in my mouth. I can laugh about it now …”), and Pat Farrell. 50- something Pat is sacked by the new owners of North Norfolk Digital, who in their efforts to transform the station into a “multiplatform content provider” going by the more Gen Yfriendly name of Shape (“the way you want it to be”), wish to replace him with a younger, brattish model lacking in taste and manners. Out go records by the likes of Glen Campbell and Neil Diamond (“You can keep Jesus Christ”, observes Partridge after playing Diamond’s Sweet Caroline in a demonstration of the crackling radio repartee for which he is by now renowned, “that was the king of the Jews”), in comes Roachford. Pat, grieving his dead wife Molly, finally snaps and turns the glitzy media launch of Shape into a hostage siege. Only Alan Partridge, it seems, can step in and talk Pat out of a looming catastrophe.

Human exposure to brominated flame retardants

Human polybrominated diphenyl ether (PBDE) exposure occurs through a range of pathways including: ingestion of dust including hand-to-mouth contact; inhalation (air/particulate matter); and ingestion via food including the unique nutrition sources of human milk and placental transfer. While inhalation has been deemed a minor source of exposure, ingestion of food and dust make greater contributions to overall PBDE body burden with intake via dust reported to be much higher in infants than in adults. PBDEs have been detected in samples of human milk, blood serum, cord blood, and adipose tissue worldwide. Concentrations have been found to be highest in populations from North America, followed by Australia, Europe, and Asia. While factors such as gender and parity may not affect concentrations, occupational exposure and age (infants and children) are associated with higher PBDE concentrations. In contrast to “traditional” persistent organic pollutants, there is an inverse relationship between PBDE body burden and age. Predicted body burden calculated using available information on intake and elimination rates of BFRs appears to underestimate measured human body burden data obtained through analysis of BFRs in blood or human milk. This may be due to unknown exposure or inaccurate elimination data. Further exposure studies should focus on younger age groups and an investigation of human PBDE half-lives.

Random Gabor based templates for facial expression recognition in images with facial occlusion

Robust facial expression recognition (FER) under occluded face conditions is challenging. It requires robust algorithms of feature extraction and investigations into the effects of different types of occlusion on the recognition performance to gain insight. Previous FER studies in this area have been limited. They have spanned recovery strategies for loss of local texture information and testing limited to only a few types of occlusion and predominantly a matched train-test strategy. This paper proposes a robust approach that employs a Monte Carlo algorithm to extract a set of Gabor based part-face templates from gallery images and converts these templates into template match distance features. The resulting feature vectors are robust to occlusion because occluded parts are covered by some but not all of the random templates. The method is evaluated using facial images with occluded regions around the eyes and the mouth, randomly placed occlusion patches of different sizes, and near-realistic occlusion of eyes with clear and solid glasses. Both matched and mis-matched train and test strategies are adopted to analyze the effects of such occlusion. Overall recognition performance and the performance for each facial expression are investigated. Experimental results on the Cohn-Kanade and JAFFE databases demonstrate the high robustness and fast processing speed of our approach, and provide useful insight into the effects of occlusion on FER. The results on the parameter sensitivity demonstrate a certain level of robustness of the approach to changes in the orientation and scale of Gabor filters, the size of templates, and occlusions ratios. Performance comparisons with previous approaches show that the proposed method is more robust to occlusion with lower reductions in accuracy from occlusion of eyes or mouth.

Securing medical devices Part A : what’s available for endotracheal tubes?

Oral endotracheal tubes (ETTs) and nasogastric tubes (NGT) are common devices used in adult intensive care and numerous options exist for safe and comfortable securement of these devices. The aim of this project was to identify the available range of ETT and NGT securement devices in Australia as a resource for clinicians seeking to explore options for tube stabilisation. This article reports part A of this project: ETT securement options. Part B will report NGT device fixation options. Securing ETTs to ensure a patent airway with minimal ETT movement, promotion of patient comfort and absence of adverse events such as ETT dislodgement, unplanned extubation and device-related injury1, are essential critical care nursing actions. The ETT requires a fixation method that is robust yet does not traumatise or injure the mucosal tissues of the mouth and soft tissue of the lips.2,3 Choice of a securement apparatus is often determined by product availability in our units or hospitals but is also driven by evidence-based practice and clinician preference. Trying to put this information together can be difficult and time-consuming for the bedside clinician...

Mothers influencing mothers : the use of virtual discussion boards and their influence on consumption

Mothers represent a large segment of marketing dollars and traditionally, word of mouth was spread from mother to mother in a face-to-face environment, such as the school car park or mother’s groups. As families have evolved, so too has the traditional mother’s group. Limited academic studies have explored online mothers’ groups and how they impact on consumption. In order to explore the nature of this online influence and how mothers are influenced by other mothers online, a study was conducted through the use of observation and qualitative questioning. The data suggests that trust between mothers is generally high and mothers tend to trust the opinions of other mothers when they recommend a product. This is similar in other reference group contexts, however, mothers are communicating about brands frequently and influencing behaviour. This leads to a number of managerial and theoretical implications discussed in the paper.

Epithelial-mesenchymal transition and mesenchymal-epithelial transition are essential for the acquisition of stem cell properties in hTERT-immortalised oral epithelial cells

BACKGROUND INFORMATION: Evidence has shown that mesenchymal-epithelial transition (MET) and epithelial-mesenchymal transition (EMT) are linked to stem cell properties. We currently lack a model showing how the occurrence of MET and EMT in immortalised cells influences the maintenance of stem cell properties. Thus, we established a project aiming to investigate the roles of EMT and MET in the acquisition of stem cell properties in immortalised oral epithelial cells. RESULTS: In this study, a retroviral transfection vector (pLXSN-hTERT) was used to immortalise oral epithelial cells by insertion of the hTERT gene (hTERT(+)-oral mucosal epithelial cell line [OME]). The protein and RNA expression of EMT transcriptional factors (Snail, Slug and Twist), their downstream markers (E-cadherin and N-cadherin) and embryonic stem cell markers (OCT4, Nanog and Sox2) were studied by reverse transcription PCR and Western blots in these cells. Some EMT markers were detected at both mRNA and protein levels. Adipocytes and bone cells were noted in the multi-differentiation assay, showing that the immortal cells underwent EMT. The differentiation assay for hTERT(+)-OME cells revealed the recovery of epithelial phenotypes, implicating the presence of MET. The stem cell properties were confirmed by the detection of appropriate markers. Altered expression of alpha-tubulin and gamma-tubulin in both two-dimensional-cultured (without serum) and three-dimensional-cultured hTERT(+)-OME spheroids indicated the re-programming of cytoskeleton proteins which is attributed to MET processes in hTERT(+)-OME cells. CONCLUSIONS: EMT and MET are essential for hTERT-immortalised cells to maintain their epithelial stem cell properties.

Online Customer Experience : What is the Experience and how is it Difference for Frequent and Infrequent Purchasers, Age Cohorts and Gender Groups?

What do we know? • Customer Experience is increasingly becoming the new standard for differentiation in both offline and online retailing, and offers a sustainable competitive advantage. o The economic value of a company’s offering has been observed to increase when the customer has a fulfilling shopping experience (Pine & Gilmore, 1998) o Crafting engaging and customer experience is a known method of generating loyalty, advocacy and word of mouth (Tynan & McKechnie, 2009). o A good experience can entice consumers to shop for longer and spend more (Kim, 2001). • The customer’s experience is made up of diverse elements occurring before, during and after the purchase itself. (Discussed further on page 5). It is cumulative over time and can be influenced by touch points across multiple channels. What remains unclear? • How do Coles customers respond to the elements of online customer experience? • How does the online customer experience differ for frequent and infrequent purchasers? • Do differences between genders and age cohorts for online customer experience exist?

Diagnostic potential of saliva : state of the art and future applications [Potenziale diagnostico della saliva: stato dell’arte e applicazioni future]

Over the past 10 years, the use of saliva as a diagnostic fluid has gained attention and has become a translational research success story. Some of the current nanotechnologies have been demonstrated to have the analytical sensitivity required for the use of saliva as a diagnostic medium to detect and predict disease progression. However, these technologies have not yet been integrated into current clinical practice and work flow. As a diagnostic fluid, saliva offers advantages over serum because it can be collected noninvasively by individuals with modest training, and it offers a cost-effective approach for the screening of large populations. Gland-specific saliva can also be used for diagnosis of pathology specific to one of the major salivary glands. There is minimal risk of contracting infections during saliva collection, and saliva can be used in clinically challenging situations, such as obtaining samples from children or handicapped or anxious patients, in whom blood sampling could be a difficult act to perform. In this review we highlight the production of and secretion of saliva, the salivary proteome, transportation of biomolecules from blood capillaries to salivary glands, and the diagnostic potential of saliva for use in detection of cardiovascular disease and oral and breast cancers. We also highlight the barriers to application of saliva testing and its advancement in clinical settings. Saliva has the potential to become a first-line diagnostic sample of choice owing to the advancements in detection technologies coupled with combinations of biomolecules with clinical relevance.

Human saliva as a tool to investigate intimate partner violence

Human saliva mirrors body’s health and well-being and many of the biomolecules present in blood or urine can also be found in salivary secretions. However, biomolecular concentrations in saliva are usually one tenth to one thousandth of the levels in blood (Pfaffe et al., 2011). Sensitive detection technology platforms are therefore required to detect biomolecules in saliva. Another road block to the advancement of salivary diagnostics is the lack of information related to healthy state saliva vs. a diseased saliva, baseline levels and reference ranges and diurnal variations. Saliva has numerous advantages over blood or urine as a diagnostic fluid: (a) the non-invasive nature of sample collection and the simple, safe, painless and cost-effective methods to collect it; (b) unskilled personnel can collect saliva samples at multiple time points; and (c) the total protein concentration is approximately a quarter of that is present in plasma, which makes it easier to investigate low abundance proteins (Pfaffe et al., 2011). Currently, saliva assays are routinely used to determine, diseases such as HIV, drugs and substances of abuse to provide information on exposure and give qualitative information on the type of illicit drug used (Kintz et al., 2009), cortisol levels for diagnosing Cushing’s syndrome (Doi et al., 2008), and use for biomonitoring of exposure to chemicals (Caporossi et al., 2010) to measure hormones (Gröschl, 2009)....

Commercial friendships between gay salesmen and straight female customers

Perhaps it is now sacrosanct in marketing to contemplate that many service encounters, especially those in retail settings, are social encounters in which bonds between and among customers and employees are critical drivers of consumption (Beatty et al., 1996; Rosenbaum, 2006). Indeed, within retail settings, it is often possible for salespeople and customers to form so-called “commercial friendships” (Price and Arnould, 1999). These friendships result in both salespeople and their customers having social interactions that are close to those experienced in personal friendships (Swan et al., 2001), and which are extremely satisfying for all parties. Outside of marketing, the social science literature (Grigoriou, 2004; Rumens, 2008; Russell, DelPriore, Butterfield, and Hill, 2013) and popular press (de la Cruz and Dolby, 2007; Hopcke and Rafaty, 1999; Tilmann-Healy, 2001, Whitney, 1990) is replete with knowledge regarding the “absolutely fabulous” friendships (Hopcke and Rafaty, 1999) that often form between gay men and straight women. In fact, Western culture regularly highlights the compatibility of gay men and straight women in film, television, and writing, to the extent that they have now influenced popular thinking on the topic, so that gay men and straight females are viewed as sharing common plights and interests (Rumens, 2008). Yet, thus far, marketing researchers have looked askance at the effect of friendships between gay male employees and heterosexual female customers in consumption settings, such as retail stores and boutiques. Indeed, with the exception of Peretz’s (1995) participant observation regarding how young and outwardly gay salesmen use their ambiguous gender to sell women’s clothing, in a Paris-based luxury boutique, any theoretical explorations regarding retail-based commercial friendships between gay salesmen and female customers are non-existent—until now. This research addresses this apparent chasm in the literature by putting forth an original framework that shows how the emotional closeness between gay salesmen and female customers, due to the absence of sexual interest and inter-female competition, results in an intense emotional closeness, that facilitates pleasurable retail transactions, customer satisfaction, loyalty, and positive word-of-mouth. In doing so, this work extends the commercial friendship paradigm by considering retail-based, commercial friendships between an under-researched marketplace dyad; gay men and straight females. It is worth noting here that some straight women may find the idea of commercial friendships with gay salesmen as undesirable, due to the very notion of having relationships with retail organizations or employees (Noble and Phillips, 2004), or a personal disdain for homosexuality.

Facial identity and facial expression matching in 5 - 12-year-old children and adults

Facial identity and facial expression matching tasks were completed by 5–12-year-old children and adults using stimuli extracted from the same set of normalized faces. Configural and feature processing were examined using speed and accuracy of responding and facial feature selection, respectively. Facial identity matching was slower than face expression matching for all age groups. Large age effects were found on both speed and accuracy of responding and feature use in both identity and expression matching tasks. Eye region preference was found on the facial identity task and mouth region preference on the facial expression task. Use of mouth region information for facial expression matching increased with age, whereas use of eye region information for facial identity matching peaked early. The feature use information suggests that the specific use of primary facial features to arrive at identity and emotion matching judgments matures across middle childhood.

An investigation of problem-solving support and relaxation motivations on e-WOM

As a consequence of greater computer-mediated consumer-to-consumer communication within the firm's marketing communications, there has been a growing need to understand these digital interactions more explicitly. That is, we still know little about the exact extrinsic and intrinsic motivations that drive electronic word-of-mouth. The purpose of the paper is to better understand why members within community-based websites develop a need to exchange and/or develop a social bond within the community. Questionnaire data were gathered from 147 members of an online beauty forum in Australia. The findings highlight that those members seeking problem-solving support in combination with elements of relaxation will be more inclined to exchange with other community members and develop a social bond within that community. Marketing managers can capitalise these findings by strengthening problem-solving support systems and creating environments where community members can also relax and unwind to increase the exchange between members and also increase the social bonds within the community.