Impact of stable angina on health status and quality of life perception of currently treated patients. The BRIDGE 2 survey.

OBJECTIVE: to explore 1) the perception of stable angina (SA) - impact on quality of life (QoL) and current condition related to SA; 2) SA burden - symptoms and frequency of anginal episodes; 3) impairment attributable to SA - limitations in daily activities and impact on work; 4) characteristics that might affect the patients' perception." METHOD: a proprietary questionnaire was administered on-line to SA patients selected using a purpose-built screening program from general population panels collaborating with IQVIA in Italy, Germany, Spain, and the UK. Exploratory analyses were performed: descriptive statistics on the total sample and different stratifications (gender, age class, time since diagnosis) were provided; we used Chi-square tests to compare subgroups. RESULTS: of more than 25,000 subjects who accessed the survey, 268 were eligible and completed the questionnaire: mean age was 61 years and women accounted for 30%. Despite being treated, about 40% of patients reported that SA impacted "completely" or "very much" their QoL, 10% rated their condition as "not good", and 45.1% stated that they felt "Fair". The majority of patients were still symptomatic and many of them perceived that SA had a major impact on their working life. Women, younger patients and those with a more recent diagnosis reported a worse self-assessment of their condition, QoL and symptom burden. CONCLUSIONS: the results of our survey provide new insights on how patients with SA perceived their own health status and suggest that any patient with SA deserves a more detailed and accurate evaluation by their physicians

Multinuclear ruthenium(II) complexes as anticancer agents

A series of dinuclear ruthenium(ii) complexes that contain labile chlorido ligands, [{Ru(tpy)Cl}2{μ-bbn}]2+ {designated Cl-Rubbn; tpy = 2,2′:6′,2′′-terpyridine, bbn = bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (n = 7, 10, 12, 14 or 16)} and derivatives containing nitro substituents on the tpy ligand and/or secondary amines within the bbn linking chain have been synthesised and their potential as anticancer agents examined. Some of the Cl-Rubbn species showed good anticancer activity against MCF-7 and MDA-MB-231 breast cancer cell lines, with the Cl-Rubb12 complex being four-times more active than cisplatin. Inclusion of nitro substituents on the tpy ligands of Cl-Rubb12 resulted in significantly decreased anticancer activity. The incorporation of amine groups into the linking ligand did not increase the anticancer activity of the Cl-Rubbn complexes. The Cl-Rubbn complexes and those containing amine groups in the linking chain aquated at approximately the same rate, with 50% aquation within 120 minutes. By comparison, the complexes containing nitro substituents on the tpy ligand aquated extremely slowly, with 60% of the chlorido complex remaining 24 hours after they were dissolved in water. Cyclic voltammetry with the model mononuclear complex [Ru{(NO2)3tpy}(Me2bpy)Cl] + {(NO2)3tpy = 4,4′,4′′- trinitro-2,2′:6′,2′′-terpyridine} showed that the nitro substituents exerted a strong effect on the ruthenium centre, with the anodic peak corresponding to the Ru(iii/ii) couple shifted positively by 300 mV compared to that from the non-nitrated parent complex [Ru(tpy)(Me 2bpy)Cl]+. 1H NMR studies of the reaction of the Cl-Rubbn complexes with GMP indicated that the ruthenium complexes covalently bound the nucleotide slowly, with 33% bound in 24 hours. However, the results of this study suggest that the cytotoxicity of the dinuclear ruthenium complexes is a combination of covalent and reversible binding with DNA. © the Partner Organisations 2014

Concussion in sport: what is known and what is new?

The aim of this article was to summarise the latest definition of concussion, signs of concussion, as well as important facts on recovery and graduated return to play, for different age groups. New technologies available to the sports physician are listed.Keywords: concussion, diagnosis, return to play, sign

Characterising gas behaviour during gas–liquid co-current up-flow in packed beds using magnetic resonance imaging

Magnetic resonance (MR) imaging techniques have been used to study gas phase dynamics during co-current up-flow in a column of inner diameter 43 mm, packed with spherical non-porous elements of diameters of 1.8, 3 and 5 mm. MR measurements of gas hold-up, bubble-size distribution, and bubble-rise velocities were made as a function of flow rate and packing size. Gas and liquid flow rates were studied in the range of 20–250 cm3 s−1 and 0–200 cm3 min−1, respectively. The gas hold-up within the beds was found to increase with gas flow rate, while decreasing with increasing packing size and to a lesser extent with increasing liquid flow rate. The gas hold-up can be separated into a dynamic gas hold-up, only weakly dependent on packing size and associated with bubbles rising up the bed, and a ‘static’ hold-up which refers to locations within the bed associated with temporally-invariant gas hold-up, over the measurement times of 512 s, associated either with gas trapped within the void structure of the bed or with gas channels within the bed. This ‘static’ gas hold-up is strongly dependent on packing size, showing an increase with decreasing packing size. The dynamic gas hold-up is comprised of small bubbles – of order of the packing size – which have rise velocities of 10–40 mm s−1 and which move between the packing elements within the bed, along with much larger bubbles, or agglomerates of bubbles, which move with higher rise velocities (100–300 mm s−1). These ‘larger’ bubbles, which may exist as streams of smaller bubbles or ‘amoeboid’ bubbles, behave as a single large bubble in terms of the observed high rise velocity. Elongation of the bubbles in the direction of flow was observed for all packings.We wish to thank ExxonMobil Research and Engineering Co. and EPSRC Platform Grant (EP/F047991/1) for financial support.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ces.2016.04.00

Using Strategic Options Development and Analysis (SODA) to understand the simulation accessibility problem

Simulation modelling is applied to a wide range of problems, including defence and healthcare. However, there is a concern within the simulation community that there is a limited use and implementation of simulation studies in practice. This suggests that despite its benefits, simulation may not be reaching its potential in making a real-world impact. The main reason for this could be that simulation tools are not widely accessible in industry. In this paper, we investigate the issues that affect simulation modelling accessibility through a workshop with simulation practitioners. We use Strategic Options Development and Analysis (SODA), a problem-structuring approach that allows for the stakeholder views to be expressed and linked in a systematic way. The causal map derived represents the emerging concepts and their effects, with the view to identifying their impact on the accessibility problem. We present our analysis of the issues and options identified. Based on our findings, we discuss the implications and recommendations for the future uptake of simulation

The views of older women towards mammographic screening: a qualitative and quantitative study

Purpose: Mammographic screening has improved breast cancer survival in the screened age group. This improved survival has not been seen in older women (>70 years) where screening uptake is low. This study explores the views, knowledge and attitudes of older women towards screening. Methods: Women (>70) were interviewed about breast screening. Interview findings informed the development of a questionnaire which was sent to 1000 women (>70) to quantify their views regarding screening. Results: Twenty-six women were interviewed and a questionnaire designed. The questionnaire response rate was 48.3% (479/992). Over half (52.9%, 241/456) of respondents were unaware they could request mammography by voluntary self-referral and were unaware of how to arrange this. Most (81.5% 383/470) had not attended breast screening since turning 70. Most (75.6%, 343/454) felt screening was beneficial and would attend if invited. Most, (90.1%, 412/457) felt screening should be offered to all women regardless of age or health. Conclusions: There is a lack of knowledge about screening in older women. The majority felt that invitation to screening should be extended to the older age group regardless of age or health. The current under-utilised system of voluntary self referral is not supported by older women

Flecainide reduces Ca2+ spark and wave frequency via inhibition of the sarcolemmal sodium current

AIMS: Ca(2+) waves are thought to be important in the aetiology of ventricular tachyarrhythmias. There have been conflicting results regarding whether flecainide reduces Ca(2+) waves in isolated cardiomyocytes. We sought to confirm whether flecainide inhibits waves in the intact cardiomyocyte and to elucidate the mechanism. METHODS AND RESULTS: We imaged spontaneous sarcoplasmic reticulum (SR) Ca(2+) release events in healthy adult rat cardiomyocytes. Variation in stimulation frequency was used to produce Ca(2+) sparks or waves. Spark frequency, wave frequency, and wave velocity were reduced by flecainide in the absence of a reduction of SR Ca(2+) content. Inhibition of I(Na) via alternative pharmacological agents (tetrodotoxin, propafenone, or lidocaine) produced similar changes. To assess the contribution of I(Na) to spark and wave production, voltage clamping was used to activate contraction from holding potentials of −80 or −40 mV. This confirmed that reducing Na(+) influx during myocyte stimulation is sufficient to reduce waves and that flecainide only causes Ca(2+) wave reduction when I(Na) is active. It was found that Na(+)/Ca(2+)-exchanger (NCX)-mediated Ca(2+) efflux was significantly enhanced by flecainide and that the effects of flecainide on wave frequency could be reversed by reducing [Na(+)](o), suggesting an important downstream role for NCX function. CONCLUSION: Flecainide reduces spark and wave frequency in the intact rat cardiomyocyte at therapeutically relevant concentrations but the mechanism involves I(Na) reduction rather than direct ryanodine receptor (RyR2) inhibition. Reduced I(Na) results in increased Ca(2+) efflux via NCX across the sarcolemma, reducing Ca(2+) concentration in the vicinity of the RyR2

A framework to assess the terrestrial risk of antibiotic resistance from antibiotics in slurry or manure amended soils

Antibiotic resistance (ABR) or the silent pandemic is a major global health and economic issue, threatening both modern healthcare and food production. There is increasing concern that the presence of antibiotics in the environment may select for the emergence and spread of antibiotic resistance. Currently environmental regulatory guidelines fail to address ABR risks, and while there is ongoing work to address this within aquatic environments, terrestrial systems have been somewhat overlooked – perhaps in part due to a focus on wastewater treatment plant effluent as the main source of antibiotics within the environment. Within agriculture there is an increasing push to move away from chemical-based fertilisers and towards the use of organic soil amendments such as slurry, manure or sludge, to improve soil health. However, these organic soil amendments have been shown to contain antibiotics and other pharmaceuticals alongside antibiotic resistant bacteria, posing a potential risk to the environment, livestock and humans through the proliferation and spread of ABR. It is therefore important that a risk framework is developed in relation to ABR and organic soil amendment use. Using current knowledge on the fate of antibiotics within soil and mathematical models, this manuscript presents a novel framework for assessing the terrestrial risk of antibiotic resistance through the use of farmyard manure as fertiliser