Clinical trial designs--made to order

At times, clinical trial design presents difficult problems for the consulting statistician. The nature of the disease under study or the inadequacies of standard methodology often suggest alternative strategies for the development of useful clinical trial designs. This paper examines two case of novel clinical trial designs that are "made-to-order" for the problem at hand. Both address disease-specific issues. The first case considers the use of adaptive allocation of treatments to patients in a trial in major depressive disorder. The second case reviews the design of a novel efficacy parameter in advanced pancreatic cancer.     

Designing a Controller for a Multi-Train Multi-Track System

The use of formal methods for analyzing and synthesizing a controller for a multi-train multi-track railway system is discussed. The research was motivated by a case study involving the Bay Area Rapid Transit (BART) system. The overall goal is to design a train acceleration control function that enables trains to be safely placed but also increases system throughput. The use of a modeling language for specifying safety properties and a control function is illustrated. The program transformation methodology supported in the HATS system is employed to generate an efficient implementation from a high-level specification of a controller. This implementation can then be used to simulate the controller behavior, thus further enhancing confidence in the design. Properties of optimization transformations can be verified using an rewrite-rule based induction theorem prover Rewrite Rule Laboratory (RRL).     

Direct integration of micromachined pipettes in a flow channel forsingle DNA molecule study by optical tweezers

We have developed a micromachined flow cell consisting of a flow channel integrated with micropipettes. The flow cell is used in combination with an optical trap setup (optical tweezers) to study mechanical and structural properties of λ-DNA molecules. The flow cell was realized using silicon micromachining including the so-called buried channel technology to fabricate the micropipettes, the wet etching of glass to create the flow channel, and the powder blasting of glass to make the fluid connections. The volume of the flow cell is 2 μl. The pipettes have a length of 130 μm, a width of 5-10 μm, a round opening of 1 μm and can be processed with different shapes. Using this flow cell we stretched single molecules (λ-DNA) showing typical force-extension curves also found with conventional techniques. These pipettes can be also used for drug delivery, for injection of small gas bubbles into a liquid flow to monitor the streamlines, and for the mixing of liquids to study diffusion effects. The paper describes the design, the fabrication and testing of the flow cell     

Real-time path planning in dynamic virtual environments using multiagent navigation graphs

We present a novel approach for efficient path planning and navigation of multiple virtual agents in complex dynamic scenes. We introduce a new data structure, Multi-agent Navigation Graph (MaNG), which is constructed using first- and second-order Voronoi diagrams. The MaNG is used to perform route planning and proximity computations for each agent in real time. Moreover, we use the path information and proximity relationships for local dynamics computation of each agent by extending a social force model [Helbing05]. We compute the MaNG using graphics hardware and present culling techniques to accelerate the computation. We also address undersampling issues and present techniques to improve the accuracy of our algorithm. Our algorithm is used for real-time multi-agent planning in pursuit-evasion, terrain exploration and crowd simulation scenarios consisting of hundreds of moving agents, each with a distinct goal.     

Optical information for car following: the driving by visual angle (DVA) model

OBJECTIVE: The present study developed and tested a model of car following by human drivers. BACKGROUND: Previous models of car following are based on 3-D parameters such as lead vehicle speed and distance information, which are not directly available to a driver. In the present paper we present the driving by visual angle (DVA) model, which is based on the visual information (visual angle and rate of change of visual angle) available to the driver. METHOD: Two experiments in a driving simulator examined car-following performance in response to speed variations of a lead vehicle defined by a sum of sine wave oscillations and ramp acceleration functions. In addition, the model was applied to six driving events using real world-driving data. RESULTS: The model provided a good fit to car-following performance in the driving simulation studies as well as in real-world driving performance. A comparison with the advanced interactive microscopic simulator for urban and nonurban networks (AIMSUN) model, which is based on 3-D parameters, suggests that the DVA was more predictive of driver behavior in matching lead vehicle speed and distance headway. CONCLUSION: Car-following behavior can be modeled using only visual information to the driver and can produce performance more predictive of driver performance than models based on 3-D (speed or distance) information. APPLICATION: The DVA model has applications to several traffic safety issues, including automated driving systems and traffic flow models.     

Patient views of adverse events: comparisons of self-reported healthcare staff attitudes with disclosure of accident information

In the present paper, we report results of surveys in 2003 in Japan and Denmark about patients' views about adverse events, focusing on the actions of healthcare staff involved in a medical accident. Results show that patients were more likely to indicate negative expectations to a doctor's reactions after a medical accident when asked in general terms than when asked in relation to concrete case stories. When asked in general terms, 66% (47%) of Japanese (Danish) respondents expected that doctors sometimes hold back on providing information to patients about a medical accident, while 37% (7%) did so when asked about a concrete, mild-outcome case. We examine some possible reasons for the relatively high level of distrust of Japanese patients, and we discuss whether the seemingly lower level of disclosure in Japan than in Denmark and the negative stories in the Japanese press may have an impact. We also suggest some implications for introducing a patient-centred or customer-centred approach to risk management in healthcare and other domains.     

Dynamic adaptation of network connections in mobile environments

Most network applications assume continuous connectivity-an assumption that does not “migrate” to wireless environments. The authors present the design of a communication layer for mobile computing that dynamically adapts to changes in network connections. Our work was part of AMIGOS (Advanced Mobile Integration in General Operating Systems), a collaboration between researchers at the University of Copenhagen in Denmark and the University of Minho in Portugal. The AMIGOS project provides transparent support for semi connected operations on mobile computers running a standard operating system; the project home page is at http://www.econ.cbs.dk/people/birger/AMIGOS/. Briefly, our design lets a mobile user connect a mobile host to a LAN, then disconnect the host from it. The user then can reconnect, for example, via a Global System for Mobile Communications (GSM) cellular modem without losing TCP/IP connections. We want to allow existing TCP/IP based applications to be used in a mobile environment, without application modifications     

Determination of estrogens in sludge and sediments by liquid extraction and GC/MS/MS

Two methods have been developed that enable the determination of estrogens down to 2 ng/g in digested and activated sludge from domestic sewage treatment plants (STPs) and down to 0.2 ng/g in freshwater sediments. The method for sludge analysis consists of solvent extraction; a gel permeation chromatography (GPC) cleanup step, a 1 g silica gel column; and finally, detection by GC-ion trap MS/MS of the silylated estrogens with MSTFA. For sediments, the solvent extraction was successively followed by silica gel cleanup, solid phase enrichment (SPE), and a HPLC cleanup before derivatization and GC/MS/MS detection. Mean recoveries of the estrogens mainly exceeded 70% in sludge and 90% in sediments. In activated and digested sewage sludge, estrone and 17beta-estradiol were detected up to 37 ng/g and 49 ng/g, respectively, and 17alpha-ethinylestradiol up to 17 ng/g. The occurrence of estrogens in digested sludge indicates that estrogens can be persistent during sludge digestion. In river sediments, estrone and 17beta-estradiol were detected up to 2 ng/g (estrone), and the contraceptive 17alpha-ethinylestradiol was found with a maximum of 0.9 ng/g. Mestranol, a prodrug for 17alpha-ethinylestradiol, was not detected either in sludge or in sediments.     

Fabrication of microfluidic networks with integrated electrodes

In this paper a method is presented for the fabrication of micro-channel networks in glass with integrated and insulated gate electrodes to control the zeta-potential at the insulator surface and therewith the electro-osmotic flow (EOF). The fabrication of the electrodes is a sequence of photolithography, etching and thin film deposition steps on a glass substrate, followed by chemical mechanical polishing (CMP) and subsequently direct thermal bonding to a second glass plate to form closed micro-channels. Plasma enhanced chemical vapor deposition (PECVD) SiO₂-layers as insulating material between the electrodes and micro-channels and different electrode materials are examined with respect to a high bonding temperature to obtain an optimal insulating result. A CMP process for the reduction of the SiO₂ topography and roughness is studied and optimized in order to obtain a surface that is smooth enough to be directly bondable to a second glass plate.