Which Combinations Of New Venture Firms Resources Payoff? A Configurational Perspective

Baldauf, Artur; Schweiger, Simone A.; Wuethrich, Adrian

Combinations of dexmedetomidine and alfaxalone with butorphanol in cats: application of an innovative stepwise optimisation method to identify optimal clinical doses for intramuscular anaesthesia

OBJECTIVES The aim of this study was to optimise dexmedetomidine and alfaxalone dosing, for intramuscular administration with butorphanol, to perform minor surgeries in cats. METHODS Initially, cats were assigned to one of five groups, each composed of six animals and receiving, in addition to 0.3 mg/kg butorphanol intramuscularly, one of the following: (A) 0.005 mg/kg dexmedetomidine, 2 mg/kg alfaxalone; (B) 0.008 mg/kg dexmedetomidine, 1.5 mg/kg alfaxalone; (C) 0.012 mg/kg dexmedetomidine, 1 mg/kg alfaxalone; (D) 0.005 mg/kg dexmedetomidine, 1 mg/kg alfaxalone; and (E) 0.012 mg/kg dexmedetomidine, 2 mg/kg alfaxalone. Thereafter, a modified 'direct search' method, conducted in a stepwise manner, was used to optimise drug dosing. The quality of anaesthesia was evaluated on the basis of composite scores (one for anaesthesia and one for recovery), visual analogue scales and the propofol requirement to suppress spontaneous movements. The medians or means of these variables were used to rank the treatments; 'unsatisfactory' and 'promising' combinations were identified to calculate, through the equation first described by Berenbaum in 1990, new dexmedetomidine and alfaxalone doses to be tested in the next step. At each step, five combinations (one new plus the best previous four) were tested. RESULTS None of the tested combinations resulted in adverse effects. Four steps and 120 animals were necessary to identify the optimal drug combination (0.014 mg/kg dexmedetomidine, 2.5 mg/kg alfaxalone and 0.3 mg/kg butorphanol). CONCLUSIONS AND RELEVANCE The investigated drug mixture, at the doses found with the optimisation method, is suitable for cats undergoing minor clinical procedures.

Bayesian adaptive designs for drug combinations in early phase clinical trials

Treating patients with combined agents is a growing trend in cancer clinical trials. Evaluating the synergism of multiple drugs is often the primary motivation for such drug-combination studies. Focusing on the drug combination study in the early phase clinical trials, our research is composed of three parts: (1) We conduct a comprehensive comparison of four dose-finding designs in the two-dimensional toxicity probability space and propose using the Bayesian model averaging method to overcome the arbitrariness of the model specification and enhance the robustness of the design; (2) Motivated by a recent drug-combination trial at MD Anderson Cancer Center with a continuous-dose standard of care agent and a discrete-dose investigational agent, we propose a two-stage Bayesian adaptive dose-finding design based on an extended continual reassessment method; (3) By combining phase I and phase II clinical trials, we propose an extension of a single agent dose-finding design. We model the time-to-event toxicity and efficacy to direct dose finding in two-dimensional drug-combination studies. We conduct extensive simulation studies to examine the operating characteristics of the aforementioned designs and demonstrate the designs' good performances in various practical scenarios.^

Simulating improved combinations tillage-rotation under dryland conditions.

The adequate combination of reduced tillage and crop rotation could increase the viability of dry land agriculture in Mediterrenean zones. Crop simulation models can support to examine various tillage-rotation combinations and explore management scenarios. The decision support system for agrotechnology transfer (DSSAT) (Hoogenboom et al., 2010) provides a suite of crop models suitable for this task. The objective of this work was to simulate the effects of two tillage systems, conventional tillage (ConvT) and no tillage (NoT), and three crop rotations, continuous cereal (CC), fallow-cereal (FallowC) and legume-cereal (LegumeC), under dry conditions, on the cereal yield, soil organic carbon (SOC) and nitrogen (SON) in a 15-year experiment, comparing these simulations with field observations.

Simulating improved combinations tillage-rotation under dryland conditions.

Crop simulation models allow analyzing various tillage-rotation combinations and exploring management scenarios. This study was conducted to test the DSSAT (Decision Support System for Agrotechnology Transfer) modelling system in rainfed semiarid central Spain. The focus is on the combined effect of tillage system and winter cereal-based rotations (cereal/legume/fallow) on the crop yield and soil quality. The observed data come from a 16-year field experiment. The CERES and CROPGRO models, included in DSSAT v4.5, were used to simulate crop growth and yield, and DSSAT- CENTURY was used in the soil organic carbon (SOC) and soil nitrogen (SN) simulations. Genetic coefficients were calibrated using part of the observed data. Field observations showed that barley grain yield was lower for continuous cereal (BB) than for vetch (VB) and fallow (FB) rotations for both tillage systems. The CERES-Barley model also reflected this trend. The model predicted higher yield in the conventional tillage (CT) than in the no tillage (NT) probably due to the higher nitrogen availability in the CT, shown in the simulations. The SOC and SN in the top layer only, were higher in NT than in CT, and decreased with depth in both simulated and observed values. These results suggest that CT-VB and CT-FB were the best combinations for the dry land conditions studied. However, CT presented lower SN and SOC content than NT. This study shows how models can be a useful tool for assessing and predicting crop growth and yield, under different management systems and under specific edapho-climatic conditions. Additional key words: CENTURY model; CERES-Barley; crop simulation models; DSSAT; sequential simula- tion; soil organic carbon.

Combinations of closely situated cis-acting elements determine tissue-specific patterns and anterior extent of early Hoxc8 expression.

We have used a transgene mutation approach to study how expression domains of Hoxc8 are established during mouse embryogenesis. A cis-regulatory region located 3 kb upstream from the Hoxc8 translational start site directs the early phase of expression. Four elements, termed A, B, C, and D, were previously shown to direct expression to the neural tube. Here we report that a fifth element, E, located immediately downstream of D directs expression to mesoderm in combination with the other four elements. These elements are interdependent and partially redundant. Different combinations of elements determine expression in different posterior regions of the embryo. Neural tube expression is determined minimally by ABC, ABD, or ACD; somite expression by ACDE; and lateral plate mesoderm expression by DE. Neural tube and lateral plate mesoderm enhancers can be separated, but independent somite expression has not been achieved. Furthermore, mutations within these elements result in posteriorization of the reporter gene expression. Thus, the anterior extent of expression is determined by the combined action of these elements. We propose that the early phase of Hoxc8 expression is directed by two separate mechanisms: one that determines tissue specificity and another that determines anterior extent of expression.

Hybrid convex combinations for IIR system identification.

The low complexity of IIR adaptive filters (AFs) is specially appealing to realtime applications but some drawbacks have been preventing their widespread use so far. For gradient based IIR AFs, adverse operational conditions cause convergence problems in system identification scenarios: underdamped and clustered poles, undermodelling or non-white input signals lead to error surfaces where the adaptation nearly stops on large plateaus or get stuck at sub-optimal local minima that can not be identified as such a priori. Furthermore, the non-stationarity in the input regressor brought by the filter recursivity and the approximations made by the update rules of the stochastic gradient algorithms constrain the learning step size to small values, causing slow convergence. In this work, we propose IIR performance enhancement strategies based on hybrid combinations of AFs that achieve higher convergence rates than ordinary IIR AFs while keeping the stability.

Corporations; a study of the origin and development of great business combinations and of their relation to the authority of the state.

Mode of access: Internet.

A manual of Gothic mouldings : a practical treatise on their formations, gradual development, combinations, and varieties /

Mode of access: Internet.

Automotive manufacturing assessment system. Volume II: product schedules of engine/drivetrain combinations. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Life-cycle cost analysis for utility combinations handbook : departmental staff and program participants.

"December 1985."

Preparation of wood-plastic combinations using gamma radiation to induce polymerization : effects of gamma radiation on wood /

"ORO-600."

Preparation of wood-plastic combinations using gamma radiation to induce polymerization /

"ORO-628."

Preparation of wood-plastic combinations using gamma radiation to induce polymerization /

"ORO-612."

Biological effects of neutrons, gamma radiation, and neutron-gamma combinations : a selective bibliography of unclassified literature /

An annotated bibliography of 190 items is presented, covering AEC report literature and selected references from the open literature on biological effects of neutrons, gamma radiations, and combinations of both.