Pre-existing chronic thromboembolic pulmonary hypertension in acute pulmonary embolism

BACKGROUND Chronic thromboembolic pulmonary hypertension (CTEPH) is considered a complication of pulmonary embolism (PE). However, signs of CTEPH may exist in patients with a first symptomatic PE. RESEARCH QUESTION Which radiologic findings on computed tomography pulmonary angiography (CTPA) at the time of acute PE could indicate the presence of a pre-existing CTEPH? RESULTS We included unselected patients with acute PE who were prospectively followed for 2 years with a structured visit schedule. Two expert radiologists independently assessed patients' baseline CTPAs for pre-existing CTEPH; in case of disagreement, a decision was reached by 2:1 majority with a third expert. In addition, the radiologists checked for predefined individual parameters suggesting chronic PE and pulmonary hypertension. Signs of chronic PE or CTEPH at baseline were identified in 46 (15%) of 303 included patients. Intravascular webs, arterial narrowing or retraction, dilated bronchial arteries and right ventricular hypertrophy were the main drivers of the assessment. Five (1.7%) patients were diagnosed with CTEPH during follow-up. All four patients diagnosed with CTEPH early (83-108 days after acute PE) could be found in enriched subgroups based on the experts' overall assessment or fulfilling a minimum number of the predefined radiologic criteria at baseline. The specificity of pre-existing CTEPH diagnosis and the level of radiologists' agreement improved as the number of required criteria increased. INTERPRETATION Searching for predefined radiologic parameters suggesting pre-existing CTEPH at the time of acute PE diagnosis may allow for targeted follow-up strategies and risk-adapted CTEPH screening, thus facilitating earlier CTEPH diagnosis

Butler enables rapid cloud-based analysis of thousands of human genomes.

We present Butler, a computational tool that facilitates large-scale genomic analyses on public and academic clouds. Butler includes innovative anomaly detection and self-healing functions that improve the efficiency of data processing and analysis by 43% compared with current approaches. Butler enabled processing of a 725-terabyte cancer genome dataset from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project in a time-efficient and uniform manner

Cardiovascular Magnetic Resonance Imaging Feature Tracking: Impact of Training on Observer Performance and Reproducibility

BACKGROUND: Cardiovascular magnetic resonance feature tracking (CMR-FT) is increasingly used for myocardial deformation assessment including ventricular strain, showing prognostic value beyond established risk markers if used in experienced centres. Little is known about the impact of appropriate training on CMR-FT performance. Consequently, this study aimed to evaluate the impact of training on observer variance using different commercially available CMR-FT software. METHODS: Intra- and inter-observer reproducibility was assessed prior to and after dedicated one-hour observer training. Employed FT software included 3 different commercially available platforms (TomTec, Medis, Circle). Left (LV) and right (RV) ventricular global longitudinal as well as LV circumferential and radial strains (GLS, GCS and GRS) were studied in 12 heart failure patients and 12 healthy volunteers. RESULTS: Training improved intra- and inter-observer reproducibility. GCS and LV GLS showed the highest reproducibility before (ICC \u3e0.86 and \u3e0.81) and after training (ICC \u3e0.91 and \u3e0.92). RV GLS and GRS were more susceptible to tracking inaccuracies and reproducibility was lower. Inter-observer reproducibility was lower than intra-observer reproducibility prior to training with more pronounced improvements after training. Before training, LV strain reproducibility was lower in healthy volunteers as compared to patients with no differences after training. Whilst LV strain reproducibility was sufficient within individual software solutions inter-software comparisons revealed considerable software related variance. CONCLUSION: Observer experience is an important source of variance in CMR-FT derived strain assessment. Dedicated observer training significantly improves reproducibility with most profound benefits in states of high myocardial contractility and potential to facilitate widespread clinical implementation due to optimized robustness and diagnostic performance

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Identification of a new European rabbit IgA with a serine-rich hinge region

<div><p>In mammals, the most striking IgA system belongs to Lagomorpha. Indeed, 14 IgA subclasses have been identified in European rabbits, 11 of which are expressed. In contrast, most other mammals have only one IgA, or in the case of hominoids, two IgA subclasses. Characteristic features of the mammalian IgA subclasses are the length and amino acid sequence of their hinge regions, which are often rich in Pro, Ser and Thr residues and may also carry Cys residues. Here, we describe a new IgA that was expressed in New Zealand White domestic rabbits of <i>IGHV</i>a1 allotype. This IgA has an extended hinge region containing an intriguing stretch of nine consecutive Ser residues and no Pro or Thr residues, a motif exclusive to this new rabbit IgA. Considering the amino acid properties, this hinge motif may present some advantage over the common IgA hinge by affording novel functional capabilities. We also sequenced for the first time the IgA14 CH2 and CH3 domains and showed that IgA14 and IgA3 are expressed.</p></div