25 research outputs found

    Concepts and action : where does the embodiment debate leave us?

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    The behavioural evidence of sensorimotor activity during conceptual processing, along with that from neurological research, ignited the debate around the extent to which concept representations are embodied or amodal. Such evidence continues to fuel the debate but it is open to interpretation as being consistent with a variety of the theoretical positions and so it is possible that further, similar evidence may not lead to its resolution. In this paper we propose that independent value accrues from following this line of research through the enhanced understanding of the factors that influence agents’ conceptual processing of action and how this interacts with the agent’s goals in real environments. This approach is in line with broad principles of embodied cognition and is worthy of pursuit regardless of what the results may (or may not) tell us about conceptual representation

    Translating microarray data for diagnostic testing in childhood leukaemia

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    BACKGROUND: Recent findings from microarray studies have raised the prospect of a standardized diagnostic gene expression platform to enhance accurate diagnosis and risk stratification in paediatric acute lymphoblastic leukaemia (ALL). However, the robustness as well as the format for such a diagnostic test remains to be determined. As a step towards clinical application of these findings, we have systematically analyzed a published ALL microarray data set using Robust Multi-array Analysis (RMA) and Random Forest (RF). METHODS: We examined published microarray data from 104 ALL patients specimens, that represent six different subgroups defined by cytogenetic features and immunophenotypes. Using the decision-tree based supervised learning algorithm Random Forest (RF), we determined a small set of genes for optimal subgroup distinction and subsequently validated their predictive power in an independent patient cohort. RESULTS: We achieved very high overall ALL subgroup prediction accuracies of about 98%, and were able to verify the robustness of these genes in an independent panel of 68 specimens obtained from a different institution and processed in a different laboratory. Our study established that the selection of discriminating genes is strongly dependent on the analysis method. This may have profound implications for clinical use, particularly when the classifier is reduced to a small set of genes. We have demonstrated that as few as 26 genes yield accurate class prediction and importantly, almost 70% of these genes have not been previously identified as essential for class distinction of the six ALL subgroups. CONCLUSION: Our finding supports the feasibility of qRT-PCR technology for standardized diagnostic testing in paediatric ALL and should, in conjunction with conventional cytogenetics lead to a more accurate classification of the disease. In addition, we have demonstrated that microarray findings from one study can be confirmed in an independent study, using an entirely independent patient cohort and with microarray experiments being performed by a different research team

    Outcomes of long-standing persistent atrial fibrillation ablation: A systematic review

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    BackgroundAblation of long-standing persistent atrial fibrillation (AF) is highly variable, with differing techniques and outcomes.ObjectiveThe purpose of this study was to undertake a systematic review of the literature with regard to the impact of ablation technique on the outcomes of long-standing persistent AF ablation.MethodsA systematic search of the contemporary English scientific literature (from January 1, 1990 to June 1, 2009) in the PubMed database identified 32 studies on persistent/long-standing persistent or long-standing persistent AF ablation (including four randomized controlled trials). Data on single-procedure, drug-free success, multiple procedure success, and pharmaceutically assisted success at longest follow-up were collated.ResultsFour studies performed pulmonary vein isolation alone (21%-22% success). Four studies performed pulmonary vein antrum ablation with isolation (PVAI; n = 2; 38%-40% success) or without confirmed isolation (PVA; n = 2; 37%-56% success). Ten studies performed linear ablation in addition to PVA (n = 5; 11%-74% success) or PVAI (n = 5; 38%-57% success). Three studies performed posterior wall box isolation (n = 3; 44%-50% success). Five studies performed complex fractionated atrial electrogram ablation (n = 5; 24%-63% success). Six studies performed complex fractionated atrial electrogram ablation as an adjunct to PVA (n = 2; 50%-51% success), PVAI (n = 3; 36%-61% success), or PVAI and linear (n = 1; 68% success) ablation. Five studies performed the stepwise ablation approach (38%-62% success).ConclusionThe variation in success within and between techniques suggests that the optimal ablation technique for long-standing persistent AF is unclear. Nevertheless, long-standing persistent AF can be effectively treated with a composite of extensive index catheter ablation, repeat procedures, and/or pharmaceuticals.Anthony G. Brooks, Martin K. Stiles, Julien Laborderie, Dennis H. Lau, Pawel Kuklik, Nicholas J. Shipp, Li-Fern Hsu, and Prashanthan Sandershttp://www.elsevier.com/wps/find/journaldescription.cws_home/702333/description#descriptio

    Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the substrate in hypertension and ageing

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    Background: Both ageing and hypertension are known risk factors for atrial fibrillation (AF) although the pathophysiological contribution or interaction of the individual factors remains poorly understood. Here we aim to delineate the arrhythmogenic atrial substrate in mature spontaneously hypertensive rats (SHR). Methods: SHR were studied at 12 and 15 months of age (n=8 per group) together with equal numbers of age-matched normotensive Wistar-Kyoto control rats (WKY). Electrophysiologic study was performed on superfused isolated right and left atrial preparations using a custom built high-density multiple-electrode array to determine effective refractory periods (ERP), atrial conduction and atrial arrhythmia inducibility. Tissue specimens were harvested for structural analysis. Results: Compared to WKY controls, the SHR demonstrated: Higher systolic blood pressure (p<0.0001), bi-atrial enlargement (p<0.05), bi-ventricular hypertrophy (p<0.05), lower atrial ERP (p = 0.008), increased atrial conduction heterogeneity (p = 0.001) and increased atrial interstitial fibrosis (p = 0.006) & CD68 - positive macrophages infiltration (p<0.0001). These changes resulted in higher atrial arrhythmia inducibility (p = 0.01) and longer induced AF episodes (p = 0.02) in 15-month old SHR. Ageing contributed to incremental bi-atrial hypertrophy (p<0.01) and atrial conduction heterogeneity (p<0.01) without affecting atrial ERP, fibrosis and arrhythmia inducibility. The limited effect of ageing on the atrial substrate may be secondary to the reduction in CD68-positive macrophages. Conclusions: Significant atrial electrical and structural remodeling is evident in the ageing spontaneously hypertensive rat atria. Concomitant hypertension appears to play a greater pathophysiological role than ageing despite their compounding effect on the atrial substrate. Inflammation is pathophysiologically linked to the pro-fibrotic changes in the hypertensive atria

    Community Based Research Network: Opportunities for Coordination of Care, Public Health Surveillance, and Farmworker Research

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    Introduction:  The lack of aggregated longitudinal health data on farmworkers has severely limited opportunities to conduct research to improve their health status. To correct this problem, we have created the infrastructure necessary to develop and maintain a national Research Data Repository of migrant and seasonal farmworker patients and other community members receiving medical care from Community and Migrant Health Centers (C/MHCs). Project specific research databases can be easily extracted from this repository.Methods:  The Community Based Research Network (CBRN) has securely imported and merged electronic health records (EHRs) data from five geographically dispersed C/MHCs.  To demonstrate the effectiveness of our data aggregation methodologies, we also conducted a small pilot study using clinical, laboratory and demographic data from the CBRN Data Repository from two initial C/MHCs to evaluate HbA1c management.Results:  Overall, there were 67,878 total patients (2,858 farmworkers) that were seen by two C/MHCs from January to August 2013.  A total of 94,189 encounters were captured and all could be linked to a unique patient. HbA1c values decreased as the number of tests or intensity of testing increased.Conclusion:   This project will inform the foundation for an expanding collection of C/MHC data for use by clinicians for medical care coordination, by clinics to assess quality of care, by public health agencies for surveillance, and by researchers under Institutional Review Board (IRB) oversight to advance understanding of the needs and capacity of the migrant and seasonal farmworker population and the health centers that serve them. Approved researchers can request data that constitute a Limited Data Set from the CBRN Data Repository to establish a specific research database for their project

    Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity

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    Background: Obesity and atrial fibrillation (AF) are public health issues with significant consequences. Objectives This study sought to delineate the development of global electrophysiological and structural substrate for AF in sustained obesity. Methods: Ten sheep fed ad libitum calorie-dense diet to induce obesity over 36 weeks were maintained in this state for another 36 weeks; 10 lean sheep with carefully controlled weight served as controls. All sheep underwent electrophysiological and electroanatomic mapping; hemodynamic and imaging assessment (echocardiography and dual-energy x-ray absorptiometry); and histology and molecular evaluation. Evaluation included atrial voltage, conduction velocity (CV), and refractoriness (7 sites, 2 cycle lengths), vulnerability for AF, fatty infiltration, atrial fibrosis, and atrial transforming growth factor (TGF)-β1 expression. Results: Compared with age-matched controls, chronically obese sheep demonstrated greater total body fat (p 0.8) or ERP heterogeneity (p > 0.3). Obesity was associated with more episodes (p = 0.02), prolongation (p = 0.01), and greater cumulative duration (p = 0.02) of AF. Epicardial fat infiltrated the posterior LA in the obese group (p < 0.001), consistent with reduced endocardial voltage in this region. Atrial fibrosis (p = 0.03) and TGF-β1 protein (p = 0.002) were increased in the obese group. Conclusions: Sustained obesity results in global biatrial endocardial remodeling characterized by LA enlargement, conduction abnormalities, fractionated electrograms, increased profibrotic TGF-β1 expression, interstitial atrial fibrosis, and increased propensity for AF. Obesity was associated with reduced posterior LA endocardial voltage and infiltration of contiguous posterior LA muscle by epicardial fat, representing a unique substrate for AF

    Myocardial infarction and atrial fibrillation: Importance of atrial ischemia

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    Background-Myocardial infarction (MI) is associated with the development of atrial fibrillation (AF). We aimed to characterize the atrial abnormalities because of MI and determine the role of ischemia to the AF substrate. Methods and Results-Forty-four s
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