Testing an alternative search algorithm for compound identification with the 'Wiley Registry of Tandem Mass Spectral Data. MSforID'

A tandem mass spectral database system consists of a library of reference spectra and a search program. State-of-the-art search programs show a high tolerance for variability in compound-specific fragmentation patterns produced by collision-induced decomposition and enable sensitive and specific 'identity search'. In this communication, performance characteristics of two search algorithms combined with the 'Wiley Registry of Tandem Mass Spectral Data, MSforID' (Wiley Registry MSMS, John Wiley and Sons, Hoboken, NJ, USA) were evaluated. The search algorithms tested were the MSMS search algorithm implemented in the NIST MS Search program 2.0g (NIST, Gaithersburg, MD, USA) and the MSforID algorithm (John Wiley and Sons, Hoboken, NJ, USA). Sample spectra were acquired on different instruments and, thus, covered a broad range of possible experimental conditions or were generated in silico. For each algorithm, more than 30,000 matches were performed. Statistical evaluation of the library search results revealed that principally both search algorithms can be combined with the Wiley Registry MSMS to create a reliable identification tool. It appears, however, that a higher degree of spectral similarity is necessary to obtain a correct match with the NIST MS Search program. This characteristic of the NIST MS Search program has a positive effect on specificity as it helps to avoid false positive matches (type I errors), but reduces sensitivity. Thus, particularly with sample spectra acquired on instruments differing in their Setup from tandem-in-space type fragmentation, a comparably higher number of false negative matches (type II errors) were observed by searching the Wiley Registry MSMS.

Weber fractions and time-order errors for long and short durations: Implications for modeling

Using a weighted up-down procedure, in each of eight conditions 28 participants compared durations of auditory (noise bursts) or visual (LED flashes) intervals; filled or unfilled with 3-ms markers; with or without feedback. Standards (Sts) were 100 and 1000 ms, and the ISI 900 ms. Intermixedly, presentation orders were St-Comparison (Co) and Co-St. TOEs were positive for St=100-ms and negative for St=1000 ms. Weber fractions (WFs, JND/St) were lowered by feedback. For visual-filled and visual-empty, WFs were highest for St=100 ms. For auditory-filled and visual-empty, St interacted with Order: lowest WFs occurred for St-Co with St=1000 ms, but for Co-St with St=100 ms. Lowest average WFs occurred with St-Co for visual-filled, but with Co-St for visual-empty. The results refute the generalization of better discrimination with St-Co than with Co-St (”type-B effect”), and support the notion of sensation weighting: flexibly differential impact weights of the compared durations in generating the response.

A Near-Real-Time Automatic Orbit Determination System for COSMIC and Its Follow-On Satellite Mission: Analysis of Orbit and Clock Errors on Radio Occultation

The COSMIC-2 mission is a follow-on mission of the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) with an upgraded payload for improved radio occultation (RO) applications. The objective of this paper is to develop a near-real-time (NRT) orbit determination system, called NRT National Chiao Tung University (NCTU) system, to support COSMIC-2 in atmospheric applications and verify the orbit product of COSMIC. The system is capable of automatic determinations of the NRT GPS clocks and LEO orbit and clock. To assess the NRT (NCTU) system, we use eight days of COSMIC data (March 24-31, 2011), which contain a total of 331 GPS observation sessions and 12 393 RO observable files. The parallel scheduling for independent GPS and LEO estimations and automatic time matching improves the computational efficiency by 64% compared to the sequential scheduling. Orbit difference analyses suggest a 10-cm accuracy for the COSMIC orbits from the NRT (NCTU) system, and it is consistent as the NRT University Corporation for Atmospheric Research (URCA) system. The mean velocity accuracy from the NRT orbits of COSMIC is 0.168 mm/s, corresponding to an error of about 0.051 μrad in the bending angle. The rms differences in the NRT COSMIC clock and in GPS clocks between the NRT (NCTU) and the postprocessing products are 3.742 and 1.427 ns. The GPS clocks determined from a partial ground GPS network [from NRT (NCTU)] and a full one [from NRT (UCAR)] result in mean rms frequency stabilities of 6.1E-12 and 2.7E-12, respectively, corresponding to range fluctuations of 5.5 and 2.4 cm and bending angle errors of 3.75 and 1.66 μrad .

Observation errors in early historical upper-air observations

Upper-air observations are a fundamental data source for global atmospheric data products, but uncertainties, particularly in the early years, are not well known. Most of the early observations, which have now been digitized, are prone to a large variety of undocumented uncertainties (errors) that need to be quantified, e.g., for their assimilation in reanalysis projects. We apply a novel approach to estimate errors in upper-air temperature, geopotential height, and wind observations from the Comprehensive Historical Upper-Air Network for the time period from 1923 to 1966. We distinguish between random errors, biases, and a term that quantifies the representativity of the observations. The method is based on a comparison of neighboring observations and is hence independent of metadata, making it applicable to a wide scope of observational data sets. The estimated mean random errors for all observations within the study period are 1.5 K for air temperature, 1.3 hPa for pressure, 3.0 ms−1for wind speed, and 21.4° for wind direction. The estimates are compared to results of previous studies and analyzed with respect to their spatial and temporal variability.

Toward a cognitive taxonomy of medical errors.

One critical step in addressing and resolving the problems associated with human errors is the development of a cognitive taxonomy of such errors. In the case of errors, such a taxonomy may be developed (1) to categorize all types of errors along cognitive dimensions, (2) to associate each type of error with a specific underlying cognitive mechanism, (3) to explain why, and even predict when and where, a specific error will occur, and (4) to generate intervention strategies for each type of error. Based on Reason's (1992) definition of human errors and Norman's (1986) cognitive theory of human action, we have developed a preliminary action-based cognitive taxonomy of errors that largely satisfies these four criteria in the domain of medicine. We discuss initial steps for applying this taxonomy to develop an online medical error reporting system that not only categorizes errors but also identifies problems and generates solutions.

Mixing-cell boundary conditions and apparent mass balance errors for advective-dispersive solute transport

In many field or laboratory situations, well-mixed reservoirs like, for instance, injection or detection wells and gas distribution or sampling chambers define boundaries of transport domains. Exchange of solutes or gases across such boundaries can occur through advective or diffusive processes. First we analyzed situations, where the inlet region consists of a well-mixed reservoir, in a systematic way by interpreting them in terms of injection type. Second, we discussed the mass balance errors that seem to appear in case of resident injections. Mixing cells (MC) can be coupled mathematically in different ways to a domain where advective-dispersive transport occurs: by assuming a continuous solute flux at the interface (flux injection, MC-FI), or by assuming a continuous resident concentration (resident injection). In the latter case, the flux leaving the mixing cell can be defined in two ways: either as the value when the interface is approached from the mixing-cell side (MC-RT -), or as the value when it is approached from the column side (MC-RT +). Solutions of these injection types with constant or-in one case-distance-dependent transport parameters were compared to each other as well as to a solution of a two-layer system, where the first layer was characterized by a large dispersion coefficient. These solutions differ mainly at small Peclet numbers. For most real situations, the model for resident injection MC-RI + is considered to be relevant. This type of injection was modeled with a constant or with an exponentially varying dispersion coefficient within the porous medium. A constant dispersion coefficient will be appropriate for gases because of the Eulerian nature of the usually dominating gaseous diffusion coefficient, whereas the asymptotically growing dispersion coefficient will be more appropriate for solutes due to the Lagrangian nature of mechanical dispersion, which evolves only with the fluid flow. Assuming a continuous resident concentration at the interface between a mixing cell and a column, as in case of the MC-RI + model, entails a flux discontinuity. This flux discontinuity arises inherently from the definition of a mixing cell: the mixing process is included in the balance equation, but does not appear in the description of the flux through the mixing cell. There, only convection appears because of the homogeneous concentration within the mixing cell. Thus, the solute flux through a mixing cell in close contact with a transport domain is generally underestimated. This leads to (apparent) mass balance errors, which are often reported for similar situations and erroneously used to judge the validity of such models. Finally, the mixing cell model MC-RI + defines a universal basis regarding the type of solute injection at a boundary. Depending on the mixing cell parameters, it represents, in its limits, flux as well as resident injections. (C) 1998 Elsevier Science B.V. All rights reserved.

Can prospective usability evaluation predict data errors?

Increasing amounts of clinical research data are collected by manual data entry into electronic source systems and directly from research subjects. For this manual entered source data, common methods of data cleaning such as post-entry identification and resolution of discrepancies and double data entry are not feasible. However data accuracy rates achieved without these mechanisms may be higher than desired for a particular research use. We evaluated a heuristic usability method for utility as a tool to independently and prospectively identify data collection form questions associated with data errors. The method evaluated had a promising sensitivity of 64% and a specificity of 67%. The method was used as described in the literature for usability with no further adaptations or specialization for predicting data errors. We conclude that usability evaluation methodology should be further investigated for use in data quality assurance.

Development of automated image analysis tools for verification of radiotherapy field accuracy with an electronic portal imaging device

The successful management of cancer with radiation relies on the accurate deposition of a prescribed dose to a prescribed anatomical volume within the patient. Treatment set-up errors are inevitable because the alignment of field shaping devices with the patient must be repeated daily up to eighty times during the course of a fractionated radiotherapy treatment. With the invention of electronic portal imaging devices (EPIDs), patient's portal images can be visualized daily in real-time after only a small fraction of the radiation dose has been delivered to each treatment field. However, the accuracy of human visual evaluation of low-contrast portal images has been found to be inadequate. The goal of this research is to develop automated image analysis tools to detect both treatment field shape errors and patient anatomy placement errors with an EPID. A moments method has been developed to align treatment field images to compensate for lack of repositioning precision of the image detector. A figure of merit has also been established to verify the shape and rotation of the treatment fields. Following proper alignment of treatment field boundaries, a cross-correlation method has been developed to detect shifts of the patient's anatomy relative to the treatment field boundary. Phantom studies showed that the moments method aligned the radiation fields to within 0.5mm of translation and 0.5$\sp\circ$ of rotation and that the cross-correlation method aligned anatomical structures inside the radiation field to within 1 mm of translation and 1$\sp\circ$ of rotation. A new procedure of generating and using digitally reconstructed radiographs (DRRs) at megavoltage energies as reference images was also investigated. The procedure allowed a direct comparison between a designed treatment portal and the actual patient setup positions detected by an EPID. Phantom studies confirmed the feasibility of the methodology. Both the moments method and the cross-correlation technique were implemented within an experimental radiotherapy picture archival and communication system (RT-PACS) and were used clinically to evaluate the setup variability of two groups of cancer patients treated with and without an alpha-cradle immobilization aid. The tools developed in this project have proven to be very effective and have played an important role in detecting patient alignment errors and field-shape errors in treatment fields formed by a multileaf collimator (MLC). ^

Electrochemical simulation of phase I metabolism for 21 drugs using four different working electrodes in an automated screening setup with MS detection.

BACKGROUND Electrochemical conversion of xenobiotics has been shown to mimic human phase I metabolism for a few compounds. MATERIALS & METHODS Twenty-one compounds were analyzed with a semiautomated electrochemical setup and mass spectrometry detection. RESULTS The system was able to mimic some metabolic pathways, such as oxygen gain, dealkylation and deiodination, but many of the expected and known metabolites were not produced. CONCLUSION Electrochemical conversion is a useful approach for the preparative synthesis of some types of metabolites, but as a screening method for unknown phase I metabolites, the method is, in our opinion, inferior to incubation with human liver microsomes and in vivo experiments with laboratory animals, for example.

Risk factors for patient-reported medical errors in eleven countries

OBJECTIVES The aim of this study was to identify common risk factors for patient-reported medical errors across countries. In country-level analyses, differences in risks associated with error between health care systems were investigated. The joint effects of risks on error-reporting probability were modelled for hypothetical patients with different health care utilization patterns. DESIGN Data from the Commonwealth Fund's 2010 lnternational Survey of the General Public's Views of their Health Care System's Performance in 11 Countries. SETTING Representative population samples of 11 countries were surveyed (total sample = 19,738 adults). Utilization of health care, coordination of care problems and reported errors were assessed. Regression analyses were conducted to identify risk factors for patients' reports of medical, medication and laboratory errors across countries and in country-specific models. RESULTS Error was reported by 11.2% of patients but with marked differences between countries (range: 5.4-17.0%). Poor coordination of care was reported by 27.3%. The risk of patient-reported error was determined mainly by health care utilization: Emergency care (OR = 1.7, P < 0.001), hospitalization (OR = 1.6, P < 0.001) and the number of providers involved (OR three doctors = 2.0, P < 0.001) are important predictors. Poor care coordination is the single most important risk factor for reporting error (OR = 3.9, P < 0.001). Country-specific models yielded common and country-specific predictors for self-reported error. For high utilizers of care, the probability that errors are reported rises up to P = 0.68. CONCLUSIONS Safety remains a global challenge affecting many patients throughout the world. Large variability exists in the frequency of patient-reported error across countries. To learn from others' errors is not only essential within countries but may also prove a promising strategy internationally.

Systematic diagonal and vertical errors in antisaccades and memory-guided saccades

Studies of memory-guided saccades in monkeys show an upward bias, while studies of antisaccades in humans show a diagonal effect, a deviation of endpoints toward the 45° diagonal. To determine if these two different spatial biases are specific to different types of saccades, we studied prosaccades, antisaccades and memory-guided saccades in humans. The diagonal effect occurred not with prosaccades but with antisaccades and memory-guided saccades with long intervals, consistent with hypotheses that it originates in computations of goal location under conditions of uncertainty. There was a small upward bias for memory-guided saccades but not prosaccades or antisaccades. Thus this bias is not a general effect of target uncertainty but a property specific to memory-guided saccades.

The impact of medical errors on Swiss anaesthesiologists: a cross-sectional survey.

BACKGROUND Clinicians involved in medical errors can experience significant distress. This study aims to examine (1) how medical errors impact anaesthesiologists in key work and life domains; (2) anaesthesiologists' attitudes regarding support after errors; (3) and which anaesthesiologists are most affected by errors. METHODS This study is a mailed cross-sectional survey completed by 281 of the 542 clinically active anaesthesiologists (52% response rate) working at Switzerland's five university hospitals between July 2012 and April 2013. RESULTS Respondents reported that errors had negatively affected anxiety about future errors (51%), confidence in their ability as a doctor (45%), ability to sleep (36%), job satisfaction (32%), and professional reputation (9%). Respondents' lives were more likely to be affected as error severity increased. Ninety per cent of respondents disagreed that hospitals adequately support them in coping with the stress associated with medical errors. Nearly all of the respondents (92%) reported being interested in psychological counselling after a serious error, but many identified barriers to seeking counselling. However, there were significant differences between departments regarding error-related stress levels and attitudes about error-related support. Respondents were more likely to experience certain distress if they were female, older, had previously been involved in a serious error, and were dissatisfied with their last error disclosure. CONCLUSION Medical errors, even minor errors and near misses, can have a serious effect on clinicians. Health-care organisations need to do more to support clinicians in coping with the stress associated with medical errors.