749 research outputs found

    The Effects of Momentary Visual Disruption on Hazard Anticipation in Driving

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    Driver distraction is known to increase crashes, especially when the driver glances for especially long periods of time inside the vehicle. While it is clear that such glances increase risk for the driver when looking inside the vehicle, it is less clear how these glances disrupt the ongoing processing of information outside the vehicle once the eyes return to the road. The present study was aimed at exploring the effect of visual disruptions on the top-down processes that guide the detection and monitoring of hazards on the forward roadway. Using a driving simulator, twelve participants were monitored with an eye tracking system while they navigated various hazardous scenarios. Six participants were momentarily interrupted by a visual secondary task (simulating a glance inside the vehicle) prior to the hazard occurrence and six were not. Eye movement analyses show that interrupted drivers often failed to continue scanning for a hazard when their forward view reappeared. Implications of this study are discussed

    Adherence to Competing Strategies for Colorectal Cancer Screening Over 3 Years

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    We have shown that, in a randomized trial comparing adherence to different colorectal cancer (CRC) screening strategies, participants assigned to either fecal occult blood testing (FOBT) or given a choice between FOBT and colonoscopy had significantly higher adherence than those assigned to colonoscopy during the first year. However, how adherence to screening changes over time is unknown

    Criticality in correlated quantum matter

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    At quantum critical points (QCP) \cite{Pfeuty:1971,Young:1975,Hertz:1976,Chakravarty:1989,Millis:1993,Chubukov:1 994,Coleman:2005} there are quantum fluctuations on all length scales, from microscopic to macroscopic lengths, which, remarkably, can be observed at finite temperatures, the regime to which all experiments are necessarily confined. A fundamental question is how high in temperature can the effects of quantum criticality persist? That is, can physical observables be described in terms of universal scaling functions originating from the QCPs? Here we answer these questions by examining exact solutions of models of correlated systems and find that the temperature can be surprisingly high. As a powerful illustration of quantum criticality, we predict that the zero temperature superfluid density, ρs(0)\rho_{s}(0), and the transition temperature, TcT_{c}, of the cuprates are related by Tcρs(0)yT_{c}\propto\rho_{s}(0)^y, where the exponent yy is different at the two edges of the superconducting dome, signifying the respective QCPs. This relationship can be tested in high quality crystals.Comment: Final accepted version not including minor stylistic correction

    Development and preliminary validation of a tool measuring concordance and belief about performing pressure-relieving activities for pressure ulcer prevention in spinal cord injury

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    Objective: To develop and examine the reliability, and validity of a questionnaire measuring concordance for performing pressure-relief for pressure ulcer (PrU) prevention in people with Spinal Cord Injury (SCI). Methods: Phase I included item development, content and face validity testing. In phase II, the questionnaire was evaluated for preliminary acceptability, reliability and validity among 48 wheelchair users with SCI. Results: Thirty-seven items were initially explored. Item and factor analysis resulted in a final 26-item questionnaire with four factors reflecting concordance, perceived benefits, perceived negative consequences, and personal practical barriers to performing pressure-relief activities. The internal consistency reliability for four domains were very good (Cronbach's α = .75-.89). Pearson correlation coefficient on a test-retest of the same subjects yielded significant correlations in concordance (r = .91, p = .005), perceived benefit (r = .71, p < .04), perceived negative consequences (r = .98, p < .0001), personal barriers (r = .93, p= .002). Participants with higher levels of concordance reported a greater amount of pressure-relieving performed. Individuals viewing PrU as a threatening illness were associated with higher scores of concordance and tended to report a greater amount of pressure-relieving performance which provides evidence of criterion related validity. Conclusion: The new questionnaire demonstrated good preliminary reliability and validity in people with SCI. Further evaluation is necessary to confirm these findings using larger samples with follow-up data for predictive validity. Such a questionnaire could be used by clinicians to identify high risk of patients and to design individualised education programme for PrU prevention

    Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

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    &lt;p&gt;Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.&lt;/p&gt; &lt;p&gt;Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).&lt;/p&gt; &lt;p&gt;Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.&lt;/p&gt; &lt;p&gt;Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.&lt;/p&gt

    DLL4-Notch signaling mediates tumor resistance to anti-VEGF therapy in vivo.

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    Resistance to VEGF inhibitors is emerging as a major clinical problem. Notch signaling has been implicated in tumor angiogenesis. Therefore, to investigate mechanisms of resistance to angiogenesis inhibitors, we transduced human glioblastoma cells with retroviruses encoding Notch delta-like ligand 4 (DLL4), grew them as tumor xenografts and then treated the murine hosts with the VEGF-A inhibitor bevacizumab. We found that DLL4-mediated tumor resistance to bevacizumab in vivo. The large vessels induced by DLL4-Notch signaling increased tumor blood supply and were insensitive to bevacizumab. However, blockade of Notch signaling by dibenzazepine, a γ-secretase inhibitor, disrupted the large vessels and abolished the tumor resistance. Multiple molecular mechanisms of resistance were shown, including decreased levels of hypoxia-induced VEGF and increased levels of the VEGF receptor VEGFR1 in the tumor stroma, decreased levels of VEGFR2 in large blood vessels, and reduced levels of VEGFR3 overall. DLL4-expressing tumors were also resistant to a VEGFR targeting multikinase inhibitor. We also observed activation of other pathways of tumor resistance driven by DLL4-Notch signaling, including the FGF2-FGFR and EphB4-EprinB2 pathways, the inhibition of which reversed tumor resistance partially. Taken together, our findings show the importance of classifying mechanisms involved in angiogenesis in tumors, and how combination therapy to block DLL4-Notch signaling may enhance the efficacy of VEGF inhibitors, particularly in DLL4-upregulated tumors, and thus provide a rational base for the development of novel strategies to overcome antiangiogenic resistance in the clinic

    Analyzing derived metallicities and ionization parameters from model-based determinations in ionized gaseous nebulae

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    We analyze the reliability of oxygen abundances and ionization parameters obtained from different diagnostic diagrams. For this, we compiled from the literature observational emission line intensities and oxygen abundance of 446 star-forming regions whose O/H abundance was determined by direct estimation of electron temperature. The abundances compiled were compared with the values calculated in this work using different diagnostic diagrams in combination with results from a grid of photoionization models. We found that the [\ion{O}{iii}]/[\ion{O}{ii}] vs. [\ion{N}{ii}]/[\ion{O}{ii}], [\ion{O}{iii}]/Hβ\beta vs. [\ion{N}{ii}]/[\ion{O}{ii}], and ([\ion{O}{iii}]/Hβ\beta)/([\ion{N}{ii}]/Hα\alpha) vs. [\ion{S}{ii}]/[\ion{S}{iii}] diagnostic diagrams give O/H values close to the TeT_{\rm e}-method, with differences of about 0.04 dex and dispersion of about 0.3 dex. Similar results were obtained by detailed models but with a dispersion of 0.08 dex. The origin of the dispersion found in the use of diagnostic diagrams is probably due to differences between the real N/O-O/H relation of the sample and the one assumed in the models. This is confirmed by the use of detailed models that do not have a fixed N/O-O/H relation. We found no correlation between ionization parameter and the metallicity for the objects of our sample. We conclude that the combination of two line ratio predicted by photoionization models, one sensitive to the metallicity and another sensitive to the ionization parameter, which takes into account the physical conditions of star-forming regions, gives O/H estimates close to the values derived using direct detections of electron temperatures.Comment: 12 pages, 9 figures, accepted by MNRA

    BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

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    Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations
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