Optimal designs for active controlled dose finding trials with efficacy-toxicity outcomes

Nonlinear regression models addressing both efficacy and toxicity outcomes are increasingly used in dose-finding trials, such as in pharmaceutical drug development. However, research on related experimental design problems for corresponding active controlled trials is still scarce. In this paper we derive optimal designs to estimate efficacy and toxicity in an active controlled clinical dose finding trial when the bivariate continuous outcomes are modeled either by polynomials up to degree 2, the Michaelis- Menten model, the Emax model, or a combination thereof. We determine upper bounds on the number of different doses levels required for the optimal design and provide conditions under which the boundary points of the design space are included in the optimal design. We also provide an analytical description of the minimally supported $D$-optimal designs and show that they do not depend on the correlation between the bivariate outcomes. We illustrate the proposed methods with numerical examples and demonstrate the advantages of the $D$-optimal design for a trial, which has recently been considered in the literature.Comment: Keywords and Phrases: Active controlled trials, dose finding, optimal design, admissible design, Emax model, Equivalence theorem, Particle swarm optimization, Tchebycheff syste

Effects of Mineral Nutrition on Components of Reproduction in Clarkia ungucilata

An experiment was conducted to determine the effects of nutritional level and flower location on factors related to flower, pollen, and ovule production, and to determine what developmental patterns would be modified to mediate any observed changes. Plants subjected to high nutrient levels developed larger leaves, more branches, more flowers on both the main stem and the branches, and opened their first flowers 6 days sooner than plants at lower levels of nutrients. Total flower number increased from 72.2 to 626.8 per plant, with most of the increase produced on the primary branches. The number of pollen grains in the entire androecium averaged 14,685, but significantly increased with higher nutrient levels and decreased with the stage of plant maturity (nodal position on the plant). The number of ovules also increased with nutrient level and decreased with maturity stage. Average ovule number decreased from about 129 in flowers at nodes produced early in the growth cycle to about 100 in flowers produced at later nodes. Despite highly significant plasticity in numbers of both pollen and ovules, the Pollen/Ovule Ratio (average 132.7) did not vary significantly with either nutrient level or plant maturity stage. Path analysis, which decomposes correlation coefficients into direct and indirect effects of factors influencing development, indicated that nutrient level had a very strong direct effect on the number of primary branches and on the number of primary-branch flowers, as well as very strong indirect effects on the latter. The primary-branch flowers directly determined over 67% of the total flower number, and indirectly determined about 24% jointly with secondary-branch flowers, and over 3% jointly with main-stem flowers. The direct effects of secondary-branch flowers and mainstem flowers were 3.8% and 0.3%, respectively. The relationship among components of yield is slightly additive. Direct determination of yield was 74.6% by the number of flowers per plant, 0.6% by the number of ovules per flower, 3.8% by the number of seeds per ovule, and 1.1 % by the weight per seed. The proportion of yield jointly determined by flower number and the developed seeds per ovule was 15.3%. It was concluded that allocation of resources increases to both male and female functions under conditions of high nutrient levels, and pollen/ovule ratios are consistent within a plant despite significant plasticity in numbers of pollen grains and ovules

Early On-Orbit Performance of the Visible Infrared Imaging Radiometer Suite Onboard the Suomi National Polar-Orbiting Partnership (S-NPP) Satellite

The Visible Infrared Imaging Radiometer Suite (VIIRS) is one of the key environmental remote-sensing instruments onboard the Suomi National Polar-Orbiting Partnership spacecraft, which was successfully launched on October 28, 2011 from the Vandenberg Air Force Base, California. Following a series of spacecraft and sensor activation operations, the VIIRS nadir door was opened on November 21, 2011. The first VIIRS image acquired signifies a new generation of operational moderate resolution-imaging capabilities following the legacy of the advanced very high-resolution radiometer series on NOAA satellites and Terra and Aqua Moderate-Resolution Imaging Spectroradiometer for NASA's Earth Observing system. VIIRS provides significant enhancements to the operational environmental monitoring and numerical weather forecasting, with 22 imaging and radiometric bands covering wavelengths from 0.41 to 12.5 microns, providing the sensor data records for 23 environmental data records including aerosol, cloud properties, fire, albedo, snow and ice, vegetation, sea surface temperature, ocean color, and nigh-time visible-light-related applications. Preliminary results from the on-orbit verification in the postlaunch check-out and intensive calibration and validation have shown that VIIRS is performing well and producing high-quality images. This paper provides an overview of the onorbit performance of VIIRS, the calibration/validation (cal/val) activities and methodologies used. It presents an assessment of the sensor initial on-orbit calibration and performance based on the efforts from the VIIRS-SDR team. Known anomalies, issues, and future calibration efforts, including the long-term monitoring, and intercalibration are also discussed

Неоміфологія постсучасної особистості

У статті аналізуються тенденції деміфологізації та деконструкції особистісного буття в умовах сучасного технологічного суспільства. Результатом цих процесів стає підміна глибинності та ієрархічності особистісного само-визначення імітацією та симуляцією у різноманітних формах: імідж, маска, аватар.В статье анализируются тенденции деконструкции и демифологизации личностного бытия в условиях современного технологического общества. Результатом этих процессов стала подмена глубинности и иерархичности личностного самоопределения имитацией и симуляцией в разнообразных формах: имидж, маска, аватар.The trends of demythologization and reconstruction of personality existence in modern technological society circumstances are analyzed in the article. As a result of such processes, an imitation and simulation in their different forms, such as: image, mask, avatar — substitute the depth and hierarchy of personal self-determination

Emission from quantum-dot high-β microcavities : transition from spontaneous emission to lasing and the effects of superradiant emitter coupling

The research is funded in part by the European Research Council under the Seventh Framework ERC Grant Agreement No. 615613 of the European Union, the German Research Foundation via the projects RE2974/5-1, Ka2318 7-1 and JA 619/10-3, and the U.S. Department of Energy under Contract No. DE-AC04-94AL85000. CG and FJ gratefully acknowledge financial support from the German Science Foundation (DFG). FJ further acknowledges support from the German Federal Ministry of Education and Research (BMBF).Measured and calculated results are presented for the emission properties of a new class of emitters operating in the cavity quantum electrodynamics regime. The structures are based on high-finesse GaAs/AlAs micropillar cavities, each with an active medium consisting of a layer of InGaAs quantum dots and the distinguishing feature of having a substantial fraction of spontaneous emission channeled into one cavity mode (high β-factor). This paper demonstrates that the usual criterion for lasing with a conventional (low β-factor) cavity, that is, a sharp non-linearity in the input-output curve accompanied by noticeable linewidth narrowing, has to be reinforced by the equal-time second-order photon autocorrelation function to confirm lasing. The paper also shows that the equal-time second-order photon autocorrelation function is useful for recognizing superradiance, a manifestation of the correlations possible in high-β microcavities operating with quantum dots. In terms of consolidating the collected data and identifying the physics underlying laser action, both theory and experiment suggest a sole dependence on intracavity photon number. Evidence for this assertion comes from all our measured and calculated data on emission coherence and fluctuation, for devices ranging from light emitting diodes (LEDs) and cavity-enhanced LEDs to lasers, lying on the same two curves: one for linewidth narrowing versus intracavity photon number and the other for g(2)(0) versus intracavity photon number.Publisher PDFPeer reviewe

Crystal Facet Effect in Plasmonic Catalysis

In the realm of plasmonic catalytic systems, much attention has been devoted to the plasmon-derived mechanisms, yet the influence of nanoparticles' crystal facets in this type of processes has been sparsely investigated. In this work, we study the plasmon-assisted electrocatalytic CO2 reduction reaction using three different shapes of plasmonic Au nanoparticles - nanocube (NC), rhombic dodecahedron (RD) and octahedron (OC) - with three different exposed facets: {100}, {110} and {111}, respectively. These particles were synthesized with similar sizes and LSPR wavelengths to reveal the role of the facet more than other contributions to the plasmon-assisted reaction. Upon plasmon excitation, Au OCs exhibited nearly a doubling in the Faradaic efficiency of CO (FE(CO)) and a remarkable threefold enhancement in the partial current density of CO (j(CO)) compared to the non-illuminated response, NCs also demonstrated an improved performance under illumination. In contrast, Au RDs showed nearly the same performance in dark or light conditions. Temperature-dependent experiments ruled out heat as the main factor in the enhanced response of Au OCs and NCs. Large-scale atomistic simulations of the nanoparticles' electronic structure and electromagnetic modeling revealed higher hot carrier abundance and electric field enhancement on Au OCs and NCs compared to RDs. Abundant hot carriers on edges facilitate molecular activation, leading to enhanced selectivity and activity. Thus, OCs with the highest edge/facet ratio exhibited the strongest enhancement in FE(CO) and j(CO) upon illumination. This observation is further supported by plasmon-assisted H2 evolution reaction experiments. Our findings highlight the dominance of low coordinated sites over facets in plasmonic catalytic processes, providing valuable insights for designing more efficient catalysts for solar fuels production

Properties of tungsten mine waste geopolymeric binder

Tungsten mine waste mud (TMWM) geopolymeric binder is a new cementitious material with a very high early age strength. It is obtained from dehydroxylated mine waste powder mix with minor quantities of calcium hydroxide and activated with NaOH and water-glass solutions. Tests on properties of TMWM binders such as workability, setting time, unrestrained shrinkage, water absorption and static modulus of elasticity were carried out and the results are reported in this paper. This is followed by comparisons with literature related data and a discussion about it. The results showed that current devices use to assess OPC fresh properties are not recommended to evaluate TMWM binders. It has also been found that traditional procedures used to evaluate unrestrained shrinkage may be responsible for misleading results when using those new binders. Water absorption data shows that TMWM has a very compacted structure. Results concerning the static modulus of elasticity are similar to the ones obtained by other authors. However the hypothesis related to modulus of elasticity decrease due to the use of high Al/Si alkali activated mixtures was not confirmed