Negative Link Prediction in Social Media

Signed network analysis has attracted increasing attention in recent years. This is in part because research on signed network analysis suggests that negative links have added value in the analytical process. A major impediment in their effective use is that most social media sites do not enable users to specify them explicitly. In other words, a gap exists between the importance of negative links and their availability in real data sets. Therefore, it is natural to explore whether one can predict negative links automatically from the commonly available social network data. In this paper, we investigate the novel problem of negative link prediction with only positive links and content-centric interactions in social media. We make a number of important observations about negative links, and propose a principled framework NeLP, which can exploit positive links and content-centric interactions to predict negative links. Our experimental results on real-world social networks demonstrate that the proposed NeLP framework can accurately predict negative links with positive links and content-centric interactions. Our detailed experiments also illustrate the relative importance of various factors to the effectiveness of the proposed framework

Long-term carriage, and transmission of methicillin-resistant Staphylococcus aureus after discharge from hospital

The purpose of this study was to determine whether patients who become carriers of methicillin-resistant Staphylococcus aureus (MRSA) during their stay in hospital, remain colonized after discharge. Thirty-six patients colonized with MRSA during one of three outbreaks at Utrecht University Hospital (1986-89) were screened 2 or 3 years after they had become carriers. Patients were also interviewed to determine factors contributing to persistent carriage, such as antibiotics, re-admissions to the hospital, presence of skin lesions and chronic diseases. At the same time transmission of MRSA to family members was determined. The epidemic MRSA strain was still found in three patients (8%). One was a cystic fibrosis patient who had had frequent re-admissions to the hospital and had received several course of antibiotic treatment. Both of the other patients had skin lesions: a fistula and a colostomy respectively. None of the 44 family members of the patients was colonized or infected with MRSA. We conclude that long-term MRSA carriage occurs with low frequency and is comparable to persistent carriage of methicillin-sensitive Staphylococcus aureus (MSSA). Transmission of MRSA to healthy individuals in an antibiotic-free environment is a rare event

Plasma ADMA associates with all-cause mortality in renal transplant recipients

Asymmetric dimethylarginine (ADMA) is a key endogenous inhibitor of endothelial NO synthase that affects endothelial function, blood pressure and vascular remodeling. Increased plasma levels of ADMA are associated with worse outcome from cardiovascular disease. Due to endothelial dysfunction before and after kidney transplantation, renal transplant recipients (RTR) are at high risk for the alleged deleterious effects of ADMA. We investigated the associations of ADMA levels with all-cause mortality and graft failure in RTR. Plasma ADMA levels were determined in 686 stable outpatient RTR (57 % male, 53 ± 13 years), with a functioning graft for ?1 year. Determinants of ADMA were evaluated with multivariate linear regression models. Associations between ADMA and mortality were assessed using multivariable Cox regression analyses. The strongest associations with plasma ADMA in the multivariable analyses were male gender, donor age, parathyroid hormone, NT-pro-BNP and use of calcium supplements. During a median follow-up of 3.1 [2.7-3.9] years, 79 (12 %) patients died and 45 (7 %) patients developed graft failure. ADMA was associated with increased all-cause mortality [HR 1.52 (95 % CI 1.26-1.83] per SD increase, P < 0.001], whereby associations remained upon adjustment for confounders. ADMA was associated with graft failure [HR 1.41 (1.08-1.83) per SD increase, P = 0.01]; however, upon addition of eGFR significance was lost. High levels of plasma ADMA are associated with increased mortality in RTR. Our findings connect disturbed NO metabolism with patient survival after kidney transplantation

Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group

Background: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models. Patients and methods: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m2 over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points. Results: Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3-18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3-12.3), with a 1-year survival rate of 31.6% (95% CI 17.7-46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination. Conclusions: No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administratio

European Organization for Research and Treatment of Cancer (EORTC) open label phase II study on glufosfamide administered as a 60-minute infusion every 3 weeks in recurrent glioblastoma multiforme

Background: Glufosfamide is a new alkylating agent in which the active metabolite of isophosphoramide mustard is covalently linked to β-d-glucose to target the glucose transporter system and increase intracellular uptake in tumor cells. We investigated this drug in a multicenter prospective phase II trial in recurrent glioblastoma multiforme (GBM). Patients and methods: Eligible patients had recurrent GBM following surgery, radiotherapy and no more than one prior line of chemotherapy. Patients were treated with glufosfamide 5000 mg/m2 administered as a 1-h intravenous infusion. Treatment success was defined as patients with either an objective response according to Macdonald's criteria or 6 months progression-free survival. Toxicity was assessed with the Common Toxicity Criteria (CTC) version 2.0. Results: Thirty-one eligible patients were included. Toxicity was modest, the main clinically relevant toxicities being leukopenia (CTC grade >3 in five patients) and hepatotoxicity (in three patients). No responses were observed; one patient (3%; 95% confidence interval 0 to 17%) was free from progression at 6 months. Pharmacokinetic analysis showed a 15% decrease in area under the curve and glufosfamide clearance in patients treated with enzyme-inducing antiepileptic drugs, but no effect of these drugs on maximum concentration and plasma half-life. Conclusion: Glufosfamide did not show significant clinical antitumor activity in patients with recurrent GB

Nitric oxide and long-term outcomes after kidney transplantation:Results of the TransplantLines cohort study

Impaired endogenous nitric oxide (NO) production may contribute to graft failure and premature mortality in kidney transplant recipients (KTR). We investigated potential associations of 24-h urinary NOx (NO3- + NO2-) excretion (uNOx) with long-term outcomes. uNOx was determined by HPLC and GC-MS in 698 KTR and in 132 kidney donors before and after donation. Additionally, we measured urinary nitroso species (RXNO) by gas-phase chemiluminescence. Median uNOx was lower in KTR compared to kidney donors (688 [393-1076] vs. 1301 [868-1863] before donation and 1312 [982-1853] μmol/24 h after donation, P < 0.001). During median follow-up of 5.4 [4.8-6.1] years, 150 KTR died (61 due to cardiovascular disease) and 83 experienced graft failure. uNOx was inversely associated with all-cause mortality (HR per doubling of uNOx: 0.84 [95% CI 0.75-0.93], P < 0.001) and cardiovascular mortality (HR 0.78 [95% CI 0.67-0.92], P = 0.002). The association of uNOx with graft failure was lost when adjusted for renal function (HR per doubling of uNOx: 0.89 [95% CI 0.76-1.05], P = 0.17). There were no significant associations of urinary RXNO with outcomes. Our study suggests that KTR have lower NO production than healthy subjects and that lower uNOx is associated with a higher risk of all-cause and cardiovascular mortality

European Organization for Research and Treatment of Cancer (EORTC) open label phase II study on glufosfamide administered as a 60-minute infusion every 3 weeks in recurrent glioblastoma multiforme

BACKGROUND: Glufosfamide is a new alkylating agent in which the active metabolite of isophosphoramide mustard is covalently linked to beta-D-glucose to target the glucose transporter system and increase intracellular uptake in tumor cells. We investigated this drug in a multicenter prospective phase II trial in recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Eligible patients had recurrent GBM following surgery, radiotherapy and no more than one prior line of chemotherapy. Patients were treated with glufosfamide 5000 mg/m(2) administered as a 1-h intravenous infusion. Treatment success was defined as patients with either an objective response according to Macdonald's criteria or 6 months progression-free survival. Toxicity was assessed with the Common Toxicity Criteria (CTC) version 2.0. RESULTS: Thirty-one eligible patients were included. Toxicity was modest, the main clinically relevant toxicities being leukopenia (CTC grade >3 in five patients) and hepatotoxicity (in three patients). No responses were observed; one patient (3%; 95% confidence interval 0 to 17%) was free from progression at 6 months. Pharmacokinetic analysis showed a 15% decrease in area under the curve and glufosfamide clearance in patients treated with enzyme-inducing antiepileptic drugs, but no effect of these drugs on maximum concentration and plasma half-life. CONCLUSION: Glufosfamide did not show significant clinical antitumor activity in patients with recurrent GBM

Serum Calcification Propensity and the Risk of Cardiovascular and All-Cause Mortality in the General Population:The PREVEND Study

Objective: Vascular calcification contributes to the cause of cardiovascular disease. The calciprotein particle maturation time (T50) in serum, a measure of calcification propensity, has been linked with adverse outcomes in patients with chronic kidney disease, but its role in the general population is unclear. We investigated whether serum T50 is associated with cardiovascular mortality in a large general population-based cohort. Approach and Results: The relationship between serum T50 and cardiovascular mortality was studied in 6231 participants of the PREVEND (Prevention of Renal and Vascular End-Stage Disease) cohort. All-cause mortality was the secondary outcome. Mean (±SD) age was 53±12 years, 50% were male, and mean serum T50 was 329±58 minutes. A shorter serum T50 is indicative of a higher calcification propensity. Serum T50 was inversely associated with circulating phosphate, age, estimated glomerular filtration rate, and alcohol consumption, whereas plasma magnesium was positively associated with serum T50 (P&lt;0.001, total multivariable model R2=0.281). During median (interquartile range) follow-up for 8.3 (7.8-8.9) years, 364 patients died (5.8%), of whom 95 (26.1%) died from a cardiovascular cause. In multivariable Cox proportional hazard models, each 60 minutes decrease in serum T50 was independently associated with a higher risk of cardiovascular mortality (fully adjusted hazard ratio [95% CI], 1.22 [1.04-1.36], P=0.021). This association was modified by diabetes mellitus; stratified analysis indicated a more pronounced association in individuals with diabetes mellitus. Conclusions: Serum T50 is independently associated with an increased risk of cardiovascular mortality in the general population and thus may be an early and potentially modifiable risk marker for cardiovascular mortality.</p

Automatic centerline extraction of coronary arteries in coronary computed tomographic angiography

Coronary computed tomographic angiography (CCTA) is a non-invasive imaging modality for the visualization of the heart and coronary arteries. To fully exploit the potential of the CCTA datasets and apply it in clinical practice, an automated coronary artery extraction approach is needed. The purpose of this paper is to present and validate a fully automatic centerline extraction algorithm for coronary arteries in CCTA images. The algorithm is based on an improved version of Frangi’s vesselness filter which removes unwanted step-edge responses at the boundaries of the cardiac chambers. Building upon this new vesselness filter, the coronary artery extraction pipeline extracts the centerlines of main branches as well as side-branches automatically. This algorithm was first evaluated with a standardized evaluation framework named Rotterdam Coronary Artery Algorithm Evaluation Framework used in the MICCAI Coronary Artery Tracking challenge 2008 (CAT08). It includes 128 reference centerlines which were manually delineated. The average overlap and accuracy measures of our method were 93.7% and 0.30 mm, respectively, which ranked at the 1st and 3rd place compared to five other automatic methods presented in the CAT08. Secondly, in 50 clinical datasets, a total of 100 reference centerlines were generated from lumen contours in the transversal planes which were manually corrected by an expert from the cardiology department. In this evaluation, the average overlap and accuracy were 96.1% and 0.33 mm, respectively. The entire processing time for one dataset is less than 2 min on a standard desktop computer. In conclusion, our newly developed automatic approach can extract coronary arteries in CCTA images with excellent performances in extraction ability and accuracy