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The Effect of Haptic Feedback on Efficiency and Safety During Preretinal Membrane Peeling Simulation.
PurposeWe determine whether haptic feedback improves surgical performance and outcome during simulated a preretinal membrane peeling procedure.MethodsA haptic-enabled virtual reality preretinal membrane peeling simulator was developed using a surgical cockpit with two multifinger haptic devices. Six subjects (three trained retina surgeons and three nonsurgeons) performed the preretinal membrane peeling surgical procedure using two modes of operation: visual and haptic feedback, and visual feedback only.ResultsTask completion time, tool tip path trajectory, tool-retina collision force, and retinal damage were all reduced with haptic feedback used and compared to modes where haptic feedback was disabled.ConclusionsHaptic feedback improves efficiency and safety during preretinal membrane peeling simulation.Translational relevanceThese findings highlight the potential benefit of haptic feedback for improving performance and safety of vitreoretinal surgery
On the packing density of the unbound protein-protein interaction interface and its implications in dynamics
Advertisement-Click Prediction Based on Mobile Big Data from HyXen AdLocus
The popularity of Internet has made advertisement marketing gone virtualized and location-based mobile advertising successful in recent years. Adlocus, an APP developed by HyXen Technology, is one good example to achieve this. This advertising software can tailor to the campaign needs and target users within a diameter of 1 km. However, the question is that is it possible to predict whether the user is willing to click on the advertisement. This paper adopts many ways to analyze how these relations influence in different kinds of mobile advertisement. A comprehensive performance comparison of different models is provided, and the analysis of different factors is also discussed, including click time, advertisement category, language, and mobile phone manufacturers
Borrelia burgdorferi sensu lato in Ixodes ricinus ticks collected from migratory birds in Southern Norway
<p>Abstract</p> <p>Background</p> <p><it>Borrelia burgdorferi </it>sensu lato (s.l.) are the causative agent for Lyme borreliosis (LB), the most common tick-borne disease in the northern hemisphere. Birds are considered important in the global dispersal of ticks and tick-borne pathogens through their migration. The present study is the first description of <it>B. burgdorferi </it>prevalence and genotypes in <it>Ixodes ricinus </it>ticks feeding on birds during spring and autumn migration in Norway.</p> <p>Methods</p> <p>6538 migratory birds were captured and examined for ticks at Lista Bird Observatory during the spring and the autumn migration in 2008. 822 immature <it>I. ricinus </it>ticks were collected from 215 infested birds. Ticks were investigated for infection with <it>B. burgdorferi </it>s.l. by real-time PCR amplification of the 16S rRNA gene, and <it>B. burgdorferi </it>s.l. were thereafter genotyped by melting curve analysis after real-time PCR amplification of the <it>hbb </it>gene, or by direct sequencing of the PCR amplicon generated from the <it>rrs </it>(16S)-<it>rrl </it>(23S) intergenetic spacer.</p> <p>Results</p> <p><it>B. burgdorferi </it>s.l. were detected in 4.4% of the ticks. The most prevalent <it>B. burgdorferi </it>genospecies identified were <it>B. garinii </it>(77.8%), followed by <it>B.valaisiana </it>(11.1%), <it>B. afzelii </it>(8.3%) and <it>B. burgdorferi </it>sensu stricto (2.8%).</p> <p>Conclusion</p> <p>Infection rate in ticks and genospecies composition were similar in spring and autumn migration, however, the prevalence of ticks on birds was higher during spring migration. The study supports the notion that birds are important in the dispersal of ticks, and that they may be partly responsible for the heterogeneous distribution of <it>B. burgdorferi </it>s.l. in Europe.</p
Nonrigid Registration of Brain Tumor Resection MR Images Based on Joint Saliency Map and Keypoint Clustering
This paper proposes a novel global-to-local nonrigid brain MR image registration to compensate for the brain shift and the unmatchable outliers caused by the tumor resection. The mutual information between the corresponding salient structures, which are enhanced by the joint saliency map (JSM), is maximized to achieve a global rigid registration of the two images. Being detected and clustered at the paired contiguous matching areas in the globally registered images, the paired pools of DoG keypoints in combination with the JSM provide a useful cluster-to-cluster correspondence to guide the local control-point correspondence detection and the outlier keypoint rejection. Lastly, a quasi-inverse consistent deformation is smoothly approximated to locally register brain images through the mapping the clustered control points by compact support radial basis functions. The 2D implementation of the method can model the brain shift in brain tumor resection MR images, though the theory holds for the 3D case
Genomic activation of the EGFR and HER2-neu genes in a significant proportion of invasive epithelial ovarian cancers
<p>Abstract</p> <p>Background</p> <p>The status of the EGFR and HER2-neu genes has not been fully defined in ovarian cancer. An integrated analysis of both genes could help define the proportion of patients that would potentially benefit from targeted therapies.</p> <p>Methods</p> <p>We determined the tumour mutation status of the entire tyrosine kinase (TK) domain of the EGFR and HER2-neu genes in a cohort of 52 patients with invasive epithelial ovarian cancer as well as the gene copy number and protein expression of both genes in 31 of these patients by DGGE and direct sequecing, immunohistochemistry and Fluorescent in Situ Hybridisation (FISH).</p> <p>Results</p> <p>The EGFR was expressed in 59% of the cases, with a 2+/3+ staining intensity in 38%. HER2-neu expression was found in 35%, with a 2/3+ staining in 18%. No mutations were found in exons 18–24 of the TK domains of EGFR and HER2-neu. High polysomy of the EGFR gene was observed in 13% of the invasive epthelial cancers and amplification of the HER2-neu gene was found in 10% and correlated with a high expression level by immunohistochemistry.</p> <p>Mutations within the tyrosine kinase domain were not found in the entire TK domain of both genes, but have been found in very rare cases by others.</p> <p>Conclusion</p> <p>Genomic alteration of the HER2-neu and EGFR genes is frequent (25%) in ovarian cancer. EGFR/HER2-neu targeted therapies should be investigated prospectively and specifically in that subset of patients.</p
Phase II study of the farnesyltransferase inhibitor R115777 in advanced melanoma (CALGB 500104)
BACKGROUND: Multiple farnesylated proteins are involved in signal transduction in cancer. Farnesyltransferase inhibitors (FTIs) have been developed as a strategy to inhibit the function of these proteins. As FTIs inhibit proliferation of melanoma cell lines, we undertook a study to assess the impact of a FTI in advanced melanoma. As farnesylated proteins are also important for T cell activation, measurement of effects on T cell function was also pursued. METHODS: A 3-stage trial design was developed with a maximum of 40 patients and early stopping if there were no responders in the first 14, or fewer than 2 responders in the first 28 patients. Eligibility included performance status of 0–1, no prior chemotherapy, at most 1 prior immunotherapy, no brain metastases, and presence of at least 2 cutaneous lesions amenable to biopsy. R115777 was administered twice per day for 21 days of a 28-day cycle. Patients were evaluated every 2 cycles by RECIST. Blood and tumor were analyzed pre-treatment and during week 7. RESULTS: Fourteen patients were enrolled. Two patients had grade 3 toxicities, which included myelosuppression, nausea/vomiting, elevated BUN, and anorexia. There were no clinical responses. All patients analyzed showed potent inhibition of FT activity (85-98%) in tumor tissue; inhibition of phosphorylated ERK and Akt was also observed. T cells showed evidence of FT inhibition and diminished IFN-γ production. CONCLUSIONS: Despite potent target inhibition, R115777 showed no evidence of clinical activity in this cohort of melanoma patients. Inhibition of T cell function by FTIs has potential clinical implications. Clinicaltrials.gov number NCT0006012
Association between biliary complications and technique of hilar division (extrahepatic vs. intrahepatic) in major liver resections
BACKGROUND: Division of major vascular and biliary structures during major hepatectomies can be carried out either extrahepatically at the porta hepatic or intrahepatically during the parenchymal transection. In this retrospective study we test the hypothesis that the intrahepatic technique is associated with less early biliary complications. METHODS: 150 patients who underwent major hepatectomies were retrospectively allocated into an intrahepatic group (n = 100) and an extrahepatic group (n = 50) based on the technique of hilar division. The two groups were operated by two different surgical teams, each one favoring one of the two approaches for hilar dissection. Operative data (warm ischemic time, operative time, blood loss), biliary complications, morbidity and mortality rates were analyzed. RESULTS: In extrahepatic patients, operative time was longer (245 ± 50 vs 214 ± 38 min, p < 0.05) while the overall complication rate (55% vs 52%), hospital stay (13 ± 7 vs 12 ± 4 days), bile leak rate (22% vs 20%) and mortality (2% vs 2%) were similar compared to intrahepatic patients. However, most (57%) bile leaks in extrahepatic patients were grade II (leaks that required non-operative interventional treatment, while most (70%) leaks in the intrahepatic group were grade I (leaks that resolved and presented two injuries (4%) of the remaining bile ducts (p < 0.05). CONCLUSION: Intrahepatic hilar division is as safe as extrahepatic hilar division in terms of intraoperative blood requirements, morbidity and mortality. The extrahepatic technique is associated with more severe bile leaks and biliary injuries
Dysbindin Promotes the Post-Endocytic Sorting of G Protein-Coupled Receptors to Lysosomes
BackgroundDysbindin, a cytoplasmic protein long known to function in the biogenesis of specialized lysosome-related organelles (LROs), has been reported to reduce surface expression of D2 dopamine receptors in neurons. Dysbindin is broadly expressed, and dopamine receptors are members of the large family of G protein-coupled receptors (GPCRs) that function in diverse cell types. Thus we asked if dysbindin regulates receptor number in non-neural cells, and further investigated the cellular basis of this regulation.Methodology/principal findingsWe used RNA interference to deplete endogenous dysbindin in HEK293 and HeLa cells, then used immunochemical and biochemical methods to assess expression and endocytic trafficking of epitope-tagged GPCRs. Dysbindin knockdown up-regulated surface expression of D2 receptors compared to D1 receptors, as reported previously in neurons. This regulation was not mediated by a change in D2 receptor endocytosis. Instead, dysbindin knockdown specifically reduced the subsequent trafficking of internalized D2 receptors to lysosomes. This distinct post-endocytic sorting function explained the minimal effect of dysbindin depletion on D1 receptors, which recycle efficiently and traverse the lysosomal pathway to only a small degree. Moreover, dysbindin regulated the delta opioid receptor, a more distantly related GPCR that is also sorted to lysosomes after endocytosis. Dysbindin was not required for lysosomal trafficking of all signaling receptors, however, as its depletion did not detectably affect down-regulation of the EGF receptor tyrosine kinase. Dysbindin co-immunoprecipitated with GASP-1 (or GPRASP-1), a cytoplasmic protein shown previously to modulate lysosomal trafficking of D2 dopamine and delta opioid receptors by direct interaction, and with HRS that is a core component of the conserved ESCRT machinery mediating lysosome biogenesis and sorting.Conclusions/significanceThese results identify a distinct, and potentially widespread function of dysbindin in promoting the sorting of specific GPCRs to lysosomes after endocytosis
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