Conference on Lasers and Electro-Optics, Apr 24, 1989
Inertial confinement fusion requires temporally shaped pulses to achieve high gain efficiency. Re... more Inertial confinement fusion requires temporally shaped pulses to achieve high gain efficiency. Recently, we demonstrated the ability to produce complex temporal pulse shapes at high power at 0.35 microns on the Nova laser system. 2 refs., 2 figs.
Conference on Lasers and Electro-Optics, Apr 24, 1989
We have broadened the output spectrum of a single-mode, Q-switched Nd: YLF oscillator (lambda = 1... more We have broadened the output spectrum of a single-mode, Q-switched Nd: YLF oscillator (lambda = 1.053 micrometer) by co-propagating it with a noisy, broadband pulse in a polarization preserving fiber. The intensity as a function of time remains smooth, despite the 10(4) increase in bandwidth.
Many diseases and other important phenotypic outcomes are the result of a combination of factors.... more Many diseases and other important phenotypic outcomes are the result of a combination of factors. For example, expression levels of genes have been used as input to various statistical methods for predicting phenotypic outcomes. One particular popular variety is the so-called gene set enrichment analysis (GSEA). This paper discusses an augmentation to an existing strategy to estimate the significance of an associations between a disease outcome and a predetermined combination of biological factors, based on a specific data adaptive regression method (the “Super Learner,” van der Laan et al., 2007). The procedure uses an aggressive search procedure, potentially resulting in final models that imply associations that would not be discovered using non data-adaptive procedures (e.g., multiple linear regression). A test statistic derived from the ”fit” of the Super Learner model to the original data is compared to the permutation distribution of the same statistic, the latter being genera...
A motivation for achieving high fourth-harmonic-generation (FHG) conversion efficiencies in glass... more A motivation for achieving high fourth-harmonic-generation (FHG) conversion efficiencies in glass laser-fusion systems lies in the increased laser-target coupling efficiency at shorter wavelengths. To investigate the factors involved in obtaining high-conversion efficiencies using KDP, we set up a laser system consisting of a Nd:YLF oscillator and glass amplifier. We apertured the output Gaussian beam to 1.7 mm to obtain a flat-topped spatial profile. The system produced peak intensities of up to 8 GW/cm2 in 150-ps Gaussian pulses at the fundamental (1.054-μm) wavelength. Conversion to the second harmonic was achieved in a separate KDP crystal using type II phase matching. With this system, we achieved 80% internal second-to-fourth harmonic conversion efficiency in a type I 1-cm thick KDP crystal. We believe this is the highest second-to-fourth harmonic conversion efficiency obtained to date in KDP and attribute it to careful aperturing of the beam to obtain a flat spatial profile.
Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the searc... more Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the search for optimized treatment regimes in ongoing treatment settings. Analyzing data for multiple time-point treatments with a view toward optimal treatment regimes is of interest in many types of afflictions: HIV infection, Attention Deficit Hyperactivity Disorder in children, leukemia, prostate cancer, renal failure, and many others. Methods for analyzing data from SRCTs exist but they are either inefficient or suffer from the drawbacks of estimating equation methodology. We describe an estimation procedure, targeted maximum likelihood estimation (TMLE), which has been fully developed and implemented in point treatment settings, including time to event outcomes, binary outcomes and continuous outcomes. Here we develop and implement TMLE in the SRCT setting. As in the former settings, the TMLE procedure is targeted toward a pre-specified parameter of the distribution of the observed data, an...
Applying targeted maximum likelihood estimation to longitudinal data can be computationally inten... more Applying targeted maximum likelihood estimation to longitudinal data can be computationally intensive. As the number of time points and/or number of intermediate factors grows, the computation resources consumed by these algorithms likewise increases. Different TMLE algorithms have different computational speeds and implementation challenges; there may also be efficiency differences of the corresponding estimators. The algorithm we describe here proceeds by solving the empirical efficient influence curve equation directly using numerical computation methods, rather than indirectly (by solving a score equation), which is the usual route. We believe that this estimator is the simplest of the TMLE procedures to implement in the longitudinal data structure simulated here, which mimics a sequential randomized controlled trial with dynamic treatment rules. Our choice of numerical methods is the well-known secant method for finding the root of a function. The resulting estimation algorithm...
Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the searc... more Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the search for optimized treatment regimes in ongoing treatment settings. Analyzing data for multiple time-point treatments with a view toward optimal treatment regimes is of interest in many types of afflictions: HIV infection, Attention Deficit Hyperactivity Disorder in children, leukemia, prostate cancer, renal failure, and many others. Methods for analyzing data from SRCTs exist but they are either inefficient or suffer from the drawbacks of estimating equation methodology. This dissertation describes the development of a general methodology for estimating parameters that would typically be of interest both in SRCTs and in observational studies which are longitudinal in nature, and have multiple time-point exposures or treatments. It is expected in such contexts that time-dependant confounding is either present (observational studies) or actually designed in as part of a study (SRCTs). The me...
Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the searc... more Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the search for optimized treatment regimes in ongoing treatment settings. Analyzing data for multiple time-point treatments with a view toward optimal treatment regimes is of interest in many types of afflictions: HIV infection, Attention Deficit Hyperactivity Disorder in children, leukemia, prostate cancer, renal failure, and many others. Methods for analyzing data from SRCTs exist but they are either inefficient or suffer from the drawbacks of estimating equation methodology. We describe an estimation procedure, targeted maximum likelihood estimation (TMLE), which has been fully developed and implemented in point treatment settings, including time to event outcomes, binary outcomes and continuous outcomes. Here we develop and implement TMLE in the SRCT setting. As in the former settings, the TMLE procedure is targeted toward a pre-specified parameter of the distribution of the observed data, and thereby achieves important bias reduction in estimation of that parameter. As with the so-called Augmented Inverse Probability of Censoring Weight (A-IPCW) estimator, TMLE is double-robust and locally efficient. We report simulation results corresponding to two data-generating distributions from a longitudinal data structure.
Conference on Lasers and Electro-Optics, Apr 24, 1989
Inertial confinement fusion requires temporally shaped pulses to achieve high gain efficiency. Re... more Inertial confinement fusion requires temporally shaped pulses to achieve high gain efficiency. Recently, we demonstrated the ability to produce complex temporal pulse shapes at high power at 0.35 microns on the Nova laser system. 2 refs., 2 figs.
Conference on Lasers and Electro-Optics, Apr 24, 1989
We have broadened the output spectrum of a single-mode, Q-switched Nd: YLF oscillator (lambda = 1... more We have broadened the output spectrum of a single-mode, Q-switched Nd: YLF oscillator (lambda = 1.053 micrometer) by co-propagating it with a noisy, broadband pulse in a polarization preserving fiber. The intensity as a function of time remains smooth, despite the 10(4) increase in bandwidth.
Many diseases and other important phenotypic outcomes are the result of a combination of factors.... more Many diseases and other important phenotypic outcomes are the result of a combination of factors. For example, expression levels of genes have been used as input to various statistical methods for predicting phenotypic outcomes. One particular popular variety is the so-called gene set enrichment analysis (GSEA). This paper discusses an augmentation to an existing strategy to estimate the significance of an associations between a disease outcome and a predetermined combination of biological factors, based on a specific data adaptive regression method (the “Super Learner,” van der Laan et al., 2007). The procedure uses an aggressive search procedure, potentially resulting in final models that imply associations that would not be discovered using non data-adaptive procedures (e.g., multiple linear regression). A test statistic derived from the ”fit” of the Super Learner model to the original data is compared to the permutation distribution of the same statistic, the latter being genera...
A motivation for achieving high fourth-harmonic-generation (FHG) conversion efficiencies in glass... more A motivation for achieving high fourth-harmonic-generation (FHG) conversion efficiencies in glass laser-fusion systems lies in the increased laser-target coupling efficiency at shorter wavelengths. To investigate the factors involved in obtaining high-conversion efficiencies using KDP, we set up a laser system consisting of a Nd:YLF oscillator and glass amplifier. We apertured the output Gaussian beam to 1.7 mm to obtain a flat-topped spatial profile. The system produced peak intensities of up to 8 GW/cm2 in 150-ps Gaussian pulses at the fundamental (1.054-μm) wavelength. Conversion to the second harmonic was achieved in a separate KDP crystal using type II phase matching. With this system, we achieved 80% internal second-to-fourth harmonic conversion efficiency in a type I 1-cm thick KDP crystal. We believe this is the highest second-to-fourth harmonic conversion efficiency obtained to date in KDP and attribute it to careful aperturing of the beam to obtain a flat spatial profile.
Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the searc... more Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the search for optimized treatment regimes in ongoing treatment settings. Analyzing data for multiple time-point treatments with a view toward optimal treatment regimes is of interest in many types of afflictions: HIV infection, Attention Deficit Hyperactivity Disorder in children, leukemia, prostate cancer, renal failure, and many others. Methods for analyzing data from SRCTs exist but they are either inefficient or suffer from the drawbacks of estimating equation methodology. We describe an estimation procedure, targeted maximum likelihood estimation (TMLE), which has been fully developed and implemented in point treatment settings, including time to event outcomes, binary outcomes and continuous outcomes. Here we develop and implement TMLE in the SRCT setting. As in the former settings, the TMLE procedure is targeted toward a pre-specified parameter of the distribution of the observed data, an...
Applying targeted maximum likelihood estimation to longitudinal data can be computationally inten... more Applying targeted maximum likelihood estimation to longitudinal data can be computationally intensive. As the number of time points and/or number of intermediate factors grows, the computation resources consumed by these algorithms likewise increases. Different TMLE algorithms have different computational speeds and implementation challenges; there may also be efficiency differences of the corresponding estimators. The algorithm we describe here proceeds by solving the empirical efficient influence curve equation directly using numerical computation methods, rather than indirectly (by solving a score equation), which is the usual route. We believe that this estimator is the simplest of the TMLE procedures to implement in the longitudinal data structure simulated here, which mimics a sequential randomized controlled trial with dynamic treatment rules. Our choice of numerical methods is the well-known secant method for finding the root of a function. The resulting estimation algorithm...
Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the searc... more Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the search for optimized treatment regimes in ongoing treatment settings. Analyzing data for multiple time-point treatments with a view toward optimal treatment regimes is of interest in many types of afflictions: HIV infection, Attention Deficit Hyperactivity Disorder in children, leukemia, prostate cancer, renal failure, and many others. Methods for analyzing data from SRCTs exist but they are either inefficient or suffer from the drawbacks of estimating equation methodology. This dissertation describes the development of a general methodology for estimating parameters that would typically be of interest both in SRCTs and in observational studies which are longitudinal in nature, and have multiple time-point exposures or treatments. It is expected in such contexts that time-dependant confounding is either present (observational studies) or actually designed in as part of a study (SRCTs). The me...
Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the searc... more Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the search for optimized treatment regimes in ongoing treatment settings. Analyzing data for multiple time-point treatments with a view toward optimal treatment regimes is of interest in many types of afflictions: HIV infection, Attention Deficit Hyperactivity Disorder in children, leukemia, prostate cancer, renal failure, and many others. Methods for analyzing data from SRCTs exist but they are either inefficient or suffer from the drawbacks of estimating equation methodology. We describe an estimation procedure, targeted maximum likelihood estimation (TMLE), which has been fully developed and implemented in point treatment settings, including time to event outcomes, binary outcomes and continuous outcomes. Here we develop and implement TMLE in the SRCT setting. As in the former settings, the TMLE procedure is targeted toward a pre-specified parameter of the distribution of the observed data, and thereby achieves important bias reduction in estimation of that parameter. As with the so-called Augmented Inverse Probability of Censoring Weight (A-IPCW) estimator, TMLE is double-robust and locally efficient. We report simulation results corresponding to two data-generating distributions from a longitudinal data structure.
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