Immediate reproducibility of electrically induced sustained monomorphic ventricular tachycardia before and during antiarrhythmic therapy

AbstractThe immediate reproducibility of sustained ventricular tachycardia induction was evaluated prospectively during 106 studies performed in 53 patients with clinical sustained monomorphic ventricular tachycardia. Programmed electrical stimulation was performed twice, using the same protocol during 53 drug-free studies and 53 subsequent studies on antiarrhythmic therapy.Sustained monomorphic ventricular tachycardia was reproduced in 104 (98%) of the 106 studies. There was no significant difference in the incidence of reproducible tachycardia in the drug-free state compared with that observed during treatment with different classes of antiarrhythmic drugs. An increase in the number of extrastimuli was required to reinitiate the tachycardia in 9 (11%) of 83 studies in which single or double extrastimuli were initially required to induce the tachycardia. In 39 (37%) of 104 studies with reproducible tachycardia induction, the two tachycardias significantly differed in electrocardiographic (ECG) configuration and cycle length.These observations suggest that the overall reproducibility of ventricular tachycardia induction is sufficiently high to provide a reliable marker for evaluating the efficacy of therapeutic interventions. However, specific tachycardia characteristics such as cycle length and ECG configuration are more variable even within the same study and may be less useful in assessing the effects of subsequent interventions

Purines and Neuronal Excitability: Links to the Ketogenic Diet [post-print]

ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A(1) receptor (A(1)R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A(1)Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A(1)R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A(1)Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms

Translations: effects of viewpoint, feature, naming and context on identifying repeatedly copied drawings

We explored the tension between bottom – up and top – down contributions to object recognition in a collaboration between a visual artist and a cognitive psychologist. Initial pictorial renderings of objects and animals from various viewpoints were iteratively copied, and a series of drawings that changed from highly concrete images into highly abstract images was produced. In drawing identification in which sets were shown in reverse order, participants were more accurate, more confident, and quicker to correctly identify the evolving image when it was originally displayed from a canonical viewpoint with all salient features present. In drawing identification in which images were shown in random order, more abstract images could be resolved as a result of previously identifying a more concrete iteration of the same drawing. The results raise issues about the influence of viewpoint and feature on the preservation of pictorial images and about the role of labelling in the interpretation of ambiguous stimuli. In addition, the study highlights a procedure in which visual stimuli can degrade without necessitating a substantial loss of complexity

Factors Influencing Appropriate Firing of the Implanted Defibrillator for Ventricular Tachycardia/Fibrillation Findings From the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II)

ObjectivesThe purpose of this study was to prospectively examine the role of clinical, laboratory, echocardiographic, and electrophysiological variables as predictors of appropriate initial implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) or death in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) population.BackgroundThere is limited information regarding the determinants of appropriate ICD therapy in patients with reduced ventricular function after a myocardial infarction.MethodsWe used secondary analysis in one arm of a multicenter randomized clinical trial in patients with a previous myocardial infarction and reduced left ventricular function.ResultsWe analyzed baseline and follow-up data on 719 patients enrolled in the ICD arm of the MADIT-II study. Appropriate ICD therapy was observed in 169 subjects. Clinical, laboratory, echocardiographic, and electrophysiological variables, along with measures of clinical instability such as interim hospitalization for congestive heart failure (IH-CHF) and interim hospitalization for coronary events (IH-CE), were examined with proportional hazards models and Kaplan-Meier time-to-event curves before and after first interim hospitalization. Interim hospitalization-CHF, IH-CE, no beta-blockers, digitalis use, blood urea nitrogen (BUN) >25, body mass index (BMI) ≥30 kg/m2, and New York Heart Association functional class >II were associated with increased risk for appropriate ICD therapy for VT, VF, or death. In a multivariate (stepwise selection) analysis, IH-CHF was associated with an increased risk for the end point of either VT or VF (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.69 to 3.74, p < 0.001) and for the combined end point of VT, VF, or death (HR 2.97, 95% CI 2.15 to 4.09, p < 0.001). Interim hospitalization-CE was associated with an increased risk for VT, VF, or death (HR 1.66, 95% CI 1.09 to 2.52, p = 0.02).ConclusionsThese results provide important mechanistic information, suggesting that worsening clinical condition and cardiac instability, as reflected by an IH-CHF or IH-CE, are subsequently associated with a significant increase in the risk for appropriate ICD therapy (for VT/VF) and death

Cross-Platform Microarray Data Normalisation for Regulatory Network Inference

Background Inferring Gene Regulatory Networks (GRNs) from time course microarray data suffers from the dimensionality problem created by the short length of available time series compared to the large number of genes in the network. To overcome this, data integration from diverse sources is mandatory. Microarray data from different sources and platforms are publicly available, but integration is not straightforward, due to platform and experimental differences. Methods We analyse here different normalisation approaches for microarray data integration, in the context of reverse engineering of GRN quantitative models. We introduce two preprocessing approaches based on existing normalisation techniques and provide a comprehensive comparison of normalised datasets. Conclusions Results identify a method based on a combination of Loess normalisation and iterative K-means as best for time series normalisation for this problem

Identifying Patients at High Risk of a Cardiovascular Event in the Near Future Current Status and Future Directions: Report of a National Heart, Lung, and Blood Institute Working Group

The National Heart, Lung, and Blood Institute convened a working group to provide basic and clinical research recommendations to the National Heart, Lung, and Blood Institute on the development of an integrated approach for identifying those individuals who are at high risk for a cardiovascular event such as acute coronary syndromes (ACS) or sudden cardiac death in the “near term.” The working group members defined near-term as occurring within 1 year of the time of assessment. The participants reviewed current clinical cardiology practices for risk assessment and state-of-the-science techniques in several areas, including biomarkers, proteomics, genetics, psychosocial factors, imaging, coagulation, and vascular and myocardial susceptibility. This report presents highlights of these reviews and a summary of suggested research directions

Comparison of evolutionary algorithms in gene regulatory network model inference

Background: The evolution of high throughput technologies that measure gene expression levels has created a data base for inferring GRNs (a process also known as reverse engineering of GRNs). However, the nature of these data has made this process very di±cult. At the moment, several methods of discovering qualitative causal relationships between genes with high accuracy from microarray data exist, but large scale quantitative analysis on real biological datasets cannot be performed, to date, as existing approaches are not suitable for real microarray data which are noisy and insu±cient. Results: This paper performs an analysis of several existing evolutionary algorithms for quantitative gene regulatory network modelling. The aim is to present the techniques used and o®er a comprehensive comparison of approaches, under a common framework. Algorithms are applied to both synthetic and real gene expression data from DNA microarrays, and ability to reproduce biological behaviour, scalability and robustness to noise are assessed and compared. Conclusions: Presented is a comparison framework for assessment of evolutionary algorithms, used to infer gene regulatory networks. Promising methods are identi¯ed and a platform for development of appropriate model formalisms is established

Accuracy of telepsychiatric assessment of new routine outpatient referrals

<p>Abstract</p> <p>Background</p> <p>Studies on the feasibility of telepsychiatry tend to concentrate only on a subset of clinical parameters. In contrast, this study utilises data from a comprehensive assessment. The main objective of this study is to compare the accuracy of findings from telepsychiatry with those from face to face interviews.</p> <p>Method</p> <p>This is a primary, cross-sectional, single-cluster, balanced crossover, blind study involving new routine psychiatric referrals. Thirty-seven out of forty cases fulfilling the selection criteria went through a complete set of independent face to face and video assessments by the researchers who were blind to each other's findings.</p> <p>Results</p> <p>The accuracy ratio of the pooled results for DSM-IV diagnoses, risk assessment, non-drug and drug interventions were all above 0.76, and the combined overall accuracy ratio was 0.81. There were substantial intermethod agreements for Cohen's kappa on all the major components of evaluation except on the Risk Assessment Scale where there was only weak agreement.</p> <p>Conclusion</p> <p>Telepsychiatric assessment is a dependable method of assessment with a high degree of accuracy and substantial overall intermethod agreement when compared with standard face to face interview for new routine outpatient psychiatric referrals.</p