A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to he stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase H and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail. Copyright (C) 2008 John Wiley & Sons, Ltd.

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.

Gene-nutrient interactions in the metabolic syndrome: single nucleotide polymorphisms in ADIPOQ and ADIPOR1 interact with plasma saturated fatty acids to modulate insulin resistance

Background: Progression of the metabolic syndrome (MetS) is determined by genetic and environmental factors. Gene-environment interactions may be important in modulating the susceptibility to the development of MetS traits. Objective: Gene-nutrient interactions were examined in MetS subjects to determine interactions between single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) and plasma fatty acid composition and their effects on MetS characteristics. Design: Plasma fatty acid composition, insulin sensitivity, plasma adiponectin and lipid concentrations, and ADIPOQ, ADIPOR1, and ADIPOR2 SNP genotypes were determined in a cross-sectional analysis of 451 subjects with the MetS who participated in the LIPGENE (Diet, Genomics, and the Metabolic Syndrome: an Integrated Nutrition, Agro-food, Social, and Economic Analysis) dietary intervention study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX (SUpplementation en VItamines et Mineraux AntioXydants) case-control study (http://www.ucd.ie/lipgene). Results: Single SNP effects were detected in the cohort. Triacylglycerols, nonesterified fatty acids, and waist circumference were significantly different between genotypes for 2 SNPs (rs266729 in ADIPOQ and rs10920533 in ADIPOR1). Minor allele homozygotes for both of these SNPs were identified as having degrees of insulin resistance, as measured by the homeostasis model assessment of insulin resistance, that were highly responsive to differences in plasma saturated fatty acids (SFAs). The SFA-dependent association between ADIPOR1 rs10920533 and insulin resistance was replicated in cases with MetS from a separate independent study, which was an association not present in controls. Conclusions: A reduction in plasma SFAs could be expected to lower insulin resistance in MetS subjects who are minor allele carriers of rs266729 in ADIPOQ and rs10920533 in ADIPOR1. Personalized dietary advice to decrease SFA consumption in these individuals may be recommended as a possible therapeutic measure to improve insulin sensitivity. This trial was registered at clinicaltrials.

A compositional framework for hardware/software co-design

We describe a compositional framework, together with its supporting toolset, for hardware/software co-design. Our framework is an integration of a formal approach within a traditional design flow. The formal approach is based on Interval Temporal Logic and its executable subset, Tempura. Refinement is the key element in our framework because it will derive from a single formal specification of the system the software and hardware parts of the implementation, while preserving all properties of the system specification. During refinement simulation is used to choose the appropriate refinement rules, which are applied automatically in the HOL system. The framework is illustrated with two case studies. The work presented is part of a UK collaborative research project between the Software Technology Research Laboratory at the De Montfort University and the Oxford University Computing Laboratory.

Pipelining considerations for an FPGA case

This paper presents a semi-synchronous pipeline scheme, here referred as single-pulse pipeline, to the problem of mapping pipelined circuits to a Field Programmable Gate Array (FPGA). Area and timing considerations are given for a general case and later applied to a systolic circuit as illustration. The single-pulse pipeline can manage asynchronous worst-case data completion and it is evaluated against two chosen asynchronous pipelining: a four-phase bundle-data pipeline and a doubly-latched asynchronous pipeline. The semi-synchronous pipeline proposal takes less FPGA area and operates faster than the two selected fully-asynchronous schemes for an FPGA case.

Community involvement in urban design: help or hindrance?

This paper examines the realities of community involvement in urban design in the context of a study of the West Itchen Neighbourhood of Southampton, a diverse inner city area accommodating some 7,000 households and 18,000 people. The findings are based on a literature review of community involvement in urban design and case study research into three government supported regeneration projects all located within the study area: a Neighbourhood Renewal Area - designated in 1994; an Estate Action Scheme - implemented between 1993 and 1996; and a Single Regeneration Budget programme - following a successful bid in 1995. The research was undertaken by Helen Gregory in 1997/8 as the basis of a dissertation, supervised by Alan Rowley, submitted for the award of an MPhil in Environmental Planning and Development from The University of Reading.

Task design and second language performance: the effect of narrative type on learner output

This article reports on a detailed empirical study of the way narrative task design influences the oral performance of second-language (L2) learners. Building on previous research findings, two dimensions of narrative design were chosen for investigation: narrative complexity and inherent narrative structure. Narrative complexity refers to the presence of simultaneous storylines; in this case, we compared single-story narratives with dual-story narratives. Inherent narrative structure refers to the order of events in a narrative; we compared narratives where this was fixed to others where the events could be reordered without loss of coherence. Additionally, we explored the influence of learning context on performance by gathering data from two comparable groups of participants: 60 learners in a foreign language context in Teheran and 40 in an L2 context in London. All participants recounted two of four narratives from cartoon pictures prompts, giving a between-subjects design for narrative complexity and a within-subjects design for inherent narrative structure. The results show clearly that for both groups, L2 performance was affected by the design of the task: Syntactic complexity was supported by narrative storyline complexity and grammatical accuracy was supported by an inherently fixed narrative structure. We reason that the task of recounting simultaneous events leads learners into attempting more hypotactic language, such as subordinate clauses that follow, for example, while, although, at the same time as, etc. We reason also that a tight narrative structure allows learners to achieve greater accuracy in the L2 (within minutes of performing less accurately on a loosely structured narrative) because the tight ordering of events releases attentional resources that would otherwise be spent on finding connections between the pictures. The learning context was shown to have no effect on either accuracy or fluency but an unexpectedly clear effect on syntactic complexity and lexical diversity. The learners in London seem to have benefited from being in the target language environment by developing not more accurate grammar but a more diverse resource of English words and syntactic choices. In a companion article (Foster & Tavakoli, 2009) we compared their performance with native-speaker baseline data and see that, in terms of nativelike selection of vocabulary and phrasing, the learners in London are closing in on native-speaker norms. The study provides empirical evidence that L2 performance is affected by task design in predictable ways. It also shows that living within the target language environment, and presumably using the L2 in a host of everyday tasks outside the classroom, confers a distinct lexical advantage, not a grammatical one.

Climate change impacts in the design of drainage systems: case study of Portugal

This paper aims to assess the necessity of updating the intensity-duration-frequency (IDF) curves used in Portugal to design building storm-water drainage systems. A comparative analysis of the design was performed for the three predefined rainfall regions in Portugal using the IDF curves currently in use and estimated for future decades. Data for recent and future climate conditions simulated by a global and regional climate model chain are used to estimate possible changes of rainfall extremes and its implications for the drainage systems. The methodology includes the disaggregation of precipitation up to subhourly scales, the robust development of IDF curves, and the correction of model bias. Obtained results indicate that projected changes are largest for the plains in southern Portugal (5–33%) than for mountainous regions (3–9%) and that these trends are consistent with projected changes in the long-term 95th percentile of the daily precipitation throughout the 21st century. The authors conclude there is a need to review the current precipitation regime classification and change the new drainage systems towards larger dimensions to mitigate the projected changes in extreme precipitation.

Fractal geometry and architecture design: case study review

The idea of buildings in harmony with nature can be traced back to ancient times. The increasing concerns on sustainability oriented buildings have added new challenges in building architectural design and called for new design responses. Sustainable design integrates and balances the human geometries and the natural ones. As the language of nature, it is, therefore, natural to assume that fractal geometry could play a role in developing new forms of aesthetics and sustainable architectural design. This paper gives a brief description of fractal geometry theory and presents its current status and recent developments through illustrative review of some fractal case studies in architecture design, which provides a bridge between fractal geometry and architecture design.

Assessing the Design of the Library's Discovery Interface and Online resources: A Case Study at the University of Maryland

This presentation was offered as part of the CUNY Library Assessment Conference, Reinventing Libraries: Reinventing Assessment, held at the City University of New York in June 2014.

Variation of System Performance with Design and Climate for Combisystems in Sweden

In Sweden, 90% of the solar heating systems are solar domestic hot water and heating systems (SDHW&H), so called combisystems. These generally supply most of the domestic hot water needs during the summer and have enough capacity to supply some energy to the heating system during spring and autumn. This paper describes a standard Swedish combisystem and how the output from it varies with heating load, climate within Sweden, and how it can be increased with improved system design. A base case is defined using the standard combi- system, a modern Swedish single family house and the climate of Stockholm. Using the simulation program Trnsys, parametric studies have been performed on the base case and improved system designs. The solar fraction could be increased from 17.1% for the base case to 22.6% for the best system design, given the same system size, collector type and load. A short analysis of the costs of changed system design is given, showing that payback times for additional investment are from 5-8 years. Measurements on system components in the laboratory have been used to verify the simulation models used. More work is being carried out in order to find even better system designs, and further improvements in system performance are expected.

Thermal energy storage in Swedish single family houses : a case study

In a Nordic climate, space heating (SH) and domestic hot water (DHW) used in buildings constitute a considerable part of the total energy use in the country. For 2010, energy used for SH and DHW amounted to almost 90 TWh in Sweden which corresponds to 60 % of the energy used in the residential and service sector, or almost 24 % of the total final energy use for the country. Storing heat and cold with the use of thermal energy storage (TES) can be one way of increasing the energy efficiency of a building by opening up possibilities for alternative sources of heat or cold through a reduced mismatch between supply and demand. Thermal energy storage without the use of specific control systems are said to be passive and different applications using passive TES have been shown to increase energy efficiency and/or reduce power peaks of systems supplying the heating and cooling needs of buildings, as well as having an effect on the indoor climate. Results are however not consistent between studies and focus tend to be on the reduction of cooling energy or cooling power peaks. In this paper, passive TES introduced through an increased thermal mass in the building envelope to two single family houses with different insulation standard is investigated with building energy simulations. A Nordic climate is used and the focus of this study is both on the reduction of space heating demand and space heating power, as well as on reduction of excess temperatures in residential single family houses without active cooling systems. Care is taken to keep the building envelope characteristics other than the thermal mass equal for all cases so that any observations made can be derived to the change in thermal mass. Results show that increasing the sensible thermal mass in a single family house can reduce the heating demand only slightly (1-4 %) and reduce excess temperatures (temperatures above 24 degrees C) by up to 20 %. Adding a layer of PCM (phase change materials) to the light building construction can give similar reduction in heating demand and excess temperatures, however the phase change temperature is important for the results.

Using system dynamics for collaborative design : a case study

Background  In order to facilitate the collaborative design, system dynamics (SD) with a group modelling approach was used in the early stages of planning a new stroke unit. During six workshops a SD model was created in a multiprofessional group. Aim To explore to which extent and how the use of system dynamics contributed to the collaborative design process. Method A case study was conducted using several data sources. Results SD supported a collaborative design, by facilitating an explicit description of stroke care process, a dialogue and a joint understanding. The construction of the model obliged the group to conceptualise the stroke care and experimentation with the model gave the opportunity to reflect on care. Conclusion SD facilitated the collaborative design process and should be integrated in the early stages of the design process as a quality improvement tool.

Evaluating And Optimizing Sustainable Drainage Design To Maximize Multiple Benefits: Case Studies In China

In the past, the focus of drainage design was on sizing pipes and storages in order to provide sufficient network capacity. This traditional approach, together with computer software and technical guidance, had been successful for many years. However, due to rapid population growth and urbanisation, the requirements of a “good” drainage design have also changed significantly. In addition to water management, other aspects such as environmental impacts, amenity values and carbon footprint have to be considered during the design process. Going forward, we need to address the key sustainability issues carefully and practically. The key challenge of moving from simple objectives (e.g. capacity and costs) to complicated objectives (e.g. capacity, flood risk, environment, amenity etc) is the difficulty to strike a balance between various objectives and to justify potential benefits and compromises. In order to assist decision makers, we developed a new decision support system for drainage design. The system consists of two main components – a multi-criteria evaluation framework for drainage systems and a multi-objective optimisation tool. The evaluation framework is used for the quantification of performance, life-cycle costs and benefits of different drainage systems. The optimisation tool can search for feasible combinations of design parameters such as the sizes, order and type of drainage components that maximise multiple benefits. In this paper, we will discuss real-world application of the decision support system. A number of case studies have been developed based on recent drainage projects in China. We will use the case studies to illustrate how the evaluation framework highlights and compares the pros and cons of various design options. We will also discuss how the design parameters can be optimised based on the preferences of decision makers. The work described here is the output of an EngD project funded by EPSRC and XP Solutions.