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The binding and interaction of proteins with nucleic acids such as DNA and RNA constitutes a fundamental biochemical and biophysical process in all living organisms. Identifying and visualizing such temporal interactions in cells is key to understanding their function. To image sites of these events in cells across scales, we developed a method, named PROMPT for PROximal Molecular Probe Transfer, which is applicable to both light and correlative electron microscopy. This method relies on the transfer of a bound photosensitizer from a protein known to associate with specific nucleic acid sequence, allowing the marking of the binding site on DNA or RNA in fixed cells. The method produces a fluorescent mark at the site of their interaction, that can be made electron dense and reimaged at high resolution in the electron microscope. As proof of principle, we labeled in situ the interaction sites between the histone H2B and nuclear DNA. As an example of application for specific RNA localizations we labeled different nuclear and nucleolar fractions of the protein Fibrillarin to mark and locate where it associates with RNAs, also using electron tomography. While the current PROMPT method is designed for microscopy, with minimal variations, it can be potentially expanded to analytical techniques. [ABSTRACT FROM AUTHOR]

Learning from demonstration, or imitation learning, is the process of learning to act in an environment from examples provided by a teacher. Inverse reinforcement learning (IRL) is a specific form of learning from demonstration that attempts to estimate the reward function of a Markov decision process from examples provided by the teacher. The reward function is often considered the most succinct description of a task. In simple applications, the reward function may be known or easily derived from properties of the system and hard coded into the learning process. However, in complex applications, this may not be possible, and it may be easier to learn the reward function by observing the actions of the teacher. This paper provides a comprehensive survey of the literature on IRL. This survey outlines the differences between IRL and two similar methods - apprenticeship learning and inverse optimal control. Further, this survey organizes the IRL literature based on the principal method, describes applications of IRL algorithms, and provides areas of future research. [ABSTRACT FROM AUTHOR]

Locally advanced cancers remain therapeutically challenging to eradicate. The most successful treatments continue to combine decades old non-targeted chemotherapies with radiotherapy that unfortunately increase normal tissue damage in the irradiated field and have systemic toxicities precluding further treatment intensification. Therefore, alternative molecularly guided systemic therapies are needed to improve patient outcomes when applied with radiotherapy. In this work, we report a trimodal precision cytotoxic chemo-radio-immunotherapy paradigm using spatially targeted auristatin warheads. Tumor-directed antibodies and peptides conjugated to radiosensitizing monomethyl auristatin E (MMAE) specifically produce CD8 T cell dependent durable tumor control of irradiated tumors and immunologic memory. In combination with ionizing radiation, MMAE sculpts the tumor immune infiltrate to potentiate immune checkpoint inhibition. Here, we report therapeutic synergies of targeted cytotoxic auristatin radiosensitization to stimulate anti-tumor immune responses providing a rationale for clinical translational of auristatin antibody drug conjugates with radio-immunotherapy combinations to improve tumor control. Monomethyl auristatin (MMAE), also known for its radiosensitizer properties, is a common antibody drug conjugate used for cancer therapy. Here the authors show that, in combination with radiotherapy, tumor-directed antibodies or peptides conjugated to MMAE promote anti-tumor immune responses, improving response to checkpoint inhibitors in preclinical cancer models. [ABSTRACT FROM AUTHOR]

Cyber-physical systems are complex systems that require the integration of diverse software, firmware, and hardware to be practical and useful. This increased complexity is impacting the management of models necessary for designing cyber-physical systems that are able to take into account a number of "-ilities", such that they are safe and secure and ultimately resilient to disruption of service. We propose an ontological metamodel for system design that augments an already existing industry metamodel to capture the relationships between various model elements (requirements, interfaces, physical, and functional) and safety, security, and resilient considerations. Employing this metamodel leads to more cohesive and structured modeling efforts with an overall increase in scalability, usability, and unification of already existing models. In turn, this leads to a mission-oriented perspective in designing security defenses and resilience mechanisms to combat undesirable behaviors. We illustrate this metamodel in an open-source GraphQL implementation, which can interface with a number of modeling languages. We support our proposed metamodel with a detailed demonstration using an oil and gas pipeline model. [ABSTRACT FROM AUTHOR]

Purpose: We aim to develop perfluorocarbon-based nanoemulsions with improved sensitivity for detection of inflammatory macrophages in situ using F-19 MRI. Towards this goal, we evaluate the feasibility of nanoemulsion formulation incorporating a metal chelate in the fluorous phase which shortens the F-19 longitudinal relaxation rate and image acquisition time.Procedures: Perfluorinated linear polymers were conjugated to metal-binding tris-diketonate, blended with unconjugated polymers, and emulsified in water. Phospholipid-based surfactant was used to stabilize nanoemulsion and provide biocompatibility. Nanoemulsions were metalated with the addition of ferric salt to the buffer. Physical stability of surfactant and nanoemulsion was evaluated by mass spectrometry and dynamic light scattering measurements. Nanoemulsions were injected intravenously into a murine granuloma inflammation model, and in vivo19F/1H MRI at 11.7 T was performed.Results: We demonstrated stability and biocompatibility of lipid-based paramagnetic nanoemulsions. We investigated potential oxidation of lipid in the presence of metal chelate. As a proof of concept, we performed non-invasive monitoring of macrophage burden in a murine inflammation model following intravenous injection of nanoemulsion using in vivo F-19 MRI.Conclusion: Lipid-based nanoemulsion probes of perfluorocarbon synthesized with iron-binding fluorinated β-diketones can be formulated for intravenous delivery and inflammation detection in vivo. [ABSTRACT FROM AUTHOR]

Feature selection is the process of reducing the number of collected features to a relevant subset of features and is often used to combat the curse of dimensionality. This paper provides a review of the literature on feature selection techniques specifically designed for Gaussian mixture models (GMMs) and hidden Markov models (HMMs), two common parametric latent variable models. The primary contribution of this work is the collection and grouping of feature selection methods specifically designed for GMMs and for HMMs. An additional contribution lies in outlining the connections between these two groups of feature selection methods. Often, feature selection methods for GMMs and HMMs are treated as separate topics. In this survey, we propose that methods developed for one model can be adapted to the other model. Further, we find that the number of feature selection methods for GMMs outweighs the number of methods for HMMs and that the proportion of methods for HMMs that require supervised data is larger than the proportion of GMM methods that require supervised data. We conclude that further research into unsupervised feature selection methods for HMMs is required and that established methods for GMMs could be adapted to HMMs. It should be noted that feature selection can also be referred to as dimensionality reduction, variable selection, attribute selection, and variable subset reduction. In this paper, we make a distinction between dimensionality reduction and feature selection. Dimensionality reduction, which we do not consider, is any process that reduces the number of features used in a model and can include methods that transform features in order to reduce the dimensionality. Feature selection, by contrast, is a specific form of dimensionality reduction that eliminates feature as inputs into the model. The primary difference is that dimensionality reduction can still require the collection of all the data sources in order to transform and reduce the feature set, while feature selection eliminates the need to collect the irrelevant data sources. [ABSTRACT FROM AUTHOR]

Simulation and data-driven models are both tools that can play an important role in reducing the energy consumption of buildings and homes. However, sophisticated control schemes and models are only as good as the data collected by sensors and provided to them. Low-quality or faulty sensor that provide inaccurate data can lead to inefficient buildings. In this paper, we investigate the relationship between sensor quality and the prediction of energy consumption. We first construct a simulation of appliance energy consumption in a smart home and then assess the predictive ability of several data-driven models while varying the quality and function of the simulated sensors. The simulation was constructed using a smart home data set collected by other researchers. We find that the predictive ability is only decreased when noise is added to the appliance energy random variable. We conclude that low-quality sensors that do not monitor the environment as accurately as the devices used in the original study could be used for humidity and temperature without significantly reducing the predictive ability of the data-driven models. The method and findings have implications for how to conduct cost-benefit analyses of IoT device requirements. [ABSTRACT FROM AUTHOR]

This paper investigates the feasibility of using inexpensive, general-purpose automated methods for recognition of worker activity in manufacturing processes. A novel aspect of this study is that it is based on live data collected from an operational manufacturing cell without any guided or scripted work. Activity in a single-worker cell was recorded using the Microsoft Kinect, a commodity-priced sensor that records depth data and includes built-in functions for the detection of human skeletal positions, including the positions of all major joints. Joint position data for two workers on different shifts was used as input to a collection of learning algorithms with the goal of classifying the activities of each worker at each moment in time. Results show that unsupervised and semisupervised algorithms, such as unsupervised hidden Markov models, show little loss of accuracy compared to supervised methods trained with ground truth data. This conclusion is important because it implies that automated activity recognition can be accomplished without the use of ground truth labels, which can only be obtained by time-consuming manual review of videos. The results of this study suggest that intelligent manufacturing can now include detailed process-control measures of human workers with systems that are affordable enough to be installed permanently for continuous data collection. [ABSTRACT FROM AUTHOR]

The Veterans Health Administration (VHA) is plagued by abnormally high no-show and cancellation rates that reduce the productivity and efficiency of its medical outpatient clinics. We address this issue by developing a dynamic scheduling system that utilizes mobile computing via geo-location data to estimate the likelihood of a patient arriving on time for a scheduled appointment. These likelihoods are used to update the clinic's schedule in real time. When a patient's arrival probability falls below a given threshold, the patient's appointment is canceled. This appointment is immediately reassigned to another patient drawn from a pool of patients who are actively seeking an appointment. The replacement patients are prioritized using their arrival probability. Real-world data were not available for this study, so synthetic patient data were generated to test the feasibility of the design. The method for predicting the arrival probability was verified on a real set of taxicab data. This study demonstrates that dynamic scheduling using geo-location data can reduce the number of unused appointments with minimal risk of double booking resulting from incorrect predictions. We acknowledge that there could be privacy concerns with regards to government possession of one's location and offer strategies for alleviating these concerns in our conclusion. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various articles within the issue on topics including Information retrieval (IR) in the intellectual property, cross-language retrieval, categorisation and image search in patents .

A comparison of the engineering schools at UC Berkeley and Stanford during the 1940s and 1950s shows that having an excellent academic program is necessary but not sufficient to make a university entrepreneurial (an engine of economic development). Key factors that made Stanford more entrepreneurial than Cal during this period were superior leadership and a focused strategy. The broader institutional context mattered as well. Stanford did not have the same access to state funding as public universities (such as Cal in the period under consideration) and some private universities (such as the Massachusetts Institute of Technology and the Johns Hopkins University in their early histories). Therefore, in order to gather resources, Stanford was forced to become entrepreneurial first, developing business skills (engaging with high-tech industry) at the same time Cal was developing political skills (protecting and increasing its state appropriation). Stanford’s early development of entrepreneurial business skills played a crucial role in the development of Silicon Valley. [ABSTRACT FROM AUTHOR]

B Correction to: Mol Imaging Biol (2020) 22: 665-674 b https://doi.org/10.1007/s11307-019-01415-5 This article was updated to correct the funding information. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The original article can be found online at https://doi.org/10.1007/s11307-019-01415-5. [Extracted from the article]

Intracellular Ca2+ regulates numerous proteins and cellular functions and can vary substantially over submicron and submillisecond scales, so precisely localized fast detection is desirable. We have created a ∼1-kDa biarsenical Ca2+ indicator, called Calcium Green FlAsH (CaGF, 1), to probe [Ca2+] surrounding genetically targeted proteins. CaGF attached to a tetracysteine motif becomes ten-fold more fluorescent upon binding Ca2+, with a Kd of ∼100 μM, <1-ms kinetics and good Mg2+ rejection. In HeLa cells expressing tetracysteine-tagged connexin 43, CaGF labels gap junctions and reports Ca2+ waves after injury. Total internal reflection microscopy of tetracysteine-tagged, CaGF-labeled α1C L-type calcium channels shows fast-rising depolarization-evoked Ca2+ transients, whose lateral nonuniformity suggests that the probability of channel opening varies greatly over micron dimensions. With moderate Ca2+ buffering, these transients decay surprisingly slowly, probably because most of the CaGF signal comes from closed channels feeling Ca2+ from a tiny minority of clustered open channels. With high Ca2+ buffering, CaGF signals decay as rapidly as the calcium currents, as expected for submicron Ca2+ domains immediately surrounding active channels. Thus CaGF can report highly localized, rapid [Ca2+] dynamics. [ABSTRACT FROM AUTHOR]

Membrane-permeant biarsenical dyes such as FlAsH and ReAsH fluoresce upon binding to genetically encoded tetracysteine motifs expressed in living cells, yet spontaneous nonspecific background staining can prevent detection of weakly expressed or dilute proteins. If the affinity of the tetracysteine peptide could be increased, more stringent dithiol washes should increase the contrast between specific and nonspecific staining. Residues surrounding the tetracysteine motif were randomized and fused to GFP, retrovirally transduced into mammalian cells and iteratively sorted by fluorescence-activated cell sorting for high FRET from GFP to ReAsH in the presence of increasing concentrations of dithiol competitors. The selected sequences show higher fluorescence quantum yields and markedly improved dithiol resistance, culminating in a >20-fold increase in contrast. The selected tetracysteine sequences, HRWCCPGCCKTF and FLNCCPGCCMEP, maintain their enhanced properties as fusions to either terminus of GFP or directly to β-actin. These improved biarsenical-tetracysteine motifs should enable detection of a much broader spectrum of cellular proteins. [ABSTRACT FROM AUTHOR]

Fluorescence resonance energy transfer (FRET) from cyan to yellow fluorescent proteins (CFP/YFP) is a well-established method to monitor protein-protein interactions or conformational changes of individual proteins. But protein functions can be perturbed by fusion of large tags such as CFP and YFP. Here we use G protein–coupled receptor (GPCR) activation in living cells as a model system to compare YFP with the small, membrane-permeant fluorescein derivative with two arsen-(III) substituents (fluorescein arsenical hairpin binder; FlAsH) targeted to a short tetracysteine sequence. Insertion of CFP and YFP into human adenosine A2A receptors allowed us to use FRET to monitor receptor activation but eliminated coupling to adenylyl cyclase. The CFP/FlAsH-tetracysteine system gave fivefold greater agonist-induced FRET signals, similar kinetics (time constant of 66–88 ms) and perfectly normal downstream signaling. Similar results were obtained for the mouse α2A-adrenergic receptor. Thus, FRET from CFP to FlAsH reports GPCR activation in living cells without disturbing receptor function and shows that the small size of the tetracysteine-biarsenical tag can be decisively advantageous. [ABSTRACT FROM AUTHOR]

Regulation of AMPA receptor (AMPAR) trafficking is important for neural plasticity. Here we examined the trafficking and synthesis of the GluR1 and GluR2 subunits using ReAsH-EDT2 and FlAsH-EDT2 staining. Activity blockade of rat cultured neurons increased dendritic GluR1, but not GluR2, levels. Examination of transected dendrites revealed that both AMPAR subunits were synthesized in dendrites and that activity blockade enhanced dendritic synthesis of GluR1 but not GluR2. In contrast, acute pharmacological manipulations increased dendritic synthesis of both subunits. AMPARs synthesized in dendrites were inserted into synaptic plasma membranes and, after activity blockade, the electrophysiological properties of native synaptic AMPARs changed in the manner predicted by the imaging experiments. In addition to providing a novel mechanism for synaptic modifications, these results point out the advantages of using FlAsH-EDT2 and ReAsH-EDT2 for studying the trafficking of newly synthesized proteins in local cellular compartments such as dendrites. [ABSTRACT FROM AUTHOR]

Studies of protein function would be facilitated by a general method to inactivate selected proteins in living cells noninvasively with high spatial and temporal precision. Chromophore-assisted light inactivation (CALI) uses photochemically generated, reactive oxygen species to inactivate proteins acutely, but its use has been limited by the need to microinject dye-labeled nonfunction-blocking antibodies. We now demonstrate CALI of connexin43 (Cx43) and a1C L-type calcium channels, each tagged with one or two small tetracysteine (TC) motifs that specifically bind the membrane-permeant, red biarsenical dye, ReAsH. ReAsH-based CALI is genetically targeted, requires no antibodies or microinjection, and inactivates each protein by ~90% in <30 s of widefield illumination. Similar light doses applied to Cx43 or a1C tagged with green fluorescent protein (GFP) had negligible to slight effects with or without ReAsH exposure, showing the expected molecular specificity. ReAsH-mediated CALI acts largely via singlet oxygen because quenchers or enhancers of singlet oxygen respectively inhibit or enhance CALI. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Cryo-Fluorescence Tomography as a Tool for Visualizing Whole-Body Inflammation Using Perfluorocarbon Nanoemulsion Tracers" published in the journal Molecular Imaging & Biology. The correction adds supplementary videos and captions to the original online version of the article. The correction notice also states that Springer Nature, the publisher, remains neutral regarding jurisdictional claims and institutional affiliations. The article was authored by Benjamin I. Leach, Deanne Lister, Stephen R. Adams, Julie Bykowski, Amy B. Schwartz, Patrick McConville, Hemi Dimant, and Eric T. Ahrens, who can be contacted via email at etanospam@gmail.com. The authors are affiliated with the Department of Radiology at the University of California, San Diego, the company Invicro LLC, and the Department of Pharmacology at the University of California, San Diego. [Extracted from the article]

This document is a correction to an article titled "Cryo-Fluorescence Tomography as a Tool for Visualizing Whole-Body Inflammation Using Perfluorocarbon Nanoemulsion Tracers" published in the journal Molecular Imaging & Biology. The correction states that the original online version of the article was revised to correct the image used as the graphical abstract. The correction does not provide any additional information or content beyond this correction. [Extracted from the article]

Purpose: We explore the use of intravenously delivered fluorescent perfluorocarbon (PFC) nanoemulsion tracers and multi-spectral cryo-fluorescence tomography (CFT) for whole-body tracer imaging in murine inflammation models. CFT is an emerging technique that provides high-resolution, three-dimensional mapping of probe localization in intact animals and tissue samples, enabling unbiased validation of probe biodistribution and minimizes reliance on laborious histological methods employing discrete tissue panels, where disseminated populations of PFC-labeled cells may be overlooked. This methodology can be used to streamline the development of new generations of non-invasive, cellular-molecular imaging probes for in vivo imaging.Mixtures of nanoemulsions with different fluorescent emission wavelengths were administered intravenously to naïve mice and models of acute inflammation, colitis, and solid tumor. Mice were euthanized 24 h post-injection, frozen en bloc, and imaged at high resolution (~ 50 µm voxels) using CFT at multiple wavelengths.PFC nanoemulsions were visualized using CFT within tissues of the reticuloendothelial system and inflammatory lesions, consistent with immune cell (macrophage) labeling, as previously reported in in vivo magnetic resonance and nuclear imaging studies. The CFT signals show pronounced differences among fluorescence wavelengths and tissues, presumably due to autofluorescence, differential fluorescence quenching, and scattering of incident and emitted light.CFT is an effective and complementary methodology to in vivo imaging for validating PFC nanoemulsion biodistribution at high spatial localization, bridging the resolution gap between in vivo imaging and histology.Procedures: We explore the use of intravenously delivered fluorescent perfluorocarbon (PFC) nanoemulsion tracers and multi-spectral cryo-fluorescence tomography (CFT) for whole-body tracer imaging in murine inflammation models. CFT is an emerging technique that provides high-resolution, three-dimensional mapping of probe localization in intact animals and tissue samples, enabling unbiased validation of probe biodistribution and minimizes reliance on laborious histological methods employing discrete tissue panels, where disseminated populations of PFC-labeled cells may be overlooked. This methodology can be used to streamline the development of new generations of non-invasive, cellular-molecular imaging probes for in vivo imaging.Mixtures of nanoemulsions with different fluorescent emission wavelengths were administered intravenously to naïve mice and models of acute inflammation, colitis, and solid tumor. Mice were euthanized 24 h post-injection, frozen en bloc, and imaged at high resolution (~ 50 µm voxels) using CFT at multiple wavelengths.PFC nanoemulsions were visualized using CFT within tissues of the reticuloendothelial system and inflammatory lesions, consistent with immune cell (macrophage) labeling, as previously reported in in vivo magnetic resonance and nuclear imaging studies. The CFT signals show pronounced differences among fluorescence wavelengths and tissues, presumably due to autofluorescence, differential fluorescence quenching, and scattering of incident and emitted light.CFT is an effective and complementary methodology to in vivo imaging for validating PFC nanoemulsion biodistribution at high spatial localization, bridging the resolution gap between in vivo imaging and histology.Results: We explore the use of intravenously delivered fluorescent perfluorocarbon (PFC) nanoemulsion tracers and multi-spectral cryo-fluorescence tomography (CFT) for whole-body tracer imaging in murine inflammation models. CFT is an emerging technique that provides high-resolution, three-dimensional mapping of probe localization in intact animals and tissue samples, enabling unbiased validation of probe biodistribution and minimizes reliance on laborious histological methods employing discrete tissue panels, where disseminated populations of PFC-labeled cells may be overlooked. This methodology can be used to streamline the development of new generations of non-invasive, cellular-molecular imaging probes for in vivo imaging.Mixtures of nanoemulsions with different fluorescent emission wavelengths were administered intravenously to naïve mice and models of acute inflammation, colitis, and solid tumor. Mice were euthanized 24 h post-injection, frozen en bloc, and imaged at high resolution (~ 50 µm voxels) using CFT at multiple wavelengths.PFC nanoemulsions were visualized using CFT within tissues of the reticuloendothelial system and inflammatory lesions, consistent with immune cell (macrophage) labeling, as previously reported in in vivo magnetic resonance and nuclear imaging studies. The CFT signals show pronounced differences among fluorescence wavelengths and tissues, presumably due to autofluorescence, differential fluorescence quenching, and scattering of incident and emitted light.CFT is an effective and complementary methodology to in vivo imaging for validating PFC nanoemulsion biodistribution at high spatial localization, bridging the resolution gap between in vivo imaging and histology.Conclusions: We explore the use of intravenously delivered fluorescent perfluorocarbon (PFC) nanoemulsion tracers and multi-spectral cryo-fluorescence tomography (CFT) for whole-body tracer imaging in murine inflammation models. CFT is an emerging technique that provides high-resolution, three-dimensional mapping of probe localization in intact animals and tissue samples, enabling unbiased validation of probe biodistribution and minimizes reliance on laborious histological methods employing discrete tissue panels, where disseminated populations of PFC-labeled cells may be overlooked. This methodology can be used to streamline the development of new generations of non-invasive, cellular-molecular imaging probes for in vivo imaging.Mixtures of nanoemulsions with different fluorescent emission wavelengths were administered intravenously to naïve mice and models of acute inflammation, colitis, and solid tumor. Mice were euthanized 24 h post-injection, frozen en bloc, and imaged at high resolution (~ 50 µm voxels) using CFT at multiple wavelengths.PFC nanoemulsions were visualized using CFT within tissues of the reticuloendothelial system and inflammatory lesions, consistent with immune cell (macrophage) labeling, as previously reported in in vivo magnetic resonance and nuclear imaging studies. The CFT signals show pronounced differences among fluorescence wavelengths and tissues, presumably due to autofluorescence, differential fluorescence quenching, and scattering of incident and emitted light.CFT is an effective and complementary methodology to in vivo imaging for validating PFC nanoemulsion biodistribution at high spatial localization, bridging the resolution gap between in vivo imaging and histology.Graphical Abstract: We explore the use of intravenously delivered fluorescent perfluorocarbon (PFC) nanoemulsion tracers and multi-spectral cryo-fluorescence tomography (CFT) for whole-body tracer imaging in murine inflammation models. CFT is an emerging technique that provides high-resolution, three-dimensional mapping of probe localization in intact animals and tissue samples, enabling unbiased validation of probe biodistribution and minimizes reliance on laborious histological methods employing discrete tissue panels, where disseminated populations of PFC-labeled cells may be overlooked. This methodology can be used to streamline the development of new generations of non-invasive, cellular-molecular imaging probes for in vivo imaging.Mixtures of nanoemulsions with different fluorescent emission wavelengths were administered intravenously to naïve mice and models of acute inflammation, colitis, and solid tumor. Mice were euthanized 24 h post-injection, frozen en bloc, and imaged at high resolution (~ 50 µm voxels) using CFT at multiple wavelengths.PFC nanoemulsions were visualized using CFT within tissues of the reticuloendothelial system and inflammatory lesions, consistent with immune cell (macrophage) labeling, as previously reported in in vivo magnetic resonance and nuclear imaging studies. The CFT signals show pronounced differences among fluorescence wavelengths and tissues, presumably due to autofluorescence, differential fluorescence quenching, and scattering of incident and emitted light.CFT is an effective and complementary methodology to in vivo imaging for validating PFC nanoemulsion biodistribution at high spatial localization, bridging the resolution gap between in vivo imaging and histology. [ABSTRACT FROM AUTHOR]

To identify perceptions that predict overall patient (dis)satisfaction with Emergency Department (ED) care, we studied responses to a survey mailed to all discharged patients over a 6-month period (Academic Hospital), and to a telephone interview of a random sample of discharged patients over a 1-year period (Community Hospital). The survey and interview both assessed overall satisfaction, as well as satisfaction with perceived waiting times, information delivery, and expressive quality of physicians, nurses, and staff. Data for 1176 patients (training sample) and 1101 patients (holdout sample) who rated overall satisfaction as either “very good” or “very poor” (Academic Hospital), and for 856 patients (training sample) and 431 patients (holdout sample) who rated overall satisfaction as either “excellent” or “poor” (Community Hospital), were retained for analysis. For both hospitals, nonlinear tree models efficiently achieved overall classification accuracy exceeding 98% in training analysis and 95% in holdout analysis (all p < .0001). The findings suggest that overall patient (dis)satisfaction with care received in the ED is nearly perfectly predictable on the basis of patient-rated expressive qualities of ED staff, particularly physicians and nurses. Interventions designed to reinforce positive (and extinguish negative) expressive health-care provider behaviors may cut the number of extremely dissatisfied patients in half. [ABSTRACT FROM AUTHOR]

Isoniazid (INH) continues to be a highly effective drug in the chemoprophylaxis and treatment of tuberculosis; however, its use is associated with hepatotoxicity (predominantly hepatic necrosis) in 1-2% of individuals. The INH metabolites, acetylhydrazine and hydrazine, have each been implicated as the causative hepatotoxin in INH-induced hepatotoxicity. Using a model of INH-induced hepatotoxicity in rabbits, in which INH-induced hepatotoxicity manifests as hepatic necrosis, hepatic steatosis (hepatic fat accumulation) and hypertriglyceridaemia (elevated plasma triglycerides), we compared the severity of these measures of toxicity with plasma levels of INH, acetylhydrazine and hydrazine. Plasma INH and acetylhydrazine were not correlated with markers of INH-induced hepatic necrosis or fatty changes. Plasma hydrazine at 32 h was correlated significantly with plasma argininosuccinic acid lyase (ASAL, a sensitive marker of hepatic necrosis) activity as area under the curve ( r =0.54, P<0.002) and log plasma ASAL activity at 48 h after the first dose of INH ( r =0.53, p<0.005), but not with fatty changes. These results show in this model of INH-induced hepatotoxicity in rabbits that hydrazine, and not INH or acetylhydrazine, is most likely involved in the pathogenic mechanism of hepatic necrosis. [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained a mistake. The name of Matthew Gerber was incorrectly spelled as Mathew Gerber. The correct spelling is now presented correctly in this correction article. [ABSTRACT FROM AUTHOR]