Decision-theoretic designs for phase II clinical trials allowing for competing studies

This article describes an approach to optimal design of phase II clinical trials using Bayesian decision theory. The method proposed extends that suggested by Stallard (1998, Biometrics54, 279–294) in which designs were obtained to maximize a gain function including the cost of drug development and the benefit from a successful therapy. Here, the approach is extended by the consideration of other potential therapies, the development of which is competing for the same limited resources. The resulting optimal designs are shown to have frequentist properties much more similar to those traditionally used in phase II trials.

An adaptive group sequential design for phase II/III clinical trials that select a single treatment from several

There is increasing interest in combining Phases II and III of clinical development into a single trial in which one of a small number of competing experimental treatments is ultimately selected and where a valid comparison is made between this treatment and the control treatment. Such a trial usually proceeds in stages, with the least promising experimental treatments dropped as soon as possible. In this paper we present a highly flexible design that uses adaptive group sequential methodology to monitor an order statistic. By using this approach, it is possible to design a trial which can have any number of stages, begins with any number of experimental treatments, and permits any number of these to continue at any stage. The test statistic used is based upon efficient scores, so the method can be easily applied to binary, ordinal, failure time, or normally distributed outcomes. The method is illustrated with an example, and simulations are conducted to investigate its type I error rate and power under a range of scenarios.

Bayesian design and conduct of phase II single-arm clinical trials with binary outcomes: a tutorial

The aim of phase II single-arm clinical trials of a new drug is to determine whether it has sufficient promising activity to warrant its further development. For the last several years Bayesian statistical methods have been proposed and used. Bayesian approaches are ideal for earlier phase trials as they take into account information that accrues during a trial. Predictive probabilities are then updated and so become more accurate as the trial progresses. Suitable priors can act as pseudo samples, which make small sample clinical trials more informative. Thus patients have better chances to receive better treatments. The goal of this paper is to provide a tutorial for statisticians who use Bayesian methods for the first time or investigators who have some statistical background. In addition, real data from three clinical trials are presented as examples to illustrate how to conduct a Bayesian approach for phase II single-arm clinical trials with binary outcomes.

A carbene insertion approach to functionalised poly(ethylene oxide)-based gels

Carbenes photogenerated from the novel bisdiazirine, 1, 3-bis(3-(trifluoromethyl)diazirin-3-yl) benzene 1, have been applied successfully to cross-linking of mono-methyl poly(ethylene oxide) (MePEO5000) in the presence of dichloromethane, leading to the simultaneous incorporation of alkylhalide functionalities. The PEO-based gels swell in a wide range of solvents with polarity index values varying from 3.1 to 9.0. Reaction of the alkylhalide functionalities present in the gels with 4-phenylazophenol provided loading capacities of up to 0.20 mmol g(-1) and demonstrated the potential of these materials for gel-phase synthesis applications. (C) 2008 Elsevier Ltd. All rights reserved.

Orientational ordering in the nematic phase of a polyethylene glycol-peptide conjugate in aqueous solution

The orientational ordering of the nematic phase of a polyethylene glycol (PEG)-peptide block copolymer in aqueous solution is probed by small-angle neutron scattering (SANS), with the sample subjected to steady shear in a Couette cell. The PEG-peptide conjugate forms fibrils that behave as semiflexible rodlike chains. The orientational order parameters (P) over bar (2) and (P) over bar (4) are obtained by modeling the data using a series expansion approach to the form factor of uniform cylinders. The method used is independent of assumptions on the form of the singlet orientational distribution function. Good agreement with the anisotropic two-dimensional SANS patterns is obtained. The results show shear alignment starting at very low shear rates, and the orientational order parameters reach a plateau at higher shear rates with a pseudologarithmic dependence on shear rate. The most probable distribution functions correspond to fibrils parallel to the flow direction under shear, but a sample at rest shows a bimodal distribution with some of the rodlike peptide fibrils oriented perpendicular to the flow direction.

Oxidation of biogenic and water-soluble compounds in aqueous and organic aerosol droplets by ozone: a kinetic and product analysis approach using laser Raman tweezers

The results of an experimental study into the oxidative degradation of proxies for atmospheric aerosol are presented. We demonstrate that the laser Raman tweezers method can be used successfully to obtain uptake coeffcients for gaseous oxidants on individual aqueous and organic droplets, whilst the size and composition of the droplets is simultaneously followed. A laser tweezers system was used to trap individual droplets containing an unsaturated organic compound in either an aqueous or organic ( alkane) solvent. The droplet was exposed to gas- phase ozone and the reaction kinetics and products followed using Raman spectroscopy. The reactions of three different organic compounds with ozone were studied: fumarate anions, benzoate anions and alpha pinene. The fumarate and benzoate anions in aqueous solution were used to represent components of humic- like substances, HULIS; a alpha- pinene in an alkane solvent was studied as a proxy for biogenic aerosol. The kinetic analysis shows that for these systems the diffusive transport and mass accommodation of ozone is relatively fast, and that liquid- phase di. ffusion and reaction are the rate determining steps. Uptake coe. ffcients, g, were found to be ( 1.1 +/- 0.7) x 10(-5), ( 1.5 +/- 0.7) x 10 (-5) and ( 3.0 - 7.5) x 10 (-3) for the reactions of ozone with the fumarate, benzoate and a- pinene containing droplets, respectively. Liquid- phase bimolecular rate coe. cients for reactions of dissolved ozone molecules with fumarate, benzoate and a- pinene were also obtained: k(fumarate) = ( 2.7 +/- 2) x 10 (5), k(benzoate) = ( 3.5 +/- 3) x 10 (5) and k(alpha-pinene) = ( 1-3) x 10(7) dm(3) mol (-1) s (- 1). The droplet size was found to remain stable over the course of the oxidation process for the HULIS- proxies and for the oxidation of a- pinene in pentadecane. The study of the alpha- pinene/ ozone system is the first using organic seed particles to show that the hygroscopicity of the particle does not increase dramatically over the course of the oxidation. No products were detected by Raman spectroscopy for the reaction of benzoate ions with ozone. One product peak, consistent with aqueous carbonate anions, was observed when following the oxidation of fumarate ions by ozone. Product peaks observed in the reaction of ozone with alpha- pinene suggest the formation of new species containing carbonyl groups.

Pervasive technologies for workplace management

Purpose – Facilities managers have less visibility of how buildings are being used due to flexible working and unpredictable workers. The purpose of this paper is to examine the current issues in workspace management and an automatic solution through radio frequency identification (RFID) that could provide real time information on the volume and capacity of buildings. Design/methodology/approach – The study described in this paper is based on a case study at a facilities management (FM) department. The department is examining a ubiquitous technology in the form of innovative RFID for security and workspace management. Interviews and observations are conducted within the facilities department for the initial phase of the implementation of RFID technology. Findings – Research suggests that work methods are evolving and becoming more flexible. With this in mind, facilities managers face new challenges to create a suitable environment for an unpredictable workforce. RFID is one solution that could provide facilities managers with an automatic way of examining space in real time and over a wider area than currently possible. RFID alone for space management is financially expensive but by making the application multiple for other areas makes more business sense. Practical implications – This paper will provide practicing FM and academics with the knowledge gained from the application of RFID in this organisation. While the concept of flexible working seems attractive, there is an emerging need to provide various forms of spaces that enable employees' satisfaction and enhance the productivity of the organisation. Originality/value – The paper introduces new thinking on the subject of “workspace management”. It highlights the current difficulties in workspace management and how an RFID solution will benefit workspace methods.

A new algorithm for OFDM joint data detection and phase noise cancellation

This paper proposes a new iterative algorithm for OFDM joint data detection and phase noise (PHN) cancellation based on minimum mean square prediction error. We particularly highlight the problem of "overfitting" such that the iterative approach may converge to a trivial solution. Although it is essential for this joint approach, the overfitting problem was relatively less studied in existing algorithms. In this paper, specifically, we apply a hard decision procedure at every iterative step to overcome the overfitting. Moreover, compared with existing algorithms, a more accurate Pade approximation is used to represent the phase noise, and finally a more robust and compact fast process based on Givens rotation is proposed to reduce the complexity to a practical level. Numerical simulations are also given to verify the proposed algorithm.

Investigating the feasibility of a swarm-array computing approach

The work reported in this paper proposes a novel synergy between parallel computing and swarm robotics to offer a new computing paradigm, 'swarm-array computing' that can harness and apply autonomic computing for parallel computing systems. One approach among three proposed approaches in swarm-array computing based on landscapes of intelligent cores, in which the cores of a parallel computing system are abstracted to swarm agents, is investigated. A task is executed and transferred seamlessly between cores in the proposed approach thereby achieving self-ware properties that characterize autonomic computing. FPGAs are considered as an experimental platform taking into account its application in space robotics. The feasibility of the proposed approach is validated on the SeSAm multi-agent simulator.

An autonomic approach in swarm-array computing

Can autonomic computing concepts be applied to traditional multi-core systems found in high performance computing environments? In this paper, we propose a novel synergy between parallel computing and swarm robotics to offer a new computing paradigm, `Swarm-Array Computing' that can harness and apply autonomic computing for parallel computing systems. One approach among three proposed approaches in swarm-array computing based on landscapes of intelligent cores, in which the cores of a parallel computing system are abstracted to swarm agents, is investigated. A task gets executed and transferred seamlessly between cores in the proposed approach thereby achieving self-ware properties that characterize autonomic computing. FPGAs are considered as an experimental platform taking into account its application in space robotics. The feasibility of the proposed approach is validated on the SeSAm multi-agent simulator.

A semi-blind reception scheme based on ICA for multiuser MIMO-STBC system

When the orthogonal space-time block code (STBC), or the Alamouti code, is applied on a multiple-input multiple-output (MIMO) communications system, the optimum reception can be achieved by a simple signal decoupling at the receiver. The performance, however, deteriorates significantly in presence of co-channel interference (CCI) from other users. In this paper, such CCI problem is overcome by applying the independent component analysis (ICA), a blind source separation algorithm. This is based on the fact that, if the transmission data from every transmit antenna are mutually independent, they can be effectively separated at the receiver with the principle of the blind source separation. Then equivalently, the CCI is suppressed. Although they are not required by the ICA algorithm itself, a small number of training data are necessary to eliminate the phase and order ambiguities at the ICA outputs, leading to a semi-blind approach. Numerical simulation is also shown to verify the proposed ICA approach in the multiuser MIMO system.

OFDM joint data detection and phase noise cancellation based on minimum mean square prediction error

This paper proposes a new iterative algorithm for orthogonal frequency division multiplexing (OFDM) joint data detection and phase noise (PHN) cancellation based on minimum mean square prediction error. We particularly highlight the relatively less studied problem of "overfitting" such that the iterative approach may converge to a trivial solution. Specifically, we apply a hard-decision procedure at every iterative step to overcome the overfitting. Moreover, compared with existing algorithms, a more accurate Pade approximation is used to represent the PHN, and finally a more robust and compact fast process based on Givens rotation is proposed to reduce the complexity to a practical level. Numerical Simulations are also given to verify the proposed algorithm. (C) 2008 Elsevier B.V. All rights reserved.

OFDM joint data detection and phase noise cancellation for constant modulus modulations

This correspondence proposes a new algorithm for the OFDM joint data detection and phase noise (PHN) cancellation for constant modulus modulations. We highlight that it is important to address the overfitting problem since this is a major detrimental factor impairing the joint detection process. In order to attack the overfitting problem we propose an iterative approach based on minimum mean square prediction error (MMSPE) subject to the constraint that the estimated data symbols have constant power. The proposed constrained MMSPE algorithm (C-MMSPE) significantly improves the performance of existing approaches with little extra complexity being imposed. Simulation results are also given to verify the proposed algorithm.

A minimum approximate-BER beamforming approach for PSK modulated wireless systems

A beamforming algorithm is introduced based on the general objective function that approximates the bit error rate for the wireless systems with binary phase shift keying and quadrature phase shift keying modulation schemes. The proposed minimum approximate bit error rate (ABER) beamforming approach does not rely on the Gaussian assumption of the channel noise. Therefore, this approach is also applicable when the channel noise is non-Gaussian. The simulation results show that the proposed minimum ABER solution improves the standard minimum mean squares error beamforming solution, in terms of a smaller achievable system's bit error rate.

Determining information requirements for e-business Systems - from activity space to information space

The study of information requirements for e-business systems reveals that the level of detail, granularity, format of presentation, and a broad range of information types are required for the applications. The provision of relevant information affects how e-business systems can efficiently support the business goals and processes. This paper presents an approach for determining information requirements for e-business systems (DIRES) which will allow the user to describe the core business processes, whose specification maps onto a business activity space. It further aids a configuration of information requirements into an information space. A case study of a logistics company in China demonstrates the use of DIRES techniques and assesses the validity of the research.