Semi-automated and fully automated mammographic density measurement and breast cancer risk prediction

The task of breast density quantification is becoming increasingly relevant due to its association with breast cancer risk. In this work, a semi-automated and a fully automated tools to assess breast density from full-field digitized mammograms are presented. The first tool is based on a supervised interactive thresholding procedure for segmenting dense from fatty tissue and is used with a twofold goal: for assessing mammographic density (MD) in a more objective and accurate way than via visual-based methods and for labeling the mammograms that are later employed to train the fully automated tool. Although most automated methods rely on supervised approaches based on a global labeling of the mammogram, the proposed method relies on pixel-level labeling, allowing better tissue classification and density measurement on a continuous scale. The fully automated method presented combines a classification scheme based on local features and thresholding operations that improve the performance of the classifier. A dataset of 655 mammograms was used to test the concordance of both approaches in measuring MD. Three expert radiologists measured MD in each of the mammograms using the semi-automated tool (DM-Scan). It was then measured by the fully automated system and the correlation between both methods was computed. The relation between MD and breast cancer was then analyzed using a case–control dataset consisting of 230 mammograms. The Intraclass Correlation Coefficient (ICC) was used to compute reliability among raters and between techniques. The results obtained showed an average ICC = 0.922 among raters when using the semi-automated tool, whilst the average correlation between the semi-automated and automated measures was ICC = 0.838. In the case–control study, the results obtained showed Odds Ratios (OR) of 1.38 and 1.50 per 10% increase in MD when using the semi-automated and fully automated approaches respectively. It can therefore be concluded that the automated and semi-automated MD assessments present a good correlation. Both the methods also found an association between MD and breast cancer risk, which warrants the proposed tools for breast cancer risk prediction and clinical decision making. A full version of the DM-Scan is freely available.     

Computer Simulations of VANETs Using Realistic City Topologies

Researchers in vehicular ad hoc networks (VANETs) commonly use simulation to test new algorithms and techniques. This is the case because of the high cost and labor involved in deploying and testing vehicles in real outdoor scenarios. However, when determining the factors that should be taken into account in these simulations, some factors such as realistic road topologies and presence of obstacles are rarely addressed. In this paper, we first evaluate the packet error rate (PER) through actual measurements in an outdoor road scenario, and deduce a close model of the PER for VANETs. Secondly, we introduce a topology-based visibility scheme such that road dimension and geometry can be accounted for, in addition to line-of-sight. We then combine these factors to determine when warning messages (i.e., messages that warn drivers of danger and hazards) are successfully received in a VANET. Through extensive simulations using different road topologies, city maps, and visibility schemes, we show these factors can impact warning message dissemination time and packet delivery rate.     

Fcgamma receptor IIA H/R131 polymorphism in patients with antiphospholipid antibodies

A role for Fcgamma receptor in the pathophysiology of thrombosis in APS has been hypothesized. The polymorphism of this receptor, FcgammaRIIA H/R131, is associated with the binding affinity for human IgG2 (i.e. FcgammaRIIA-H131 isoform has a higher affinity than FcgammaRIIA-R131). Since anti-beta2 glycoprotein I antibodies (anti beta2GPI), which play a major pathogenic role in APS, show IgG2 dominant distribution, we investigated the prevalence of receptor isoforms in patients with antiphospholipid antibodies (aPL) by a PCR-RFLP method. We studied 100 Caucasian patients with aPL (57 primary APS, 32 secondary APS to SLE and 11 other diseases with aPL) and 41 healthy controls. H131/H131, H131/R131 and R131/R131 genotypes were found in 21 (21%), 50 (50%) and 29 (29%) in the patient group, and 9 (22%), 23 (56%) and 9 (22%) in control group, respectively. Thus there was no statistically significant difference in the prevalence of each genotype in these groups. None of the clinical manifestations of primary APS (arterial/venous thrombosis, recurrent pregnancy loss and thrombocytopenia) was significantly correlated with any FcgammaRIIA genotype. In conclusion, FcgammaRIIA polymorphism did not correlate with the manifestations of APS, and FcgammaRIIA genotype is not a genetic marker of APS.     

Arterial disease and thrombosis in the antiphospholipid syndrome: a pathogenic role for endothelin 1

PURPOSE: It has been proposed that inferior vena cava filter placement should be the initial treatment of deep venous thrombosis (DVT) or pulmonary embolus (PE) in patients with coexisting malignant disease. We have chosen instead to selectively place filters only in patients with either a contraindication to anticoagulation therapy or a subsequent complication from anticoagulation therapy. The treatment efficacy and mortality rates in patients with concomitant malignant disease and venous thromboembolism using this approach was determined. METHODS: We retrospectively reviewed all patients at our institution with malignant disease in whom venous thromboembolism developed between August 1991 through August 1996 and identified 166 patients with PE (n = 8), DVT (n = 147), and DVT/PE (n = 11). Of these patients, 138 (83.1%) were initially treated with anticoagulation therapy, and 28 (16.9%) had primary filter placement because of contraindications to anticoagulation therapy (10 for intracranial tumors, 11 for recent or upcoming operations, 6 for recent hemorrhage, and 1 for a malignant bloody pericardial effusion). RESULTS: Thirty-two (23%) of the 138 patients who initially underwent anticoagulation therapy subsequently required a filter for the following reasons: bleeding (n = 15, 10.9%); recurrent thromboembolism (n = 6, 4.3%); heparin-induced thrombocytopenia (n = 1, 0.7%); and perceived high risk for bleeding with continued anticoagulation therapy (n = 11, 8%). Both bleeding and recurrent thromboembolism developed in 1 patient. Sixty patients (36%) received filters. No major technical complications occurred from filter placement. Major recurrent thromboembolic complications developed in 10 patients: DVT (n = 6, 10%), PE (n = 2, 3.3%), inferior vena cava thrombosis and phlegmasia cerulea dolens (n = 1, 1.7%), superior vena cava thrombosis (n = 1, 1.7%). Venous gangrene developed in 1 patient with DVT. The 1-year actuarial survival rates for patients treated with filter and anticoagulation therapy were 35% and 38%, respectively (P = NS). CONCLUSION: In summary, our experience suggests that 64% of patients with malignant disease and venous thromboembolism are effectively treated with anticoagulation alone; 17% require primary filter placement for standard indications, and an additional 19% require subsequent filter placement because of complications (primarily bleeding) or failure of anticoagulation therapy. Although technical complications of filter placement are low, serious life-threatening or limb-threatening thromboembolic complications developed in 17% of patients. Survival was poor in all patients, regardless of treatment. These data support a conservative approach of routine anticoagulation therapy with selective filter placement.     

Thermal spikes in Ag/Fe and Cu/Fe ion beam mixing

Ion beam mixing has been studied since 1980, and since then a lot of experimental and theoretical work has been done and knowledge has been gathered. Nevertheless, there are still many fundamental aspects that need to be clarified and with that aim many experiments need to be performed. Copper and iron are miscible in the liquid state, while silver and iron are not. However, both systems are thermally immiscible in the solid state. In order to have an insight into the importance of mixing within thermal spikes during ion beam irradiation, we deposited Cu/Fe and Ag/Fe bilayers onto Si substrates and irradiated them at room temperature with 2 MeV Cu and 2.5 MeV Au ions. A combination of Rutherford backscattering spectrometry (RBS) and atomic force microscopy (AFM) was used to analyze the atomic transport at the interface and the morphology changes of the samples. From the element profiles at the interface we conclude a mixing efficiency, which is indeed larger than the prediction of the ballistic model in the Cu/Fe system and smaller in the Ag/Fe system. Since ballistic mixing is expected in any case, we argue that demixing and phase separation in the Ag/Fe system occur in the thermal spike phase of the cascade as a consequence of the positive heat of mixing. Further mixing does occur in the thermal spike in the Cu/Fe system and they remain mixed even at the solid state because of the high cooling rate. In addition, ion irradiation induces a large surface roughening of the Ag and Cu top layers as proven by AFM. This effect is important for the correct interpretation of the results. Furthermore, this recrystallization affects also the interface, producing a rough interface, that appears in the RBS spectra as an atomic ‘diffusion’ at the interface.     

Activation of trehalase during growth induction by nitrogen sources in the yeast Saccharomyces cerevisiae depends on the free catalytic subunits of camp-dependent protein kinase,but not on functional ras proteins

Addition of a nitrogen-source to glucose-repressed, nitrogen-starved G0 cells of the yeast Saccharomyces cerevisiae in the presence of a fermentable carbon source induces growth and causes within a few minutes a five-fold, protein-synthesis-independent increase in the activity of trehalase. Nitrogen-activated trehalase could be deactivated in vitro by alkaline phosphatase treatment, supporting the idea that the activation is triggered by phosphorylation. Yeast strains containing only one of the three TPK genes (which encode the catalytic subunit of cAMP-dependent protein kinase) showed different degrees of nitrogen-induced trehalase activation. The order of effectiveness was different from that previously reported for glucose-induced activation of trehalase in glucose-derepressed yeast cells. Further reduction of TPK-encoded catalytic subunit activity by partially inactivating point mutations in the remaining TPK gene further diminished nitrogen-induced trehalase activation, while deletion of the BCY1 gene (which encodes the regulatory subunit) in the same strains resulted in an increase in the extent of activation. Deletion of the RAS genes in such a tpk^w1 bcy1 strain had no effect. These results are consistent with mediation of nitrogen-induced trehalase activation by the free catalytic subunits alone. They support our previous conclusion that cAMP does not act as second messenger in this nitrogen-induced activation process and our suggestion that a novel nitrogen-induced signaling pathway integrates with the cAMP pathway at the level of the free catalytic subunits of protein kinase A. Western blot experiments showed that the differences in the extent of trehalase activation were not due to differences in trehalase expression. On the other hand, we cannot completely exclude that protein kinase A influences the nitrogen-induced activation mechanism itself rather than acting directly on trehalase. However, any such alternative explanation requires the existence of an additional, yet unknown, mechanism for activation of trehalase besides the well-established regulation by protein kinase A.     

Selection of Strategies for Collision-free Motion in Multi-manipulator Systems

Strategy-based path planning was introduced by the authors as a way to give robotic manipulators some sort of reactive behaviour in dynamic and unpredictable environments. This approach is based on making robots react to moving obstacles using a restricted subset of the configuration space, and on using an off-line pre-planning stage to choose the restricted subset. In this paper, strategy-based path planning is applied and explored, focusing our attention on the off-line stage. It is applied to the joint motion of two and three robots that perform pick and place tasks sharing common working areas.     

An overview of vertical handover techniques: Algorithms, protocols and tools

Wireless technologies, under the “Anywhere, Anytime” paradigm, offer users the promise of being always attached to the network. Mobile devices enabled with multiple wireless technologies make possible to maintain seamless connectivity in highly dynamic scenarios such as vehicular networks (VNs), switching from one wireless network to another by using vertical handover techniques (VHO). In this paper we present an overview of VHO techniques, along with the main algorithms, protocols and tools proposed in the literature. In addition we suggest the most appropriate VHO techniques to efficiently communicate in VN environments considering the particular characteristics of this type of networks.