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

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

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 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

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

Changes in Scottish suicide rates during the Second World War

BACKGROUND: It is believed that total reported suicide rates tend to decrease during wartime. However, analysis of suicide rates during recent conflicts suggests a more complex picture, with increases in some age groups and changes in method choice. As few age and gender specific analyses of more distant conflicts have been conducted, it is not clear if these findings reflect a change in the epidemiology of suicide in wartime. Therefore, we examined suicide rates in Scotland before, during and after the Second World War to see if similar features were present. METHODS: Data on deaths in Scotland recorded as suicide during the period 1931 – 1952, and population estimates for each of these years, were obtained from the General Register Office for Scotland. Using computer spreadsheets, suicide rates by gender, age and method were calculated. Forward stepwise logistic regression was used to assess the effect of gender, war and year on suicide rates using SAS V8.2. RESULTS: The all-age suicide rate among both men and women declined during the period studied. However, when this long-term decline is taken into account, the likelihood of suicide during the Second World War was higher than during both the pre-War and post-War periods. Suicide rates among men aged 15–24 years rose during the Second World War, peaking at 148 per million (41 deaths) during 1942 before declining to 39 per million (10 deaths) by 1945, while the rate among men aged 25–34 years reached 199 per million (43 deaths) during 1943 before falling to 66 per million (23 deaths) by 1946. This was accompanied by an increase in male suicides attributable to firearms and explosives during the War years which decreased following its conclusion. CONCLUSION: All age male and female suicide rates decreased in Scotland during World War II. However, once the general background decrease in suicide rates over the whole period is accounted for, the likelihood of suicide among the entire Scottish population during the Second World War was elevated. The overall decrease in suicide rates concealed large increases in younger male age groups during the War years, and an increase in male suicides recorded as due to the use of firearms. We conclude that the effects of war on younger people, reported in recent conflicts in Central Europe, were also seen in Scotland during the Second World War. The results support the findings of studies of recent conflicts which have found a heterogeneous picture with respect to age specific suicide rates during wartime

Author Correction: Circulating Haptoglobin and Metabolic Syndrome in Renal Transplant Recipients

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper

Circulating Haptoglobin and Metabolic Syndrome in Renal Transplant Recipients

Haptoglobin (Hp) is an acute phase protein that has recently been linked to components of the metabolic syndrome (MetS). We aimed to evaluate Hp as marker of MetS, and to assess its association with long-term outcome in renal transplant recipients (RTR). We measured plasma Hp in a prospective cohort of 699 stable RTR and 149 healthy controls. Median plasma Hp concentration in RTR was 1.4 [interquartile range (IQR), 1.0–1.8] g/L, which was higher compared to 1.1 [0.9–1.4] g/L in controls (P<0.001). Hp was independently associated with the MetS (β=0.10) (P=0.005). During follow-up of 5.4 [4.8–6.1] years, 150 (21%) recipients died, of whom 60 (9%) due to cardiovascular causes, and 83 (12%) RTR developed graft failure. High (≥2.0g/L) and low (≤0.9g/L) plasma Hp were associated with increased risk of mortality (HR’s 2.3 [1.3–4.1] and 1.9 [1.0–3.5], resp.), predominantly cardiovascular. The association of high Hp lost signifcance upon adjustment for infammation markers (HR 1.5 [0.8–2.7]), while low Hp was independently associated with mortality (HR 2.2 [1.2–4.0]). Hp was not associated with graft failure (P=0.49). In conclusion, plasma Hp is independently associated with MetS in RTR. Importantly, high and low Hp are associated with increased mortality risk, independent of MetS