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

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

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

Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation

<p>Abstract</p> <p>Background</p> <p>In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m²weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting.</p> <p>Methods</p> <p>40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m²to 100 mg/m². Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.</p> <p>Results</p> <p>Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine.</p> <p>Conclusion</p> <p>Low-dose fotemustine at 65–75 mg/m²(induction phase) followed by 75–85 mg/m²(maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.</p

A new schedule of fotemustine in temozolomide-pretreated patients with relapsing glioblastoma

In the present study we investigated the feasibility and effectiveness of a new biweekly schedule of fotemustine (FTM) in patients with recurrent glioblastoma, after at least one previous treatment. The primary endpoint was progression-free survival at 6 months; secondary objectives were clinical response, overall survival, disease-free survival, and toxicity. Forty patients (median age 52.8 years; median Karnofsky Performance Status at progression 90) underwent second-line chemotherapy with FTM. Selected patients were previously treated with a standard radiotherapy course with concomitant temozolomide (TMZ). After tumor relapse or progression proven by magnetic resonance imaging (MRI), all patients underwent chemotherapy with FTM, given intravenously at dose of 80 mg/m2 every 2 weeks for five consecutive administrations (induction phase), and then every 3 weeks at 100 mg/m2 as maintenance. A total of 329 infusions were administered; the median number of cycles administered was 8. All patients completed the induction phase, and 29 patients received at least one maintenance infusion. Response to treatment was assessed using MacDonald criteria. One complete response [2.5%, 95% confidence interval (CI): 0–10%], 9 partial responses (22.5%, 95% CI: 15–37%), and 16 stable diseases (40%, 95% CI: 32–51%) were observed. Median time to progression was 6.7 months (95% CI: 3.9–9.1 months). Progression-free survival at 6 months was 61%. Median survival from beginning of FTM chemotherapy was 11.1 months. The schedule was generally well tolerated; the main toxicities were hematologic (grade 3 thrombocytopenia in two cases). To the best of our knowledge, this is the first report specifically dealing with the use of a biweekly induction schedule of FTM. The study demonstrates that FTM has therapeutic efficacy as single-drug second-line chemotherapy with a favorable safety profile

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