Adding epoetin alfa to intense dose-dense adjuvant chemotherapy for breast cancer : randomized clinical trial

BACKGROUND: The AGO-ETC trial compared 5-year relapse-free survival of intense dose-dense (IDD) sequential chemotherapy with epirubicin (E), paclitaxel (T), and cyclophosphamide (C) (IDD-ETC) every 2 weeks vs conventional scheduled epirubicin/cyclophosphamide followed by paclitaxel (EC→T) (every 3 weeks) as adjuvant treatment in high-risk breast cancer patients. The objective of this study was to evaluate the safety and efficacy of epoetin alfa in a second randomization of the intense dose-dense arm. METHODS: One thousand two hundred eighty-four patients were enrolled; 658 patients were randomly assigned to the IDD-ETC treatment group. Within the IDD-ETC group, 324 patients were further randomly assigned to the epoetin alfa group, and 319 were randomly assigned to the non-erythropoiesis-stimulating agent (ESA) control group. Primary efficacy endpoints included change in hemoglobin level from baseline to Cycle 9 and the percentage of subjects requiring red blood cell transfusion. Relapse-free survival, overall survival, and intramammary relapse were secondary endpoints estimated with Kaplan-Meier and Cox regression methods. Except for the primary hypothesis, all statistical tests were two-sided. RESULTS: Epoetin alfa avoided the decrease in hemoglobin level (no decrease in the epoetin alfa group vs -2.20g/dL change for the control group; P < .001) and statistically significantly reduced the percentage of subjects requiring red blood cell transfusion (12.8% vs 28.1%; P < .0001). The incidence of thrombotic events was 7% in the epoetin alfa arm vs 3% in the control arm. After a median follow-up of 62 months, epoetin alfa treatment did not affect overall survival, relapse-free survival, or intramammary relapse. CONCLUSIONS: Epoetin alfa resulted in improved hemoglobin levels and decreased transfusions without an impact on relapse-free or overall survival. However, epoetin alfa had an adverse effect, resulting in increased thrombosis

Ludii -- The Ludemic General Game System

While current General Game Playing (GGP) systems facilitate useful research in Artificial Intelligence (AI) for game-playing, they are often somewhat specialised and computationally inefficient. In this paper, we describe the "ludemic" general game system Ludii, which has the potential to provide an efficient tool for AI researchers as well as game designers, historians, educators and practitioners in related fields. Ludii defines games as structures of ludemes -- high-level, easily understandable game concepts -- which allows for concise and human-understandable game descriptions. We formally describe Ludii and outline its main benefits: generality, extensibility, understandability and efficiency. Experimentally, Ludii outperforms one of the most efficient Game Description Language (GDL) reasoners, based on a propositional network, in all games available in the Tiltyard GGP repository. Moreover, Ludii is also competitive in terms of performance with the more recently proposed Regular Boardgames (RBG) system, and has various advantages in qualitative aspects such as generality.Comment: Accepted at ECAI 202

Protocol TOP-Study (tacrolimus organ perfusion): a prospective randomized multicenter trial to reduce ischemia reperfusion injury in transplantation of marginal liver grafts with an "ex vivo" tacrolimus perfusion

Background: Critical organ shortage results in the utilization of extended donor criteria (EDC) liver grafts. These marginal liver grafts are prone to increased ischemia reperfusion injury (IRI) which may contribute to deteriorated graft function and survival. Experimental data have shown that the calcineurin inhibitor tacrolimus exerts protective effects on hepatic IRI when applied intravenously or directly as a hepatic rinse. Therefore, the aim of the present study is to examine the effects of an ex vivo tacrolimus perfusion on IRI in transplantation of EDC liver grafts. Methods/Design: The TOP-Study (tacrolimus organ perfusion) is a randomized multicenter trial comparing the ex vivo tacrolimus perfusion of marginal liver grafts with placebo. We hypothesize that a tacrolimus rinse reduces IRI, potentially improving organ survival following transplantation of EDC livers. The study includes livers with two or more EDC, according to Eurotransplant International Foundation’s definition of EDC livers. Prior to implantation, livers randomized to the treatment group are rinsed with tacrolimus at a concentration of 20 ng/ml in 1000 ml Custodiol solution and in the placebo group with Custodiol alone. The primary endpoint is the maximum serum alanine transamninase (ALT) level within the first 48 hours after surgery; however, the study design also includes a 1-year observation period following transplantation. The TOP-Study is an investigator-initiated trial sponsored by the University of Munich Hospital. Seven other German transplant centers are participating (Berlin, Frankfurt, Heidelberg, Mainz, Münster, Regensburg, Tübingen) and aim to include a total of 86 patients. Discussion: Tacrolimus organ perfusion represents a promising strategy to reduce hepatic IRI following the transplantation of marginal liver grafts. This treatment may help to improve the function of EDC grafts and therefore safely expand the donor pool in light of critical organ shortage. Trial register: EudraCT number: 2010-021333-31, ClinicalTrials.gov identifier: NCT0156409

Acute effects of Hibiscus sabdariffa calyces on postprandial blood pressure, vascular function, blood lipids, biomarkers of insulin resistance and inflammation in humans

The acute impact of Hibiscus sabdariffa calyces (HSC) extract on postprandial vascular function and other cardiometabolic risk factors have not been studied previously. This study investigated the acute impact of HSC extract consumption on blood pressure (BP), vascular function and other cardiometabolic risk markers. Twenty-five men with 1% to 10% cardiovascular disease (CVD) risk (determined by QRISK 2) were randomised to consume either 250 mL of the aqueous extract of HSC or water with breakfast in a randomised, controlled, single-blinded, 2-meal cross-over study (ClinicalTrials.gov, NTC02165553) with a two weeks washout period between study days. BP was measured at baseline and hourly for 4 h. Flow mediated dilatation (FMD) of the branchial artery was measured at baseline, 2 and 4 h post intervention drink consumption. Acute consumption of aqueous extract of HSC caused a significant increase in % FMD ( < 0.001), a non-significant decrease in systolic BP (SBP) and diastolic BP (DBP); non-significant increase in urinary and plasma nitric oxide (NOx) and reduced response of serum glucose, plasma insulin, serum triacylglycerol and C-reactive protein (CRP) levels; significant ( = 0.026) improvement in the area under systemic antioxidant response curve (0 to 2 h); no significant changes in arterial stiffness following the acute consumption of the extract of HSC. Gallic acid, 4-O-methylgallic acid, 3-O-methylgallic acid and hippuric acid reached a maximum plasma concentration at 1 to 2 h post consumption of the extract of HSC. The extract of HSC improved postprandial vascular function and may be a useful dietary strategy to reduce endothelial dysfunction and CVD risk, although this requires confirmation

Effect of Vegetative Propagation Materials on Globe Artichoke Production in Semi-Arid Developing Countries: Agronomic, Marketable and Qualitative Traits

Abstract: In Tunisia, globe artichoke is mainly propagated by underground dormant axillary buds (ovoli), which are removed from the field in August during the quiescence period. The high cost of in vitro-plants and the absence of specialized nurseries were among the reasons for the rise of heterogeneity and spread of diseases. The aim was to help farmers to improve artichoke yield and quality by ameliorating their vegetative propagation technique with low cost methods. Three plant cuttings management methods were tested: summer ovoli (T0); spring offshoots nursery\u2019s cuttings forced to pass a vegetative rest period by stopping irrigation (T1); and offshoots nursery\u2019s cuttings not forced (T2). The cuttings management can affect both yield and qualitative traits of artichoke. T1 nursery plants produced the heaviest primary heads, 7% and 23% higher than T2 and T0, respectively. T1 plants exhibited the highest yield during the harvest season, with +17.7% and +12.2% compared to T0 and T2, respectively. T0 and T1 showed the highest total antioxidant capacity and inulin content; the propagation method also affected the short-chain sugars ratio. T1 is a viable and sustainable alternative to the traditional one that does not heavily impact on growing costs and improves yield and quality of artichoke

Oxidative stress, telomeres and cellular senescence: What non-drug interventions might break the link?

Telomeres are higher order structures that cap and protect chromosome ends. Telomeric DNA naturally shortens during somatic cell division and as a result of oxidative stress. Excessive shortening disrupts the integrity of the telomere, causing cellular senescence, one of the hallmarks of organismal ageing. The accumulation of senescent cells with ageing contributes to the loss of tissue homeostasis and the development of age-related pathologies. Hence, counteracting telomere shortening may be one relevant approach to develop strategies for healthier ageing. In this review I present the case for the existence of a link between oxidative stress, accelerated telomere shortening and cellular senescence. I also examine findings from human observational studies exploring associations between telomere length and oxidative stress-related parameters. Finally, I discuss results from randomised control trials testing the impact of non-pharmacological lifestyle interventions on the maintenance of telomere length, considering the potential mechanisms that might be involved

Educational Technology Topic Guide

This guide aims to contribute to what we know about the relationship between educational technology (edtech) and educational outcomes by addressing the following overarching question: What is the evidence that the use of edtech, by teachers or students, impacts teaching and learning practices, or learning outcomes? It also offers recommendations to support advisors to strengthen the design, implementation and evaluation of programmes that use edtech. We define edtech as the use of digital or electronic technologies and materials to support teaching and learning. Recognising that technology alone does not enhance learning, evaluations must also consider how programmes are designed and implemented, how teachers are supported, how communities are developed and how outcomes are measured (see http://tel.ac.uk/about-3/, 2014). Effective edtech programmes are characterised by: a clear and specific curriculum focus the use of relevant curriculum materials a focus on teacher development and pedagogy evaluation mechanisms that go beyond outputs. These findings come from a wide range of technology use including: interactive radio instruction (IRI) classroom audio or video resources accessed via teachers’ mobile phones student tablets and eReaders computer-assisted learning (CAL) to supplement classroom teaching. However, there are also examples of large-scale investment in edtech – particularly computers for student use – that produce limited educational outcomes. We need to know more about: how to support teachers to develop appropriate, relevant practices using edtech how such practices are enacted in schools, and what factors contribute to or mitigate against successful outcomes. Recommendations: 1. Edtech programmes should focus on enabling educational change, not delivering technology. In doing so, programmes should provide adequate support for teachers and aim to capture changes in teaching practice and learning outcomes in evaluation. 2. Advisors should support proposals that further develop successful practices or that address gaps in evidence and understanding. 3. Advisors should discourage proposals that have an emphasis on technology over education, weak programmatic support or poor evaluation. 4. In design and evaluation, value-for-money metrics and cost-effectiveness analyses should be carried out