Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer

OBJECTIVE: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). METHODS: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II-IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. RESULTS: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805-1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863-2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713-0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. CONCLUSION: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov: NCT00866697. ispartof: Gynecol Oncol vol:155 issue:2 pages:186-191 ispartof: location:United States status: publishe

Adsorption of Cd, Cu, Ni and Zn in tropical soils under competitive and non-competitive systems

The adsorption of heavy metals in soils affects their behavior in the environment and their bioavailability to plants. The knowledge of the adsorption mechanisms in competitive systems allows a more realistic evaluation of the metals' behavior in the soil than the single metal adsorption. The objectives of this study were (i) to evaluate Cd, Cu, Ni, and Zn adsorption in 14 surface samples (0-0.2 m) of representative soils of the Brazilian humid-tropical region, in competitive and non-competitive systems, and (ii) to establish metal affinity sequences for each soil, based in the maximum adsorption capacity (MAC) estimated by the Langmuir model. The Rhodic Eutrudox, the Kandiudalf Eutrudox, the Arenic Hapludalf, the Arenic Hapludult and the Typic Argiudoll had the highest metals' adsorption capacity, whereas the Typic Quartzipsamment and the sandy-textured Arenic Hapludult had the lowest values. In general, the MAC values for metals were lower in the competitive than in the non-competitive system. In the non-competitive system, the most common affinity sequence was Cu > Zn > Ni > Cd, whereas the most common sequence was Cu > Cd > Zn > Ni in the competitive system. In general, the Langmuir model fitted well the adsorption data of metals on the studied soils.A adsorção de metais pesados em solos afeta seu comportamento e biodisponibilidade às plantas. O conhecimento dos mecanismos de adsorção em sistemas competitivos permite uma avaliação mais realista do comportamento dos metais no solo do que estudos com adsorção de cada metal, isoladamente. Os objetivos desse trabalho foram: (i) avaliar a adsorção de Cd, Cu, Ni e Zn em amostras superficiais (0-0,2 m) de 14 solos representativos da região tropical úmida, em sistema competitivo e não-competitivo, e (ii) estabelecer sequências de afinidade metálica para cada solo, com base nos valores de capacidade máxima de adsorção (CMA) dos metais estimados por meio do modelo de Langmuir. O Rhodic Eutrudox, o Kandiudalfic Eutrudox, o Arenic Hapludalf (Alf2), o Arenic Hapludult (Ult2) e o Typic Argiudoll apresentaram elevadas capacidades de adsorção dos metais, ocorrendo o inverso para o Typic Quartzipsamment e para o Arenic Hapludult textura arenosa. No geral, a CMA dos metais aos solos foi menor no sistema competitivo. A sequência de afinidade mais comumente encontrada no sistema não-competitivo foi Cu > Zn > Ni > Cd. No sistema competitivo, a sequência foi Cu > Cd > Zn > Ni. Em geral, o modelo de Langmuir simulou de maneira satisfatória a adsorção dos metais nas amostras de solo

Development of the motion perception toolbox

The goal of this paper is to give an overview and some practical examples of the Motion Perception Toolbox developed by TNO (Netherlands Organization for Applied Research) as a freeware Matlab Simulink library. The MPT library provides a documented set of building blocks that model human perception and are easily coupled to existing simulation models. For example, when implemented behind an existing aircraft model the MPT library could be used to predict pilot motion perception, or the occurrence of motion illusions. Although the implementation in the brain is certainly not a set of transfer functions or differential equations, some of the global characteristics of human behaviour can be modelled as input-output relations by mathematical transfer functions that were identified in a long tradition of human perception research. We have tried to put together the most fundamental of these relations based on consensus in the literature and own insights. Examples of building blocks in the MPT library, explained and applied in this paper, are: 1) calculation of inertial head motion from vehicle and pilot motion to be used as sensory input, 2) transfer functions of the visual and vestibular system, as well as their interactions in velocity perception, and 3) a 3D animation tool to intuitively visualize perception output. The Motion Perception Toolbox offers engineers a starting point from which they can analyze the results of simulations (e.g. aircraft, cars, etc.) from a human perception and control point-of-view. The vast amounts of (ambiguous) experimental data, different physiological models, and expert opinions, seem to make it impossible to develop the universal Motion Perception Toolbox. With this in mind, we invite the AIAA community to actively participate in its development. To that end, the MPT is open source and can be downloaded from www.desdemona.eu. The simulation examples in this paper are incorporated as demos in the MPT and can also be downloaded

Event-related potentials in a visual discrimination task: negative waves related to detection and attention

Event‐related potential effects of deviant stimuli were investigated in a visual discrimination task. The stimuli (two angles within a frame) were either frequent (Standard) or one of two types of infrequent deviant (Deviant 1 or Deviant 2) stimuli. In comparison to the Standard stimuli, for Deviant 1 the two angles differed in their orientation, whereas for Deviant 2 the angles were identical but the frame was thicker. In Condition 1 the subjects counted the number of Deviant 1 stimuli. Of the 13 subjects, 12 did not detect the fact that some of the frames were thicker in this condition (i.e., for the Deviant 2 stimuli in Condition 2). The task in Condition 2 was the same (i.e., the target was Deviant 1), but the subjects were instructed about the thicker frame of Deviant 2 stimuli. In Condition 3, Deviant 2 stimuli became the targets. In comparison to the Standard, Deviant 1 elicited two posterior negative waves in the 120–180 and 240–300 ms latency ranges respectively. In addition, when Deviant 1 was the target stimulus (Conditions 1 and 2), this stimulus elicited the N2 and the P300 as well. In contrast, the irrelevant Deviant 2 elicited no such waves. In the target position (Condition 3), Deviant 2 elicited the second posterior negativity, the N2, and the late positivity. The earlier negativity is considered to be a correlate of processes connected to the automatic detection of the deviant features, whereas the later negativity is considered to be related to attentive processes, i.e., this wave is considered to be a member of the family of processing negativities