Quantifying data quality for clinical trials using electronic data capture.

BACKGROUND: Historically, only partial assessments of data quality have been performed in clinical trials, for which the most common method of measuring database error rates has been to compare the case report form (CRF) to database entries and count discrepancies. Importantly, errors arising from medical record abstraction and transcription are rarely evaluated as part of such quality assessments. Electronic Data Capture (EDC) technology has had a further impact, as paper CRFs typically leveraged for quality measurement are not used in EDC processes. METHODS AND PRINCIPAL FINDINGS: The National Institute on Drug Abuse Treatment Clinical Trials Network has developed, implemented, and evaluated methodology for holistically assessing data quality on EDC trials. We characterize the average source-to-database error rate (14.3 errors per 10,000 fields) for the first year of use of the new evaluation method. This error rate was significantly lower than the average of published error rates for source-to-database audits, and was similar to CRF-to-database error rates reported in the published literature. We attribute this largely to an absence of medical record abstraction on the trials we examined, and to an outpatient setting characterized by less acute patient conditions. CONCLUSIONS: Historically, medical record abstraction is the most significant source of error by an order of magnitude, and should be measured and managed during the course of clinical trials. Source-to-database error rates are highly dependent on the amount of structured data collection in the clinical setting and on the complexity of the medical record, dependencies that should be considered when developing data quality benchmarks.

Information-theoretic analysis of a stimulated-Brillouin-scattering-based slow-light system.

We use an information-theoretic method developed by Neifeld and Lee [J. Opt. Soc. Am. A 25, C31 (2008)] to analyze the performance of a slow-light system. Slow-light is realized in this system via stimulated Brillouin scattering in a 2 km-long, room-temperature, highly nonlinear fiber pumped by a laser whose spectrum is tailored and broadened to 5 GHz. We compute the information throughput (IT), which quantifies the fraction of information transferred from the source to the receiver and the information delay (ID), which quantifies the delay of a data stream at which the information transfer is largest, for a range of experimental parameters. We also measure the eye-opening (EO) and signal-to-noise ratio (SNR) of the transmitted data stream and find that they scale in a similar fashion to the information-theoretic method. Our experimental findings are compared to a model of the slow-light system that accounts for all pertinent noise sources in the system as well as data-pulse distortion due to the filtering effect of the SBS process. The agreement between our observations and the predictions of our model is very good. Furthermore, we compare measurements of the IT for an optimal flattop gain profile and for a Gaussian-shaped gain profile. For a given pump-beam power, we find that the optimal profile gives a 36% larger ID and somewhat higher IT compared to the Gaussian profile. Specifically, the optimal (Gaussian) profile produces a fractional slow-light ID of 0.94 (0.69) and an IT of 0.86 (0.86) at a pump-beam power of 450 mW and a data rate of 2.5 Gbps. Thus, the optimal profile better utilizes the available pump-beam power, which is often a valuable resource in a system design.

Design of Latent Thermal Energy Storage Systems

This dissertation documents the results of a theoretical and numerical study of time dependent storage of energy by melting a phase change material. The heating is provided along invading lines, which change from single-line invasion to tree-shaped invasion. Chapter 2 identifies the special design feature of distributing energy storage in time-dependent fashion on a territory, when the energy flows by fluid flow from a concentrated source to points (users) distributed equidistantly on the area. The challenge in this chapter is to determine the architecture of distributed energy storage. The chief conclusion is that the finite amount of storage material should be distributed proportionally with the distribution of the flow rate of heating agent arriving on the area. The total time needed by the source stream to ‘invade’ the area is cumulative (the sum of the storage times required at each storage site), and depends on the energy distribution paths and the sequence in which the users are served by the source stream. Chapter 3 shows theoretically that the melting process consists of two phases: “invasion” thermal diffusion along the invading line, which is followed by “consolidation” as heat diffuses perpendicularly to the invading line. This chapter also reports the duration of both phases and the evolution of the melt layer around the invading line during the two-dimensional and three-dimensional invasion. It also shows that the amount of melted material increases in time according to a curve shaped as an S. These theoretical predictions are validated by means of numerical simulations in chapter 4. This chapter also shows that the heat transfer rate density increases (i.e., the S curve becomes steeper) as the complexity and number of degrees of freedom of the structure are increased, in accord with the constructal law. The optimal geometric features of the tree structure are detailed in this chapter. Chapter 5 documents a numerical study of time-dependent melting where the heat transfer is convection dominated, unlike in chapter 3 and 4 where the melting is ruled by pure conduction. In accord with constructal design, the search is for effective heat-flow architectures. The volume-constrained improvement of the designs for heat flow begins with assuming the simplest structure, where a single line serves as heat source. Next, the heat source is endowed with freedom to change its shape as it grows. The objective of the numerical simulations is to discover the geometric features that lead to the fastest melting process. The results show that the heat transfer rate density increases as the complexity and number of degrees of freedom of the structure are increased. Furthermore, the angles between heat invasion lines have a minor effect on the global performance compared to other degrees of freedom: number of branching levels, stem length, and branch lengths. The effect of natural convection in the melt zone is documented.

Passive Acoustics: A Multifaceted Tool for Marine Mammal Conservation

Marine mammals exploit the efficiency of sound propagation in the marine environment for essential activities like communication and navigation. For this reason, passive acoustics has particularly high potential for marine mammal studies, especially those aimed at population management and conservation. Despite the rapid realization of this potential through a growing number of studies, much crucial information remains unknown or poorly understood. This research attempts to address two key knowledge gaps, using the well-studied bottlenose dolphin (Tursiops truncatus) as a model species, and underwater acoustic recordings collected on four fixed autonomous sensors deployed at multiple locations in Sarasota Bay, Florida, between September 2012 and August 2013. Underwater noise can hinder dolphin communication. The ability of these animals to overcome this obstacle was examined using recorded noise and dolphin whistles. I found that bottlenose dolphins are able to compensate for increased noise in their environment using a wide range of strategies employed in a singular fashion or in various combinations, depending on the frequency content of the noise, noise source, and time of day. These strategies include modifying whistle frequency characteristics, increasing whistle duration, and increasing whistle redundancy. Recordings were also used to evaluate the performance of six recently developed passive acoustic abundance estimation methods, by comparing their results to the true abundance of animals, obtained via a census conducted within the same area and time period. The methods employed were broadly divided into two categories – those involving direct counts of animals, and those involving counts of cues (signature whistles). The animal-based methods were traditional capture-recapture, spatially explicit capture-recapture (SECR), and an approach that blends the “snapshot” method and mark-recapture distance sampling, referred to here as (SMRDS). The cue-based methods were conventional distance sampling (CDS), an acoustic modeling approach involving the use of the passive sonar equation, and SECR. In the latter approach, detection probability was modelled as a function of sound transmission loss, rather than the Euclidean distance typically used. Of these methods, while SMRDS produced the most accurate estimate, SECR demonstrated the greatest potential for broad applicability to other species and locations, with minimal to no auxiliary data, such as distance from sound source to detector(s), which is often difficult to obtain. This was especially true when this method was compared to traditional capture-recapture results, which greatly underestimated abundance, despite attempts to account for major unmodelled heterogeneity. Furthermore, the incorporation of non-Euclidean distance significantly improved model accuracy. The acoustic modelling approach performed similarly to CDS, but both methods also strongly underestimated abundance. In particular, CDS proved to be inefficient. This approach requires at least 3 sensors for localization at a single point. It was also difficult to obtain accurate distances, and the sample size was greatly reduced by the failure to detect some whistles on all three recorders. As a result, this approach is not recommended for marine mammal abundance estimation when few recorders are available, or in high sound attenuation environments with relatively low sample sizes. It is hoped that these results lead to more informed management decisions, and therefore, more effective species conservation.

Experimental Study of Storage Ring Free-Electron Laser with Novel Capabilities

The Duke Free-electron laser (FEL) system, driven by the Duke electron storage ring, has been at the forefront of developing new light source capabilities over the past two decades. In 1999, the Duke FEL demonstrated the first lasing of a storage ring FEL in the vacuum ultraviolet (VUV) region at $194$ nm using two planar OK-4 undulators. With two helical undulators added to the outboard sides of the planar undulators, in 2005 the highest FEL gain ($47.8\%$) of a storage ring FEL was achieved using the Duke FEL system with a four-undulator configuration. In addition, the Duke FEL has been used as the photon source to drive the High Intensity $\gamma$-ray Source (HIGS) via Compton scattering of the FEL beam and electron beam inside the FEL cavity. Taking advantage of FEL's wavelength tunability as well as the adjustability of the energy of the electron beam in the storage ring, the nearly monochromatic $\gamma$-ray beam has been produced in a wide energy range from $1$ to $100$ MeV at the HIGS. To further push the FEL short wavelength limit and enhance the FEL gain in the VUV regime for high energy $\gamma$-ray production, two additional helical undulators were installed in 2012 using an undulator switchyard system to allow switching between the two planar and two helical undulators in the middle section of the FEL system. Using different undulator configurations made possible by the switchyard, a number of novel capabilities of the storage ring FEL have been developed and exploited for a wide FEL wavelength range from infrared (IR) to VUV. These new capabilities will eventually be made available to the $\gamma$-ray operation, which will greatly enhance the $\gamma$-ray user research program, creating new opportunities for certain types of nuclear physics research.

With the wide wavelength tuning range, the FEL is an intrinsically well-suited device to produce lasing with multiple colors. Taking advantage of the availability of an undulator system with multiple undulators, we have demonstrated the first two-color lasing of a storage ring FEL. Using either a three- or four-undulator configuration with a pair of dual-band high reflectivity mirrors, we have achieved simultaneous lasing in the IR and UV spectral regions. With the low-gain feature of the storage ring FEL, the power generated at the two wavelengths can be equally built up and precisely balanced to reach FEL saturation. A systematic experimental program to characterize this two-color FEL has been carried out, including precise power control, a study of the power stability of two-color lasing, wavelength tuning, and the impact of the FEL mirror degradation. Using this two-color laser, we have started to develop a new two-color $\gamma$-ray beam for scientific research at the HIGS.

Using the undulator switchyard, four helical undulators installed in the beamline can be configured to not only enhance the FEL gain in the VUV regime, but also allow for the full polarization control of the FEL beams. For the accelerator operation, the use of helical undulators is essential to extend the FEL mirror lifetime by reducing radiation damage from harmonic undulator radiation. Using a pair of helical undulators with opposite helicities, we have realized (1) fast helicity switching between left- and right-circular polarizations, and (2) the generation of fully controllable linear polarization. In order to extend these new capabilities of polarization control to the $\gamma$-ray operation in a wide energy range at the HIGS, a set of FEL polarization diagnostic systems need to be developed to cover the entire FEL wavelength range. The preliminary development of the polarization diagnostics for the wavelength range from IR to UV has been carried out.

Estimation of in-canopy ammonia sources and sinks in a fertilized Zea mays field.

An analytical model was developed to describe in-canopy vertical distribution of ammonia (NH(3)) sources and sinks and vertical fluxes in a fertilized agricultural setting using measured in-canopy mean NH(3) concentration and wind speed profiles. This model was applied to quantify in-canopy air-surface exchange rates and above-canopy NH(3) fluxes in a fertilized corn (Zea mays) field. Modeled air-canopy NH(3) fluxes agreed well with independent above-canopy flux estimates. Based on the model results, the urea fertilized soil surface was a consistent source of NH(3) one month following the fertilizer application, whereas the vegetation canopy was typically a net NH(3) sink with the lower portion of the canopy being a constant sink. The model results suggested that the canopy was a sink for some 70% of the estimated soil NH(3) emissions. A logical conclusion is that parametrization of within-canopy processes in air quality models are necessary to explore the impact of agricultural field level management practices on regional air quality. Moreover, there are agronomic and environmental benefits to timing liquid fertilizer applications as close to canopy closure as possible. Finally, given the large within-canopy mean NH(3) concentration gradients in such agricultural settings, a discussion about the suitability of the proposed model is also presented.

A subcortical source of visual input to the frontal eye field

Many neurons in the frontal eye field (FEF) exhibit visual responses and are thought to play important roles in visuosaccadic behavior. The FEF, however, is far removed from striate cortex. Where do the FEF's visual signals come from? Usually they are reasonably assumed to enter the FEF through afferents from extrastriate cortex. Here we show that, surprisingly, visual signals also enter the FEF through a subcortical route: a disynaptic, ascending pathway originating in the intermediate layers of the superior colliculus (SC). We recorded from identified neurons at all three stages of this pathway (n=30-40 in each sample): FEF recipient neurons, orthodromically activated from the SC; mediodorsal thalamus (MD) relay neurons, antidromically activated from FEF and orthodromically activated from SC; and SC source neurons, antidromically activated from MD. We studied the neurons while monkeys performed delayed saccade tasks designed to temporally resolve visual responses from presaccadic discharges. We found, first, that most neurons at every stage in the pathway had visual responses, presaccadic bursts, or both. Second, we found marked similarities between the SC source neurons and MD relay neurons: in both samples, about 15% of the neurons had only a visual response, 10% had only a presaccadic burst, and 75% had both. In contrast, FEF recipient neurons tended to be more visual in nature: 50% had only a visual response, none had only a presaccadic burst, and 50% had both a visual response and a presaccadic burst. This suggests that in addition to their subcortical inputs, these FEF neurons also receive other visual inputs, e.g. from extrastriate cortex. We conclude that visual activity in the FEF results not only from cortical afferents but also from subcortical inputs. Intriguingly, this implies that some of the visual signals in FEF are pre-processed by the SC.