Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Bioinformatics and molecular modeling in glycobiology

The field of glycobiology is concerned with the study of the structure, properties, and biological functions of the family of biomolecules called carbohydrates. Bioinformatics for glycobiology is a particularly challenging field, because carbohydrates exhibit a high structural diversity and their chains are often branched. Significant improvements in experimental analytical methods over recent years have led to a tremendous increase in the amount of carbohydrate structure data generated. Consequently, the availability of databases and tools to store, retrieve and analyze these data in an efficient way is of fundamental importance to progress in glycobiology. In this review, the various graphical representations and sequence formats of carbohydrates are introduced, and an overview of newly developed databases, the latest developments in sequence alignment and data mining, and tools to support experimental glycan analysis are presented. Finally, the field of structural glycoinformatics and molecular modeling of carbohydrates, glycoproteins, and protein–carbohydrate interaction are reviewed

Genetic signals of high-altitude adaptation in amphibians : A comparative transcriptome analysis

Background: High-altitude adaptation provides an excellent system for studying how organisms cope with multiple environmental stressors and interacting genetic modifications. To explore the genetic basis of high-altitude adaptation in poikilothermic animals, we acquired transcriptome sequences from a high-altitude population and a low-altitude population of the Asiatic toad (Bufo gargarizans). Transcriptome data from another high-altitude amphibian, Rana kukunoris and its low-altitude relative R. chensiensis, which are from a previous study, were also incorporated into our comparative analysis. Results: More than 40,000 transcripts were obtained from each transcriptome, and 5107 one-to-one orthologs were identified among the four taxa for comparative analysis. A total of 29 (Bufo) and 33 (Rana) putative positively selected genes were identified for the two high-altitude species, which were mainly concentrated in nutrient metabolism related functions. Using SNP-tagging and FST outlier analysis, we further tested 89 other nutrient metabolism related genes for signatures of natural selection, and found that two genes, CAPN2 and ITPR1, were likely under balancing selection. We did not detect any positively selected genes associated with response to hypoxia. Conclusions: Amphibians clearly employ different genetic mechanisms for high-altitude adaptation compared to endotherms. Modifications of genes associated with nutrient metabolism feature prominently while genes related to hypoxia tolerance appear to be insignificant. Poikilotherms represent the majority of animal diversity, and we hope that our results will provide useful directions for future studies of amphibians as well as other poikilotherms