Use Of Innovative Designs Research Articles

The new big is small: Leveraging knowledge from small trials for rare disease drug development: Blarcamesine for Rett syndrome.

Big data in drug development may not satisfactorily address the demands of precision medicine in a rare disease population, making the use of smaller clinical trials necessary. Consequently, the use of innovative design and analysis of these clinical trials using model-informed approaches have become indispensable. This requires informative exposure-outcome analysis, together with formal statistical analysis, which should include the strength of evidence for a study outcome. We demonstrate how knowledge can be gained, with supporting strength of evidence, from a small (data) clinical trial with a low dose of blarcamesine in the treatment of Rett syndrome. Based on a small data paradigm, pharmacometrics item response theory modelling and Bayes factor analysis were used to demonstrate the efficacy of blarcamesine in Rett syndrome.

Climate change mitigation and adaptation strategies for construction activities within planetary boundaries: Limitations of developing countries

Continued unsustainable human activities have ushered in a new climate regime where storms have become more intense, droughts periods are now longer, floods are incessant and the occurrence of wild fires more frequent. Mitigating the effects of climate change is crucial for minimizing the occurrence of hazards associated with climate change. Adapting to this new climate era is important for the continued existence of life on planet earth. This paper presents a review of climate mitigation and adaptation strategies with specific focus on the construction industry. It discusses the following climate mitigation and adaptation strategies: use of green energy, use of sustainable building materials, construction of high rise buildings and living building elements, use of innovative designs and construction methods and recycling of urban waste. The paper also argues that developing countries are most vulnerable to climate change effects but certain factors limit them from mitigating and adapting to climate change.

Comparing oncology clinical programs by use of innovative designs and expected net present value optimization: Which adaptive approach leads to the best result?

ABSTRACTDesigning an oncology clinical program is more challenging than designing a single study. The standard approaches have been proven to be not very successful during the last decade; the failure rate of Phase 2 and Phase 3 trials in oncology remains high. Improving a development strategy by applying innovative statistical methods is one of the major objectives of a drug development process. The oncology sub-team on Adaptive Program under the Drug Information Association Adaptive Design Scientific Working Group (DIA ADSWG) evaluated hypothetical oncology programs with two competing treatments and published the work in the Therapeutic Innovation and Regulatory Science journal in January 2014. Five oncology development programs based on different Phase 2 designs, including adaptive designs and a standard two parallel arm Phase 3 design were simulated and compared in terms of the probability of clinical program success and expected net present value (eNPV). In this article, we consider eight Phase2/Phase3 development programs based on selected combinations of five Phase 2 study designs and three Phase 3 study designs. We again used the probability of program success and eNPV to compare simulated programs. For the development strategies, we considered that the eNPV showed robust improvement for each successive strategy, with the highest being for a three-arm response adaptive randomization design in Phase 2 and a group sequential design with 5 analyses in Phase 3.

Use of master curves based on time-temperature superposition to predict creep failure of aluminium-glass adhesive joints

Advancements in materials technology and the use of innovative designs have led to extensive application of adhesive bonding techniques in the electric appliance industry. While the static strength of such joints is sufficient for the intended applications, long term durability remains a major concern, mainly due to creep effects. Conventional creep testing can be performed at the service temperature but it is a long test that can take decades, although it can be accelerated using high temperatures. In this work, glass-aluminium joints were studied under static and creep loads. Glass-aluminium specimens were subjected to creep testing at various temperatures. Using the time temperature superposition principle, the results of these individual creep tests were combined in a master curve that approximates the creep behaviour of the adhesive joint in a long time period. These master curves were used to guarantee a minimum service life of the joint.

Comparing oncology clinical programs by use of innovative designs and expected net present value optimization: Which adaptive approach leads to the best result?

Comparing oncology clinical programs by use of innovative designs and expected net present value optimization: Which adaptive approach leads to the best result?

Improving Oncology Clinical Programs by Use of Innovative Designs and Comparing Them via Simulations.

The design of an oncology clinical program is much more challenging than the design of a single study. The standard approach has been proven to be not very successful during the past decade; the failure rate of phase 3 studies in oncology is about 66%. Improving the development strategy by applying innovative statistical methods is one of the major objectives for study teams designing and supporting oncology clinical programs. However, evaluating trial design alternatives is difficult; the designs may have different advantages-better power, better type I error control, shorter duration, or more accuracy-and their relative performance may depend on assumptions about the drugs' performance. Evaluating different early phase designs in particular suffers from both these problems. This paper is built on the work of the DIA's Adaptive Design Scientific Working Group oncology subteam on an Adaptive Program. With representatives from a number of institutions, this group compared 4 hypothetical oncology development programs that each was to select between 2 treatments and decide whether to proceed to phase 3, using probability of the clinical program's success and expected net present value (eNPV). Simulated scenarios were used to motivate and illustrate the key ideas. For the development strategies, we believed that the eNPV showed a distinct and robust improvement for each successive strategy.

Natural and urban soundscapes: The need for multi-disciplined research

Characterizing soundscapes represents a broad variety of approaches (ecological, sociological, phenomenological) in a continuum from completely natural to highly urban environments. There is an urgent need for the use of innovative designs which integrate the different levels of current analyses (qualitative and quantitative; individual and aggregate levels). The criteria (beyond sound level) of a good soundscape (What is a sensitive soundscape? What are soundscape requirements for a resort area or natural quiet?), that should be protected are central to the origin of the soundscape idea. Other classical acoustics questions, such as the use of audibility intrusiveness under critical conditions and under condition of mixed sources and time pattern, should be asked differently to deepen insight and understanding. A first attempt was made to monitor acoustical changes in an Italian mountain resort: Classical indicators (L95, L5, Leq) were used to locate geographical areas of increases in intrusiveness of the soundscape and linked to the activity pattern of the area. Several projects were conducted to define and localize quiet areas for a nature conservation program. Descriptive and analytical techniques, such as participatory sound and listening walks, cognitive maps, acoustical spectrographic maps, and soundscapegraphy are new techniques to consider for multi-disciplined approaches in different environments.

Materials Science in the Electron Microscope

This issue of the MRS Bulletin aims to highlight the innovative and exciting materials science research now being done using in situ electron microscopy. Techniques which combine real-time image acquisition with high spatial resolution have contributed to our understanding of a remarkably diverse range of physical phenomena. The articles in this issue present recent advances in materials science which have been made using the techniques of transmission electron microscopy (TEM), including holography, scanning electron microscopy (SEM), low-energy electron microscopy (LEEM), and high-voltage electron microscopy (HVEM).The idea of carrying out dynamic experiments involving real-time observation of microscopic phenomena has always had an attraction for materials scientists. Ever since the first static images were obtained in the electron microscope, materials scientists have been interested in observing processes in real time: we feel that we obtain a true understanding of a microscopic phenomenon if we can actually watch it taking place. The idea behind “materials science in the electron microscope” is therefore to use the electron microscope—with its unique ability to image subtle changes in a material at or near the atomic level—as a laboratory in which a remarkable variety of experiments can be carried out. In this issue you will read about dynamic experiments in areas such as phase transformations, thin-film growth, and electromigration, which make use of innovative designs for the specimen, the specimen holder, or the microscope itself. These articles speak for themselves in demonstrating the power of real-time analysis in the quantitative exploration of reaction mechanisms.The first transmission electron microscopes operated at low accelerating voltages, up to about 100 kV. This placed a severe limitation on the thickness of foils that could be examined: Heavy elements, for example, had to be made into foils thinner than 0.1 μm. It was felt that any phenomenon whose “mean free path” was comparable to the foil thickness would be significantly affected by the foil surfaces, and therefore would be unsuitable for study in situ. However, technology quickly generated ever higher accelerating voltages, culminating in the giant 3 MeV electron microscopes. At these voltages, electrons can penetrate materials as thick as 6–9 μm for light elements such as Si and Al, and 1 μm for very heavy ones such as Au and U.

Covers of Political Journals, 1910–40

This section illustrates covers of political journals of varying political factions, both Rightist (often identified with the government) and Leftist (usually affiliated with the Communist Party), dated from 1919 to 1936. The degree of sectarian partisanship generally reflected the progressive radicalization of liberal and Leftist groups from the teens through the early mid-thirties. Despite the increasingly overt political focus of these journals, their covers reveal a consistent use of innovative design and modernist imagery.