Multicentre trials: a US regulatory perspective

Multicentre trials are very common in the field of drug development. In recent years, multicentre trials have taken on a multinational and multiregional aspect. We provide a conceptual framework for the use of multicentre trials in the context of drug development, from the perspective of drug regulation in the United States. In this paper, we review some regulatory history, milestones and standards as they relate to multicentre trials. Special attention is given to the similarities and differences in the approaches to multicentre trials in the following documents; Guideline for the Format and Content of the Clinical and Statistical Sections of New Drug Applications, International Conference on Harmonization, Draft Guideline on Statistical Principles for clinical trials and the Guidance for Industry Providing Clinical Evidence of Effectiveness for Human Drug and Biologic Products. The paper includes a consideration of some of the issues in the analysis of data from multicentre trials.     

Probability Limits for Life Test Data

In this paper a general theory for constructing probability limits for life test data is briefly discussed. It is then applied to a set of life test data to determine which of three specified Weibull distributions give the best fit.     

A simplified expression for the minimum hotspot current in long,thin-film superconductors

A generalization of the Skocpol-Beasley-Tinkham hotspot theory to include an approximate temperature dependence of the conductive heat transfer term of the heat flow equations clearly indicates that the role of the thermal conductivity of the material of the film is not reflected in the observed temperature dependence of the minimum current I _h required to sustain a hotspot in a long, thin-film superconductor. This observation leads to the derivation of a simplified expression for I _h valid for a wider range of bath temperatures.     

Negative bias temperature instability in strain-engineered p-MOSFETs: a simulation study

Negative Bias Temperature Instability (NBTI) in p-MOSFETs is a serious reliability concern for digital and analog CMOS circuit applications. Strain in the channel region affects negative bias temperature instabilities, low frequency noise, radiation hardness, gate oxide quality and hot carrier performance. The understanding of these phenomena in strain-engineered p-MOSFETs from fundamental physics is essential. In this paper, technology CAD (TCAD) has been used to study the effects of strain on the negative bias temperature instabilities in p-MOSFETs. A quasi two dimensional (quasi-2D) physics-based Coulomb scattering mobility model for strained-Si has been developed and implemented in Synopsys Sentaurus Device tool for device simulation to understand NBTI in strain-engineered p-MOSFETs.     

Physicochemical Studies on the Interfacial and Bulk Behaviors of Sodium N-Dodecanoyl Sarcosinate (SDDS)

Sodium N-dodecanoyl sarcosinate (SDDS), a novel amino-acid based surfactant, has immense biological and industrial importance. Although it is being used in a number of cosmetic formulations, systematic analysis of the bulk and interfacial properties of the surfactant is scarce in the literature. In this study, effects of salt, temperature, and pH on the self-association and related properties of SDDS have been examined in detail using methods such as tensiometry, conductometry, fluorimetry, pH-metry, spectrophotometry, calorimetry, and circular dichroism. The nature of amphiphilic packing and the aggregation numbers of the assemblies have been deciphered. Properties of the acid form of the surfactant have also been explored. The results have been conceptually rationalized and systematically presented together with associated energetics of the interfacial adsorption and self-aggregation of the surfactant in the bulk.

A kinetic study of xylose recovery from a hemicellulose-rich biomass for xylitol fermentative production

Hemicellulose in the complex structure of lignocellulosic substances is mainly composed of xylan which is a polymer based on monosaccharide xylose. Using acidic or enzymatic hydrolysis, hemicellulose can be depolymerized into its constituent monomer. The kinetics of hemicellulose depolymerization and decomposition in oat hull was investigated under moderate pressures with catalyst (H₂SO₄) concentration up to 0.55?N and temperatures of up to 130?°C for a total residence time of 150?min. Different trends of recovery or generation and kinetic mechanisms obtained for the components in the hydrolysate which could be described by different kinetic models, that is, a single-phase kinetic mechanism with product decomposition (two-step sequential reaction) could describe xylose generation. However, generation of arabinose, furfural, and acetic acid followed a single-phase mechanism with no decomposition (one-step reaction). Generation of glucose in the hydrolysate followed a biphasic mechanism due to the fast- and slow-releasing fractions into the liquid phase which was apparently with no decomposition. A pentose recovery of almost 80% was achieved under optimal conditions. Parameters of xylitol bioproduction indicated that a xylitol/xylose conversion yield of 0.80?g/g is achievable from the concentrated hydrolysate with no complementary treatment proving its low toxicity compared to other hemicellulose resources.     

Evaluation of Non-Ambiguous Critical Micelle Concentration of Surfactants in Relation to Solution Behaviors of Pure and Mixed Surfactant Systems: A Physicochemical Documentary and Analysis

Critical micelle concentration (CMC) is a fundamental physical parameter of surfactant aggregation in solution. The CMC is determined by different methods, tensiometry, conductometry, microcalorimetry, fluorimetry, and so on. However, it is known that though CMC is reported as a single value, in reality, micelle formation occurs over a narrow range of concentration for different experimental procedures produce different results. We shall discuss about a unique procedure of measuring correct CMC applicable to all potential methods used in practice. This is essential for the evaluation of thermodynamic properties of the micelle forming process in pure and mixed states in terms of solution theories. As we in this short documentary want to deal with various aspects of Milton Rosen's research—wherein we have also worked—a few other facets of surfactant chemistry research, besides the micelle formation, are also briefly discussed. In mixed surfactant systems, synergistic effects in various surfactant properties like detergency, foaming, solubilization, and so on are found whereas in some others non-synergistic effects are observed. Dehydration of micelles with an increase in temperature or by the addition of hydrophilic substances may cause clouding to the system. Soluble amphiphilic systems produce Gibbs monolayer at the air/water interface; insoluble amphiphiles form Langmuir monolayers. A documentary of the above aspects will be herein presented and discussed. We mention that this article is neither an original research article nor a review article. This is a mixture of the two: a documentary of both original research and some review of our works presented in memory of Prof. Milton Rosen.     

The case of significant variations in gold–green and black open access: evidence from Indian research output

Scientometrics - Open Access has emerged as an important movement worldwide during the last decade. There are several initiatives now that persuade researchers to publish in open access journals...     

Estimation of Antenna Correlation Coefficient of N-Port Lossy MIMO Array

This paper proposes a simple yet accurate method for estimating the antenna correlation coefficient (ACC) of a high-order multiple-input multiple-output (MIMO) antenna. The conventional method employed to obtain the ACC from three-dimensional radiation patterns is costly and difficult to measure. An alternate method is to use the S-parameters, which can be easily measured using a network analyzer. However, this method assumes that the antennas are highly efficient, and it is therefore not suitable for lossy MIMO antenna arrays. To overcome this limitation, we define and utilize the non-coupled radiation efficiency in the S-parameter-based ACC formula. The accuracy of the proposed method is verified by the simulation results of a 4-port highly coupled lossy MIMO array. Further, the proposed method can be applied to N-port arrays by expanding the calculation matrix.     

Effect of Ni on Microstructure and Mechanical Properties of CrMnFeCoNi High Entropy Alloy

The effect of Ni content on microstructure and mechanical properties of the CrMnFeCoNi high entropy alloy (HEA) has been studied. The Ni content varied from 0 to 20 at% in the composition (CrMnFeMn)_100?xNi_x, where x?=?0, 2.5, 5, 10, 15, and 20 at%. The alloys were synthesized by vacuum arc melting and the microstructure as well as hardness of the as-cast alloys were studied. Alloys with low Ni content (x?≤?2.5%) consists of a two-phase microstructure of dendritic and inter-dendritic regions with fcc (matrix) and tetragonal (sigma) crystal structure, respectively. When the Ni content is 5 at%, two-phase structure with fcc (matrix) and bcc (secondary phase) is observed, with the addition of Mn-rich inclusions that are present in the entire matrix. Alloys with higher Ni content (x?≥?10, at%) exhibit a single phase of fcc structure. Hardness of the HEAs decreases from 320 to 120 Hv with increase in Ni content, and the high hardness of these alloys with low Ni content is due to the mixture of both fcc and hard tetragonal (sigma) phases.