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Background: Platform trials improve the efficiency of the drug development process through flexible features such as adding and dropping arms as evidence emerges. The benefits and practical challenges of implementing novel trial designs have been discussed widely in the literature, yet less consideration has been given to the statistical implications of adding arms. Main: We explain different statistical considerations that arise from allowing new research interventions to be added in for ongoing studies. We present recent methodology development on addressing these issues and illustrate design and analysis approaches that might be enhanced to provide robust inference from platform trials. We also discuss the implication of changing the control arm, how patient eligibility for different arms may complicate the trial design and analysis, and how operational bias may arise when revealing some results of the trials. Lastly, we comment on the appropriateness and the application of platform trials in phase II and phase III settings, as well as publicly versus industry-funded trials. Conclusion: Platform trials provide great opportunities for improving the efficiency of evaluating interventions. Although several statistical issues are present, there are a range of methods available that allow robust and efficient design and analysis of these trials.

Background: Platform trials improve the efficiency of the drug development process through flexible features such as adding and dropping arms as evidence emerges. The benefits and practical challenges of implementing novel trial designs have been discussed widely in the literature, yet less consideration has been given to the statistical implications of adding arms. Main: We explain different statistical considerations that arise from allowing new research interventions to be added in for ongoing studies. We present recent methodology development on addressing these issues and illustrate design and analysis approaches that might be enhanced to provide robust inference from platform trials. We also discuss the implication of changing the control arm, how patient eligibility for different arms may complicate the trial design and analysis, and how operational bias may arise when revealing some results of the trials. Lastly, we comment on the appropriateness and the application of platform trials in phase II and phase III settings, as well as publicly versus industry-funded trials. Conclusion: Platform trials provide great opportunities for improving the efficiency of evaluating interventions. Although several statistical issues are present, there are a range of methods available that allow robust and efficient design and analysis of these trials.

Stimulation of the sandstone reservoir requires a mixture of acids such as mud acid, which assist in enlarging the microscopic paths by dissolving the siliceous fines or clays near the well-bore region. As a result, the formation permeability and porosity can be enhanced. In deeper wells, the temperature exceeds 200 °F, at these temperature ranges, problems can arise. For example, the use of mud acid mixtures can lead to issues like precipitations, corrosion, early consumption of acids, leading to lesser acid efficiency. In this study, the core flooding apparatus was used for acidizing experiments, designed to dissolve minerals and to analyze the changes in petrophysical parameters such as porosity, permeability, and mineralogy. Conventional and tight sandstone core samples were acidized using different chelating acids such as Hydroxyethylethylenediaminetriacetic acid (HEDTA), Ethylenediaminetetraacetic acid (EDTA) and Glutamic acid (GLDA) at high-temperature conditions. Analytical studies (mineral mass, pore size distribution, topology, grain size distribution, and density distribution were conducted using Tescan Integrated Mineral Analysis (TIMA). The obtained results showed that chelating agent HEDTA created more pore spaces in the core samples and is effective in dissolving positive ions. Also, the permeability was observed to be doubled by its application which could be effective in alteration of pore topology of the sandstone cores.

Multiarm trials with follow-up on participants are commonly implemented to assess treatment effects on a population over the course of the studies. Dropout is an unavoidable issue especially when the duration of the multiarm study is long. Its impact is often ignored at the design stage, which may lead to less accurate statistical conclusions. We develop an optimal design framework for trials with repeated measurements, which takes potential dropouts into account, and we provide designs for linear mixed models where the presence of dropouts is noninformative and dependent on design variables. Our framework is illustrated through redesigning a clinical trial on Alzheimer's disease, whereby the benefits of our designs compared with standard designs are demonstrated through simulations. © 2019 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Multiarm trials with follow-up on participants are commonly implemented to assess treatment effects on a population over the course of the studies. Dropout is an unavoidable issue especially when the duration of the multiarm study is long. Its impact is often ignored at the design stage, which may lead to less accurate statistical conclusions. We develop an optimal design framework for trials with repeated measurements, which takes potential dropouts into account, and we provide designs for linear mixed models where the presence of dropouts is noninformative and dependent on design variables. Our framework is illustrated through redesigning a clinical trial on Alzheimer's disease, whereby the benefits of our designs compared with standard designs are demonstrated through simulations. © 2019 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

This paper reviews the first NTIRE challenge on video super-resolution (restoration of rich details in low-resolution video frames) with focus on proposed solutions and results. A new REalistic and Diverse Scenes dataset (REDS) was employed. The challenge was divided into 2 tracks. Track 1 employed standard bicubic downscaling setup while Track 2 had realistic dynamic motion blurs. Each competition had 124 and 104 registered participants. There were total 14 teams in the final testing phase. They gauge the state-of-the-art in video super-resolution., NA

Ticks are important vectors of pathogens and secreted neurotoxins with approximately 69 out of 692 tick species having the ability to induce severe toxicoses in their hosts. The Australian paralysis tick (Ixodes holocyclus) is known to be one of the most virulent tick species producing a flaccid paralysis and fatalities caused by a family of neurotoxins known as holocyclotoxins (HTs). The paralysis mechanism of these toxins is temperature dependent and is thought to involve inhibition of acetylcholine levels at the neuromuscular junction. However, the target and mechanism of this inhibition remain uncharacterised. Here, we report that three members of the holocyclotoxin family; HT-1 (GenBank AY766147), HT-3 (GenBank KP096303) and HT-12 (GenBank KP963967) induce muscle paralysis by inhibiting the dependence of transmitter release on extracellular calcium. Previous study was conducted using extracts from tick salivary glands, while the present study is the first to use pure toxins from I. holocyclus. Our findings provide greater insight into the mechanisms by which these toxins act to induce paralysis.

Ticks are important vectors of pathogens and secreted neurotoxins with approximately 69 out of 692 tick species having the ability to induce severe toxicoses in their hosts. The Australian paralysis tick (Ixodes holocyclus) is known to be one of the most virulent tick species producing a flaccid paralysis and fatalities caused by a family of neurotoxins known as holocyclotoxins (HTs). The paralysis mechanism of these toxins is temperature dependent and is thought to involve inhibition of acetylcholine levels at the neuromuscular junction. However, the target and mechanism of this inhibition remain uncharacterised. Here, we report that three members of the holocyclotoxin family; HT-1 (GenBank AY766147), HT-3 (GenBank KP096303) and HT-12 (GenBank KP963967) induce muscle paralysis by inhibiting the dependence of transmitter release on extracellular calcium. Previous study was conducted using extracts from tick salivary glands, while the present study is the first to use pure toxins from I. holocyclus. Our findings provide greater insight into the mechanisms by which these toxins act to induce paralysis.

Lightly cemented scrap rubber tyre chips have been proposed as a ductile, porous and lightweight geomaterial for various engineering applications. Both drained and undrained triaxial compression tests on the material were conducted. Despite the high flexibility of the rubber chips and hence their higher ductility, the material behaviour was found to be generally similar to that of typical cemented soils. Data points with the same deviatoric strain in p'-q space were linked up to form a series of equideviatoric strain lines, and a degradable cohesion intercept is observed in the plot. There was also a tentative critical state line in p'-q-e space (e being the void ratio) that was consistent with the corresponding 'parent soil' (unbonded, cement-coated chips). In an unloading-reloading stress-strain curve the unloading path was practically identical to the reloading path in a constant-p' test, but more curved in a consolidated drained test.

Lightly cemented scrap rubber tyre chips have been proposed as a ductile, porous and lightweight geomaterial for various engineering applications. Both drained and undrained triaxial compression tests on the material were conducted. Despite the high flexibility of the rubber chips and hence their higher ductility, the material behaviour was found to be generally similar to that of typical cemented soils. Data points with the same deviatoric strain in p'-q space were linked up to form a series of equideviatoric strain lines, and a degradable cohesion intercept is observed in the plot. There was also a tentative critical state line in p'-q-e space (e being the void ratio) that was consistent with the corresponding 'parent soil' (unbonded, cement-coated chips). In an unloading-reloading stress-strain curve the unloading path was practically identical to the reloading path in a constant-p' test, but more curved in a consolidated drained test.

Lightly cemented scrap rubber tyre chips have been proposed as a ductile, porous and lightweight geomaterial for various engineering applications. Both drained and undrained triaxial compression tests on the material were conducted. Despite the high flexibility of the rubber chips and hence their higher ductility, the material behaviour was found to be generally similar to that of typical cemented soils. Data points with the same deviatoric strain in p'-q space were linked up to form a series of equideviatoric strain lines, and a degradable cohesion intercept is observed in the plot. There was also a tentative critical state line in p'-q-e space (e being the void ratio) that was consistent with the corresponding 'parent soil' (unbonded, cement-coated chips). In an unloading-reloading stress-strain curve the unloading path was practically identical to the reloading path in a constant-p' test, but more curved in a consolidated drained test.

Het doel van dit onderzoek was het vinden van alternatieven voor het gebruik van Ethrel in de tomatenteelt. Ethrel wordt gebruikt om aan het einde van het teeltseizoen de laatste trossen versneld te laten afrijpen. Onduidelijkheid over een mogelijk negatief effect van de consumptie van tomaten met ethephon (de werkzame stof in Ethrel) op de gezondheid heeft geleid tot discussie over het gebruik van Ethrel. In 2007 heeft de EU besloten de MRL (Maximum Residue Level) voor ethephon te verlagen van 3,0 naar 1,0 mg/kg tomaat. In 2008 dreigde het gebruik van Ethrel zelfs verboden te worden. Inmiddels is door de Europese Commissie besloten dat de verlaagde MRL van 1,0 mg/vrucht in principe gehandhaafd kan blijven. De kans is dus groot dat het gebruik van Ethrel in de tomatenteelt in Nederland wel toegelaten blijft.

Eight fly ashes collected from Missouri coal-fired power plants were characterized and used to prepare porous ceramic filters, which can potentially be used for high temperature gas cleaning. Amongst the fly ashes investigated, samples from Meramec silo and Labadie plants were found to have suitable chemical composition. Fly ash particles were mixed with organic additives in a suspension, which was then coated onto a stainless mesh support. The pressure drops across the fly ash filters were found to obey Darcy's relation. Results of the study indicate that the filters produced have the potential to be used for fine particle removal in gas streams, and with the addition of suitable catalyst may even be used for simultaneous removal of gaseous and solid pollutant materials.

Eight fly ashes collected from Missouri coal-fired power plants were characterized and used to prepare porous ceramic filters, which can potentially be used for high temperature gas cleaning. Amongst the fly ashes investigated, samples from Meramec silo and Labadie plants were found to have suitable chemical composition. Fly ash particles were mixed with organic additives in a suspension, which was then coated onto a stainless mesh support. The pressure drops across the fly ash filters were found to obey Darcy's relation. Results of the study indicate that the filters produced have the potential to be used for fine particle removal in gas streams, and with the addition of suitable catalyst may even be used for simultaneous removal of gaseous and solid pollutant materials.

Eight fly ashes collected from Missouri coal-fired power plants were characterized and used to prepare porous ceramic filters, which can potentially be used for high temperature gas cleaning. Amongst the fly ashes investigated, samples from Meramec silo and Labadie plants were found to have suitable chemical composition. Fly ash particles were mixed with organic additives in a suspension, which was then coated onto a stainless mesh support. The pressure drops across the fly ash filters were found to obey Darcy's relation. Results of the study indicate that the filters produced have the potential to be used for fine particle removal in gas streams, and with the addition of suitable catalyst may even be used for simultaneous removal of gaseous and solid pollutant materials.

Eight fly ashes collected from Missouri coal-fired power plants were characterized and used to prepare porous ceramic filters, which can potentially be used for high temperature gas cleaning. Amongst the fly ashes investigated, samples from Meramec silo and Labadie plants were found to have suitable chemical composition. Fly ash particles were mixed with organic additives in a suspension, which was then coated onto a stainless mesh support. The pressure drops across the fly ash filters were found to obey Darcy's relation. Results of the study indicate that the filters produced have the potential to be used for fine particle removal in gas streams, and with the addition of suitable catalyst may even be used for simultaneous removal of gaseous and solid pollutant materials.

The use of New Austrian Tunnelling Method (NATM) in soft ground has been increased worldwide in recent years because of its great flexibility. Tunnel excavation adopting the NATM is usually divided into sub-sections which are to be excavated under sequential steps. The excavation of each subsection is then followed by the application of temporary reinforcements. Different unsupported span lengths in the longitudinal direction at each step has considerable effects on stress redistribution in the ground, soil deformations as well as stress induced in tunnel supporting systems. In this study, Type 2 construction sequence in the Heathrow Express Trial Tunnel is simulated by 3D elasto-plastic coupled-consolidation finite element analyses. Ground deformations, stress changes and excess pore water pressure around the tunnel opening are predicted by the numerical analyses. Results are compared with those measured on site. Stress paths of those representative positions around the tunnel opening during the excavation are obtained and discussed.

The use of New Austrian Tunnelling Method (NATM) in soft ground has been increased worldwide in recent years because of its great flexibility. Tunnel excavation adopting the NATM is usually divided into sub-sections which are to be excavated under sequential steps. The excavation of each subsection is then followed by the application of temporary reinforcements. Different unsupported span lengths in the longitudinal direction at each step has considerable effects on stress redistribution in the ground, soil deformations as well as stress induced in tunnel supporting systems. In this study, Type 2 construction sequence in the Heathrow Express Trial Tunnel is simulated by 3D elasto-plastic coupled-consolidation finite element analyses. Ground deformations, stress changes and excess pore water pressure around the tunnel opening are predicted by the numerical analyses. Results are compared with those measured on site. Stress paths of those representative positions around the tunnel opening during the excavation are obtained and discussed.

The use of New Austrian Tunnelling Method (NATM) in soft ground has been increased worldwide in recent years because of its great flexibility. Tunnel excavation adopting the NATM is usually divided into sub-sections which are to be excavated under sequential steps. The excavation of each subsection is then followed by the application of temporary reinforcements. Different unsupported span lengths in the longitudinal direction at each step has considerable effects on stress redistribution in the ground, soil deformations as well as stress induced in tunnel supporting systems. In this study, Type 2 construction sequence in the Heathrow Express Trial Tunnel is simulated by 3D elasto-plastic coupled-consolidation finite element analyses. Ground deformations, stress changes and excess pore water pressure around the tunnel opening are predicted by the numerical analyses. Results are compared with those measured on site. Stress paths of those representative positions around the tunnel opening during the excavation are obtained and discussed.

In this study, an extension of the variational model proposed by Vallabhan and Mustafa (1996) for the settlement analysis of an axially loaded pile embedded in a multi-layered soil profile is presented. In this model, the soil profile and the embedded pile are divided into a number of sub-layers according to the actual number of soil layers observed in the field. The displacement shape function of each soil layer is given as the product of an exponential equation along the pile depth and Bessel's solution in the radial direction. The displacement relationship in each layer can be derived through transformation matrices. One of the major features of this method is that the total number of pile elements is the same as the total number of soil sub-layers. All the field components, such as displacements, stresses, and strains in the soil, can be calculated by closed-form solutions except the only unknown variable, β, which is a variable as expressed by the modified Bessel's functions of the second kind, and which can be determined by iteration techniques. Comparisons were made with the results of finite element analysis and field pile-loaded tests. Reasonable results were obtained for all cases.

This research paper has two major objectives. First, it explains the variations in public support for the British-led democratic reform in late June 1994. Second, it attempts to account for why the reform has only received mild rather than overwhelming backing from the local public. The significance of the research lies in the fact that according to comparative studies, public attitudes do shape democratic prospects. It shows that the low priority attached to democratic reform since the handover of Hong Kong can be better understood by referring to the basis of public support for the non-democratic political system before 1997. Models of political culture and rational choice are put to the test in comparing their explanatory power for public support of the British-led democratic reform and the rational choice model has been found to be more powerful. The social base of the political reform, as well as the political implications of the research are also discussed in this essay.

This paper presents the results of a detailed field instrumentation program conducted on an Earth Pressure Balanced (EPB) shield driven tunnel for the construction of the Shanghai Metro Tunnel-Line 2 in China. A twin 6.2 m diameter precast, concrete-segmental tunnel system was constructed in a soft silty clay, which is compressible, sensitive, saturated and with low permeability. In order to study the response of the soft clay and the ground movement during and after the advance of the tunneling machine, the surface and subsurface ground displacements, pore water pressure changes, and earth pressure development around the concrete lining were monitored during construction. Based on the field results, the influences of tunnel construction control processes on the resulting ground responses are interpreted and discussed in this paper. Correlation between the ground response and surface settlement are developed taking into consideration the control factors in the excavation process as well as the grouting process. Particular attention is also given to the development of correlations between the construction control processes and the associated tunnel performance under both short-term and long-term conditions.

This research paper has two major objectives. First, it explains the variations in public support for the British-led democratic reform in late June 1994. Second, it attempts to account for why the reform has only received mild rather than overwhelming backing from the local public. The significance of the research lies in the fact that according to comparative studies, public attitudes do shape democratic prospects. It shows that the low priority attached to democratic reform since the handover of Hong Kong can be better understood by referring to the basis of public support for the non-democratic political system before 1997. Models of political culture and rational choice are put to the test in comparing their explanatory power for public support of the British-led democratic reform and the rational choice model has been found to be more powerful. The social base of the political reform, as well as the political implications of the research are also discussed in this essay.

This research paper has two major objectives. First, it explains the variations in public support for the British-led democratic reform in late June 1994. Second, it attempts to account for why the reform has only received mild rather than overwhelming backing from the local public. The significance of the research lies in the fact that according to comparative studies, public attitudes do shape democratic prospects. It shows that the low priority attached to democratic reform since the handover of Hong Kong can be better understood by referring to the basis of public support for the non-democratic political system before 1997. Models of political culture and rational choice are put to the test in comparing their explanatory power for public support of the British-led democratic reform and the rational choice model has been found to be more powerful. The social base of the political reform, as well as the political implications of the research are also discussed in this essay.

This paper presents the results of a detailed field instrumentation program conducted on an Earth Pressure Balanced (EPB) shield driven tunnel for the construction of the Shanghai Metro Tunnel-Line 2 in China. A twin 6.2 m diameter precast, concrete-segmental tunnel system was constructed in a soft silty clay, which is compressible, sensitive, saturated and with low permeability. In order to study the response of the soft clay and the ground movement during and after the advance of the tunneling machine, the surface and subsurface ground displacements, pore water pressure changes, and earth pressure development around the concrete lining were monitored during construction. Based on the field results, the influences of tunnel construction control processes on the resulting ground responses are interpreted and discussed in this paper. Correlation between the ground response and surface settlement are developed taking into consideration the control factors in the excavation process as well as the grouting process. Particular attention is also given to the development of correlations between the construction control processes and the associated tunnel performance under both short-term and long-term conditions.

Seismic response analysis was carried out to examine the liquefaction potential of hydraulic sand-fills for land reclamation works in Hong Kong. A fully coupled effective stress 1-D finite element code formulated on the basis of vectored motion and generalized material stiffness was adopted for the analysis. The selection of model parameters for the finite element code was described, results from in-situ field testing and laboratory static and cyclic triaxial tests were used to define model parameters. Ground motions, pore water pressure response and ground settlement at the Tseung Kwan O reclamation site induced by an earthquake loading up to M = 7.0 on the Richter scale were described. Analysis on a scale-down ground motions by adjusting the maximum horizontal ground surface acceleration to 0.07 g was also conducted. Results of the analysis indicated that liquefaction at the site is not likely to occur under the original and scaled-down earthquake loading.

Seismic response analysis was carried out to examine the liquefaction potential of hydraulic sand-fills for land reclamation works in Hong Kong. A fully coupled effective stress 1-D finite element code formulated on the basis of vectored motion and generalized material stiffness was adopted for the analysis. The selection of model parameters for the finite element code was described, results from in-situ field testing and laboratory static and cyclic triaxial tests were used to define model parameters. Ground motions, pore water pressure response and ground settlement at the Tseung Kwan O reclamation site induced by an earthquake loading up to M = 7.0 on the Richter scale were described. Analysis on a scale-down ground motions by adjusting the maximum horizontal ground surface acceleration to 0.07 g was also conducted. Results of the analysis indicated that liquefaction at the site is not likely to occur under the original and scaled-down earthquake loading.

Seismic response analysis was carried out to examine the liquefaction potential of hydraulic sand-fills for land reclamation works in Hong Kong. A fully coupled effective stress 1-D finite element code formulated on the basis of vectored motion and generalized material stiffness was adopted for the analysis. The selection of model parameters for the finite element code was described, results from in-situ field testing and laboratory static and cyclic triaxial tests were used to define model parameters. Ground motions, pore water pressure response and ground settlement at the Tseung Kwan O reclamation site induced by an earthquake loading up to M = 7.0 on the Richter scale were described. Analysis on a scale-down ground motions by adjusting the maximum horizontal ground surface acceleration to 0.07 g was also conducted. Results of the analysis indicated that liquefaction at the site is not likely to occur under the original and scaled-down earthquake loading.

The problem of cracking at interfaces is pertinent not only to composite materials but also to structures with adhesive joints, thin films and coatings. Criteria are needed for the study of the crack growth scenarios in the interfacial region where relative magnitudes of the fracture energy for the constitutent materials and that of the interface play an important role in cracking behavior. Interface fracture occurs when the interfacial energy release rate G is equal to the interfacial fracture energy Γi, that is characterized as a function of the loading phase ψ. Therefore, for the analysis of interfacial fracture both the energy release rate (G) and the loading phase angle (ψ) must be evaluated. In this paper, a numerical method is presented to obtain the values of these two parameters at the tip of an existing interface crack. Numerical analyses of three models containing interface cracks are performed using the ADINA finite element program. In general, good agreement between the results from the numerical calculation and the analytical solutions is obtained. © 1993.