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Accompanying Paper (accompanying + paper)
Selected AbstractsExperience in adverse events detection in an emergency department: Nature of eventsEMERGENCY MEDICINE AUSTRALASIA, Issue 1 2007James Hendrie Abstract Objective:, The study was performed to determine the nature of adverse events in an ED. Methods:, The methodology has been described in the accompanying paper. Two by two tables were analysed using the two-tailed Fisher's exact test. A P -value of ,0.05 was considered significant. Statistical analysis was performed using MINITAB. Results:, One hundred and ninety-four events were detected, from a sample of 3222 patients. Except where specified, events with management causation ,3 were excluded. This excluded 24 events (12.4%) leaving 170 for analysis. Errors of commission occurred in 55% and omission in 45%. Errors of commission were significantly associated with prior events, errors of omission with ED events (P , 0.0001, respectively). The most common cause of events was drug reactions. 1.35% had a Naranjo score , 1, 0.54% , 4. Prior events were significantly associated with adverse drug reactions (P , 0.0001). Drug reactions were associated with a lower preventability score (P , 0.0001). Diagnostic issues were present in 1.2%. All three categories, that is diagnosis not considered, diagnosis within the differential and seriousness not appreciated were associated preventability ,4 (P , 0.0001, P , 0.02 and P , 0.004, respectively). Diagnostic problems were significantly associated with ED events (P , 0.0001). Conclusion:, In conclusion, the data demonstrate that events fall into two sets: prior events which are associated with errors of commission, drug reactions and lower preventability; and ED events which are associated with errors of omission, diagnostic issues and high preventability. [source] Defective translocation of a signal sequence mutant in a prlA4 suppressor strain of Escherichia coliFEBS JOURNAL, Issue 22 2002Hendrik Adams In the accompanying paper [Adams, H., Scotti, P.A., de Cock, H., Luirink, J. & Tommassen, J. (2002) Eur. J. Biochem.269, 5564,5571], we showed that the precursor of outer-membrane protein PhoE of Escherichia coli with a Gly to Leu substitution at position ,10 in the signal sequence (G-10L) is targeted to the SecYEG translocon via the signal-recognition particle (SRP) route, instead of via the SecB pathway. Here, we studied the fate of the mutant precursor in a prlA4 mutant strain. prlA mutations, located in the secY gene, have been isolated as suppressors that restore the export of precursors with defective signal sequences. Remarkably, the G-10L mutant precursor, which is normally exported in a wild-type strain, accumulated strongly in a prlA4 mutant strain. In vitro cross-linking experiments revealed that the precursor is correctly targeted to the prlA4 mutant translocon. However, translocation across the cytoplasmic membrane was defective, as appeared from proteinase K-accessibility experiments in pulse-labeled cells. Furthermore, the mutant precursor was found to accumulate when expressed in a secY40 mutant, which is defective in the insertion of integral-membrane proteins but not in protein translocation. Together, these data suggest that SecB and SRP substrates are differently processed at the SecYEG translocon. [source] Ab Initio Structure/Reactivity Investigations of Illudin-Based Antitumor Agents: A Model for Reaction in vivoHELVETICA CHIMICA ACTA, Issue 12 2003Laura (Hydroxymethyl)acylfulvene (HMAF, irofulven; 4), a third-generation derivative of a natural product extracted from the mushroom Omphalotus illudens, is selectively toxic towards certain forms of malignant tumors. Conversion of HMAF and cognates to stable aromatic derivatives is triggered by thiol attack in vitro and in vivo. Quantum-chemical methods predict well the structure for several functionalized derivatives of irofulven as compared to known X-ray crystallographic structures. Computational reaction profiles for thiol attack and aromatic rearrangement of irofulven and illudin S, a toxin from which irofulven is derived, provide insight into HMAF's selectivity and toxicity. Methods used include hybrid density-functional theory (HDFT), HartreeFock (HF), and MøllerPlesset second-order perturbation theory (MP2). Solvent effects have been explored by means of the new continuum-solvation method, COSab, presented in an accompanying paper. [source] Kinematic models for non-coaxial granular materials.INTERNATIONAL JOURNAL FOR NUMERICAL AND ANALYTICAL METHODS IN GEOMECHANICS, Issue 7 2005Part II: evaluation Abstract In this paper we present results of numerical simulations for the evaluation of kinematic models for non-coaxial granular materials by the distinct element method (DEM). Strain-rate controlled monotonic and cyclic un-drained simple shear tests were specifically designed and evaluation criteria established for this purpose. The models examined are the double-shearing model, the double-sliding free-rotating model, and the double slip and rotation rate model (DSR2 model) proposed by the authors (see the accompanying paper). It is shown that the assumption used in the double-shearing model appears to not be in agreement with the DEM data. It is also shown that in the double-sliding free-rotating model the energy dissipation requirements appear to be unduly restrictive as a constitutive assumption. The DSR2 model, which is a hybrid of discrete micro-mechanics and continuum modelling, gives better agreement with the results of our DEM simulations, than either the double-shearing model or the double-sliding free-rotating model. Copyright © 2005 John Wiley & Sons, Ltd. [source] Two-dimensional electrophoresis with cationic detergents, a powerful tool for the proteomic analysis of myelin proteins.JOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2008Part 1: Technical aspects of electrophoresis Abstract The analysis of proteins in damaged myelin is crucial to clarify the mechanisms of dysmyelination and demyelination. In the present study, proteomic analysis of myelin using a modified two-dimensional electrophoresis (2-DE) method was carried out to obtain a better understanding of myelin biology. Although standard 2-DE (immobilized pH gradient isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis; IPG/SDS-PAGE) methods of analysis provide high resolutions of soluble proteins with isoelectric focusing points in the pH range of 4,8, major myelin components include highly basic proteins are compacted at the basic edge of the 2-DE gels and are not sufficiently separated for satisfactory analysis. In an attempt to improve the separation of these proteins, an alternative 2-DE method using the cationic detergents was applied. In part 1 of this study, we describe technical aspects of conditioning 2-DE using cationic detergent. In the accompanying paper (part 2), practical 2-DE analysis using cationic detergents is described to identify proteins in the purified CNS myelin fraction. We carried out benzyldimethyl- n -hexadecylammonium chloride (16-BAC)/SDS-PAGE 2-DE and tested 2-DE with four other cationic detergents. We found that 16-BAC was the most effective agent for separation of myelin proteins and that hexadecyltrimethylammonium bromide (cetyltrimethylammonium bromide; CTAB) was the most effective agent for solubilization of myelin proteins. The combination of 16-BAC/SDS-PAGE and CTAB/SDS-PAGE is a powerful tool for the analysis of myelin proteins, including highly basic, high-MW (MW > 100K), and integral membrane proteins. © 2007 Wiley-Liss, Inc. [source] Deep spectroscopy of distant 3CR radio galaxies: the dataMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2000P. N. Best Deep long-slit spectroscopic data are presented for a sample of 14 3CR radio galaxies at redshift z,1, previously studied in detail using the Hubble Space Telescope, the Very Large Array, and the UK Infrared Telescope (UKIRT). Analysis of the [O ii] 3727 emission-line structures at ,5 Å spectral resolution is carried out to derive the kinematic properties of the emission-line gas. In line with previous lower resolution studies, a wide variety of kinematics are seen, from gas consistent with a mean rotational motion through to complex structures with velocity dispersions exceeding 1000 km s ,1. The data confirm the presence of a high-velocity gas component in 3C 265 and detached emission-line systems in 3C 356 and 3C 441, and show for the first time that the emission-line gas in the central regions of 3C 324 is composed of two kinematically distinct components. Emission-line fluxes and the colour of the continuum emission are determined down to unprecedentedly low observed wavelengths, ,<3500 Å, sufficiently short that any contribution of an evolved stellar population is negligible. An accompanying paper investigates the variation in the emission-line ratios and velocity structures within the sample, and draws conclusions as to the origin of the ionization and kinematics of these galaxies. [source] Ionization, shocks and evolution of the emission-line gas of distant 3CR radio galaxiesMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2000P. N. Best An analysis of the kinematics and ionization state of the emission-line gas of a sample of 14 3CR radio galaxies with redshifts z,1 is carried out. The data used for these studies, deep long-slit spectroscopic exposures from the William Herschel Telescope, are presented in an accompanying paper. It is found that radio sources with small linear sizes (,150 kpc) have lower ionization states, higher emission-line fluxes and broader line widths than larger radio sources. An analysis of the low-redshift sample of Baum et al. demonstrates that radio galaxies at low redshift show similar evolution in their velocity structures and emission-line ratios from small to large radio sources. The emission-line ratios of small radio sources are in agreement with theoretical shock ionization predictions, and their velocity profiles are distorted. Together with the other emission-line properties, this indicates that shocks associated with the radio source dominate the kinematics and ionization of the emission-line gas during the period that the radio source is expanding through the interstellar medium. Gas clouds are accelerated by the shocks, giving rise to the irregular velocity structures observed, whilst shock compression of emission-line gas clouds and the presence of the ionizing photons associated with the shocks combine to lower the ionization state of the emission-line gas. By contrast, in larger sources the shock fronts have passed well beyond the emission-line regions; the emission-line gas of these larger radio sources has much more settled kinematical properties, indicative of rotation, and emission-line ratios consistent with the dominant source of ionizing photons being the active galactic nucleus. This strong evolution with radio size of the emission-line gas properties of powerful radio galaxies mirrors the radio size evolution seen in the nature of the optical,ultraviolet continuum emission of these sources, implying that the continuum alignment effect is likely to be related to the same radio source shocks. [source] Qualitative methodologies I: asking research questions with reflexive insightMUSCULOSKELETAL CARE, Issue 3 2007CPsychol, Elizabeth D. Hale BA Abstract The purpose of this paper, the first of a series of two discussion pieces, is to introduce some of the issues in the debate surrounding qualitative research to the readers of Musculoskeletal Care. Recent issues of the Journal have seen an informative focus on quantitative methods and statistical analysis, and here we provide an equivalent introduction to semi-structured interviewing and qualitative analysis in this series. In the qualitative tradition, we have tried to keep our discussion reflexive, transparent and contextualized within the history of the approach and the theoretical considerations that underlie it, including the origins, nature, methods and limits of the approach. We provide information that we hope is useful for readers with all levels of familiarity with qualitative research, building from an introduction to some basic assumptions and ethical issues. We also introduce one specific qualitative approach, interpretative phenomenological analysis, which researchers might wish to apply. In the accompanying paper in a subsequent issue of Musculoskeletal Care, we will describe the potential application of this approach. Copyright © 2007 John Wiley & Sons, Ltd. [source] Numerical and experimental investigation of shrinkage behavior of precision injection molded articles.POLYMER ENGINEERING & SCIENCE, Issue 8 2008In the accompanying paper, Part I, presented are the physical modeling and numerical formulation of new lateral motion modelings. In Part II, new models developed in Part I are validated by the successful comparison of calculated residual stress profile with the literature data. The predicted results of the birefringence, residual stress distribution, and shrinkage from new lateral motion modeling are in better agreement with corresponding experimental data than those from the conventional ones. The new model prediction falls between those of two extreme cases corresponding to conventional models. As a result of extensive parametric study of processing conditions, the developed analysis system is found to be capable of successfully predicting the tendency of shrinkage behavior varying with most of processing conditions. In this regard, the new model enables better analysis based design and optimization of precision injection-molded products. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers [source] Non-identical monozygotic twins, intermediate twin types, zygosity testing, and the non-random nature of monozygotic twinning: A review,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2009Geoffrey Machin Abstract Monozygotic twins (MZ) are rarely absolutely "identical." This review discusses the types of genetic/epigenetic and prenatal environmental post-zygotic mechanisms that cause discordance within such twin pairs. Some of these mechanisms,ranging from heterokaryotypia to skewed X-chromosome inactivation,may cause extreme discordance, but these extremes are merely the more emphatic examples of discordance that, to some degree, underlies the majority of MZ twin pairs. Because of the entrenched misconception that MZ twins are necessarily identical, many MZ twin pairs are mistakenly designated as dizygotic (DZ). Clinical benefits to accurate zygosity determination include correct solid organ transplantation matching, if one twin requires donation for a non-genetically mediated disease; the opportunity of preventive management for disorders that do not manifest synchronously; and better counseling to parents regarding their individually unique, and often psychologically puzzling, twin offspring. In twin pairs with complex and confusing biological origins, more detailed zygosity testing may be required. For example, intermediate trigametic and tetragametic chimeric dizygotic twins are reviewed, some of whom are, nevertheless, monochorionic (MC). Because of inter-fetal vascular anastomoses in MC twins, genetic results from blood samples may not accurately reflect discordance in solid organs. Previously, it was thought that MZ twinning was some sort of embryological fluke. However, familial monozygotic twinning is more common than suggested by the literature. Seven new families are presented in an accompanying paper. Despite the difficulties and dangers of twin pregnancy (especially so for MC twins), human twinning persists, and continues to both challenge and fascinate parents, clinicians and geneticists. © 2009 Wiley-Liss, Inc. [source] Integrated biophysical studies implicate partial unfolding of NBD1 of CFTR in the molecular pathogenesis of F508del cystic fibrosisPROTEIN SCIENCE, Issue 10 2010Chi Wang Abstract The lethal genetic disease cystic fibrosis is caused predominantly by in-frame deletion of phenylalanine 508 in the cystic fibrosis transmembrane conductance regulator (CFTR). F508 is located in the first nucleotide-binding domain (NBD1) of CFTR, which functions as an ATP-gated chloride channel on the cell surface. The F508del mutation blocks CFTR export to the surface due to aberrant retention in the endoplasmic reticulum. While it was assumed that F508del interferes with NBD1 folding, biophysical studies of purified NBD1 have given conflicting results concerning the mutation's influence on domain folding and stability. We have conducted isothermal (this paper) and thermal (accompanying paper) denaturation studies of human NBD1 using a variety of biophysical techniques, including simultaneous circular dichroism, intrinsic fluorescence, and static light-scattering measurements. These studies show that, in the absence of ATP, NBD1 unfolds via two sequential conformational transitions. The first, which is strongly influenced by F508del, involves partial unfolding and leads to aggregation accompanied by an increase in tryptophan fluorescence. The second, which is not significantly influenced by F508del, involves full unfolding of NBD1. Mg-ATP binding delays the first transition, thereby offsetting the effect of F508del on domain stability. Evidence suggests that the initial partial unfolding transition is partially responsible for the poor in vitro solubility of human NBD1. Second-site mutations that increase the solubility of isolated F508del-NBD1 in vitro and suppress the trafficking defect of intact F508del-CFTR in vivo also stabilize the protein against this transition, supporting the hypothesize that it is responsible for the pathological trafficking of F508del-CFTR. [source] | ||||||||||||||||