Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study.

BACKGROUND: Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter. METHODS: Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1-6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1-6), followed by TMZ maintenance therapy (TMZ/RT→TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability. RESULTS: Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated. CONCLUSIONS: Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study

A psychophysiological investigation of the interplay between orienting and executive control during stimulus conflict: A heart rate variability study

Background It has been hypothesized that resting state cardiac vagal activity (CVA) - an indicator of parasympathetic nervous system activity - is a specific psychophysiological marker of executive control function. Here, we propose an alternative hypothesis - that CVA is associated with early stage attention orientation, promoting the flexible uptake of new information, on which the later operation of such executive control functions depends. We therefore predicted that CVA would predict the interaction between orienting and executive control. This was tested using the revised version of the Attention Network Test (ANT-R) that was developed to distinguish between orienting and executive attention during a stimulus conflict task. Methods Healthy adults (N = 48) performed the ANT-R and their resting CVA was measured over a 5 min period using ECG recordings. Results Multiple regression analyses indicated that, when other factors were controlled for, CVA was more strongly associated with the interaction between the orienting and executive control terms than with either factor individually. Conclusion Higher levels of CVA are specifically implicated in the modulation of executive control by intrinsic orientation operating at early stages of conflict detection. These initial findings of higher CVA on orienting attention in conflict detection need to be replicated in larger samples

Neutral pion and η\eta meson production in proton-proton collisions at s=0.9\sqrt{s}=0.9 TeV and s=7\sqrt{s}=7 TeV

The first measurements of the invariant differential cross sections of inclusive $\pi^0$ and $\eta$ meson production at mid-rapidity in proton-proton collisions at $\sqrt{s}=0.9$ TeV and $\sqrt{s}=7$ TeV are reported. The $\pi^0$ measurement covers the ranges $0.4<p_T<7$ GeV/$c$ and $0.3<p_T<25$ GeV/$c$ for these two energies, respectively. The production of $\eta$ mesons was measured at $\sqrt{s}=7$ TeV in the range $0.4<p_T<15$ GeV/$c$. Next-to-Leading Order perturbative QCD calculations, which are consistent with the $\pi^0$ spectrum at $\sqrt{s}=0.9$ TeV, overestimate those of $\pi^0$ and $\eta$ mesons at $\sqrt{s}=7$ TeV, but agree with the measured $\eta/\pi^0$ ratio at $\sqrt{s}=7$ TeV.Comment: 17 pages, 5 captioned figures, 2 tables, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/310

Strengthening conceptual foundations: Analysing frameworks for ecosystem services and poverty alleviation research

AbstractA research agenda is currently developing around the linkages between ecosystem services and poverty alleviation. It is therefore timely to consider which conceptual frameworks can best support research at this nexus. Our review of frameworks synthesises existing research on poverty/environment linkages that should not be overlooked with the adoption of the topical language of ecosystem services. A total of nine conceptual frameworks were selected on the basis of relevance. These were reviewed and compared to assess their ability to illuminate the provision of ecosystem services, the condition, determinants and dynamics of poverty, and political economy factors that mediate the relationship between poverty and ecosystem services. The paper synthesises the key contributions of each of these frameworks, and the gaps they expose in one another, drawing out lessons that can inform emerging research. Research on poverty alleviation must recognize social differentiation, and be able to distinguish between constraints of access and constraints of aggregate availability of ecosystem services. Different frameworks also highlight important differences between categories of services, their pathways of production, and their contribution to poverty alleviation. Furthermore, we highlight that it is important to acknowledge the limits of ecosystem services for poverty alleviation, given evidence that ecosystem services tend to be more associated with poverty prevention than reduction. We conclude by reflecting on the relative merits of dynamic Social–Ecological Systems frameworks versus more static checklists, and suggest that research on ecosystem services and poverty alleviation would be well served by a new framework distilling insights from the frameworks we review

Associations of anticoagulant use with outcome in newly diagnosed glioblastoma.

To test the hypothesis that despite bleeding risk, anticoagulants improve the outcome in glioblastoma because of reduced incidence of venous thromboembolic events and modulation of angiogenesis, infiltration and invasion. We assessed survival associations of anticoagulant use from baseline up to the start of temozolomide chemoradiotherapy (TMZ/RT) (period I) and from there to the start of maintenance TMZ chemotherapy (period II) by pooling data of three randomised clinical trials in newly diagnosed glioblastoma including 1273 patients. Progression-free survival (PFS) and overall survival (OS) were compared between patients with anticoagulant use versus no use; therapeutic versus prophylactic versus no use; different durations of anticoagulant use versus no use; anticoagulant use versus use of anti-platelet agents versus neither anticoagulant nor anti-platelet agent use. Cox regression models were stratified by trial and adjusted for baseline prognostic factors. Anticoagulant use was documented in 75 patients (5.9%) in period I and in 104 patients (10.2%) in period II. Anticoagulant use during period II, but not period I, was associated with inferior OS than no use on multivariate analysis (p = 0.001, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.18-1.95). No decrease in OS became apparent when only patients with prophylactic anticoagulant use were considered. No survival association was established for anti-platelet agent use. Anticoagulant use was not associated with improved OS. Anticoagulants may not exert relevant anti-tumour properties in glioblastoma

Learning from Difference: The Potentially Transforming Experience of Community-University Collaboration

The University of Michigan's Detroit Community Outreach Partnership Center generates faculty-student teams who work on community development projects with Detroit's community organizations. Projects are designed to enrich students' experiential learning in community settings and to help build communities' organizational capacity. This relationship has exposed a culture clash between universities and community organizations in at least three major areas: the style of work, social justice understanding, and power relations. Further, although the COPC is committed to a community-driven planning model, the nature of the community-university relationship tends to push the work toward a consultant-driven model. Improving community-university collaboration will require restructuring of university pedagogy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68355/2/10.1177_0739456X9801700408.pd