How a sequential design would have affected the GAIN international study of Gavestinel in stroke

While planning the GAIN International Study of gavestinel in acute stroke, a sequential triangular test was proposed but not implemented. Before the trial commenced it was agreed to evaluate the sequential design retrospectively to evaluate the differences in the resulting analyses, trial durations and sample sizes in order to assess the potential of sequential procedures for future stroke trials. This paper presents four sequential reconstructions of the GAIN study made under various scenarios. For the data as observed, the sequential design would have reduced the trial sample size by 234 patients and shortened its duration by 3 or 4 months. Had the study not achieved a recruitment rate that far exceeded expectation, the advantages of the sequential design would have been much greater. Sequential designs appear to be an attractive option for trials in stroke. Copyright 2004 S. Karger AG, Basel

Implementation of a Bayesian design in a dose-escalation study of an experimental agent in healthy volunteers

Bayesian decision procedures have recently been developed for dose escalation in phase I clinical trials concerning pharmacokinetic responses observed in healthy volunteers. This article describes how that general methodology was extended and evaluated for implementation in a specific phase I trial of a novel compound. At the time of writing, the study is ongoing, and it will be some time before the sponsor will wish to put the results into the public domain. This article is an account of how the study was designed in a way that should prove to be safe, accurate, and efficient whatever the true nature of the compound. The study involves the observation of two pharmacokinetic endpoints relating to the plasma concentration of the compound itself and of a metabolite as well as a safety endpoint relating to the occurrence of adverse events. Construction of the design and its evaluation via simulation are presented.

Design and development of a haptic dental training system - hapTEL

This paper presents a novel design of a virtual dental training system (hapTEL) using haptic technology. The system allows dental students to learn and practice procedures such as dental drilling, caries removal and cavity preparation for tooth restoration. This paper focuses on the hardware design, development and evaluation aspects in relation to the dental training and educational requirements. Detailed discussions on how the system offers dental students a natural operational position are documented. An innovative design of measuring and connecting the dental tools to the haptic device is also shown. Evaluation of the impact on teaching and learning is discussed.

Design considerations in the sequential analysis of matched case–control data

A role for sequential test procedures is emerging in genetic and epidemiological studies using banked biological resources. This stems from the methodology's potential for improved use of information relative to comparable fixed sample designs. Studies in which cost, time and ethics feature prominently are particularly suited to a sequential approach. In this paper sequential procedures for matched case–control studies with binary data will be investigated and assessed. Design issues such as sample size evaluation and error rates are identified and addressed. The methodology is illustrated and evaluated using both real and simulated data sets.

Safe construction through design: perspectives from the site team

How does the work of designers impact on the safety of operatives at the construction site? Safety research and policy emphasize the importance of designing for safe construction, yet the interface between design and construction is poorly understood: accidents have multiple causes making it hard to establish causal links between design choices and safety outcomes. An in-depth case study of a major station project examines how professionals on the construction site perceive and manage the safety challenges of a building design. Analyses reveal understandings that, on the project studied, design has an impact on safety because of: (1) the timing of design work, where the volume of late design changes increased the difficulty of planning safe procedures, e.g. for working at height, lifting heavy items, refurbishing and demolishing old buildings; and (2) inputs from design stakeholders with insufficient practical knowledge of construction and operation required unplanned work-arounds, e.g. to coordinate different sub-systems, provide maintenance access, and manage loads during construction. These findings suggest that safety suffers where projects are under-designed, and that alongside regulation, there is a need for robust management attention to the contractual structures, incentives, processes and tools that enable clients and designers to understand material practices of construction and operation.

Design, implementation and interpretation of in vitro batchculture experiments to assess enteric methane mitigation in ruminants—a review

In vitro fermentation techniques (IVFT) have been widely used to evaluate the nutritivevalue of feeds for ruminants and in the last decade to assess the effect of different nutritionalstrategies on methane (CH4) production. However, many technical factors may influencethe results obtained. The present review has been prepared by the ‘Global Network’ FACCE-JPI international research consortium to provide a critical evaluation of the main factorsthat need to be considered when designing, conducting and interpreting IVFT experimentsthat investigate nutritional strategies to mitigate CH4emission from ruminants. Given theincreasing and wide-scale use of IVFT, there is a need to critically review reports in the lit-erature and establish what criteria are essential to the establishment and implementationof in vitro techniques. Key aspects considered include: i) donor animal species and numberof animal used, ii) diet fed to donor animals, iii) collection and processing of rumen fluidas inoculum, iv) choice of substrate and incubation buffer, v) incubation procedures andCH4measurements, vi) headspace gas composition and vii) comparability of in vitro andin vivo measurements. Based on an evaluation of experimental evidence, a set of techni-cal recommendations are presented to harmonize IVFT for feed evaluation, assessment ofrumen function and CH4production.

Nutritional intervention programme among a Japanese-Brazilian community: procedures and results according to gender

Objective: To describe the results of a nutritional intervention programme among Japanese-Brazilians according to gender. Design: A non-controlled experimental study. Setting: The research included three points of clinical, nutritional and physical activity evaluation: at baseline (in 2005), after the first year and at the end of the second year (in 2007). The paired Student t test and multiple linear regression analysis were used to evaluate changes in the subjects` profile (clinical, nutritional and physical activity variables). Subjects: Japanese-Brazilians (n 575) of both genders, aged over 30 years. Results: We verified statistically significant reductions in body weight (0.9 kg), waist circumference (2.9 cm), blood pressure, fasting blood glucose (>3 mg/dl) and total cholesterol (>20 mg/dl) and its fractions, in both genders. We also found reductions in intake of energy (among men), protein (among women) and fat (both genders) and increases in intake of total fibre (among women) and carbohydrate (among men). Conclusions: The intervention programme indicated meaningful benefits for the intervention subjects, with changes in their habits that led to a `healthier` lifestyle positively impacting their nutritional and metabolic profile.

Road Design for Future Maintenance : Life-cycle Cost Analyses for Road Barriers

The cost of a road construction over its service life is a function of design, quality of construction as well as maintenance strategies and operations. An optimal life-cycle cost for a road requires evaluations of the above mentioned components. Unfortunately, road designers often neglect a very important aspect, namely, the possibility to perform future maintenance activities. Focus is mainly directed towards other aspects such as investment costs, traffic safety, aesthetic appearance, regional development and environmental effects. This doctoral thesis presents the results of a research project aimed to increase consideration of road maintenance aspects in the planning and design process. The following subgoals were established: Identify the obstacles that prevent adequate consideration of future maintenance during the road planning and design process; and Examine optimisation of life-cycle costs as an approach towards increased efficiency during the road planning and design process. The research project started with a literature review aimed at evaluating the extent to which maintenance aspects are considered during road planning and design as an improvement potential for maintenance efficiency. Efforts made by road authorities to increase efficiency, especially maintenance efficiency, were evaluated. The results indicated that all the evaluated efforts had one thing in common, namely ignorance of the interrelationship between geometrical road design and maintenance as an effective tool to increase maintenance efficiency. Focus has mainly been on improving operating practises and maintenance procedures. This fact might also explain why some efforts to increase maintenance efficiency have been less successful. An investigation was conducted to identify the problems and difficulties, which obstruct due consideration of maintainability during the road planning and design process. A method called “Change Analysis” was used to analyse data collected during interviews with experts in road design and maintenance. The study indicated a complex combination of problems which result in inadequate consideration of maintenance aspects when planning and designing roads. The identified problems were classified into six categories: insufficient consulting, insufficient knowledge, regulations and specifications without consideration of maintenance aspects, insufficient planning and design activities, inadequate organisation and demands from other authorities. Several urgent needs for changes to eliminate these problems were identified. One of the problems identified in the above mentioned study as an obstacle for due consideration of maintenance aspects during road design was the absence of a model for calculating life-cycle costs for roads. Because of this lack of knowledge, the research project focused on implementing a new approach for calculating and analysing life-cycle costs for roads with emphasis on the relationship between road design and road maintainability. Road barriers were chosen as an example. The ambition is to develop this approach to cover other road components at a later stage. A study was conducted to quantify repair rates for barriers and associated repair costs as one of the major maintenance costs for road barriers. A method called “Case Study Research Method” was used to analyse the effect of several factors on barrier repairs costs, such as barrier type, road type, posted speed and seasonal effect. The analyses were based on documented data associated with 1625 repairs conducted in four different geographical regions in Sweden during 2006. A model for calculation of average repair costs per vehicle kilometres was created. Significant differences in the barrier repair costs were found between the studied barrier types. In another study, the injuries associated with road barrier collisions and the corresponding influencing factors were analysed. The analyses in this study were based on documented data from actual barrier collisions between 2005 and 2008 in Sweden. The result was used to calculate the cost for injuries associated with barrier collisions as a part of the socio-economic cost for road barriers. The results showed significant differences in the number of injuries associated with collisions with different barrier types. To calculate and analyse life-cycle costs for road barriers a new approach was developed based on a method called “Activity-based Life-cycle Costing”. By modelling uncertainties, the presented approach gives a possibility to identify and analyse factors crucial for optimising life-cycle costs. The study showed a great potential to increase road maintenance efficiency through road design. It also showed that road components with low investment costs might not be the best choice when including maintenance and socio-economic aspects. The difficulties and problems faced during the collection of data for calculating life-cycle costs for road barriers indicated a great need for improving current data collecting and archiving procedures. The research focused on Swedish road planning and design. However, the conclusions can be applied to other Nordic countries, where weather conditions and road design practices are similar. The general methodological approaches used in this research project may be applied also to other studies.

Design of boundary-scan testing in CMOS image sensors for industrial applications: internship repor

Tests on printed circuit boards and integrated circuits are widely used in industry,resulting in reduced design time and cost of a project. The functional and connectivity tests in this type of circuits soon began to be a concern for the manufacturers, leading to research for solutions that would allow a reliable, quick, cheap and universal solution. Initially, using test schemes were based on a set of needles that was connected to inputs and outputs of the integrated circuit board (bed-of-nails), to which signals were applied, in order to verify whether the circuit was according to the specifications and could be assembled in the production line. With the development of projects, circuit miniaturization, improvement of the production processes, improvement of the materials used, as well as the increase in the number of circuits, it was necessary to search for another solution. Thus Boundary-Scan Testing was developed which operates on the border of integrated circuits and allows testing the connectivity of the input and the output ports of a circuit. The Boundary-Scan Testing method was converted into a standard, in 1990, by the IEEE organization, being known as the IEEE 1149.1 Standard. Since then a large number of manufacturers have adopted this standard in their products. This master thesis has, as main objective: the design of Boundary-Scan Testing in an image sensor in CMOS technology, analyzing the standard requirements, the process used in the prototype production, developing the design and layout of Boundary-Scan and analyzing obtained results after production. Chapter 1 presents briefly the evolution of testing procedures used in industry, developments and applications of image sensors and the motivation for the use of architecture Boundary-Scan Testing. Chapter 2 explores the fundamentals of Boundary-Scan Testing and image sensors, starting with the Boundary-Scan architecture defined in the Standard, where functional blocks are analyzed. This understanding is necessary to implement the design on an image sensor. It also explains the architecture of image sensors currently used, focusing on sensors with a large number of inputs and outputs.Chapter 3 describes the design of the Boundary-Scan implemented and starts to analyse the design and functions of the prototype, the used software, the designs and simulations of the functional blocks of the Boundary-Scan implemented. Chapter 4 presents the layout process used based on the design developed on chapter 3, describing the software used for this purpose, the planning of the layout location (floorplan) and its dimensions, the layout of individual blocks, checks in terms of layout rules, the comparison with the final design and finally the simulation. Chapter 5 describes how the functional tests were performed to verify the design compliancy with the specifications of Standard IEEE 1149.1. These tests were focused on the application of signals to input and output ports of the produced prototype. Chapter 6 presents the conclusions that were taken throughout the execution of the work.

Assessment of the ergonomic design of diagnostic ultrasound transducers through wrist movements and subjective evaluation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Patient perceptions about anesthesia and anesthesiologists before and after surgical procedures

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fatigue strength: effect of welding type and joint design executed in Ti-6Al-4V structures

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Computer-aided design of a novel ligand for retinoic acid receptor in cancer chemotherapy

The isotypes of RAR and RXR are retinoic acid and retinoid X acid receptors, respectively, whose ligand-binding domain contains the ligand-dependent activation function, with distinct pharmacological targets for retinoids, involved in the treatment of various cancers and skin diseases. Due to the major challenge which cancer treatment and cure still imposes after many decades to the international scientific community, there is actually considerable interest in new ligands with increased bioactivity. We have focused on the retinoid acid receptor, which is considered an interesting target for drug design. In this work, we carried out density functional geometry optimizations, and different docking procedures. We performed screening in a large database (hundreds of thousands of molecules which we optimized at the AM1 level) yielding a set of potential bioactive ligands. A new ligand was selected and optimized at the B3LYP/6-31G* level. A flexible docking program was used to investigate the interactions between the receptor and the new ligand. The result of this work is compared with several crystallographic ligands of RAR. Our theoretically more bioactive new-ligand indicates stronger and more hydrogen bonds as well as hydrophobic interactions with the receptor. (c) 2005 Wiley Periodicals, Inc.

Design of a simplified neuro-fuzzy system based on CMAC Architectures

This work presents the design of a fuzzy controller with simplified architecture that use an artificial neural network working as the aggregation operator for several active fuzzy rules. The simplified architecture of the fuzzy controller is used to minimize the time processing used in the closed loop system operation, the basic procedures of fuzzification are simplified to maximum while all the inference procedures are computed in a private way. As consequence, this simplified architecture allows a fast and easy configuration of the simplified fuzzy controller. The structuring of the fuzzy rules that define the control actions is previously computed using an artificial neural network based on CMAC Cerebellar Model Articulation Controller. The operational limits are standardized and all the control actions are previously calculated and stored in memory. For applications, results and conclusions several configurations of this fuzzy controller are considered.

Design of a fuzzy controller with simplified architecture

This work presents the design of a fuzzy controller with simplified architecture. This architecture tries to minimize the time processing used in? the several stages of hazy modeling of systems and processes. The basic procedures of fuzzification and defuzzification are simplified to the maximum while the inference procedures are computed in private way. Therefore, the simplified architecture allows a fast and easy configuration of the fuzzy controller.All rules that define the control actions are determined by inference procedures and the defuzzification is made automatically using a simplified algorithm. The fuzzy controller operation is standardized and the control actions are previously calculated For general-purpose application? ann results, the industrial systems of fluid pow cona ol will be considered.