Unbalanced and Partial Group Sequential Methods for Normal Responses in Clinical Trials

Abstract

Group sequential methods for a two-treatment clinical trial with normal responses are discussed. First we consider the case where the sample sizes for two treatments are possibly unequal between the treatments due to an unequal randomization. Then we discuss group sequential design in the context of a historical control study, that is, under the partial sequential sampling scheme, in which the samples on one treatment, say control, are available at the outset, and the samples on the other treatment, say experimental, are obtained in the group sequential way. We discuss the cases of known and unknown variance for both unbalanced and partial group sequential setups. All of the procedures are discussed with numerical studies.     

Silicone Rubber Compatibilized Syndiotactic Polystyrene and Thermotropic Liquid Crystalline Polymer (Vectra A950) Blend

Blends of syndiotactic polystyrene (s-PS), thermotropic liquid crystalline polymer (Vectra A-950), and silicone rubber with two different loading levels, have been prepared through melt processing in internal mixer at 285°C. Silicone rubber was used as a compatibilizer for this blend system. The effect of silicon rubber on crystalline, dynamic mechanical, rhelogical, thermal properties, and phase morphology of the (s-PS/TLCP) blend has been investigated in details. With the addition of compatibilizer the viscosity of the blend system increased to an order of magnitude. Dynamic mechanical analysis (DMTA) and differential scanning calorimetry (DSC) results showed that the glass transition temperature (T_g) of the blend, in presence of silicone rubber, shifted towards lower temperature region. From FTIR analysis it is evident that the ‘C=O’ stretching frequency has shifted towards lower side. SEM analysis suggested that, the TLCP domain size is reduced in ternary blend in comparison to binary blend system.     

Host-Assisted Delivery of a Model Drug to Genomic DNA: Key Information from Ultrafast Spectroscopy and in silico Study

Drug delivery to a target without adverse effects is one of the major criteria for clinical use. Herein, we have made an attempt to explore the delivery efficacy of SDS surfactant in a monomer and micellar stage during the delivery of the model drug, Toluidine Blue (TB) from the micellar cavity to DNA. Molecular recognition of pre-micellar SDS encapsulated TB with DNA occurs at a rate constant of k₁ ∼652 s⁻¹. However, no significant release of encapsulated TB at micellar concentration was observed within the experimental time frame. This originated from the higher binding affinity of TB towards the nano-cavity of SDS at micellar concentration which does not allow the delivery of TB from the nano-cavity of SDS micelles to DNA. Thus, molecular recognition controls the extent of DNA recognition by TB which in turn modulates the rate of delivery of TB from SDS in a concentration-dependent manner.     

Whole Body Ip6k1 Deletion Protects Mice from Age-Induced Weight Gain,Insulin Resistance and Metabolic Dysfunction

(1) Background: We previously demonstrated that disruption of IP6K1 improves metabolism, protecting mice from high-fat diet-induced obesity, insulin resistance, and non-alcoholic fatty liver disease and steatohepatitis. Age-induced metabolic dysfunction is a major risk factor for metabolic diseases. The involvement of IP6K1 in this process is unknown. (2) Methods: Here, we compared body and fat mass, insulin sensitivity, energy expenditure and serum-, adipose tissue- and liver-metabolic parameters of chow-fed, aged, wild type (aWT) and whole body Ip6k1 knockout (aKO) mice. (3) Results: IP6K1 was upregulated in the adipose tissue and liver of aWT mice compared to young WT mice. Moreover, Ip6k1 deletion blocked age-induced increase in body- and fat-weight and insulin resistance in mice. aKO mice oxidized carbohydrates more efficiently. The knockouts displayed reduced levels of serum insulin, triglycerides, and non-esterified fatty acids. Ip6k1 deletion partly protected age-induced decline of the thermogenic uncoupling protein UCP1 in inguinal white adipose tissue. Targets inhibited by IP6K1 activity such as the insulin sensitivity- and energy expenditure-inducing protein kinases, protein kinase B (PKB/Akt) and AMP-activated protein kinase (AMPK), were activated in the adipose tissue and liver of aKO mice. (4) Conclusions: Ip6k1 deletion maintains healthy metabolism in aging and thus, targeting this kinase may delay the development of age-induced metabolic dysfunction.     

Microstructure and properties of flame sprayed tungsten carbide coatings

This article reports on feasibility experiments carried out with oxy-acetylene spray system with various oxygen to fuel ratios using two different tungsten carbide powders and powder feeding methods, to evaluate the newly developed fused WC, synthesised by transferred arc thermal plasma method. Transferred arc thermal plasma method is more economical and less energy intensive than the conventional arc method and results in a fused carbide powder with higher hardness. The microstructure and phase composition of powders and coatings were analysed by optical and scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction. Carbon content of the powders and coatings were determined to study the decarburisation of the material during spraying process. Coatings were also characterised by their hardness and abrasive wear. The effects of metallurgical transformation and phase content are related to wear performance. The results demonstrate that the powders exhibit various degree of phase transformation during the spray process depending on the type of powder, powder feeding and spray parameters. The carbon loss during the spray process in excess of 45% resulted in reduced hardness and wear resistance of the coatings. Coatings with high amount of WC and W₂C along with FeW₃C showed higher wear resistance. Thus, coatings of high wear resistance can be produced using fused tungsten carbide powder with WC and W₂C phases, which can be economically synthesised by thermal plasma transferred arc method.     

Numerical Modeling of Ti Deformation for the Development of a Titanium and Stainless Steel Transition Joint

Finite element analysis (FEA) was used to model the joining of titanium grade 2 (Ti) to AISI 321 stainless steel (SS) transition joint of lap configuration with grooves at the interface on SS side. The hot forming of Ti for filling the grooves without defects was simulated. FEA involving large plastic flow with sticking friction condition was initially validated using compression test on cylindrical specimen at 900 °C. The barreled shape and a no-deformation zone in the sample predicted by FEA matched with those of the compression experiments. For the joining process, FEA computed the distribution of strain and hydrostatic stress in Ti and the minimum ram load required for a defect-free joint. The hot forming parameters for Ti to fill the grooves without defects and any geometrical distortion of the die were found to be 0.001 s^?1 at 900 °C. Using these conditions a defect-free Ti-SS joint was experimentally produced.     

Synthesis,structure, CO oxidation,and H2 production activities of CaCu3−xMnxTi4−xMnxO12 (x = 0, 0.5, and 1.0)

Synthesis of nanocrystalline pristine and Mn-doped calcium copper titanate quadruple perovskites, CaCu_3?xMn_xTi_4?xMn_xO₁₂ (x = 0, 0.5, and 1.0) by modified citrate solution combustion method has been reported. Powder X-ray diffraction patterns attest the phase purity of the perovskite materials. Average particle sizes of all the materials obtained from the Scherrer's formula are in the range of 55–70 nm. The specific surface areas for all the perovskites obtained from BET isotherms are found to be low as expected for the condensed oxide systems and fall in the range of 13–17 m² g^?1. Transmission electron microscopy studies show a reduction in particle size of CaCu₃Ti₄O₁₂ with increase in Mn doping. Ca and Ti are present in +2 and +4 oxidation states in all the materials as demonstrated by X-ray photoelectron spectroscopy analyses. Cu²⁺ gets reduced in CaCu₃Ti₄O₁₂ with higher Mn content. Mn is observed to be present only in +3 oxidation state. All the materials have been examined to be active in CO oxidation as well as H₂ production from methanol steam reforming. CaCu₃Ti₄O₁₂ with ~14 at.% Mn is found to show best catalytic activities among these materials. A comprehensive analysis of the catalytic activities of these perovskites toward CO oxidation and H₂ production from MSR reveal the cooperative activity of copper-manganese in the doped perovskites and it is more effective at lower manganese content.     

Classification of Hydrogels Based on Their Source: A Review and Application in Stem Cell Regulation

Stem cells are recognized by their self-renewal ability and can give rise to specialized progeny. Hydrogels are an established class of biomaterials with the ability to control stem cell fate via mechanotransduction. They can mimic various physiological conditions to influence the fate of stem cells and are an ideal platform to support stem cell regulation. This review article provides a summary of recent advances in the application of different classes of hydrogels based on their source (e.g., natural, synthetic, or hybrid). This classification is important because the chemistry of substrate affects stem cell differentiation and proliferation. Natural and synthetic hydrogels have been widely used in stem cell regulation. Nevertheless, they have limitations that necessitate a new class of material. Hybrid hydrogels obtained by manipulation of the natural and synthetic ones can potentially overcome these limitations and shape the future of research in application of hydrogels in stem cell regulation.     

Sustaining Urban Water Supplies in India: Increasing Role of Large Reservoirs

Urban water demand is rapidly growing in India due to high growth in urban population and rapid industrialization. Meeting this demand is a big challenge for the urban planners in India. Incidentally, the large urban areas are experiencing faster growth in population, and most of them are in arid and semi arid regions, which are naturally water-scarce. As a result, water supplies from local water resources including aquifers are falling far short of the high and concentrated demands in most urban areas. Under such situations, these large cities have to rely on distant large reservoirs. The analysis of 302 urban centers shows that cities with larger population size have much higher level of dependence on surface water sources. Also, greater the share of surface water in the city water supplies, higher was the level of per capita water supply. Multiple regression models are estimated for Class I cities and Class II towns in India. The results show that Population Elasticity of Water Supply (PEWS) change with time and space—for Class I cities it was 1.127 in 1988, whereas that with respect to 1999 population is 1.289. It also shows that Class I cities have better water supply (PEWS is 1.127 in 1988 and 1.289 in 1999) than Class II towns (PEWS is 0.396 in 1988 and 0.675 in 1999). Given the structure and pattern of urban population growth, economic conditions and water demands, large reservoirs will have a much bigger role in meeting urban water supply needs.     

Disaster-aware service provisioning with manycasting in cloud networks

Cloud services delivered by high-capacity optical datacenter networks are subject to disasters which may cause large-area failures, leading to huge data loss. Survivable service provisioning is crucial to minimize the effects of network/datacenter failures and maintain critical services in case of a disaster. We propose a novel disaster-aware service-provisioning scheme that multiplexes service over multiple paths destined to multiple servers/datacenters with manycasting. Our scheme maintains some bandwidth (i.e., degraded service) after a disaster failure vs. no service at all. We formulate this problem into a mathematical model which turns out to be an Integer Linear Program (ILP), and we provide heuristic optimization approaches as ILP is intractable for large problem instances. Numerical examples show that exploiting manycasting by intelligently selecting destinations in a risk-aware manner for service provisioning offers high level of survivability against link and node failures that may be caused by disasters and post-disaster failures at no extra cost compared to the other survivable schemes.