Cost minimisation study of transdermal glyceryl trinitrate in reducing failures of peripheral intravenous infusion

This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 1989 BMJ Publishing Group

Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus

abstract: Surveillance of Barrett’s oesophagus allows us to study the evolutionary dynamics of a human neoplasm over time. Here we use multicolour fluorescence in situ hybridization on brush cytology specimens, from two time points with a median interval of 37 months in 195 non-dysplastic Barrett's patients, and a third time point in a subset of 90 patients at a median interval of 36 months, to study clonal evolution at single-cell resolution. Baseline genetic diversity predicts progression and remains in a stable dynamic equilibrium over time. Clonal expansions are rare, being detected once every 36.8 patient years, and growing at an average rate of 1.58 cm[superscript 2] (95% CI: 0.09–4.06) per year, often involving the p16 locus. This suggests a lack of strong clonal selection in Barrett’s and that the malignant potential of ‘benign’ Barrett’s lesions is predetermined, with important implications for surveillance programs.The final version of this article, as published in Nature Communications, can be viewed online at: https://www.nature.com/articles/ncomms1215

Change or control? Developing dialogues between research and public protection

This paper aims to scope out some of the implications of desistance research for the community management of high risk offenders. Acknowledging the limited empirical research exploring this interface, this paper outlines the evolving evidence base and what this tells us about the process of desistance and what supports it. The evidence as to whether 'high risk offenders' desist and what we know about this process is discussed prior to outlining the landscape of current and principal practice approaches which can be located in the community/public protection model. Potential dialogues between desistance research and public protection practices are discussed to explore ensuing implications and opportunities for practice

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Greenhouse gas emissions of realistic dietary choices in Denmark: the carbon footprint and nutritional value of dairy products

Background: Dairy products are important in a healthy diet due to their high nutritional value; they are, however, associated with relatively large greenhouse gas emissions (GHGE) per kg product. When discussing the need to reduce the GHGE caused by the food system, it is crucial to consider the nutritional value of alternative food choices. Objective: The objective of this study was to elucidate the role of dairy products in overall nutrition and to clarify the effects of dietary choices on GHGE, and to combine nutritional value and GHGE data. Methods: We created eight dietary scenarios with different quantity of dairy products using data from the Danish National Dietary Survey (1995–2006). Nutrient composition and GHGE data for 71 highly consumed foods were used to estimate GHGE and nutritional status for each dietary scenario. An index was used to estimate nutrient density in relation to nutritional recommendation and climate impact for solid food items; high index values were those with the highest nutrient density scores in relation to the GHGE. Results: The high-dairy scenario resulted in 27% higher protein, 13% higher vitamin D; 55% higher calcium; 48% higher riboflavin; and 18% higher selenium than the non-dairy scenario. There was a significant correlation between changes in calcium and changes in vitamin D, selenium, and riboflavin content (P=0.0001) throughout all of the diets. The estimated GHGE for the dietary scenario with average-dairy consumption was 4,631 g CO2e/day. Conclusions: When optimizing a diet with regard to sustainability, it is crucial to account for the nutritional value and not solely focus on impact per kg product. Excluding dairy products from the diet does not necessarily mitigate climate change but in contrast may have nutritional consequences

Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives

Dietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2- dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Methods: Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30-55 years of age with a reported EPA+DHA consumption of ≤ 300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments. Results: 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. Conclusions: The endogenous detection of these electro.©2014 Cipollina et al

MicroRNA-135b Regulates Leucine Zipper Tumor Suppressor 1 in Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and it presents a therapeutic challenge in organ transplant recipient patients. Despite the need, there are only a few targeted drug treatment options. Recent studies have revealed a pivotal role played by microRNAs (miRNAs) in multiple cancers, but only a few studies tested their function in cSCC. Here, we analyzed differential expression of 88 cancer related miRNAs in 43 study participants with cSCC; 32 immunocompetent, 11 OTR patients, and 15 non-lesional skin samples by microarray analysis. Of the examined miRNAs, miR-135b was the most upregulated (13.3-fold, 21.5-fold; p=0.0001) in both patient groups. Similarly, the miR-135b expression was also upregulated in three cSCC cell lines when evaluated by quantitative real-time PCR. In functional studies, inhibition of miR-135b by specific anti-miR oligonucleotides resulted in upregulation of its target gene LZTS1 mRNA and protein levels and led to decreased cell motility and invasion of both primary and metastatic cSCC cell lines. In contrast, miR-135b overexpression by synthetic miR-135b mimic induced further down-regulation of LZTS1 mRNA in vitro and increased cancer cell motility and invasiveness. Immunohistochemical evaluation of 67 cSCC tumor tissues demonstrated that miR-135b expression inversely correlated with LZTS1 staining intensity and the tumor grade. These results indicate that miR-135b functions as an oncogene in cSCC and provide new understanding into its pathological role in cSCC progression and invasiveness

Corporate philanthropy through the lens of ethical subjectivity

The dynamic organisational processes in businesses dilute the boundaries between the individual, organisational, and societal drivers of corporate philanthropy. This creates a complex framework in which charitable project selection occurs. Using the example of European tour operators, this study investigates the mechanisms through which companies invest in charitable projects in overseas destinations. Inextricably linked to this is the increasing contestation by local communities as to how they are able to engage effectively with tourism in order to realise the benefits tourism development can bring. This research furthers such debates by exploring the processes through which tour operators facilitate community development through charitable giving. Findings show, with no formal frameworks in existence, project selection depends upon emergent strategies that connect the professional with the personal, with trust being positioned as a central driver of these informal processes. Discretionary responsibilities are reworked through business leaders’ commitment to responsible business practises and the ethical subjectivity guiding these processes

A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis

Extracellular matrix interactions have essential roles in normal physiology and many pathological processes. Although the importance of extracellular matrix interactions in metastasis is well documented, systematic approaches to identify their roles in distinct stages of tumorigenesis have not been described. Here we report a novel-screening platform capable of measuring phenotypic responses to combinations of extracellular matrix molecules. Using a genetic mouse model of lung adenocarcinoma, we measure the extracellular matrix-dependent adhesion of tumour-derived cells. Hierarchical clustering of the adhesion profiles differentiates metastatic cell lines from primary tumour lines. Furthermore, we uncovered that metastatic cells selectively associate with fibronectin when in combination with galectin-3, galectin-8 or laminin. We show that these molecules correlate with human disease and that their interactions are mediated in part by α3β1 integrin. Thus, our platform allowed us to interrogate interactions between metastatic cells and their microenvironments, and identified extracellular matrix and integrin interactions that could serve as therapeutic targets.National Institutes of Health (U.S.) (Grant K99-CA151968)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service AwardStand Up To Cancer (SU2C/AACR)David H. Koch Institute for Integrative Cancer Research at MIT (CTC Project)Harvard Stem Cell Institute (SG-0046-08-00)National Cancer Center (Postdoctoral Fellowship)National Cancer Institute (U.S.) (U54CA126515)National Cancer Institute (U.S.) (U54CA112967)Howard Hughes Medical InstituteMassachusetts Institute of Technology. Ludwig Center for Molecular Oncolog

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications