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

A modular tethering complex for endosomal recycling.

How proteins migrate through the interconnected organelles of the endolysosomal system is poorly understood. A piece of the puzzle has been added with the identification of a complex of tethering factors that functions in the recycling of proteins towards the cell surface

Flexible prey handling, preference and a novel capture technique in invasive, sub-adult Chinese mitten crabs

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Predicting Inactive Conformations of Protein Kinases Using Active Structures: Conformational Selection of Type-II Inhibitors

Protein kinases have been found to possess two characteristic conformations in their activation-loops: the active DFG-in conformation and the inactive DFG-out conformation. Recently, it has been very interesting to develop type-II inhibitors which target the DFG-out conformation and are more specific than the type-I inhibitors binding to the active DFG-in conformation. However, solving crystal structures of kinases with the DFG-out conformation remains a challenge, and this seriously hampers the application of the structure-based approaches in development of novel type-II inhibitors. To overcome this limitation, here we present a computational approach for predicting the DFG-out inactive conformation using the DFG-in active structures, and develop related conformational selection protocols for the uses of the predicted DFG-out models in the binding pose prediction and virtual screening of type-II ligands. With the DFG-out models, we predicted the binding poses for known type-II inhibitors, and the results were found in good agreement with the X-ray crystal structures. We also tested the abilities of the DFG-out models to recognize their specific type-II inhibitors by screening a database of small molecules. The AUC (area under curve) results indicated that the predicted DFG-out models were selective toward their specific type-II inhibitors. Therefore, the computational approach and protocols presented in this study are very promising for the structure-based design and screening of novel type-II kinase inhibitors

Gaze-grasp coordination in obstacle avoidance: differences between binocular and monocular viewing

Most adults can skillfully avoid potential obstacles when acting in everyday cluttered scenes. We examined how gaze and hand movements are normally coordinated for obstacle avoidance and whether these are altered when binocular depth information is unavailable. Visual fixations and hand movement kinematics were simultaneously recorded, while 13 right-handed subjects reached-to-precision grasp a cylindrical household object presented alone or with a potential obstacle (wine glass) located to its left (thumb's grasp side), right or just behind it (both closer to the finger's grasp side) using binocular or monocular vision. Gaze and hand movement strategies differed significantly by view and obstacle location. With binocular vision, initial fixations were near the target's centre of mass (COM) around the time of hand movement onset, but usually shifted to end just above the thumb's grasp site at initial object contact, this mainly being made by the thumb, consistent with selecting this digit for guiding the grasp. This strategy was associated with faster binocular hand movements and improved end-point grip precision across all trials than with monocular viewing, during which subjects usually continued to fixate the target closer to its COM despite a similar prevalence of thumb-first contacts. While subjects looked directly at the obstacle at each location on a minority of trials and their overall fixations on the target were somewhat biased towards the grasp side nearest to it, these gaze behaviours were particularly marked on monocular vision-obstacle behind trials which also commonly ended in finger-first contact. Subjects avoided colliding with the wine glass under both views when on the right (finger side) of the workspace by producing slower and straighter reaches, with this and the behind obstacle location also resulting in 'safer' (i.e. narrower) peak grip apertures and longer deceleration times than when the goal object was alone or the obstacle was on its thumb side. But monocular reach paths were more variable and deceleration times were selectively prolonged on finger-side and behind obstacle trials, with this latter condition further resulting in selectively increased grip closure times and corrections. Binocular vision thus provided added advantages for collision avoidance, known to require intact dorsal cortical stream processing mechanisms, particularly when the target of the grasp and potential obstacle to it were fairly closely separated in depth. Different accounts of the altered monocular gaze behaviour converged on the conclusion that additional perceptual and/or attentional resources are likely engaged compared to when continuous binocular depth information is available. Implications for people lacking binocular stereopsis are briefly considered

Daily intake of antioxidants in relation to survival among adult patients diagnosed with malignant glioma

<p>Abstract</p> <p>Background</p> <p>Malignant glioma is a rare cancer with poor survival. The influence of diet and antioxidant intake on glioma survival is not well understood. The current study examines the association between antioxidant intake and survival after glioma diagnosis.</p> <p>Methods</p> <p>Adult patients diagnosed with malignant glioma during 1991-1994 and 1997-2001 were enrolled in a population-based study. Diagnosis was confirmed by review of pathology specimens. A modified food-frequency questionnaire interview was completed by each glioma patient or a designated proxy. Intake of each food item was converted to grams consumed/day. From this nutrient database, 16 antioxidants, calcium, a total antioxidant index and 3 macronutrients were available for survival analysis. Cox regression estimated mortality hazard ratios associated with each nutrient and the antioxidant index adjusting for potential confounders. Nutrient values were categorized into tertiles. Models were stratified by histology (Grades II, III, and IV) and conducted for all (including proxy) subjects and for a subset of self-reported subjects.</p> <p>Results</p> <p>Geometric mean values for 11 fat-soluble and 6 water-soluble individual antioxidants, antioxidant index and 3 macronutrients were virtually the same when comparing all cases (n = 748) to self-reported cases only (n = 450). For patients diagnosed with Grade II and Grade III histology, moderate (915.8-2118.3 mcg) intake of fat-soluble lycopene was associated with poorer survival when compared to low intake (0.0-914.8 mcg), for self-reported cases only. High intake of vitamin E and moderate/high intake of secoisolariciresinol among Grade III patients indicated greater survival for all cases. In Grade IV patients, moderate/high intake of cryptoxanthin and high intake of secoisolariciresinol were associated with poorer survival among all cases. Among Grade II patients, moderate intake of water-soluble folate was associated with greater survival for all cases; high intake of vitamin C and genistein and the highest level of the antioxidant index were associated with poorer survival for all cases.</p> <p>Conclusions</p> <p>The associations observed in our study suggest that the influence of some antioxidants on survival following a diagnosis of malignant glioma are inconsistent and vary by histology group. Further research in a large sample of glioma patients is needed to confirm/refute our results.</p

Coronary microvascular resistance: methods for its quantification in humans

Coronary microvascular dysfunction is a topic that has recently gained considerable interest in the medical community owing to the growing awareness that microvascular dysfunction occurs in a number of myocardial disease states and has important prognostic implications. With this growing awareness, comes the desire to accurately assess the functional capacity of the coronary microcirculation for diagnostic purposes as well as to monitor the effects of therapeutic interventions that are targeted at reversing the extent of coronary microvascular dysfunction. Measurements of coronary microvascular resistance play a pivotal role in achieving that goal and several invasive and noninvasive methods have been developed for its quantification. This review is intended to provide an update pertaining to the methodology of these different imaging techniques, including the discussion of their strengths and weaknesses

Mechanisms of HIV-associated lymphocyte apoptosis: 2010

The inevitable decline of CD4T cells in untreated infection with the Human immunodeficiency virus (HIV) is due in large part to apoptosis, one type of programmed cell death. There is accumulating evidence that the accelerated apoptosis of CD4T cells in HIV infection is multifactorial, with direct viral cytotoxicity, signaling events triggered by viral proteins and aberrant immune activation adding to normal immune defense mechanisms to contribute to this phenomenon. Current antiviral treatment strategies generally lead to reduced apoptosis, but this approach may come at the cost of preserving latent viral reservoirs. It is the purpose of this review to provide an update on the current understanding of the role and mechanisms of accelerated apoptosis of T cells in the immunopathogenesis of HIV infection, and to highlight potential ways in which this seemingly deleterious process could be harnessed to not just control, but treat HIV infection