Orbital-dependent metamagnetic response in Sr4Ru3O10

We show that the metamagnetic transition in Sr$_4$Ru$_3$O$_{10}$ bifurcates into two transitions as the field is rotated away from the conducting planes. This two-step process comprises partial or total alignment of moments in ferromagnetic bands followed by an itinerant metamagnetic transition whose critical field increases with rotation. Evidence for itinerant metamagnetism is provided by the Shubnikov-de Hass effect which shows a non-trivial evolution of the geometry of the Fermi surface and an enhancement of the quasiparticles effective-mass across the transition. The metamagnetic response of Sr$_4$Ru$_3$O$_{10}$ is orbital-dependent and involves ferromagnetic and metamagnetic bands.Comment: Physical Review B (in press

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C

The cost-effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost-effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes (quality-adjusted life-years; QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four treatment strategies: testing with NITs and treating patients with fibrosis stage ≥F2; testing with liver biopsy and treating patients with ≥F2; treat none; and treat all irrespective of fibrosis. We compared all NITs and tested the cost-effectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more-potent antivirals. Treating all patients without any previous NIT was the most effective strategy and had an incremental cost-effectiveness ratio (ICER) of £9,204 per additional QALY gained. The exploratory analysis of currently licensed sofosbuvir treatment regimens found that treat all was cost-effective, compared to using an NIT to decide on treatment, with an ICER of £16,028 per QALY gained. The exploratory analysis to assess the possible effect on results of new treatments, found that if SVR rates increased to >90% for genotypes 1-4, the incremental treatment cost threshold for the "treat all" strategy to remain the most cost-effective strategy would be £37,500. Above this threshold, the most cost-effective option would be noninvasive testing with magnetic resonance elastography (ICER=£9,189). Conclusions: Treating all adult patients with CHC, irrespective of fibrosis stage, is the most cost-effective strategy with currently available drugs in developed countries. © 2014 The Authors

A comparative study of adhesion of melanoma and breast cancer cells to blood and lymphatic endothelium

Background: Lymphovascular invasion (LVI) is an important step in the metastatic cascade; tumor cell migration and adhesion to blood and lymphatic vessels is followed by invasion through the vessel wall and subsequent systemic spread. Although primary breast cancers and melanomas have rich blood vascular networks, LVI is predominately lymphatic in nature. Whilst the adhesion of tumor cells to blood endothelium has been extensively investigated, there is a paucity of information on tumor cell adhesion to lymphatic endothelium. Methods and Results: Breast cancer (MDA-MB-231 and MCF7) and melanoma (MeWo and SKMEL-30) cell adhesion to lymphatic (hTERT-LEC and HMVEC dLy Neo) and blood (HUVEC and hMEC-1) endothelial cells were assessed using static adhesion assays. The effect of inflammatory conditions, tumor necrosis factor-a (TNF-a) stimulation of endothelial and tumor cells, on the adhesive process was also examined. In addition, the effects of TNF-a stimulation on tumor cell migration was investigated using haplotaxis (scratch wound) assays. Breast cancer and melanoma cells exhibited higher levels of adhesion to blood compared to lymphatic endothelial cells ( p < 0.001). TNF-a stimulation of endothelial cells, or of tumor cells alone, did not significantly alter tumor–endothelial cell adhesion or patterns.When both tumor and endothelial cells were stimulated with TNF-a, a significant increase in adhesion was observed ( p < 0.01), which was notably higher in the lymphatic cell models ( p < 0.001). TNF-a-stimulation of all tumor cell lines significantly increased their migration rate ( p < 0.01). Conclusions: Results suggest that metastasis resultant from lymphatic vessel-tumor cell adhesion may be modulated by cytokine stimulation, which could represent an important therapeutic target in breast cancer and melanoma

Genetic evaluation supports differential diagnosis in adolescent patients with delayed puberty

Context: Pubertal delay can be the clinical presentation of both idiopathic hypogonadotropic hypogonadism (IHH) and self-limited delayed puberty (SLDP). Distinction between these conditions is a common but important diagnostic challenge in adolescents. Objective: To assess whether gene panel testing can assist with clinical differential diagnosis and to allow accurate and timely management of delayed puberty patients. Design: Retrospective study. Methods: Patients presenting with delayed puberty to UK Paediatric services, followed up to final diagnosis, were included. Whole-exome sequencing was analysed using a virtual panel of genes previously reported to cause either IHH or SLDP to identify rarely predicted deleterious variants. Deleterious variants were verified by in silico prediction tools. The correlation between clinical and genotype diagnosis was analysed. Results: Forty-six patients were included, 54% with a final clinical diagnosis of SLDP and 46% with IHH. Red flags signs of IHH were present in only three patients. Fifteen predicted deleterious variants in 12 genes were identified in 33% of the cohort, with most inherited in a heterozygous manner. A fair correlation between final clinical diagnosis and genotypic diagnosis was found. Panel testing was able to confirm a diagnosis of IHH in patients with pubertal delay. Genetic analysis identified three patients with IHH that had been previously diagnosed as SLDP. Conclusion: This study supports the use of targeted exome sequencing in the clinical setting to aid the differential diagnosis between IHH and SLDP in adolescents presenting with pubertal delay. Genetic evaluation thus facilitates earlier and more precise diagnosis, allowing clinicians to direct treatment appropriately

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis B in the UK: systematic review and economic evaluation

The copyright line for this article was changed on 18 November 2016 after original online publication. Abbreviations: CEAF cost-effectiveness frontier. CHB chronic hepatitis B. CI confidence intervals. FN false negative. FP false positive. HBV hepatitis B virus. HCC hepatocellular carcinoma. ICER incremental cost-effectiveness ratio. NITs noninvasive tests. QUADAS Quality Assessment of Diagnostic Accuracy Studies. QUALYs quality-adjusted-life-years. TN true negative. TP true positive.Copyright © 2015 The Authors. We compared the cost-effectiveness of various noninvasive tests (NITs) in patients with chronic hepatitis B and elevated transaminases and/or viral load who would normally undergo liver biopsy to inform treatment decisions. We searched various databases until April 2012. We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes quality-adjusted-life-years (QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four decision-making strategies: testing with NITs and treating patients with fibrosis stage ≥F2, testing with liver biopsy and treating patients with ≥F2, treat none (watchful waiting) and treat all irrespective of fibrosis. Treating all patients without prior fibrosis assessment had an incremental cost-effectiveness ratio (ICER) of £28 137 per additional QALY gained for HBeAg-negative patients. For HBeAg-positive patients, using Fibroscan was the most cost-effective option with an ICER of £23 345. The base case results remained robust in the majority of sensitivity analyses, but were sensitive to changes in the ≥F2 prevalence and the benefit of treatment in patients with F0–F1. For HBeAg-negative patients, strategies excluding NITs were the most cost-effective: treating all patients regardless of fibrosis level if the high cost-effectiveness threshold of £30 000 is accepted; watchful waiting if not. For HBeAg-positive patients, using Fibroscan to identify and treat those with ≥F2 was the most cost-effective option.The analysis for Hepatitis B was part of a larger project funded by The National Institute for Health Research Health Technology Assessment (HTA project 09/114/02) and will be published in full in the Health Technology Assessment journal series. Visit the HTA programme website for more details www.hta.ac.uk/link to project page

Assessing Student Mindset, Interest, Participation, and Rapport in the Post-Pandemic Public Speaking Classroom: Effects of Modality Change and Communication Growth Mindset

The COVID-19 pandemic created an exigency for educators to reevaluate their approaches to the classroom with one major dimension being course modality. This study uses the Instructional Beliefs Model to examine the impacts of course modality (i.e., hybrid versus face-to-face formats) and students’ communication growth mindset on student engagement in the foundational public speaking course. Consistent with pre-COVID-19 findings, the results indicated that modality does not significantly impact student engagement, with one exception: higher cognitive interest scores were reported among students in the hybrid modality. Communication growth mindset associated positively with all student engagement variables examined: student interest–emotional, student interest–cognitive, participation, and class rapport. The findings offer tentative optimism about the promise of blended public speaking course modalities, and evidence for the necessity of mindset intervention to maximize student success

Real world challenges in delivering person centred care: A community based case study

Community nurses face many challenges when trying to practice evidence-based, person-centred care. Ongoing concerns regarding the impact of the 2013 Francis Report (Ford and Lintern, 2017) suggest that individualised and holistic care is an impossible dream, one made harder when the client appears uncooperative. This paper presents a case study that sets out how some of these challenges were met in a potentially difficult situation experienced by a student nurse and her mentor in practice, in which the student was supported to further examine and explore issues that may have influenced the situation. In this instance, the solution came with the recognition that the client had expertise and knowledge that needed to be taken into account, alongside that of the nurses looking after him. His care became a partnership, not an imposition of expertise; a principle which is transferable to many other situations. Underpinning it was the recognition of our shared humanity, wherein lies the essence of truly holistic care, and student nurses learning this, through the guidance and support of their mentor.