Hypoxia and hyperglycaemia determine why some endometrial tumours fail to respond to metformin

High expression of Ki67, a proliferation marker, is associated with reduced endometrial cancer-specific survival. Pre-surgical metformin reduces tumour Ki-67 expression in some women with endometrial cancer. Metformin's anti-cancer activity may relate to effects on cellular energy metabolism. Since tumour hypoxia and glucose availability are major cellular redox determinants, we evaluated their role in endometrial cancer response to metformin. Endometrial cancer biopsies from women treated with pre-surgical metformin were tested for the hypoxia markers, HIF-1α and CA-9. Endometrial cancer cell lines were treated with metformin in variable glucose concentrations in normoxia or hypoxia and cell viability, mitochondrial biogenesis, function and energy metabolism were assessed. In women treated with metformin (n = 28), Ki-67 response was lower in hypoxic tumours. Metformin showed minimal cytostatic effects towards Ishikawa and HEC1A cells in conventional medium (25 mM glucose). In low glucose (5.5 mM), a dose-dependent cytostatic effect was observed in normoxia but attenuated in hypoxia. Tumours treated with metformin showed increased mitochondrial mass (n = 25), while in cultured cells metformin decreased mitochondrial function. Metformin targets mitochondrial respiration, however, in hypoxic, high glucose conditions, there was a switch to glycolytic metabolism and decreased metformin response. Understanding the metabolic adaptations of endometrial tumours may identify patients likely to derive clinical benefit from metformin

Gluon flux-tube distribution and linear confinement in baryons

We have observed the formation of gluon flux-tubes within baryons using lattice QCD techniques. A high-statistics approach, based on translational and rotational symmetries of the four-dimensional lattice, enables us to observe correlations between vacuum action density and quark positions in a completely gauge independent manner. This contrasts with earlier studies which used gauge-dependent smoothing techniques. We used 200 O(a^2) improved quenched QCD gauge-field configurations on a 16^3x32 lattice with a lattice spacing of 0.123 fm. In the presence of static quarks flux tubes representing the suppression of gluon-field fluctuations are observed. We have analyzed 11 L-shapes and 8 T and Y shapes of varying sizes in order to explore a variety of flux-tube topologies, including the ground state. At large separations, Y-shape flux-tube formation is observed. T-shaped paths are observed to relax towards a Y-shaped topology, whereas L-shaped paths give rise to a large potential energy. We do not find any evidence for the formation of a Delta-shaped flux-tube (empty triangle) distribution. However, at small quark separations, we observe an expulsion of gluon-field fluctuations in the shape of a filled triangle with maximal expulsion at the centre of the triangle. Having identified the precise geometry of the flux distribution, we are able to perform quantitative comparison between the length of the flux-tube and the associated static quark potential. For every source configuration considered we find a universal string tension, and conclude that, for large quark separations, the ground state potential is that which minimizes the length of the flux-tube. The flux tube radius of the baryonic ground state potential is found to be 0.38 \pm 0.03 fm, with vacuum fluctuations suppressed by 7.2 \pm 0.6 %.Comment: 16 pages, final version as accepted for publication in Physical review D1. Abstract, text, references and some figures have been revise

Computer simulation of bistable switching in a nematic device containing pear-shaped particles

We study the microscopic basis of bistable switching of a confined liquid crystal via Monte Carlo simulations of hard pear-shaped particles. Using both dielectric and dipolar field couplings to this intrinsically flexoelectric fluid, it is shown that pulsed fields of opposing polarity can be used to switch between the vertical and hybrid aligned states. Further, it is shown that the field-susceptibility of the surface polarisation, rather than the bulk flexoelectricity, is the main driver of this switching behaviour.</p

The challenges of communicating research evidence in practice: perspectives from UK health visitors and practice nurses

&lt;p&gt;Background: Health practitioners play a pivotal role in providing patients with up-to-date evidence and health information. Evidence-based practice and patient-centred care are transforming the delivery of healthcare in the UK. Health practitioners are increasingly balancing the need to provide evidence-based information against that of facilitating patient choice, which may not always concur with the evidence base. There is limited research exploring how health practitioners working in the UK, and particularly those more autonomous practitioners such as health visitors and practice nurses working in community practice settings, negotiate this challenge. This research provides a descriptive account of how health visitors and practice nurses negotiate the challenges of communicating health information and research evidence in practice.&lt;/p&gt; &lt;p&gt;Methods: A total of eighteen in-depth telephone interviews were conducted in the UK between September 2008 and May 2009. The participants comprised nine health visitors and nine practice nurses, recruited via adverts on a nursing website, posters at a practitioner conference and through recommendation. Thematic analysis, with a focus on constant comparative method, was used to analyse the data.&lt;/p&gt; &lt;p&gt;Results: The data were grouped into three main themes: communicating evidence to the critically-minded patient; confidence in communicating evidence; and maintaining the integrity of the patient-practitioner relationship. These findings highlight some of the daily challenges that health visitors and practice nurses face with regard to the complex and dynamic nature of evidence and the changing attitudes and expectations of patients. The findings also highlight the tensions that exist between differing philosophies of evidence-based practice and patient-centred care, which can make communicating about evidence a daunting task.&lt;/p&gt; &lt;p&gt;Conclusions: If health practitioners are to be effective at communicating research evidence, we suggest that more research and resources need to be focused on contextual factors, such as how research evidence is negotiated, appraised and communicated within the dynamic patient-practitioner relationship.&lt;/p&gt

Single photon generation by pulsed excitation of a single dipole

The fluorescence of a single dipole excited by an intense light pulse can lead to the generation of another light pulse containing a single photon. The influence of the duration and energy of the excitation pulse on the number of photons in the fluorescence pulse is studied. The case of a two-level dipole with strongly damped coherences is considered. The presence of a metastable state leading to shelving is also investigated.Comment: 17 pages, 4 figures, submitted to PR

Chemogenomic Profiling of Antileishmanial Efficacy and Resistance in the Related Kinetoplastid Parasite <i>Trypanosoma brucei</i>

The arsenal of drugs used to treat leishmaniasis, caused by Leishmania spp., is limited and beset by emergent resistance and toxicity. Our understanding of drug mode-of-action and potential routes to resistance is also limited. Forward genetic approaches have revolutionised our understanding of drug mode-of-action in the related kinetoplastid parasite, Trypanosoma brucei. Therefore, we screened our genome-scale T. brucei RNAi library for knockdowns that render cells resistant to the current anti-leishmanial drugs, sodium stibogluconate (antimonial), paromomycin, miltefosine and amphotericin-B. Identification of T. brucei orthologues of the known Leishmania antimonial and miltefosine plasma membrane transporters effectively validated our approach, while a cohort of 42 novel drug efficacy determinants provides new insights and serves as a resource

Quality of life among cervical cancer patients undergoing radiotherapy.

IntroductionThere has been an increasing rate of the incidence and mortality of cervical cancer in Ghana. Cancer and the treatment's side effects have adverse effects on the patients and this affects patient's well-being and lifestyle during and after radiotherapy. The study sought to assess the impact of demographic and clinical characteristics on Quality of Life (QoL) among cervical cancer patients undergoing radiotherapy in Ghana.MethodsA cross sectional quantitative study design was carried out on 120 cervical cancer patients who were conveniently sampled from the study site. The data was collected between the months of December, 2017 and February, 2018. QoL was measured using the FACT-G questionnaire. The mean scores of QoL were determined, whiles the chi-square test was used to determine the impact of socio-demographic and clinical characteristics on the QoL of the patients.ResultsThe mean age of the patients was 56.8 years. Majority of the patients reported stable QoL. The social well-being of the older patients was more affected than other patients. The unmarried, widows and patients who underwent surgery with radiotherapy were emotionally affected. Majority (56%) of the participants had stable QoL whiles 22% each had poor and good QoL. Significant association was found among 35-39 age group with physical well-being and overall QoL (p=0.017 and 0.029) respectively.ConclusionThere is a need to embrace a QoL assessment instrument in the study site so as to help the oncology team in the identification and addressing of specific indicators that affect the QoL of cervical cancer patients

Evaluation of the Casimir Force for a Dielectric-diamagnetic Cylinder with Light Velocity Conservation Condition and the Analogue of Sellmeir's Dispersion Law

We study the Casimir pressure for a dielectric-diamagnetic cylinder subject to light velocity conservation and with a dispersion law analogous to Sellmeir's rule. Similarities to and differences from the spherical case are pointed out.Comment: 19 pages Latex, no figures; discussion expanded. To appear in Physica Script

Development and formative evaluation of the e-Health implementation toolkit

&lt;b&gt;Background&lt;/b&gt; The use of Information and Communication Technology (ICT) or e-Health is seen as essential for a modern, cost-effective health service. However, there are well documented problems with implementation of e-Health initiatives, despite the existence of a great deal of research into how best to implement e-Health (an example of the gap between research and practice). This paper reports on the development and formative evaluation of an e-Health Implementation Toolkit (e-HIT) which aims to summarise and synthesise new and existing research on implementation of e-Health initiatives, and present it to senior managers in a user-friendly format.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; The content of the e-HIT was derived by combining data from a systematic review of reviews of barriers and facilitators to implementation of e-Health initiatives with qualitative data derived from interviews of "implementers", that is people who had been charged with implementing an e-Health initiative. These data were summarised, synthesised and combined with the constructs from the Normalisation Process Model. The software for the toolkit was developed by a commercial company (RocketScience). Formative evaluation was undertaken by obtaining user feedback. There are three components to the toolkit - a section on background and instructions for use aimed at novice users; the toolkit itself; and the report generated by completing the toolkit. It is available to download from http://www.ucl.ac.uk/pcph/research/ehealth/documents/e-HIT.xls&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; The e-HIT shows potential as a tool for enhancing future e-Health implementations. Further work is needed to make it fully web-enabled, and to determine its predictive potential for future implementations