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Warm versus cold cardioplegia in cardiac surgeries: a meta-analysis with trial sequential analysis
No full textObjectiveThis meta-analysis aimed to compare clinical outcomes of warm and cold cardioplegia in cardiac surgeries, with trial sequential analysis used to determine the conclusiveness of the results.MethodsElectronic searches were performed on PubMed, Medline, Scopus, EMBASE and Cochrane library to identify all studies that compared warm and cold cardioplegia in cardiac surgeries. Primary endpoints were in-hospital or 30-day mortality, myocardial infarction (MI), low cardiac output syndrome (LCOS), intra-aortic balloon pump (IABP) use, stroke, and new atrial fibrillation (AF). Secondary endpoints were acute kidney injury (AKI), hospital length of stay (LOS), intensive care unit length of stay (ICU LOS), aortic cross-clamp (ACx) time and cardiopulmonary bypass (CPB) time. Pre-specified subgroup analysis were performed for (1) studies published since publication of Fan et al in 2010 1, (2) studies with low risk of bias, (3) coronary artery bypass graft (CABG) surgeries, and (4) studies with cold blood versus those with cold crystalloid cardioplegia. Trial sequential analysis (TSA) was performed to determine conclusiveness of the results, using on all outcomes without significant heterogeneity from studies of low risk of bias. ResultsNo significant differences were found between post-operative rates of mortality, MI, LCOS, IABP use, stroke, new AF, and AKI between warm and cold cardioplegia. TSA concluded that current evidence was sufficient to rule out a 20% relative risk reduction in these outcomes.ConclusionsConcerning safety outcomes, current evidence suggests that the choice between warm and cold cardioplegia remains in the surgeon’s preference.<br/
Picturing Music in the English Renaissance
No full textMusic in the early modern period was profoundly visual. This is not simply in terms of the spectacle of performance, in masques, court entertainments and the playhouses, but also because music became a ‘read’ thing for the first time. This article seeks to bridge the gap between the ways in which renaissance England is understood by art history, and the ways in which it is understood by musicology. In so doing, it aims to establish a dialogue between these methodologies. The English Renaissance was a period of great musical innovation, spawning the works of John Taverner, Thomas Tallis, William Byrd and Orlando Gibbons amongst others, despite the religious upheavals of the Reformation and Marian counterreformations. However in art history it is still largely seen as a cultural backwater. This article argues that, on the contrary, music is a crucial source of visual interest in the English Renaissance
Long-term Treatment with Telotristat Ethyl in Patients with Carcinoid Syndrome Symptoms: Results from the TELEPATH Study
No full textIntroductionTelotristat ethyl is indicated for use in combination with somatostatin analogs (SSAs) to treat carcinoid syndrome (CS) diarrhea uncontrolled by SSAs alone in adults, but long-term safety and efficacy data beyond 48 weeks are needed.ObjectiveEvaluate the long-term safety and tolerability of telotristat ethyl and its effect on quality of life (QOL) in patients with CS.MethodsIn this phase 3, nonrandomized, multicenter, open-label, long-term extension study (TELEPATH), patients who participated in phase 2 or 3 trials of telotristat ethyl continued treatment at their present dose level (250 or 500 mg thrice daily) for 84 weeks. Safety and tolerability, the primary endpoint, were assessed by monitoring adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs, including liver-related AEs, depression, and gastrointestinal AEs), and deaths. The secondary objective was to evaluate changes in patients’ QOL using validated cancer questionnaires and a subjective global assessment of CS symptoms.ResultsIn 124 patients exposed to telotristat ethyl for a mean of 102.6 ± 53.2 weeks, the type and frequency of AEs were consistent with those reported in previous trials. The occurrence of AESIs was not related to dosage or duration of therapy. Most AEs were mild to moderate in severity, and no deaths were related to telotristat ethyl. QOL scores remained stable and the majority of patients reported adequate symptom relief throughout the study.ConclusionsSafety results of TELEPATH support the long-term use of telotristat ethyl in patients with CS diarrhea. Telotristat ethyl was well tolerated and associated with sustained improvement in QOL scores (NCT02026063). <br/
Envisioning treating genetically-defined urinary tract malformations with viral vector-mediated gene therapy
No full textHuman urinary tract malformations can cause dysfunctional voiding, urosepsis and kidney failure. Other affected individuals, with severe phenotypes on fetal ultrasound screening, undergo elective termination. Currently, there exist no specific treatments that target the primary biological disease mechanisms that generate these urinary tract malformations.Historically, the pathogenesis of human urinary tract malformations has been obscure. It is now established that some such individuals have defined monogenic causes for their disease. In health, the implicated genes are expressed in either differentiating urinary tract smooth muscle cells, urothelial cells or peripheral nerve cells supplying the bladder. The phenotypes arising from mutations of these genes include megabladder, congenital functional bladder outflow obstruction, and vesicoureteric reflux. We contend that these genetic and molecular insights can now inform the design of novel therapies involving viral vector-mediated gene transfer. Indeed, this technology is being used to treat individuals with early onset monogenic disease outside the urinary tract, such as spinal muscular atrophy. Moreover, it has been contended that human fetal gene therapy, which may be necessary to ameliorate developmental defects, could become a reality in the coming decades. We suggest that viral vector-mediated gene therapies should first be tested in existing mouse models with similar monogenic and anatomical aberrations as found in people with urinary tract malformations. Indeed, gene transfer protocols have been successfully pioneered in newborn and fetal mice to treat non-urinary tract diseases. If similar strategies were successful in animals with urinary tract malformations, this would pave the way for personalized and potentially curative treatments for people with urinary tract malformations.<br/
Duality bounds for discrete-time Zames–Falb multipliers
No full textThis note presents phase conditions under which there is no suitable Zames–Falb multiplier for a given discrete time system. Our conditions can be seen as the discrete-time counterpart of Jönsson’s duality conditions for Zames–Falb multipliers. By contrast with their continuous-time counterparts and other phase limitations in the literature, they lead to numerically efficient results that can be computed either in closed form or via a linear program. The closed-form phase limitations are tight in the sense that we can construct multipliers that meet them with equality. The numerical results allow us to conclude that the current state-of-the-art in searches for Zames–Falb multipliers are not conservative. Moreover, they allow us to show, by construction, that the set of plants for which a suitable Zames– Falb multiplier exists is non-convex
Differential Weil Descent
No full textIn this short note a differential version of the classical Weil descent is established in all characteristics. This yields a ready-to-deploy tool of differential restriction of scalars for differential varieties over finite differential field extensions
Online Counselling and Psychotherapy text books for the person-centred and experiential psychotherapies: from COVID-19 and beyond
No full textControlled trials and meta-analyses of electroconvulsive therapy (ECT) against sham ECT for depression: do study limitations invalidate the evidence (and mean we should stop using ECT)?:Commentary on … Electroconvulsive Therapy for Depression: A Review of the Quality of ECT versus Sham ECT Trials and Meta-Analyses, Read et al (2020)
No full textElectroconvulsive therapy (ECT) for depression is a controversial treatment with highly polarised views about the balance between therapeutic benefits and adverse effects. Studies investigating whether ECT is more effective than a placebo treatment started in the 1950s, with the most important randomised controlled studies carried out about four decades ago in which ECT was compared with sham ECT involving anaesthesia but no electrically-induced seizure. Subsequently the data have been pooled in a number of meta-analyses which have found that ECT is an effective treatment. However a recent review of the quality of the sham ECT-controlled studies, and the meta-analyses based on them, concludes that their quality is too poor to allow assessment of the efficacy of ECT, and that given its risks (permanent memory loss and death) the use of ECT should be suspended. This commentary critically discusses the methodology of this review and its conclusions
Channel Estimation of IRS-Aided Communication Systems with Hybrid Multiobjective optimization
No full textIn this paper, we propose a compressive channel estimation techniques for IRS-assisted mmWave multi-input and multi-output (MIMO) system. To reduce the training overhead, the inherent sparsity in mmWave channels is exploited. By utilizing the properties of Kronecker products, IRS-assisted mmWave channel estimation are converted into a sparse signal recovery problem, which involves two competing cost function terms (measurement error and a sparsity term). Existing sparse recovery algorithms solve the combined contradictory objectives function using a regularization parameter, which leads to a suboptimal solution. To address this concern, a hybrid multiobjective evolutionary paradigm is developed to solve the sparse recovery problem, which can overcome the difficulty in the choice of regularization parameter value. Simulation results show that under a wide range of simulation settings, the proposed algorithm achieves competitive error performance compared to existing channel estimation algorithms
Model Checking C++ Programs
No full textIn the last three decades, memory safety issues in system programming languages such as C or C++ have been one of the most significant sources of security vulnerabilities. However, there exist only a few attempts with limited success to cope with the complexity of C++ program verification. We describe and evaluate a novel verification approach based on bounded model checking (BMC) and satisfiability modulo theories (SMT) to verify C++ programs. Our verification approach analyzes bounded C++ programs by encoding into SMT various sophisticated features that the C++ programming language oers, such as templates, inheritance, polymorphism, exception handling, and the Standard Template Libraries. We formalize these features within our formal verification framework using a decidable fragment of first-order logic and then show how state-of-the-art SMT solvers can eciently handle that. We implemented our verification approach on top of ESBMC. We compare ESBMC to LLBMC and DIVINE, which are state-of-the-art verifiers to check C++ programs directly from the LLVM bitcode. Experimental results show that ESBMC can handle a wide range of C++ programs, presenting a higher number of correct verification results. Additionally, ESBMC has been applied to a commercial C++ application in the telecommunication domain and successfully detected arithmetic-overflow errors, which could potentially lead to security vulnerabilities