New therapies for recurrent glioblastomas

Glioblastomas are the most common and deadliest form of malignant primary brain tumor. Until recently, therapies for tumors that recur after standard treatment have been largely ineffective. Recent phase II studies with the humanized monoclonal antibody against vascular endothelial growth factor bevacizumab suggest that this agent is active in recurrent glioblastomas, producing response rates of 26-40% and prolonging 6-month progression-free survival to 36-50%. As a result of these studies, the US Food and Drug Administration recently granted accelerated approval for bevacizumab as a treatment for recurrent glioblastomas

TO USE A TREE OR A FOREST IN BEHAVIORAL INTENTION

Cloud computing is a new technology that has been applied to education and has e nabled the development of cloud computing classrooms; however, student behavioral intentions toward cloud computing remain unclear. Most researchers have evaluated, integrated, or compared few (1 to 3) theories to examine user behavioral intentions and few have addressed additional theories or models. In this study, we test, compare, and unify six well -known theories, namely, service quality (SQ), self - efficacy (SE), the motivational model (MM), technology acceptance model (TAM), theory of reason action (TRA)/theory of planned behavior (TPB), and innovation diffusion theory (IDT) in the context of cloud computing classrooms. This empirical study was conducted using an online survey. The data collected from the samples (n=478) were analyzed using structural equation modeling. We independently analyzed each of the six theories, formulating a united model. The analysis yielded three valuable findings. First, comparing the explained variance and degree of freedom (df) difference, yielded the following ranking in explained variance: MM=TAM\u3eIDT\u3eTPB\u3eSE=SQ (equal =; superior to\u3e). Second, comparing the explained variance yielded the following ranking in explained variance: MM\u3eTAM\u3eIDT\u3eTPB\u3eSE=SQ. Third, based on the united model of six theories, some factors significantly affect behavioral intention and others do not. The implications of this study are critical for both researchers and practitioners

First-in-Human Phase I Study to Evaluate the Brain-Penetrant PI3K/mTOR Inhibitor GDC-0084 in Patients with Progressive or Recurrent High-Grade Glioma.

PurposeGDC-0084 is an oral, brain-penetrant small-molecule inhibitor of PI3K and mTOR. A first-in-human, phase I study was conducted in patients with recurrent high-grade glioma.Patients and methodsGDC-0084 was administered orally, once daily, to evaluate safety, pharmacokinetics (PK), and activity. Fluorodeoxyglucose-PET (FDG-PET) was performed to measure metabolic responses.ResultsForty-seven heavily pretreated patients enrolled in eight cohorts (2-65 mg). Dose-limiting toxicities included 1 case of grade 2 bradycardia and grade 3 myocardial ischemia (15 mg), grade 3 stomatitis (45 mg), and 2 cases of grade 3 mucosal inflammation (65 mg); the MTD was 45 mg/day. GDC-0084 demonstrated linear and dose-proportional PK, with a half-life (∼19 hours) supportive of once-daily dosing. At 45 mg/day, steady-state concentrations exceeded preclinical target concentrations producing antitumor activity in xenograft models. FDG-PET in 7 of 27 patients (26%) showed metabolic partial response. At doses ≥45 mg/day, a trend toward decreased median standardized uptake value in normal brain was observed, suggesting central nervous system penetration of drug. In two resection specimens, GDC-0084 was detected at similar levels in tumor and brain tissue, with a brain tissue/tumor-to-plasma ratio of >1 and >0.5 for total and free drug, respectively. Best overall response was stable disease in 19 patients (40%) and progressive disease in 26 patients (55%); 2 patients (4%) were nonevaluable.ConclusionsGDC-0084 demonstrated classic PI3K/mTOR-inhibitor related toxicities. FDG-PET and concentration data from brain tumor tissue suggest that GDC-0084 crossed the blood-brain barrier

Contact resistance in carbon nanostructure via interconnects

We present an in-depth electrical characterization of contact resistance in carbon nanostructure via interconnects. Test structures designed and fabricated for via applications contain vertically aligned arrays of carbon nanofibers (CNFs) grown on a thin titanium film on silicon substrate and embedded in silicon dioxide. Current-voltage measurements are performed on single CNFs using atomic force microscope current-sensing technique. By analyzing the dependence of measured resistance on CNF diameter, we extract the CNF resistivity and the metal-CNF contact resistance

Theory of Underdoped Cuprates

We develop a slave-boson theory for the t-J model at finite doping which respects an SU(2) symmetry -- a symmetry previously known to be important at half filling. The mean field phase diagram is found to be consistent with the phases observed in the cuprate superconductors, which contains d-wave superconductor, spin gap, strange metal, and Fermi liquid phases. The spin gap phase is best understood as the staggered flux phase, which is nevertheless translationally invariant for physical quantities. The electron spectral function shows small Fermi pockets at low doping which continuously evolve into the large Fermi surface at high doping concentrations.Comment: 4 pages, latex(revtex,epsf), 3 figure

Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials

Radiographic endpoints including response and progression are important for the evaluation of new glioblastoma therapies. The current RANO criteria was developed to overcome many of the challenges identified with previous guidelines for response assessment, however, significant challenges and limitations remain. The current recommendations build on the strengths of the current RANO criteria, while addressing many of these limitations. Modifications to the current RANO criteria include suggestions for volumetric response evaluation, use contrast enhanced T1 subtraction maps to increase lesion conspicuity, removal of qualitative non-enhancing tumor assessment requirements, use of the post-radiation time point as the baseline for newly diagnosed glioblastoma response assessment, and “treatment-agnostic” response assessment rubrics for identifying pseudoprogression, pseudoresponse, and a confirmed durable response in newly diagnosed and recurrent glioblastoma trials. Electronic supplementary material The online version of this article (doi:10.1007/s13311-016-0507-6) contains supplementary material, which is available to authorized users

The Unusual Superconducting State of Underdoped Cuprates

There is increasing experimental evidence that the superconducting energy gap $\Delta_0$ in the underdoped cuprates is independent of doping concentration $x$ while the superfluid density is linear in $x$. We show that under these conditions, thermal excitation of the quasiparticles is very effective in destroying the superconducting state, so that $T_c$ is proportional to $x\Delta_0$ and part of the gap structure remains in the normal state. We then estimate $H_{c2}$ and predict it to be proportional to $x^2$. We also discuss to what extent the assumptions that go into the quasiparticle description can be derived in the U(1) and SU(2) formulations of the t-J model.Comment: 4 pages RevTe

Massless Dirac Fermions, Gauge Fields, and Underdoped Cuprates

We study 2+1 dimensional massless Dirac fermions and bosons coupled to a U(1) gauge field as a model for underdoped cuprates. We find that the uniform susceptibility and the specific heat coefficient are logarithmically enhanced (compared to linear-in-T behavior) due to the fluctuation of transverse gauge field which is the only massless mode at finite boson density. We analyze existing data, and find good agreement in the spin gap phase. Within our picture, the drop of the susceptibility below the superconducting T_c arises from the suppression of gauge fluctuations.Comment: 4 pages, REVTEX, 1 eps figur