Comparison of Gadoterate Meglumine and Gadobutrol in the MRI Diagnosis of Primary Brain Tumors: A Double-Blind Randomized Controlled Intraindividual Crossover Study (the REMIND Study)

ABSTRACT BACKGROUNDANDPURPOSE: Effective management of patients with brain tumors depends on accurate detection and characterization of lesions. This study aimed to demonstrate the noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors. MATERIALS AND METHODS: This multicenter, double-blind, randomized, controlled intraindividual, crossover, noninferiority study included279patients.Bothcontrastagents(dose=0.1mmol/kgofbodyweight)wereassessedwith2identicalMRIsatatimeintervalof 2–14 days. The primary end point was overall lesion visualization and characterization, scored independently by 3 off-site readers on a 4-point scale, ranging from “poor” to “excellent.” Secondary end points were qualitative assessments (lesion border delineation, internal morphology, degree of contrast enhancement, diagnostic confidence), quantitative measurements (signal intensity), and safety (adverse events). All qualitative assessments were also performed on-site. RESULTS: Forall3readers,imagesofmostpatients(>90%)werescoredgoodorexcellentforoveralllesionvisualizationandcharacterizationwitheithercontrastagent;andthenoninferiorityofgadoteratemeglumineversusgadobutrolwasstatisticallydemonstrated.No significant differences were observed between the 2 contrast agents regarding qualitative end points despite quantitative mean lesion percentageenhancementbeinghigherwithgadobutrol(P81%ofthe patientswithbothcontrastagents.Similarpercentagesofpatientswithadverseeventsrelatedtothecontrastagentswereobservedwith gadoterate meglumine (7.8%) and gadobutrol (7.3%), mainly injection site pain. CONCLUSIONS: Thenoninferiorityofgadoteratemeglumineversusgadobutrolforoverallvisualizationandcharacterizationofprimary brain tumors was demonstrated

Assessment of the Noise Reduction Potential of Advanced Subsonic Transport Concepts for NASA's Environmentally Responsible Aviation Project

Aircraft system noise is predicted for a portfolio of NASA advanced concepts with 2025 entry-into-service technology assumptions. The subsonic transport concepts include tube-and-wing configurations with engines mounted under the wing, over the wing nacelle integration, and a double deck fuselage with engines at a mid-fuselage location. Also included are hybrid wing body aircraft with engines upstream of the fuselage trailing edge. Both advanced direct drive engines and geared turbofan engines are modeled. Recent acoustic experimental information was utilized in the prediction for several key technologies. The 301-passenger class hybrid wing body with geared ultra high bypass engines is assessed at 40.3 EPNLdB cumulative below the Stage 4 certification level. Other hybrid wing body and unconventional tube-and-wing configurations reach levels of 33 EPNLdB or more below the certification level. Many factors contribute to the system level result; however, the hybrid wing body in the 301-passenger class, as compared to a tubeand- wing with conventional engine under wing installation, has 11.9 EPNLdB of noise reduction due to replacing reflection with acoustic shielding of engine noise sources. Therefore, the propulsion airframe aeroacoustic interaction effects clearly differentiate the unconventional configurations that approach levels close to or exceed the 42 EPNLdB goal

An enrichment method for temperature-sensitive and auxotrophic mutants of yeast

An enrichment procedure that exploits the difference in heat-sensitivity between exponentially growing and stationary phase cells has been developed for the isolation of yeast mutants. Enrichments of up to 12-fold for temperature-sensitive lethal mutants and of up to 15-fold for auxotrophs have been obtained with single cycles of selection. Still higher enrichments (to frequencies of greater than 90% and 80% for temperature-sensitive lethals and auxotrophs, respectively) have been obtained with multiple cycles of selection. The method requires no special parent strain, and seems adaptable to the selection of a wide variety of types of mutants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47545/1/438_2004_Article_BF00274022.pd

Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability

There are no biological treatments for fetal alcohol spectrum disorders (FASDs), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In preclinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children aged 2.5 to 4.9 years with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg choline or placebo daily for 9 months (10 active, 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82% to 87%, as evidenced by parent-completed log sheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This phase I pilot study demonstrates that choline supplementation at 500 mg/d for 9 months in children aged 2 to 5 years is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway

Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder

Background: Despite the high prevalence of fetal alcohol spectrum disorder (FASD), there are few interventions targeting its core neurocognitive and behavioral deficits. FASD is often conceptualized as static and permanent, but interventions that capitalize on brain plasticity and critical developmental windows are emerging. We present a long-term follow-up study evaluating the neurodevelopmental effects of choline supplementation in children with FASD 4 years after an initial efficacy trial. Methods: The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2-5-year-olds with FASD. Participants include 31 children (16 placebo; 15 choline) seen 4 years after trial completion. The mean age at follow-up was 8.6 years. Diagnoses were 12.9% fetal alcohol syndrome (FAS), 41.9% partial FAS, and 45.1% alcohol-related neurodevelopmental disorder. The follow-up included measures of intelligence, memory, executive functioning, and behavior. Results: Children who received choline had higher non-verbal intelligence, higher visual-spatial skill, higher working memory ability, better verbal memory, and fewer behavioral symptoms of attention deficit hyperactivity disorder than the placebo group. No differences were seen for verbal intelligence, visual memory, or other executive functions. Conclusions: These data support choline as a potential neurodevelopmental intervention for FASD and highlight the need for long-term follow-up to capture treatment effects on neurodevelopmental trajectories. Trial registration: ClinicalTrials.Gov #NCT01149538; Registered: June 23, 2010; first enrollment July 2, 2010

Large-amplitude driving of a superconducting artificial atom: Interferometry, cooling, and amplitude spectroscopy

Superconducting persistent-current qubits are quantum-coherent artificial atoms with multiple, tunable energy levels. In the presence of large-amplitude harmonic excitation, the qubit state can be driven through one or more of the constituent energy-level avoided crossings. The resulting Landau-Zener-Stueckelberg (LZS) transitions mediate a rich array of quantum-coherent phenomena. We review here three experimental works based on LZS transitions: Mach-Zehnder-type interferometry between repeated LZS transitions, microwave-induced cooling, and amplitude spectroscopy. These experiments exhibit a remarkable agreement with theory, and are extensible to other solid-state and atomic qubit modalities. We anticipate they will find application to qubit state-preparation and control methods for quantum information science and technology.Comment: 13 pages, 5 figure

Quantum Interference in Superconducting Wire Networks and Josephson Junction Arrays: Analytical Approach based on Multiple-Loop Aharonov-Bohm Feynman Path-Integrals

We investigate analytically and numerically the mean-field superconducting-normal phase boundaries of two-dimensional superconducting wire networks and Josephson junction arrays immersed in a transverse magnetic field. The geometries we consider include square, honeycomb, triangular, and kagome' lattices. Our approach is based on an analytical study of multiple-loop Aharonov-Bohm effects: the quantum interference between different electron closed paths where each one of them encloses a net magnetic flux. Specifically, we compute exactly the sums of magnetic phase factors, i.e., the lattice path integrals, on all closed lattice paths of different lengths. A very large number, e.g., up to $10^{81}$ for the square lattice, exact lattice path integrals are obtained. Analytic results of these lattice path integrals then enable us to obtain the resistive transition temperature as a continuous function of the field. In particular, we can analyze measurable effects on the superconducting transition temperature, $T_c(B)$, as a function of the magnetic filed $B$, originating from electron trajectories over loops of various lengths. In addition to systematically deriving previously observed features, and understanding the physical origin of the dips in $T_c(B)$ as a result of multiple-loop quantum interference effects, we also find novel results. In particular, we explicitly derive the self-similarity in the phase diagram of square networks. Our approach allows us to analyze the complex structure present in the phase boundaries from the viewpoint of quantum interference effects due to the electron motion on the underlying lattices.Comment: 18 PRB-type pages, plus 8 large figure

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

Genetic, abiotic and social influences on sex differentiation in cichlid fishes and the evolution of sequential hermaphroditism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73799/1/j.1467-2979.2005.00184.x.pd