Learning and validating clinically meaningful phenotypes from electronic health data

The ever-growing adoption of electronic health records (EHR) to record patients' health journeys has resulted in vast amounts of heterogeneous, complex, and unwieldy information [Hripcsak and Albers, 2013]. Distilling this raw data into clinical insights presents great opportunities and challenges for the research and medical communities. One approach to this distillation is called computational phenotyping. Computational phenotyping is the process of extracting clinically relevant and interesting characteristics from a set of clinical documentation, such as that which is recorded in electronic health records (EHRs). Clinicians can use computational phenotyping, which can be viewed as a form of dimensionality reduction where a set of phenotypes form a latent space, to reason about populations, identify patients for randomized case-control studies, and extrapolate patient disease trajectories. In recent years, high-throughput computational approaches have made strides in extracting potentially clinically interesting phenotypes from data contained in EHR systems. Tensor factorization methods have shown particular promise in deriving phenotypes. However, phenotyping methods via tensor factorization have the following weaknesses: 1) the extracted phenotypes can lack diversity, which makes them more difficult for clinicians to reason about and utilize in practice, 2) many of the tensor factorization methods are unsupervised and do not utilize side information that may be available about the population or about the relationships between the clinical characteristics in the data (e.g., diagnoses and medications), and 3) validating the clinical relevance of the extracted phenotypes requires domain training and expertise. This dissertation addresses all three of these limitations. First, we present tensor factorization methods that discover sparse and concise phenotypes in unsupervised, supervised, and semi-supervised settings. Second, via two tools we built, we show how to leverage domain expertise in the form of publicly available medical articles to evaluate the clinical validity of the discovered phenotypes. Third, we combine tensor factorization and the phenotype validation tools to guide the discovery process to more clinically relevant phenotypes.Computational Science, Engineering, and Mathematic

Quantum information with continuous variables

Quantum information is a rapidly advancing area of interdisciplinary research. It may lead to real-world applications for communication and computation unavailable without the exploitation of quantum properties such as nonorthogonality or entanglement. We review the progress in quantum information based on continuous quantum variables, with emphasis on quantum optical implementations in terms of the quadrature amplitudes of the electromagnetic field.Comment: accepted for publication in Reviews of Modern Physic

Design and performance analysis of a picosecond-pulsed laser raman spectrometer for fluorescence rejection in raman spectroscopy

Many attempts have been made to reduce fluorescence backgrounds in Raman spectra. A critical appraisal of fluoresence rejection techniques reveals that while many techniques are available which improve the Raman/fluorescence ratio (R/F), very few actually increase the spectral signal/noise (R/N), which is the most important parameter. Temporal-resolution of Raman and fluorescence photons was investigated in this laboratory, using a picosecond-laser system and gated photon detection. Two detection methods were evaluated. The first, an intensified diode array detector (DAD), could be gated "on" for periods of ca. 5 ns, at rates of up to 5kHz. This gave a 5-fold increase in R/F, but a slight reduction in R/N, for a fluorescor with τ(_f) ̴̱ 1O.5 ns. The R/N degradation arose as a result of the low laser output intensity at kHz pulse rates, rather than inefficiency in fluorescence rejection. The second method used a continuously-operated photomultiplie tube (PMT), and time-correlated photon counting with ca. 1 ns timing-resolution. This yielded R/F and R/N improvements of ca. 15 and 3 respectively (τ(_f) ̴̱ 12 ns).Although efficient fluorescence rejection was obtained with each system, the corresponding R/N enhancements were not practically significant. However, the development of theoretical models describing the performance of each system has identified modifications which should give valuable improvements. These include the use of a laser with MW peak powers at kHz pulse rates (DAD system), and use of a microchannel-plate PMT with 50 ps timing resolution. When these (and other) modifications are made, significant R/N enhancements (ca. 7 and 13 (DAD and PMT systems respectively)) are expected, thus enabling the study of the majority of "real world" samples. In addition, the limiting theoretical and practical performance of time-resolved rejection is considered, and several hitherto unreported aspects of the behaviour of the laser and detection systems are discussed. Other techniques were also evaluated, in particular utilising the differing Raman and fluorescence response to variations in laser intensity. While the non-linear fluorescence responseto intensity variations of cw lasers has been previously exploited, simple calculations indicate that the use of high-powered pulsed sources could allow discrimination at ca. 100- fold lower average powers. However, a satisfactory test of the calculations requires the construction of apparatus not presently available in this .laboratory

Proceedings of the Thirteenth International Conference on Time-Resolved Vibrational Spectroscopy

The thirteenth meeting in a long-standing series of “Time-Resolved Vibrational Spectroscopy” (TRVS) conferences was held May 19th to 25th at the Kardinal Döpfner Haus in Freising, Germany, organized by the two Munich Universities - Ludwig-Maximilians-Universität and Technische Universität München. This international conference continues the illustrious tradition of the original in 1982, which took place in Lake Placid, NY. The series of meetings was initiated by leading, world-renowned experts in the field of ultrafast laser spectroscopy, and is still guided by its founder, Prof. George Atkinson (University of Arizona and Science and Technology Advisor to the Secretary of State). In its current format, the conference contributes to traditional areas of time resolved vibrational spectroscopies including infrared, Raman and related laser methods. It combines them with the most recent developments to gain new information for research and novel technical applications. The scientific program addressed basic science, applied research and advancing novel commercial applications. The thirteenth conference on Time Resolved Vibrational Spectroscopy promoted science in the areas of physics, chemistry and biology with a strong focus on biochemistry and material science. Vibrational spectra are molecule- and bond-specific. Thus, time-resolved vibrational studies provide detailed structural and kinetic information about primary dynamical processes on the picometer length scale. From this perspective, the goal of achieving a complete understanding of complex chemical and physical processes on the molecular level is well pursued by the recent progress in experimental and theoretical vibrational studies. These proceedings collect research papers presented at the TRVS XIII in Freising, German

Charge, spin and pseudospin in graphene

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 2008.Includes bibliographical references (p. 167-180).Graphene, a one-atom-thick form of carbon, has emerged in the last few years as a fertile electron system, highly promising for both fundamental research and applications. In this thesis we consider several topics in electronic and spin properties of graphene, with a particular emphasis on the quantum Hall effect (QHE) regime, where this material exhibits most interesting behavior. We shall start with analyzing general properties of the two-terminal conductance for graphene mono- and bilayer samples. Using conformal invariance and the theory of conformal mappings, we characterize the dependence of conductance on the sample shape. We identify the features which distinguish monolayers and bilayers and illustrate the use of the two-terminal conductance as a tool for sample diagnostic. Next, we present a microscopic study of the edge states in the QHE regime. This analysis provides a simple and general explanation of the half-integer Hall quantization in graphene. We discuss the edge states dispersion for different orientations of the boundary, and propose a way to image the edge states using STM spectroscopy. Then, we extend the picture of edge states to describe QHE in spatially nonuniform systems, recently demonstrated p-n and p-n-p devices. We show that the bipolar p-n and p-n-p junctions can host counter-circulating QHE edge states, which mix at the p-n interfaces, giving rise to fractional and integer quantization of the two-terminal conductance, observed in this structures. Graphene exhibits interesting spin- and valley-polarized QH ferromagnetic (FM) states. We show that spin-polarized QH state at zero doping hosts counter-circulating edge states carrying opposite spins, and propose to use this regime as a vehicle to study spin transport. We study ordering in the valley-polarized QH state.(cont.) Coupling of valley QHFM order parameter to random strain-induced vector potential yields an easy-plane-type ordering of the valley QHFM, giving rise to Berezinskii-Kosterlitz-Thouless transition, with fractionally charged vortices (merons) in the ordered state.by Dmitry A. Abanin.Ph.D

Vibrational Spectroscopic Map, Vibrational Spectroscopy, and Intermolecular Interaction

© 2020 American Chemical Society. Vibrational spectroscopy is an essential tool in chemical analyses, biological assays, and studies of functional materials. Over the past decade, various coherent nonlinear vibrational spectroscopic techniques have been developed and enabled researchers to study time-correlations of the fluctuating frequencies that are directly related to solute-solvent dynamics, dynamical changes in molecular conformations and local electrostatic environments, chemical and biochemical reactions, protein structural dynamics and functions, characteristic processes of functional materials, and so on. In order to gain incisive and quantitative information on the local electrostatic environment, molecular conformation, protein structure and interprotein contacts, ligand binding kinetics, and electric and optical properties of functional materials, a variety of vibrational probes have been developed and site-specifically incorporated into molecular, biological, and material systems for time-resolved vibrational spectroscopic investigation. However, still, an all-encompassing theory that describes the vibrational solvatochromism, electrochromism, and dynamic fluctuation of vibrational frequencies has not been completely established mainly due to the intrinsic complexity of intermolecular interactions in condensed phases. In particular, the amount of data obtained from the linear and nonlinear vibrational spectroscopic experiments has been rapidly increasing, but the lack of a quantitative method to interpret these measurements has been one major obstacle in broadening the applications of these methods. Among various theoretical models, one of the most successful approaches is a semiempirical model generally referred to as the vibrational spectroscopic map that is based on a rigorous theory of intermolecular interactions. Recently, genetic algorithm, neural network, and machine learning approaches have been applied to the development of vibrational solvatochromism theory. In this review, we provide comprehensive descriptions of the theoretical foundation and various examples showing its extraordinary successes in the interpretations of experimental observations. In addition, a brief introduction to a newly created repository Web site (http://frequencymap.org) for vibrational spectroscopic maps is presented. We anticipate that a combination of the vibrational frequency map approach and state-of-the-art multidimensional vibrational spectroscopy will be one of the most fruitful ways to study the structure and dynamics of chemical, biological, and functional molecular systems in the future

Third International Workshop on Squeezed States and Uncertainty Relations

The purpose of these workshops is to bring together an international selection of scientists to discuss the latest developments in Squeezed States in various branches of physics, and in the understanding of the foundations of quantum mechanics. At the third workshop, special attention was given to the influence that quantum optics is having on our understanding of quantum measurement theory. The fourth meeting in this series will be held in the People's Republic of China

Recent Progress in Optical Fiber Research

This book presents a comprehensive account of the recent progress in optical fiber research. It consists of four sections with 20 chapters covering the topics of nonlinear and polarisation effects in optical fibers, photonic crystal fibers and new applications for optical fibers. Section 1 reviews nonlinear effects in optical fibers in terms of theoretical analysis, experiments and applications. Section 2 presents polarization mode dispersion, chromatic dispersion and polarization dependent losses in optical fibers, fiber birefringence effects and spun fibers. Section 3 and 4 cover the topics of photonic crystal fibers and a new trend of optical fiber applications. Edited by three scientists with wide knowledge and experience in the field of fiber optics and photonics, the book brings together leading academics and practitioners in a comprehensive and incisive treatment of the subject. This is an essential point of reference for researchers working and teaching in optical fiber technologies, and for industrial users who need to be aware of current developments in optical fiber research areas

Aeronautical engineerng: A special bibliography with indexes, supplement 36

This special bibliography lists 628 reports, articles, and other documents introduced into the NASA scientific and technical information system in September 1973