BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma

The rapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine-induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine-induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down-regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re-activation of vinorelbine-induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development

Glutamine is conditionally essential in cancer cells, being utilized as a carbon and nitrogen source for macromolecule production, as well as for anaplerotic reactions fuelling the tricarboxylic acid (TCA) cycle. In this study, we demonstrated that the glutamine transporter ASCT2 (SLC1A5) is highly expressed in prostate cancer patient samples. Using LNCaP and PC-3 prostate cancer cell lines, we showed that chemical or shRNA-mediated inhibition of ASCT2 function in vitro decreases glutamine uptake, cell cycle progression through E2F transcription factors, mTORC1 pathway activation and cell growth. Chemical inhibition also reduces basal oxygen consumption and fatty acid synthesis, showing that downstream metabolic function is reliant on ASCT2-mediated glutamine uptake. Furthermore, shRNA knockdown of ASCT2 in PC-3 cell xenografts significantly inhibits tumour growth and metastasis in vivo, associated with the down-regulation of E2F cell cycle pathway proteins. In conclusion, ASCT2-mediated glutamine uptake is essential for multiple pathways regulating the cell cycle and cell growth, and is therefore a putative therapeutic target in prostate cancer.

Comparing international television news : the case of violence presentation in Germany, Great Britain and Russia -- [in German : Gewalt in internationalen Fernsehnachrichten - eine komparative Analyse medialer Gewaltpräsentation in Deutschland, Großbritannien und Russland]

This is an important book that ought to launch a debate about how we research our understanding of the world, it is an innovative intervention in a vital public issue, and it is an elegant and scholarly hard look at what is actually happening. Jean Seaton, Prof of Media History, U of Westminster, UK & Official Historian of the BBC -- Summary: This book investigates the question of how comparative studies of international TV news (here: on violence presentation) can best be conceptualized in a way that allows for crossnational, comparative conclusions on an empirically validated basis. This book shows that such a conceptualization is necessary in order to overcome existing restrictions in the comparability of international analysis on violence presentation. Investigated examples include the most watched news bulletins in Great Britain (10o'clock news on the BBC), Germany (Tagesschau on ARD) and Russia (Vremja on Channel 1). This book highlights a substantial cross-national violence news flow as well as a cross-national visual violence flow (key visuals) as distinct transnational components. In addition, event-related textual analysis reveals how the historical rootedness of nations and its symbols of power are still manifested in televisual mediations of violence. In conclusion, this study lobbies for a conscientious use of comparative data/analysis both in journalism research and practice in order to understand what it may convey in the different arenas of today’s newsmaking.

Medicines related dysphagia in primary care: The prevalence of and impact on community pharmacists

Dysphagia is a common and problematic symptom characterised by varying degrees of difficulty swallowing food, fluids and medicines of differing consistencies. International primary care based studies have identified that between 1 in 4 and 1 in 5 patients have some form of dysphagia, it can affect medicines taking behaviour and healthcare professionals are largely unaware of this1,2. Similar research has not been undertaken in the UK. Adherence related pharmacy based services in the UK provide an opportunity for community pharmacists to identify the problem and facilitate better medicines use. The aim of this pilot study was to estimate the level of patient reported dysphagia in older persons using community pharmacies in the UK, describe how it affects their medicine taking behaviour and identify whether advanced pharmacy services are related to improved awareness of this.

Bike share's impact on car use : evidence from the United States, Great Britain, and Australia

There are currently more than 400 cities operating bike share programs. Purported benefits of bike share programs include flexible mobility, physical activity, reduced congestion, emissions and fuel use. Implicit or explicit in the calculation of program benefits are assumptions regarding the modes of travel replaced by bike share journeys. This paper examines the degree to which car trips are replaced by bike share, through an examination of survey and trip data from bike share programs in Melbourne, Brisbane, Washing, D.C., London, and Minneapolis/St. Paul. A secondary and unique component of this analysis examines motor vehicle support services required for bike share fleet rebalancing and maintenance. These two components are then combined to estimate bike share’s overall contribution to changes in vehicle kilometres traveled. The results indicate that the estimated mean reduction in car use due to bike share is at least twice the distance covered by operator support vehicles, with the exception of London, in which the relationship is reversed, largely due to a low car mode substitution rate. As bike share programs mature, evaluation of their effectiveness in reducing car use may become increasingly important. This paper reveals that by increasing the convenience of bike share relative to car use and by improving perceptions of safety, the capacity of bike share programs to reduce vehicle trips and yield overall net benefits will be enhanced. Researchers can adapt the analytical approach proposed in this paper to assist in the evaluation of current and future bike share programs.

Bike share's impact on car use : evidence from the United States, Great Britain, and Australia

There are currently more than 700 cities operating bike share programs. Purported benefits of bike share include flexible mobility, physical activity, reduced congestion, emissions and fuel use. Implicit or explicit in the calculation of program benefits are assumptions regarding the modes of travel replaced by bike share journeys. This paper examines the degree to which car trips are replaced by bike share, through an examination of survey and trip data from bike share programs in Melbourne, Brisbane, Washington, D.C., London, and Minneapolis/St. Paul. A secondary and unique component of this analysis examines motor vehicle support services required for bike share fleet rebalancing and maintenance. These two components are then combined to estimate bike share’s overall contribution to changes in vehicle kilometers traveled. The results indicate an estimated reduction in motor vehicle use due to bike share of approx. 90,000 km per annum in Melbourne and Minneapolis/St. Paul and 243,291 km for Washington, D.C. London’s bike share program however recorded an additional 766,341 km in motor vehicle use. This was largely due to a low car mode substitution rate and substantial truck use for rebalancing of bicycles. As bike share programs mature, evaluation of their effectiveness in reducing car use may become increasingly important. Researchers can adapt the analytical approach proposed in this paper to assist in the evaluation of current and future bike share programs.

Bikeshare's impact on active travel: Evidence from the United States, Great Britain, and Australia

Over 800 cities globally now offer bikeshare programs. One of their purported benefits is increased physical activity. Implicit in this claim is that bikeshare replaces sedentary modes of transport, particularly car use. This paper estimates the median changes in physical activity levels as a result of bikeshare in the cities of Melbourne, Brisbane, Washington, D.C., London, and Minneapolis/St. Paul. This study is the first known multi-city evaluation of the active travel impacts of bikeshare programs. To perform the analysis, data on mode substitution (i.e. the modes that bikeshare replaces) were used to determine the extent of shift from sedentary to active transport modes (e.g. when a car trip is replaced by bikeshare). Potentially offsetting these gains, reductions in physical activity when walking trips are replaced by bikeshare was also estimated. Finally a Markov Chain Monte Carlo analysis was conducted to estimate confidence bounds on estimated impacts on active travel given uncertainties in data sources. The results indicate that on average 60% of bikeshare trips replace sedentary modes of transport (from 42% in Minneapolis/St. Paul to 67% in Brisbane). When bikeshare replaces a walking trip, there is a reduction in active travel time because walking a given distance takes longer than cycling. Considering the active travel balance sheet for the cities included in this analysis, bikeshare activity in 2012 has an overall positive impact on active travel time. This impact ranges from an additional 1.4 million minutes of active travel for the Minneapolis/St. Paul bikeshare program, to just over 74 million minutes of active travel for the London program The analytical approach adopted to estimate bikeshare’s impact on active travel may act as the basis for future bikeshare evaluations or feasibility studies.

Nurses’ views on the implementation of Individualised Medication Administration Guides in patients with dysphagia in care homes

As conditions such as stroke, cancer, Parkinson's disease and Huntingdon's chorea are commonly found in care homes between 15% and 30% of residents in care homes have been found to have difficulties in swallowing their medicines.To address the difficulties associated with administering medicines to patients who cannot swallow (with dysphagia), Individualised Medication Administration Guides (I-MAGs) were introduced by a specialised pharmacist in Care for Elderly wards in a general hospital in East Anglia. The guides contained detailed information about how to administer each medication and they were individualised to the needs of the patient. The I-MAGs were printed in green forms and attached to the medication chart in order to be used in conjunction with it. The ward nurses reported an increase in their confidence when administering medication when I-MAGs were present in the ward. Some patients with I-MAG were discharged to care homes where the I-MAG might have been equally useful. However, the design of such guides is not known to be suitable for care homes environment where they have never been used before. This study aims to explore the opinions of nurses and carers within care homes on the relevance and acceptability of individualised medication administration guides for patients with dysphagia (PWD).

A systematic review of capnography for sedation

We included six trials with 2524 participants. Capnography reduced hypoxaemic episodes, relative risk (95% CI) 0.71 (0.56-0.91), but the quality of evidence was poor due to high risks of performance bias and detection bias and substantial statistical heterogeneity. The reduction in hypoxaemic episodes was statistically homogeneous in the subgroup of three trials of 1823 adults sedated for colonoscopy, relative risk (95% CI) 0.59 (0.48-0.73), although the risks of performance and detection biases were high. There was no evidence that capnography affected other outcomes, including assisted ventilation, relative risk (95% CI) 0.58 (0.26-1.27), p = 0.17.

Journeys to health services in Great Britain : an analysis of changing travel patterns 1985-2006

This paper examines changing patterns in the utilisation and geographic access to health services in Great Britain using National Travel Survey data (1985-2006). The utilisation rate was derived using the proportion of journeys made to access health services. Geographic access was analysed by separating the concept into its accessibility and mobility dimensions. Regression analyses were conducted to investigate the differences between different socio-spatial groups in these indicators over the period 1985-2006. This study found that journey distances to health facilities were significantly shorter and also gradually reduced over the period in question for Londoners, females, those without a car or on low incomes, and older people. However, most of their rates of utilisation of health services were found to be significantly lower because their journey times were significantly longer and also gradually increased over the periods. These findings indicate that the rate of utilisation of health services largely depends on mobility level although previous research studies have traditionally overlooked the mobility dimension.

Significant Dot: The 1769 transit of Venus - a tale of astronomy, medicine and empire

This article places the 6 June 2012 transit of Venus in the context of James Cook’s voyage from England to the South Pacific to observe the 1769 transit of Venus. A description is given on how to use a computer program called Stellarium to ‘observe’ the 1769 transit of Venus exactly as Cook saw it from the island of Tahiti in the South Pacific.