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

Perspectives of frailty and frailty screening: Protocol for a collaborative knowledge translation approach and qualitative study of stakeholder understandings and experiences

Accompanying the unprecedented growth in the older adult population worldwide is an increase in the prevalence of frailty, an age-related clinical state of increased vulnerability to stressor events. This increased vulnerability results in lower social engagement and quality of life, increased dependency, and higher rates of morbidity, health service utilization and mortality. Early identification of frailty is necessary to guide implementation of interventions to prevent associated functional decline. Consensus is lacking on how to clinically recognize and manage frailty. It is unknown how healthcare providers and healthcare consumers understand and perceive frailty, whether or not they regard frailty as a public health concern; and information on the indirect and direct experiences of consumer and healthcare provider groups towards frailty are markedly limited.We will conduct a qualitative study of consumer, practice nurse, general practitioner, emergency department physician, and orthopedic surgeons' perspectives of frailty and frailty screening in metropolitan and non-metropolitan South Australia. We will use tailored combinations of semi-structured interviews and arts-based data collection methods depending on each stakeholder group, followed by inductive and iterative analysis of data using qualitative description.Using stakeholder driven approaches to understanding and addressing frailty and frailty screening in context is critical as the prevalence and burden of frailty is likely to increase worldwide. We will use the findings from the Perceptions of Frailty and Frailty Screening study to inform a context-driven identification, implementation and evaluation of a frailty-screening tool; drive awareness, knowledge, and skills development strategies across stakeholder groups; and guide future efforts to embed emerging knowledge about frailty and its management across diverse South Australian contexts using a collaborative knowledge translation approach. Study findings will help achieve a coordinated frailty and healthy ageing strategy with relevance to other jurisdictions in Australia and abroad, and application of the stakeholder driven approach will help illuminate how its applicability to other jurisdictions.Mandy M. Archibald, Rachel Ambagtsheer, Justin Beilby, Mellick J. Chehade, Tiffany K. Gill, Renuka Visvanathan, and Alison L. Kitso

Teaching climate change and sustainability: A survey of teachers in England

This report shares detailed findings as to the current state of climate change and sustainability education in England in 2022-23, with a particular focus on teachers’ practice and professional development. The results reveal both strengths and gaps in the provision of climate change and sustainability education in England. The report serves as an evidence base for researchers, policymakers and practitioners who seek to support teachers to fulfil their important roles in society’s transformation to a sustainable future. UCL’s Centre for Climate Change and Sustainability Education (CCCSE) conducted a survey of teachers in England entitled ‘What do climate change and sustainability education have to do with me?’. Between October and December 2022, teachers were invited to respond to an online questionnaire about their views and experiences. Teachers were recruited through email lists, professional networks, social media and via the CCCSE website. The questionnaire investigated their teaching practice, professional development, and sense of confidence and preparedness to incorporate climate change and sustainability into their teaching. It included a range of question types and generated quantitative and qualitative data. The survey gathered 870 responses, with over two thirds (70.7%) teaching at secondary level, and geography (41.3%) and science (37.2%) being the most frequently reported subjects taught. Those who responded represented a wide range of teaching experience, from one year to 20+ years, with university-led PGCE programmes the most commonly reported route into teaching (87.2%). The significant majority of respondents were female (73.9%) and from white backgrounds (90.5%)

Quinone synthesis and a visual introduction to column chromatography : an undergraduate experiment

An introductory normal phase column chromatography experiment is described and evaluated for second year undergraduate chemistry laboratory class. The experiment involves a nucleophilic substitution yielding a crude mixture of reactant and one product, both of which are brightly colored and contrasting, creating a clearly visual separation when purified using column chromatography. A student survey was conducted which showed that 75.4% of students (n = 53, approximately 50% of year group) agreed or strongly agreed that the experiment worked well for them, and 88.7% agreed or strongly agreed that the experiment was enjoyable. Every student was also assessed in the lab on their practical technique, with the year group achieving an average of 72.1% in this assessment

Desistance from crime: working with protective factors

There is no universal definition of desistance from crime. However, it is generally accepted that it is an ongoing, subjective journey towards an offence-free life, complete with relapses and recoveries, rather than just abstinence from offending (Willis et al., 2010). ‘Protective factors’ are social, environmental, or psychological features that help with desistance, such as prosocial relationships and employment. Helping individuals by promoting and supporting these protective factors in their lives gives us the opportunity to boost their chances of desisting from crime. This report focuses on three key areas relating to desistance and explores what the evidence base tells us about how these protective factors can be applied in people’s lives

The Casimir Effect in Spheroidal Geometries

We study the zero point energy of massless scalar and vector fields subject to spheroidal boundary conditions. For massless scalar fields and small ellipticity the zero-point energy can be found using both zeta function and Green's function methods. The result agrees with the conjecture that the zero point energy for a boundary remains constant under small deformations of the boundary that preserve volume (the boundary deformation conjecture), formulated in the case of an elliptic-cylindrical boundary. In the case of massless vector fields, an exact solution is not possible. We show that a zonal approximation disagrees with the result of the boundary deformation conjecture. Applying our results to the MIT bag model, we find that the zero point energy of the bag should stabilize the bag against deformations from a spherical shape.Comment: 24 pages, 3 figures. To appear in Phys. Rev.

Local and Global Casimir Energies for a Semitransparent Cylindrical Shell

The local Casimir energy density and the global Casimir energy for a massless scalar field associated with a $\lambda\delta$-function potential in a 3+1 dimensional circular cylindrical geometry are considered. The global energy is examined for both weak and strong coupling, the latter being the well-studied Dirichlet cylinder case. For weak-coupling,through $\mathcal{O}(\lambda^2)$, the total energy is shown to vanish by both analytic and numerical arguments, based both on Green's-function and zeta-function techniques. Divergences occurring in the calculation are shown to be absorbable by renormalization of physical parameters of the model. The global energy may be obtained by integrating the local energy density only when the latter is supplemented by an energy term residing precisely on the surface of the cylinder. The latter is identified as the integrated local energy density of the cylindrical shell when the latter is physically expanded to have finite thickness. Inside and outside the delta-function shell, the local energy density diverges as the surface of the shell is approached; the divergence is weakest when the conformal stress tensor is used to define the energy density. A real global divergence first occurs in $\mathcal{O}(\lambda^3)$, as anticipated, but the proof is supplied here for the first time; this divergence is entirely associated with the surface energy, and does {\em not} reflect divergences in the local energy density as the surface is approached.Comment: 28 pages, REVTeX, no figures. Appendix added on perturbative divergence

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

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

<p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p&gt