Treatment rationale study design for the MetLung trial : a randomized, double-blind phase III study of onartuzumab (MetMAb) in combination with erlotinib versus erlotinib alone in patients who have received standard chemotherapy for stage IIIB or IV met-positive non-small-cell lung cancer

We present the treatment rationale and study design of the MetLung phase III study. This study will investigate onartuzumab (MetMAb) in combination with erlotinib compared with erlotinib alone, as second- or third-line treatment, in patients with advanced non-small-cell lung cancer (NSCLC) who are Met-positive by immunohistochemistry. Approximately 490 patients (245 per treatment arm) will receive erlotinib (150 mg oral daily) plus onartuzumab or placebo (15 mg/kg intravenous every 3 weeks) until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death. The efficacy objectives of this study are to compare overall survival (OS) (primary endpoint), progression-free survival, and response rates between the 2 treatment arms. In addition, safety, quality of life, pharmacokinetics, and translational research will be investigated across treatment arms. If the primary objective (OS) is achieved, this study will provide robust results toward an alternative treatment option for patients with Met-positive second- or third-line NSCLC. © 2012 Elsevier Inc. All Rights Reserved.

Perceptions of organ donors and willingness to donate organs upon death : a test of the prototype/willingness model

Understanding people's organ donation decisions may narrow the gap between organ supply and demand. In two studies, participants who had not recorded their posthumous organ donation decision (Study 1, N = 210; Study 2, N = 307) completed items assessing prototype/willingness model (PWM; attitude, subjective norm, donor prototype favorability and similarity, willingness) constructs. Attitude, subjective norm, and prototype similarity predicted willingness to donate. Prototype favorability and a Prototype Favorability × Similarity interaction predicted willingness (Study 2). These findings provide support for the PWM in altruistic health contexts, highlighting the importance of people's perceptions about organ donors in their donation decisions.

Consistent HMM parameter estimation using Kerridge inaccuracy rates

In this paper, we propose a novel online hidden Markov model (HMM) parameter estimator based on Kerridge inaccuracy rate (KIR) concepts. Under mild identifiability conditions, we prove that our online KIR-based estimator is strongly consistent. In simulation studies, we illustrate the convergence behaviour of our proposed online KIR-based estimator and provide a counter-example illustrating the local convergence properties of the well known recursive maximum likelihood estimator (arguably the best existing solution).

A stepped-wedge cluster randomised controlled trial for evaluating rates of falls among inpatients in aged care rehabilitation units receiving tailored multimedia education in addition to usual care : a trial protocol

Introduction Falls are the most frequent adverse event reported in hospitals. Approximately 30% of in-hospital falls lead to an injury and up to 2% result in a fracture. A large randomised trial found that a trained health professional providing individualised falls prevention education to older inpatients reduced falls in a cognitively intact subgroup. This study aims to investigate whether this efficacious intervention can reduce falls and be clinically useful and cost-effective when delivered in the real-life clinical environment. Methods A stepped-wedge cluster randomised trial will be used across eight subacute units (clusters) which will be randomised to one of four dates to start the intervention. Usual care on these units includes patient's screening, assessment and implementation of individualised falls prevention strategies, ongoing staff training and environmental strategies. Patients with better levels of cognition (Mini-Mental State Examination >23/30) will receive the individualised education from a trained health professional in addition to usual care while patient's feedback received during education sessions will be provided to unit staff. Unit staff will receive training to assist in intervention delivery and to enhance uptake of strategies by patients. Falls data will be collected by two methods: case note audit by research assistants and the hospital falls reporting system. Cluster-level data including patient's admissions, length of stay and diagnosis will be collected from hospital systems. Data will be analysed allowing for correlation of outcomes (clustering) within units. An economic analysis will be undertaken which includes an incremental cost-effectiveness analysis. Ethics and dissemination The study was approved by The University of Notre Dame Australia Human Research Ethics Committee and local hospital ethics committees. Results The results will be disseminated through local site networks, and future funding and delivery of falls prevention programmes within WA Health will be informed. Results will also be disseminated through peer-reviewed publications and medical conferences.

Suicide and the therapeutic coroner : inquests, governance and the grieving family

This study of English Coronial practice raises a number of questions about the role played by the Coroner within contemporary governance. Following observations at over 20 inquests into possible suicides and in-depth interviews with six Coroners, three preliminary issue emerged, all of which pointed to a broader and, in many ways, more significant issue. These preliminary issues are concerned with: (1) the existence of considerable slippages between different Coroners over which deaths are likely to be classified as suicide; (2) the high standard of proof required and immense pressure faced by Coroners from family members at inquest to reach any verdict other than suicide, which significantly depresses likely suicide rates, and; (3) Coroners feeling no professional obligation, either individually or collectively, to contribute to the production of consistent and useful social data regarding suicide, arguably rendering comparative suicide statistics relatively worthless. These concerns lead, ultimately, to the second more important question about the role expected of Coroners within social governance and within an effective, contemporary democracy. That is, are Coroners the principal officers in the public administration of death; or are they, first and foremost, a crucial part of the grieving process, one that provides important therapeutic interventions into the mental and emotional health of the community?

Investigating the individual and organisational predictors of work-related driving crash involvement in Ethiopia

The rate of road traffic injury and death in Ethiopia is at a critical level when compared to rates in high-income countries. Considering the enormity of this issue, research is to identify groups of high-risk road users and the factors contributing to their crash involvement. This study focuses on work-related drivers. This study explores driving behaviour as a mediator of the relationship between organisational and individual attribute factors and self-reported crashes in a sample of 213 work-related drivers in Addis Ababa, Ethiopia. The hypothesised framework identifies driving behaviour as the most proximal determinant of self-reported crashes, and safety values, role overload and self-efficacy as antecedents of driving behaviour. With the exception of the relationship between self-efficacy and driving behaviour, all the hypothesised relationships were supported. We make recommendations for intervention approaches that are theoretically focused and sensitive to the cultural context.

Escape from apoptosis after prolonged serum deprivation is associated with the regulation of the mitochondrial death pathway by Bcl-x(l)

Bcl-x(l) and Bax play important roles in the regulation of apoptosis. This study investigated the involvement of the mitochondrial death pathway and the role of Bcl-x(l) and Bax in the escape from apoptosis after prolonged serum deprivation in Madin-Darby canine kidney (MDCK) cells. Low level apoptosis and basal activity of the mitochondrial death pathway were detectable in normal cell growth. In serum deprivation, mitosis was partially suppressed, and the mitochondrial activity was stimulated. The level of apoptosis continuously rose over 48 h. This rise was concomitant with the increasing presence of cytochrome c in cytosol. However, both apoptosis and cytosolic cytochrome c fell dramatically at 72 h. Elevation of whole cell Bcl-x(l) and redistribution of Bcl-x(l) protein from cytosol to the membrane at 48 h and 72 h was observed. Redistribution of Bax protein from the membrane to cytosol occurred at 24 h, and remained steady to 72 h. Bax/Bcl-x(l) coimmunoprecipitation by anti-Bax antibody showed reduced Bax/Bcl-x(l) interaction at the membrane at 72 h, but not at 24 or 48 h. These results suggest that apoptosis upon serum withdrawal results from the leakage of cytochrome c to cytosol. Amelioration of the leakage of cytochrome c and apoptosis requires not only the increase of Bcl-x(l)/Bax ratio, but also the release of Bcl-x(l) from Bax at the membrane.

Alcohol ingestion impairs maximal post-exercise rates of myofibrillar protein synthesis following a single bout of concurrent training

Introduction The culture in many team sports involves consumption of large amounts of alcohol after training/competition. The effect of such a practice on recovery processes underlying protein turnover in human skeletal muscle are unknown. We determined the effect of alcohol intake on rates of myofibrillar protein synthesis (MPS) following strenuous exercise with carbohydrate (CHO) or protein ingestion. Methods In a randomized cross-over design, 8 physically active males completed three experimental trials comprising resistance exercise (8×5 reps leg extension, 80% 1 repetition maximum) followed by continuous (30 min, 63% peak power output (PPO)) and high intensity interval (10×30 s, 110% PPO) cycling. Immediately, and 4 h post-exercise, subjects consumed either 500 mL of whey protein (25 g; PRO), alcohol (1.5 g·kg body mass−1, 12±2 standard drinks) co-ingested with protein (ALC-PRO), or an energy-matched quantity of carbohydrate also with alcohol (25 g maltodextrin; ALC-CHO). Subjects also consumed a CHO meal (1.5 g CHO·kg body mass−1) 2 h post-exercise. Muscle biopsies were taken at rest, 2 and 8 h post-exercise. Results Blood alcohol concentration was elevated above baseline with ALC-CHO and ALC-PRO throughout recovery (P<0.05). Phosphorylation of mTORSer2448 2 h after exercise was higher with PRO compared to ALC-PRO and ALC-CHO (P<0.05), while p70S6K phosphorylation was higher 2 h post-exercise with ALC-PRO and PRO compared to ALC-CHO (P<0.05). Rates of MPS increased above rest for all conditions (~29–109%, P<0.05). However, compared to PRO, there was a hierarchical reduction in MPS with ALC-PRO (24%, P<0.05) and with ALC-CHO (37%, P<0.05). Conclusion We provide novel data demonstrating that alcohol consumption reduces rates of MPS following a bout of concurrent exercise, even when co-ingested with protein. We conclude that alcohol ingestion suppresses the anabolic response in skeletal muscle and may therefore impair recovery and adaptation to training and/or subsequent performance.

Sensationalizing death? Graphic disaster images in the tabloid and broadsheet press

Debates over the extent of graphic imagery of death in newspapers often suffer from generalized assertions that are based on inadequate or incomplete empirical evidence. Newspapers are believed to display death in very graphic ways, with particularly the tabloid press assumedly leading a race to the bottom. This article reports the results of a study of tabloid and broadsheet images of death from the 2010 Haiti earthquake in eight Western European and North American countries. It shows that, far from omnipresent, graphic images of death are relatively rare. While tabloids overall display a larger percentage of graphic images, this was not the case everywhere, with particularly the UK, Canada and the US displaying strong similarities between tabloids and broadsheets. In Austria, Germany, Norway and Switzerland, on the other hand, there were distinct differences between the two types. The article argues that different extents of tabloidization may account for these differences.

Oscar Pistorius and the death of Reeva Steenkamp : mapping public opinions on Twitter using frame analysis and data mining

This paper uses innovative content analysis techniques to map how the death of Oscar Pistorius' girlfriend, Reeva Steenkamp, was framed on Twitter conversations. Around 1.5 million posts from a two-week timeframe are analyzed with a combination of syntactic and semantic methods. This analysis is grounded in the frame analysis perspective and is different than sentiment analysis. Instead of looking for explicit evaluations, such as “he is guilty” or “he is innocent”, we showcase through the results how opinions can be identified by complex articulations of more implicit symbolic devices such as examples and metaphors repeatedly mentioned. Different frames are adopted by users as more information about the case is revealed: from a more episodic one, highly used in the very beginning, to more systemic approaches, highlighting the association of the event with urban violence, gun control issues, and violence against women. A detailed timeline of the discussions is provided.

In vitro assessment of migratory behavior of two cell populations in a simple multichannel microdevice

Recent literature suggests that mesenchymal stem/stromal cells (MSC) could be used as Trojan Horses to deliver “death-signals” to cancer cells. Herein, we describe the development of a novel multichannel cell migration device, and use it to investigate the relative migration rates of bone marrow-derived MSC and breast cancer cells (MCF-7) towards each other. Confluent monolayers of MSC and MCF-7 were established in adjacent chambers separated by an array of 14 microchannels. Initially, culture chambers were isolated by air bubbles (air-valves) contained within each microchannel, and then bubbles were displaced to initiate the assay. The MCF-7 cells migrated preferentially towards MSC, whilst the MSC did not migrate preferentially towards the MCF-7 cells. Our results corroborate previous literature that suggests MSC migration towards cancer cells in vivo is in response to the associated inflammation rather than directly to signals secreted by the cancer cells themselves.

Valuing those close to us : A comparison of German and Australian quality newspapers’ reporting of death in foreign news

A number of studies into the coverage of death have provided some evidence of journalists giving preference to events from certain regions and to certain types of death. This comprehensive evaluation of how two German and two Australian newspapers cover death specifically in foreign news finds clear evidence that journalists primarily look for events in countries which are culturally proximate to their own. The cultural proximity thesis here includes links such as cultural, political, economic or linguistic connections with a country. Some important national differences in how journalists at the Frankfurter Allgemeine Zeitung, Süddeutsche Zeitung, The Australian and The Sydney Morning Herald report on death were also identified. These could be traced to some important cultural differences between the two countries, underlining the need for more research which locates culture at the core of news analysis.

Graphic death in the news media : present or absent?

The debate over the absence or presence of death in public discourse has dominated death studies for some time. While the argument that death had been removed from public discourse and only existed in the private realm dominated at first, in recent years scholars have come to accept that death has moved back into public discourse. An important aspect has been the role played by the mass media. However, there has been little empirical research as to what level of death is actually visible, for example in terms of photographs. To this end, this paper examines how two German and two Australian newspapers cover death in terms of graphic photographs. By examining the number and types of photographs published during a 2-month timeframe, as well as through in-depth interviews with journalists, this paper argues that visible death is still largely absent from public discourse. Importantly, there exist differences as to what level of graphic death is acceptable between individual newspapers, as well as countries, supporting the argument that the absence/presence of death dichotomy needs to be viewed in a much more complex light.