User-Centered Evaluation of a Visual Annotation Tool for Rapid Assessment of Pediatric Weight Entry Errors.

Weight entry errors can cause significant patient harm in pediatrics due to pervasive weight-based dosing practices. While computerized algorithms can assist in error detection, they have not achieved high sensitivity and specificity to be further developed as a clinical decision support tool. To train an advanced algorithm, expert-annotated weight errors are essential but difficult to collect. In this study, we developed a visual annotation tool to gather large amounts of expertly annotated pediatric weight charts and conducted a formal user-centered evaluation. Key features of the tool included configurable grid sizes and annotation styles. The user feedback was collected through a structured survey and user clicks on the interface. The results show that the visual annotation tool has high usability (average SUS=86.4). Different combinations of the key features, however, did not significantly improve the annotation efficiency and duration. We have used this tool to collect expert annotations for algorithm development and benchmarking.

An interactive online dashboard for tracking COVID-19 in U.S. counties, cities, and states in real time.

OBJECTIVE: The study sought to create an online resource that informs the public of coronavirus disease 2019 (COVID-19) outbreaks in their area. MATERIALS AND METHODS: This R Shiny application aggregates data from multiple resources that track COVID-19 and visualizes them through an interactive, online dashboard. RESULTS: The Web resource, called the COVID-19 Watcher, can be accessed online (https://covid19watcher.research.cchmc.org/). It displays COVID-19 data from every county and 188 metropolitan areas in the United States. Features include rankings of the worst-affected areas and auto-generating plots that depict temporal changes in testing capacity, cases, and deaths. DISCUSSION: The Centers for Disease Control and Prevention does not publish COVID-19 data for local municipalities, so it is critical that academic resources fill this void so the public can stay informed. The data used have limitations and likely underestimate the scale of the outbreak. CONCLUSIONS: The COVID-19 Watcher can provide the public with real-time updates of outbreaks in their area.

Feedback at the Point of Care to Decrease Medication Alert Rates in an Electronic Health Record.

Frequently overridden alerts in the electronic health record can highlight alerts that may need revision. This method is a way of fine-tuning clinical decision support. We evaluated the feasibility of a complementary, yet different method that directly involved pediatric emergency department (PED) providers in identifying additional medication alerts that were potentially incorrect or intrusive. We then evaluated the effect subsequent resulting modifications had on alert salience. METHODS: We performed a prospective, interventional study over 34 months (March 6, 2014, to December 31, 2016) in the PED. We implemented a passive alert feedback mechanism by enhancing the native electronic health record functionality on alert reviews. End-users flagged potentially incorrect/bothersome alerts for review by the study's team. The alerts were updated when clinically appropriate and trends of the impact were evaluated. RESULTS: More than 200 alerts were reported from both inside and outside the PED, suggesting an intuitive approach. On average, we processed 4 reviews per week from the PED, with attending physicians as major contributors. The general trend of the impact of these changes seems favorable. DISCUSSION: The implementation of the review mechanism for user-selected alerts was intuitive and sustainable and seems to be able to detect alerts that are bothersome to the end-users. The method should be run in parallel with the traditional data-driven approach to support capturing of inaccurate alerts. CONCLUSIONS: User-centered, context-specific alert feedback can be used for selecting suboptimal, interruptive medication alerts.

Development and Preliminary Evaluation of a Visual Annotation Tool to Rapidly Collect Expert-Annotated Weight Errors in Pediatric Growth Charts.

Patient weights can be entered incorrectly into electronic health record (EHR) systems. These weight errors can cause significant patient harm especially in pediatrics where weight-based dosing is pervasively used. Determining weight errors through manual chart reviews is impractical in busy clinics, and current EHR alerts are rudimentary. To address these issues, we seek to develop an advanced algorithm to detect weight errors using supervised machine learning techniques. The critical first step is to collect labelled weight errors for algorithm training. In this paper, we designed and preliminarily evaluated a visual annotation tool using Agile software development to achieve the goal of supporting the rapid collection of expert-annotated weight errors. The design was based on the fact that weight errors are infrequent and medical experts can easily spot potential errors. The results show positive user feedback and prepared us for the formal user-centered evaluation as the next step.

Ion association in model ionic fluids.

Monte Carlo simulations are used to investigate the temperature and pressure (density) dependence of ion association in the restricted primitive model. It is shown that at temperatures below the critical temperature T(c) the vapor consists almost exclusively of strongly bound ion pairs at or near contact. Significant ion-pair dissociation begins at temperatures very near T(c). This raises the possibility that compositional fluctuations between strongly bound and free ions influence the critical behavior. We note qualitative similarities between the present results and the Kosterlitz-Thouless transition in the two-dimensional Coulomb gas.

Orientational order in model dipolar fluids.

Fluids of hard spheres each carrying two parallel point dipoles have been investigated using constant-volume Monte Carlo computer simulations. The results show that both ferroelectric and antiferroelectric fluid phases can be stabilized at high density and low temperature by dipolar interactions alone, if the separation between the dipoles on each sphere is sufficiently large. A simple lattice calculation provides some insight into the balance between dipole energy and orientational entropy which governs the polarization state.

Degradation of immunoglobulin G by periodontal bacteria.

Several subgingival microorganisms were tested for their ability to utilize human immunoglobulin G (IgG) as a substrate for growth. This was done using a protein-free chemically defined medium, supplemented with IgG. Stimulation of growth was observed for Capnocytophaga ochracea, Porphyromonas asaccharolytica, Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella intermedia, Prevotella oralis, Lactobacillus catenaforme and Streptococcus intermedius. Immunoelectrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a protein assay demonstrated that P. intermedia and P. endodontalis completely degraded the protein chains of IgG. Partial breakdown of IgG was observed for P. asaccharolytica and C. ochracea, whereas P. oralis cleaved the IgG heavy chain, yielding Fc and Fab fragments. All these bacteria utilized IgG as a substrate for growth. Binding studies using an enzyme-linked immunosorbent assay, revealed complete loss of in vitro antigen-antibody binding capacity after incubation of specific IgG with P. endodontalis and partial loss of binding with P. intermedia, P. gingivalis, C. ochracea or Fusobacterium nucleatum. Degradation or inactivation of IgG by oral bacteria is thought to be important in the causation of polymicrobial infections.

The use of lectins in monitoring degradation of oligosaccharide chains in mucin by oral streptococci.

The ability of utilize mucin oligosaccharides as sources of carbohydrate and energy is believed to be an important mechanism in the ecology of oral streptococci. In this study we have used digoxigenin-labelled lectins of various specificities to monitor changes in the nonreducing end groups of oligosaccharide chains following their degradation by Streptococcus oralis Ny 586 and Streptococcus sanguis Ny 584. The reaction of degraded mucin with peanut lectin, that recognizes the core disaccharide Gal (1,3)GalNAc in O-glycans, revealed a more extensive degradation of oligosaccharide by S. oralis than by S. sanguis. This corresponds to better growth of S. oralis on the mucin. Analyses with Datura stramonium lectin showed that terminal Gal (1,4)GlcNAc, or GlcNAc (1,4)GlcNAc moieties, in the oligosaccharides are attacked by both strains. Reaction patterns with alpha-L-fucose-specific lectins indicated that terminal fucose was released by S. oralis but not by S. sanguis. This was in accordance with sugar analyses which showed that approximately 40% of the fucose units were released. The results extend previously observed losses of sugars from oligosaccharide chains during growth of these organisms on mucin.

Mixed continuous cultures of Streptococcus mutans with Streptococcus sanguis or with Streptococcus oralis as a model to study the ecological effects of the lactoperoxidase system.

Mixed continuous cultures of Streptococcus species were obtained, using complex carbohydrate (mucin) as a source of nutrients, to study the ecological effects of oxygen and the lactoperoxidase system. S. mutans NCTC 10449 was unable to grow as a pure culture on mucin, but attained a significant population size in the presence of S. oralis and S. sanguis strains. The cell densities of the anaerobic mixed cultures decreased when oxygen was supplied, and S. mutans was more suppressed by oxygen than were S. sanguis and S. oralis. However, the concentrations of hydrogen peroxide (30 mumol/l in the mixed culture of S. mutans with S. sanguis and 640 mumol/l in the culture with S. oralis) indicated a certain resistance of the organisms to hydrogen peroxide. Addition of lactoperoxidase and thiocyanate to the oxygen-supplied cultures had a differential effect on the streptococcal populations. While S. mutans was inhibited, and even disappeared in the culture with S. oralis, the growth of S. sanguis and S. oralis was unaffected. This latter observation was in accordance with the OSCN- reductase activities of these organisms. When hydrogen peroxide was also added together with lactoperoxidase and thiocyanate, a further inhibition of S. mutans in the culture with S. sanguis was observed. Under these conditions, S. oralis was also inhibited, perhaps by the strong accumulation of OSCN-, exceeding the capacity of the OSCN- reductase. The effects of lactoperoxidase on mixed cultures may reflect the situation in the mouth.(ABSTRACT TRUNCATED AT 250 WORDS)

Synergistic degradation of mucin by Streptococcus oralis and Streptococcus sanguis in mixed chemostat cultures.

Oral streptococci can grow in mucin by utilizing the oligosaccharide chains as a source of carbohydrate. The degradation of the oligosaccharides by these species is accomplished by exoglycosidase activities. In this experiment, it was investigated whether strains from different species could cooperate in the release of sugars from the mucin oligosaccharide. To this end, Streptococcus sanguis Ny 584 and Streptococcus oralis strain Ny 586 were grown continuously in a chemically-defined medium, with pig gastric mucin as the growth-limiting source of carbohydrate. In pure cultures, strain Ny 586 attained approximately three-fold-higher cell densities than did strain Ny 584 in the mucin medium. This was in accordance with the observation that S. oralis Ny 586 exhibited fucosidase activity, as indicated by the presence of fucose in the culture fluid. In contrast, strain Ny 584 has no fucosidase activity against mucin, and therefore cannot attack fucose-ending oligosaccharide chains. Stable mixed cultures of the strains were obtained. It appeared that S. sanguis Ny 584 reached significantly higher cell densities in mixed cultures with S. oralis Ny 586 than in pure culture. Stimulation of the growth of strain Ny 584 was probably due to the generation of non-fucose-ending oligosaccharide chains by fucosidase from strain Ny 586. It is concluded that the synergistic degradation of oligosaccharides in glycoproteins is a potential factor influencing the streptococcal populations in the mouth.

Utilization of mucin by oral Streptococcus species.

The ability of oral Streptococcus strains to utilize oligosaccharide chains in mucin as a source of carbohydrate was studied in batch cultures. Pig gastric mucin, as a substitute of human salivary mucin, was added to chemically defined medium containing no other carbohydrates. Strains of S. mitior attained the highest cell density, while mutans streptococci: S. mutans, S. sobrinus, S. rattus, grew very little in the medium with mucin. S. mitis, S. sanguis, and S. milleri in decreasing order, showed intermediate growth. Mucin breakdown as measured by sugar analyses indicated that oligosaccharide chains were only partially degraded. Every strain produced one or more exoglycosidases potentially involved in hydrolysis of oligosaccharide. The enzyme activities occurred mainly associated with the cells, and very little activity was found in the culture fluids. The relationships between glycosidase activities and growth, or mucin degradation were not always clear.

Purification and Characterization of the Pea Chloroplast Pyruvate Dehydrogenase Complex : A Source of Acetyl-CoA and NADH for Fatty Acid Biosynthesis.

The pyruvate dehydrogenase complex has been purified 76-fold, to a specific activity of 0.6 mumoles per minute per milligram protein, beginning with isolated pea (Pisum sativum L. var Little Marvel) chloroplasts. Purification was accomplished by rate zonal sedimentation, polyethyleneglycol precipitation, and ethyl-agarose affinity chromatography. Characterization of the substrates as pyruvate, NAD(+), and coenzyme-A and the products as NADH, CO(2), and acetyl-CoA, in a 1:1:1 stoichiometry unequivocally established that activity was the result of the pyruvate dehydrogenase complex. Immunochemical analysis demonstrated significant differences in structure and organization between the chloroplast pyruvate dehydrogenase complex and the more thoroughly characterized mitochondrial complex. Chloroplast complex has a higher magnesium requirement and a more alkaline pH optimum than mitochondrial complex, and these properties are consistent with light-mediated regulation in vivo. The chloroplast pyruvate dehydrogenase complex is not, however, regulated by ATP-dependent inactivation. The properties and subcellular localization of the chloroplast pyruvate dehydrogenase complex are consistent with its role of providing acetyl-CoA and NADH for fatty acid synthesis.

A conceptual model for the co-existence of Streptococcus spp. and Actinomyces spp. in dental plaque.

One of the most important questions in ecology is how to explain the co-existence of the variety of physiologically related organisms in the same habitat. A model is presented for the co-existence of Streptococcus species and Actinomyces species in dental plaque. The hypothesis is that these organisms co-exist because they simultaneously utilize several carbon and energy substrates. The hypothesis follows from the observation that the growth yield of oral streptococci and actinomyces in saliva is limited by carbohydrate. Preliminary experiments were undertaken to test the hypothesis using mixed chemostat cultures and gnotobiotic rats. Competition between S. mutans K1R and A. viscosus Ut2 in mixed chemostat cultures on glucose and asparagine was hampered by the early appearance of high-glucose-affinity variants of A. viscosus. From the physiological characteristics of S. sanguis and S. milleri, it might be predicted that simultaneous utilization of carbohydrate and arginine would enable these organisms to co-exist with S. mutans in an ecosystem. To test this mechanism under natural conditions, germ-free rats were inoculated with a combination of S. mutans K1R and S. sanguis P4A7 or the combination S. mutans K1R and S. milleri B448. The rats were fed on three different diets: (1) 58% cornstarch; (2) 48% cornstarch and 10% sucrose; and (3) 53% cornstarch and 5% arginine. The results of this experiment demonstrated that dietary arginine caused a significant decrease of the ratios K1R/P4A7 and K1R/B448 in dental plaque.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical Changes that Occur during Senescence of Wheat Leaves : I. Basis for the Reduction of Photosynthesis.

Changes in activities of photosynthetic enzymes and photochemical processes were followed with aging of vegetative and flag leaves of wheat (Triticum aestivum L. cv Roy). Activities of stromal enzymes began to decline prior to photochemical activities. In general, total soluble protein and the activities of ribulose-1,5-bisphosphate carboxylase and NADP-triose-phosphate dehydrogenase declined in parallel and at an earlier age than leaf chlorophyll (Chl), leaf photosynthesis, and photosynthetic electron transport activity. Leaves appeared to lose whole chloroplasts as opposed to a general degradation of all chloroplasts based on three lines of evidence: (a) electron transport activity calculated on an area basis declined much earlier than the same data expressed on a Chl basis; (b) Chl content per chloroplast was similar for mature and senescent tissue; and (c) the absorbance at 550 nanometers (light scattering) per unit of Chl remained essentially constant until the end of senescence. Chloroplasts did, however, undergo some modifications before they were lost (e.g. loss of stromal enzyme activities), but the reduction in leaf photosynthesis was apparently caused by a loss of whole chloroplasts.

Light or ethylene treatments induce transverse cell enlargement in etiolated maize mesocotyls.

Dark-grown maize seedlings (hybrid WF-9 x 38-11) exposed for 1 or more hours to white light and then returned to darkness developed mesocotyls with enlarged apical diameters. This swelling response was an all-or-none response, and the fraction of the seedling population that showed the response depended on seedling age at irradiation. Irradiation of the coleoptile alone was nearly as effective in causing this response as was irradiation of the nodal region of the epicotyl, but irradiation of the mesocotyl base was ineffective. Removal of the coleoptile prior to irradiation did not prevent the formation of the light-induced swelling. Exogenously applied C(2)H(4) (10 microliters per liter) for 24 hours in dark also induced swelling of the mesocotyl. The swelling induced in the intact seedlings was localized in the apical mesocotyl tissues with either light or C(2)H(4) treatment, and maximal response to both treatments occurred with 3- to 4-day-old seedlings. Swelling of the mesocotyl was the result of transverse cell enlargement, not increase of cell numbers. The evidence suggests that light and C(2)H(4) induce mesocotyl swelling in intact maize shoots by a common mechanism.

Analysis of bacterial fermentation products by isotachophoresis.

Various carboxylic acids from bacterial fermentation could easily be separated by isotachophoresis. The analyses were performed on an LKB 2127 Tachophor, and under the conditions used the minimum amount of sample that could be quantitatively estimated was approximately 0.1 nmol. The reproducibility of the method was good (ca. 5 percent). The time of analysis using a 23-cm column was 12 min. No pretreatment of the samples was required.