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Designing Randomized Clinical Trials for Rare DiseasesAbrahamyan, Lusine 14 January 2011 (has links)
Objectives: 1) To evaluate the quality of randomized clinical trials (RCTs) in rare diseases using Juvenile Idiopathic Arthritis (JIA) as an example, 2) to evaluate the time to treatment response in patients with rheumatic diseases, 3) to evaluate the power of the Randomized Placebo-Phase Design (RPPD) under various response time distributions, and 4) to examine the use of Value of Information (VOI) methodology in the optimal design of clinical trials for rare disease using hemophilia prophylaxis with factor VIII as an example.
Methods. The methods include a systematic review, a secondary analysis of data from an RCT and from a patient registry, a computer simulation study, and an evaluation of hypothetical RCT scenarios with VOI methodology.
Results. The quality of RCTs in JIA based on selected quality indicators was poor with some positive changes over time. In the data sets used for the assessment of hazard distributions, the response times followed mostly generalized gamma or lognormal distributions. The impact of time-to-event distribution on the power of RCTs was assessed in computer simulations. Based on the simulation results, the highest sample sizes were observed for response times following the exponential distribution. In most scenarios, the parallel groups RCT design had higher power than the RPPD. The conclusion of the VOI analyses indicated that at threshold values lower than 400,000 the current evidence supported the use of on-demand therapy. Threshold values higher than 1,000,000 supported the use of tailored or alternate day prophylaxis. At threshold values between 400,000 - 1,000,000 the optimal decision varied from on-demand to prophylaxis therapies.
Conclusions. New, more powerful and acceptable designs should be developed for rare diseases. When time-to-event outcomes are used, investigators should use various sources of information to evaluate response time distributions before the new trial is designed, and consider this information in sample size calculation and analysis. VOI methodology should be used in the planning stage of studies to determine the relevant costs and benefits of future research, and to determine the optimal trial parameters that maximize the cost-benefit trade-off.
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An investigation of novel reactivity and bonding in rare earth metal complexesJohnson, Kevin Ross David January 2012 (has links)
The synthesis, structure and reactivity of organolanthanide complexes supported
by a family of novel bis(phosphinimine)carbazole and bis(phosphinimine)pyrrole pincer
ligands is presented. Through the systematic development of the ligand frameworks, rare
earth metal species with unique structure and reactivity were encountered. A variety of
complexes that exhibited unusual bonding modes were prepared and characterized by
single-crystal X-ray diffraction and multinuclear NMR spectroscopy.
Modulation of the ligand frameworks allowed for rational manipulation of the
steric and electronic environment imparted to the metal. Incorporation of a variety of
N-aryl rings (mesityl, phenyl, para-isopropylphenyl and 2-pyrimidine) and PR2 moieties
(PPh2, PO2C2H4 and PMe2) into the ligand design led to rare earth complexes that
revealed diverse reaction behaviour. In particular, C–H bond activation, sigmatropic alkyl
migration and ring opening insertion reactivity were observed. Kinetic and deuterium
labeling studies are discussed with respect to the unique reaction mechanisms
encountered during the study of these highly reactive organometallic rare earth
complexes. / xxvi, 247 leaves : ill. (some col.) ; 29 cm + 1 CD-ROM
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Designing Randomized Clinical Trials for Rare DiseasesAbrahamyan, Lusine 14 January 2011 (has links)
Objectives: 1) To evaluate the quality of randomized clinical trials (RCTs) in rare diseases using Juvenile Idiopathic Arthritis (JIA) as an example, 2) to evaluate the time to treatment response in patients with rheumatic diseases, 3) to evaluate the power of the Randomized Placebo-Phase Design (RPPD) under various response time distributions, and 4) to examine the use of Value of Information (VOI) methodology in the optimal design of clinical trials for rare disease using hemophilia prophylaxis with factor VIII as an example.
Methods. The methods include a systematic review, a secondary analysis of data from an RCT and from a patient registry, a computer simulation study, and an evaluation of hypothetical RCT scenarios with VOI methodology.
Results. The quality of RCTs in JIA based on selected quality indicators was poor with some positive changes over time. In the data sets used for the assessment of hazard distributions, the response times followed mostly generalized gamma or lognormal distributions. The impact of time-to-event distribution on the power of RCTs was assessed in computer simulations. Based on the simulation results, the highest sample sizes were observed for response times following the exponential distribution. In most scenarios, the parallel groups RCT design had higher power than the RPPD. The conclusion of the VOI analyses indicated that at threshold values lower than 400,000 the current evidence supported the use of on-demand therapy. Threshold values higher than 1,000,000 supported the use of tailored or alternate day prophylaxis. At threshold values between 400,000 - 1,000,000 the optimal decision varied from on-demand to prophylaxis therapies.
Conclusions. New, more powerful and acceptable designs should be developed for rare diseases. When time-to-event outcomes are used, investigators should use various sources of information to evaluate response time distributions before the new trial is designed, and consider this information in sample size calculation and analysis. VOI methodology should be used in the planning stage of studies to determine the relevant costs and benefits of future research, and to determine the optimal trial parameters that maximize the cost-benefit trade-off.
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Unidirectional solidification of rare earth oxide-metal composites.Stendera, James Windsor January 1974 (has links)
No description available.
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A dynamic model for calculating the uptake of an inhaled noble gasHarmer, Muffin Louise Blakeney 12 1900 (has links)
No description available.
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Reexamination of kimuraite : the occurrence of lanthanite in the cleavages of kimuraiteKATO, Takenori, KAWABE, Iwao, JIAO, Wenfang January 2013 (has links)
No description available.
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Computational Investigation of Intense Short-Wavelength Laser Interaction with Rare Gas ClustersBigaouette, Nicolas 28 January 2014 (has links)
Clusters of atoms have remarkable optical properties that were exploited since the antiquity. It was only during the late 20th century though that their production was better controlled and opened the door to a better understanding of matter. Lasers are the tool of choice to study these nanoscopic objects so scientists have been blowing clusters with high intensities and short duration laser pulses to gain insights on the dynamics at the nanoscale. Clusters of atoms are an excellent first step in the study of bio-molecules imaging. New advancements in laser technology in the shape of Free Electron Lasers (FEL) made shorter and shorter wavelengths accessible from the infrared (IR) to the vacuum and extreme ultra-violet (VUV and XUV) to even X-rays. Experiments in these short wavelengths regimes revealed surprisingly high energy absorption that are yet to be fully explained.
This thesis tries to increase the global knowledge of clusters of rare-gas atoms interacting with short duration and high intensity lasers in the VUV and XUV regime. Theoretical and numerical tools were developed and a novel model of energy transfer based on excited states will be presented.
The first part describes the current knowledge of laser-cluster interaction in the short wavelength regime followed by the description of the new model. In the second part of the thesis the different tools and implementations used throughout this work are presented. Third, a series of journal articles (of which four are published and one to be submitted) are included where our models and tools were successfully used to explain experimental results.
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The Jianfengling granite complex and the associated polymetallic mineralisation, Hunan Province, P.R. ChinaWang, Can Sheng January 1993 (has links)
No description available.
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Theoretical studies of Van der Waals clustersBryan, Robert January 1997 (has links)
The vibrational energy levels of various rare gas trimers, Ar(_3), Ne(_3), He(_3), Ar(_2)Ne and Ne(_2)Ar, have been calculated using a coupled channel approach. We have compared results obtained with previous calculations. The existence of Efi-mov states in He(_3) has been investigated, and no evidence of their existence has been found. The affect of the Eckart conditions on embedding axis into a rotating-vibrating system has been investigated for several rare gas systems. A wide range of rare gas trimers have been studied, Ar(_3), He(_2)Ar, Ar(_2)He, Ar(_2)Ne and Ne(_2)Ar. For each trimer the full range of molecular motion is investigated. The low energy minima for the Ar(_n)N(_2) and Ne(_n)N(_2) systems have been found using simulated annealing search, and a gradient based minimisation technique, of a pairwise potential energy surface. Clusters with n ≥ 12 have been studied, and first solvation shells for both systems have been proposed. For each value of n, for n = 1 - 12, the first few low energy minima of the potential energy surface have been found. From these studies, we have gained a detailed understanding of the interplay of forces that determine the low energy structures for these systems. The affect of three-body interactions on the low energy minima both rare gas-N(_2) systems has been studied. In both system, rare gas-rare gas and rare gas- threebody interactions have been taken into account. This study has shown that the three-body forces have a small affect on the low energy structures of each system.
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Magnetism and magnetic excitations in narrow band metals and rare-earth compoundsBahurmuz, Abdulrahim A. January 1976 (has links)
No description available.
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