Litigation-Generated Science: Why Should We Care?

BACKGROUND: In a 1994 Ninth Circuit decision on the remand of Daubert v. Merrell Dow Pharmaceuticals, Inc., Judge Alex Kosinski wrote that science done for the purpose of litigation should be subject to more stringent standards of admissibility than other science. OBJECTIVES: We analyze this proposition by considering litigation-generated science as a subset of science involving conflict of interest. DISCUSSION: Judge Kosinski's formulation suggests there may be reasons to treat science involving conflict of interest differently but raises questions about whether litigation-generated science should be singled out. In particular we discuss the similar problems raised by strategically motivated science done in anticipation of possible future litigation or otherwise designed to benefit the sponsor and ask what special treatment, if any, should be given to science undertaken to support existing or potential future litigation. CONCLUSION: The problems with litigation-generated science are not special. On the contrary, they are very general and apply to much or most science that is relevant and reliable in the courtroom setting.

SOUND PROPAGATION AND SCATTERING IN BUBBLY LIQUIDS

In the ocean, natural and artificial processes generate clouds of bubbles which scatter and attenuate sound. Measurements have shown that at the individual bubble resonance frequency, sound propagation in this medium is highly attenuated and dispersive. Theory to explain this behavior exists in the literature, and is adequate away from resonance. However, due to excessive attenuation near resonance, little experimental data exists for comparison. An impedance tube was developed specifically for exploring this regime. Using the instrument, unique phase speed and attenuation measurements were made for void fractions ranging from 6.2 × 10^−5 to 2.7 × 10^−3 and bubble sizes centered around 0.62 mm in radius. Improved measurement speed, accuracy and precision is possible with the new instrument, and both instantaneous and time-averaged measurements were obtained. Behavior at resonance was observed to be sensitive to the bubble population statistics and agreed with existing theory, within the uncertainty of the bubble population parameters. Scattering from acoustically compact bubble clouds can be predicted from classical scattering theory by using an effective medium description of the bubbly fluid interior. Experimental verification was previously obtained up to the lowest resonance frequency. A novel bubble production technique has been employed to obtain unique scattering measurements with a bubbly-liquid-filled latex tube in a large indoor tank. The effective scattering model described these measurements up to three times the lowest resonance frequency of the structure.

ACOUSTO-OPTIC IMAGING IN DIFFUSE MEDIA USING PULSED ULTRASOUND AND THE PHOTOREFRACTIVE EFFECT

Acousto-optic imaging (AOI) in optically diffuse media is a hybrid imaging modality in which a focused ultrasound beam is used to locally phase modulate light inside of turbid media. The modulated optical field carries with it information about the optical properties in the region where the light and sound interact. The motivation for the development of AOI systems is to measure optical properties at large depths within biological tissue with high spatial resolution. A photorefractive crystal (PRC) based interferometry system is developed for the detection of phase modulated light in AOI applications. Two-wave mixing in the PRC creates a reference beam that is wavefront matched to the modulated optical field collected from the specimen. The phase modulation is converted to an intensity modulation at the optical detector when these two fields interfere. The interferometer has a high optical etendue, making it well suited for AOI where the scattered light levels are typically low. A theoretical model for the detection of acoustically induced phase modulation in turbid media using PRC based interferometry is detailed. An AOI system, using a single element focused ultrasound transducer to pump the AO interaction and the PRC based detection system, is fabricated and tested on tissue mimicking phantoms. It is found that the system has sufficient sensitivity to detect broadband AO signals generated using pulsed ultrasound, allowing for AOI at low time averaged ultrasound output levels. The spatial resolution of the AO imaging system is studied as a function of the ultrasound pulse parameters. A theoretical model of light propagation in turbid media is used to explore the dependence of the AO response on the experimental geometry, light collection aperture, and target optical properties. Finally, a multimodal imaging system combining pulsed AOI and conventional B- mode ultrasound imaging is developed. B-mode ultrasound and AO images of targets embedded in both highly diffuse phantoms and biological tissue ex vivo are obtained, and millimeter resolution is demonstrated in three dimensions. The AO images are intrinsically co-registered with the B-mode ultrasound images. The results suggest that AOI can be used to supplement conventional B-mode ultrasound imaging with optical information.

PHOTOREFRACTIVE CRYSTAL-BASED ACOUSTO-OPTIC IMAGING IN THE NEAR-INFRARED AND ITS APPLICATIONS

Acousto-optic (AO) sensing and imaging (AOI) is a dual-wave modality that combines ultrasound with diffusive light to measure and/or image the optical properties of optically diffusive media, including biological tissues such as breast and brain. The light passing through a focused ultrasound beam undergoes a phase modulation at the ultrasound frequency that is detected using an adaptive interferometer scheme employing a GaAs photorefractive crystal (PRC). The PRC-based AO system operating at 1064 nm is described, along with the underlying theory, validating experiments, characterization, and optimization of this sensing and imaging apparatus. The spatial resolution of AO sensing, which is determined by spatial dimensions of the ultrasound beam or pulse, can be sub-millimeter for megahertz-frequency sound waves.A modified approach for quantifying the optical properties of diffuse media with AO sensing employs the ratio of AO signals generated at two different ultrasound focal pressures. The resulting “pressure contrast signal” (PCS), once calibrated for a particular set of pressure pulses, yields a direct measure of the spatially averaged optical transport attenuation coefficient within the interaction volume between light and sound. This is a significant improvement over current AO sensing methods since it produces a quantitative measure of the optical properties of optically diffuse media without a priori knowledge of the background illumination. It can also be used to generate images based on spatial variations in both optical scattering and absorption. Finally, the AO sensing system is modified to monitor the irreversible optical changes associated with the tissue heating from high intensity focused ultrasound (HIFU) therapy, providing a powerful method for noninvasively sensing the onset and growth of thermal lesions in soft tissues. A single HIFU transducer is used to simultaneously generate tissue damage and pump the AO interaction. Experimental results performed in excised chicken breast demonstrate that AO sensing can identify the onset and growth of lesion formation in real time and, when used as feedback to guide exposure parameters, results in more predictable lesion formation.

AN IMPEDANCE TUBE FOR THE IN-SITU CLASSIFICATION OF BUBBLY LIQUIDS

It is well documented that the presence of even a few air bubbles in water can signifi- cantly alter the propagation and scattering of sound. Air bubbles are both naturally and artificially generated in all marine environments, especially near the sea surface. The abil- ity to measure the acoustic propagation parameters of bubbly liquids in situ has long been a goal of the underwater acoustics community. One promising solution is a submersible, thick-walled, liquid-filled impedance tube. Recent water-filled impedance tube work was successful at characterizing low void fraction bubbly liquids in the laboratory [1]. This work details the modifications made to the existing impedance tube design to allow for submersed deployment in a controlled environment, such as a large tank or a test pond. As well as being submersible, the useable frequency range of the device is increased from 5 - 9 kHz to 1 - 16 kHz and it does not require any form of calibration. The opening of the new impedance tube is fitted with a large stainless steel flange to better define the boundary condition on the plane of the tube opening. The new device was validated against the classic theoretical result for the complex reflection coefficient of a tube opening fitted with an infinite flange. The complex reflection coefficient was then measured with a bubbly liquid (order 250 micron radius and 0.1 - 0.5 % void fraction) outside the tube opening. Results from the bubbly liquid experiments were inconsistent with flanged tube theory using current bubbly liquid models. The results were more closely matched to unflanged tube theory, suggesting that the high attenuation and phase speeds in the bubbly liquid made the tube opening appear as if it were radiating into free space.

PROPAGATION OF SONIC BOOMS THROUGH A REAL, STRATIFIED ATMOSPHERE

Sonic boom propagation in a quiet) stratified) lossy atmosphere is the subject of this dissertation. Two questions are considered in detail: (1) Does waveform freezing occur? (2) Are sonic booms shocks in steady state? Both assumptions have been invoked in the past to predict sonic boom waveforms at the ground. A very general form of the Burgers equation is derived and used as the model for the problem. The derivation begins with the basic conservation equations. The effects of nonlinearity) attenuation and dispersion due to multiple relaxations) viscosity) and heat conduction) geometrical spreading) and stratification of the medium are included. When the absorption and dispersion terms are neglected) an analytical solution is available. The analytical solution is used to answer the first question. Geometrical spreading and stratification of the medium are found to slow down the nonlinear distortion of finite-amplitude waves. In certain cases the distortion reaches an absolute limit) a phenomenon called waveform freezing. Judging by the maturity of the distortion mechanism, sonic booms generated by aircraft at 18 km altitude are not frozen when they reach the ground. On the other hand, judging by the approach of the waveform to its asymptotic shape, N waves generated by aircraft at 18 km altitude are frozen when they reach the ground. To answer the second question we solve the full Burgers equation and for this purpose develop a new computer code, THOR. The code is based on an algorithm by Lee and Hamilton (J. Acoust. Soc. Am. 97, 906-917, 1995) and has the novel feature that all its calculations are done in the time domain, including absorption and dispersion. Results from the code compare very well with analytical solutions. In a NASA exercise to compare sonic boom computer programs, THOR gave results that agree well with those of other participants and ran faster. We show that sonic booms are not steady state waves because they travel through a varying medium, suffer spreading, and fail to approximate step shocks closely enough. Although developed to predict sonic boom propagation, THOR can solve other problems for which the extended Burgers equation is a good propagation model.

Genetically Generated Neural Networks I: Representational Effects

This paper studies several applications of genetic algorithms (GAs) within the neural networks field. After generating a robust GA engine, the system was used to generate neural network circuit architectures. This was accomplished by using the GA to determine the weights in a fully interconnected network. The importance of the internal genetic representation was shown by testing different approaches. The effects in speed of optimization of varying the constraints imposed upon the desired network were also studied. It was observed that relatively loose constraints provided results comparable to a fully constrained system. The type of neural network circuits generated were recurrent competitive fields as described by Grossberg (1982).

Genetically Generated Neural Networks II: Searching for an Optimal Representation

Genetic Algorithms (GAs) make use of an internal representation of a given system in order to perform optimization functions. The actual structural layout of this representation, called a genome, has a crucial impact on the outcome of the optimization process. The purpose of this paper is to study the effects of different internal representations in a GA, which generates neural networks. A second GA was used to optimize the genome structure. This structure produces an optimized system within a shorter time interval.