Evaluation of the effect of ultrasonic degassing on components produced by low pressure die casting

Ultrasonic processing is known to be an efficient means of aluminium melt degassing with additional benefits of being economical and environment friendly. This paper describes the performance of ultrasonic degassing in preparing melt for low pressure die casting (LPDC). Efficiency of ultrasonic degassing is compared with conventional Ar rotary degassing by direct measurements of hydrogen concentration in the melt with a Foseco Alspek-H probe and by reduced pressure test in different stages of the casting process. Significant reduction in dross formation along with similar efficiency of hydrogen degassing was shown for ultrasonic degassing as compared with conventional Ar rotary degassing. Mechanical properties, microstructure and porosity level of the components produced by LPDC after both degassing techniques are determined. Results show that the components produced after ultrasonic degassing treatment have similar hardness, tensile properties, porosity level and microstructure as the components degassed with conventional Ar rotary degassing.The European Union’s Seventh Framework Program managed by the Research Executive Agency (REA;FP7/2007–2013) under grant agreement number 286344 (www.ultragassing.eu)

Tachycardiomyopathy entails a dysfunctional pattern of interrelated mitochondrial functions

Tachycardiomyopathy is characterised by reversible left ventricular dysfunction, provoked by rapid ventricular rate. While the knowledge of mitochondria advanced in most cardiomyopathies, mitochondrial functions await elucidation in tachycardiomyopathy. Pacemakers were implanted in 61 rabbits. Tachypacing was performed with 330 bpm for 10 days (n = 11, early left ventricular dysfunction) or with up to 380 bpm over 30 days (n = 24, tachycardiomyopathy, TCM). In n = 26, pacemakers remained inactive (SHAM). Left ventricular tissue was subjected to respirometry, metabolomics and acetylomics. Results were assessed for translational relevance using a human-based model: induced pluripotent stem cell derived cardiomyocytes underwent field stimulation for 7 days (TACH–iPSC–CM). TCM animals showed systolic dysfunction compared to SHAM (fractional shortening 37.8 ± 1.0% vs. 21.9 ± 1.2%, SHAM vs. TCM, p < 0.0001). Histology revealed cardiomyocyte hypertrophy (cross-sectional area 393.2 ± 14.5 µm2 vs. 538.9 ± 23.8 µm2, p < 0.001) without fibrosis. Mitochondria were shifted to the intercalated discs and enlarged. Mitochondrial membrane potential remained stable in TCM. The metabolite profiles of ELVD and TCM were characterised by profound depletion of tricarboxylic acid cycle intermediates. Redox balance was shifted towards a more oxidised state (ratio of reduced to oxidised nicotinamide adenine dinucleotide 10.5 ± 2.1 vs. 4.0 ± 0.8, p < 0.01). The mitochondrial acetylome remained largely unchanged. Neither TCM nor TACH–iPSC–CM showed relevantly increased levels of reactive oxygen species. Oxidative phosphorylation capacity of TCM decreased modestly in skinned fibres (168.9 ± 11.2 vs. 124.6 ± 11.45 pmol·O2·s−1·mg−1 tissue, p < 0.05), but it did not in isolated mitochondria. The pattern of mitochondrial dysfunctions detected in two models of tachycardiomyopathy diverges from previously published characteristic signs of other heart failure aetiologies

Enhanced Heart Failure in Redox‐Dead Cys17Ser PKARIα Knock‐In Mice

Background PKARIα (protein kinase A type I‐α regulatory subunit) is redox‐active independent of its physiologic agonist cAMP. However, it is unknown whether this alternative mechanism of PKARIα activation may be of relevance to cardiac excitation–contraction coupling. Methods and Results We used a redox‐dead transgenic mouse model with homozygous knock‐in replacement of redox‐sensitive cysteine 17 with serine within the regulatory subunits of PKARIα (KI). Reactive oxygen species were acutely evoked by exposure of isolated cardiac myocytes to AngII (angiotensin II, 1 µmol/L). The long‐term relevance of oxidized PKARIα was investigated in KI mice and their wild‐type (WT) littermates following transverse aortic constriction (TAC). AngII increased reactive oxygen species in both groups but with RIα dimer formation in WT only. AngII induced translocation of PKARI to the cell membrane and resulted in protein kinase A–dependent stimulation of ICa (L‐type Ca current) in WT with no effect in KI myocytes. Consequently, Ca transients were reduced in KI myocytes as compared with WT cells following acute AngII exposure. Transverse aortic constriction–related reactive oxygen species formation resulted in RIα oxidation in WT but not in KI mice. Within 6 weeks after TAC, KI mice showed an enhanced deterioration of contractile function and impaired survival compared with WT. In accordance, compared with WT, ventricular myocytes from failing KI mice displayed significantly reduced Ca transient amplitudes and lack of ICa stimulation. Conversely, direct pharmacological stimulation of ICa using Bay K8644 rescued Ca transients in AngII‐treated KI myocytes and contractile function in failing KI mice in vivo. Conclusions Oxidative activation of PKARIα with subsequent stimulation of ICa preserves cardiac function in the setting of acute and chronic oxidative stress

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.

INTRODUCTION: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice. METHODS: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide. ETHICS/DISSEMINATION: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ISRCTN39653756.The OPTIMISE II trial is supported by Edwards Lifesciences (Irvine, CA) and the UK National Institute for Health Research through RMP’s NIHR Professorship

Travel review website usage: A cultural perspective

Pabel, A ORCiD: 0000-0003-1409-5496Purpose: This study aims to investigate tourists’ propensity to use travel review websites (TRWs) during the pre- and post-travel stages from a cultural perspective. Design/methodology/approach: This quantitative study is guided by the positivist paradigm. Data were obtained from an online survey, focussing on Australia, Canada, India and Malaysia. Findings: The results indicate significant relationships between country of residence and the time research begins prior to an international or domestic holiday being undertaken; between country of residence and trust levels for information on TRWs; and country of residence and whether or not respondents post reviews on TRWs. These results are discussed using Hofstede’s cultural dimensions. Long-term orientation shows a moderate cultural influence of respondents’ trust of information on TRWs, while a country’s individualistic or collectivist orientation has a strong influence on respondents’ posting/not posting a review on a TRW. Research limitations/implications: Care should be taken when generalising the findings beyond the study population, as no randomisation occurred with survey distribution. Practical implications: The results of this study have implications for managers of tourism businesses wishing to better facilitate information-sharing behaviours of their customers through TRWs. Social implications: The cross-cultural comparisons used in this study add value to tourism studies, particularly when comparing Eastern and Western societies. Originality/value: The study adds to the knowledge base on consumer pre- and post-trip online behaviours, considering the effect of country of residence and any influence from Hofstede’s cultural dimensions

Embarking on the Paradigm Journey

[Extract] This book provides you as HDR candidates and emerging scholars with information about the experiences and reflections of other scholars as they sought to understand their paradigm and its influence on their approach to research. Hence, the book is oriented mainly towards postgraduate HDR candidates and emerging scholars who are curious about paradigms and have questions about paradigmatic issues. A secondary target audience is higher-degree supervisors or ‘lecturers of research courses’ seeking to enhance their understanding of a specific paradigm in their supervisory activities or who might like to use this text as a resource for their students. For all readers, the book presents insights into the lived experiences of researchers as they have journeyed through the undulating terrain of exploring paradigms