Simulation of Boundary-Layer Cumulus and Stratocumulus Clouds using a Cloud-Resolving Model With Low- and Third-Order Turbulence Closures

NASA Technical Reports Server (NTRS)

Xu, Kuan-Man; Cheng, Anning

2007-01-01

The effects of subgrid-scale condensation and transport become more important as the grid spacings increase from those typically used in large-eddy simulation (LES) to those typically used in cloud-resolving models (CRMs). Incorporation of these effects can be achieved by a joint probability density function approach that utilizes higher-order moments of thermodynamic and dynamic variables. This study examines how well shallow cumulus and stratocumulus clouds are simulated by two versions of a CRM that is implemented with low-order and third-order turbulence closures (LOC and TOC) when a typical CRM horizontal resolution is used and what roles the subgrid-scale and resolved-scale processes play as the horizontal grid spacing of the CRM becomes finer. Cumulus clouds were mostly produced through subgrid-scale transport processes while stratocumulus clouds were produced through both subgrid-scale and resolved-scale processes in the TOC version of the CRM when a typical CRM grid spacing is used. The LOC version of the CRM relied upon resolved-scale circulations to produce both cumulus and stratocumulus clouds, due to small subgrid-scale transports. The mean profiles of thermodynamic variables, cloud fraction and liquid water content exhibit significant differences between the two versions of the CRM, with the TOC results agreeing better with the LES than the LOC results. The characteristics, temporal evolution and mean profiles of shallow cumulus and stratocumulus clouds are weakly dependent upon the horizontal grid spacing used in the TOC CRM. However, the ratio of the subgrid-scale to resolved-scale fluxes becomes smaller as the horizontal grid spacing decreases. The subcloud-layer fluxes are mostly due to the resolved scales when a grid spacing less than or equal to 1 km is used. The overall results of the TOC simulations suggest that a 1-km grid spacing is a good choice for CRM simulation of shallow cumulus and stratocumulus.

A Scalable Cloud Library Empowering Big Data Management, Diagnosis, and Visualization of Cloud-Resolving Models

NASA Astrophysics Data System (ADS)

Zhou, S.; Tao, W. K.; Li, X.; Matsui, T.; Sun, X. H.; Yang, X.

2015-12-01

A cloud-resolving model (CRM) is an atmospheric numerical model that can numerically resolve clouds and cloud systems at 0.25~5km horizontal grid spacings. The main advantage of the CRM is that it can allow explicit interactive processes between microphysics, radiation, turbulence, surface, and aerosols without subgrid cloud fraction, overlapping and convective parameterization. Because of their fine resolution and complex physical processes, it is challenging for the CRM community to i) visualize/inter-compare CRM simulations, ii) diagnose key processes for cloud-precipitation formation and intensity, and iii) evaluate against NASA's field campaign data and L1/L2 satellite data products due to large data volume (~10TB) and complexity of CRM's physical processes. We have been building the Super Cloud Library (SCL) upon a Hadoop framework, capable of CRM database management, distribution, visualization, subsetting, and evaluation in a scalable way. The current SCL capability includes (1) A SCL data model enables various CRM simulation outputs in NetCDF, including the NASA-Unified Weather Research and Forecasting (NU-WRF) and Goddard Cumulus Ensemble (GCE) model, to be accessed and processed by Hadoop, (2) A parallel NetCDF-to-CSV converter supports NU-WRF and GCE model outputs, (3) A technique visualizes Hadoop-resident data with IDL, (4) A technique subsets Hadoop-resident data, compliant to the SCL data model, with HIVE or Impala via HUE's Web interface, (5) A prototype enables a Hadoop MapReduce application to dynamically access and process data residing in a parallel file system, PVFS2 or CephFS, where high performance computing (HPC) simulation outputs such as NU-WRF's and GCE's are located. We are testing Apache Spark to speed up SCL data processing and analysis.With the SCL capabilities, SCL users can conduct large-domain on-demand tasks without downloading voluminous CRM datasets and various observations from NASA Field Campaigns and Satellite data to a local computer, and inter-compare CRM output and data with GCE and NU-WRF.

The quest to make accessibility a corporate article of faith at Microsoft: case study of corporate culture and human resource dimensions.

PubMed

Sandler, Leonard A; Blanck, Peter

2005-01-01

This case study examines efforts by Microsoft Corporation to enhance the diversity of its workforce and improve the accessibility and usability of its products and services for persons with disabilities. The research explores the relation among the Americans with Disabilities Act of 1990, corporate leadership, attitudes and behaviors towards individuals with disabilities, and dynamics that shape organizational culture at Microsoft. Implications for Microsoft, other employers, researchers, and the disability community are discussed. 2005 John Wiley & Sons, Ltd.

Application of Microsoft's ActiveX and DirectX technologies to the visulization of physical system dynamics

NASA Astrophysics Data System (ADS)

Mann, Christopher; Narasimhamurthi, Natarajan

1998-08-01

This paper discusses a specific implementation of a web and complement based simulation systems. The overall simulation container is implemented within a web page viewed with Microsoft's Internet Explorer 4.0 web browser. Microsoft's ActiveX/Distributed Component Object Model object interfaces are used in conjunction with the Microsoft DirectX graphics APIs to provide visualization functionality for the simulation. The MathWorks' Matlab computer aided control system design program is used as an ActiveX automation server to provide the compute engine for the simulations.

Health system tests CRM data base. Community Health Network uses direct mail to boost physicians.

PubMed

Botvin, Judith D

2003-01-01

A six-month pilot patient retention project for Community Health Network (CHN), Indianapolis, ran from July 2002 to January 2003. It was a direct mail campaign on behalf of some members of the group practices owned by CHN, designed to test the use of the system's CRM database. Patients of the physicians received personal, dynamically-generated cards reminding them to schedule appointments and tests. Each mailing cost $1.76, including production and mailing.

AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1.

PubMed

Corum, Daniel G; Tsichlis, Philip N; Muise-Helmericks, Robin C

2014-01-01

Our previous work has shown that Akt3 is required for mitochondrial biogenesis in primary human endothelial cells (ECs) and in Akt3-null mice; Akt3 affects subcellular localization of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α), the master regulator of mitochondrial biogenesis. The purpose of this study is to determine the mechanism by which Akt3 controls the subcellular distribution of PGC-1α and to explore the effect on mitochondrial biogenesis and turnover during angiogenesis. Here we use standard biochemical analyses and Akt3-knockdown strategies to show that Akt3 controls the stabilization of chromosome maintenance region-1 (CRM-1), the major nuclear export receptor. Site-directed mutagenesis and association analyses show that PGC-1α nuclear export is CRM-1 dependent. Akt3 knockdown and CRM-1 overexpression cause 3-fold reductions in PGC-1α target gene expression, compared to control levels. Akt3 inhibition causes autophagy, as measured by autophagosome formation, in a CRM-1-dependent, Akt1/mTOR-independent pathway. In vivo, Akt3-null and heterozygous mice show dose-dependent decreases in angiogenesis compared to wild-type littermates (~5- and 2.5-fold decreases, respectively), as assessed by Matrigel plug assays. This correlates with an ~1.5-fold decrease in mitochondrial Cox IV expression. Our studies suggest that Akt3 is a regulator of mitochondrial dynamics in the vasculature via regulation of CRM-1-dependent nuclear export.

AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1

PubMed Central

Corum, Daniel G.; Tsichlis, Philip N.; Muise-Helmericks, Robin C.

2014-01-01

Our previous work has shown that Akt3 is required for mitochondrial biogenesis in primary human endothelial cells (ECs) and in Akt3-null mice; Akt3 affects subcellular localization of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α), the master regulator of mitochondrial biogenesis. The purpose of this study is to determine the mechanism by which Akt3 controls the subcellular distribution of PGC-1α and to explore the effect on mitochondrial biogenesis and turnover during angiogenesis. Here we use standard biochemical analyses and Akt3-knockdown strategies to show that Akt3 controls the stabilization of chromosome maintenance region-1 (CRM-1), the major nuclear export receptor. Site-directed mutagenesis and association analyses show that PGC-1α nuclear export is CRM-1 dependent. Akt3 knockdown and CRM-1 overexpression cause 3-fold reductions in PGC-1α target gene expression, compared to control levels. Akt3 inhibition causes autophagy, as measured by autophagosome formation, in a CRM-1-dependent, Akt1/mTOR-independent pathway. In vivo, Akt3-null and heterozygous mice show dose-dependent decreases in angiogenesis compared to wild-type littermates (∼5- and 2.5-fold decreases, respectively), as assessed by Matrigel plug assays. This correlates with an ∼1.5-fold decrease in mitochondrial Cox IV expression. Our studies suggest that Akt3 is a regulator of mitochondrial dynamics in the vasculature via regulation of CRM-1-dependent nuclear export.—Corum, D. G., Tsichlis, P. N., Muise-Helmericks, R. C. AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1. PMID:24081905

Cervical Rotatory Manipulation Decreases Uniaxial Tensile Properties of Rabbit Atherosclerotic Internal Carotid Artery

PubMed Central

Qi, Ji; Zhang, Lei; Chen, Chao; Mondal, Shubhro; Ping, Kaike; Chen, Yili

2017-01-01

Objective. To investigate the effects of one of the Chinese massage therapies, cervical rotatory manipulation (CRM), on uniaxial tensile properties of rabbit atherosclerotic internal carotid artery (ICA). Methods. 40 male purebred New Zealand white rabbits were randomly divided into CRM-Model group, Non-CRM-Model group, CRM-Normal group, and Non-CRM-Normal group. After modeling (atherosclerotic model) and intervention (CRM or Non-CRM), uniaxial tensile tests were performed on the ICAs to assess the differences in tensile mechanical properties between the four groups. Results. Both CRM and modeling were the main effects affecting physiological elastic modulus (PEM) of ICA. PEM in CRM-Model group was 1.81 times as much as Non-CRM-Model group, while the value in CRM-Model group was 1.34 times as much as CRM-Normal group. Maximum elastic modulus in CRM-Model group was 1.80 times as much as CRM-Normal group. Max strains in CRM-Model group and Non-CRM-Model group were 30.98% and 28.71% lower than CRM-Normal group and Non-CRM-Normal group, respectively. However, whether treated with CRM or not, the uniaxial tensile properties of healthy ICAs were not statistically different. Conclusion. CRM may decrease the uniaxial tensile properties of rabbit arteriosclerotic ICA, but with no effect on normal group. The study will aid in the meaningful explanation of the controversy about the harmfulness of CRM and the suitable population of CRM. PMID:28303160

Multi-Layer Arctic Mixed-Phase Clouds Simulated by a Cloud-Resolving Model: Comparison with ARM Observations and Sensitivity Experiments

NASA Technical Reports Server (NTRS)

Luo, Yali; Xu, Kuan-Man; Morrison, Hugh; McFarquhar, Greg M.; Wang, Zhien; Zhang, Gong

2007-01-01

A cloud-resolving model (CRM) is used to simulate the multiple-layer mixed-phase stratiform (MPS) clouds that occurred during a three-and-a-half day subperiod of the Department of Energy-Atmospheric Radiation Measurement Program s Mixed-Phase Arctic Cloud Experiment (M-PACE). The CRM is implemented with an advanced two-moment microphysics scheme, a state-of-the-art radiative transfer scheme, and a complicated third-order turbulence closure. Concurrent meteorological, aerosol, and ice nucleus measurements are used to initialize the CRM. The CRM is prescribed by time-varying large-scale advective tendencies of temperature and moisture and surface turbulent fluxes of sensible and latent heat. The CRM reproduces the occurrences of the single- and double-layer MPS clouds as revealed by the M-PACE observations. However, the simulated first cloud layer is lower and the second cloud layer thicker compared to observations. The magnitude of the simulated liquid water path agrees with that observed, but its temporal variation is more pronounced than that observed. As in an earlier study of single-layer cloud, the CRM also captures the major characteristics in the vertical distributions and temporal variations of liquid water content (LWC), total ice water content (IWC), droplet number concentration and ice crystal number concentration (nis) as suggested by the aircraft observations. However, the simulated mean values differ significantly from the observed. The magnitude of nis is especially underestimated by one order of magnitude. Sensitivity experiments suggest that the lower cloud layer is closely related to the surface fluxes of sensible and latent heat; the upper cloud layer is probably initialized by the large-scale advective cooling/moistening and maintained through the strong longwave (LW) radiative cooling near the cloud top which enhances the dynamical circulation; artificially turning off all ice-phase microphysical processes results in an increase in LWP by a factor of 3 due to interactions between the excessive LW radiative cooling and extra cloud water; heating caused by phase change of hydrometeors could affect the LWC and cloud top height by partially canceling out the LW radiative cooling. It is further shown that the resolved dynamical circulation appears to contribute more greatly to the evolution of the MPS cloud layers than the parameterized subgrid-scale circulation.

Vertical dynamic deflection measurement in concrete beams with the Microsoft Kinect.

PubMed

Qi, Xiaojuan; Lichti, Derek; El-Badry, Mamdouh; Chow, Jacky; Ang, Kathleen

2014-02-19

The Microsoft Kinect is arguably the most popular RGB-D camera currently on the market, partially due to its low cost. It offers many advantages for the measurement of dynamic phenomena since it can directly measure three-dimensional coordinates of objects at video frame rate using a single sensor. This paper presents the results of an investigation into the development of a Microsoft Kinect-based system for measuring the deflection of reinforced concrete beams subjected to cyclic loads. New segmentation methods for object extraction from the Kinect's depth imagery and vertical displacement reconstruction algorithms have been developed and implemented to reconstruct the time-dependent displacement of concrete beams tested in laboratory conditions. The results demonstrate that the amplitude and frequency of the vertical displacements can be reconstructed with submillimetre and milliHz-level precision and accuracy, respectively.

Vertical Dynamic Deflection Measurement in Concrete Beams with the Microsoft Kinect

PubMed Central

Qi, Xiaojuan; Lichti, Derek; El-Badry, Mamdouh; Chow, Jacky; Ang, Kathleen

2014-01-01

The Microsoft Kinect is arguably the most popular RGB-D camera currently on the market, partially due to its low cost. It offers many advantages for the measurement of dynamic phenomena since it can directly measure three-dimensional coordinates of objects at video frame rate using a single sensor. This paper presents the results of an investigation into the development of a Microsoft Kinect-based system for measuring the deflection of reinforced concrete beams subjected to cyclic loads. New segmentation methods for object extraction from the Kinect's depth imagery and vertical displacement reconstruction algorithms have been developed and implemented to reconstruct the time-dependent displacement of concrete beams tested in laboratory conditions. The results demonstrate that the amplitude and frequency of the vertical displacements can be reconstructed with submillimetre and milliHz-level precision and accuracy, respectively. PMID:24556668

Comparative ultrastructure of CRM1-Nucleolar bodies (CNoBs), Intranucleolar bodies (INBs) and hybrid PML/p62 bodies uncovers new facets of nuclear body dynamic and diversity

PubMed Central

Souquere, Sylvie; Weil, Dominique; Pierron, Gérard

2015-01-01

In order to gain insights on the nuclear organization in mammalian cells, we characterized ultrastructurally nuclear bodies (NBs) previously described as fluorescent foci. Using high resolution immunoelectron microscopy (I-EM), we provide evidence that CNoBs (CRM1-Nucleolar bodies) and INBs (Intranucleolar bodies) are distinct genuine nucleolar structures in untreated HeLa cells. INBs are fibrillar and concentrate the post-translational modifiers SUMO1 and SUMO-2/3 as strongly as PML bodies. In contrast, the smallest CRM1-labeled CNoBs are vitreous, preferentially located at the periphery of the nucleolus and, intricately linked to the chromatin network. Upon blockage of the CRM1-dependent nuclear export by leptomycin B (LMB), CNoBs disappear while p62/SQSTM1-containing fibrillar nuclear bodies are induced. These p62 bodies are enriched in ubiquitinated proteins. They progressively associate with PML bodies to form hybrid bodies of which PML decorates the periphery while p62/SQSTM1 is centrally-located. Our study is expanding the repertoire of nuclear bodies; revealing a previously unrecognized composite nucleolar landscape and a new mode of interactions between ubiquitous (PML) and stress-induced (p62) nuclear bodies, resulting in the formation of hybrid bodies. PMID:26275159

Onboard autonomous mission re-planning for multi-satellite system

NASA Astrophysics Data System (ADS)

Zheng, Zixuan; Guo, Jian; Gill, Eberhard

2018-04-01

This paper presents an onboard autonomous mission re-planning system for Multi-Satellites System (MSS) to perform onboard re-planing in disruptive situations. The proposed re-planning system can deal with different potential emergency situations. This paper uses Multi-Objective Hybrid Dynamic Mutation Genetic Algorithm (MO-HDM GA) combined with re-planning techniques as the core algorithm. The Cyclically Re-planning Method (CRM) and the Near Real-time Re-planning Method (NRRM) are developed to meet different mission requirements. Simulations results show that both methods can provide feasible re-planning sequences under unforeseen situations. The comparisons illustrate that using the CRM is average 20% faster than the NRRM on computation time. However, by using the NRRM more raw data can be observed and transmitted than using the CRM within the same period. The usability of this onboard re-planning system is not limited to multi-satellite system. Other mission planning and re-planning problems related to autonomous multiple vehicles with similar demands are also applicable.

Mutated form (G52E) of inactive diphtheria toxin CRM197: molecular simulations clearly display effect of the mutation to NAD binding.

PubMed

Salmas, Ramin Ekhteiari; Mestanoglu, Mert; Unlu, Ayhan; Yurtsever, Mine; Durdagi, Serdar

2016-11-01

Mutated form (G52E) of diphtheria toxin (DT) CRM197 is an inactive and nontoxic enzyme. Here, we provided a molecular insight using comparative molecular dynamics (MD) simulations to clarify the influence of a single point mutation on overall protein and active-site loop. Post-processing MD analysis (i.e. stability, principal component analysis, hydrogen-bond occupancy, etc.) is carried out on both wild and mutated targets to investigate and to better understand the mechanistic differences of structural and dynamical properties on an atomic scale especially at nicotinamide adenine dinucleotide (NAD) binding site when a single mutation (G52E) happens at the DT. In addition, a docking simulation is performed for wild and mutated forms. The docking scoring analysis and docking poses results revealed that mutant form is not able to properly accommodate the NAD molecule.

The interaction of RNA helicase DDX3 with HIV-1 Rev-CRM1-RanGTP complex during the HIV replication cycle

DOE PAGES

Mahboobi, Seyed Hanif; Javanpour, Alex A.; Mofrad, Mohammad R. K.

2015-02-27

Molecular traffic between the nucleus and the cytoplasm is regulated by the nuclear pore complex (NPC), which acts as a highly selective channel perforating the nuclear envelope in eukaryotic cells. The human immunodeficiency virus (HIV) exploits the nucleocytoplasmic pathway to export its RNA transcripts across the NPC to the cytoplasm. Despite extensive study on the HIV life cycle and the many drugs developed to target this cycle, no current drugs have been successful in targeting the critical process of viral nuclear export, even though HIV’s reliance on a single host protein, CRM1, to export its unspliced and partially spliced RNAmore » transcripts makes it a tempting target. Due to recent findings implicating a DEAD-box helicase, DDX3, in HIV replication and a member of the export complex, it has become an appealing target for anti-HIV drug inhibition. In the present research, we have applied a hybrid computational protocol to analyze protein-protein interactions in the HIV mRNA export cycle. This method is based on molecular docking followed by molecular dynamics simulation and accompanied by approximate free energy calculation (MM/GBSA), computational alanine scanning, clustering, and evolutionary analysis. We highlight here some of the most likely binding modes and interfacial residues between DDX3 and CRM1 both in the absence and presence of RanGTP. This work shows that although DDX3 can bind to free CRM1, addition of RanGTP leads to more concentrated distribution of binding modes and stronger binding between CRM1 and RanGTP.« less

The interaction of RNA helicase DDX3 with HIV-1 Rev-CRM1-RanGTP complex during the HIV replication cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahboobi, Seyed Hanif; Javanpour, Alex A.; Mofrad, Mohammad R. K.

Molecular traffic between the nucleus and the cytoplasm is regulated by the nuclear pore complex (NPC), which acts as a highly selective channel perforating the nuclear envelope in eukaryotic cells. The human immunodeficiency virus (HIV) exploits the nucleocytoplasmic pathway to export its RNA transcripts across the NPC to the cytoplasm. Despite extensive study on the HIV life cycle and the many drugs developed to target this cycle, no current drugs have been successful in targeting the critical process of viral nuclear export, even though HIV’s reliance on a single host protein, CRM1, to export its unspliced and partially spliced RNAmore » transcripts makes it a tempting target. Due to recent findings implicating a DEAD-box helicase, DDX3, in HIV replication and a member of the export complex, it has become an appealing target for anti-HIV drug inhibition. In the present research, we have applied a hybrid computational protocol to analyze protein-protein interactions in the HIV mRNA export cycle. This method is based on molecular docking followed by molecular dynamics simulation and accompanied by approximate free energy calculation (MM/GBSA), computational alanine scanning, clustering, and evolutionary analysis. We highlight here some of the most likely binding modes and interfacial residues between DDX3 and CRM1 both in the absence and presence of RanGTP. This work shows that although DDX3 can bind to free CRM1, addition of RanGTP leads to more concentrated distribution of binding modes and stronger binding between CRM1 and RanGTP.« less

Properties of the recombinant TNF-binding proteins from variola, monkeypox, and cowpox viruses are different.

PubMed

Gileva, Irina P; Nepomnyashchikh, Tatiana S; Antonets, Denis V; Lebedev, Leonid R; Kochneva, Galina V; Grazhdantseva, Antonina V; Shchelkunov, Sergei N

2006-11-01

Tumor necrosis factor (TNF), a potent proinflammatory and antiviral cytokine, is a critical extracellular immune regulator targeted by poxviruses through the activity of virus-encoded family of TNF-binding proteins (CrmB, CrmC, CrmD, and CrmE). The only TNF-binding protein from variola virus (VARV), the causative agent of smallpox, infecting exclusively humans, is CrmB. Here we have aligned the amino acid sequences of CrmB proteins from 10 VARV, 14 cowpox virus (CPXV), and 22 monkeypox virus (MPXV) strains. Sequence analyses demonstrated a high homology of these proteins. The regions homologous to cd00185 domain of the TNF receptor family, determining the specificity of ligand-receptor binding, were found in the sequences of CrmB proteins. In addition, a comparative analysis of the C-terminal SECRET domain sequences of CrmB proteins was performed. The differences in the amino acid sequences of these domains characteristic of each particular orthopoxvirus species were detected. It was assumed that the species-specific distinctions between the CrmB proteins might underlie the differences in these physicochemical and biological properties. The individual recombinant proteins VARV-CrmB, MPXV-CrmB, and CPXV-CrmB were synthesized in a baculovirus expression system in insect cells and isolated. Purified VARV-CrmB was detectable as a dimer with a molecular weight of 90 kDa, while MPXV- and CPXV-CrmBs, as monomers when fractioned by non-reducing SDS-PAGE. The CrmB proteins of VARV, MPXV, and CPXV differed in the efficiencies of inhibition of the cytotoxic effects of human, mouse, or rabbit TNFs in L929 mouse fibroblast cell line. Testing of CrmBs in the experimental model of LPS-induced shock using SPF BALB/c mice detected a pronounced protective effect of VARV-CrmB. Thus, our data demonstrated the difference in anti-TNF activities of VARV-, MPXV-, and CPXV-CrmBs and efficiency of VARV-CrmB rather than CPXV- or MPXV-CrmBs against LPS-induced mortality in mice.

The Need for Consensus and Transparency in Assessing Population-Based Rates of Positive Circumferential Radial Margins in Rectal Cancer: Data from Consecutive Cases in a Large Region of Ontario, Canada.

PubMed

Keng, Christine; Coates, Angela; Grubac, Vanja; Lovrics, Peter; DeNardi, Franco; Thabane, Lehana; Simunovic, Marko

2016-02-01

A positive circumferential radial margin (CRM) after rectal cancer surgery is an important predictor of local recurrence. The definition of a positive CRM differs internationally, and reported rates vary greatly in the literature. This study used time-series population-based data to assess positive CRM rates in a region over time and to inform future methods of CRM analysis in a defined geographic area. Chart reviews provided relevant data from consecutive patients undergoing rectal cancer surgery between 2006 and 2012 in all hospitals of the authors' region. Outcomes included rates for pathologic examination of CRM, CRM distance reporting, and positive CRM. The rate of positive CRM was calculated using various definitions. The variations included positive margin cutoffs of CRM at 1 mm or less versus 2 mm or less and inclusion or exclusion of cases without CRM assessment. In this study, 1222 consecutive rectal cancer cases were analyzed. The rate for pathology reporting of CRM distance increased from 54.7 to 93.2 % during the study. Depending on how the rate of positive CRM was defined, its value varied 8.5 to 19.4 % in 2006 and 6.0 to 12.5 % in 2012. Using a pre-specified definition, the rate of positive CRM decreased over time from 14.0 to 6.3 %. A marked increase in CRM distance reporting was observed, whereas the rates of positive CRM dropped, suggesting improved pathologist and surgeon performance over time. Changing definitions greatly influenced the rates of positive CRM, indicating the need for more transparency when such population-based rates are reported in the literature.

Understanding the Degrees of Freedom of Sample Variance by Using Microsoft Excel

ERIC Educational Resources Information Center

Ding, Jian-Hua; Jin, Xian-Wen; Shuai, Ling-Ying

2017-01-01

In this article, the degrees of freedom of the sample variance are simulated by using the Visual Basic for Applications of Microsoft Excel 2010. The simulation file dynamically displays why the sample variance should be calculated by dividing the sum of squared deviations by n-1 rather than n, which is helpful for students to grasp the meaning of…

Predictors of circumferential resection margin involvement in surgically resected rectal cancer: A retrospective review of 23,464 patients in the US National Cancer Database.

PubMed

Al-Sukhni, Eisar; Attwood, Kristopher; Gabriel, Emmanuel; Nurkin, Steven J

2016-04-01

The circumferential resection margin (CRM) is a key prognostic factor after rectal cancer resection. We sought to identify factors associated with CRM involvement (CRM+). A retrospective review was performed of the National Cancer Database, 2004-2011. Patients with rectal cancer who underwent radical resection and had a recorded CRM were included. Multivariable analysis of the association between clinicopathologic characteristics and CRM was performed. Tumor <1 mm from the cut margin defined CRM+. Of 23,464 eligible patients, 13.3% were CRM+. Factors associated with CRM+ were diagnosis later in the study period, lack of insurance, advanced stage, higher grade, undergoing APR, and receiving radiation. Nearly half of CRM+ patients did not receive neoadjuvant therapy. CRM+ patients who did not receive neoadjuvant therapy were more likely to be female, older, with more comorbidities, smaller tumors, earlier clinical stage, advanced pathologic stage, and CEA-negative disease compared to those who received it. Factors associated with CRM+ include features of advanced disease, undergoing APR, and lack of health insurance. Half of CRM+ patients did not receive neoadjuvant treatment. These represent cases where CRM status may be modifiable with appropriate pre-operative selection and multidisciplinary management. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM(197) conjugate vaccine co-localizes with MHC II on the antigen processing cell surface.

PubMed

Lai, Zengzu; Schreiber, John R

2009-05-21

Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM(197) induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but the fate of the PS attached to the carrier is unknown. To determine the location of the PS component of PnPS-CRM(197) in the APC, we separately labeled PS and protein and tracked their location. The PS of types 14-CRM(197) and 19F-CRM(197) was specifically labeled by Alexa Fluor 594 hydrazide (red). The CRM(197) was separately labeled red in a reaction that did not label PS. Labeled antigens were incubated with APC which were fixed, permeabilized and incubated with anti-MHC II antibody labeled green by Alexa Fluor 488, followed by confocal microscopy. Labeled CRM(197) was presented on APC surface and co-localized with MHC II (yellow). Labeled unconjugated 14 or 19F PS did not go to the APC surface, but PS labeled 14-CRM(197) and 19F-CRM(197) was internalized and co-localized with MHC II. Monoclonal antibody to type 14 PS bound to intracellular type 14 PS and PS-CRM(197). Brefeldin A and chloroquine blocked both CRM(197) and PS labeled 14-CRM(197) and 19F-CRM(197) from co-localizing with MHC II. These data suggest that the PS component of the CRM(197) glycoconjugate enters the endosome, travels with CRM(197) peptides to the APC surface and co-localizes with MHC II.

Construction and Development of CRM Technology and Industry Chain in China

NASA Astrophysics Data System (ADS)

Liu, Chunnian; Wang, Yonglong; Pan, Qin

CRM is any application or initiative designed to help an organization optimize interactions with customers, suppliers, or prospects via one or more touch points. CRM has been interpreted and used in different ways by researchers in the various disciplines and researchers have identified a variety of technologies related to CRM. This paper highlights the implementation from the technology level and contributes to some successful factors in CRM application. The development of CRM is not fully developed in China. There are many critical factors that determine the CRM market development. Construction and development of CRM industry chain in China is a valuable research field and the paper provided some suggestions and analyses on it. In future, it requires our joint efforts of many aspects from every walk of life to make sure that CRM industry chain can improve and maturate gradually.

Bioavailability of a Lipidic Formulation of Curcumin in Healthy Human Volunteers

PubMed Central

Pawar, Yogesh B.; Munjal, Bhushan; Arora, Saurabh; Karwa, Manoj; Kohli, Gunjan; Paliwal, Jyoti K.; Bansal, Arvind K.

2012-01-01

Numerous publications have reported the significant pharmacodynamic activity of Curcumin (CRM) despite low or undetectable levels in plasma. The objective of the present study was to perform a detailed pharmacokinetic evaluation of CRM after the oral administration of a highly bioavailable lipidic formulation of CRM (CRM-LF) in human subjects. Cmax, Tmax and AUC0–∞ were found to be 183.35 ± 37.54 ng/mL, 0.60 ± 0.05 h and 321.12 ± 25.55 ng/mL respectively, at a dose of 750 mg. The plasma profile clearly showed three distinct phases, viz., absorption, distribution and elimination. A close evaluation of the primary pharmacokinetic parameters provided valuable insight into the behavior of the CRM after absorption by CRM-LF. CRM-LF showed a lag time (Tlag) of 0.18 h (around 12 min). Pharmacokinetic modeling revealed that CRM-LF followed a two-compartment model with first order absorption, lag time and first order elimination. A high absorption rate constant (K01, 4.51/h) signifies that CRM-LF ensured rapid absorption of the CRM into the central compartment. This was followed by the distribution of CRM from the central to peripheral compartment (K12, 2.69/h). The rate of CRM transfer from the peripheral to central compartment (K21, 0.15/h) was slow. This encourages higher tissue levels of CRM as compared with plasma levels. The study provides an explanation of the therapeutic efficacy of CRM, despite very low/undetectable levels in the plasma. PMID:24300368

Maize centromere structure and evolution: sequence analysis of centromeres 2 and 5 reveals dynamic Loci shaped primarily by retrotransposons.

PubMed

Wolfgruber, Thomas K; Sharma, Anupma; Schneider, Kevin L; Albert, Patrice S; Koo, Dal-Hoe; Shi, Jinghua; Gao, Zhi; Han, Fangpu; Lee, Hyeran; Xu, Ronghui; Allison, Jamie; Birchler, James A; Jiang, Jiming; Dawe, R Kelly; Presting, Gernot G

2009-11-01

We describe a comprehensive and general approach for mapping centromeres and present a detailed characterization of two maize centromeres. Centromeres are difficult to map and analyze because they consist primarily of repetitive DNA sequences, which in maize are the tandem satellite repeat CentC and interspersed centromeric retrotransposons of maize (CRM). Centromeres are defined epigenetically by the centromeric histone H3 variant, CENH3. Using novel markers derived from centromere repeats, we have mapped all ten centromeres onto the physical and genetic maps of maize. We were able to completely traverse centromeres 2 and 5, confirm physical maps by fluorescence in situ hybridization (FISH), and delineate their functional regions by chromatin immunoprecipitation (ChIP) with anti-CENH3 antibody followed by pyrosequencing. These two centromeres differ substantially in size, apparent CENH3 density, and arrangement of centromeric repeats; and they are larger than the rice centromeres characterized to date. Furthermore, centromere 5 consists of two distinct CENH3 domains that are separated by several megabases. Succession of centromere repeat classes is evidenced by the fact that elements belonging to the recently active recombinant subgroups of CRM1 colonize the present day centromeres, while elements of the ancestral subgroups are also found in the flanking regions. Using abundant CRM and non-CRM retrotransposons that inserted in and near these two centromeres to create a historical record of centromere location, we show that maize centromeres are fluid genomic regions whose borders are heavily influenced by the interplay of retrotransposons and epigenetic marks. Furthermore, we propose that CRMs may be involved in removal of centromeric DNA (specifically CentC), invasion of centromeres by non-CRM retrotransposons, and local repositioning of the CENH3.

Maize Centromere Structure and Evolution: Sequence Analysis of Centromeres 2 and 5 Reveals Dynamic Loci Shaped Primarily by Retrotransposons

PubMed Central

Albert, Patrice S.; Koo, Dal-Hoe; Shi, Jinghua; Gao, Zhi; Han, Fangpu; Lee, Hyeran; Xu, Ronghui; Allison, Jamie; Birchler, James A.; Jiang, Jiming; Dawe, R. Kelly; Presting, Gernot G.

2009-01-01

We describe a comprehensive and general approach for mapping centromeres and present a detailed characterization of two maize centromeres. Centromeres are difficult to map and analyze because they consist primarily of repetitive DNA sequences, which in maize are the tandem satellite repeat CentC and interspersed centromeric retrotransposons of maize (CRM). Centromeres are defined epigenetically by the centromeric histone H3 variant, CENH3. Using novel markers derived from centromere repeats, we have mapped all ten centromeres onto the physical and genetic maps of maize. We were able to completely traverse centromeres 2 and 5, confirm physical maps by fluorescence in situ hybridization (FISH), and delineate their functional regions by chromatin immunoprecipitation (ChIP) with anti-CENH3 antibody followed by pyrosequencing. These two centromeres differ substantially in size, apparent CENH3 density, and arrangement of centromeric repeats; and they are larger than the rice centromeres characterized to date. Furthermore, centromere 5 consists of two distinct CENH3 domains that are separated by several megabases. Succession of centromere repeat classes is evidenced by the fact that elements belonging to the recently active recombinant subgroups of CRM1 colonize the present day centromeres, while elements of the ancestral subgroups are also found in the flanking regions. Using abundant CRM and non-CRM retrotransposons that inserted in and near these two centromeres to create a historical record of centromere location, we show that maize centromeres are fluid genomic regions whose borders are heavily influenced by the interplay of retrotransposons and epigenetic marks. Furthermore, we propose that CRMs may be involved in removal of centromeric DNA (specifically CentC), invasion of centromeres by non-CRM retrotransposons, and local repositioning of the CENH3. PMID:19956743

Crisis Resource Management in the Delivery Room: Development of Behavioral Markers for Team Performance in Emergency Simulation

PubMed Central

de Tonetti, Gabriele; Geretto, Francesca; Celleno, Danilo

2018-01-01

Human factors are the most relevant issues contributing to adverse events in obstetrics. Specific training of Crisis Resource Management (CRM) skills (i.e., problem solving and team management, resource allocation, awareness of environment, and dynamic decision-making) is now widespread and is often based on High Fidelity Simulation. In order to be used as a guideline in simulated scenarios, CRM skills need to be mapped to specific and observable behavioral markers. For this purpose, we developed a set of observable behaviors related to the main elements of CRM in the delivery room. The observational tool was then adopted in a two-days seminar on obstetric hemorrhage where teams working in obstetric wards of six Italian hospitals took part in simulations. The tool was used as a guide for the debriefing and as a peer-to-peer feedback. It was then rated for its usefulness in facilitating the reflection upon one’s own behavior, its ease of use, and its usefulness for the peer-to-peer feedback. The ratings were positive, with a median of 4 on a 5-point scale. The CRM observational tool has therefore been well-received and presents a promising level of inter-rater agreement. We believe the tool could have value in facilitating debriefing and in the peer-to-peer feedback. PMID:29510491

CRM System Implementation in a Multinational Enterprise

NASA Astrophysics Data System (ADS)

Mishra, Alok; Mishra, Deepti

The concept of customer relationship management (CRM) resonates with managers in today's competitive economy. As more and more organizations realize the significance of becoming customer-centric in today's competitive era, they embrace CRM as a core business strategy. CRM an integration of information technology and relationship marketing provides the infrastructure that facilitates long-term relationship building with customers at an enterprise-wide level. Successful CRM implementation is a complex, expensive and rarely technical projects. This paper presents the successful implementation of CRM in a multinational organization. This study will facilitate in understanding transition, constraints and implementation of CRM in multinational enterprises.

Impact of crisis resource management simulation-based training for interprofessional and interdisciplinary teams: A systematic review.

PubMed

Fung, Lillia; Boet, Sylvain; Bould, M Dylan; Qosa, Haytham; Perrier, Laure; Tricco, Andrea; Tavares, Walter; Reeves, Scott

2015-01-01

Crisis resource management (CRM) abilities are important for different healthcare providers to effectively manage critical clinical events. This study aims to review the effectiveness of simulation-based CRM training for interprofessional and interdisciplinary teams compared to other instructional methods (e.g., didactics). Interprofessional teams are composed of several professions (e.g., nurse, physician, midwife) while interdisciplinary teams are composed of several disciplines from the same profession (e.g., cardiologist, anaesthesiologist, orthopaedist). Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ERIC were searched using terms related to CRM, crisis management, crew resource management, teamwork, and simulation. Trials comparing simulation-based CRM team training versus any other methods of education were included. The educational interventions involved interprofessional or interdisciplinary healthcare teams. The initial search identified 7456 publications; 12 studies were included. Simulation-based CRM team training was associated with significant improvements in CRM skill acquisition in all but two studies when compared to didactic case-based CRM training or simulation without CRM training. Of the 12 included studies, one showed significant improvements in team behaviours in the workplace, while two studies demonstrated sustained reductions in adverse patient outcomes after a single simulation-based CRM team intervention. In conclusion, CRM simulation-based training for interprofessional and interdisciplinary teams show promise in teaching CRM in the simulator when compared to didactic case-based CRM education or simulation without CRM teaching. More research, however, is required to demonstrate transfer of learning to workplaces and potential impact on patient outcomes.

A non-canonical mechanism for Crm1-export cargo complex assembly.

PubMed

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Faza, Marius Boulos; Panse, Vikram Govind

2015-04-21

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export.

Culture in the Cockpit-CRM in a Multicultural World

NASA Technical Reports Server (NTRS)

Engle, Michael

2000-01-01

Crew Resource Management (CRM) is fundamentally a method for enhancing personal interactions among crewmembers so that safety and efficiency are increased, and at its core involves issues of culture and social interaction. Since CRM is increasingly being adopted by foreign carriers, it is important to evaluate standard CRM techniques from a cultural standpoint, especially if some of these techniques may be enhanced by adapting them to particular cultures. The purpose of this paper is to propose a model for an ideal CRM culture, and to suggest ways that CRM may be adapted to suit particular cultures. The research method was a simple literature search to gather data on CRM techniques and multicultural crews. The results indicate that CRM can be tailored to specific cultures for maximum effectiveness.

14 CFR 121.406 - Credit for previous CRM/DRM training.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Credit for previous CRM/DRM training. 121... previous CRM/DRM training. (a) For flightcrew members, the Administrator may credit CRM training received before March 19, 1998 toward all or part of the initial ground CRM training required by § 121.419. (b...

14 CFR 121.406 - Credit for previous CRM/DRM training.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Credit for previous CRM/DRM training. 121... previous CRM/DRM training. (a) For flightcrew members, the Administrator may credit CRM training received before March 19, 1998 toward all or part of the initial ground CRM training required by § 121.419. (b...

Increasing Intelligence, Surveillance, and Reconnaissance (ISR) Operational Agility through Mission Command

DTIC Science & Technology

2016-06-10

Counterinsurgency COM Collections Operations Management CONOP Concept of Operations CRM Collections Requirements Management DOD Department of...collection requirements management ( CRM ) and collection operations management (COM). CRM is the authoritative development and control of collection...management ( CRM ) and collections operations management (COM) (see figure 6). In general, CRM advocates and prioritizes customer requirements while

Assessing hospitals' clinical risk management: Development of a monitoring instrument

PubMed Central

2010-01-01

Background Clinical risk management (CRM) plays a crucial role in enabling hospitals to identify, contain, and manage risks related to patient safety. So far, no instruments are available to measure and monitor the level of implementation of CRM. Therefore, our objective was to develop an instrument for assessing CRM in hospitals. Methods The instrument was developed based on a literature review, which identified key elements of CRM. These elements were then discussed with a panel of patient safety experts. A theoretical model was used to describe the level to which CRM elements have been implemented within the organization. Interviews with CRM practitioners and a pilot evaluation were conducted to revise the instrument. The first nationwide application of the instrument (138 participating Swiss hospitals) was complemented by in-depth interviews with 25 CRM practitioners in selected hospitals, for validation purposes. Results The monitoring instrument consists of 28 main questions organized in three sections: 1) Implementation and organizational integration of CRM, 2) Strategic objectives and operational implementation of CRM at hospital level, and 3) Overview of CRM in different services. The instrument is available in four languages (English, German, French, and Italian). It allows hospitals to gather comprehensive and systematic data on their CRM practice and to identify areas for further improvement. Conclusions We have developed an instrument for assessing development stages of CRM in hospitals that should be feasible for a continuous monitoring of developments in this important area of patient safety. PMID:21144039

A non-canonical mechanism for Crm1-export cargo complex assembly

PubMed Central

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Boulos Faza, Marius; Panse, Vikram Govind

2015-01-01

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export. DOI: http://dx.doi.org/10.7554/eLife.05745.001 PMID:25895666

A fraction of Crm1 locates at centrosomes by its CRIME domain and regulates the centrosomal localization of pericentrin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Qinying; Jiang, Qing; Zhang, Chuanmao, E-mail: zhangcm@pku.edu.cn

Crm1 plays a role in exporting proteins containing nuclear export signals (NESs) from the nucleus to the cytoplasm. Some proteins that are capable of interacting with Ran/Crm1 were reported to be localized at centrosomes and to function as centrosome checkpoints. But it remains unclear how Crm1 locates at centrosomes. In this study, we found that a fraction of Crm1 is located at centrosomes through its N-terminal CRM1, importin {beta} etc. (CRIME) domain, which is responsible for interacting with RanGTP, suggesting that Crm1 might target to centrosomes through binding centrosomal RanGTP. Moreover, overexpression of the CRIME domain, which is free ofmore » NES binding domain, resulted in the dissociation of pericentrin and {gamma}-tubulin complex from centrosomes and the disruption of microtubule nucleation. Deficiency of Crm1 provoked by RNAi also decreased the spindle poles localization of pericentrin and {gamma}-tubulin complex, coupled with mitotic defects. Since pericentrin was sensitive to Crm1 specific inhibitor leptomycin B, we propose that the centrosomal Crm1 might interact with pericentrin and regulate the localization and function of pericentrin at centrosomes.« less

Reduced Circumferential Resection Margin Involvement in Rectal Cancer Surgery: Results of the Dutch Surgical Colorectal Audit.

PubMed

Gietelink, Lieke; Wouters, Michel W J M; Tanis, Pieter J; Deken, Marion M; Ten Berge, Martijn G; Tollenaar, Rob A E M; van Krieken, J Han; de Noo, Mirre E

2015-09-01

The circumferential resection margin (CRM) is a significant prognostic factor for local recurrence, distant metastasis, and survival after rectal cancer surgery. Therefore, availability of this parameter is essential. Although the Dutch total mesorectal excision trial raised awareness about CRM in the late 1990s, quality assurance on pathologic reporting was not available until the Dutch Surgical Colorectal Audit (DSCA) started in 2009. The present study describes the rates of CRM reporting and involvement since the start of the DSCA and analyzes whether improvement of these parameters can be attributed to the audit. Data from the DSCA (2009-2013) were analyzed. Reporting of CRM and CRM involvement was plotted for successive years, and variations of these parameters were analyzed in a funnelplot. Predictors of CRM involvement were determined in univariable analysis and the independent influence of year of registration on CRM involvement was analyzed in multivariable analysis. A total of 12,669 patients were included for analysis. The mean percentage of patients with a reported CRM increased from 52.7% to 94.2% (2009-2013) and interhospital variation decreased. The percentage of patients with CRM involvement decreased from 14.2% to 5.6%. In multivariable analysis, the year of DSCA registration remained a significant predictor of CRM involvement. After the introduction of the DSCA, a dramatic improvement in CRM reporting and a major decrease of CRM involvement after rectal cancer surgery have occurred. This study suggests that a national quality assurance program has been the driving force behind these achievements. Copyright © 2015 by the National Comprehensive Cancer Network.

Label-free in situ imaging of oil body dynamics and chemistry in germination

PubMed Central

Waschatko, Gustav; Billecke, Nils; Schwendy, Sascha; Jaurich, Henriette; Bonn, Mischa; Vilgis, Thomas A.

2016-01-01

Plant oleosomes are uniquely emulsified lipid reservoirs that serve as the primary energy source during seed germination. These oil bodies undergo significant changes regarding their size, composition and structure during normal seedling development; however, a detailed characterization of these oil body dynamics, which critically affect oil body extractability and nutritional value, has remained challenging because of a limited ability to monitor oil body location and composition during germination in situ. Here, we demonstrate via in situ, label-free imaging that oil bodies are highly dynamic intracellular organelles that are morphologically and biochemically remodelled extensively during germination. Label-free, coherent Raman microscopy (CRM) combined with bulk biochemical measurements revealed the temporal and spatial regulation of oil bodies in native soya bean cotyledons during the first eight days of germination. Oil bodies undergo a cycle of growth and shrinkage that is paralleled by lipid and protein compositional changes. Specifically, the total protein concentration associated with oil bodies increases in the first phase of germination and subsequently decreases. Lipids contained within the oil bodies change in saturation and chain length during germination. Our results show that CRM is a well-suited platform to monitor in situ lipid dynamics and local chemistry and that oil bodies are actively remodelled during germination. This underscores the dynamic role of lipid reservoirs in plant development. PMID:27798279

Immunogenicity of MenACWY-CRM in Korean Military Recruits: Influence of Tetanus-Diphtheria Toxoid Vaccination on the Vaccine Response to MenACWY-CRM.

PubMed

Kim, Han Wool; Park, In Ho; You, Sooseong; Yu, Hee Tae; Oh, In Soo; Sung, Pil Soo; Shin, Eui Cheol; Kim, Kyung Hyo

2016-11-01

The quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) has been introduced for military recruits in Korea since 2012. This study was performed to evaluate the immunogenicity of MenACWY-CRM in Korean military recruits. In addition, the influence of tetanus-diphtheria toxoids (Td) vaccination on the vaccine response to MenACWY-CRM was analyzed. A total of 75 military recruits were enrolled. Among them, 18 received a dose of MenACWY-CRM only (group 1), and 57 received Td three days before MenACWY-CRM immunization (group 2). The immunogenicity of MenACWY-CRM was compared between the two groups. The serum bactericidal activity with baby rabbit complement was measured before and three weeks after immunization against serogroups A, C, W-135, and Y. The geometric mean titers (GMTs) against four serogroups were significantly increased in both groups after immunization. Compared to group 2, group 1 exhibited significantly higher vaccine responses in several aspects: post-immune GMTs against serogroup A and C, seroresponse rates against serogroup A, and a fold increases of titers against serogroup A, C, and Y. MenACWY-CRM was immunogenic against all vaccine-serogroups in Korean military recruits. Vaccine response to MenACWY-CRM was influenced by Td administered three days earlier.

A cellular reporter to evaluate CRM1 nuclear export activity: functional analysis of the cancer-related mutant E571K.

PubMed

García-Santisteban, Iraia; Arregi, Igor; Alonso-Mariño, Marián; Urbaneja, María A; Garcia-Vallejo, Juan J; Bañuelos, Sonia; Rodríguez, Jose A

2016-12-01

The exportin CRM1 binds nuclear export signals (NESs), and mediates active transport of NES-bearing proteins from the nucleus to the cytoplasm. Structural and biochemical analyses have uncovered the molecular mechanisms underlying CRM1/NES interaction. CRM1 binds NESs through a hydrophobic cleft, whose open or closed conformation facilitates NES binding and release. Several cofactors allosterically modulate the conformation of the NES-binding cleft through intramolecular interactions involving an acidic loop and a C-terminal helix in CRM1. This current model of CRM1-mediated nuclear export has not yet been evaluated in a cellular setting. Here, we describe SRV100, a cellular reporter to interrogate CRM1 nuclear export activity. Using this novel tool, we provide evidence further validating the model of NES binding and release by CRM1. Furthermore, using both SRV100-based cellular assays and in vitro biochemical analyses, we investigate the functional consequences of a recurrent cancer-related mutation, which targets a residue near CRM1 NES-binding cleft. Our data indicate that this mutation does not necessarily abrogate the nuclear export activity of CRM1, but may increase its affinity for NES sequences bearing a more negatively charged C-terminal end.

77 FR 20010 - Proposed Information Collection; Comment Request; Online Customer Relationship Management (CRM...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-03

... DEPARTMENT OF COMMERCE Minority Business Development Agency Proposed Information Collection; Comment Request; Online Customer Relationship Management (CRM)/Performance Databases, the Online Phoenix... of program goals via the Online CRM/Performance Databases. The data collected through the Online CRM...

Acquisition of chemical remanent magnetization during experimental ferrihydrite-hematite conversion in Earth-like magnetic field-implications for paleomagnetic studies of red beds

NASA Astrophysics Data System (ADS)

Jiang, Zhaoxia; Liu, Qingsong; Dekkers, Mark J.; Tauxe, Lisa; Qin, Huafeng; Barrón, Vidal; Torrent, José

2015-10-01

Hematite-bearing red beds are renowned for their chemical remanent magnetization (CRM). If the CRM was acquired substantially later than the sediment was formed, this severely compromises paleomagnetic records. To improve our interpretation of the natural remanent magnetization, the intricacies of the CRM acquisition process must be understood. Here, we contribute to this issue by synthesizing hematite under controlled 'Earth-like' field conditions (≲ 100 μ T). CRM was imparted in 90 oriented samples with varying inclinations. The final synthesis product appeared to be dominated by hematite with traces of ferrimagnetic iron oxides. When the magnetic field intensity is ≳ 40 μ T, the CRM records the field direction faithfully. However, for field intensities ≲ 40 μ T, the CRM direction may deviate considerably from that of the applied field during synthesis. The CRM intensity normalized by the isothermal remanent magnetization (CRM/IRM@2.5 T) increases linearly with the intensity of growth field, implying that CRM could potentially be useful for relative paleointensity studies if hematite particles of chemical origins have consistent properties. CRM in hematite has a distributed unblocking temperature spectrum from ∼200 to ∼650 °C, while hematite with a depositional remanent magnetization (DRM) has a more confined spectrum from ∼ 600to 680 °C because it is usually coarser-grained and more stoichiometric. Therefore, the thermal decay curves of CRM with their concave shape are notably different from their DRM counterparts which are convex. These differences together are suggested to be a potential discriminator of CRM from DRM carried by hematite in natural red beds, and of significance for the interpretation of paleomagnetic studies on red beds.

A Technical Infrastructure to Integrate Dynamics AX ERP and CRM into University Curriculum

ERIC Educational Resources Information Center

Wimmer, Hayden; Hall, Kenneth

2016-01-01

Enterprise Resource Planning and Customer Relationship Management are becoming important topics at the university level, and are increasingly receiving course-level attention in the curriculum. In fact, the Information Systems Body of Knowledge specifically identifies Enterprise Architecture as an Information Systems-specific knowledge area. The…

CRM - I Want It My Way!

NASA Technical Reports Server (NTRS)

Henwood, Bart

2007-01-01

This viewgraph presentation provides an overview of crew resource management (CRM). Topics include what makes a good participant in a team process, human perception and response of individual behavior, characteristics of a bad participant, factors that affect performance, CRM assumptions and techniques, and CRM and individuality.

NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1.

PubMed

Güttler, Thomas; Madl, Tobias; Neumann, Piotr; Deichsel, Danilo; Corsini, Lorenzo; Monecke, Thomas; Ficner, Ralf; Sattler, Michael; Görlich, Dirk

2010-11-01

Classic nuclear export signals (NESs) confer CRM1-dependent nuclear export. Here we present crystal structures of the RanGTP-CRM1 complex alone and bound to the prototypic PKI or HIV-1 Rev NESs. These NESs differ markedly in the spacing of their key hydrophobic (Φ) residues, yet CRM1 recognizes them with the same rigid set of five Φ pockets. The different Φ spacings are compensated for by different conformations of the bound NESs: in the case of PKI, an α-helical conformation, and in the case of Rev, an extended conformation with a critical proline docking into a Φ pocket. NMR analyses of CRM1-bound and CRM1-free PKI NES suggest that CRM1 selects NES conformers that pre-exist in solution. Our data lead to a new structure-based NES consensus, and explain why NESs differ in their affinities for CRM1 and why supraphysiological NESs bind the exportin so tightly.

A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine.

PubMed

Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France

2008-08-18

CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.

Theory underlying CRM training: Psychological issues in flight crew performance and crew coordination

NASA Technical Reports Server (NTRS)

Helmreich, Robert L.

1987-01-01

What psychological theory and research can reveal about training in Cockpit Resource Management (CRM) is summarized. A framework is provided for the critical analysis of current approaches to CRM training. Background factors and definitions critical to evaluating CRM are reviewed, followed by a discussion of issues directly related to CRM training effectiveness. Some of the things not known about the optimization of crew performance and the research needed to make these efforts as effective as possible are described.

Evaluation of moisture damage in asphalt concrete with CRM motorcycle tire waste passing #50 sieve size

NASA Astrophysics Data System (ADS)

Siswanto, Henri; Supriyanto, Bambang; Pranoto, Pranoto; Chandra, Pria Rizky; Hakim, Arief Rahman

2017-09-01

The objective of this experimental research is to evaluate moisture damage in Asphalt Concrete (AC) with Crumb Rubber Modified (CRM) motorcycle tire waste passing #50 and retaining #100 sieve size. Two gradations were used in this research, the first gradation is usual for asphalt concrete base (ACB) and the second gradation is for asphalt concrete wearing course (ACWC). Marshall testing apparatus was used for testing the Marshall specimens. Seven levels of CRM content were used, namely 0%, 0.5%, 1%, 1.5%, 3%, 4.5% and 6% by weight of mixtures. Retained stability represent the level of moisture damage of AC pavement. The result indicates that addition CRM to the AC mixture increases their the stability to a maximum value and subsequent addition decrease the stability. The addition CRM to AC decreases their moisture damage susceptibility. AC with 1% CRM is the best asphalt-CRM mix.

The ontology model of FrontCRM framework

NASA Astrophysics Data System (ADS)

Budiardjo, Eko K.; Perdana, Wira; Franshisca, Felicia

2013-03-01

Adoption and implementation of Customer Relationship Management (CRM) is not merely a technological installation, but the emphasis is more on the application of customer-centric philosophy and culture as a whole. CRM must begin at the level of business strategy, the only level that thorough organizational changes are possible to be done. Changes agenda can be directed to each departmental plans, and supported by information technology. Work processes related to CRM concept include marketing, sales, and services. FrontCRM is developed as framework to guide in identifying business processes related to CRM in which based on the concept of strategic planning approach. This leads to processes and practices identification in every process area related to marketing, sales, and services. The Ontology model presented on this paper by means serves as tools to avoid framework misunderstanding, to define practices systematically within process area and to find CRM software features related to those practices.

Structural determinants of nuclear export signal orientation in binding to exportin CRM1

DOE PAGES

Fung, Ho Yee Joyce; Fu, Szu -Chin; Brautigam, Chad A.; ...

2015-09-08

The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). A comparison of minus and plus NESs identified structural and sequencemore » determinants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome.« less

An observational analysis of surgical team compliance with perioperative safety practices after crew resource management training.

PubMed

France, Daniel J; Leming-Lee, Susie; Jackson, Tom; Feistritzer, Nancye R; Higgins, Michael S

2008-04-01

Acknowledging the need to improve team communication and coordination among health care providers, health care administrators and improvement officers have been quick to endorse and invest in aviation crew resource management (CRM). Despite the increased interest in CRM there exists limited data on the effectiveness of CRM to change team behavior and performance in clinical settings. Direct observational analyses were performed on 30 surgical teams (15 neurosurgery cases and 15 cardiac cases) to evaluate surgical team compliance with integrated safety and CRM practices after extensive CRM training. Observed surgical teams were compliant with only 60% of the CRM and perioperative safety practices emphasized in the training program. The results highlight many of the challenges the health care industry faces in its efforts to adapt CRM from aviation to medicine. Additional research is needed to develop and test new team training methods and performance feedback mechanisms for clinical teams.

CRM Implementation in Nonprofits: An Analysis of the Success Factors

ERIC Educational Resources Information Center

Grattan, Kelly E.

2012-01-01

Constituent Relationship Management ("CRM") is defined as an organization-wide strategy designed to enable the organization to better manage, track and steward its constituents. CRM has benefited for-profit enterprises for nearly three decades. In the nonprofit sector, the concept of CRM is fairly new. Despite the increase in CRM…

Hospital CRM: unexplored frontier of revenue growth?

PubMed

Young, Thomas

2007-10-01

Customer relationship management (CRM) has a less-than-stellar reputation, in large part because efforts to implement it have been piecemeal and not well funded. The technologies now exist to make CRM much more effective than it has been in the past. Many hospitals today are demonstrating a substantial ROI from implementing a comprehensive CRM program.

Differences in serum thyroglobulin measurements by 3 commercial immunoradiometric assay kits and laboratory standardization using Certified Reference Material 457 (CRM-457).

PubMed

Lee, Ji In; Kim, Ji Young; Choi, Joon Young; Kim, Hee Kyung; Jang, Hye Won; Hur, Kyu Yeon; Kim, Jae Hyeon; Kim, Kwang-Won; Chung, Jae Hoon; Kim, Sun Wook

2010-09-01

Serum thyroglobulin (Tg) is essential in the follow-up of patients with differentiated thyroid carcinoma (DTC). However, interchangeability and standardization between Tg assays have not yet been achieved, even with the development of an international Tg standard (Certified Reference Material 457 [CRM-457]). Serum Tg from 30 DTC patients and serially diluted CRM-457 were measured using 3 different immunoradiometric assays (IRMA-1, IRMA-2, IRMA-3). The intraclass correlation coefficient (ICC) method was used to describe the concordance of each IRMA to CRM-457. The serum Tg measured by 3 different IRMAs correlated well (r > .85, p < .0001), but clinically relevant discrepancies were found in 13.3% of patients. IRMA-3, which claims to be standardized to CRM-457, showed the best ICC (p(1) = .98) for the CRM-457. Hospitals caring for patients with DTC should either set their own cutoffs for IRMAs for Tg based on their patient pools, or adopt IRMAs standardized to CRM-457 and calibrate their laboratory using CRM-457.

The Randomized CRM: An Approach to Overcoming the Long-Memory Property of the CRM

PubMed Central

Koopmeiners, Joseph S.; Wey, Andrew

2017-01-01

The primary object of a phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent subjects are treated at progressively higher dose levels until the MTD is identified. The continual reassessment method (CRM) is a popular model-based dose-escalation design, which utilizes a formal model for the relationship between dose and toxicity to guide dose-finding. Recently, it was shown that the CRM has a tendency to get “stuck” on a dose-level, with little escalation or de-escalation in the late stages of the trial, due to the long-memory property of the CRM. We propose the randomized CRM (rCRM), which introduces random escalation and de-escalation into the standard CRM dose-finding algorithm, as well as a hybrid approach that incorporates escalation and de-escalation only when certain criteria are met. Our simulation results show that both the rCRM and the hybrid approach reduce the trial-to-trial variability in the number of cohorts treated at the MTD but that the hybrid approach has a more favorable trade-off with respect to the average number treated at the MTD. PMID:28340333

The Randomized CRM: An Approach to Overcoming the Long-Memory Property of the CRM.

PubMed

Koopmeiners, Joseph S; Wey, Andrew

2017-01-01

The primary object of a Phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent subjects are treated at progressively higher dose levels until the MTD is identified. The continual reassessment method (CRM) is a popular model-based dose-escalation design, which utilizes a formal model for the relationship between dose and toxicity to guide dose finding. Recently, it was shown that the CRM has a tendency to get "stuck" on a dose level, with little escalation or de-escalation in the late stages of the trial, due to the long-memory property of the CRM. We propose the randomized CRM (rCRM), which introduces random escalation and de-escalation into the standard CRM dose-finding algorithm, as well as a hybrid approach that incorporates escalation and de-escalation only when certain criteria are met. Our simulation results show that both the rCRM and the hybrid approach reduce the trial-to-trial variability in the number of cohorts treated at the MTD but that the hybrid approach has a more favorable tradeoff with respect to the average number treated at the MTD.

Characterization of the molecular basis of group II intron RNA recognition by CRS1-CRM domains.

PubMed

Keren, Ido; Klipcan, Liron; Bezawork-Geleta, Ayenachew; Kolton, Max; Shaya, Felix; Ostersetzer-Biran, Oren

2008-08-22

CRM (chloroplast RNA splicing and ribosome maturation) is a recently recognized RNA-binding domain of ancient origin that has been retained in eukaryotic genomes only within the plant lineage. Whereas in bacteria CRM domains exist as single domain proteins involved in ribosome maturation, in plants they are found in a family of proteins that contain between one and four repeats. Several members of this family with multiple CRM domains have been shown to be required for the splicing of specific plastidic group II introns. Detailed biochemical analysis of one of these factors in maize, CRS1, demonstrated its high affinity and specific binding to the single group II intron whose splicing it facilitates, the plastid-encoded atpF intron RNA. Through its association with two intronic regions, CRS1 guides the folding of atpF intron RNA into its predicted "catalytically active" form. To understand how multiple CRM domains cooperate to achieve high affinity sequence-specific binding to RNA, we analyzed the RNA binding affinity and specificity associated with each individual CRM domain in CRS1; whereas CRM3 bound tightly to the RNA, CRM1 associated specifically with a unique region found within atpF intron domain I. CRM2, which demonstrated only low binding affinity, also seems to form specific interactions with regions localized to domains I, III, and IV. We further show that CRM domains share structural similarities and RNA binding characteristics with the well known RNA recognition motif domain.

The German clinical risk management survey for hospitals: Implementation levels and areas for improvement in 2015.

PubMed

Manser, Tanja; Frings, Janina; Heuser, Gregory; Mc Dermott, Fiona

2016-01-01

Despite the growing recognition of the need to implement systematic approaches for managing the risks associated with healthcare, few studies have investigated the level of implementation for clinical risk management (CRM) at a national level. Therefore, this study aimed to assess the current level of CRM implementation in German hospitals and to explore differences across hospital types. From March to June 2015, persons responsible for CRM in 2,617 hospitals and rehabilitation clinics in Germany were invited to participate in a voluntary online survey assessing the level of implementation for various aspects of CRM: CRM strategy, structures and processes; risk assessment (risk identification, risk analysis, risk evaluation) with a focus on incident reporting systems; risk mitigation measures; and risk monitoring and reporting. 572 hospitals participated in the survey (response rate 22 %). Most of these hospitals had a formalised, binding CRM strategy (72 %). 66 % had a centralised and 34 % a decentralised CRM structure. We also found that, despite a broad range of risk assessment methods being applied, there was a lack of integration of risk information from different data sources. Hospitals also reported a high level of implementation of critical incident reporting systems with a strong preference for local (74 %) over transorganisational systems. This study provides relevant data to inform targeted interventions concerning CRM implementation at a national level and to consider the specific context of different types of hospitals more carefully in this process. The approach to CRM assessment illustrated in this article could be the basis of a system for monitoring CRM over time and, thus, for evaluating the impact of strategy decisions at the policy level on CRM development. Copyright © 2016. Published by Elsevier GmbH.

NBL CRM 112-A: A new certified isotopic composition

NASA Astrophysics Data System (ADS)

Thomas, R. B.; Essex, R. M.; Mason, P.

2007-12-01

NBL CRM 112-A Uranium Metal Assay Standard is commonly used as a natural uranium isotopic reference material within the earth science mass spectrometry community. The metal is from the same parent material as NBS SRM 960, the uranyl nitrate solution, CRM 145, and the high-purity uranyl nitrate solution CRM 145-B. Because CRM 112-A has not yet been certified for isotopic composition, it has been assumed that this material has a natural 235U/238U (0.0072527), and the δ234U has been determined by measurement (e.g. -37.1‰; Cheng et al., 2000). These values have been widely used to calibrate the concentration of spikes and standards, and to correct measurements for instrument or mass bias. New, preliminary, isotopic measurements on CRM 145 and CRM 112-A performed at New Brunswick Laboratory suggest that these reference materials have a slightly lower 235U/238U and δ234U than have been commonly used. If this is the case, then data using the accepted values may be slightly biased. The significance of this bias will depend on the uncertainty of the measurement, how the CRM 112-A data is used to correct measurement data, the cited values that were used to correct the data, and the final certified values of the CRM. This fall, New Brunswick Laboratory is certifying the isotopic composition of the CRM 112-A metal using high precision thermal ionization mass spectrometry techniques. Upon completion of certification, the new CRM 112- A standard with certified isotopic ratios will provide the earth science community with a well characterized and traceable reference for calibrating and correcting their mass spectrometry measurement systems.

Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study.

PubMed

Taylor, Fiona G M; Quirke, Philip; Heald, Richard J; Moran, Brendan J; Blomqvist, Lennart; Swift, Ian R; Sebag-Montefiore, David; Tekkis, Paris; Brown, Gina

2014-01-01

The prognostic relevance of preoperative high-resolution magnetic resonance imaging (MRI) assessment of circumferential resection margin (CRM) involvement is unknown. This follow-up study of 374 patients with rectal cancer reports the relationship between preoperative MRI assessment of CRM staging, American Joint Committee on Cancer (AJCC) TNM stage, and clinical variables with overall survival (OS), disease-free survival (DFS), and time to local recurrence (LR). Patients underwent protocol high-resolution pelvic MRI. Tumor distance to the mesorectal fascia of ≤ 1 mm was recorded as an MRI-involved CRM. A Cox proportional hazards model was used in multivariate analysis to determine the relationship of MRI assessment of CRM to survivorship after adjusting for preoperative covariates. Surviving patients were followed for a median of 62 months. The 5-year OS was 62.2% in patients with MRI-clear CRM compared with 42.2% in patients with MRI-involved CRM with a hazard ratio (HR) of 1.97 (95% CI, 1.27 to 3.04; P < .01). The 5-year DFS was 67.2% (95% CI, 61.4% to 73%) for MRI-clear CRM compared with 47.3% (95% CI, 33.7% to 60.9%) for MRI-involved CRM with an HR of 1.65 (95% CI, 1.01 to 2.69; P < .05). Local recurrence HR for MRI-involved CRM was 3.50 (95% CI, 1.53 to 8.00; P < .05). MRI-involved CRM was the only preoperative staging parameter that remained significant for OS, DFS, and LR on multivariate analysis. High-resolution MRI preoperative assessment of CRM status is superior to AJCC TNM-based criteria for assessing risk of LR, DFS, and OS. Furthermore, MRI CRM involvement is significantly associated with distant metastatic disease; therefore, colorectal cancer teams could intensify treatment and follow-up accordingly to improve survival outcomes.

A comparison of global rating scale and checklist scores in the validation of an evaluation tool to assess performance in the resuscitation of critically ill patients during simulated emergencies (abbreviated as "CRM simulator study IB").

PubMed

Kim, John; Neilipovitz, David; Cardinal, Pierre; Chiu, Michelle

2009-01-01

Crisis resource management (CRM) skills are a set of nonmedical skills required to manage medical emergencies. There is currently no gold standard for evaluation of CRM performance. A prior study examined the use of a global rating scale (GRS) to evaluate CRM performance. This current study compared the use of a GRS and a checklist as formal rating instruments to evaluate CRM performance during simulated emergencies. First-year and third-year residents participated in two simulator scenarios each. Three raters then evaluated resident performance in CRM using edited video recordings using both a GRS and a checklist. The Ottawa GRS provides a seven-point anchored ordinal scale for performance in five categories of CRM, and an overall performance score. The Ottawa CRM checklist provides 12 items in the five categories of CRM, with a maximum cumulative score of 30 points. Construct validity was measured on the basis of content validity, response process, internal structure, and response to other variables. T-test analysis of Ottawa GRS scores was conducted to examine response to the variable of level of training. Intraclass correlation coefficient (ICC) scores were used to measure inter-rater reliability for both scenarios. Thirty-two first-year and 28 third-year residents participated in the study. Third-year residents produced higher mean scores for overall CRM performance than first-year residents (P < 0.05), and in all individual categories within the Ottawa GRS (P < 0.05) and the Ottawa CRM checklist (P < 0.05). This difference was noted for both scenarios and for each individual rater (P < 0.05). No statistically significant difference in resident scores was observed between scenarios for both instruments. ICC scores of 0.59 and 0.61 were obtained for Scenarios 1 and 2 with the Ottawa GRS, whereas ICC scores of 0.63 and 0.55 were obtained with the Ottawa CRM checklist. Users indicated a strong preference for the Ottawa GRS given ease of scoring, presence of an overall score, and the potential for formative evaluation. Construct validity seems to be present when using both the Ottawa GRS and CRM checklist to evaluate CRM performance during simulated emergencies. Data also indicate the presence of moderate inter-rater reliability when using both the Ottawa GRS and CRM checklist.

Cooperativity among Rev-Associated Nuclear Export Signals Regulates HIV-1 Gene Expression and Is a Determinant of Virus Species Tropism

PubMed Central

Aligeti, Mounavya; Behrens, Ryan T.; Pocock, Ginger M.; Schindelin, Johannes; Dietz, Christian; Eliceiri, Kevin W.; Swanson, Chad M.; Malim, Michael H.; Ahlquist, Paul

2014-01-01

ABSTRACT Murine cells exhibit a profound block to HIV-1 virion production that was recently mapped to a species-specific structural attribute of the murine version of the chromosomal region maintenance 1 (mCRM1) nuclear export receptor and rescued by the expression of human CRM1 (hCRM1). In human cells, the HIV-1 Rev protein recruits hCRM1 to intron-containing viral mRNAs encoding the Rev response element (RRE), thereby facilitating viral late gene expression. Here we exploited murine 3T3 fibroblasts as a gain-of-function system to study hCRM1's species-specific role in regulating Rev's effector functions. We show that Rev is rapidly exported from the nucleus by mCRM1 despite only weak contributions to HIV-1's posttranscriptional stages. Indeed, Rev preferentially accumulates in the cytoplasm of murine 3T3 cells with or without hCRM1 expression, in contrast to human HeLa cells, where Rev exhibits striking en masse transitions between the nuclear and cytoplasmic compartments. Efforts to bias Rev's trafficking either into or out of the nucleus revealed that Rev encoding a second CRM1 binding domain (Rev-2xNES) or Rev-dependent viral gag-pol mRNAs bearing tandem RREs (GP-2xRRE), rescue virus particle production in murine cells even in the absence of hCRM1. Combined, these results suggest a model wherein Rev-associated nuclear export signals cooperate to regulate the number or quality of CRM1's interactions with viral Rev/RRE ribonucleoprotein complexes in the nucleus. This mechanism regulates CRM1-dependent viral gene expression and is a determinant of HIV-1's capacity to produce virions in nonhuman cell types. IMPORTANCE Cells derived from mice and other nonhuman species exhibit profound blocks to HIV-1 replication. Here we elucidate a block to HIV-1 gene expression attributable to the murine version of the CRM1 (mCRM1) nuclear export receptor. In human cells, hCRM1 regulates the nuclear export of viral intron-containing mRNAs through the activity of the viral Rev adapter protein that forms a multimeric complex on these mRNAs prior to recruiting hCRM1. We demonstrate that Rev-dependent gene expression is poor in murine cells despite the finding that, surprisingly, the bulk of Rev interacts efficiently with mCRM1 and is rapidly exported from the nucleus. Instead, we map the mCRM1 defect to the apparent inability of this factor to engage Rev multimers in the context of large viral Rev/RNA ribonucleoprotein complexes. These findings shed new light on HIV-1 gene regulation and could inform the development of novel antiviral strategies that target viral gene expression. PMID:25275125

Dynamic training devices in CRM training

NASA Technical Reports Server (NTRS)

Lawver, J.

1984-01-01

Pilot training effectiveness and flying safety of a seasonal tour flight company are described. The change from single pilot to two pilot operated twin otters is examined. The use of the ATC 810 training device, its possibilities and training capacity is outlined. Problem areas which may arise, emergency system and pilot/passenger interaction are analyzed.

AFC-Enabled Simplified High-Lift System Integration Study

NASA Technical Reports Server (NTRS)

Hartwich, Peter M.; Dickey, Eric D.; Sclafani, Anthony J.; Camacho, Peter; Gonzales, Antonio B.; Lawson, Edward L.; Mairs, Ron Y.; Shmilovich, Arvin

2014-01-01

The primary objective of this trade study report is to explore the potential of using Active Flow Control (AFC) for achieving lighter and mechanically simpler high-lift systems for transonic commercial transport aircraft. This assessment was conducted in four steps. First, based on the Common Research Model (CRM) outer mold line (OML) definition, two high-lift concepts were developed. One concept, representative of current production-type commercial transonic transports, features leading edge slats and slotted trailing edge flaps with Fowler motion. The other CRM-based design relies on drooped leading edges and simply hinged trailing edge flaps for high-lift generation. The relative high-lift performance of these two high-lift CRM variants is established using Computational Fluid Dynamics (CFD) solutions to the Reynolds-Averaged Navier-Stokes (RANS) equations for steady flow. These CFD assessments identify the high-lift performance that needs to be recovered through AFC to have the CRM variant with the lighter and mechanically simpler high-lift system match the performance of the conventional high-lift system. Conceptual design integration studies for the AFC-enhanced high-lift systems were conducted with a NASA Environmentally Responsible Aircraft (ERA) reference configuration, the so-called ERA-0003 concept. These design trades identify AFC performance targets that need to be met to produce economically feasible ERA-0003-like concepts with lighter and mechanically simpler high-lift designs that match the performance of conventional high-lift systems. Finally, technical challenges are identified associated with the application of AFC-enabled highlift systems to modern transonic commercial transports for future technology maturation efforts.

The evolution of Crew Resource Management training in commercial aviation

NASA Technical Reports Server (NTRS)

Helmreich, R. L.; Merritt, A. C.; Wilhelm, J. A.

1999-01-01

In this study, we describe changes in the nature of Crew Resource Management (CRM) training in commercial aviation, including its shift from cockpit to crew resource management. Validation of the impact of CRM is discussed. Limitations of CRM, including lack of cross-cultural generality are considered. An overarching framework that stresses error management to increase acceptance of CRM concepts is presented. The error management approach defines behavioral strategies taught in CRM as error countermeasures that are employed to avoid error, to trap errors committed, and to mitigate the consequences of error.

Determination of the amino acid change responsible for the nontoxic, cross-reactive exotoxin A protein (CRM 66) of Pseudomonas aeruginosa PAO-PR1.

PubMed Central

Wick, M J; Iglewski, B H

1988-01-01

Analysis of purified exotoxin A from parental Pseudomonas aeruginosa PAO1 and mutant strain PAO-PR1, which produces enzymatically inactive exotoxin A (CRM 66), revealed that CRM 66 lost 90% of parental enzymatic activity. Nucleotide sequence analysis of cloned exotoxin A genes showed a single amino acid substitution in CRM 66. Position 426 in the mature protein of parental (PAO1) exotoxin A is histidine, whereas in CRM 66, it is tyrosine. Images PMID:3141388

A Novel Technique for Running the NASA Legacy Code LAPIN Synchronously With Simulations Developed Using Simulink

NASA Technical Reports Server (NTRS)

Vrnak, Daniel R.; Stueber, Thomas J.; Le, Dzu K.

2012-01-01

This report presents a method for running a dynamic legacy inlet simulation in concert with another dynamic simulation that uses a graphical interface. The legacy code, NASA's LArge Perturbation INlet (LAPIN) model, was coded using the FORTRAN 77 (The Portland Group, Lake Oswego, OR) programming language to run in a command shell similar to other applications that used the Microsoft Disk Operating System (MS-DOS) (Microsoft Corporation, Redmond, WA). Simulink (MathWorks, Natick, MA) is a dynamic simulation that runs on a modern graphical operating system. The product of this work has both simulations, LAPIN and Simulink, running synchronously on the same computer with periodic data exchanges. Implementing the method described in this paper avoided extensive changes to the legacy code and preserved its basic operating procedure. This paper presents a novel method that promotes inter-task data communication between the synchronously running processes.

Clinical risk management in mental health: a qualitative study of main risks and related organizational management practices.

PubMed

Briner, Matthias; Manser, Tanja

2013-02-04

A scientific understanding of clinical risk management (CRM) in mental health care is essential for building safer health systems and for improving patient safety. While evidence on patient safety and CRM in physical health care has increased, there is limited research on these issues in mental health care. This qualitative study provides an overview of the most important clinical risks in mental health and related organizational management practices. We conducted in-depth expert interviews with professionals responsible for CRM in psychiatric hospitals. Interviews were transcribed and analyzed applying qualitative content analysis to thematically sort the identified risks. The main concerns for CRM in mental health are a) violence and self-destructive behavior (i.e. protecting patients and staff from other patients, and patients from themselves), b) treatment errors, especially in the process of therapy, and c) risks associated with mental illnesses (e.g. psychosis or depression). This study identified critical differences to CRM in hospitals for physical disorder and challenges specific to CRM in mental health. Firstly, many psychiatric patients do not believe that they are ill and are therefore in hospital against their will. Secondly, staff safety is a much more prominent theme for CRM in mental health care as it is directly related to the specifics of mental illnesses. The current study contributes to the understanding of patient safety and raises awareness for CRM in mental health. The mental health specific overview of central risks and related organizational management practices offers a valuable basis for CRM development in mental health and an addition to CRM in general.

Centromeric retrotransposon lineages predate the maize/rice divergence and differ in abundance and activity.

PubMed

Sharma, Anupma; Presting, Gernot G

2008-02-01

Centromeric retrotransposons (CR) are located almost exclusively at the centromeres of plant chromosomes. Analysis of the emerging Zea mays inbred B73 genome sequence revealed two novel subfamilies of CR elements of maize (CRM), bringing the total number of known CRM subfamilies to four. Orthologous subfamilies of each of these CRM subfamilies were discovered in the rice lineage, and the orthologous relationships were demonstrated with extensive phylogenetic analyses. The much higher number of CRs in maize versus Oryza sativa is due primarily to the recent expansion of the CRM1 subfamily in maize. At least one incomplete copy of a CRM1 homolog was found in O. sativa ssp. indica and O. officinalis, but no member of this subfamily could be detected in the finished O. sativa ssp. japonica genome, implying loss of this prolific subfamily in that subspecies. CRM2 and CRM3, as well as the corresponding rice subfamilies, have been recently active but are present in low numbers. CRM3 is a full-length element related to the non-autonomous CentA, which is the first described CRM. The oldest subfamily (CRM4), as well as its rice counterpart, appears to contain only inactive members that are not located in currently active centromeres. The abundance of active CR elements is correlated with chromosome size in the three plant genomes for which high quality genomic sequence is available, and the emerging picture of CR elements is one in which different subfamilies are active at different evolutionary times. We propose a model by which CR elements might influence chromosome and genome size.

The Implementation of CRM at FISC Norfolk Detachment Philadelphia

DTIC Science & Technology

2003-06-01

Customer Relationship Management system. [28] If FISC decides to implement a CRM system, the decision will impact the duties of the...distribution is unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) Customer Relations Management ( CRM ) can be defined in many ways. In...Norfolk Philadelphia Mission Statement. 15. NUMBER OF PAGES 91 14. SUBJECT TERMS Customer Relations Management System, CRM ,

Avoid the four perils of CRM.

PubMed

Rigby, Darrell K; Reichheld, Frederick F; Schefter, Phil

2002-02-01

Customer relationship management is one of the hottest management tools today. But more than half of all CRM initiatives fail to produce the anticipated results. Why? And what can companies do to reverse that negative trend? The authors--three senior Bain consultants--have spent the past ten years analyzing customer-loyalty initiatives, both successful and unsuccessful, at more than 200 companies in a wide range of industries. They've found that CRM backfires in part because executives don't understand what they are implementing, let alone how much it will cost or how long it will take. The authors' research unveiled four common pitfalls that managers stumble into when trying to implement CRM. Each pitfall is a consequence of a single flawed assumption--that CRM is software that will automatically manage customer relationships. It isn't. Rather, CRM is the creation of customer strategies and processes to build customer loyalty, which are then supported by the technology. This article looks at best practices in CRM at several companies, including the New York Times Company, Square D, GE Capital, Grand Expeditions, and BMC Software. It provides an intellectual framework for any company that wants to start a CRM program or turn around a failing one.

crm-1 facilitates BMP signaling to control body size in Caenorhabditis elegans.

PubMed

Fung, Wong Yan; Fat, Ko Frankie Chi; Eng, Cheah Kathryn Song; Lau, Chow King

2007-11-01

We have identified in Caenorhabditis elegans a homologue of the vertebrate Crim1, crm-1, which encodes a putative transmembrane protein with multiple cysteine-rich (CR) domains known to have bone morphogenetic proteins (BMPs) binding activity. Using the body morphology of C. elegans as an indicator, we showed that attenuation of crm-1 activity leads to a small body phenotype reminiscent of that of BMP pathway mutants. We showed that the crm-1 loss-of-function phenotype can be rescued by constitutive supply of sma-4 activity. crm-1 can enhance BMP signaling and this activity is dependent on the presence of the DBL-1 ligand and its receptors. crm-1 is expressed in neurons at the ventral nerve cord, where the DBL-1 ligand is produced. However, ectopic expression experiments reveal that crm-1 gene products act outside the DBL-1 producing cells and function non-autonomously to facilitate dbl/sma pathway signaling to control body size.

The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.

PubMed

Booth, David S; Cheng, Yifan; Frankel, Alan D

2014-12-08

The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

Social customer relationship management: taking advantage of Web 2.0 and Big Data technologies.

PubMed

Orenga-Roglá, Sergio; Chalmeta, Ricardo

2016-01-01

The emergence of Web 2.0 and Big Data technologies has allowed a new customer relationship strategy based on interactivity and collaboration called Social Customer Relationship Management (Social CRM) to be created. This enhances customer engagement and satisfaction. The implementation of Social CRM is a complex task that involves different organisational, human and technological aspects. However, there is a lack of methodologies to assist companies in these processes. This paper shows a novel methodology that helps companies to implement Social CRM, taking into account different aspects such as social customer strategy, the Social CRM performance measurement system, the Social CRM business processes, or the Social CRM computer system. The methodology was applied to one company in order to validate and refine it.

Judo strategy. The competitive dynamics of Internet time.

PubMed

Yoffie, D B; Cusumano, M A

1999-01-01

Competition on the Internet is creating fierce battles between industry giants and small-scale start-ups. Smart start-ups can avoid those conflicts by moving quickly to uncontested ground and, when that's no longer possible, turning dominant players' strengths against them. The authors call this competitive approach judo strategy. They use the Netscape-Microsoft battles to illustrate the three main principles of judo strategy: rapid movement, flexibility, and leverage. In the early part of the browser wars, for instance, Netscape applied the principle of rapid movement by being the first company to offer a free stand-alone browser. This allowed Netscape to build market share fast and to set the market standard. Flexibility became a critical factor later in the browser wars. In December 1995, when Microsoft announced that it would "embrace and extend" competitors' Internet successes, Netscape failed to give way in the face of superior strength. Instead it squared off against Microsoft and even turned down numerous opportunities to craft deep partnerships with other companies. The result was that Netscape lost deal after deal when competing with Microsoft for common distribution channels. Netscape applied the principle of leverage by using Microsoft's strengths against it. Taking advantage of Microsoft's determination to convert the world to Windows or Windows NT, Netscape made its software compatible with existing UNIX systems. While it is true that these principles can't replace basic execution, say the authors, without speed, flexibility, and leverage, very few companies can compete successfully on Internet time.

Mineral oil certified reference materials for the determination of polychlorinated biphenyls from the National Metrology Institute of Japan (NMIJ)

PubMed Central

Aoyagi, Yoshie; Matsuo, Mayumi; Ishikawa, Keiichiro; Hanari, Nobuyasu; Otsuka, Satoko; Tsuda, Yoko; Yarita, Takashi

2008-01-01

Four mineral oil certified reference materials (CRMs), NMIJ CRM 7902-a, CRM 7903-a, CRM 7904-a, and CRM 7905-a, have been issued by the National Metrology Institute of Japan, which is part of the National Institute of Advanced Industrial Science and Technology (NMIJ/AIST), for the determination of polychlorinated biphenyls (PCBs). The raw materials for the CRMs were an insulation oil (CRM 7902-a and CRM 7903-a) and a fuel oil (CRM7904-a and CRM 7905-a). A solution of PCB3, PCB8, and technical PCB products, comprising four types of Kaneclor, was added to the oil matrices. The total PCB concentrations in the PCB-fortified oils (CRM 7902-a and CRM 7904-a) are approximately 6 mg kg−1. In addition, the mineral oils which were not fortified with PCBs were also distributed as CRMs (CRM 7903-a and CRM 7905-a). Characterization of these CRMs was conducted by the NMIJ/AIST, where the mineral oils and the PCB solution were analyzed using multiple analytical methods such as dimethylsulfoxide extraction, normal-phase liquid chromatography, gel permeation chromatography, reversed-phase liquid chromatography, and chromatography using sulfoxide-bonded silica; and/or various capillary columns for gas chromatography, and two ionization modes for mass spectrometry. The target compounds in the mineral oils and those in the PCB solution were determined by one of the primary methods of measurement, isotope dilution–mass spectrometry (ID-MS). Certified values have been provided for 11 PCB congeners (PCB3, 8, 28, 52, 101, 118, 138, 153, 180, 194, and 206) in the CRMs. These CRMs have information values for PCB homologue concentrations determined by using a Japanese official method for determination of PCBs in wastes and densities determined with an oscillational density meter. Because oil samples having arbitrary PCB concentrations between respective property values of the PCB-fortified and nonfortified CRMs can be prepared by gravimetric mixing of the CRM pairs, these CRMs can be used for validation of PCB analyses using various instruments which have different sensitivities. Figure Preparation and certification processes of the mineral oil CRMs (example shown is polychlorinated biphenyls in insulation oil, high/low concentrations) Electronic supplementary material The online version of this article (doi:10.1007/s00216-008-2010-3) contains supplementary material, which is available to authorized users. PMID:18415091

Systematic implementation of clinical risk management in a large university hospital: the impact of risk managers.

PubMed

Sendlhofer, Gerald; Brunner, Gernot; Tax, Christa; Falzberger, Gebhard; Smolle, Josef; Leitgeb, Karina; Kober, Brigitte; Kamolz, Lars Peter

2015-01-01

For health care systems in recent years, patient safety has increasingly become a priority issue. National and international strategies have been considered to attempt to overcome the most prominent hazards while patients are receiving health care. Thereby, clinical risk management (CRM) plays a dominant role in enabling the identification, analysis, and management of potential risks. CRM implementation into routine procedures within complex hospital organizations is challenging, as in the past, organizational change strategies using a top-down approach have often failed. Therefore, one of our main objectives was to educate a certain number of risk managers in facilitating CRM using a bottom-up approach. To achieve our primary purpose, five project strands were developed, and consequently followed, introducing CRM: corporate governance, risk management (RM) training, CRM process, information, and involvement. The core part of the CRM process involved the education of risk managers within each organizational unit. To account for the size of the existing organization, we assumed that a minimum of 1 % of the workforce had to be trained in RM to disseminate the continuous improvement of quality and safety. Following a roll-out plan, CRM was introduced in each unit and potential risks were identified. Alongside the changes in the corporate governance, a hospital-wide CRM process was introduced resulting in 158 trained risk managers correlating to 2.0 % of the total workforce. Currently, risk managers are present in every unit and have identified 360 operational risks. Among those, 176 risks were scored as strategic and clustered together into top risks. Effective meeting structures and opportunities to share information and knowledge were introduced. Thus far, 31 units have been externally audited in CRM. The CRM approach is unique with respect to its dimension; members of all health care professions were trained to be able to identify potential risks. A network of risk managers supported the centrally coordinated CRM process. There is a strong commitment among management, academia, clinicians, and administration to foster cooperation. The introduction of CRM led to a visible shift with regard to patient safety culture throughout the entire organization. Still, there is a long way to go to keep people engaged in CRM and work on national and international patient safety initiatives to continuously decrease potential hazards.

DDDAS-based Resilient Cyberspace (DRCS)

DTIC Science & Technology

2016-08-03

Resilient Middleware ( CRM ), Supervisor VMs (SVMs), and Master VMs (MVMs). In what follows, we briefly highlight the main functions to be provided by each...phases. 4.5.1.2 Cloud Resilient Middleware ( CRM ) The CRM provides the control and management services to deploy and configure the software and...To speedup the process of selecting the appropriate resilient algorithms and execution environments, the CRM repository contains a set of SBE

Role of Knowledge Management and Analytical CRM in Business: Data Mining Based Framework

ERIC Educational Resources Information Center

Ranjan, Jayanthi; Bhatnagar, Vishal

2011-01-01

Purpose: The purpose of the paper is to provide a thorough analysis of the concepts of business intelligence (BI), knowledge management (KM) and analytical CRM (aCRM) and to establish a framework for integrating all the three to each other. The paper also seeks to establish a KM and aCRM based framework using data mining (DM) techniques, which…

CRM Systems with Social Networking Capabilities: The Value of Incorporating a CRM 2.0 System in Sales/Marketing Education

ERIC Educational Resources Information Center

Wang, Xin; Dugan, Riley; Sojka, Jane

2013-01-01

Implementation of a customer relationship management (CRM) 2.0 system can provide both a valuable pedagogical tool and a needed skill set in a marketing and sales curriculum. A CRM 2.0 system incorporated in the sales and marketing curriculum can help manage relationships between students, practitioners, and faculty while teaching students a…

Defense AT and L. Volume 45, Number 3

DTIC Science & Technology

2016-06-01

CRM ). During the 1980s, the commercial airlines and military invested heavily in CRM training, aiming to increase crew coordination and improve...cockpit management. These CRM training programs focused on human factors train- ing—also called man-machine interfaces—with specific concentration on...leadership and decision making. CRM has evolved over the years with emphasis now placed on the acquisition of timely, appropriate infor- mation

Carrier priming with CRM 197 or diphtheria toxoid has a different impact on the immunogenicity of the respective glycoconjugates: biophysical and immunochemical interpretation.

PubMed

Pecetta, S; Lo Surdo, P; Tontini, M; Proietti, D; Zambonelli, C; Bottomley, M J; Biagini, M; Berti, F; Costantino, P; Romano, M R

2015-01-03

Glycoconjugate vaccines play an enormous role in preventing infectious diseases. The main carrier proteins used in commercial conjugate vaccines are the non-toxic mutant of diphtheria toxin (CRM197), diphtheria toxoid (DT) and tetanus toxoid (TT). Modern childhood routine vaccination schedules include the administration of several vaccines simultaneously or in close sequence, increasing the concern that the repeated exposure to conjugates based on these carrier proteins might interfere with the anti-polysaccharide response. Extending previous observations we show here that priming mice with CRM197 or DT does not suppress the response to the carbohydrate moiety of CRM197 meningococcal serogroup A (MenA) conjugates, while priming with DT can suppress the response to DT-MenA conjugates. To explain these findings we made use of biophysical and immunochemical techniques applied mainly to MenA conjugates. Differential scanning calorimetry and circular dichroism data revealed that the CRM197 structure was altered by the chemical conjugation, while DT and the formaldehyde-treated form of CRM197 were less impacted, depending on the degree of glycosylation. Investigating the binding and avidity properties of IgGs induced in mice by non-conjugated carriers, we found that CRM197 induced low levels of anti-carrier antibodies, with decreased avidity for its MenA conjugates and poor binding to DT and respective MenA conjugates. In contrast, DT induced high antibody titers able to bind with comparable avidity both the protein and its conjugates but showing very low avidity for CRM197 and related conjugates. The low intrinsic immunogenicity of CRM197 as compared to DT, the structural modifications induced by glycoconjugation and detoxification processes, resulting in conformational changes in CRM197 and DT epitopes with consequent alteration of the antibody recognition and avidity, might explain the different behavior of CRM197 and DT in a carrier priming context. Copyright © 2014 Elsevier Ltd. All rights reserved.

Safety and immunogenicity of a novel quadrivalent meningococcal CRM-conjugate vaccine given concomitantly with routine vaccinations in infants.

PubMed

Klein, Nicola P; Reisinger, Keith S; Johnston, William; Odrljin, Tatjana; Gill, Christopher J; Bedell, Lisa; Dull, Peter

2012-01-01

In phase II studies, MenACWY-CRM elicited robust immunologic responses in young infants. We now present results from our pivotal phase III infant immunogenicity/safety study. In this open-label phase III study, we randomized full-term 2-month-old infants to 4 doses of MenACWY-CRM coadministered with routine vaccines at 2, 4, 6, and 12 months of age or with routine vaccines alone. We monitored for local and systemic reactions and serious adverse events among all study participants and evaluated for sufficiency of the immune responses to MenACWY-CRM through serum bactericidal activity assay with human complement. Bactericidal antibodies were present in 94% to 100% of subjects against each of the serogroups in MenACWY-CRM after the 4-dose series and were 67% to 97% after the first 3 doses. Geometric mean titers were higher after the fourth dose of MenACWY-CRM compared with a single dose of MenACWY-CRM at 12 months of age for all serogroups (range of ratios, 4.5-38). Responses to 3 doses of routine vaccines coadministered with MenACWY-CRM were noninferior to routine vaccinations alone, except for small differences in pneumococcal serotype 6B responses after dose 3 but not dose 4 and pertactin after dose 3. Inclusion of MenACWY-CRM did not affect the safety or reactogenicity profiles of the routine infant vaccine series. A 4-dose series of MenACWY-CRM was highly immunogenic and well tolerated in young infants, and it can be coadministered with routine infant vaccines. Substantial immunity was conferred after the first 3 doses administered at 2, 4, and 6 months of age.

CRM1 and its ribosome export adaptor NMD3 localize to the nucleolus and affect rRNA synthesis.

PubMed

Bai, Baoyan; Moore, Henna M; Laiho, Marikki

2013-01-01

CRM1 is an export factor that together with its adaptor NMD3 transports numerous cargo molecules from the nucleus to cytoplasm through the nuclear pore. Previous studies have suggested that CRM1 and NMD3 are detected in the nucleolus. However, their localization with subnucleolar domains or participation in the activities of the nucleolus are unclear. We demonstrate here biochemically and using imaging analyses that CRM1 and NMD3 co-localize with nucleolar marker proteins in the nucleolus. In particular, their nucleolar localization is markedly increased by inhibition of RNA polymerase I (Pol I) transcription by actinomycin D or by silencing Pol I catalytic subunit, RPA194. We show that CRM1 nucleolar localization is dependent on its activity and the expression of NMD3, whereas NMD3 nucleolar localization is independent of CRM1. This suggests that NMD3 provides nucleolar tethering of CRM1. While inhibition of CRM1 by leptomycin B inhibited processing of 28S ribosomal (r) RNA, depletion of NMD3 did not, suggesting that their effects on 28S rRNA processing are distinct. Markedly, depletion of NMD3 and inhibition of CRM1 reduced the rate of pre-47S rRNA synthesis. However, their inactivation did not lead to nucleolar disintegration, a hallmark of Pol I transcription stress, suggesting that they do not directly regulate transcription. These results indicate that CRM1 and NMD3 have complex functions in pathways that couple rRNA synthetic and processing engines and that the rRNA synthesis rate may be adjusted according to proficiency in rRNA processing and export.

Clinical risk management in mental health: a qualitative study of main risks and related organizational management practices

PubMed Central

2013-01-01

Background A scientific understanding of clinical risk management (CRM) in mental health care is essential for building safer health systems and for improving patient safety. While evidence on patient safety and CRM in physical health care has increased, there is limited research on these issues in mental health care. This qualitative study provides an overview of the most important clinical risks in mental health and related organizational management practices. Methods We conducted in-depth expert interviews with professionals responsible for CRM in psychiatric hospitals. Interviews were transcribed and analyzed applying qualitative content analysis to thematically sort the identified risks. Results The main concerns for CRM in mental health are a) violence and self-destructive behavior (i.e. protecting patients and staff from other patients, and patients from themselves), b) treatment errors, especially in the process of therapy, and c) risks associated with mental illnesses (e.g. psychosis or depression). This study identified critical differences to CRM in hospitals for physical disorder and challenges specific to CRM in mental health. Firstly, many psychiatric patients do not believe that they are ill and are therefore in hospital against their will. Secondly, staff safety is a much more prominent theme for CRM in mental health care as it is directly related to the specifics of mental illnesses. Conclusions The current study contributes to the understanding of patient safety and raises awareness for CRM in mental health. The mental health specific overview of central risks and related organizational management practices offers a valuable basis for CRM development in mental health and an addition to CRM in general. PMID:23379842

Introduction to MAC CRM training

NASA Technical Reports Server (NTRS)

Brown, Donald D.

1987-01-01

The author introduces the Military Airlift Command (MAC) and its mission. A brief history of Cockpit Resource Management (CRM) as it relates to MAC is given. He also states why MAC is currently interested in CRM.

Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.

PubMed

Stamboulian, D; Lopardo, G; Lopez, P; Cortes-Barbosa, C; Valencia, A; Bedell, L; Karsten, A; Dull, P M

2010-10-01

This study compared the investigational quadrivalent meningococcal CRM₁₉₇ conjugate vaccine, MenACWY-CRM, with licensed quadrivalent polysaccharide (MPSV4) and conjugate (MenACWY-D) meningococcal vaccines. In this phase III multicenter study, 2505 adults (aged 19-55 years) were randomized to receive either MenACWY-CRM or MenACWY-D, and 326 adults (aged 56-65 years) were randomized to receive either MenACWY-CRM or MPSV4. Sera obtained pre-vaccination and at 1-month post-vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA) for immunogenicity non-inferiority and superiority analyses. The vaccines in all groups were well tolerated. In the 19-55 years age group, post-vaccination geometric mean titers (GMTs) were consistently higher for MenACWY-CRM than for MenACWY-D for all four serogroups. MenACWY-CRM was non-inferior to MenACWY-D for all serogroups, and superior for serogroup Y. In the 56-65 years age group, post-vaccination GMTs were 1.2- to 5.4-fold higher for MenACWY-CRM than for MPSV4 for the four serogroups. MenACWY-CRM is well tolerated and immunogenic in adults aged 19-65 years, with at least non-inferior immunogenicity compared with the currently licensed meningococcal vaccines. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Co-administration of a meningococcal glycoconjugate ACWY vaccine with travel vaccines: a randomized, open-label, multi-center study.

PubMed

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Meyer, Seetha; Forleo-Neto, Eduardo; Gniel, Dieter; Dagnew, Alemnew F; Arora, Ashwani Kumar

2014-01-01

Potential interactions between vaccines may compromise the immunogenicity and/or safety of individual vaccines so must be assessed before concomitant administration is recommended. In this study, the immunogenicity and safety of travel vaccines against Japanese encephalitis (JEV) and rabies (PCECV) administered together with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine were evaluated (NCT01466387). Healthy adults aged 18 to ≤60 years were randomized to one of four vaccine regimens: JEV + PCECV + MenACWY-CRM, JEV + PCECV, PCECV or MenACWY-CRM. Immunogenicity at baseline and 28 days post-complete vaccination was assessed by serum bactericidal assay using human complement or neutralization tests. Adverse events (AEs) were collected throughout the study period. JEV + PCECV + MenACWY-CRM was non-inferior to JEV + PCECV. Post-vaccination seroprotective neutralizing titers or concentrations were achieved in 98-99% (JE) and 100% (rabies) of subjects across the vaccine groups. Antibody responses to vaccine meningococcal serogroups were in the same range for MenACWY-CRM and JEV + PCECV + MenACWY-CRM. Rates of reporting of AEs were similar for JEV + PCECV and JEV + PCECV + MenACWY-CRM. MenACWY-CRM was administered with an inactivated adjuvanted JE and a purified chick embryo cell-culture rabies vaccine without compromising immunogenicity or safety of the individual vaccines. These data provide evidence that MenACWY-CRM could be effectively incorporated into travel vaccination programs. NCT01466387. Copyright © 2014 Elsevier Ltd. All rights reserved.

Novel selective inhibitors of nuclear export CRM1 antagonists for therapy in mantle cell lymphoma.

PubMed

Zhang, Kejie; Wang, Michael; Tamayo, Archito T; Shacham, Sharon; Kauffman, Michael; Lee, John; Zhang, Liang; Ou, Zhishuo; Li, Changping; Sun, Luhong; Ford, Richard J; Pham, Lan V

2013-01-01

Overexpression of the cellular nuclear exportin 1, more commonly called chromosomal region maintenance 1 (CRM1), has been associated with malignant progression and mortality. Therefore, activation of nuclear export can play a significant etiologic role in some forms of human neoplasia and serve as a novel target for the treatment of these cancers. Mantle cell lymphoma (MCL) is an aggressive histotype of B-cell non-Hodgkin lymphoma that remains incurable. The objective of this study was to investigate the functional significance of CRM1 in MCL by evaluating the therapeutic efficacy of CRM1 inhibition in MCL in vitro and in vivo. Our results showed that CRM1 is highly expressed in MCL cells and is involved in regulating growth and survival mechanisms through the critical nuclear factor-κB survival pathway, which is independent of p53 status. Inhibition of CRM1 by two novel selective inhibitors of nuclear export (SINE), KPT-185 and KPT-276, in MCL cells resulted in significant growth inhibition and apoptosis induction. KPT-185 also induced CRM1 accumulation in the nucleus, resulting in CRM1 degradation by the proteasome. Oral administration of KPT-276 significantly suppressed tumor growth in an MCL-bearing severe combined immunodeficient mouse model, without severe toxicity. Our data suggest that SINE CRM1 antagonists are a potential novel therapy for patients with MCL, particular in relapsed/refractory disease. Copyright © 2013 ISEH - Society for Hematology and Stem Cells. All rights reserved.

Cockpit Resource Management Proficiency as a Factor of Primary Flight Training

DTIC Science & Technology

1992-07-01

Cockpit Resource Management ( CRM ). CRM attempts to explain and address the need and importance of "the communication process in the cockpit, and an...6 Definition of Terms Cockpit Resource Management ( CRM ) : The effective use and coordination of all skills and resources- hardware, software, liveware...E. & Williams K. R. (1987). The Application of CRM to Military Operations. In: Cockpit Resource Management Training-NASA Conference’Publication 2455

Variations in pelvic dimensions do not predict the risk of circumferential resection margin (CRM) involvement in rectal cancer.

PubMed

Salerno, G; Daniels, I R; Brown, G; Norman, A R; Moran, B J; Heald, R J

2007-06-01

The objective of this study was to assess the value of preoperative pelvimetry, using magnetic resonance imaging (MRI), in predicting the risk of an involved circumferential resection margin (CRM) in a group of patients with operable rectal cancer. A cohort of 186 patients from the MERCURY study was selected. These patients' histological CRM status was compared against 14 pelvimetry parameters measured from the preoperative MRI. These measurements were taken by one of the investigators (G.S.), who was blinded to the final CRM status. There was no correlation between the pelvimetry and the CRM status. However, there was a difference in the height of the rectal cancer and the positive CRM rate (p = 0.011). Of 61 patients with low rectal cancer, 10 had positive CRM at histology (16.4% with CI 8.2%-22.1%) compared with 5 of 110 patients with mid/upper rectal cancers (4.5% with CI 0.7%-8.4%). Magnetic resonance imaging can predict clear margins in most cases of rectal cancer. Circumferential resection margin positivity cannot be predicted from pelvimetry in patients with rectal cancer selected for curative surgery. The only predictive factor for a positive CRM in the patients studied was tumor height.

Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression

PubMed Central

Dunipace, Leslie; Ozdemir, Anil; Stathopoulos, Angelike

2011-01-01

It has been shown in several organisms that multiple cis-regulatory modules (CRMs) of a gene locus can be active concurrently to support similar spatiotemporal expression. To understand the functional importance of such seemingly redundant CRMs, we examined two CRMs from the Drosophila snail gene locus, which are both active in the ventral region of pre-gastrulation embryos. By performing a deletion series in a ∼25 kb DNA rescue construct using BAC recombineering and site-directed transgenesis, we demonstrate that the two CRMs are not redundant. The distal CRM is absolutely required for viability, whereas the proximal CRM is required only under extreme conditions such as high temperature. Consistent with their distinct requirements, the CRMs support distinct expression patterns: the proximal CRM exhibits an expanded expression domain relative to endogenous snail, whereas the distal CRM exhibits almost complete overlap with snail except at the anterior-most pole. We further show that the distal CRM normally limits the increased expression domain of the proximal CRM and that the proximal CRM serves as a `damper' for the expression levels driven by the distal CRM. Thus, the two CRMs interact in cis in a non-additive fashion and these interactions may be important for fine-tuning the domains and levels of gene expression. PMID:21813571

Simple criteria to predict margin involvement after chemoradiotherapy and sphincter-sparing for low rectal cancer.

PubMed

Dumont, F; Tilly, C; Dartigues, P; Goéré, D; Honoré, C; Elias, D

2015-09-01

Low rectal cancers carry a high risk of circumferential margin involvement (CRM+). The anatomy of the lower part of the rectum and a long course of chemoradiotherapy (CRT) limit the accuracy of imaging to predict the CRM+. Additional criteria are required. Eighty six patients undergoing rectal resection with a sphincter-sparing procedure after CRT for low rectal cancer between 2000 and 2013 were retrospectively reviewed. Risk factors of CRM+ and the cut-off number of risk factors required to accurately predict the CRM+ were analyzed. The CRM+ rate was 9.3% and in the multivariate analysis, the significant risk factors were a tumor size exceeding 3 cm, poor response to CRT and a fixed tumor. The best cut-off to predict CRM+ was the presence of 2 risk factors. Patients with 0-1 and 2-3 risk factors had a CRM+ respectively in 1.3% and 50% of cases and a 3-year recurrence rate of 7% and 35% after a median follow-up of 50 months. Poor response, a residual tumor greater than 3 cm and a fixed tumor are predictive of CRM+. Sphincter sparing is an oncological safety procedure for patients with 0-1 criteria but not for patients with 2-3 criteria. Copyright © 2015 Elsevier Ltd. All rights reserved.

CRM1 Inhibitors for Antiviral Therapy

PubMed Central

Mathew, Cynthia; Ghildyal, Reena

2017-01-01

Infectious diseases are a major global concern and despite major advancements in medical research, still cause significant morbidity and mortality. Progress in antiviral therapy is particularly hindered by appearance of mutants capable of overcoming the effects of drugs targeting viral components. Alternatively, development of drugs targeting host proteins essential for completion of viral lifecycle holds potential as a viable strategy for antiviral therapy. Nucleocytoplasmic trafficking pathways in particular are involved in several pathological conditions including cancer and viral infections, where hijacking or alteration of function of key transporter proteins, such as Chromosome Region Maintenance1 (CRM1) is observed. Overexpression of CRM1-mediated nuclear export is evident in several solid and hematological malignancies. Interestingly, CRM1-mediated nuclear export of viral components is crucial in various stages of the viral lifecycle and assembly. This review summarizes the role of CRM1 in cancer and selected viruses. Leptomycin B (LMB) is the prototypical inhibitor of CRM1 potent against various cancer cell lines overexpressing CRM1 and in limiting viral infections at nanomolar concentrations in vitro. However, the irreversible shutdown of nuclear export results in high cytotoxicity and limited efficacy in vivo. This has prompted search for synthetic and natural CRM1 inhibitors that can potentially be developed as broadly active antivirals, some of which are summarized in this review. PMID:28702009

Rrp12 and the Exportin Crm1 participate in late assembly events in the nucleolus during 40S ribosomal subunit biogenesis.

PubMed

Moriggi, Giulia; Nieto, Blanca; Dosil, Mercedes

2014-12-01

During the biogenesis of small ribosomal subunits in eukaryotes, the pre-40S particles formed in the nucleolus are rapidly transported to the cytoplasm. The mechanisms underlying the nuclear export of these particles and its coordination with other biogenesis steps are mostly unknown. Here we show that yeast Rrp12 is required for the exit of pre-40S particles to the cytoplasm and for proper maturation dynamics of upstream 90S pre-ribosomes. Due to this, in vivo elimination of Rrp12 leads to an accumulation of nucleoplasmic 90S to pre-40S transitional particles, abnormal 35S pre-rRNA processing, delayed elimination of processing byproducts, and no export of intermediate pre-40S complexes. The exportin Crm1 is also required for the same pre-ribosome maturation events that involve Rrp12. Thus, in addition to their implication in nuclear export, Rrp12 and Crm1 participate in earlier biosynthetic steps that take place in the nucleolus. Our results indicate that, in the 40S subunit synthesis pathway, the completion of early pre-40S particle assembly, the initiation of byproduct degradation and the priming for nuclear export occur in an integrated manner in late 90S pre-ribosomes.

Using the time-to-event continual reassessment method in the presence of partial orders

PubMed Central

Wages, Nolan A.; Conaway, Mark R.; O'Quigley, John

2012-01-01

The time-to-event continual reassessment method (TITE-CRM) was proposed to handle the problem of long trial duration in Phase 1 trials as a result of late-onset toxicities. Here, we implement the TITE-CRM in dose–finding trials of combinations of agents. When studying multiple agents, monotonicity of the dose-toxicity curve is not clearly defined. Therefore, the toxicity probabilities follow a partial order, meaning that there are pairs of treatments for which the ordering of the toxicity probabilities is not known at the start of the trial. A CRM design for partially ordered trials (PO-CRM) was recently proposed. Simulation studies show that extending the TITE-CRM to the partial order setting produces results similar to those of the PO-CRM in terms of maximum tolerated dose recommendation yet reduces the duration of the trial. PMID:22806898

Segregating Variation in the Polycomb Group Gene cramped Alters the Effect of Temperature on Multiple Traits

PubMed Central

Gibert, Jean-Michel; Karch, François; Schlötterer, Christian

2011-01-01

The phenotype produced by a given genotype can be strongly modulated by environmental conditions. Therefore, natural populations continuously adapt to environment heterogeneity to maintain optimal phenotypes. It generates a high genetic variation in environment-sensitive gene networks, which is thought to facilitate evolution. Here we analyze the chromatin regulator crm, identified as a candidate for adaptation of Drosophila melanogaster to northern latitudes. We show that crm contributes to environmental canalization. In particular, crm modulates the effect of temperature on a genomic region encoding Hedgehog and Wingless signaling effectors. crm affects this region through both constitutive heterochromatin and Polycomb silencing. Furthermore, we show that crm European and African natural variants shift the reaction norms of plastic traits. Interestingly, traits modulated by crm natural variants can differ markedly between Drosophila species, suggesting that temperature adaptation facilitates their evolution. PMID:21283785

Evaluating multidisciplinary health care teams: taking the crisis out of CRM.

PubMed

Sutton, Gigi

2009-08-01

High-reliability organisations are those, such as within the aviation industry, which operate in complex, hazardous environments and yet despite this are able to balance safety and effectiveness. Crew resource management (CRM) training is used to improve the non-technical skills of aviation crews and other high-reliability teams. To date, CRM within the health sector has been restricted to use with "crisis teams" and "crisis events". The purpose of this discussion paper is to examine the application of CRM to acute, ward-based multidisciplinary health care teams and more broadly to argue for the repositioning of health-based CRM to address effective everyday function, of which "crisis events" form just one part. It is argued that CRM methodology could be applied to evaluate ward-based health care teams and design non-technical skills training to increase their efficacy, promote better patient outcomes, and facilitate a range of positive personal and organisational level outcomes.

The production and certification of a plutonium equal-atom reference material: NBL CRM 128

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crawford, D.W.; Gradle, C.G.; Soriano, M.D.

This report describes the design, production, and certification of the New Brunswick Laboratory plutonium equal-atom certified reference material (CRM), NBL CRM 128. The primary use of this CRM is for the determination of bias corrections encountered in the operation of a mass spectrometer. This reference material is available to the US Department of Energy contractor-operated and government-operated laboratories, as well as to the international nuclear safeguards community. The absolute, or unbiased, certified value for the CRM's Pu-242/Pu-239 ratio is 1.00063 {plus minus} 0.00026 (95% confidence interval) as of October 1, 1984. This value was obtained through the quantitative blending ofmore » high-purity, chemically and isotopically characterized separated isotopes, as well as through intercomparisons of CRM samples with calibration mixtures using thermal ionization mass spectrometry. 32 tabs.« less

Transfer of learning and patient outcome in simulated crisis resource management: a systematic review.

PubMed

Boet, Sylvain; Bould, M Dylan; Fung, Lillia; Qosa, Haytham; Perrier, Laure; Tavares, Walter; Reeves, Scott; Tricco, Andrea C

2014-06-01

Simulation-based learning is increasingly used by healthcare professionals as a safe method to learn and practice non-technical skills, such as communication and leadership, required for effective crisis resource management (CRM). This systematic review was conducted to gain a better understanding of the impact of simulation-based CRM teaching on transfer of learning to the workplace and subsequent changes in patient outcomes. Studies on CRM, crisis management, crew resource management, teamwork, and simulation published up to September 2012 were searched in MEDLINE(®), EMBASE™, CINAHL, Cochrane Central Register of Controlled Trials, and ERIC. All studies that used simulation-based CRM teaching with outcomes measured at Kirkpatrick Level 3 (transfer of learning to the workplace) or 4 (patient outcome) were included. Studies measuring only learners' reactions or simple learning (Kirkpatrick Level 1 or 2, respectively) were excluded. Two authors independently reviewed all identified titles and abstracts for eligibility. Nine articles were identified as meeting the inclusion criteria. Four studies measured transfer of simulation-based CRM learning into the clinical setting (Kirkpatrick Level 3). In three of these studies, simulation-enhanced CRM training was found significantly more effective than no intervention or didactic teaching. Five studies measured patient outcomes (Kirkpatrick Level 4). Only one of these studies found that simulation-based CRM training made a clearly significant impact on patient mortality. Based on a small number of studies, this systematic review found that CRM skills learned at the simulation centre are transferred to clinical settings, and the acquired CRM skills may translate to improved patient outcomes, including a decrease in mortality.

CRM done right.

PubMed

Rigby, Darrell K; Ledingham, Dianne

2004-11-01

Disappointed by the high costs and elusive benefits, early adopters of customer relationship management systems came, in the post dot-com era, to view the technology as just another overhyped IT investment whose initial promise would never be fulfilled. But this year, something unexpected is happening. System sales are rising, and executives are reporting satisfaction with their CRM investments. What's changed? A wide range of companies are successfully taking a pragmatic, disciplined approach to CRM. Rather than use it to transform entire businesses, they've directed their investments toward solving clearly defined problems within their customer relationship cycle. The authors have distilled the experiences of these CRM leaders into four questions that all companies should ask themselves as they launch their own CRM initiatives: Is the problem strategic? Is the system focused on the pain point? Do we need perfect data? What's the right way to expand an initial implementation? The questions reflect a new realism about when and how to deploy CRM to best advantage. Understanding that highly accurate and timely data are not required everywhere in their businesses, CRM leaders have tailored their real-time initiatives to those customer relationships that can be significantly enhanced by "perfect" information. Once they've succeeded with their first targeted CRM project, they can use it as a springboard for solving additional problems. CRM, in other words, is coming to resemble any other valuable management tool, and the keys to successful implementation are also becoming familiar: strong executive and business-unit leadership, careful strategic planning, clear performance measures, and a coordinated program that combines organizational and process changes with the application of new technology.

Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents

PubMed Central

Turner, Joel G.; Dawson, Jana; Cubitt, Christopher L.; Baz, Rachid; Sullivan, Daniel M.

2014-01-01

Nuclear-cytoplasmic trafficking of proteins is a significant factor in the development of cancer and drug resistance. Subcellular localization of exported proteins linked to cancer development include those involved in cell growth and proliferation, apoptosis, cell cycle regulation, transformation, angiogenesis, cell adhesion, invasion, and metastasis. Here, we examined the basic mechanisms involved in the export of proteins from the nucleus to the cytoplasm. All proteins over 40 kDa use the nuclear pore complex to gain entry or exit from the nucleus, with the primary nuclear export molecule involved in these processes being chromosome region maintenance 1 (CRM1, exportin 1 or XPO1). Proteins exported from the nucleus must possess a hydrophobic nuclear export signal (NES) peptide that binds to a hydrophobic groove containing an active-site Cys528 in the CRM1 protein. CRM1 inhibitors function largely by covalent modification of the active site Cys528 and prevent binding to the cargo protein NES. In the absence of a CRM1 inhibitor, CRM1 binds cooperatively to the NES of the cargo protein and RanGTP, forming a trimer that is actively transported out of the nucleus by facilitated diffusion. Nuclear export can be blocked by CRM1 inhibitors, NES peptide inhibitors or by preventing post-translational modification of cargo proteins. Clinical trials using the classic CRM1 inhibitor leptomycin B proved too toxic for patients; however, a new generation of less toxic small molecule inhibitors are being used in clinical trials in patients with both hematological malignancies and solid tumors. Additional trials are being initiated using small-molecule CRM1 inhibitors in combination with chemotherapeutics such as pegylated liposomal doxorubicin. In this review, we present evidence that combining the new CRM1 inhibitors with other classes of therapeutics may prove effective in the treatment of cancer. Potential combinatorial therapies discussed include the use of CRM1 inhibitors and the addition of alkylating agents (melphalan), anthracyclines (doxorubicin and daunomycin), BRAF inhibitors, platinum drugs (cisplatin and oxaliplatin), proteosome inhibitors (bortezomib and carfilzomib), or tyrosine-kinase inhibitors (imatinib). Also, the sequence of treatment may be important for combination therapy. We found that the most effective treatment regimen involved first priming the cancer cells with the CRM1 inhibitor followed by doxorubicin, bortezomib, carfilzomib, or melphalan. This order sensitized both de novo and acquired drug-resistant cancer cell lines. PMID:24631834

Immunogenicity and safety of concomitant administration of a combined hepatitis A/B vaccine and a quadrivalent meningococcal conjugate vaccine in healthy adults.

PubMed

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil C; Meyer, Seetha; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani Kumar

2015-01-01

This phase 3b randomized, open-label study evaluated the immunogenicity and safety of coadministration of a hepatitis A and/or B vaccine with a quadrivalent oligosaccharide meningococcal CRM197 -conjugate vaccine (MenACWY-CRM), in the context of an accelerated hepatitis A and/or B immunization schedule. A total of 252 healthy adult subjects were randomized to three groups to receive hepatitis A/B only (HepA/B), hepatitis A/B coadministered with MenACWY-CRM (HepA/B+MenACWY-CRM), or MenACWY-CRM only (MenACWY-CRM). Hepatitis A and/or B vaccination was administered in the form of a single booster dose or a primary three-dose series, depending on the hepatitis A and/or B vaccination history of subjects. Antibody responses to hepatitis A/B vaccination were assessed 1 month following the last hepatitis A and/or B dose. Serum bactericidal activity with human complement (hSBA) against meningococcal serogroups A, C, W-135, and Y was assessed 1 month post-MenACWY-CRM vaccination. Safety was monitored throughout the study. At 1 month following the final hepatitis A and/or B vaccination, concomitant administration of hepatitis A/B and MenACWY-CRM was non-inferior to administration of hepatitis A/B alone in terms of geometric mean concentrations of antibodies against the hepatitis A and B antigens. One month post-MenACWY-CRM vaccination, the percentages of subjects achieving hSBA titers ≥8 for serogroups A, C, W-135, and Y in the HepA/B+MenACWY-CRM group (76, 87, 99, and 94%, respectively) were comparable to those in the MenACWY-CRM group (67, 82, 96, and 88%, respectively). The percentages of subjects reporting adverse events (AEs) were similar across study groups and a majority of the reported AEs were mild to moderate in nature. There were no study vaccine-related serious AEs. MenACWY-CRM can be administered concomitantly with a hepatitis A and/or B vaccine in the context of an accelerated hepatitis A and/or B immunization schedule without increasing safety concerns or compromising the immune responses to any of the vaccine antigens. [NCT01453348]. © 2014 International Society of Travel Medicine.

Sensitivity simulations of superparameterised convection in a general circulation model

NASA Astrophysics Data System (ADS)

Rybka, Harald; Tost, Holger

2015-04-01

Cloud Resolving Models (CRMs) covering a horizontal grid spacing from a few hundred meters up to a few kilometers have been used to explicitly resolve small-scale and mesoscale processes. Special attention has been paid to realistically represent cloud dynamics and cloud microphysics involving cloud droplets, ice crystals, graupel and aerosols. The entire variety of physical processes on the small-scale interacts with the larger-scale circulation and has to be parameterised on the coarse grid of a general circulation model (GCM). Since more than a decade an approach to connect these two types of models which act on different scales has been developed to resolve cloud processes and their interactions with the large-scale flow. The concept is to use an ensemble of CRM grid cells in a 2D or 3D configuration in each grid cell of the GCM to explicitly represent small-scale processes avoiding the use of convection and large-scale cloud parameterisations which are a major source for uncertainties regarding clouds. The idea is commonly known as superparameterisation or cloud-resolving convection parameterisation. This study presents different simulations of an adapted Earth System Model (ESM) connected to a CRM which acts as a superparameterisation. Simulations have been performed with the ECHAM/MESSy atmospheric chemistry (EMAC) model comparing conventional GCM runs (including convection and large-scale cloud parameterisations) with the improved superparameterised EMAC (SP-EMAC) modeling one year with prescribed sea surface temperatures and sea ice content. The sensitivity of atmospheric temperature, precipiation patterns, cloud amount and types is observed changing the embedded CRM represenation (orientation, width, no. of CRM cells, 2D vs. 3D). Additionally, we also evaluate the radiation balance with the new model configuration, and systematically analyse the impact of tunable parameters on the radiation budget and hydrological cycle. Furthermore, the subgrid variability (individual CRM cell output) is analysed in order to illustrate the importance of a highly varying atmospheric structure inside a single GCM grid box. Finally, the convective transport of Radon is observed comparing different transport procedures and their influence on the vertical tracer distribution.

An allele of the crm gene blocks cyanobacterial circadian rhythms.

PubMed

Boyd, Joseph S; Bordowitz, Juliana R; Bree, Anna C; Golden, Susan S

2013-08-20

The SasA-RpaA two-component system constitutes a key output pathway of the cyanobacterial Kai circadian oscillator. To date, rhythm of phycobilisome associated (rpaA) is the only gene other than kaiA, kaiB, and kaiC, which encode the oscillator itself, whose mutation causes completely arrhythmic gene expression. Here we report a unique transposon insertion allele in a small ORF located immediately upstream of rpaA in Synechococcus elongatus PCC 7942 termed crm (for circadian rhythmicity modulator), which results in arrhythmic promoter activity but does not affect steady-state levels of RpaA. The crm ORF complements the defect when expressed in trans, but only if it can be translated, suggesting that crm encodes a small protein. The crm1 insertion allele phenotypes are distinct from those of an rpaA null; crm1 mutants are able to grow in a light:dark cycle and have no detectable oscillations of KaiC phosphorylation, whereas low-amplitude KaiC phosphorylation rhythms persist in the absence of RpaA. Levels of phosphorylated RpaA in vivo measured over time are significantly altered compared with WT in the crm1 mutant as well as in the absence of KaiC. Taken together, these results are consistent with the hypothesis that the Crm polypeptide modulates a circadian-specific activity of RpaA.

The effects of Crew Resource Management (CRM) training on flight attendants' safety attitudes.

PubMed

Ford, Jane; Henderson, Robert; O'Hare, David

2014-02-01

A number of well-known incidents and accidents had led the aviation industry to introduce Crew Resource Management (CRM) training designed specifically for flight attendants, and joint (pilot and flight attendant) CRM training as a way to improve teamwork and communication. The development of these new CRM training programs during the 1990s highlighted the growing need for programs to be evaluated using research tools that had been validated for the flight attendant population. The FSAQ (Flight Safety Attitudes Questionnaire-Flight Attendants) was designed specifically to obtain safety attitude data from flight attendants working for an Asia-Pacific airline. Flight attendants volunteered to participate in a study before receiving CRM training (N=563) and again (N=526) after CRM training. Almost half (13) of the items from the 36-item FSAQ showed highly significant changes following CRM training. Years of experience, crew position, seniority, leadership roles, flight attendant crew size, and length of route flown were all predictive of safety attitudes. CRM training for flight attendants is a valuable tool for increasing positive teamwork behaviors between the flight attendant and pilot sub-groups. Joint training sessions, where flight attendants and pilots work together to find solutions to in-flight emergency scenarios, provide a particularly useful strategy in breaking down communication barriers between the two sub-groups. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

Human error and crew resource management failures in Naval aviation mishaps: a review of U.S. Naval Safety Center data, 1990-96.

PubMed

Wiegmann, D A; Shappell, S A

1999-12-01

The present study examined the role of human error and crew-resource management (CRM) failures in U.S. Naval aviation mishaps. All tactical jet (TACAIR) and rotary wing Class A flight mishaps between fiscal years 1990-1996 were reviewed. Results indicated that over 75% of both TACAIR and rotary wing mishaps were attributable, at least in part, to some form of human error of which 70% were associated with aircrew human factors. Of these aircrew-related mishaps, approximately 56% involved at least one CRM failure. These percentages are very similar to those observed prior to the implementation of aircrew coordination training (ACT) in the fleet, suggesting that the initial benefits of the program have not persisted and that CRM failures continue to plague Naval aviation. Closer examination of these CRM-related mishaps suggest that the type of flight operations (preflight, routine, emergency) do play a role in the etiology of CRM failures. A larger percentage of CRM failures occurred during non-routine or extremis flight situations when TACAIR mishaps were considered. In contrast, a larger percentage of rotary wing CRM mishaps involved failures that occurred during routine flight operations. These findings illustrate the complex etiology of CRM failures within Naval aviation and support the need for ACT programs tailored to the unique problems faced by specific communities in the fleet.

Use of simplifier scenarios for CRM training

NASA Technical Reports Server (NTRS)

Weatherly, D.

1984-01-01

Cockpit resource management (CRM) at Metro Airlines is discussed. The process by which the program of CRM training was initiated is mentioned. Management aspects of various flying scenarios are considered. The transfer of training from the classroom to the field is assessed.

Matrix solid phase dispersion-assisted BCR sequential extraction method for metal partitioning in surface estuarine sediments.

PubMed

Martínez-Fernández, Marta; Barciela-Alonso, María Carmen; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar

2011-01-15

The BCR (the Community Bureau of Reference) of the European Union sequential extraction scheme for metal partitioning in estuarine sediments has been accelerated by using a matrix solid phase dispersion (MSPD) approach. The MSPD assisted BCR procedure consists of passing the extractants proposed by conventional BCR protocol (0.11 M acetic acid, 0.1M hydroxylammonium chloride and 8.8M hydrogen peroxide plus 1M ammonium acetate) through the dispersed sample packaged inside a disposable syringe. Different silica-, magnesium- and aluminium-based materials were tested as dispersing agents and sea sand was found to offer the best performances. Variables for assisting the three stages of the BCR protocol were optimized, and accurate results were obtained when assisting the first and the third stages (exchangeable and oxidizable fractions, respectively). However, lack of accuracy was observed when assisting the second step (reducible fraction) and this result agrees with most of the assisted BCR procedures for which extracting the reducible fraction is the most troublesome stage. The organic matter oxidation (third stage) was successfully assisted by passing hydrogen peroxide at 50°C through the dispersed sample inside de syringe just before passing ammonium acetate. Therefore, the time-consuming and unsafe conventional organic matter oxidation processes, commonly performed even for microwave/ultrasounds assisted BCR procedures, are totally avoided. Inductively coupled plasma-mass spectrometry (ICP-MS) was used as a selective detector. The target elements were Cd, Co, Cr, Mn, Ni, Sr and Zn (first stage), Cd, Co and Ni (second stage), and Co, Cr, Mn, Ni, Sr and Zn (third stage). Repeatability of the method (n=7) was good, and RSDs values of 9, 10, 10, 8, 8, 3 and 8% was obtained for Cd, Co, Cr, Mn, Ni, Sr and Zn, respectively (first stage); 10, 9 and 9% for Cd, Co and Ni, respectively (second stage); and 6, 2, 3, 4, 7 and 9% Co, Cr, Mn, Ni, Sr and Zn, respectively (third stage). The procedure was also validated by analysing two certified reference materials (CRM 601 and CRM 701). Good accuracy was obtained for the target elements extracted at the first stage: Cd (4.0 ± 0.1 and 7.3 ± 0.09 μg g(-1) in CRM 601 and CRM 701, respectively), Cr (0.36 ± 0.008 and 2.21 ± 0.08 μg g(-1) in CRM 601 and CRM 701, respectively), Ni (8.0 ± 0.3 and 15.4 ± 0.3 μg g(-1) in CRM 601 and CRM 701, respectively) and Zn (262 ± 3 and 203 ± 3 μg g(-1) in CRM 601 and CRM 701, respectively). Also, good accuracy was observed for elements extracted at the third step: Cd (1.8 ± 0.09 and 0.29 ± 0.03 μg g(-1) in CRM 601 and CRM 701, respectively), Cr (145 ± 4 μg g(-1) in CRM 701), Ni (8.2 ± 0.7 and 15.1 ± 0.5 μg g(-1) in CRM 601 and CRM 701, respectively) and Zn (45 ± 0.7 μg g(-1) in CRM 701). Copyright © 2010 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Xiao-han; Deng, Suo; Li, Meng

Highlights: Black-Right-Pointing-Pointer HB-EGF over-expression in A2780/Taxol, A2780/CDDP cells and the matched xenografts. Black-Right-Pointing-Pointer CRM197 induces enhanced apoptosis in A2780/Taxol and A2780/CDDP cells. Black-Right-Pointing-Pointer CRM197 arrests A2780/Taxol and A2780/CDDP cells at G0/G1 phase. Black-Right-Pointing-Pointer CRM197 suppressed the A2780/Taxol and A2780/CDDP growth of xenografts. -- Abstract: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. Cross-reacting material 197 (CRM197), a specific HB-EGF inhibitor, has been proven to represent possible chemotherapeutic agent for ovarian cancer. However, the effect of CRM197 on the resistant ovarian carcinoma cells has not been sufficiently elucidated. Here, we found that HB-EGF wasmore » over-expressed in a paclitaxel-resistant human ovarian carcinoma cell line (A2780/Taxol) and a cisplatin-resistant cell line (A2780/CDDP), as well as the xenograft mouse tissue samples with these cells. To investigate the possible significance of the HB-EGF over-expression in A2780/Taxol and A2780/CDDP cells, we inhibited HB-EGF expression by CRM197 to investigate the effect of CRM197 treatment on these cells. We observed that CRM197 significantly induced anti-proliferative activity in a dose-dependent manner with the cell-cycle arrest at the G0/G1 phase and enhanced apoptosis in A2780/Taxol and A2780/CDDP cells. The sensitive ovarian carcinoma parental cell line (A2780), A2780/Taxol and A2780/CDDP cells formed tumors in nude mice, and enhanced tumorigenicity was observed in drug-resistant tumors. Furthermore, we observed that CRM197 significantly suppressed the growth of drug-resistant ovarian cancer xenografts in vivo (p < 0.001). These results suggest that CRM197 as an HB-EGF-targeted agent has potent anti-tumor activity in paclitaxel- and cisplatin-resistant ovarian cancer which over-express HB-EGF.« less

Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.

PubMed

Reisinger, Keith S; Baxter, Roger; Block, Stanley L; Shah, Jina; Bedell, Lisa; Dull, Peter M

2009-12-01

Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals > or = 15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of > or = 1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than -10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra.

Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population

PubMed Central

Apland, James P.; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H.; Pidoplichko, Volodymyr I.; Rossetti, Katia

2018-01-01

The currently Food and Drug Administration–approved anticonvulsant for the treatment of status epilepticus (SE) induced by nerve agents is the benzodiazepine diazepam; however, diazepam does not appear to offer neuroprotective benefits. This is of particular concern with respect to the protection of children because, in the developing brain, synaptic transmission mediated via GABAA receptors, the target of diazepam, is weak. In the present study, we exposed 21-day-old male rats to 1.2 × LD50 soman and compared the antiseizure, antilethality, and neuroprotective efficacy of diazepam (10 mg/kg), LY293558 (an AMPA/GluK1 receptor antagonist; 15 mg/kg), caramiphen (CRM, an antimuscarinic with NMDA receptor-antagonistic properties; 50 mg/kg), and LY293558 (15 mg/kg) + CRM (50 mg/kg), administered 1 hour after exposure. Diazepam, LY293558, and LY293558 + CRM, but not CRM alone, terminated SE; LY293558 + CRM treatment acted significantly faster and produced a survival rate greater than 85%. Thirty days after soman exposure, neurodegeneration in limbic regions was most severe in the CRM-treated group, minimal to severe—depending on the region—in the diazepam group, absent to moderate in the LY293558-treated group, and totally absent in the LY293558 + CRM group. Amygdala and hippocampal atrophy, a severe reduction in spontaneous inhibitory activity in the basolateral amygdala, and increased anxiety-like behavior in the open-field and acoustic startle response tests were present in the diazepam and CRM groups, whereas the LY293558 and LY293558 + CRM groups did not differ from controls. The combined administration of LY293558 and CRM, by blocking mainly AMPA, GluK1, and NMDA receptors, is a very effective anticonvulsant and neuroprotective therapy against soman in young rats. PMID:29467308

Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins.

PubMed

Takeda, Akiko; Sarma, Nayan J; Abdul-Nabi, Anmaar M; Yaseen, Nabeel R

2010-05-21

NUP98 is a nucleoporin that plays complex roles in the nucleocytoplasmic trafficking of macromolecules. Rearrangements of the NUP98 gene in human leukemia result in the expression of numerous fusion oncoproteins whose effect on nucleocytoplasmic trafficking is poorly understood. The present study was undertaken to determine the effects of leukemogenic NUP98 fusion proteins on CRM1-mediated nuclear export. NUP98-HOXA9, a prototypic NUP98 fusion, inhibited the nuclear export of two known CRM1 substrates: mutated cytoplasmic nucleophosmin and HIV-1 Rev. In vitro binding assays revealed that NUP98-HOXA9 binds CRM1 through the FG repeat motif in a Ran-GTP-dependent manner similar to but stronger than the interaction between CRM1 and its export substrates. Two NUP98 fusions, NUP98-HOXA9 and NUP98-DDX10, whose fusion partners are structurally and functionally unrelated, interacted with endogenous CRM1 in myeloid cells as shown by co-immunoprecipitation. These leukemogenic NUP98 fusion proteins interacted with CRM1, Ran, and the nucleoporin NUP214 in a manner fundamentally different from that of wild-type NUP98. NUP98-HOXA9 and NUP98-DDX10 formed characteristic aggregates within the nuclei of a myeloid cell line and primary human CD34+ cells and caused aberrant localization of CRM1 to these aggregates. These NUP98 fusions caused nuclear accumulation of two transcription factors, NFAT and NFkappaB, that are regulated by CRM1-mediated export. The nuclear entrapment of NFAT and NFkappaB correlated with enhanced transcription from promoters responsive to these transcription factors. Taken together, the results suggest a new mechanism by which NUP98 fusions dysregulate transcription and cause leukemia, namely, inhibition of CRM1-mediated nuclear export with aberrant nuclear retention of transcriptional regulators.

The Influence of Hospital Volume on Circumferential Resection Margin Involvement: Results of the Dutch Surgical Colorectal Audit.

PubMed

Gietelink, Lieke; Henneman, Daniel; van Leersum, Nicoline J; de Noo, Mirre; Manusama, Eric; Tanis, Pieter J; Tollenaar, Rob A E M; Wouters, Michel W J M

2016-04-01

This population-based study evaluates the association between hospital volume and CRM (circumferential resection margin) involvement, adjusted for other confounders, in rectal cancer surgery. A low hospital volume (<20 cases/year) was independently associated with a higher risk of CRM involvement (odds ratio=1.54; 95% CI: 1.12-2.11). To evaluate the association between hospital volume and CRM (circumferential resection margin) involvement in rectal cancer surgery. To guarantee the quality of surgical treatment of rectal cancer, the Association of Surgeons of the Netherlands has stated a minimal annual volume standard of 20 procedures per hospital. The influence of hospital volume has been examined for different outcome variables in rectal cancer surgery. Its influence on the pathological outcome (CRM) however remains unclear. As long-term outcomes are best predicted by the CRM status, this parameter is of essential importance in the debate on the justification of minimal volume standards in rectal cancer surgery. Data from the Dutch Surgical Colorectal Audit (2011-2012) were used. Hospital volume was divided into 3 groups, and baseline characteristics were described. The influence of hospital volume on CRM involvement was analyzed, in a multivariate model, between low- and high-volume hospitals, according to the minimal volume standards. This study included 5161 patients. CRM was recorded in 86% of patients. CRM involvement was 11% in low-volume group versus 7.7% and 7.9% in the medium- and high-volume group (P≤0.001). After adjustment for relevant confounders, the influence of hospital volume on CRM involvement was still significant odds ratio (OR) = 1.54; 95% CI: 1.12-2.11). The outcomes of this pooled analysis support minimal volume standards in rectal cancer surgery. Low hospital volume was independently associated with a higher risk of CRM involvement (OR = 1.54; 95% CI: 1.12-2.11).

THE CIDOC CRM GAME: A Serious Game Approach to Ontology Learning

NASA Astrophysics Data System (ADS)

Guillem, A.; Bruseker, G.

2017-08-01

Formal ontologies such as CIDOC CRM (Conceptual Reference Model) form part of the central strategy for the medium and longterm integration of cultural heritage data to allow for its greater valorization and dissemination. Despite this, uptake of CIDOC CRM at the ground level of Cultural Heriage (CH) practice is limited. Part of the reason behind this lack of uptake lies in the fact that ontologies are considered too complicated and abstract for application in real life scenarios. This paper presents the rationale behind and the design of a CIDOC CRM game, the intent of which is to provide a learning mechanism to allow learners of wide backgrounds and interests to approach CIDOC CRM in a hands-on and interactive fashion. The CIDOC CRM game consist of decks of cards and game boards that allow players to engage with the concepts of a formal ontology in relation to real data in an entertaining and informative way. It is argued that the CIDOC CRM Game can form an important part of introducing the basic elements of formal ontology and this standard to a wider audience in order to aid wider understanding and adoption of the same.

77 FR 75045 - Locomotive Safety Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-19

...), the Central Railway MFG (CRM), D. P. Honold (Honold), David Lombardi (Lombardi), Paul, Reich & Myers... more expensive and less effective. 6. Small Businesses According to the CRM's petition, the... consistent with the railroads and vendors business philosophy. Thus, FRA disagrees with the assertions of CRM...

77 FR 38581 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-28

...: Minority Business Development Agency. Title: Online Customer Relationship Management (CRM)/Performance... client information, service activities and progress on attainment of program goals via the Online CRM/Performance Databases. The data collected through the Online CRM/Performance Databases is used to regularly...

TOF-SIMS for Rapid Nuclear Forensics Evaluation of Uranium Oxide Particles

DTIC Science & Technology

2011-03-01

Fraction U-238 nU U metal CRM 112-A NBL Metal Assay and Isotopic .000052458 .0072017 --- .9927458 nUO2 UO2 --- NBL Commercial material...0 .992745 dU U metal CRM 115 NBL Uranium Assay .0000076 .0020291 .0000322 .9979311 dUO2 UO2 --- IBI Labs Commercial material --- .002- .0035...U500* U3O8 CRM U500 NBL Isotopic .005181 .49696 .000755 .49711 U900* U3O8 CRM U900 NBL Isotopic .007777 .90196 .003327 .08693 *Sample

Workshop on Integrated Crew Resource Management (CRM), 19-21 November 1991

DTIC Science & Technology

1992-03-01

VI DOT/FAAIRD-92/5 Workshop on Integrated Research and Development Service Crew Resource Washington, DC 20591 Management ( CRM ) AD-A252 980 II! Ir H... Management ( CRM ) Page i Technical Report Documentation Page 1. Report No. 2. Government Accession No. 3. Recipient’s Catalog No. DOT/FAA/RD-92/5I 4. Title and...Subtitle S. Report Date May 1992 Workshop on Integrated Crew Resource Management ( CRM ) 6. Performing Organization Code ARD-1 8. Performing

Pediatric crisis resource management training improves emergency medicine trainees' perceived ability to manage emergencies and ability to identify teamwork errors.

PubMed

Bank, Ilana; Snell, Linda; Bhanji, Farhan

2014-12-01

Improved pediatric crisis resource management (CRM) training is needed in emergency medicine residencies because of the variable nature of exposure to critically ill pediatric patients during training. We created a short, needs-based pediatric CRM simulation workshop with postactivity follow-up to determine retention of CRM knowledge. Our aims were to provide a realistic learning experience for residents and to help the learners recognize common errors in teamwork and improve their perceived abilities to manage ill pediatric patients. Residents participated in a 4-hour objectives-based workshop derived from a formal needs assessment. To quantify their subjective abilities to manage pediatric cases, the residents completed a postworkshop survey (with a retrospective precomponent to assess perceived change). Ability to identify CRM errors was determined via a written assessment of scripted errors in a prerecorded video observed before and 1 month after completion of the workshop. Fifteen of the 16 eligible emergency medicine residents (postgraduate year 1-5) attended the workshop and completed the surveys. There were significant differences in 15 of 16 retrospective pre to post survey items using the Wilcoxon rank sum test for non-parametric data. These included ability to be an effective team leader in general (P < 0.008), delegating tasks appropriately (P < 0.009), and ability to ensure closed-loop communication (P < 0.008). There was a significant improvement in identification of CRM errors through the use of the video assessment from 3 of the 12 CRM errors to 7 of the 12 CRM errors (P < 0.006). The pediatric CRM simulation-based workshop improved the residents' self-perceptions of their pediatric CRM abilities and improved their performance on a video assessment task.

imDEV: a graphical user interface to R multivariate analysis tools in Microsoft Excel.

PubMed

Grapov, Dmitry; Newman, John W

2012-09-01

Interactive modules for Data Exploration and Visualization (imDEV) is a Microsoft Excel spreadsheet embedded application providing an integrated environment for the analysis of omics data through a user-friendly interface. Individual modules enables interactive and dynamic analyses of large data by interfacing R's multivariate statistics and highly customizable visualizations with the spreadsheet environment, aiding robust inferences and generating information-rich data visualizations. This tool provides access to multiple comparisons with false discovery correction, hierarchical clustering, principal and independent component analyses, partial least squares regression and discriminant analysis, through an intuitive interface for creating high-quality two- and a three-dimensional visualizations including scatter plot matrices, distribution plots, dendrograms, heat maps, biplots, trellis biplots and correlation networks. Freely available for download at http://sourceforge.net/projects/imdev/. Implemented in R and VBA and supported by Microsoft Excel (2003, 2007 and 2010).

Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals.

PubMed

Fung, Ho Yee Joyce; Fu, Szu-Chin; Chook, Yuh Min

2017-03-10

Nuclear export receptor CRM1 binds highly variable nuclear export signals (NESs) in hundreds of different cargoes. Previously we have shown that CRM1 binds NESs in both polypeptide orientations (Fung et al., 2015). Here, we show crystal structures of CRM1 bound to eight additional NESs which reveal diverse conformations that range from loop-like to all-helix, which occupy different extents of the invariant NES-binding groove. Analysis of all NES structures show 5-6 distinct backbone conformations where the only conserved secondary structural element is one turn of helix that binds the central portion of the CRM1 groove. All NESs also participate in main chain hydrogen bonding with human CRM1 Lys568 side chain, which acts as a specificity filter that prevents binding of non-NES peptides. The large conformational range of NES backbones explains the lack of a fixed pattern for its 3-5 hydrophobic anchor residues, which in turn explains the large array of peptide sequences that can function as NESs.

Immunogenicity and safety of a quadrivalent meningococcal polysaccharide CRM conjugate vaccine in infants and toddlers.

PubMed

Tregnaghi, Miguel; Lopez, Pio; Stamboulian, Daniel; Graña, Gabriela; Odrljin, Tatjana; Bedell, Lisa; Dull, Peter M

2014-09-01

This phase III study assessed the safety and immunogenicity of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, administered with routine vaccines starting at 2 months of age. Healthy infants received MenACWY-CRM in a two- or three-dose primary infant series plus a single toddler dose. In addition, a two-dose toddler catch-up series was evaluated. Immune responses to MenACWY-CRM were assessed for serum bactericidal activity with human complement (hSBA). Reactogenicity and safety results were collected systematically. After a full infant/toddler series or two-dose toddler catch-up series, MenACWY-CRM elicited immune responses against the four serogroups in 94-100% of subjects. Noninferiority of the two- versus three-dose MenACWY-CRM infant dosing regimen was established for geometric mean titers for all serogroups. Following the three-dose infant primary series, 89-98% of subjects achieved an hSBA ≥ 8 across all serogroups. Immune responses to concomitant routine vaccines given with MenACWY-CRM were noninferior to responses to routine vaccines alone, except for pertactin after the two-dose infant series. Noninferiority criteria were met for all concomitant antigens after the three-dose infant series. MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated. No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Targeted delivery of rosmarinic acid across the blood-brain barrier for neuronal rescue using polyacrylamide-chitosan-poly(lactide-co-glycolide) nanoparticles with surface cross-reacting material 197 and apolipoprotein E.

PubMed

Kuo, Yung-Chih; Rajesh, Rajendiran

2017-08-07

Rosmarinic acid-loaded polyacrylamide-chitosan-poly(lactide-co-glycolide) nanoparticles (RA-PAAM-CH-PLGA NPs) were grafted with cross-reacting material 197 (CRM197) and apolipoprotein E (ApoE) for targeting of the blood-brain barrier (BBB) and rescuing degenerated neurons. The polymeric nanocarriers were prepared by microemulsion, solvent diffusion, grafting, and surface modification, and CRM197-ApoE-RA-PAAM-CH-PLGA NPs were used to treat human brain-microvascular endothelial cells, RWA264.7 cells, and Aβ-insulted SK-N-MC cells. Experimental results revealed that an increase in the weight percentage of PAAM decreased the particle size, zeta potential, and grafting efficiency of CRM197 and ApoE. In addition, surface DSPE-PEG(2000) could protect CRM197-ApoE-RA-PAAM-CH-PLGA NPs against uptake by RWA264.7 cells. An increase in the concentration of CRM197 and ApoE decreased the transendothelial electrical resistance and increased the ability of propidium iodide and RA to cross the BBB. The order in the viability of apoptotic SK-N-MC cells was CRM197-ApoE-RA-PAAM-CH-PLGA NPs > CRM197-RA-PAAM-CH-PLGA NPs > RA. Thus, CRM197-ApoE-RA-PAAM-CH-PLGA NPs can be a promising formulation to deliver RA to Aβ-insulted neurons in the pharmacotherapy of Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Pneumococcal Conjugate Vaccines and Otitis Media: An Appraisal of the Clinical Trials

PubMed Central

Fletcher, Mark A.; Fritzell, Bernard

2012-01-01

Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POET; vaccine, 11-valent PCV [PCV11]-PD). For the microbiological endpoint, vaccine efficacy against vaccine-serotype pneumococcal otitis media was about 60% across trials. Against the clinical endpoint of all episodes, vaccine efficacy was 7% (PCV7-CRM/NCKP), 6% (PCV7-CRM/FinOM), −1% (PCV7-OMPC/FinOM), and −0.4% (PCV7-CRM/Native American Trial); 34% against first episodes of ear, nose, and throat specialist-referral cases (PCV11-PD/POET). Both follow-up through 2 years of age, for the 5 trials, and long-term follow-up, for PCV7-CRM/NCKP and PCV7-CRM/FinOM, demonstrated greater vaccine efficacy against recurrent AOM and tympanostomy-tube placement, suggesting that vaccination against early episodes of AOM may prevent subsequent episodes of complicated otitis media. Although study designs varied by primary endpoint measured, age at follow-up, source of middle-ear fluid for culture, case ascertainment, and type of randomization, each clinical trial demonstrated vaccine efficacy against microbiological and/or clinical otitis media. PMID:22701486

78 FR 78359 - Agency Information Collection Activities; Proposed Collection; Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

...: Regional Extension Center Cooperative Agreement Program (CRM Tool). OMB No.: 0955-0009 Abstract: The Customer Relationship Management (CRM) application is a nimble business intelligence tool being used by more than 1,500 users at ONC partner organizations and grantees. The CRM collects data from a large...

Molecular analysis of citrus rust (Phyllocoptruta oleivora) populations in Texas

USDA-ARS?s Scientific Manuscript database

Phyllocoptruta olevoria (Acari: Eriophyidae) or the citrus rust mite (CRM) is one of the most economically important mite pests of citrus worldwide. CRM originated from Asia, however it is found in most citrus producing areas, such as, Brazil, Morocco and the United States. Though CRM is a major pes...

78 FR 69097 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

... (CRM) system to improve the response to correspondences from individuals seeking information from a... and private sector sources.'' The SalesForce CRM provides a centralized portal to manage frequently... topics. Depending on the topic searched, the CRM queries the database of pre-approved questions and...

Marshall properties of asphalt concrete using crumb rubber modified of motorcycle tire waste

NASA Astrophysics Data System (ADS)

Siswanto, Henri; Supriyanto, Bambang; Pranoto, Chandra, Pria Rizky; Hakim, Arief Rahman

2017-09-01

The aim of this study is to explain the effect of Crumb Rubber Modified (CRM) of motorcycle tire waste on Marshall properties of asphalt mix. Two types of aggregate gradation, asphalt concrete wearing course (ACWC) and asphalt concrete base (ACB), and CRM passing #50 sieve size were used. Seven levels of CRM content were investigated in this study, namely 0%, 0.5%, 1%, 1.5%, 3%, 4.5%, and 6% by weight of aggregate. Marshall test is conducted on Marshall specimens. The specimens are tested in their optimum binder content (OBC). The results indicate that CRM addition of motorcycle tire waste increases the Marshall stability of the both mix, ACWC and ACB. In addition, 1% CRM addition of motorcycle tire waste of the total mix weight is the best mix.

A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation

PubMed Central

Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A.; Gong, Yongquan; Fischbein, Michael P.; Robbins, Robert C.; Naesens, Maarten

2013-01-01

Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design. PMID:24127489

A CRM domain protein functions dually in group I and group II intron splicing in land plant chloroplasts.

PubMed

Asakura, Yukari; Barkan, Alice

2007-12-01

The CRM domain is a recently recognized RNA binding domain found in three group II intron splicing factors in chloroplasts, in a bacterial protein that associates with ribosome precursors, and in a family of uncharacterized proteins in plants. To elucidate the functional repertoire of proteins with CRM domains, we studied CFM2 (for CRM Family Member 2), which harbors four CRM domains. RNA coimmunoprecipitation assays showed that CFM2 in maize (Zea mays) chloroplasts is associated with the group I intron in pre-trnL-UAA and group II introns in the ndhA and ycf3 pre-mRNAs. T-DNA insertions in the Arabidopsis thaliana ortholog condition a defective-seed phenotype (strong allele) or chlorophyll-deficient seedlings with impaired splicing of the trnL group I intron and the ndhA, ycf3-int1, and clpP-int2 group II introns (weak alleles). CFM2 and two previously described CRM proteins are bound simultaneously to the ndhA and ycf3-int1 introns and act in a nonredundant fashion to promote their splicing. With these findings, CRM domain proteins are implicated in the activities of three classes of catalytic RNA: group I introns, group II introns, and 23S rRNA.

A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.

PubMed

Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A; Gong, Yongquan; Fischbein, Michael P; Robbins, Robert C; Naesens, Maarten; Butte, Atul J; Sarwal, Minnie M

2013-10-21

Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.

A certified urea reference material (NMIJ CRM 6006-a) as a reliable calibrant for the elemental analyses of amino acids and food samples.

PubMed

Itoh, Nobuyasu; Yamazaki, Taichi; Sato, Ayako; Numata, Masahiko; Takatsu, Akiko

2014-01-01

We examined the reliability of a certified reference material (CRM) for urea (NMIJ CRM 6006-a) as a calibrant for N, C, and H in elemental analyzers. Only the N content for this CRM is provided as an indicative value. To estimate the C and H contents of the urea CRM, we took into account the purity of the urea and the presence of other identified impurities. When we examined the use of various masses of the calibrant (0.2 to 2 mg), we unexpectedly observed low signal intensities for small masses of H and N, but these plateaued at about 2 mg. We therefore analyzed four amino acid CRMs and four food CRMs on a 2-mg scale with the urea CRM as the calibrant. For the amino acid CRMs, the differences in the analytical and theoretical contents (≤0.0026 kg/kg) were acceptable with good repeatability (≤0.0013 kg/kg in standard deviation; n = 4). For food CRMs, comparable repeatabilities to those obtained with amino acid CRMs (≤0.0025 kg/kg in standard deviation; n = 4) were obtained. The urea CRM can therefore be used as a reliable calibrant for C, H, and N in an elemental analyzer.

TNF binding protein of variola virus acts as a TNF antagonist at epicutaneous application.

PubMed

Gileva, Irina P; Viazovaia, Elena A; Toporkova, Ludmila B; Tsyrendorzhiev, Dondok D; Shchelkunov, Sergei N; Orlovskaya, Irina A

2015-01-01

VARV-CrmB is a TNF binding protein of variola virus. VARV-CrmB protein was previously shown to be active as a TNF-antagonist in a number of in vivo and in vitro models. Here we investigated the epicutaneous effect of recombinant VARV-CrmB protein using an experimental model of muTNFinduced migration of skin leukocytes as well as colony forming activity of bone marrow cells (BMC). Epiсutaneous applications of muTNF enhanced the number of cells migrating from skin flaps of BALB/c mice, whereas subsequent applications of VARV-CrmB protein in 30 min after muTNF, abolished that effect. Epicutaneously applied muTNF influenced the activity of committed hematopoietic progenitors causing a reduction of erythroid (BFUe+CFUe) colonies and increase of granulocyte-macrophage (CFU-GM) colonies in the colony-forming tests. VARV-CrmB, applied in combination with muTNF, demonstrated an ability to reverse this effect, namely, to increase BFUe+CFUe and reduce CFU-GM back to the control levels. Taking together, these data demonstrate the TNF-blocking properties of VARV-CrmB in vivo at epicutaneous applications. As effective TNF antagonist VARV-CrmB protein might be conceded as a beneficial candidate for future research and development of therapeutic approaches in the field of inflammatory skin diseases.

Development and co-validation of porcine insulin certified reference material by high-performance liquid chromatography-isotope dilution mass spectrometry.

PubMed

Wu, Liqing; Takatsu, Akiko; Park, Sang-Ryoul; Yang, Bin; Yang, Huaxin; Kinumi, Tomoya; Wang, Jing; Bi, Jiaming; Wang, Yang

2015-04-01

This article concerns the development and co-validation of a porcine insulin (pINS) certified reference material (CRM) produced by the National Institute of Metrology, People's Republic of China. Each CRM unit contained about 15 mg of purified solid pINS. The moisture content, amount of ignition residue, molecular mass, and purity of the pINS were measured. Both high-performance liquid chromatography-isotope dilution mass spectrometry and a purity deduction method were used to determine the mass fraction of the pINS. Fifteen units were selected to study the between-bottle homogeneity, and no inhomogeneity was observed. A stability study concluded that the CRM was stable for at least 12 months at -20 °C. The certified value of the CRM was (0.892 ± 0.036) g/g. A co-validation of the CRM was performed among Chinese, Japanese, and Korean laboratories under the framework of the Asian Collaboration on Reference Materials. The co-validation results agreed well with the certified value of the CRM. Consequently, the pINS CRM may be used as a calibration material or as a validation standard for pharmaceutical purposes to improve the quality of pharmaceutical products.

Effect of CRM team leader training on team performance and leadership behavior in simulated cardiac arrest scenarios: a prospective, randomized, controlled study.

PubMed

Fernandez Castelao, Ezequiel; Boos, Margarete; Ringer, Christiane; Eich, Christoph; Russo, Sebastian G

2015-07-24

Effective team leadership in cardiopulmonary resuscitation (CPR) is well recognized as a crucial factor influencing performance. Generally, leadership training focuses on task requirements for leading as well as non-leading team members. We provided crisis resource management (CRM) training only for designated team leaders of advanced life support (ALS) trained teams. This study assessed the impact of the CRM team leader training on CPR performance and team leader verbalization. Forty-five teams of four members each were randomly assigned to one of two study groups: CRM team leader training (CRM-TL) and additional ALS-training (ALS add-on). After an initial lecture and three ALS skill training tutorials (basic life support, airway management and rhythm recognition/defibrillation) of 90-min each, one member of each team was randomly assigned to act as the team leader in the upcoming CPR simulation. Team leaders of the CRM-TL groups attended a 90-min CRM-TL training. All other participants received an additional 90-min ALS skill training. A simulated CPR scenario was videotaped and analyzed regarding no-flow time (NFT) percentage, adherence to the European Resuscitation Council 2010 ALS algorithm (ADH), and type and rate of team leader verbalizations (TLV). CRM-TL teams showed shorter, albeit statistically insignificant, NFT rates compared to ALS-Add teams (mean difference 1.34 (95% CI -2.5, 5.2), p = 0.48). ADH scores in the CRM-TL group were significantly higher (difference -6.4 (95% CI -10.3, -2.4), p = 0.002). Significantly higher TLV proportions were found for the CRM-TL group: direct orders (difference -1.82 (95% CI -2.4, -1.2), p < 0.001); undirected orders (difference -1.82 (95% CI -2.8, -0.9), p < 0.001); planning (difference -0.27 (95% CI -0.5, -0.05) p = 0.018) and task assignments (difference -0.09 (95% CI -0.2, -0.01), p = 0.023). Training only the designated team leaders in CRM improves performance of the entire team, in particular guideline adherence and team leader behavior. Emphasis on training of team leader behavior appears to be beneficial in resuscitation and emergency medical course performance.

A putative N-terminal nuclear export sequence is sufficient for Mps1 nuclear exclusion during interphase.

PubMed

Jia, Haiwei; Zhang, Xiaojuan; Wang, Wenjun; Bai, Yuanyuan; Ling, Youguo; Cao, Cheng; Ma, Runlin Z; Zhong, Hui; Wang, Xue; Xu, Quanbin

2015-02-27

Mps1, an essential component of the mitotic checkpoint, is also an important interphase regulator and has roles in DNA damage response, cytokinesis and centrosome duplication. Mps1 predominantly resides in the cytoplasm and relocates into the nucleus at the late G2 phase. So far, the mechanism underlying the Mps1 translocation between the cytoplasm and nucleus has been unclear. In this work, a dynamic export process of Mps1 from the nucleus to cytoplasm in interphase was revealed- a process blocked by the Crm1 inhibitor, Leptomycin B, suggesting that export of Mps1 is Crm1 dependent. Consistent with this speculation, a direct association between Mps1 and Crm1 was found. Furthermore, a putative nuclear export sequence (pNES) motif at the N-terminal of Mps1 was identified by analyzing the motif of Mps1. This motif shows a high sequence similarity to the classic NES, a fusion of this motif with EGFP results in dramatic exclusion of the fusion protein from the nucleus. Additionally, Mps1 mutant loss of pNES integrity was shown by replacing leucine with alanine which produced a diffused subcellular distribution, compared to the wild type protein which resides predominantly in cytoplasm. Taken these findings together, it was concluded that the pNES sequence is sufficient for the Mps1 export from nucleus during interphase.

Assessment of Clinical Risk Management System in Hospitals: An Approach for Quality Improvement

PubMed Central

Farokhzadian, Jamileh; Nayeri, Nahid Dehghan; Borhani, Fariba

2015-01-01

Background: Clinical risks have created major problems in healthcare system such as serious adverse effects on patient safety and enhancing the financial burden for the healthcare. Thus, clinical risk management (CRM) system has been introduced for improving the quality and safety of services to health care. The aim of this study was to assess the status of CRM in the hospitals. Methods: A cross-sectional study was conducted on 200 nursing staff from three teaching hospitals affiliated with the Kerman University of Medical Sciences in southeast of Iran. Data were collected from the participants using questionnaire and observational checklist in quality improvement offices and selected wards. The data were analyzed using SPSS version 20. Results: Almost, 57% of persons participated in at least one of training sessions on CRM. The status of CRM system was rated from weak to moderate (2.93±0.72- 3.18±0.66). Among the six domains of CRM system, the highest mean belonged to domain the monitoring of analysis, evaluation and risk control (3.18±0.72); the lowest mean belonged to domain the staff’s knowledge, recognition and understanding of CRM (2.93±0.66). There were no integrated electronic systems for recording and analyzing clinical risks and incidents in the hospitals. Conclusion: Attempts have been made to establish CRM through improvement quality approach such as clinical governance and accreditation, but not enough, however, health care should move toward quality improvement and safe practice through the effective integration of CRM in organizational process. PMID:26156927

Nuclear Export Factor CRM1 Interacts with Nonstructural Proteins NS2 from Parvovirus Minute Virus of Mice

PubMed Central

Bodendorf, Ursula; Cziepluch, Celina; Jauniaux, Jean-Claude; Rommelaere, Jean; Salomé, Nathalie

1999-01-01

The nonstructural NS2 proteins of autonomous parvoviruses are known to act in a host cell-dependent manner and to play a role in viral DNA replication, efficient translation of viral mRNA, and/or encapsidation. Their exact function during the parvovirus life cycle remains, however, still obscure. We report here the characterization of the interaction with the NS2 proteins from the parvovirus minute virus of mice (MVM) and rat as well as mouse homologues of the human CRM1 protein, a member of the importin-beta family recently identified as an essential nuclear export factor. Using the two-hybrid system, we could detect the interaction between the carboxy-terminal region of rat CRM1 and each of the three isoforms of NS2 (P [or major], Y [or minor], and L [or rare]). NS2 proteins were further shown to interact with the full-length CRM1 by coimmunoprecipitation experiments using extracts from both mouse and rat cell lines. Our data show that CRM1 preferentially binds to the nonphosphorylated isoforms of NS2. Moreover, we observed that the treatment of MVM-infected cells with leptomycin B, a drug that specifically inhibits the CRM1-dependent nuclear export pathway, leads to a drastic accumulation of NS2 proteins in the nucleus. Both NS2 interaction with CRM1 and nuclear accumulation upon leptomycin B treatment strongly suggest that these nonstructural viral proteins are actively exported out of the nuclei of infected cells via a CRM1-mediated nuclear export pathway. PMID:10438867

14 CFR 121.427 - Recurrent training.

Code of Federal Regulations, 2011 CFR

2011-01-01

... required by §§ 121.421(b) and 121.422(b), respectively. (4) Approved recurrent CRM training. For flight... operational flight training (LOFT) session. The recurrent CRM training requirement does not apply until a person has completed the applicable initial CRM training required by §§ 121.419, 121.421, or 121.422. (c...

Contrasting Norm Referenced and Criterion Referenced Measures.

ERIC Educational Resources Information Center

Randall, Robert S.

Differences in design between norm referenced measures (NRM) and criterion referenced measures (CRM) are reviewed, and some of the procedures proposed on designing and evaluating CRM are examined. Differences in design of NRM and CRM are said to arise from the different purposes that underlie each measure. In addition, there are differences among…

28 CFR 16.91 - Exemption of Criminal Division Systems-limited access, as indicated.

Code of Federal Regulations, 2010 CFR

2010-07-01

...: (1) Central Criminal Division, Index File and Associated Records System of Records (JUSTICE/CRM-001... System of Records (JUSTICE/CRM-004)—Limited Access. These exemptions apply to the extent that information... Security File System of Records(JUSTICE/CRM-002). These exemptions apply to the extent that information in...

14 CFR 121.427 - Recurrent training.

Code of Federal Regulations, 2010 CFR

2010-01-01

... required by §§ 121.421(b) and 121.422(b), respectively. (4) Approved recurrent CRM training. For flight... operational flight training (LOFT) session. The recurrent CRM training requirement does not apply until a person has completed the applicable initial CRM training required by §§ 121.419, 121.421, or 121.422. (c...

Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults.

PubMed

Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M; Ceddia, Francesca

2010-04-01

This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.

Application of the 226Ra– 230Th– 234U and 227Ac– 231Pa– 235U radiochronometers to uranium certified reference materials

DOE PAGES

Rolison, John M.; Treinen, Kerri C.; McHugh, Kelly C.; ...

2017-11-06

Uranium certified reference materials (CRM) issued by New Brunswick Laboratory were subjected to dating using four independent uranium-series radiochronometers. In all cases, there was acceptable agreement between the model ages calculated using the 231Pa– 235U, 230Th– 234U, 227Ac– 235U or 226Ra– 234U radiochronometers and either the certified 230Th– 234U model date (CRM 125-A and CRM U630), or the known purification date (CRM U050 and CRM U100). Finally, the agreement between the four independent radiochronometers establishes these uranium certified reference materials as ideal informal standards for validating dating techniques utilized in nuclear forensic investigations in the absence of standards with certifiedmore » model ages for multiple radiochronometers.« less

Application of the 226Ra– 230Th– 234U and 227Ac– 231Pa– 235U radiochronometers to uranium certified reference materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rolison, John M.; Treinen, Kerri C.; McHugh, Kelly C.

Uranium certified reference materials (CRM) issued by New Brunswick Laboratory were subjected to dating using four independent uranium-series radiochronometers. In all cases, there was acceptable agreement between the model ages calculated using the 231Pa– 235U, 230Th– 234U, 227Ac– 235U or 226Ra– 234U radiochronometers and either the certified 230Th– 234U model date (CRM 125-A and CRM U630), or the known purification date (CRM U050 and CRM U100). Finally, the agreement between the four independent radiochronometers establishes these uranium certified reference materials as ideal informal standards for validating dating techniques utilized in nuclear forensic investigations in the absence of standards with certifiedmore » model ages for multiple radiochronometers.« less

Preparation and provisional certification of NBL Spectrographic Impurity Standards, CRM 123 (1-7) and 124 (1-7)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santoliquido, P.M.

This report describes the design, production, and provisional certification of two new certified reference materials (CRMs): CRM No. 123 (1-7), U/sub 3/O/sub 8/ containing 18 trace elements, and CRM No. 124 (1-7), U/sub 3/O/sub 8/ containing 24 trace elements. The elements to be included and concentrations to be used were decided on the basis of information gathered from users of a previous CRM of this type, CRM No. 98 (1-7). The new CRMs were prepared by the addition of trace elements to high purity U/sub 3/O/sub 8/. Provisional certification was accomplished by an interlaboratory program in which four different laboratoriesmore » analyzed the materials by carrier distillation dc arc emission spectrography.« less

78 FR 12234 - Promotions and Incentive Programs for First-Class Mail and Standard Mail

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

...] (BRM) or Courtesy Reply Mail TM (CRM) card or letter bearing a qualifying Intelligent Mail[supreg... mechanism for their customers and to keep the BRM/ CRM envelopes in their outgoing mail pieces by providing a financial benefit when the BRM/CRM envelopes are used. Registration is January 15 to March 31...

Customer Relationship Management in Higher Education: Using Information Systems to Improve the Student-School Relationship

ERIC Educational Resources Information Center

Seeman, Elaine D.; O'Hara, Margaret

2006-01-01

Purpose: The purpose of this paper is to explore customer relationship management (CRM) in a higher education setting. Design/methodology/approach: The development and implementation of a CRM project in a state community college was examined as were the benefits realized by implementing CRM. As colleges increasingly embrace distance learning and…

Adapting Criterion-Referenced Measurement to Individualization of Instruction for Handicapped Children: Some Issues and a First Attempt.

ERIC Educational Resources Information Center

Proger, Barton B.; And Others

Criterion-referenced measurement (CRM) has received increasing attention in regular education. However, it is in education for handicapped children that CRM's flexibility for individualization of both instruction and evaluation become even more fully realized. Research is described on one of the first CRM systems (Individual Achievement Monitoring…

Exploring Use of the Coordinate Response Measure in a Multitalker Babble Paradigm

ERIC Educational Resources Information Center

Humes, Larry E.; Kidd, Gary R.; Fogerty, Daniel

2017-01-01

Purpose: Three experiments examined the use of competing coordinate response measure (CRM) sentences as a multitalker babble. Method: In Experiment I, young adults with normal hearing listened to a CRM target sentence in the presence of 2, 4, or 6 competing CRM sentences with synchronous or asynchronous onsets. In Experiment II, the condition with…

Management training for cockpit crews at Piedmont flight

NASA Technical Reports Server (NTRS)

Sifford, J. C.

1984-01-01

A brief history of Piedmont Airlines' flight operations is presented. A captain-management seminar conducted regularly by Piedmont is discussed. Piedmont's approach to cockpit resource management (CRM) is reviewed, and the relationship of CRM training to other aspects of flight training is addressed. Future leadership research plans and CRM training is considered along with critical training issues.

Lack of independent significance of a close (<1 mm) circumferential resection margin involvement in esophageal and junctional cancer.

PubMed

O'Farrell, N J; Donohoe, C L; Muldoon, C; Costelloe, J M; King, S; Ravi, N; Reynolds, J V

2013-08-01

For rectal cancer, an involved circumferential resection margin (CRM), defined as tumor cells within 1 mm of the CRM, is of established prognostic significance. This definition for the esophagus, however, is controversial, with the UK Royal College of Pathologists (RCP) recommending the 1 mm definition, while the College of American Pathologists (CAP) advises that only tumor cells at the cut margin (0 mm) define an incomplete (R1) resection. The aim of this study was to compare the clinical significance of both definitions in patients with pT3 tumors. CAP- and RCP-defined CRM status in patients treated by surgery only or by multimodal therapy was recorded prospectively in a comprehensive database from May 2003 to May 2011. Kaplan-Meier survival curves were generated, and factors affecting survival were assessed by univariate and multivariate analysis. A total of 157 of 340 patients had pT3 esophageal tumors, with RCP-positive CRM in 60 %, and 18 % by CAP. There were no significant differences between RCP-positive CRM and negative margins for node-positive disease, local recurrence, and survival. CAP-positive CRM was associated with positive nodes (P = 0.036) and poorer survival (P = 0.023). Multivariate analysis revealed nodal invasion to be the only independent prognostic variable (P = 0.004). A CRM margin of <1 mm is common in pT3 esophageal tumors, a finding consistent with other reports. The <1 mm definition was not associated with node positivity, local recurrence, or survival, in contrast to actual involvement at the margin, suggesting lack of independent prognostic significance of the RCP definition and possible superiority of the CAP criteria for prospective registration of CRM.

The impact of administration of conjugate vaccines containing cross reacting material on Haemophilus influenzae type b antibody responses in infants: A systematic review and meta-analysis of randomised controlled trials.

PubMed

Voysey, Merryn; Sadarangani, Manish; Clutterbuck, Elizabeth; Bolgiano, Barbara; Pollard, Andrew J

2016-07-25

Protein-polysaccharide conjugate vaccines such as Haemophilus influenzae type b (Hib), meningococcal, and pneumococcal vaccine, induce immunological memory and longer lasting protection than plain polysaccharide vaccines. The most common proteins used as carriers are tetanus toxoid (TT) and cross reacting material-197 (CRM), a mutant form of diphtheria toxoid. CRM conjugate vaccines have been reported to suppress antibody responses to co-administered Hib-TT vaccine. We conducted a systematic review and meta-analysis of randomised controlled trials in which infants were randomised to receive meningococcal or pneumococcal conjugate vaccines along with Hib-TT. Trials of licensed vaccines with different carrier proteins were included for group C meningococcal (MenC), quadrivalent ACWY meningococcal (MenACWY), and pneumococcal vaccines. Twenty-three trials were included in the meta-analyses. Overall, administration of MenC-CRM in a 2 or 3 dose schedule resulted in a 45% reduction in Hib antibody concentrations (GMR 0.55, 95% CI 0.49-0.62). MenACWY-CRM boosted Hib antibody responses by 22% (GMR 1.22, 95% CI 1.06-1.41) whilst pneumococcal CRM conjugate vaccines had no impact on Hib antibody responses (GMR 0.91, 95% CI 0.68-1.22). The effect of CRM protein-polysaccharide conjugate vaccines on Hib antibody responses varies greatly between vaccines. Co-administration of a CRM conjugate vaccine can produce either positive or negative effects on Hib antibody responses. These inconsistencies suggest that CRM itself may not be the main driver of variability in Hib responses, and challenge current perspectives on this issue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Continuous Effect of Radial Resection Margin on Recurrence and Survival in Rectal Cancer Patients Who Receive Preoperative Chemoradiation and Curative Surgery: A Multicenter Retrospective Analysis.

PubMed

Sung, SooYoon; Kim, Sung Hwan; Lee, Joo Hwan; Nam, Taek Keun; Jeong, Songmi; Jang, Hong Seok; Song, Jin Ho; Lee, Jeong Won; Bae, Jung Min; Lee, Jong Hoon

2017-07-01

To elucidate the proper length and prognostic value of resection margins in rectal cancer patients who received preoperative chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME). A total of 1476 rectal cancer patients staging cT3-4N0-2M0 were analyzed. All patients received radiation dose of 50.4 Gy in 28 fractions with concurrent 5-fluorouracil or capecitabine. Total mesorectal excision was performed 4 to 8 weeks after radiation therapy. The recurrence-free survival (RFS) at 5 years showed a significant difference between 3 groups: patients with circumferential resection margin (CRM) ≤1 mm, CRM 1.1 to 5 mm, and CRM >5 mm (46.2% vs 68.6% vs 77.5%, P<.001). Patients with CRM ≤1 mm showed a significantly higher cumulative incidence of locoregional recurrence (P<.001) and distant metastasis (P<.001) at 5 years compared with the other 2 groups. Patients with CRM 1.1 to 5 mm showed a significantly higher cumulative incidence of distant metastasis (P<.001), but not locoregional recurrence (P=.192), compared with those with CRM >5 mm. Distal resection margin (≤5 vs >5 mm) did not show any significant difference in cumulative incidence of locoregional recurrence (P=.310) and distant metastasis (P=.926). Rectal cancer patients with CRM ≤1 mm are a high-risk group, with the lowest RFS. Patients with CRM 1.1 to 5 mm may be at intermediate risk, with moderately increased distant recurrence. Distal resection margin was not significantly associated with RFS in rectal cancer after neoadjuvant CRT and total mesorectal excision. Copyright © 2017 Elsevier Inc. All rights reserved.

Building a simulation-based crisis resource management course for emergency medicine, phase 1: Results from an interdisciplinary needs assessment survey.

PubMed

Hicks, Christopher M; Bandiera, Glen W; Denny, Christopher J

2008-11-01

Emergency department (ED) resuscitation requires the coordinated efforts of an interdisciplinary team. Human errors are common and have a negative impact on patient safety. Although crisis resource management (CRM) skills are utilized in other clinical domains, most emergency medicine (EM) caregivers currently receive no formal CRM training. The objectives were to compile and compare attitudes toward CRM training among EM staff physicians, nurses, and residents at two Canadian academic teaching hospitals. Emergency physicians (EPs), residents, and nurses were asked to complete a Web survey that included Likert scales and short answer questions. Focus groups and pilot testing were used to inform survey development. Thematic content analysis was performed on the qualitative data set and compared to quantitative results. The response rate was 75.7% (N = 84). There was strong consensus regarding the importance of core CRM principles (i.e., effective communication, team leadership, resource utilization, problem-solving, situational awareness) in ED resuscitation. Problems with coordinating team actions (58.8%), communication (69.6%), and establishing priorities (41.3%) were among factors implicated in adverse events. Interdisciplinary collaboration (95.1%), efficiency of patient care (83.9%), and decreased medical error (82.6%) were proposed benefits of CRM training. Communication between disciplines is a barrier to effective ED resuscitation for 94.4% of nurses and 59.7% of EPs (p = 0.008). Residents reported a lack of exposure to (64.3%), yet had interest in (96.4%) formal CRM education using human patient simulation. Nurses rate communication as a barrier to teamwork more frequently than physicians. EM residents are keen to learn CRM skills. An opportunity exists to create a novel interdisciplinary CRM curriculum to improve EM team performance and mitigate human error.

Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial

PubMed Central

Lähteenmäki, Ritva; Puustinen, Juha; Vahlberg, Tero; Lyles, Alan; Neuvonen, Pertti J; Partinen, Markku; Räihä, Ismo; Kivelä, Sirkka-Liisa

2014-01-01

Aim We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here ‘BZD’) use. Methods A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) with primary insomnia and chronic BZD use received controlled release melatonin 2 mg (CRM) (n = 46) or placebo (n = 46) during the 1 month withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for up to 6 months. Successful BZD withdrawal by the end of 1 month was confirmed by BZD plasma determinations, while reduction in BZD use and abstinence continuing for 6 months were noted. Results There were two drop-outs on CRM and one on placebo. After a 1 month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat analysis between groups, P = 0.051; per protocol P = 0.043). Reduction in BZD use was similar or even more rare in the CRM than in the placebo group (P = 0.052 per protocol). After 6 months, 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD (NS between groups). BZD doses were higher in the CRM than in the placebo group at the end of the 6 month follow-up (P = 0.025). Withdrawal symptoms did not differ between the groups. Conclusions Gradual dose reduction of BZDs combined with CRM or placebo, and psychosocial support produced high short term and moderate long term BZD abstinence. CRM showed no withdrawal benefit compared with placebo. PMID:24286360

Immunological detection of phenylalanine hydroxylase protein in Drosophila melanogaster.

PubMed Central

Silva, F J; Bel, Y; Botella, L M; Cotton, R G; Ferré, J

1992-01-01

A monoclonal antibody raised against monkey liver phenylalanine hydroxylase (PAH) has been used to detect this protein in Drosophila melanogaster. A cross-reacting material (CRM) band of apparent molecular mass 50-52 kDa, equivalent to that deduced for the Drosophila melanogaster PAH protein based on the pah gene cDNA sequence, has been detected. This CRM was analysed throughout development and showed an equivalent pattern to that reported for PAH activity in this insect, with maxima at pupariation and at pharate adult formation. Distribution of this CRM in larval tissues, the haemolymph and the adult body is mainly restricted to the larval fat body and the adult head. Demonstration of this CRM as the PAH protein comes from the correlation between the decreased PAH enzyme activities of two mutant strains and their decreased amounts of CRM by Western blotting. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:1417795

Inhibiting cancer cell hallmark features through nuclear export inhibition.

PubMed

Sun, Qingxiang; Chen, Xueqin; Zhou, Qiao; Burstein, Ezra; Yang, Shengyong; Jia, Da

2016-01-01

Treating cancer through inhibition of nuclear export is one of the best examples of basic research translation into clinical application. Nuclear export factor chromosomal region maintenance 1 (CRM1; Xpo1 and exportin-1) controls cellular localization and function of numerous proteins that are critical for the development of many cancer hallmarks. The diverse actions of CRM1 are likely to explain the broad ranging anti-cancer potency of CRM1 inhibitors observed in pre-clinical studies and/or clinical trials (phase I-III) on both advanced-stage solid and hematological tumors. In this review, we compare and contrast the mechanisms of action of different CRM1 inhibitors, and discuss the potential benefit of unexplored non-covalent CRM1 inhibitors. This emerging field has uncovered that nuclear export inhibition is well poised as an attractive target towards low-toxicity broad-spectrum potent anti-cancer therapy.

The design and delivery of crew resource management training: exploiting available resources.

PubMed

Salas, E; Rhodenizer, L; Bowers, C A

2000-01-01

Despite widespread acceptance throughout commercial and military settings, crew resource management (CRM) training programs have not escaped doubts about their effectiveness. The current state of CRM training is an example of how an entire body of pertinent research and development has not had the impact on practice that it could. In this paper we outline additional resources (i.e., principles, information, findings, and guidelines) from the team training and training effectiveness research literatures that can be used to improve the design and delivery of CRM training. Some of the resources discussed include knowledge about training effectiveness, training teamwork-related skills, scenario design, and performance measurement. We conclude with a discussion of emerging resources as well as those that need to be developed. The purpose of this paper is to provide the CRM training developer with better access to resources that can be applied to the design and delivery of CRM training programs.

Poxvirus-encoded TNF decoy receptors inhibit the biological activity of transmembrane TNF.

PubMed

Pontejo, Sergio M; Alejo, Ali; Alcami, Antonio

2015-10-01

Poxviruses encode up to four different soluble TNF receptors, named cytokine response modifier B (CrmB), CrmC, CrmD and CrmE. These proteins mimic the extracellular domain of the cellular TNF receptors to bind and inhibit the activity of TNF and, in some cases, other TNF superfamily ligands. Most of these ligands are released after the enzymic cleavage of a membrane precursor. However, transmembrane TNF (tmTNF) is not only a precursor of soluble TNF but also exerts specific pro-inflammatory and immunological activities. Here, we report that viral TNF receptors bound and inhibited tmTNF and describe some interesting differences in their activity against the soluble cytokine. Thus, CrmE, which does not inhibit mouse soluble TNF, could block murine tmTNF-induced cytotoxicity. We propose that this anti-tmTNF effect should be taken into consideration when assessing the role of viral TNF decoy receptors in the pathogenesis of poxvirus.

Antibody-based analysis reveals “filamentous vs. non-filamentous” and “cytoplasmic vs. nuclear” crosstalk of cytoskeletal proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumeta, Masahiro, E-mail: kumeta@lif.kyoto-u.ac.jp; Hirai, Yuya; Yoshimura, Shige H.

2013-12-10

To uncover the molecular composition and dynamics of the functional scaffold for the nucleus, three fractions of biochemically-stable nuclear protein complexes were extracted and used as immunogens to produce a variety of monoclonal antibodies. Many helix-based cytoskeletal proteins were identified as antigens, suggesting their dynamic contribution to nuclear architecture and function. Interestingly, sets of antibodies distinguished distinct subcellular localization of a single isoform of certain cytoskeletal proteins; distinct molecular forms of keratin and actinin were found in the nucleus. Their nuclear shuttling properties were verified by the apparent nuclear accumulations under inhibition of CRM1-dependent nuclear export. Nuclear keratins do notmore » take an obvious filamentous structure, as was revealed by non-filamentous cytoplasmic keratin-specific monoclonal antibody. These results suggest the distinct roles of the helix-based cytoskeletal proteins in the nucleus. - Highlights: • A set of monoclonal antibodies were raised against nuclear scaffold proteins. • Helix-based cytoskeletal proteins were involved in nuclear scaffold. • Many cytoskeletal components shuttle into the nucleus in a CRM1-dependent manner. • Sets of antibodies distinguished distinct subcellular localization of a single isoform. • Nuclear keratin is soluble and does not form an obvious filamentous structure.« less

A development and integration of database code-system with a compilation of comparator, k0 and absolute methods for INAA using microsoft access

NASA Astrophysics Data System (ADS)

Hoh, Siew Sin; Rapie, Nurul Nadiah; Lim, Edwin Suh Wen; Tan, Chun Yuan; Yavar, Alireza; Sarmani, Sukiman; Majid, Amran Ab.; Khoo, Kok Siong

2013-05-01

Instrumental Neutron Activation Analysis (INAA) is often used to determine and calculate the elemental concentrations of a sample at The National University of Malaysia (UKM) typically in Nuclear Science Programme, Faculty of Science and Technology. The objective of this study was to develop a database code-system based on Microsoft Access 2010 which could help the INAA users to choose either comparator method, k0-method or absolute method for calculating the elemental concentrations of a sample. This study also integrated k0data, Com-INAA, k0Concent, k0-Westcott and Abs-INAA to execute and complete the ECC-UKM database code-system. After the integration, a study was conducted to test the effectiveness of the ECC-UKM database code-system by comparing the concentrations between the experiments and the code-systems. 'Triple Bare Monitor' Zr-Au and Cr-Mo-Au were used in k0Concent, k0-Westcott and Abs-INAA code-systems as monitors to determine the thermal to epithermal neutron flux ratio (f). Calculations involved in determining the concentration were net peak area (Np), measurement time (tm), irradiation time (tirr), k-factor (k), thermal to epithermal neutron flux ratio (f), parameters of the neutron flux distribution epithermal (α) and detection efficiency (ɛp). For Com-INAA code-system, certified reference material IAEA-375 Soil was used to calculate the concentrations of elements in a sample. Other CRM and SRM were also used in this database codesystem. Later, a verification process to examine the effectiveness of the Abs-INAA code-system was carried out by comparing the sample concentrations between the code-system and the experiment. The results of the experimental concentration values of ECC-UKM database code-system were performed with good accuracy.

The Oncogenic Fusion Proteins SET-Nup214 and Sequestosome-1 (SQSTM1)-Nup214 Form Dynamic Nuclear Bodies and Differentially Affect Nuclear Protein and Poly(A)+ RNA Export.

PubMed

Port, Sarah A; Mendes, Adélia; Valkova, Christina; Spillner, Christiane; Fahrenkrog, Birthe; Kaether, Christoph; Kehlenbach, Ralph H

2016-10-28

Genetic rearrangements are a hallmark of several forms of leukemia and can lead to oncogenic fusion proteins. One example of an affected chromosomal region is the gene coding for Nup214, a nucleoporin that localizes to the cytoplasmic side of the nuclear pore complex (NPC). We investigated two such fusion proteins, SET-Nup214 and SQSTM1 (sequestosome)-Nup214, both containing C-terminal portions of Nup214. SET-Nup214 nuclear bodies containing the nuclear export receptor CRM1 were observed in the leukemia cell lines LOUCY and MEGAL. Overexpression of SET-Nup214 in HeLa cells leads to the formation of similar nuclear bodies that recruit CRM1, export cargo proteins, and certain nucleoporins and concomitantly affect nuclear protein and poly(A) + RNA export. SQSTM1-Nup214, although mostly cytoplasmic, also forms nuclear bodies and inhibits nuclear protein but not poly(A) + RNA export. The interaction of the fusion proteins with CRM1 is RanGTP-dependent, as shown in co-immunoprecipitation experiments and binding assays. Further analysis revealed that the Nup214 parts mediate the inhibition of nuclear export, whereas the SET or SQSTM1 part determines the localization of the fusion protein and therefore the extent of the effect. SET-Nup214 nuclear bodies are highly mobile structures, which are in equilibrium with the nucleoplasm in interphase and disassemble during mitosis or upon treatment of cells with the CRM1-inhibitor leptomycin B. Strikingly, we found that nucleoporins can be released from nuclear bodies and reintegrated into existing NPC. Our results point to nuclear bodies as a means of preventing the formation of potentially insoluble and harmful protein aggregates that also may serve as storage compartments for nuclear transport factors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The Oncogenic Fusion Proteins SET-Nup214 and Sequestosome-1 (SQSTM1)-Nup214 Form Dynamic Nuclear Bodies and Differentially Affect Nuclear Protein and Poly(A)+ RNA Export*

PubMed Central

Port, Sarah A.; Mendes, Adélia; Valkova, Christina; Spillner, Christiane; Fahrenkrog, Birthe; Kaether, Christoph; Kehlenbach, Ralph H.

2016-01-01

Genetic rearrangements are a hallmark of several forms of leukemia and can lead to oncogenic fusion proteins. One example of an affected chromosomal region is the gene coding for Nup214, a nucleoporin that localizes to the cytoplasmic side of the nuclear pore complex (NPC). We investigated two such fusion proteins, SET-Nup214 and SQSTM1 (sequestosome)-Nup214, both containing C-terminal portions of Nup214. SET-Nup214 nuclear bodies containing the nuclear export receptor CRM1 were observed in the leukemia cell lines LOUCY and MEGAL. Overexpression of SET-Nup214 in HeLa cells leads to the formation of similar nuclear bodies that recruit CRM1, export cargo proteins, and certain nucleoporins and concomitantly affect nuclear protein and poly(A)+ RNA export. SQSTM1-Nup214, although mostly cytoplasmic, also forms nuclear bodies and inhibits nuclear protein but not poly(A)+ RNA export. The interaction of the fusion proteins with CRM1 is RanGTP-dependent, as shown in co-immunoprecipitation experiments and binding assays. Further analysis revealed that the Nup214 parts mediate the inhibition of nuclear export, whereas the SET or SQSTM1 part determines the localization of the fusion protein and therefore the extent of the effect. SET-Nup214 nuclear bodies are highly mobile structures, which are in equilibrium with the nucleoplasm in interphase and disassemble during mitosis or upon treatment of cells with the CRM1-inhibitor leptomycin B. Strikingly, we found that nucleoporins can be released from nuclear bodies and reintegrated into existing NPC. Our results point to nuclear bodies as a means of preventing the formation of potentially insoluble and harmful protein aggregates that also may serve as storage compartments for nuclear transport factors. PMID:27613868

Trace element determination using static high-sensitivity inductively coupled plasma optical emission spectrometry (SHIP-OES).

PubMed

Engelhard, Carsten; Scheffer, Andy; Nowak, Sascha; Vielhaber, Torsten; Buscher, Wolfgang

2007-02-05

A low-flow air-cooled inductively coupled plasma (ICP) design for optical emission spectrometry (OES) with axial plasma viewing is described and an evaluation of its analytical capabilities in trace element determinations is presented. Main advantage is a total argon consumption of 0.6 L min(-1) in contrast to 15 L min(-1) using conventional ICP sources. The torch was evaluated in trace element determinations and studied in direct comparison with a conventional torch under the same conditions with the same OES system, ultrasonic nebulization (USN) and single-element optimization. A variety of parameters (x-y-position of the torch, rf power, external air cooling, gas flow rates and USN operation parameters) was optimized to achieve limits of detection (LOD) which are competitive to those of a conventional plasma source. Ionic to atomic line intensity ratios for magnesium were studied at different radio frequency (rf) power conditions and different sample carrier gas flows to characterize the robustness of the excitation source. A linear dynamic range of three to five orders of magnitude was determined under compromise conditions in multi-element mode. The accuracy of the system was investigated by the determination of Co, Cr, Mn, Zn in two certified reference materials (CRM): CRM 075c (Copper with added impurities), and CRM 281 (Trace elements in rye grass). With standard addition values of 2.44+/-0.04 and 3.19+/-0.21 microg g(-1) for Co and Mn in the CRM 075c and 2.32+/-0.09, 81.8+/-0.4, 32.2+/-3.9 for Cr, Mn and Zn, respectively, were determined in the samples and found to be in good agreement with the reported values; recovery rates in the 98-108% range were obtained. No influence on the analysis by the matrix load in the sample was observed.

Do-It-Yourself: A Special Library's Approach to Creating Dynamic Web Pages Using Commercial Off-The-Shelf Applications

NASA Technical Reports Server (NTRS)

Steeman, Gerald; Connell, Christopher

2000-01-01

Many librarians may feel that dynamic Web pages are out of their reach, financially and technically. Yet we are reminded in library and Web design literature that static home pages are a thing of the past. This paper describes how librarians at the Institute for Defense Analyses (IDA) library developed a database-driven, dynamic intranet site using commercial off-the-shelf applications. Administrative issues include surveying a library users group for interest and needs evaluation; outlining metadata elements; and, committing resources from managing time to populate the database and training in Microsoft FrontPage and Web-to-database design. Technical issues covered include Microsoft Access database fundamentals, lessons learned in the Web-to-database process (including setting up Database Source Names (DSNs), redesigning queries to accommodate the Web interface, and understanding Access 97 query language vs. Standard Query Language (SQL)). This paper also offers tips on editing Active Server Pages (ASP) scripting to create desired results. A how-to annotated resource list closes out the paper.

78 FR 46339 - Medicare, Medicaid, and Children's Health Insurance Programs: Announcement of Temporary Moratoria...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

...-crm-510.html . \\10\\ Department of Justice, ``Owners of Miami Home Health Companies Sentenced to Prison in $48 million Health Care Fraud Scheme.'' See http://www.justice.gov/opa/pr/2013/February/13-crm-243... Convicted in Medicare Fraud Scheme.'' See http://www.justice.gov/opa/pr/2013/March/13-crm-273.html . \\24...

76 FR 5061 - Special Conditions: TTF Aerospace, LLC, Modification to Boeing Model 767-300 Series Airplanes...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

..., will have a novel or unusual design features associated with the pilot lower lobe crew rest module (CRM...) for installation of a lower lobe pilot crew rest module (CRM) in Boeing Model 767-300 series airplanes. The CRM will be a one-piece, self-contained unit for installation in the forward portion of the aft...

Cockpit resource management skills enhance combat mission performance in a B-52 simulator

NASA Technical Reports Server (NTRS)

Povenmire, H. Kingsley; Rockway, Marty R.; Bunecke, Joseph L.; Patton, Mark W.

1989-01-01

A cockpit resource management (CRM) program for mission-ready B-52 aircrew is developed. The relationship between CRM performance and combat mission performance is studied. The performances of six crew members flying a simulated high workload mission in a B-52 weapon system trainer are evaluated. The data reveal that CRM performance enhances tactical maneuvers and bombing accuracy.

AFMC Customer Satisfaction Study at the Air Logistics Centers

DTIC Science & Technology

2008-03-01

research was guided by a previous Graduate Research Project (GRP) effort, which sought to determine how customer relationship management ( CRM ...and effectively. To accomplish this, AFMC is implementing Customer Relationship Management ( CRM ) as one of its initiatives. Problem Statement...for improvement. More than fifty-one percent of the participants were not aware that Customer Relationship Management ( CRM ) was a transformation

Customer relationship management in the contract pharmaceutical industry: an exploratory study for measuring success.

PubMed

Kros, John F; Nadler, Scott; Molis, Justin

2007-01-01

Managing customer relationships is a very important issue in business-to-business markets. This research investigates the growing number of available resources defining Customer Relationship Management (CRM) efforts, and how they are being applied within the Contract Pharmaceutical Manufacturing industry. Exploratory study results using face-to-face and telephone questionnaires based on four criteria for rating a company's CRM efforts are presented. Data was collected from large Contract Pharmaceutical Manufacturing companies in the US market. The results and conclusions are discussed relating how the Contract Pharmaceutical Manufacturing industry is implementing CRM including some potential steps to take when considering a CRM initiative.

Evaluation on the stability of Hg in ABS disk CRM during measurements by wavelength dispersive X-ray fluorescence spectrometry.

PubMed

Ohata, Masaki; Kidokoro, Toshihiro; Hioki, Akiharu

2012-01-01

The stability of Hg in an acrylonitrile-butadiene-styrene disk certified reference material (ABS disk CRM, NMIJ CRM 8116-a) during measurements by wavelength dispersion X-ray fluorescence (WD-XRF) analysis was evaluated in this study. The XRF intensities of Hg (L(α)) and Pb (L(α)) as well as the XRF intensity ratios of Hg (L(α))/Pb (L(α)) observed under different X-ray tube current conditions as well as their irradiation time were examined to evaluate the stability of Hg in the ABS disk CRM. The observed XRF intensities and the XRF intensity ratios for up to 32 h of measurements under 80 mA of X-ray tube current condition were constant, even though the surface of the ABS disk CRM was charred by the X-ray irradiation with high current for a long time. Moreover, the measurements on Hg and Pb in the charred disks by an energy dispersive XRF (ED-XRF) spectrometer showed constant XRF intensity ratios of Hg (L(α))/Pb (L(α)). From these results, Hg in the ABS disk CRM was evaluated to be sufficiently stable for XRF analysis.

Selection of the initial design for the two-stage continual reassessment method.

PubMed

Jia, Xiaoyu; Ivanova, Anastasia; Lee, Shing M

2017-01-01

In the two-stage continual reassessment method (CRM), model-based dose escalation is preceded by a pre-specified escalating sequence starting from the lowest dose level. This is appealing to clinicians because it allows a sufficient number of patients to be assigned to each of the lower dose levels before escalating to higher dose levels. While a theoretical framework to build the two-stage CRM has been proposed, the selection of the initial dose-escalating sequence, generally referred to as the initial design, remains arbitrary, either by specifying cohorts of three patients or by trial and error through extensive simulations. Motivated by a currently ongoing oncology dose-finding study for which clinicians explicitly stated their desire to assign at least one patient to each of the lower dose levels, we proposed a systematic approach for selecting the initial design for the two-stage CRM. The initial design obtained using the proposed algorithm yields better operating characteristics compared to using a cohort of three initial design with a calibrated CRM. The proposed algorithm simplifies the selection of initial design for the two-stage CRM. Moreover, initial designs to be used as reference for planning a two-stage CRM are provided.

Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.

PubMed

Togashi, Takehiro; Mitsuya, Nodoka; Kogawara, Osamu; Sumino, Shuji; Takanami, Yohei; Sugizaki, Kayoko

2016-08-31

Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (p<0.0001). Furthermore, the "short-term seroprotection rate" (anti-PRP antibody titer ⩾0.15μg/mL) before booster vaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. Registered on ClinicalTrials.gov: NCT01379846. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

imDEV: a graphical user interface to R multivariate analysis tools in Microsoft Excel

PubMed Central

Grapov, Dmitry; Newman, John W.

2012-01-01

Summary: Interactive modules for Data Exploration and Visualization (imDEV) is a Microsoft Excel spreadsheet embedded application providing an integrated environment for the analysis of omics data through a user-friendly interface. Individual modules enables interactive and dynamic analyses of large data by interfacing R's multivariate statistics and highly customizable visualizations with the spreadsheet environment, aiding robust inferences and generating information-rich data visualizations. This tool provides access to multiple comparisons with false discovery correction, hierarchical clustering, principal and independent component analyses, partial least squares regression and discriminant analysis, through an intuitive interface for creating high-quality two- and a three-dimensional visualizations including scatter plot matrices, distribution plots, dendrograms, heat maps, biplots, trellis biplots and correlation networks. Availability and implementation: Freely available for download at http://sourceforge.net/projects/imdev/. Implemented in R and VBA and supported by Microsoft Excel (2003, 2007 and 2010). Contact: John.Newman@ars.usda.gov Supplementary Information: Installation instructions, tutorials and users manual are available at http://sourceforge.net/projects/imdev/. PMID:22815358

Boundary-layer diabatic processes, the virtual effect, and convective self-aggregation

NASA Astrophysics Data System (ADS)

Yang, D.

2017-12-01

The atmosphere can self-organize into long-lasting large-scale overturning circulations over an ocean surface with uniform temperature. This phenomenon is referred to as convective self-aggregation and has been argued to be important for tropical weather and climate systems. Here we use a 1D shallow water model and a 2D cloud-resolving model (CRM) to show that boundary-layer diabatic processes are essential for convective self-aggregation. We will show that boundary-layer radiative cooling, convective heating, and surface buoyancy flux help convection self-aggregate because they generate available potential energy (APE), which sustains the overturning circulation. We will also show that evaporative cooling in the boundary layer (cold pool) inhibits convective self-aggregation by reducing APE. Both the shallow water model and CRM results suggest that the enhanced virtual effect of water vapor can lead to convective self-aggregation, and this effect is mainly in the boundary layer. This study proposes new dynamical feedbacks for convective self-aggregation and complements current studies that focus on thermodynamic feedbacks.

Effect of skin barrier disruption on immune responses to topically applied cross-reacting material, CRM(197), of diphtheria toxin.

PubMed

Godefroy, S; Peyre, M; Garcia, N; Muller, S; Sesardic, D; Partidos, C D

2005-08-01

The high accessibility of the skin and the presence of immunocompetent cells in the epidermis makes this surface an attractive route for needle-free administration of vaccines. However, the lining of the skin by the stratum corneum is a major obstacle to vaccine delivery. In this study we examined the effect of skin barrier disruption on the immune responses to the cross-reacting material CRM(197), a nontoxic mutant of diphtheria toxin (DTx) that is considered as a vaccine candidate. Application of CRM(197), together with cholera toxin (CT), onto the tape-stripped skin of mice elicited antibody responses that had anti-DTx neutralizing activity. Vaccine delivery onto mildly ablated skin or intact skin did not elicit any detectable anti-CRM(197) antibodies. Mice immunized with CRM(197) alone onto the tape-stripped skin mounted a vigorous antigen-specific proliferative response. In contrast, the induction of cellular immunity after CRM(197) deposition onto mildly ablated or intact skin was adjuvant dependent. Furthermore, epidermal cells were activated and underwent apoptosis that was more pronounced when the stratum corneum was removed by tape stripping. Overall, these findings highlight the potential for transcutaneous delivery of CRM(197) and establish a correlation between the degree of barrier disruption and levels of antigen-specific immune responses. Moreover, these results provide the first evidence that the development of a transcutaneous immunization strategy for diphtheria, based on simple and practical methods to disrupt the skin barrier, is feasible.

The application of CRM to military operations

NASA Technical Reports Server (NTRS)

Cavanagh, Dale E.; Williams, Kenneth R.

1987-01-01

The detailed content of the CRM training component of the C-5 Aircrew Training System (ATS) was left to the discretion of the contractor. As a part of determining what the content should be, United Airlines Services Corporation has made an effort to understand how the needs of MAC crews compare with those of civilian airline crews. There are distinct similarities between the crew roles in the cockpits of civilian airliners and military air transports. Many of the attitudes and behaviors exhibited by civil and military crew members are comparable, hence much of the training in the field referred to as Cockpit Resource Management (CRM) is equally appropriate to civil or military aircrews. At the same time, there are significant differences which require assessment to determine if modifications to what might be termed generic CRM are necessary. The investigation enabled the definition and specification of CRM training which is believed to address the needs of the C-5 operational community. The study has concentrated largely on military airlift, but the training objectives and course content of the CRM training are readily adaptable to a wider range of military cockpits than are found in strategic airlift. For instance, CRM training focusing on communication, leadership, situational awareness, and crew coordination is just as appropriate, with some modification, to the pilots manning a flight to Tactical Airlift Command A-7's as it is to the pilots, flight engineers, and loadmasters crewing a C-5.

Speech Intelligibility and Hearing Protector Selection

DTIC Science & Technology

2016-08-29

for use.   8     Another nonstandardized speech intelligibility test relevant to military environments is the Coordinate Response Measure ( CRM ...developed by the U.S. Air Force Research Laboratory (Bolia, Nelson, Ericson, and Simpson, 2000). The phrases in the CRM are comprised of a call...detections and the percentage of correctly identified color-number combinations. The CRM is particularly useful in evaluating speech intelligibility over

Safety and immunogenicity of typhoid fever and yellow fever vaccines when administered concomitantly with quadrivalent meningococcal ACWY glycoconjugate vaccine in healthy adults.

PubMed

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Hlavata, Lucie Cerna; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani K

2015-01-01

Compact and short pre-travel immunization schedules, which include several vaccinations in a single visit, are desirable for many travelers. However, concomitant vaccination could potentially compromise immunogenicity and/or safety of the individual vaccines and, therefore, possible vaccine interferences should be carefully assessed. This article discusses the immunogenicity and safety of travel vaccines for typhoid fever (TF) and yellow fever (YF), when administered with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine (MenACWY-CRM). Healthy adults (18-≤60 years) were randomized to one of three vaccine regimens: TF + YF + MenACWY-CRM (group I; n = 100), TF + YF (group II; n = 101), or MenACWY-CRM (group III; n = 100). Immunogenicity at baseline and 4 weeks post-vaccination (day 29) was assessed by serum bactericidal assay using human complement (hSBA), enzyme-linked immunosorbent assay (ELISA), or a neutralization test. Adverse events (AEs) and serious adverse events (SAEs) were collected throughout the study period. Non-inferiority of post-vaccination geometric mean concentrations (GMCs) and geometric mean titers (GMTs) was established for TF and YF vaccines, respectively, when given concomitantly with MenACWY-CRM vaccine versus when given alone. The percentages of subjects with seroprotective neutralizing titers against YF on day 29 were similar in groups I and II. The antibody responses to meningococcal serogroups A, C, W-135, and Y were within the same range when MenACWY-CRM was given separately or together with TF and YF vaccines. The percentage of subjects reporting AEs was the same for TF and YF vaccines with or without MenACWY-CRM vaccine. There were no reports of SAEs or AEs leading to study withdrawals. These data provide evidence that MenACWY-CRM can be administered with typhoid Vi polysaccharide vaccine and live attenuated YF vaccine without compromising antibody responses stimulated by the individual vaccines. MenACWY-CRM can, therefore, be incorporated into travelers' vaccination programs without necessitating an additional clinic visit (NCT01466387). © 2014 International Society of Travel Medicine.

Dose-escalation designs in oncology: ADEPT and the CRM.

PubMed

Shu, Jianfen; O'Quigley, John

2008-11-20

The ADEPT software package is not a statistical method in its own right as implied by Gerke and Siedentop (Statist. Med. 2008; DOI: 10.1002/sim.3037). ADEPT implements two-parameter CRM models as described in O'Quigley et al. (Biometrics 1990; 46(1):33-48). All of the basic ideas (use of a two-parameter logistic model, use of a two-dimensional prior for the unknown slope and intercept parameters, sequential estimation and subsequent patient allocation based on minimization of some loss function, flexibility to use cohorts instead of one by one inclusion) are strictly identical. The only, and quite trivial, difference arises in the setting of the prior. O'Quigley et al. (Biometrics 1990; 46(1):33-48) used priors having an analytic expression whereas Whitehead and Brunier (Statist. Med. 1995; 14:33-48) use pseudo-data to play the role of the prior. The question of interest is whether two-parameter CRM works as well, or better, than the one-parameter CRM recommended in O'Quigley et al. (Biometrics 1990; 46(1):33-48). Gerke and Siedentop argue that it does. The published literature suggests otherwise. The conclusions of Gerke and Siedentop stem from three highly particular, and somewhat contrived, situations. Unlike one-parameter CRM (Biometrika 1996; 83:395-405; J. Statist. Plann. Inference 2006; 136:1765-1780; Biometrika 2005; 92:863-873), no statistical properties appear to have been studied for two-parameter CRM. In particular, for two-parameter CRM, the parameter estimates are inconsistent. This ought to be a source of major concern to those proposing its use. Worse still, for finite samples the behavior of estimates can be quite wild despite having incorporated the kind of dampening priors discussed by Gerke and Siedentop. An example in which we illustrate this behavior describes a single patient included at level 1 of 6 levels and experiencing a dose limiting toxicity. The subsequent recommendation is to experiment at level 6! Such problematic behavior is not common. Even so, we show that the allocation behavior of two-parameter CRM is very much less stable than that of one-parameter CRM.

Mathematical modeling of mutant transferrin-CRM107 molecular conjugates for cancer therapy.

PubMed

Yoon, Dennis J; Chen, Kevin Y; Lopes, André M; Pan, April A; Shiloach, Joseph; Mason, Anne B; Kamei, Daniel T

2017-03-07

The transferrin (Tf) trafficking pathway is a promising mechanism for use in targeted cancer therapy due to the overexpression of transferrin receptors (TfRs) on cancerous cells. We have previously developed a mathematical model of the Tf/TfR trafficking pathway to improve the efficiency of Tf as a drug carrier. By using diphtheria toxin (DT) as a model toxin, we found that mutating the Tf protein to change its iron release rate improves cellular association and efficacy of the drug. Though this is an improvement upon using wild-type Tf as the targeting ligand, conjugated toxins like DT are unfortunately still highly cytotoxic at off-target sites. In this work, we address this hurdle in cancer research by developing a mathematical model to predict the efficacy and selectivity of Tf conjugates that use an alternative toxin. For this purpose, we have chosen to study a mutant of DT, cross-reacting material 107 (CRM107). First, we developed a mathematical model of the Tf-DT trafficking pathway by extending our Tf/TfR model to include intracellular trafficking via DT and DT receptors. Using this mathematical model, we subsequently investigated the efficacy of several conjugates in cancer cells: DT and CRM107 conjugated to wild-type Tf, as well as to our engineered mutant Tf proteins (K206E/R632A Tf and K206E/R534A Tf). We also investigated the selectivity of mutant Tf-CRM107 against non-neoplastic cells. Through the use of our mathematical model, we predicted that (i) mutant Tf-CRM107 exhibits a greater cytotoxicity than wild-type Tf-CRM107 against cancerous cells, (ii) this improvement was more drastic with CRM107 conjugates than with DT conjugates, and (iii) mutant Tf-CRM107 conjugates were selective against non-neoplastic cells. These predictions were validated with in vitro cytotoxicity experiments, demonstrating that mutant Tf-CRM107 conjugates is indeed a more suitable therapeutic agent. Validation from in vitro experiments also confirmed that such whole-cell kinetic models can be useful in cancer therapeutic design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biological effects of individually synthesized TNF-binding domain of variola virus CrmB protein.

PubMed

Tsyrendorzhiev, D D; Orlovskaya, I A; Sennikov, S V; Tregubchak, T V; Gileva, I P; Tsyrendorzhieva, M D; Shchelkunov, S N

2014-06-01

The biological characteristics of a 17-kDa protein synthesized in bacterial cells, a TNF-binding domain (VARV-TNF-BP) of a 47-kDa variola virus CrmB protein (VARV-CrmB) consisting of TNF-binding and chemokine-binding domains, were studied. Removal of the C-terminal chemokine-binding domain from VARV-CrmB protein was inessential for the efficiency of its inhibition of TNF cytotoxicity towards L929 mouse fibroblast culture and for TNF-induced oxidative metabolic activity of mouse blood leukocytes. The results of this study could form the basis for further studies of VARV-TNF-BP mechanisms of activity for prospective use in practical medicine.

Effect of increased CRM₁₉₇ carrier protein dose on meningococcal C bactericidal antibody response.

PubMed

Lee, Lucia H; Blake, Milan S

2012-04-01

New multivalent CRM(197)-based conjugate vaccines are available for childhood immunization. Clinical studies were reviewed to assess meningococcal group C (MenC) antibody responses following MenC-CRM(197) coadministration with CRM(197)-based pneumococcal or Haemophilus influenzae type b conjugate vaccines. Infants receiving a total CRM(197) carrier protein dose of ∼50 μg and concomitant diphtheria-tetanus-acellular pertussis (DTaP)-containing vaccine tended to have lower MenC geometric mean antibody titers and continued to have low titers after the toddler dose. Nevertheless, at least 95% of children in the reported studies achieved a MenC serum bactericidal antibody (SBA) titer of ≥ 1:8 after the last infant or toddler dose. SBA was measured using an assay with a baby rabbit or human complement source. Additional studies are needed to assess long-term antibody persistence and MenC CRM(197) conjugate vaccine immunogenicity using alternative dosing schedules.

Combat Mission Training Research at the 58th Special Operations Wing: A Summary

DTIC Science & Technology

1998-07-01

Air Force Base during 1995-1997. The first study examined the relationship between crew resource management ( CRM ) processes and mission performance for...next three sections, we summarize the three major empirical studies that were conducted: (a) measuring crew resource management ( CRM ) behaviors... customized measurement procedures and data collection instruments. At the squadron level, there are two problems in implementing an effective CRM training

A Critical Role for CRM1 in Regulating HOXA Gene Transcription in CALM-AF10 Leukemias

PubMed Central

Conway, Amanda E.; Haldeman, Jonathan M.; Wechsler, Daniel S.; Lavau, Catherine P.

2014-01-01

The leukemogenic CALM-AF10 fusion protein is found in patients with immature acute myeloid and T-lymphoid malignancies. CALM-AF10 leukemias display abnormal H3K79 methylation and increased HOXA cluster gene transcription. Elevated expression of HOXA genes is critical for leukemia maintenance and progression; however, the precise mechanism by which CALM-AF10 alters HOXA gene expression is unclear. We previously determined that CALM contains a CRM1-dependent nuclear export signal (NES), which is both necessary and sufficient for CALM-AF10-mediated leukemogenesis. Here, we find that interaction of CALM-AF10 with the nuclear export receptor CRM1 is necessary for activating HOXA gene expression. We show that CRM1 localizes to HOXA loci where it recruits CALM-AF10, leading to transcriptional and epigenetic activation of HOXA genes. Genetic and pharmacological inhibition of the CALM-CRM1 interaction prevents CALM-AF10 enrichment at HOXA chromatin, resulting in immediate loss of transcription. These results provide a comprehensive mechanism by which the CALM-AF10 translocation activates the critical HOXA cluster genes. Furthermore, this report identifies a novel function of CRM1: the ability to bind chromatin and recruit the NES-containing CALM-AF10 transcription factor. PMID:25027513

A Computer-Aided Analysis Method of SPECT Brain Images for Quantitative Treatment Monitoring: Performance Evaluations and Clinical Applications.

PubMed

Zheng, Xiujuan; Wei, Wentao; Huang, Qiu; Song, Shaoli; Wan, Jieqing; Huang, Gang

2017-01-01

The objective and quantitative analysis of longitudinal single photon emission computed tomography (SPECT) images are significant for the treatment monitoring of brain disorders. Therefore, a computer aided analysis (CAA) method is introduced to extract a change-rate map (CRM) as a parametric image for quantifying the changes of regional cerebral blood flow (rCBF) in longitudinal SPECT brain images. The performances of the CAA-CRM approach in treatment monitoring are evaluated by the computer simulations and clinical applications. The results of computer simulations show that the derived CRMs have high similarities with their ground truths when the lesion size is larger than system spatial resolution and the change rate is higher than 20%. In clinical applications, the CAA-CRM approach is used to assess the treatment of 50 patients with brain ischemia. The results demonstrate that CAA-CRM approach has a 93.4% accuracy of recovered region's localization. Moreover, the quantitative indexes of recovered regions derived from CRM are all significantly different among the groups and highly correlated with the experienced clinical diagnosis. In conclusion, the proposed CAA-CRM approach provides a convenient solution to generate a parametric image and derive the quantitative indexes from the longitudinal SPECT brain images for treatment monitoring.

Effectiveness of classroom based crew resource management training in the intensive care unit: study design of a controlled trial

PubMed Central

2011-01-01

Background Crew resource management (CRM) has the potential to enhance patient safety in intensive care units (ICU) by improving the use of non-technical skills. However, CRM evaluation studies in health care are inconclusive with regard to the effect of this training on behaviour and organizational outcomes, due to weak study designs and the scarce use of direct observations. Therefore, the aim of this study is to determine the effectiveness and cost-effectiveness of CRM training on attitude, behaviour and organization after one year, using a multi-method approach and matched control units. The purpose of the present article is to describe the study protocol and the underlying choices of this evaluation study of CRM in the ICU in detail. Methods/Design Six ICUs participated in a paired controlled trial, with one pre-test and two post test measurements (respectively three months and one year after the training). Three ICUs were trained and compared to matched control ICUs. The 2-day classroom-based training was delivered to multidisciplinary groups. Typical CRM topics on the individual, team and organizational level were discussed, such as situational awareness, leadership and communication. All levels of Kirkpatrick's evaluation framework (reaction, learning, behaviour and organisation) were assessed using questionnaires, direct observations, interviews and routine ICU administration data. Discussion It is expected that the CRM training acts as a generic intervention that stimulates specific interventions. Besides effectiveness and cost-effectiveness, the assessment of the barriers and facilitators will provide insight in the implementation process of CRM. Trial registration Netherlands Trial Register (NTR): NTR1976 PMID:22073981

Comparative Biochemical and Functional Analysis of Viral and Human Secreted Tumor Necrosis Factor (TNF) Decoy Receptors*

PubMed Central

Pontejo, Sergio M.; Alejo, Ali; Alcami, Antonio

2015-01-01

The blockade of tumor necrosis factor (TNF) by etanercept, a soluble version of the human TNF receptor 2 (hTNFR2), is a well established strategy to inhibit adverse TNF-mediated inflammatory responses in the clinic. A similar strategy is employed by poxviruses, encoding four viral TNF decoy receptor homologues (vTNFRs) named cytokine response modifier B (CrmB), CrmC, CrmD, and CrmE. These vTNFRs are differentially expressed by poxviral species, suggesting distinct immunomodulatory properties. Whereas the human variola virus and mouse ectromelia virus encode one vTNFR, the broad host range cowpox virus encodes all vTNFRs. We report the first comprehensive study of the functional and binding properties of these four vTNFRs, providing an explanation for their expression profile among different poxviruses. In addition, the vTNFRs activities were compared with the hTNFR2 used in the clinic. Interestingly, CrmB from variola virus, the causative agent of smallpox, is the most potent TNFR of those tested here including hTNFR2. Furthermore, we demonstrate a new immunomodulatory activity of vTNFRs, showing that CrmB and CrmD also inhibit the activity of lymphotoxin β. Similarly, we report for the first time that the hTNFR2 blocks the biological activity of lymphotoxin β. The characterization of vTNFRs optimized during virus-host evolution to modulate the host immune response provides relevant information about their potential role in pathogenesis and may be used to improve anti-inflammatory therapies based on soluble decoy TNFRs. PMID:25940088

Crew resource management and teamwork training in health care: a review of the literature and recommendations for how to leverage such interventions to enhance patient safety.

PubMed

Maynard, M Travis; Marshall, David; Dean, Matthew D

2012-01-01

In an attempt to enhance patient safety, health care facilities are increasingly turning to crew resource management (CRM) and other teamwork training interventions. However, there is still quite a bit about such training interventions that remain unclear. Accordingly, our primary intent herein is to provide some clarity by providing a review of the literature, in hopes of highlighting the current state of the literature as well as identifying the areas that should be addressed by researchers in this field going forward. We searched various electronic databases and utilized numerous relevant search terms to maximize the likelihood of identifying all empirical research related to the use of CRM training within health care. Additionally, we conducted a manual search of the most relevant journals and also conducted a legacy search to identify even more articles. Furthermore, given that as a research team we have experience with CRM initiatives, we also integrate the lessons learned through this experience. Based on our review of the literature, CRM and teamwork training programs generally appear beneficial to individual employees, the groups and teams within such settings, and overall health care organizations. In addition to reviewing the literature that addressed CRM and teamwork training, we also highlight some of the more critical aspects of CRM training programs in order for such initiatives to be as successful as possible. Additionally, we detail various factors that appear essential to sustaining any benefits of CRM over the long haul.

Effectiveness of classroom based crew resource management training in the intensive care unit: study design of a controlled trial.

PubMed

Kemper, Peter F; de Bruijne, Martine; van Dyck, Cathy; Wagner, Cordula

2011-11-10

Crew resource management (CRM) has the potential to enhance patient safety in intensive care units (ICU) by improving the use of non-technical skills. However, CRM evaluation studies in health care are inconclusive with regard to the effect of this training on behaviour and organizational outcomes, due to weak study designs and the scarce use of direct observations. Therefore, the aim of this study is to determine the effectiveness and cost-effectiveness of CRM training on attitude, behaviour and organization after one year, using a multi-method approach and matched control units. The purpose of the present article is to describe the study protocol and the underlying choices of this evaluation study of CRM in the ICU in detail. Six ICUs participated in a paired controlled trial, with one pre-test and two post test measurements (respectively three months and one year after the training). Three ICUs were trained and compared to matched control ICUs. The 2-day classroom-based training was delivered to multidisciplinary groups. Typical CRM topics on the individual, team and organizational level were discussed, such as situational awareness, leadership and communication. All levels of Kirkpatrick's evaluation framework (reaction, learning, behaviour and organisation) were assessed using questionnaires, direct observations, interviews and routine ICU administration data. It is expected that the CRM training acts as a generic intervention that stimulates specific interventions. Besides effectiveness and cost-effectiveness, the assessment of the barriers and facilitators will provide insight in the implementation process of CRM. Netherlands Trial Register (NTR): NTR1976.

Randomized Trial to Compare the Immunogenicity and Safety of a CRM or TT Conjugated Quadrivalent Meningococcal Vaccine in Teenagers who Received a CRM or TT Conjugated Serogroup C Vaccine at Preschool Age.

PubMed

Ishola, David A; Andrews, Nick; Waight, Pauline; Yung, Chee-Fu; Southern, Jo; Bai, Xilian; Findlow, Helen; Matheson, Mary; England, Anna; Hallis, Bassam; Findlow, Jamie; Borrow, Ray; Miller, Elizabeth

2015-08-01

Protection after meningococcal C (MenC) conjugate (MCC) vaccination in early childhood is short-lived. Boosting with a quadrivalent vaccine in teenage years, a high-risk period for MenC disease, should protect against additional serogroups but might compromise MenC response. The carrier protein in the primary MCC vaccine determines the response to MCC booster in toddlers, but the relationship between primary vaccine and booster given later is unclear. This study compared responses to a CRM-conjugated or tetanus toxoid (TT)-conjugated MenACWY vaccine in teenagers primed with different MCC vaccines at preschool age. Ninety-three teenagers (16-19 years), who were previously randomized at age 3-6 years to receive single-dose MCC-CRM or MCC-TT, were randomized to receive either MenACWY-CRM or MenACWY-TT booster. Serum bactericidal antibodies (SBA, protective titer ≥ 8) were measured before, 1 month and 6 or 9 months after boosting. Preboosting, MCC-TT-primed teenagers had significantly higher MenC SBA titers than those MCC-CRM-primed (P = 0.02). Postboosting, both MenACWY vaccines induced protective SBA titers to all 4 serogroups in most participants (≥ 98% at 1 month and ≥ 90% by 9 months postboost). The highest MenC SBA titers were seen in those MCC-TT-primed and MenACWY-TT-boosted [geometric mean titer (GMT) ~ 22,000] followed by those boosted with MenACWY-CRM irrespective of priming (GMT ~ 12,000) and then those MCC-CRM-primed and MenACWY-TT-boosted (GMT ~ 5500). The estimated postbooster MenC SBA decline beyond 1 month was ~40% as time since booster doubles. Both vaccines were well tolerated with no attributable serious adverse events. Both MenACWY vaccines safely induced protective sustained antibody responses against all targeted serogroups in MCC-primed teenagers.

Cardiovascular Risk and the American Dream: Life Course Observations From the BHS (Bogalusa Heart Study).

PubMed

Pollock, Benjamin D; Harville, Emily W; Mills, Katherine T; Tang, Wan; Chen, Wei; Bazzano, Lydia A

2018-02-06

Economic literature shows that a child's future earnings are predictably influenced by parental income, providing an index of "socioeconomic mobility," or the ability of a person to move towards a higher socioeconomic status from childhood to adulthood. We adapted this economic paradigm to examine cardiovascular risk mobility (CRM), or whether there is life course mobility in relative cardiovascular risk. Participants from the BHS (Bogalusa Heart Study) with 1 childhood and 1 adult visit from 1973 to 2016 (n=7624) were considered. We defined population-level CRM as the rank-rank slope (β) from the regression of adult cardiovascular disease (CVD) risk percentile ranking onto childhood CVD risk percentile ranking (β=0 represents complete mobility; β=1 represents no mobility). After defining and measuring relative CRM, we assessed its correlation with absolute cardiovascular health using the American Heart Association's Ideal Cardiovascular Health metrics. Overall, there was substantial mobility, with black participants having marginally better CRM than whites (β black =0.10 [95% confidence interval, 0.05-0.15]; β white =0.18 [95% confidence interval, 0.14-0.22]; P =0.01). Having high relative CVD risk at an earlier age significantly reduced CRM (β age×slope =-0.02; 95% confidence interval, -0.03 to -0.01; P <0.001). Relative CRM was strongly correlated with life course changes in Ideal Cardiovascular Health sum ( r =0.62; 95% confidence interval, 0.60-0.65). Results from this novel application of an economic mobility index to cardiovascular epidemiology indicated substantial CRM, supporting the paradigm that life course CVD risk is highly modifiable. High CRM implies that the children with the best relative CVD profiles may only maintain a slim advantage over their peers into adulthood. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Certification of the Uranium Isotopic Ratios in Nbl Crm 112-A, Uranium Assay Standard (Invited)

NASA Astrophysics Data System (ADS)

Mathew, K. J.; Mason, P.; Narayanan, U.

2010-12-01

Isotopic reference materials are needed to validate measurement procedures and to calibrate multi-collector ion counting detector systems. New Brunswick Laboratory (NBL) provides a suite of certified isotopic and assay standards for the US and international nuclear safeguards community. NBL Certified Reference Material (CRM) 112-A Uranium Metal Assay Standard with a consensus value of 137.88 for the 238U/235U ratio [National Bureau of Standards -- NBS, currently named National Institute for Standards and Technology, Standard Reference Material (SRM) 960 had been renamed CRM 112-A] is commonly used as a natural uranium isotopic reference material within the earth science community. We have completed the analytical work for characterizing the isotopic composition of NBL CRM 112-A Uranium Assay Standard and NBL CRM 145 (uranyl nitrate solution prepared from CRM 112-A). The 235U/238U isotopic ratios were characterized using the total evaporation (TE) and the modified total evaporation (MTE) methods. The 234U/238U isotope ratios were characterized using a conventional analysis technique and verified using the ratios measured in the MTE analytical technique. The analysis plan for the characterization work was developed such that isotopic ratios that are traceable to NBL CRM U030-A are obtained. NBL is preparing a certificate of Analysis and will issue a certificate for Uranium Assay and Isotopics. The results of the CRM 112-A certification measurements will be discussed. These results will be compared with the average values from Richter et al (2010). A comparison of the precision and accuracy of the measurement methods (TE, MTE and Conventional) employed in the certification will be presented. The uncertainties in the 235U/238U and 234U/238U ratios, calculated according to the Guide to the Expression of Uncertainty in Measurements (GUM) and the dominant contributors to the combined standard uncertainty will be discussed.

Character-Defining Features of Contributing Buildings and Structures in the Fort Gordon, Georgia, Signal School Campus Historic District

DTIC Science & Technology

2016-07-01

conditioning CRM Cultural Resources Manager DPW Directorate of Public Works ERDC- CERL Engineer Research and Development Center – Construction Engineering...the interior character-defining features are unknown, but for undertakings that effect the interior the Cultural Resources Man- ager ( CRM ) should use...to the interior; the interior character-defining features are unknown but for undertakings that effect the interior, the CRM should use examples from

Applying Systems Thinking to Law Enforcement Safety: Recommendation for a Comprehensive Safety Management Framework

DTIC Science & Technology

2015-12-01

Occupational Injuries COPS Community Oriented Policing Services CRM Crew Resource Management DA Department of the Army FEMA Federal Emergency...establishes composite risk management ( CRM ), also known as crew resource management, “as the Army’s principal risk reduction methodology and assures...regulatory and statutory compliance.”106 CRM , also utilized by other branches within the military and by the aviation industry, is intended “to minimize

Guidance on the Use of Historic Human Remains Detection Dogs for Locating Unmarked Cemeteries

DTIC Science & Technology

2015-12-01

ERDC/CERL TR-15-36 x Abbreviations Term Spell-out 3D three-dimensional CRM Cultural Resource Management DOAD Decompositional Odor Analysis...cultural resource man- agement ( CRM ) settings now focus on enhanced applications (often in the area of improved data processing and display) and...with activities such as military training, timbering, and vehicle traffic. Fort Gordon CRM staff indicated that the 19th and early 20th century popu

Other Defense Organizations and Defense Finance and Accounting Service Controls Over High-Risk Transactions Were Not Effective

DTIC Science & Technology

2016-03-28

Management (DHA- CRM ), agreed with Recommendations 1 and 2. The Chief stated that the service-level agreements should be updated to provide...descriptive language on the defined roles and responsibilities. In some instances, DHA- CRM personnel find it difficult to identify responsible parties at...that it maintains a universe of all accounting transactions processed daily to include disbursements. Additionally, DHA- CRM personnel perform a

An Evaluation of the Effectiveness of U.S. Naval Aviation Crew Resource Management Training Programs: A Reassessment for the Twenty-First Century Operating Environment

DTIC Science & Technology

2009-06-01

3. Previous Navy CRM Assessments ....................................................24 4. Applying Kirkpatrick’s Topology of Evaluation...development within each aviation community. Kirkpatrick’s (1976) hierarchy of training evaluation technique was applied to examine three levels of... Applying methods and techniques used in previous CRM evaluation research, this thesis provided an updated evaluation of the Naval CRM program to fill

The Common Risk Model for Dams: A Portfolio Approach to Security Risk Assessments

DTIC Science & Technology

2013-06-01

and threat estimates in a way that accounts for the relationships among these variables. The CRM -D can effectively quantify the benefits of...consequence, vulnerability, and threat estimates in a way that properly accounts for the relationships among these variables. The CRM -D can effectively...Common RiskModel ( CRM ) for evaluating and comparing risks associated with the nation’s critical infrastructure. This model incorporates commonly used risk

Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) in healthy Korean adolescents and adults.

PubMed

Lee, Hoan Jong; Chung, Moon-Hyun; Kim, Woo Joo; Hong, Young Jin; Choi, Kyong Min; Lee, Jina; Oh, Chi Eun; Welsch, Jo Anne; Kim, Kyung-Hyo; Hong, Ki Bae; Dagnew, Alemnew F; Bock, Hans; Dull, Peter M; Odrljin, Tatjana

2014-11-01

This phase III placebo-controlled study evaluated the immunogenicity and safety of MenACWY-CRM vaccination in healthy Korean adolescents and adults. Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination against all four meningococcal serogroups. The IgG concentration specific for serogroup W capsular polysaccharide was measured in a subset of subjects in a post-hoc analysis. Adverse reactions were monitored throughout the study. Four hundred and fifty subjects were randomized 2:1 to receive MenACWY-CRM (N=297) or a saline placebo (N=153). MenACWY-CRM induced a good immune response against all four serogroups, with seroprotection rates (hSBA titers ≥8) of 79%, 99%, 98%, and 94% for serogroups A, C, W, and Y, respectively. Seroresponse rates were high for serogroups A, C, and Y, i.e. 76%, 86%, and 69%, respectively; the rate for serogroup W was 28%. MenACWY-CRM vaccine induced serum bactericidal antibodies against all four serogroups in a majority of subjects regardless of their baseline hSBA titers. MenACWY-CRM was generally well tolerated with most reactions being transient and mild to moderate in severity. Findings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects) and geometric mean titers (48, 231, 147, and 107) against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.

Antibodies to Staphylococcus aureus Serotype 8 Capsular Polysaccharide React with and Protect against Serotype 5 and 8 Isolates

PubMed Central

Park, Saeyoung; Gerber, Sabina

2014-01-01

Most Staphylococcus aureus isolates produce either a serotype 5 (CP5) or 8 (CP8) capsular polysaccharide, and the CP antigens are targets for vaccine development. Since CP5 and CP8 have similar trisaccharide repeating units, it is important to identify an epitope shared by both CP5 and CP8. To characterize cross-reactivity between CP5 and CP8, the immunogenicity of CP5 and CP8 conjugate vaccines in mice and rabbits was evaluated by serological assays. Immune sera were also tested for functional activity by in vitro opsonophagocytic-killing assays and a murine bacteremia model. Antibodies to the CP5-cross-reactive material 197 (CRM197) conjugate vaccine bound only to purified CP5. In contrast, antibodies to the CP8-CRM conjugate vaccine reacted with CP8 and (to a lesser extent) CP5. De-O-acetylation of CP5 increased its reactivity with CP8 antibodies. Moreover, CP8 antibodies bound to Pseudomonas aeruginosa O11 lipopolysaccharide, which has a trisaccharide repeating unit similar to that of the S. aureus CPs. CP8-CRM antibodies mediated in vitro opsonophagocytic killing of S. aureus expressing CP5 or CP8, whereas CP5-CRM antibodies were serotype specific. Passive immunization with antiserum to CP5-CRM or CP8-CRM protected mice against bacteremia induced by a serotype 5 S. aureus isolate, suggesting that CP8-CRM elicits antibodies cross-reactive to CP5. The identification of epitopes shared by CP5 and CP8 may inform the rational design of a vaccine to protect against infections caused by CP5- or CP8-producing strains of S. aureus. PMID:25245803

Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age

PubMed Central

Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

2014-01-01

Background: Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Results: Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76–98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. Conclusion: MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Methods: Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period. PMID:24220326

Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age.

PubMed

Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

2014-01-01

Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76-98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period.

A cross-national comparison of incident reporting systems implemented in German and Swiss hospitals.

PubMed

Manser, Tanja; Imhof, Michael; Lessing, Constanze; Briner, Matthias

2017-06-01

This study aimed to empirically compare incident reporting systems (IRS) in two European countries and to explore the relationship of IRS characteristics with context factors such as hospital characteristics and characteristics of clinical risk management (CRM). We performed exploratory, secondary analyses of data on characteristics of IRS from nationwide surveys of CRM practices. The survey was originally sent to 2136 hospitals in Germany and Switzerland. Persons responsible for CRM in 622 hospitals completed the survey (response rate 29%). None. Differences between IRS in German and Swiss hospitals were assessed using Chi2, Fisher's Exact and Freeman-Halton-Tests, as appropriate. To explore interrelations between IRS characteristics and context factors (i.e. hospital and CRM characteristics) we computed Cramer's V. Comparing participating hospitals across countries, Swiss hospitals had implemented IRS earlier, more frequently and more often provided introductory IRS training systematically. German hospitals had more frequently systematically implemented standardized procedures for event analyses. IRS characteristics were significantly associated with hospital characteristics such as hospital type as well as with CRM characteristics such as existence of strategic CRM objectives and of a dedicated position for central CRM coordination. This study contributes to an improved understanding of differences in the way IRS are set up in two European countries and explores related context factors. This opens up new possibilities for empirically informed, strategic interventions to further improve dissemination of IRS and thus support hospitals in their efforts to move patient safety forward. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Comparative Biochemical and Functional Analysis of Viral and Human Secreted Tumor Necrosis Factor (TNF) Decoy Receptors.

PubMed

Pontejo, Sergio M; Alejo, Ali; Alcami, Antonio

2015-06-26

The blockade of tumor necrosis factor (TNF) by etanercept, a soluble version of the human TNF receptor 2 (hTNFR2), is a well established strategy to inhibit adverse TNF-mediated inflammatory responses in the clinic. A similar strategy is employed by poxviruses, encoding four viral TNF decoy receptor homologues (vTNFRs) named cytokine response modifier B (CrmB), CrmC, CrmD, and CrmE. These vTNFRs are differentially expressed by poxviral species, suggesting distinct immunomodulatory properties. Whereas the human variola virus and mouse ectromelia virus encode one vTNFR, the broad host range cowpox virus encodes all vTNFRs. We report the first comprehensive study of the functional and binding properties of these four vTNFRs, providing an explanation for their expression profile among different poxviruses. In addition, the vTNFRs activities were compared with the hTNFR2 used in the clinic. Interestingly, CrmB from variola virus, the causative agent of smallpox, is the most potent TNFR of those tested here including hTNFR2. Furthermore, we demonstrate a new immunomodulatory activity of vTNFRs, showing that CrmB and CrmD also inhibit the activity of lymphotoxin β. Similarly, we report for the first time that the hTNFR2 blocks the biological activity of lymphotoxin β. The characterization of vTNFRs optimized during virus-host evolution to modulate the host immune response provides relevant information about their potential role in pathogenesis and may be used to improve anti-inflammatory therapies based on soluble decoy TNFRs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A Proactive and Top-Down Approach to Managing Risk at NASA

NASA Technical Reports Server (NTRS)

Dezfuli, Homayoon

2010-01-01

Our ultimate goal is to manage risk in a holistic and coherent fashion across the Agency: a) The RIDM process is intended to risk-inform direction-setting decisions. c) The CRM process is intended to manage risk associated with the implementation of baseline performance requirements. Currently we are working on: a) Enhancements to the CRM process. b) Better integration of the RIDM and CRM processes. c) Better integration of institutional risk considerations into RM framework.

Wheat germ agglutinin-conjugated liposomes incorporated with cardiolipin to improve neuronal survival in Alzheimer’s disease treatment

PubMed Central

Kuo, Yung-Chih; Lin, Che-Yu; Li, Jay-Shake; Lou, Yung-I

2017-01-01

Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with surface wheat germ agglutinin (WGA) to downregulate the phosphorylation of kinases in Alzheimer’s disease (AD) therapy. Cardiolipin (CL)-conjugated LIP carrying CRM (CRM-CL/LIP) and also carrying NGF (NGF-CL/LIP) were used with AD models of SK-N-MC cells and Wistar rats after an insult with β-amyloid peptide (Aβ). We found that CRM-CL/LIP inhibited the expression of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 and prevented neurodegeneration of SK-N-MC cells. In addition, NGF-CL/LIP could enhance the quantities of p-neurotrophic tyrosine kinase receptor type 1 and p-extracellular signal-regulated kinase 5 for neuronal rescue. Moreover, WGA-grafted CRM-CL/LIP and WGA-grafted NGF-CL/LIP significantly improved the permeation of CRM and NGF across the blood–brain barrier, reduced Aβ plaque deposition and the malondialdehyde level, and increased the percentage of normal neurons and cholinergic activity in the hippocampus of AD rats. Based on the marker expressions and in vivo evidence, current LIP carriers can be promising drug delivery systems to protect nervous tissue against Aβ-induced apoptosis in the brain during the clinical management of AD. PMID:28280340

Evaluation of endorectal ultrasound (ERUS) and MRI for prediction of circumferential resection margin (CRM) for rectal cancer.

PubMed

Tsai, Catherine; Hague, Cameron; Xiong, Wei; Raval, Manoj; Karimuddin, Ahmer; Brown, Carl; Phang, P Terry

2017-05-01

ERUS and MRI are used for preoperative imaging of rectal cancer. Here, we compare ERUS and MRI for accuracy of CRM prediction at mid- and distal rectal locations. In retrospective review, 20 rectal cancer patients having TME surgery had both ERUS and MRI preoperatively: 8 mid rectum and 12 in distal rectum. Predicted CRM by ERUS and MRI were compared to TME pathology. Overall, predicted CRM was 6.5 ± 3.6 mm by ERUS, 7.7 ± 5.0 mm by MRI, and 6.0 ± 4.6 mm by pathology. Overall, correlation coefficients to pathology were 0.77 (p = 0.0004) for ERUS and 0.64 (p = 0.008) for MRI. In distal rectum, correlation coefficients were 0.71 (p = 0.02) for ERUS and -0.10 (p = 0.79) for MRI. In mid rectum, correlation coefficients were 0.92 (p = 0.01) for ERUS and 0.44 (p = 0.38) for MRI. While MRI is used routinely for preoperative rectal cancer imaging, ERUS can provide additional assessment of CRM for mid or distal rectal lesions. Further investigation is needed to support these preliminary ERUS CRM findings in mid and distal rectum. Copyright © 2017 Elsevier Inc. All rights reserved.

The Effect of Powder Ball Milling on the Microstructure and Mechanical Properties of Sintered Fe-Cr-Mo-Mn-(Cu) Steel

NASA Astrophysics Data System (ADS)

Kulecki, P.; Lichańska, E.

2017-12-01

The effect of ball milling powder mixtures of Höganäs pre-alloyed iron Astaloy CrM, low-carbon ferromanganese Elkem, elemental electrolytic Cu and C-UF graphite on the sintered structure and mechanical properties was evaluated. The mixing was conducted using Turbula mixer for 30 minutes and CDI-EM60 frequency inverter for 1 and 2 hours. Milling was performed on 150 g mixtures with (in weight %) CrM + 1% Mn, CrM + 2% Mn, CrM + 1% Mn + 1% Cu and CrM + 2% Mn + 1% Cu, all with 0.6%C. The green compacts were single pressed at 660 MPa according to PN-EN ISO 2740. Sintering was carried out in a laboratory horizontal furnace Carbolite STF 15/450 at 1250°C for 60 minutes in 5%H2 - 95%N2 atmosphere with a heating rate of 75°C/min, followed by sintering hardening at 60°C/min cooling rate. All the steels were characterized by martensitic structures. Mechanical testing revealed that steels based on milled powders have slightly higher mechanical properties compared to those only mixed and sintered. The best combination of mechanical properties, for ball milled CrM + 1% Mn + 1% Cu was UTS 1046 MPa, TRS 1336 MPa and A 1.94%.

Information system success model for customer relationship management system in health promotion centers.

PubMed

Choi, Wona; Rho, Mi Jung; Park, Jiyun; Kim, Kwang-Jum; Kwon, Young Dae; Choi, In Young

2013-06-01

Intensified competitiveness in the healthcare industry has increased the number of healthcare centers and propelled the introduction of customer relationship management (CRM) systems to meet diverse customer demands. This study aimed to develop the information system success model of the CRM system by investigating previously proposed indicators within the model. THE EVALUATION AREAS OF THE CRM SYSTEM INCLUDES THREE AREAS: the system characteristics area (system quality, information quality, and service quality), the user area (perceived usefulness and user satisfaction), and the performance area (personal performance and organizational performance). Detailed evaluation criteria of the three areas were developed, and its validity was verified by a survey administered to CRM system users in 13 nationwide health promotion centers. The survey data were analyzed by the structural equation modeling method, and the results confirmed that the model is feasible. Information quality and service quality showed a statistically significant relationship with perceived usefulness and user satisfaction. Consequently, the perceived usefulness and user satisfaction had significant influence on individual performance as well as an indirect influence on organizational performance. This study extends the research area on information success from general information systems to CRM systems in health promotion centers applying a previous information success model. This lays a foundation for evaluating health promotion center systems and provides a useful guide for successful implementation of hospital CRM systems.

Information System Success Model for Customer Relationship Management System in Health Promotion Centers

PubMed Central

Choi, Wona; Rho, Mi Jung; Park, Jiyun; Kim, Kwang-Jum; Kwon, Young Dae

2013-01-01

Objectives Intensified competitiveness in the healthcare industry has increased the number of healthcare centers and propelled the introduction of customer relationship management (CRM) systems to meet diverse customer demands. This study aimed to develop the information system success model of the CRM system by investigating previously proposed indicators within the model. Methods The evaluation areas of the CRM system includes three areas: the system characteristics area (system quality, information quality, and service quality), the user area (perceived usefulness and user satisfaction), and the performance area (personal performance and organizational performance). Detailed evaluation criteria of the three areas were developed, and its validity was verified by a survey administered to CRM system users in 13 nationwide health promotion centers. The survey data were analyzed by the structural equation modeling method, and the results confirmed that the model is feasible. Results Information quality and service quality showed a statistically significant relationship with perceived usefulness and user satisfaction. Consequently, the perceived usefulness and user satisfaction had significant influence on individual performance as well as an indirect influence on organizational performance. Conclusions This study extends the research area on information success from general information systems to CRM systems in health promotion centers applying a previous information success model. This lays a foundation for evaluating health promotion center systems and provides a useful guide for successful implementation of hospital CRM systems. PMID:23882416

Development and evaluation of the British English coordinate response measure speech-in-noise test as an occupational hearing assessment tool.

PubMed

Semeraro, Hannah D; Rowan, Daniel; van Besouw, Rachel M; Allsopp, Adrian A

2017-10-01

The studies described in this article outline the design and development of a British English version of the coordinate response measure (CRM) speech-in-noise (SiN) test. Our interest in the CRM is as a SiN test with high face validity for occupational auditory fitness for duty (AFFD) assessment. Study 1 used the method of constant stimuli to measure and adjust the psychometric functions of each target word, producing a speech corpus with equal intelligibility. After ensuring all the target words had similar intelligibility, for Studies 2 and 3, the CRM was presented in an adaptive procedure in stationary speech-spectrum noise to measure speech reception thresholds and evaluate the test-retest reliability of the CRM SiN test. Studies 1 (n = 20) and 2 (n = 30) were completed by normal-hearing civilians. Study 3 (n = 22) was completed by hearing impaired military personnel. The results display good test-retest reliability (95% confidence interval (CI) < 2.1 dB) and concurrent validity when compared to the triple-digit test (r ≤ 0.65), and the CRM is sensitive to hearing impairment. The British English CRM using stationary speech-spectrum noise is a "ready to use" SiN test, suitable for investigation as an AFFD assessment tool for military personnel.

77 FR 6482 - Conductor Certification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-08

... resource management'' (CRM), a concept perfected in aviation and urgently pressed on the railroad industry..., 1999). Major railroads have included CRM in their training programs. It is particularly important that...

CRISPR/Cas9 and active genetics-based trans-species replacement of the endogenous Drosophila kni-L2 CRM reveals unexpected complexity.

PubMed

Xu, Xiang-Ru Shannon; Gantz, Valentino Matteo; Siomava, Natalia; Bier, Ethan

2017-12-23

The knirps ( kni ) locus encodes transcription factors required for induction of the L2 wing vein in Drosophila . Here, we employ diverse CRISPR/Cas9 genome editing tools to generate a series of targeted lesions within the endogenous cis-regulatory module (CRM) required for kni expression in the L2 vein primordium. Phenotypic analysis of these ' in locus ' mutations based on both expression of Kni protein and adult wing phenotypes, reveals novel unexpected features of L2-CRM function including evidence for a chromosome pairing-dependent process that promotes transcription. We also demonstrate that self-propagating active genetic elements (CopyCat elements) can efficiently delete and replace the L2-CRM with orthologous sequences from other divergent fly species. Wing vein phenotypes resulting from these trans-species enhancer replacements parallel features of the respective donor fly species. This highly sensitive phenotypic readout of enhancer function in a native genomic context reveals novel features of CRM function undetected by traditional reporter gene analysis. © 2017, Xu et al.

CRISPR/Cas9 and active genetics-based trans-species replacement of the endogenous Drosophila kni-L2 CRM reveals unexpected complexity

PubMed Central

Siomava, Natalia

2017-01-01

The knirps (kni) locus encodes transcription factors required for induction of the L2 wing vein in Drosophila. Here, we employ diverse CRISPR/Cas9 genome editing tools to generate a series of targeted lesions within the endogenous cis-regulatory module (CRM) required for kni expression in the L2 vein primordium. Phenotypic analysis of these ‘in locus’ mutations based on both expression of Kni protein and adult wing phenotypes, reveals novel unexpected features of L2-CRM function including evidence for a chromosome pairing-dependent process that promotes transcription. We also demonstrate that self-propagating active genetic elements (CopyCat elements) can efficiently delete and replace the L2-CRM with orthologous sequences from other divergent fly species. Wing vein phenotypes resulting from these trans-species enhancer replacements parallel features of the respective donor fly species. This highly sensitive phenotypic readout of enhancer function in a native genomic context reveals novel features of CRM function undetected by traditional reporter gene analysis. PMID:29274230

[Hi-Fi simulation: Teaching crisis resource management to surgery residents].

PubMed

Georgescu, Mihai; Tanoubi, Issam; Drolet, Pierre; Robitaille, Arnaud; Perron, Roger; Patenaude, Jean Victor

2015-02-01

High-fidelity (HiFi) simulation has shown its effectiveness for teaching crisis resource management (CRM) principles, and our institutional experience in this area is mainly with anesthesiology residents. We recently added to our postgraduate curriculum a new CRM course designed to cater to the specific needs of surgical residents. This short communication describes the experience of the University of Montreal Simulation Centre (Centre d'Apprentissage des Attitudes et Habiletés Cliniques CAAHC) regarding HiFi simulationbased CRM and communication skills teaching for surgical residents. Thirty residents agreed to participate in a simulation course with pre-established scenarios and educational CRM objectives on a voluntary basis. When surveyed immediately after the activity, all residents agreed that the educational objectives were well defined (80% "strongly agree" and 20% "agree"). The survey also showed that the course was well accepted by all participants (96% "strongly agree" and 4% "agree"). Further trials with randomized groups and more reliable assessment tools are needed to validate our results. Still, integrating HiFi simulation based CRM learning in the surgical residency curriculum seems like an interesting step.

NESDIS OSPO Data Access Policy and CRM

NASA Astrophysics Data System (ADS)

Seybold, M. G.; Donoho, N. A.; McNamara, D.; Paquette, J.; Renkevens, T.

2012-12-01

The Office of Satellite and Product Operations (OSPO) is the NESDIS office responsible for satellite operations, product generation, and product distribution. Access to and distribution of OSPO data was formally established in a Data Access Policy dated February, 2011. An extension of the data access policy is the OSPO Customer Relationship Management (CRM) Database, which has been in development since 2008 and is reaching a critical level of maturity. This presentation will provide a summary of the data access policy and standard operating procedure (SOP) for handling data access requests. The tangential CRM database will be highlighted including the incident tracking system, reporting and notification capabilities, and the first comprehensive portfolio of NESDIS satellites, instruments, servers, applications, products, user organizations, and user contacts. Select examples of CRM data exploitation will show how OSPO is utilizing the CRM database to more closely satisfy the user community's satellite data needs with new product promotions, as well as new data and imagery distribution methods in OSPO's Environmental Satellite Processing Center (ESPC). In addition, user services and outreach initiatives from the Satellite Products and Services Division will be highlighted.

Potential protective immunogenicity of tetanus toxoid, diphtheria toxoid and Cross Reacting Material 197 (CRM197) when used as carrier proteins in glycoconjugates.

PubMed

Bröker, Michael

2016-03-03

When tetanus toxoid (TT), diphtheria toxoid (DT) or Cross Reacting Material 197 (CRM197), a non-toxic diphtheria toxin mutant protein, are used as carrier proteins in glycoconjugate vaccines, these carriers induce a protein specific antibody response as measured by in vitro assays. Here, it was evaluated whether or not glycoconjugates based on TT, DT or CRM197 can induce a protective immune response as measured by potency tests according to the European Pharmacopoeia. It could be shown, that the conjugate carriers TT and DT can induce a protective immune response against a lethal challenge by toxins in animals, while glycoconjugates based on CRM197 failed to induce a protective immune response. Opportunities for new applications of glycoconjugates are discussed.

Evaluating the effectiveness of cockpit resource management training

NASA Technical Reports Server (NTRS)

Helmreich, Robert L.

1989-01-01

The concept of providing flight crews with intensive training in crew coordination and interpersonal skills (cockpit resource management training - CRM) is outlined with emphasis on full mission simulator training (line-oriented flight training - LOFT). Findings from several airlines that have instituted CRM and LOFT are summarized. Four types of criteria used for evaluating CRM programs: observer ratings of crew behavior, measures of attitudes regarding cockpit management, self-reports by participants on the value of the training, and case studies of CRM-related incidents and accidents are covered. Attention is focused on ratings of the performance of crews during line flights and during simulator sessions conducted as a part of LOFT. A boomerang effect - the emergence of a subgroup that has changed the attitudes in the opposite direction from that desired is emphasized.

Comprehensive reimbursement model: an alternative to fee-for-service reimbursement by blood centers.

PubMed

Fuller, M J; Holland, P V

1997-01-01

"If we could first know where we are, and whither we are tending, we could then better judge what to do and how to do it." This quote from Abraham Lincoln epitomizes where SMF and its CRM hospital customers are today. The CRM has been received by SMF's hospital customers as a step in the right direction. Currently, it seems to be the best way to partner with hospitals by sharing risk in the current health care delivery system milieu. The CRM focus on patient outcomes will provide hospitals and blood centers a common goal. Modifications to the CRM will most certainly be necessary. With input from customers and the community over time, and flexibility from SMF, a revised model will evolve that will be even more mutually beneficial.

A strategy for representing the effects of convective momentum transport in multiscale models: Evaluation using a new superparameterized version of the Weather Research and Forecast model (SP-WRF)

NASA Astrophysics Data System (ADS)

Tulich, S. N.

2015-06-01

This paper describes a general method for the treatment of convective momentum transport (CMT) in large-scale dynamical solvers that use a cyclic, two-dimensional (2-D) cloud-resolving model (CRM) as a "superparameterization" of convective-system-scale processes. The approach is similar in concept to traditional parameterizations of CMT, but with the distinction that both the scalar transport and diagnostic pressure gradient force are calculated using information provided by the 2-D CRM. No assumptions are therefore made concerning the role of convection-induced pressure gradient forces in producing up or down-gradient CMT. The proposed method is evaluated using a new superparameterized version of the Weather Research and Forecast model (SP-WRF) that is described herein for the first time. Results show that the net effect of the formulation is to modestly reduce the overall strength of the large-scale circulation, via "cumulus friction." This statement holds true for idealized simulations of two types of mesoscale convective systems, a squall line, and a tropical cyclone, in addition to real-world global simulations of seasonal (1 June to 31 August) climate. In the case of the latter, inclusion of the formulation is found to improve the depiction of key synoptic modes of tropical wave variability, in addition to some aspects of the simulated time-mean climate. The choice of CRM orientation is also found to importantly affect the simulated time-mean climate, apparently due to changes in the explicit representation of wide-spread shallow convective regions.

Video concepts in CRM training

NASA Technical Reports Server (NTRS)

Yocum, M.

1984-01-01

Cockpit resource management (CRM) is discussed in the context of programs developed by Pennsylvania Airlines and Ransome Airlines. Video techniques in flight training are emphasized. Problems in cockpit interpersonal communication are addressed.

14 CFR 121.907 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... definitions apply to this subpart: Crew Resource Management (CRM) means the effective use of all the resources... technical and CRM skills. Line Operational Simulation (LOS) means a training or evaluation session, as...

Tomorrow’s Handgun: Ensuring the Right Gun for All Military Law Enforcement Officers

DTIC Science & Technology

2016-02-01

www.military.com/equipment/m9-pistol. 23 Ibid. 24 Russell, Sara M. Soldier Perspectives on Small Arms in Combat. Tech. no. CRM D0015259.A2. Alexandria...pistol-of- choice-1749620057. Russell, Sara M. Soldier Perspectives on Small Arms in Combat. Tech. no. CRM D0015259.A2. Alexandria, VA: CNA...Tech. no. CRM D0015259.A2. Alexandria, VA: CNA, 2006. Print. "The Avalon Project: Laws of War - Declaration on the Use of Bullets Which Expand or

Persistence of immune responses after a single dose of Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo®) or Menactra® among healthy adolescents.

PubMed

Gill, Christopher J; Baxter, Roger; Anemona, Alessandra; Ciavarro, Giuseppe; Dull, Peter

2010-11-01

The persistence of human bactericidal activity (hSBA) responses in adolescents was assessed 22 months after vaccination with one dose of Menveo® (MenACWY-CRM; Novartis) or Menactra® (MCV4) (sanofi pasteur). The proportion of subjects with hSBA titers ≥8 was significantly higher among recipients of MenACWY-CRM than MCV4 for serogroups A, W-135 and Y.

Extending and Applying the EPIC Architecture for Human Cognition and Performance: Auditory and Spatial Components

DTIC Science & Technology

2016-03-01

manual rather than verbal responses. The coordinate response measure ( CRM ) task and speech corpus is a highly simplified form of the command and...in multi-talker speech experiments. The CRM corpus is a collection of recorded command utterances in the form of Ready <Callsign> go to <Color...In the two-talker CRM listening task, participants respond to commands by pointing to the appropriate Color/Digit pair on a computer display. A

Comparative Assessment of a Single Dose and a 2-dose Vaccination Series of a Quadrivalent Meningococcal CRM-conjugate Vaccine (MenACWY-CRM) in Children 2-10 Years of Age.

PubMed

Johnston, William; Essink, Brandon; Kirstein, Judith; Forleo-Neto, Eduardo; Percell, Sandra; Han, Linda; Keshavan, Pavitra; Smolenov, Igor

2016-01-01

We compared the immunogenicity, safety and 1-year antibody persistence of a single-dose and a 2-dose series of a licensed meningococcal ACWY-CRM conjugate vaccine (MenACWY-CRM) in 2- to 10-year-old children. In this phase III, multicenter, observer-blind study, children aged 2-5 years (n = 359) and 6-10 years (n = 356) were randomized 1:1 to receive 2 doses of MenACWY-CRM (ACWY2) or 1 dose of placebo followed by 1 dose of MenACWY-CRM (ACWY1), 2 months apart. Immunogenicity was measured using serum bactericidal activity with human complement (hSBA). Primary outcomes were to assess the immunologic noninferiority and superiority of ACWY2 versus ACWY1. One-month after the second dose, the hSBA seroresponse in ACWY2 was noninferior to ACWY1 for all 4 serogroups, in both age cohorts, and was superior for serogroups C and Y in the 2- to 5-year-old age cohort and for serogroup Y in the 6- to 10-year-old age cohort. Overall, 90%-99% of subjects in ACWY2 and 65%-96% in ACWY1 had hSBA titers ≥ 8; geometric mean titers were 1.8- to 6.4-fold higher in ACWY2 than ACWY1 across serogroups. At 1 year postvaccination, geometric mean titers declined, and the differences between ACWY2 and ACWY1 remained significant for serogroups A and C in the 2- to 5-year-old age cohort and for serogroups C and Y in the 6- to 10-year-old age cohort. The safety profile of MenACWY-CRM was similar in both groups. The single dose and 2-dose MenACWY-CRM series were immunogenic and well tolerated. Although antibody responses were greater after 2 doses, especially in the 2- to 5-year-old age cohort, this difference was less pronounced at 1 year postvaccination.

WASP (Write a Scientific Paper) using Excel - 13: Correlation and Regression.

PubMed

Grech, Victor

2018-07-01

Correlation and regression measure the closeness of association between two continuous variables. This paper explains how to perform these tests in Microsoft Excel and their interpretation, as well as how to apply these tests dynamically using Excel's functions. Copyright © 2018 Elsevier B.V. All rights reserved.

Cloud-System Resolving Models: Status and Prospects

NASA Technical Reports Server (NTRS)

Tao, Wei-Kuo; Moncreiff, Mitch

2008-01-01

Cloud-system resolving models (CRM), which are based on the nonhydrostatic equations of motion and typically have a grid-spacing of about a kilometer, originated as cloud-process models in the 1970s. This paper reviews the status and prospects of CRMs across a wide range of issues, such as microphysics and precipitation; interaction between clouds and radiation; and the effects of boundary-layer and surface-processes on cloud systems. Since CRMs resolve organized convection, tropical waves and the large-scale circulation, there is the prospect for several advances in both basic knowledge of scale-interaction requisite to parameterizing mesoscale processes in climate models. In superparameterization, CRMs represent convection, explicitly replacing many of the assumptions necessary in contemporary parameterization. Global CRMs have been run on an experimental basis, giving prospect to a new generation of climate weather prediction in a decade, and climate models due course. CRMs play a major role in the retrieval of surface-rain and latent heating from satellite measurements. Finally, enormous wide dynamic ranges of CRM simulations present new challenges for model validation against observations.

Acidified pressurized hot water for the continuous extraction of cadmium and lead from plant materials prior to ETAAS

NASA Astrophysics Data System (ADS)

Morales-Muñoz, S.; Luque-García, J. L.; Luque de Castro, M. D.

2003-01-01

Acidified and pressurized hot water is proposed for the continuous leaching of Cd and Pb from plants prior to determination by electrothermal atomic absorption spectrometry. Beech leaves (a certified reference material—CRM 100—where the analytes were not certified) were used for optimizing the method by a multivariate approach. The samples (0.5 g) were subjected to dynamic extraction with water modified with 1% v/v HNO 3 at 250 °C as leachant. A kinetics study was performed in order to know the pattern of the extraction process. The method was validated with a CRM (olive leaves, 062 from the BCR) where the analytes had been certified. The agreement between the certified values and those found using the proposed method demonstrates its usefulness. The repeatability and within-laboratory reproducibility were 3.7 and 2.3% for Cd and 1.04% and 6.3% for Pb, respectively. The precision of the method, together with its efficiency, rapidity, and environmental acceptability, makes it a good alternative for the determination of trace metals in plant material.

A Dynamic Recommender System for Improved Web Usage Mining and CRM Using Swarm Intelligence.

PubMed

Alphy, Anna; Prabakaran, S

2015-01-01

In modern days, to enrich e-business, the websites are personalized for each user by understanding their interests and behavior. The main challenges of online usage data are information overload and their dynamic nature. In this paper, to address these issues, a WebBluegillRecom-annealing dynamic recommender system that uses web usage mining techniques in tandem with software agents developed for providing dynamic recommendations to users that can be used for customizing a website is proposed. The proposed WebBluegillRecom-annealing dynamic recommender uses swarm intelligence from the foraging behavior of a bluegill fish. It overcomes the information overload by handling dynamic behaviors of users. Our dynamic recommender system was compared against traditional collaborative filtering systems. The results show that the proposed system has higher precision, coverage, F1 measure, and scalability than the traditional collaborative filtering systems. Moreover, the recommendations given by our system overcome the overspecialization problem by including variety in recommendations.

A Dynamic Recommender System for Improved Web Usage Mining and CRM Using Swarm Intelligence

PubMed Central

Alphy, Anna; Prabakaran, S.

2015-01-01

In modern days, to enrich e-business, the websites are personalized for each user by understanding their interests and behavior. The main challenges of online usage data are information overload and their dynamic nature. In this paper, to address these issues, a WebBluegillRecom-annealing dynamic recommender system that uses web usage mining techniques in tandem with software agents developed for providing dynamic recommendations to users that can be used for customizing a website is proposed. The proposed WebBluegillRecom-annealing dynamic recommender uses swarm intelligence from the foraging behavior of a bluegill fish. It overcomes the information overload by handling dynamic behaviors of users. Our dynamic recommender system was compared against traditional collaborative filtering systems. The results show that the proposed system has higher precision, coverage, F1 measure, and scalability than the traditional collaborative filtering systems. Moreover, the recommendations given by our system overcome the overspecialization problem by including variety in recommendations. PMID:26229978

Crew Resource Management An Introductory Handbook

DOT National Transportation Integrated Search

1992-08-01

Recent research findings suggest that crew resource management (CRM) training can : result in significant improvements in flightcrew performance. The objectives of this : handbook are to foster an understanding of the background and philosophy of CRM...

Potential protective immunogenicity of tetanus toxoid, diphtheria toxoid and Cross Reacting Material 197 (CRM197) when used as carrier proteins in glycoconjugates

PubMed Central

Bröker, Michael

2016-01-01

abstract When tetanus toxoid (TT), diphtheria toxoid (DT) or Cross Reacting Material 197 (CRM197), a non-toxic diphtheria toxin mutant protein, are used as carrier proteins in glycoconjugate vaccines, these carriers induce a protein specific antibody response as measured by in vitro assays. Here, it was evaluated whether or not glycoconjugates based on TT, DT or CRM197 can induce a protective immune response as measured by potency tests according to the European Pharmacopoeia. It could be shown, that the conjugate carriers TT and DT can induce a protective immune response against a lethal challenge by toxins in animals, while glycoconjugates based on CRM197 failed to induce a protective immune response. Opportunities for new applications of glycoconjugates are discussed. PMID:26327602

Phase behavior and oral bioavailability of amorphous Curcumin.

PubMed

Pawar, Yogesh B; Shete, Ganesh; Popat, Dharmesh; Bansal, Arvind K

2012-08-30

Amorphous form has been used as a means to improve aqueous solubility and oral bioavailability of poorly water soluble drugs. The objective of present study was to characterize thermodynamic and kinetic parameters of amorphous form of Curcumin (CRM-A). CRM-A was found to be a good glass former with glass transition temperature (T(g)) of 342.64K and critical cooling rate below 1K/min. CRM-A had a moderate tendency of crystallization and exhibited Kauzmann temperature (T(KS)) of 294.23 K. CRM-A was found to be fragile in nature as determined by T(m)/T(g) (1.32), C(p)(1 iq):C(p)(glass) (1.22), strength parameter (D<10), fragility index (m>75), T(K)/T(g) (0.85), and T(g)-T(K) (48.41). Theoretically predicted aqueous solubility advantage of 43.15-folds, was reduced to 17-folds under practical conditions. This reduction in solubility was attributed to water induced devitrification, as evident through PXRD and SEM analysis. Further, oral bioavailability study of CRM-A was undertaken to investigate bioavailability benefits, if any. C(max) was improved by 1.97-folds (statistically significant difference over control). However, oral bioavailability (AUC(0-)(∞)) was improved by 1.45-folds (statistically non significant difference over control). These observations pointed towards role of rapid devitrification of CRM-A in GIT milieu, thus limiting its oral bioavailability advantage. Copyright © 2012 Elsevier B.V. All rights reserved.

Magnetic resonance imaging (MRI)-based indication for neoadjuvant treatment of rectal carcinoma and the surrogate endpoint CRM status.

PubMed

Strassburg, Joachim; Junginger, Theo; Trinh, Trong; Püttcher, Olaf; Oberholzer, Katja; Heald, Richard J; Hermanek, Paul

2008-11-01

Is it possible to reduce the frequency of neoadjuvant therapy for rectal carcinoma and nevertheless achieve a rate of more than 90% circumferential resection margin (CRM)-negative resection specimens by a novel concept of magnetic resonance imaging (MRI)-based therapy planning? One hundred eighty-one patients from Berlin and Mainz, Germany, with primary rectal carcinoma, without distant metastasis, underwent radical surgery with curative intention. Surgical procedures applied were anterior resection with total mesorectal excision (TME) or partial mesorectal excision (PME; PME for tumours of the upper rectum) or abdominoperineal excision with TME. With MRI selection of the highest-risk cases, neoadjuvant therapy was given to only 62 of 181 (34.3%). The rate of CRM-negative resection specimens on histology was 170 of 181 (93.9%) for all patients, and in Berlin, only 1 of 93 (1%) specimens was CRM-positive. Patients selected for primary surgery had CRM-negative specimens on histology in 114 of 119 (95.8%). Those selected for neoadjuvant therapy had a lower rate of clear margin: 56 of 62 (90%). By applying a MRI-based indication, the frequency of neoadjuvant treatment with its acute and late adverse effects can be reduced to 30-35% without reduction of pathologically CRM-negative resection specimens and, thus, without the danger of worsening the oncological long-term results. This concept should be confirmed in prospective multicentre observation studies with quality assurance of MRI, surgery and pathology.

Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

PubMed

Arguedas, A; Soley, C; Loaiza, C; Rincon, G; Guevara, S; Perez, A; Porras, W; Alvarado, O; Aguilar, L; Abdelnour, A; Grunwald, U; Bedell, L; Anemona, A; Dull, P M

2010-04-19

This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity. Copyright 2010 Elsevier Ltd. All rights reserved.

Transcutaneous immunization with cross-reacting material CRM(197) of diphtheria toxin boosts functional antibody levels in mice primed parenterally with adsorbed diphtheria toxoid vaccine.

PubMed

Stickings, Paul; Peyre, Marisa; Coombes, Laura; Muller, Sylviane; Rappuoli, Rino; Del Giudice, Giuseppe; Partidos, Charalambos D; Sesardic, Dorothea

2008-04-01

Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM(197)) of diphtheria toxin was used as the boosting antigen and was administered alone or together with either one of two commonly used mucosal adjuvants, cholera toxin (CT) and a partially detoxified mutant of heat-labile enterotoxin of Escherichia coli (LTR72). We report that TCI with CRM(197) significantly boosted preexisting immune responses elicited after parenteral priming with aluminum hydroxide-adsorbed diphtheria toxoid (DTxd) vaccine. In the presence of LTR72 as an adjuvant, toxin-neutralizing antibody titers were significantly higher than those elicited by CRM(197) alone and were comparable to the functional antibody levels induced after parenteral booster immunization with the adsorbed DTxd vaccine. Time course study showed that high levels of toxin-neutralizing antibodies persisted for at least 14 weeks after the transcutaneous boost. In addition, TCI resulted in a vigorous antigen-specific proliferative response in all groups of mice boosted with the CRM(197) protein. These findings highlight the promising prospect of using booster administrations of CRM(197) via the transcutaneous route to establish good herd immunity against diphtheria.

[Report of the NEDO project "Research and development to promote the creation and utilization of an intellectual infrastructure: development of reference materials for laboratory medicine" "Development of pure substance-type certified reference materials"].

PubMed

Takatsu, Akiko

2009-06-01

There is an increasing demand to establish a metrological traceability system for in vitro diagnostics and medical devices. Pure substance-type reference materials are playing key roles in metrological traceability, because they form the basis for many traceability chains in chemistry. The National Metrology Institute of Japan (NMIJ), in the National Institute of Advanced Industrial Science and Technology (AIST), has been developing purity-certified reference materials (CRMs) in this field, such as cholesterol, creatinine, and urea. In the New Energy and Industrial Technology Development Organization (NEDO) project, entitled: "Research and Development to Promote the Creation and Utilization of an Intellectual Infrastructure: Development of Reference Materials for Laboratory Medicine", several pure substance-type CRMs were developed. For a pure protein solution CRM, amino acid analysis and nitrogen determination were chosen as the certification methods. The development and certification processes for the C-reactive protein (CRP) solution CRM were completed, with the recombinant human CRP solution as a candidate material. This CRP solution CRM is now available as NMIJ CRM. For cortisol CRM, a purified candidate material and highly pure primary reference material were prepared. Each impure compound in the materials was identified and quantified. The pure cortisol CRM will be available in 2009. These two CRMs provide a traceability link between routine clinical methods and the SI unit.

Building a Values-Informed Mental Model for New Orleans Climate Risk Management.

PubMed

Bessette, Douglas L; Mayer, Lauren A; Cwik, Bryan; Vezér, Martin; Keller, Klaus; Lempert, Robert J; Tuana, Nancy

2017-10-01

Individuals use values to frame their beliefs and simplify their understanding when confronted with complex and uncertain situations. The high complexity and deep uncertainty involved in climate risk management (CRM) lead to individuals' values likely being coupled to and contributing to their understanding of specific climate risk factors and management strategies. Most mental model approaches, however, which are commonly used to inform our understanding of people's beliefs, ignore values. In response, we developed a "Values-informed Mental Model" research approach, or ViMM, to elicit individuals' values alongside their beliefs and determine which values people use to understand and assess specific climate risk factors and CRM strategies. Our results show that participants consistently used one of three values to frame their understanding of risk factors and CRM strategies in New Orleans: (1) fostering a healthy economy, wealth, and job creation, (2) protecting and promoting healthy ecosystems and biodiversity, and (3) preserving New Orleans' unique culture, traditions, and historically significant neighborhoods. While the first value frame is common in analyses of CRM strategies, the latter two are often ignored, despite their mirroring commonly accepted pillars of sustainability. Other values like distributive justice and fairness were prioritized differently depending on the risk factor or strategy being discussed. These results suggest that the ViMM method could be a critical first step in CRM decision-support processes and may encourage adoption of CRM strategies more in line with stakeholders' values. © 2017 Society for Risk Analysis.

Local government units initiatives on coastal resource management in adjacent municipalities in Camarines Sur, Philippines

NASA Astrophysics Data System (ADS)

Faustino, A. Z.; Madela, H. L.

2018-03-01

This research was conducted to determine the local government units (LGUs) initiatives on coastal resource management (CRM) in adjacent municipalities in Camarines Sur, Philippines. The respondents of this study are 100 fisherfolk leaders in the municipalities of Calabanga, Tinambac and Siruma. Descriptive, comparative and evaluative methods of research were employed and a survey questionnaire was used as the primary tool in data gathering. On the test of difference, the computed F-value of 12.038 and p-value of .001 revealed a very high difference in the implementation of CRM initiatives in the adjacent municipalities. The respondents in this study live below the poverty threshold. The intrusion of commercial fishers and the use of active fishing gears inside the 15-km municipal waters significantly affect the marine habitat while fishpond conversion kills the natural cycle in the mangrove forests. However, the FOs membership in the Municipal Fisheries and Aquatic Resources Management Council empower them to engage in governance which can be a venue for them to recommend policies related to CRM. As a result of this study, a CRM monitoring and evaluation model was crafted to guide the LGUs in the review, revision and crafting of CRM programs.

[siRNAs with high specificity to the target: a systematic design by CRM algorithm].

PubMed

Alsheddi, T; Vasin, L; Meduri, R; Randhawa, M; Glazko, G; Baranova, A

2008-01-01

'Off-target' silencing effect hinders the development of siRNA-based therapeutic and research applications. Common solution to this problem is an employment of the BLAST that may miss significant alignments or an exhaustive Smith-Waterman algorithm that is very time-consuming. We have developed a Comprehensive Redundancy Minimizer (CRM) approach for mapping all unique sequences ("targets") 9-to-15 nt in size within large sets of sequences (e.g. transcriptomes). CRM outputs a list of potential siRNA candidates for every transcript of the particular species. These candidates could be further analyzed by traditional "set-of-rules" types of siRNA designing tools. For human, 91% of transcripts are covered by candidate siRNAs with kernel targets of N = 15. We tested our approach on the collection of previously described experimentally assessed siRNAs and found that the correlation between efficacy and presence in CRM-approved set is significant (r = 0.215, p-value = 0.0001). An interactive database that contains a precompiled set of all human siRNA candidates with minimized redundancy is available at http://129.174.194.243. Application of the CRM-based filtering minimizes potential "off-target" silencing effects and could improve routine siRNA applications.

Characterization of NIES CRM No. 23 Tea Leaves II for the determination of multielements.

PubMed

Mori, Ikuko; Ukachi, Miyuki; Nagano, Kimiyo; Ito, Hiroyasu; Yoshinaga, Jun; Nishikawa, Masataka

2010-05-01

A candidate environmental certified reference material (CRM) for the determination of multielements in tea leaves and materials of similar matrix, NIES CRM No. 23 Tea Leaves II, has been developed and characterized by the National Institute for Environmental Studies (NIES), Japan. The origin of the material was tea leaves, which were ground, sieved through a 106-microm mesh, homogenized, and then subdivided into amber glass bottles. The results of homogeneity and stability tests indicated that the material was sufficiently homogeneous and stable for use as a reference material. The property values of the material were statistically determined based on chemical analyses by a network of laboratories using a wide range of methods. Sixteen laboratories participated in the characterization, and nine certified values and five reference values were obtained. These property values of the candidate CRM, which are expressed as mass fractions, were close to the median and/or mean values of the mass fractions of elements in various tea products. The candidate CRM is appropriate for use in analytical quality control and in the evaluation of methods used in the analysis of tea and materials of similar matrix.

The RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 ligase is a disassembly machine for Crm1-dependent nuclear export complexes

PubMed Central

Ritterhoff, Tobias; Das, Hrishikesh; Hofhaus, Götz; Schröder, Rasmus R.; Flotho, Annette; Melchior, Frauke

2016-01-01

Continuous cycles of nucleocytoplasmic transport require disassembly of transport receptor/Ran-GTP complexes in the cytoplasm. A basic disassembly mechanism in all eukaryotes depends on soluble RanGAP and RanBP1. In vertebrates, a significant fraction of RanGAP1 stably interacts with the nucleoporin RanBP2 at a binding site that is flanked by FG-repeats and Ran-binding domains, and overlaps with RanBP2's SUMO E3 ligase region. Here, we show that the RanBP2/RanGAP1*SUMO1/Ubc9 complex functions as an autonomous disassembly machine with a preference for the export receptor Crm1. We describe three in vitro reconstituted disassembly intermediates, which show binding of a Crm1 export complex via two FG-repeat patches, cargo-release by RanBP2's Ran-binding domains and retention of free Crm1 at RanBP2 after Ran-GTP hydrolysis. Intriguingly, all intermediates are compatible with SUMO E3 ligase activity, suggesting that the RanBP2/RanGAP1*SUMO1/Ubc9 complex may link Crm1- and SUMO-dependent functions. PMID:27160050

NXT1, a Novel Influenza A NP Binding Protein, Promotes the Nuclear Export of NP via a CRM1-Dependent Pathway.

PubMed

Chutiwitoonchai, Nopporn; Aida, Yoko

2016-07-28

Influenza remains a serious worldwide public health problem. After infection, viral genomic RNA is replicated in the nucleus and packed into viral ribonucleoprotein, which will then be exported to the cytoplasm via a cellular chromosome region maintenance 1 (CRM1)-dependent pathway for further assembly and budding. However, the nuclear export mechanism of influenza virus remains controversial. Here, we identify cellular nuclear transport factor 2 (NTF2)-like export protein 1 (NXT1) as a novel binding partner of nucleoprotein (NP) that stimulates NP-mediated nuclear export via the CRM1-dependent pathway. NXT1-knockdown cells exhibit decreased viral replication kinetics and nuclear accumulated viral RNA and NP. By contrast, NXT1 overexpression promotes nuclear export of NP in a CRM1-dependent manner. Pull-down assays suggest the formation of an NXT1, NP, and CRM1 complex, and demonstrate that NXT1 binds to the C-terminal region of NP. These findings reveal a distinct mechanism for nuclear export of the influenza virus and identify the NXT1/NP interaction as a potential target for antiviral drug development.

Crew resource management training within the automotive industry: does it work?

PubMed

Marquardt, Nicki; Robelski, Swantje; Hoeger, Rainer

2010-04-01

This article presents the development, implementation, and evaluation of a crew resource management (CRM) training program specifically designed for employees within the automotive industry. The central objective of this training program was to improve communication, teamwork, and stress management skills as well to increase the workers' situational awareness of potential errors that can occur during the production process. Participants in the training program of this study were 80 employees, all of whom were working in a production unit for gearbox manufacturing. Effectiveness of the CRM training course was evaluated two times (1 month and 6 months after the training program). The results showed a significant improvement in a wide range of CRM-relevant categories, especially in teamwork-related attitudes, in addition to an increase in the workers' situational awareness after the training program. On the basis of the results, it can be stated that CRM training, which was originally developed for the aviation industry, can be transferred to the automotive industry. However, because of the lack of behavioral observations, these effects are limited to CRM attitudes and knowledge changes. Several recommendations for future research and training development in the field of human factors training are made.

78 FR 46330 - Public ICWG Announcement-2013

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

... Resolution Matrix (CRM) form. These forms along with the Was/Is Matrix, current versions of the documents... Compatibility (ABC) Study Group Kickoff Please provide them in the CRM form and submit to the SMC/GPER mailbox...

The benefits of CRM: is your home care agency missing out?

PubMed

Bishop, Adam D

2009-12-01

Home care executives today have at their disposal all the means necessary to manage information and strengthen relationships with customers, thanks to innovative customer relationship management (CRM) tools, Adam D. Bishop explains.

An Integrated Approach for Physical and Cyber Security Risk Assessment: The U.S. Army Corps of Engineers Common Risk Model for Dams

DTIC Science & Technology

2016-07-01

Common Risk Model for Dams ( CRM -D) Methodology,” for the Director, Cost Assessment and Program Evaluation, Office of Secretary of Defense and the...for Dams ( CRM -D), developed by the U.S. Army Corps of Engineers (USACE) in collaboration with the Institute for Defense Analyses (IDA) and the U.S...and cyber security risks across a portfolio of dams, and informing decisions on how to mitigate those risks. The CRM -D can effectively quantify the

A Coulomb-Like Off-Shell T-Matrix with the Correct Coulomb Phase Shift

NASA Astrophysics Data System (ADS)

Oryu, Shinsho; Watanabe, Takashi; Hiratsuka, Yasuhisa; Togawa, Yoshio

2017-03-01

We confirm the reliability of the well-known Coulomb renormalization method (CRM). It is found that the CRM is only available for a very-long-range screened Coulomb potential (SCP). However, such an SCP calculation in momentum space is considerably difficult because of the cancelation of significant digits. In contrast to the CRM, we propose a new method by using an on-shell equivalent SCP and the rest term. The two-potential theory with r-space is introduced, which defines fully the off-shell Coulomb amplitude.

Lessons from cross-fleet/cross-airline observations - Evaluating the impact of CRM/LOFT training

NASA Technical Reports Server (NTRS)

Butler, Roy E.

1991-01-01

A review is presented of the crew resource management/line oriented flight training (CRM/LOFT) program to help determine the level of standardization across fleets and airlines in the critical area of evaluating crew behavior and performance. One of the goals of the project is to verify that check airmen and LOFT instructors within organizations are evaluating CRM issues consistently and that differences observed between fleets are not a function of idiosyncracies on the part of observers. Attention is given to the research tools for crew evaluation.

High-power picosecond fiber source for coherent Raman microscopy

PubMed Central

Kieu, Khanh; Saar, Brian G.; Holtom, Gary R.; Xie, X. Sunney; Wise, Frank W.

2011-01-01

We report a high-power picosecond fiber pump laser system for coherent Raman microscopy (CRM). The fiber laser system generates 3.5 ps pulses with 6 W average power at 1030 nm. Frequency doubling yields more than 2 W of green light, which can be used to pump an optical parametric oscillator to produce the pump and the Stokes beams for CRM. Detailed performance data on the laser and the various wavelength conversion steps are discussed, together with representative CRM images of fresh animal tissue obtained with the new source. PMID:19571996

ModuleMiner - improved computational detection of cis-regulatory modules: are there different modes of gene regulation in embryonic development and adult tissues?

PubMed Central

Van Loo, Peter; Aerts, Stein; Thienpont, Bernard; De Moor, Bart; Moreau, Yves; Marynen, Peter

2008-01-01

We present ModuleMiner, a novel algorithm for computationally detecting cis-regulatory modules (CRMs) in a set of co-expressed genes. ModuleMiner outperforms other methods for CRM detection on benchmark data, and successfully detects CRMs in tissue-specific microarray clusters and in embryonic development gene sets. Interestingly, CRM predictions for differentiated tissues exhibit strong enrichment close to the transcription start site, whereas CRM predictions for embryonic development gene sets are depleted in this region. PMID:18394174

Sumoylation in p27kip1 via RanBP2 promotes cancer cell growth in cholangiocarcinoma cell line QBC939.

PubMed

Yang, Jun; Liu, Yan; Wang, Bing; Lan, Hongzhen; Liu, Ying; Chen, Fei; Zhang, Ju; Luo, Jian

2017-09-07

Cholangiocarcinoma is one of the deadly disease with poor 5-year survival and poor response to conventional therapies. Previously, we found that p27kip1 nuclear-cytoplasmic translocation confers proliferation potential to cholangiocarcinoma cell line QBC939 and this process is mediated by crm-1. However, no other post-transcriptional regulation was found in this process including sumoylation in cholangiocarcinoma. In this study, we explored the role of sumoylation in the nuclear-cytoplasmic translocation of p27kip1 and its involvement of QBC939 cells' proliferation. First, we identified K73 as the sumoylation site in p27kip1. By utilizing plasmid flag-p27kip1, HA-RanBP2, GST-RanBP2 and His-p27kip1 and immunoprecipitation assay, we validated that p27kip1 can serve as the sumoylation target of RanBP2 in QBC939. Furthermore, we confirmed crm-1's role in promoting nuclear-cytoplasmic translocation of p27kip1 and found that RanBP2's function relies on crm-1. However, K73R mutated p27kip1 can't be identified by crm-1 or RanBP2 in p27kip1 translocation process, suggesting sumoylation of p27kip1 via K73 site is necessary in this process by RanBP2 and crm-1. Phenotypically, the overexpression of either RanBP2 or crm-1 can partially rescue the anti-proliferative effect brought by p27kip1 overexpression in both the MTS and EdU assay. For the first time, we identified and validated the K73 sumoylation site in p27kip1, which is critical to RanBP2 and crm-1 in p27kip1 nuclear-cytoplasmic translocation process. Taken together, targeted inhibition of sumoylation of p27kip1 may serve as a potentially potent therapeutic target in the eradication of cholangiocarcinoma development and relapses.

Assessment of immunogenicity and safety following primary and booster immunisation with a CRM197 -conjugated Haemophilus influenzae type B vaccine in healthy Chinese infants.

PubMed

Jun, L; Yuguo, C; Zhiguo, W; Jinfeng, L; Huawei, M; Xiuhua, L; Yonggui, Z; Yanhua, X; Kong, Y; Hongtao, L; Yuliang, Z

2013-10-01

Invasive meningitis and pneumonia caused by Haemophilus influenzae type b (Hib) is an important cause of childhood mortality in countries where Hib vaccination is not routine. We evaluated the non-inferiority of a licensed Hib vaccine, PRP-CRM(197) compared with a second licensed Hib vaccine, PRP-T, following the recommended Chinese immunisation schedule for infants between 6 months and 1 year of age. In the first study phase, 6-12 month-old infants received two primary doses of either PRP-CRM(197) (n = 335) or PRP-T (n = 335) vaccine administered 1 month apart. In the second study phase 8 months later, the same children received a single booster dose of vaccine identical to that use for priming (PRP-CRM(197), n = 327; PRP-T, n = 333). Serum levels of anti-polyribosylribitol phosphate (PRP) antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Non-inferiority of primary and booster doses was assessed in terms of percentages of subjects with anti-PRP antibody levels associated with providing short-term (≥ 0.15 μg/ml) and long-term (≥ 1.0 μg/ml) protection; the non-inferiority margin was set at -5%. PRP-CRM(197) was demonstrated to be non-inferior to PRP-T. Anti-PRP antibodies levels ≥ 0.15 μg/ml and ≥ 1.0 μg/ml were achieved by 97% of infants in the PRP-CRM(197) group and 98% of infants in the PRP-T group 1 month after primary immunisation, and by all subjects (100%) in both vaccine groups 1 month after booster administration. Safety profiles for both vaccines were similar; no serious adverse events, deaths or adverse events leading to withdrawal occurred during the study. PRP-CRM(197) was well-tolerated and immunologically non-inferior to a licensed comparator Hib vaccine in Chinese infants (Clinicaltrials.gov: NCT01044316 & NCT01226953). © 2013 John Wiley & Sons Ltd.

Investigation on Sugar-Protein Connectivity in Salmonella O-Antigen Glycoconjugate Vaccines.

PubMed

De Benedetto, Gianluigi; Salvini, Laura; Gotta, Stefano; Cescutti, Paola; Micoli, Francesca

2018-05-16

Invasive nontyphoidal Salmonella disease, for which licensed vaccines are not available, is a leading cause of bloodstream infections in Africa. The O-antigen portion of lipopolysaccharide is a good target for protective immunity. Covalent conjugation of the O-antigen to a carrier protein increases its immunogenicity and O-antigen based glycoconjugate vaccines are currently under investigation at the preclinical stage. We developed a conjugation chemistry for linking O-antigen to CRM 197 carrier protein, through sequential insertion of adipic acid dihydrazide (ADH) and adipic acid bis( N-hydroxysuccinimide) ester (SIDEA) as linkers, without impacting O-antigen chain epitopes. Here the resulting sugar-protein connectivity has been investigated in detail. The core portion of the lipopolysaccharide was used as a model molecule to prepare CRM 197 conjugates, making structural investigations easier. The first step of reductive amination with ADH involves the terminal 3-deoxy-d- manno-oct-2-ulosonic acid (KDO) residue of the core region. The second reaction step resulted not to be selective, as SIDEA reacted with both ADH and pyrophosphorylethanolamine (PPEtN) of the core region, independently from the pH at which the reaction was performed. Peptide mapping analysis of the deglycosylated core-CRM 197 conjugates confirmed that lysine residues of CRM 197 were linked to SIDEA not only through KDO-ADH but also through PPEtN. This analysis also confirmed that the conjugation chemistry is random on the protein, involving a large number of lysine residues, particularly the surface exposed ones. The method for core-CRM 197 characterization was successfully extended to O-antigen-CRM 197 conjugate, confirming the results obtained with the core. This study not only allowed full characterization of OAg-CRM 197 conjugates, but can be applied to optimize synthesis and characterization of other OAg-based glycoconjugate vaccines. Analytical methods to investigate saccharide-protein connectivity are also of fundamental importance to study the relationship between glycoconjugate structure and immune response induced.

A cooperative reduction model for regional air pollution control in China that considers adverse health effects and pollutant reduction costs.

PubMed

Xie, Yujing; Zhao, Laijun; Xue, Jian; Hu, Qingmi; Xu, Xiang; Wang, Hongbo

2016-12-15

How to effectively control severe regional air pollution has become a focus of global concern recently. The non-cooperative reduction model (NCRM) is still the main air pollution control pattern in China, but it is both ineffective and costly, because each province must independently fight air pollution. Thus, we proposed a cooperative reduction model (CRM), with the goal of maximizing the reduction in adverse health effects (AHEs) at the lowest cost by encouraging neighboring areas to jointly control air pollution. CRM has two parts: a model of optimal pollutant removal rates using two optimization objectives (maximizing the reduction in AHEs and minimizing pollutant reduction cost) while meeting the regional pollution control targets set by the central government, and a model that allocates the cooperation benefits (i.e., health improvement and cost reduction) among the participants according to their contributions using the Shapley value method. We applied CRM to the case of sulfur dioxide (SO 2 ) reduction in Yangtze River Delta region. Based on data from 2003 to 2013, and using mortality due to respiratory and cardiovascular diseases as the health endpoints, CRM saves 437 more lives than NCRM, amounting to 12.1% of the reduction under NCRM. CRM also reduced costs by US $65.8×10 6 compared with NCRM, which is 5.2% of the total cost of NCRM. Thus, CRM performs significantly better than NCRM. Each province obtains significant benefits from cooperation, which can motivate them to actively cooperate in the long term. A sensitivity analysis was performed to quantify the effects of parameter values on the cooperation benefits. Results shown that the CRM is not sensitive to the changes in each province's pollutant carrying capacity and the minimum pollutant removal capacity, but sensitive to the maximum pollutant reduction capacity. Moreover, higher cooperation benefits will be generated when a province's maximum pollutant reduction capacity increases. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of crumb rubber modification of Louisiana mixtures : [research project capsule].

DOT National Transportation Integrated Search

2015-11-01

The Louisiana Department of : Transportation and Development : (DOTD) has been allowing crumb rubber : modi cation (CRM) of asphalt mixtures : since 2008. Initially, the performance : of roadways constructed with CRM was : adequate. The in uenc...

77 FR 60695 - Agency Information Collection Activities: Announcement of Board Approval Under Delegated...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-04

... (CRM) surcharge data item to the annual schedule, and revise the quarterly schedule to include the... reflect the Market Risk rule's CRM, (6) revising the Credit RWA associated with Credit Valuation...

75 FR 5328 - Agency Information Collection Request; 60-Day Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-02

... center (REC) will be provided with a customer relationship management (CRM) software tool, which they... selecting a CRM vendor. Once this is completed it will submit the specific reports for clearance. [[Page...

75 FR 62543 - Agency Information Collection Request. 30-Day Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

... Total burden respondents respondent response hours CRM Tool Regional Extension Center......... 60 12 1.5 1080 CRM Tool Community College Consortia....... 84 20 1.5 2,520 Total 3600 Seleda Perryman, Office of...

Certified reference material of volatile organic compounds for environmental analysis: BTEX in methanol.

PubMed

Neves, Laura A; Almeida, Renato R R; Rego, Eliane P; Rodrigues, Janaína Marques; de Carvalho, Lucas Junqueira; de M Goulart, Ana Letícia

2015-04-01

The Brazilian Metrology Institute (National Institute of Metrology, Quality, and Technology, Inmetro) has been developing a certified reference material (CRM) of the volatile organic compounds benzene; toluene; ethylbenzene; and ortho, meta, and para-xylenes (BTEX) in methanol, to ensure quality control for environmental-analysis measurements. The objective of this paper is to present the results of certification studies: uncertainty estimates related to characterization, a homogeneity study, and a stability study on a single lot of CRM composed of BTEX in methanol. The method used analysis of variance (ANOVA), a statistical tool, to evaluate the homogeneity and stability of the BTEX CRM, which complies with ISO Guide 30 series. The homogeneity and stability of the BTEX CRM was confirmed for all analytes and their respective properties. All the procedures used in this study complied with ISO GUIDE 34, ISO GUIDE 35, and the guide to the expression of uncertainty of measurement (GUM).

Development of a new chlorogenic acid certified reference material for food and drug analysis.

PubMed

Yang, Dezhi; Jiao, LingTai; Zhang, Baoxi; Du, Guanhua; Lu, Yang

2017-06-05

This paper reports the preparation and characterization of a new chlorogenic acid (CHA) certified reference material (CRM), which is unavailable commercially. CHA is an active ingredient found in many geo-authentic Chinese medicinal materials and developed as an anti-cancer drug. In this work, trace impurities were isolated and identified through various techniques. CHA CRM was quantified with two analytical methods, and their results were in good agreement with each other. The certified value and corresponding expanded uncertainty of CHA CRM reached 99.4%±0.2%, which was calculated by multiplying the combined standard uncertainty by the coverage factor (k=2), at a confidence level of 95%. This CRM can be used to calibrate measurement system, evaluate or validate measurement procedures, assign traceable property values to non-CRMs, and conduct quality control assays. Copyright © 2017 Elsevier B.V. All rights reserved.

CIDOC-CRM extensions for conservation processes: A methodological approach

NASA Astrophysics Data System (ADS)

Vassilakaki, Evgenia; Zervos, Spiros; Giannakopoulos, Georgios

2015-02-01

This paper aims to report the steps taken to create the CIDOC Conceptual Reference Model (CIDOC-CRM) extensions and the relationships established to accommodate the depiction of conservation processes. In particular, the specific steps undertaken for developing and applying the CIDOC-CRM extensions for defining the conservation interventions performed on the cultural artifacts of the National Archaeological Museum of Athens, Greece are presented in detail. A report on the preliminary design of the DOC-CULTURE project (Development of an integrated information environment for assessment and documentation of conservation interventions to cultural works/objects with nondestructive testing techniques [NDTs], www.ndt-lab.gr/docculture), co-financed by the European Union NSRF THALES program, can be found in Kyriaki-Manessi, Zervos & Giannakopoulos (1) whereas the NDT&E methods and their output data through CIDOC-CRM extension of the DOC-CULTURE project approach to standardize the documentation of the conservation were further reported in Kouis et al. (2).

Cockpit resource management training at People Express

NASA Technical Reports Server (NTRS)

Bruce, Keith D.; Jensen, Doug

1987-01-01

In January 1986 in a continuing effort to maintain and improve flight safety and solve some Cockpit Resource Management (CRM) problems, People Express implemented a new CRM training program. It is a continuously running program, scheduled over the next three years and includes state-of-the-art full-mission simulation (LOFT), semi-annual seminar workshops and a comprehensive academic program authored by Robert W. Mudge of Cockpit Management Resources Inc. That program is outlined and to maximize its contribution to the workshop's goals, is organized into four topic areas: (1) Program content: the essential elements of resource management training; (2) Training methods: the strengths and weaknesses of current approaches; (3) Implementation: the implementation of CRM training; and (4) Effectiveness: the effectiveness of training. It is confined as much as possible to concise descriptions of the program's basic components. Brief discussions of rationale are included, however no attempt is made to discuss or review popular CRM tenets or the supporting research.

Comparison of CRM197, diphtheria toxoid and tetanus toxoid as protein carriers for meningococcal glycoconjugate vaccines.

PubMed

Tontini, M; Berti, F; Romano, M R; Proietti, D; Zambonelli, C; Bottomley, M J; De Gregorio, E; Del Giudice, G; Rappuoli, R; Costantino, P; Brogioni, G; Balocchi, C; Biancucci, M; Malito, E

2013-10-01

Glycoconjugate vaccines are among the most effective and safest vaccines ever developed. Diphtheria toxoid (DT), tetanus toxoid (TT) and CRM197 have been mostly used as protein carriers in licensed vaccines. We evaluated the immunogenicity of serogroup A, C, W-135 and Y meningococcal oligosaccharides conjugated to CRM197, DT and TT in naïve mice. The three carriers were equally efficient in inducing an immune response against the carbohydrate moiety in immunologically naïve mice. The effect of previous exposure to different dosages of the carrier protein on the anti-carbohydrate response was studied using serogroup A meningococcal (MenA) saccharide conjugates as a model. CRM197 showed a strong propensity to positively prime the anti-carbohydrate response elicited by its conjugates or those with the antigenically related carrier DT. Conversely in any of the tested conditions TT priming did not result in enhancement of the anti-carbohydrate response elicited by the corresponding conjugates. Repeated exposure of mice to TT or to CRM197 before immunization with the respective MenA conjugates resulted in a drastic suppression of the anti-carbohydrate response in the case of TT conjugate and only in a slight reduction in the case of CRM197. The effect of carrier priming on the anti-MenA response of DT-based conjugates varied depending on their carbohydrate to protein ratio. These data may have implications for human vaccination since conjugate vaccines are widely used in individuals previously immunized with DT and TT carrier proteins. Copyright © 2013 Elsevier Ltd. All rights reserved.

Barriers and facilitators to ED physician use of the test and treatment for BPPV

PubMed Central

Forman, Jane; Damschroder, Laura; Telian, Steven A.; Fagerlin, Angela; Johnson, Patricia; Brown, Devin L.; An, Lawrence C.; Morgenstern, Lewis B.; Meurer, William J.

2017-01-01

Abstract Background: The test and treatment for benign paroxysmal positional vertigo (BPPV) are evidence-based practices supported by clinical guideline statements. Yet these practices are underutilized in the emergency department (ED) and interventions to promote their use are needed. To inform the development of an intervention, we interviewed ED physicians to explore barriers and facilitators to the current use of the Dix-Hallpike test (DHT) and the canalith repositioning maneuver (CRM). Methods: We conducted semi-structured in-person interviews with ED physicians who were recruited at annual ED society meetings in the United States. We analyzed data thematically using qualitative content analysis methods. Results: Based on 50 interviews with ED physicians, barriers that contributed to infrequent use of DHT/CRM that emerged were (1) prior negative experiences or forgetting how to perform them and (2) reliance on the history of present illness to identify BPPV, or using the DHT but misattributing patterns of nystagmus. Based on participants' responses, the principal facilitator of DHT/CRM use was prior positive experiences using these, even if infrequent. When asked which clinical supports would facilitate more frequent use of DHT/CRM, participants agreed supports needed to be brief, readily accessible, and easy to use, and to include well-annotated video examples. Conclusions: Interventions to promote the use of the DHT/CRM in the ED need to overcome prior negative experiences with the DHT/CRM, overreliance on the history of present illness, and the underuse and misattribution of patterns of nystagmus. Future resources need to be sensitive to provider preferences for succinct information and video examples. PMID:28680765

Microsoft Repository Version 2 and the Open Information Model.

ERIC Educational Resources Information Center

Bernstein, Philip A.; Bergstraesser, Thomas; Carlson, Jason; Pal, Shankar; Sanders, Paul; Shutt, David

1999-01-01

Describes the programming interface and implementation of the repository engine and the Open Information Model for Microsoft Repository, an object-oriented meta-data management facility that ships in Microsoft Visual Studio and Microsoft SQL Server. Discusses Microsoft's component object model, object manipulation, queries, and information…

78 FR 53128 - Initiation of Antidumping and Countervailing Duty Administrative Reviews and Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

...., Ltd Weifang East Steel Pipe Co., Ltd WISCO & CRM Wuhan Materials & Trade Zhejiang Kingland Pipeline... Longshenghua Import & Export Tianjin Shuangjie Steel Pipe Co., Ltd Weifang East Steel Pipe Co., Ltd WISCO & CRM...

77 FR 77017 - Initiation of Antidumping and Countervailing Duty Administrative Reviews and Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-31

... Co., Ltd. Wenzhou Juxing Special Steel Co. Ltd. Widesea Industrial Corporation Ltd. Wisco & Crm Wuhan... Corporation Ltd. Wisco & Crm Wuhan Materials & Trade WSP Pipe Co., Ltd. Wuhan Iron & Steel (Group) Corp. Wuxi...

77 FR 26185 - POSTNET Barcode Discontinuation

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-03

....17.2 regarding Courtesy Reply Mail (CRM). [Revise the title and text of 3.17.2 as follows:] 3.17.2 Courtesy Reply Mail Courtesy reply mail (CRM) is reply mail other than BRM or MRM enclosed in other mail...

Evaluation of field projects using crumb rubber modified asphaltic concrete.

DOT National Transportation Integrated Search

2007-03-01

In 1994, the Louisiana Department of Transportation and Development (LADOTD) initiated a research project to evaluate different crumb-rubber modified (CRM) applications in which the long-term pavement performance of the CRM asphalt pavements was comp...

Improving patient safety in the radiation oncology setting through crew resource management.

PubMed

Sundararaman, Srinath; Babbo, Angela E; Brown, John A; Doss, Richard

2014-01-01

This paper demonstrates how the communication patterns and protocol rigors of a methodology called crew resource management (CRM) can be adapted to a radiation oncology environment to create a culture of patient safety. CRM training was introduced to our comprehensive radiation oncology department in the autumn of 2009. With 34 full-time equivalent staff, we see 100-125 patients daily on 2 hospital campuses. We were assisted by a consulting group with considerable experience in helping hospitals incorporate CRM principles and practices. Implementation steps included developing change initiative skills for key leaders, providing training in teamwork and communications, creating site-specific tools for safety and efficiency, and collecting data to document results. Our goals were to improve patient safety, teamwork, communication, and efficiency through the use of tools we developed that emphasized teamwork and communication, cross-checking, and routinizing specific protocols. Our CRM plan relies on the following 4 pillars: patient identification methods; "pause for the cause"; enabling all staff to halt treatment and question decisions; and daily morning meetings. We discuss some of the hurdles to change we encountered. Our safety record has improved. Our near-miss rate before CRM implementation averaged 11 per month; our near-miss rate currently averages 1.2 per month. In the 5 years prior to CRM implementation, we experienced 1 treatment deviation per year, although none rose to the level of "mis-administration." Since implementing CRM, our current patient treatment setup and delivery process has eliminated all treatment deviations. Our practices have identified situations where ambiguity or conflicting documentation could have resulted in inappropriate treatment or treatment inefficiencies. Our staff members have developed an extraordinary sense of teamwork combined with a high degree of personal responsibility to assure patient safety and have spoken up when they considered something potentially unsafe. We have increased our efficiency (and profitability); in 2012, our units of service were up 11.3% over 2009 levels with the same staffing level. The rigor and standardization introduced into our practice, combined with the increase in communication and teamwork have improved both safety and efficiency while improving both staff and patient satisfaction. CRM principles are highly adaptable and applicable to the radiation oncology setting. © 2014. Published by Elsevier Inc. All rights reserved.

Progress in the Development of a Global Quasi-3-D Multiscale Modeling Framework

NASA Astrophysics Data System (ADS)

Jung, J.; Konor, C. S.; Randall, D. A.

2017-12-01

The Quasi-3-D Multiscale Modeling Framework (Q3D MMF) is a second-generation MMF, which has following advances over the first-generation MMF: 1) The cloud-resolving models (CRMs) that replace conventional parameterizations are not confined to the large-scale dynamical-core grid cells, and are seamlessly connected to each other, 2) The CRMs sense the three-dimensional large- and cloud-scale environment, 3) Two perpendicular sets of CRM channels are used, and 4) The CRMs can resolve the steep surface topography along the channel direction. The basic design of the Q3D MMF has been developed and successfully tested in a limited-area modeling framework. Currently, global versions of the Q3D MMF are being developed for both weather and climate applications. The dynamical cores governing the large-scale circulation in the global Q3D MMF are selected from two cube-based global atmospheric models. The CRM used in the model is the 3-D nonhydrostatic anelastic Vector-Vorticity Model (VVM), which has been tested with the limited-area version for its suitability for this framework. As a first step of the development, the VVM has been reconstructed on the cubed-sphere grid so that it can be applied to global channel domains and also easily fitted to the large-scale dynamical cores. We have successfully tested the new VVM by advecting a bell-shaped passive tracer and simulating the evolutions of waves resulted from idealized barotropic and baroclinic instabilities. For improvement of the model, we also modified the tracer advection scheme to yield positive-definite results and plan to implement a new physics package that includes a double-moment microphysics and an aerosol physics. The interface for coupling the large-scale dynamical core and the VVM is under development. In this presentation, we shall describe the recent progress in the development and show some test results.

Field test of coordinated ramp metering (CRM).

DOT National Transportation Integrated Search

2017-03-15

This project has focused on field implementation and testing of a Coordinated Ramp Metering (CRM) algorithm at California State Route 99 : Northbound corridor in Sacramento between Calvine Road and the SR50 interchange after 12th Ave. It is a 9 mile ...

Molecularly uniform poly(ethylene glycol) certified reference material

NASA Astrophysics Data System (ADS)

Takahashi, Kayori; Matsuyama, Shigetomo; Kinugasa, Shinichi; Ehara, Kensei; Sakurai, Hiromu; Horikawa, Yoshiteru; Kitazawa, Hideaki; Bounoshita, Masao

2015-02-01

A certified reference material (CRM) for poly(ethylene glycol) with no distribution in the degree of polymerization was developed. The degree of polymerization of the CRM was accurately determined to be 23. Supercritical fluid chromatography (SFC) was used to separate the molecularly uniform polymer from a standard commercial sample with wide polydispersity in its degree of polymerization. Through the use of a specific fractionation system coupled with SFC, we are able to obtain samples of poly(ethylene glycol) oligomer with exact degrees of polymerization, as required for a CRM produced by the National Metrology Institute of Japan.

Extended cox regression model: The choice of timefunction

NASA Astrophysics Data System (ADS)

Isik, Hatice; Tutkun, Nihal Ata; Karasoy, Durdu

2017-07-01

Cox regression model (CRM), which takes into account the effect of censored observations, is one the most applicative and usedmodels in survival analysis to evaluate the effects of covariates. Proportional hazard (PH), requires a constant hazard ratio over time, is the assumptionofCRM. Using extended CRM provides the test of including a time dependent covariate to assess the PH assumption or an alternative model in case of nonproportional hazards. In this study, the different types of real data sets are used to choose the time function and the differences between time functions are analyzed and discussed.

Reengineering ribosome export.

PubMed

Lo, Kai-Yin; Johnson, Arlen W

2009-03-01

Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appears to be conserved for 60S export in higher eukaryotes. We asked if export of the large subunit requires specific receptors. We made protein fusions between mutant Nmd3 and various export receptors. Surprisingly, fusions of Mex67, the tRNA exportin Los1, Mtr2, Cse1, or Msn5 to Nmd3, lacking its Crm1-dependent nuclear export signal (NES), all functioned in export. Furthermore, these chimeric proteins supported 60S export even in the presence of the Crm1 inhibitor leptomycin B, indicating that export was now independent of Crm1. These results suggest that there is not a requirement for a specific export receptor for the large subunit, as recruitment of any receptor will suffice. Finally we show that the addition of an NES directly to the 60S ribosomal subunit protein Rpl3 promotes export. These results imply remarkable flexibility in the export pathway for the 60S subunit and help explain how different export receptors could have evolved in different eukaryotic lineages.

Reengineering Ribosome Export

PubMed Central

Lo, Kai-Yin

2009-01-01

Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appears to be conserved for 60S export in higher eukaryotes. We asked if export of the large subunit requires specific receptors. We made protein fusions between mutant Nmd3 and various export receptors. Surprisingly, fusions of Mex67, the tRNA exportin Los1, Mtr2, Cse1, or Msn5 to Nmd3, lacking its Crm1-dependent nuclear export signal (NES), all functioned in export. Furthermore, these chimeric proteins supported 60S export even in the presence of the Crm1 inhibitor leptomycin B, indicating that export was now independent of Crm1. These results suggest that there is not a requirement for a specific export receptor for the large subunit, as recruitment of any receptor will suffice. Finally we show that the addition of an NES directly to the 60S ribosomal subunit protein Rpl3 promotes export. These results imply remarkable flexibility in the export pathway for the 60S subunit and help explain how different export receptors could have evolved in different eukaryotic lineages. PMID:19144820

Assessing Strain Mapping by Electron Backscatter Diffraction and Confocal Raman Microscopy Using Wedge-indented Si

PubMed Central

Friedman, Lawrence H.; Vaudin, Mark D.; Stranick, Stephan J.; Stan, Gheorghe; Gerbig, Yvonne B.; Osborn, William; Cook, Robert F.

2016-01-01

The accuracy of electron backscatter diffraction (EBSD) and confocal Raman microscopy (CRM) for small-scale strain mapping are assessed using the multi-axial strain field surrounding a wedge indentation in Si as a test vehicle. The strain field is modeled using finite element analysis (FEA) that is adapted to the near-indentation surface profile measured by atomic force microscopy (AFM). The assessment consists of (1) direct experimental comparisons of strain and deformation and (2) comparisons in which the modeled strain field is used as an intermediate step. Direct experimental methods (1) consist of comparisons of surface elevation and gradient measured by AFM and EBSD and of Raman shifts measured and predicted by CRM and EBSD, respectively. Comparisons that utilize the combined FEA-AFM model (2) consist of predictions of distortion, strain, and rotation for comparison with EBSD measurements and predictions of Raman shift for comparison with CRM measurements. For both EBSD and CRM, convolution of measurements in depth-varying strain fields is considered. The interconnected comparisons suggest that EBSD was able to provide an accurate assessment of the wedge indentation deformation field to within the precision of the measurements, approximately 2 × 10−4 in strain. CRM was similarly precise, but was limited in accuracy to several times this value. PMID:26939030

76 FR 31943 - Global Positioning System Directorate (Gpsd); Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

...) Durations. All comments must be submitted in Comments Resolution Matrix (CRM) form. These forms along with... process for IS-GPS-200, IS-GPS-705, and IS-GPS-800. Please provide them in the CRM form and submit to Tony...

77 FR 37660 - ICWG Meeting for the NAVSTAR GPS Public Signals in Space

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-22

... comments must be submitted in Comments Resolution Matrix (CRM) form. These forms along with the Was/Is...-GPS-705, and IS-GPS-800. Please provide them in the CRM form and submit to Tony Marquez by July 20...

Psychology's Contributions to Classroom Management

ERIC Educational Resources Information Center

Little, Steven G.; Akin-Little, Angeleque

2008-01-01

Classroom management (CRM) has been associated with discipline, control, or other terms that connote reducing unacceptable student behavior. However, CRM involves not merely responding effectively when problems occur, but also preventing problems from occurring by creating environments that encourage learning and appropriate behavior. Teachers'…

Meeting the needs of customers with health CRM.

PubMed

Phillips, Jon; Panchal, Samir

2002-01-01

Customer relationship management (CRM) is a business strategy, supported by applications and technologies, that can fundamentally transform how healthcare delivery organizations manage patient and physician interactions, reduce cost, improve customer-facing processes, drive market and revenue growth, and manage regulatory compliance processes.

Positive impact of crisis resource management training on no-flow time and team member verbalisations during simulated cardiopulmonary resuscitation: a randomised controlled trial.

PubMed

Fernandez Castelao, Ezequiel; Russo, Sebastian G; Cremer, Stephan; Strack, Micha; Kaminski, Lea; Eich, Christoph; Timmermann, Arnd; Boos, Margarete

2011-10-01

To evaluate the impact of video-based interactive crisis resource management (CRM) training on no-flow time (NFT) and on proportions of team member verbalisations (TMV) during simulated cardiopulmonary resuscitation (CPR). Further, to investigate the link between team leader verbalisation accuracy and NFT. The randomised controlled study was embedded in the obligatory advanced life support (ALS) course for final-year medical students. Students (176; 25.35±1.03 years, 63% female) were alphabetically assigned to 44 four-person teams that were then randomly (computer-generated) assigned to either CRM intervention (n=26), receiving interactive video-based CRM-training, or to control intervention (n=18), receiving an additional ALS-training. Primary outcomes were NFT and proportions of TMV, which were subdivided into eight categories: four team leader verbalisations (TLV) with different accuracy levels and four follower verbalisation categories (FV). Measurements were made of all groups administering simulated adult CPR. NFT rates were significantly lower in the CRM-training group (31.4±6.1% vs. 36.3±6.6%, p=0.014). Proportions of all TLV categories were higher in the CRM-training group (p<0.001). Differences in FV were only found for one category (unsolicited information) (p=0.012). The highest correlation with NFT was found for high accuracy TLV (direct orders) (p=0.06). The inclusion of CRM training in undergraduate medical education reduces NFT in simulated CPR and improves TLV proportions during simulated CPR. Further research will test how these results translate into clinical performance and patient outcome. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Safety, efficacy, and performance of implanted recycled cardiac rhythm management (CRM) devices in underprivileged patients.

PubMed

Hasan, Reema; Ghanbari, Hamid; Feldman, Dustin; Menesses, Daniel; Rivas, Daniel; Zakhem, Nicole C; Duarte, Carlos; Machado, Christian

2011-06-01

Patients in underdeveloped nations have limited access to life-saving medical technology including cardiac rhythm management (CRM) devices. We evaluated alternative means to provide such technology to this patient population while assessing the safety and efficacy of such a practice. Patients in the United States with clinical indications for extraction of CRM devices were consented. Antemortem CRM devices were cleaned and sterilized following a protocol established at our institution. Surveillance in vitro cultures were performed for quality assurance. The functional status of pulse generators was tested with a pacing system analyzer to confirm at least 70% battery life. Most generators were transported, in person, to an implanting institution in Nicaragua. Recipients with a Class I indication for CRM implantation, and meeting economical criteria set forth, were consented for implantation of a recycled device. Between 2003 and 2009, implantation was performed in 17 patients with an average age of 42.1 ± 20.3 years. Of the 17 patients, nine were male and eight were female. Mean follow-up was 68 ± 38 months. Device evaluation occurred prior to discharge, 4 weeks post implantation, and every 6 months thereafter. There were three deaths during the follow-up period secondary to myocardial infarction, stroke, and heart failure. Hematoma formation occurred in one patient. No infections, early battery depletion, or device malfunction were identified during follow-up. Our case series is the longest follow-up of recipients of recycled antemortem CRM devices. Our findings support the feasibility and safety of this alternative acquisition of life-saving technology. ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

Improved accuracy of supervised CRM discovery with interpolated Markov models and cross-species comparison

PubMed Central

Kazemian, Majid; Zhu, Qiyun; Halfon, Marc S.; Sinha, Saurabh

2011-01-01

Despite recent advances in experimental approaches for identifying transcriptional cis-regulatory modules (CRMs, ‘enhancers’), direct empirical discovery of CRMs for all genes in all cell types and environmental conditions is likely to remain an elusive goal. Effective methods for computational CRM discovery are thus a critically needed complement to empirical approaches. However, existing computational methods that search for clusters of putative binding sites are ineffective if the relevant TFs and/or their binding specificities are unknown. Here, we provide a significantly improved method for ‘motif-blind’ CRM discovery that does not depend on knowledge or accurate prediction of TF-binding motifs and is effective when limited knowledge of functional CRMs is available to ‘supervise’ the search. We propose a new statistical method, based on ‘Interpolated Markov Models’, for motif-blind, genome-wide CRM discovery. It captures the statistical profile of variable length words in known CRMs of a regulatory network and finds candidate CRMs that match this profile. The method also uses orthologs of the known CRMs from closely related genomes. We perform in silico evaluation of predicted CRMs by assessing whether their neighboring genes are enriched for the expected expression patterns. This assessment uses a novel statistical test that extends the widely used Hypergeometric test of gene set enrichment to account for variability in intergenic lengths. We find that the new CRM prediction method is superior to existing methods. Finally, we experimentally validate 12 new CRM predictions by examining their regulatory activity in vivo in Drosophila; 10 of the tested CRMs were found to be functional, while 6 of the top 7 predictions showed the expected activity patterns. We make our program available as downloadable source code, and as a plugin for a genome browser installed on our servers. PMID:21821659

Improved recognition of ineffective chest compressions after a brief Crew Resource Management (CRM) training: a prospective, randomised simulation study.

PubMed

Haffner, Leopold; Mahling, Moritz; Muench, Alexander; Castan, Christoph; Schubert, Paul; Naumann, Aline; Reddersen, Silke; Herrmann-Werner, Anne; Reutershan, Jörg; Riessen, Reimer; Celebi, Nora

2017-03-03

Chest compressions are a core element of cardio-pulmonary resuscitation. Despite periodic training, real-life chest compressions have been reported to be overly shallow and/or fast, very likely affecting patient outcomes. We investigated the effect of a brief Crew Resource Management (CRM) training program on the correction rate of improperly executed chest compressions in a simulated cardiac arrest scenario. Final-year medical students (n = 57) were randomised to receive a 10-min computer-based CRM or a control training on ethics. Acting as team leaders, subjects performed resuscitation in a simulated cardiac arrest scenario before and after the training. Team members performed standardised overly shallow and fast chest compressions. We analysed how often the team leader recognised and corrected improper chest compressions, as well as communication and resuscitation quality. After the CRM training, team leaders corrected improper chest compressions (35.5%) significantly more often compared with those undergoing control training (7.7%, p = 0.03*). Consequently, four students have to be trained (number needed to treat = 3.6) for one improved chest compression scenario. Communication quality assessed by the Leader Behavior Description Questionnaire significantly increased in the intervention group by a mean of 4.5 compared with 2.0 (p = 0.01*) in the control group. A computer-based, 10-min CRM training improved the recognition of ineffective of chest compressions. Furthermore, communication quality increased. As guideline-adherent chest compressions have been linked to improved patient outcomes, our CRM training might represent a brief and affordable approach to increase chest compression quality and potentially improve patient outcomes.

Rocky milieu: challenges of effective integration of clinical risk management into hospitals in Iran.

PubMed

Farokhzadian, Jamileh; Nayeri, Nahid Dehghan; Borhani, Fariba

2015-01-01

Healthcare risks and clinical risks have been recognized as a major challenge in healthcare. Clinical risks can never be eliminated and can have serious adverse effects on patient safety. Thus, a clinical risk management (CRM) system has been introduced in the healthcare system to improve quality services. The aim of this study was to explore nurses' experiences related to the challenges of implementing CRM in the organizational context. This qualitative study was based on the conventional content analysis of the Lundman and Graneheim approach, and it consisted of 22 interview sessions with 20 nurses. The purposive sampling method was used to choose the participants from three hospitals affiliated with the Kerman University of Medical Sciences. We used semi-structured interviews and review of relevant documents to collect data. The analysis of the data led to the emergence of "rocky milieu" as the main theme, and it consisted of three categories that, along with their subcategories, explain the challenges of implementing CRM. The three categories and their subcategories were (1) organizational culture and leadership challenges (decision and performance of leadership and cultural resistance to change), (2) limitation of resources (financial, human, and physical and equipment resources), and (3) variations and complexities in working conditions (the emotional, psychological, and social atmosphere and the heaviness of workload). Attempts have been made to establish CRM through clinical governance and accreditation, but organizational challenges have created a rocky milieu for implementing CRM. However, from an organizational context concerning the suitability of healthcare in Iran, there are obvious needs to move toward quality improvement and safe practices through the effective implementation of CRM.

Direct activation of a notochord cis-regulatory module by Brachyury and FoxA in the ascidian Ciona intestinalis.

PubMed

Passamaneck, Yale J; Katikala, Lavanya; Perrone, Lorena; Dunn, Matthew P; Oda-Ishii, Izumi; Di Gregorio, Anna

2009-11-01

The notochord is a defining feature of the chordate body plan. Experiments in ascidian, frog and mouse embryos have shown that co-expression of Brachyury and FoxA class transcription factors is required for notochord development. However, studies on the cis-regulatory sequences mediating the synergistic effects of these transcription factors are complicated by the limited knowledge of notochord genes and cis-regulatory modules (CRMs) that are directly targeted by both. We have identified an easily testable model for such investigations in a 155-bp notochord-specific CRM from the ascidian Ciona intestinalis. This CRM contains functional binding sites for both Ciona Brachyury (Ci-Bra) and FoxA (Ci-FoxA-a). By combining point mutation analysis and misexpression experiments, we demonstrate that binding of both transcription factors to this CRM is necessary and sufficient to activate transcription. To gain insights into the cis-regulatory criteria controlling its activity, we investigated the organization of the transcription factor binding sites within the 155-bp CRM. The 155-bp sequence contains two Ci-Bra binding sites with identical core sequences but opposite orientations, only one of which is required for enhancer activity. Changes in both orientation and spacing of these sites substantially affect the activity of the CRM, as clusters of identical sites found in the Ciona genome with different arrangements are unable to activate transcription in notochord cells. This work presents the first evidence of a synergistic interaction between Brachyury and FoxA in the activation of an individual notochord CRM, and highlights the importance of transcription factor binding site arrangement for its function.

A new body moisturizer increases skin hydration and improves atopic dermatitis symptoms among children and adults.

PubMed

Simpson, Eric; Dutronc, Yves

2011-07-01

Moisturizers result in an increase of skin hydration and restoration of the skin barrier function and play a prominent role in the longterm management of atopic dermatitis (AD). Cetaphil RestoradermTM Moisturizer (CRM) contains novel ingredients specifically designed for AD, and its effects on skin hydration, skin barrier function and signs of AD were assessed in four studies, three of which were evaluator-blinded, randomized and intra-individual comparison trials. A single application of CRM induced significantly greater hydration than the untreated control for at least 24 hours (P is less than 0.001). After the skin was disrupted with 0.5% sodium dodecyl sulfate (SDS), applications of CRM led to a more rapid restoration of skin barrier function and maintained significantly greater skin hydration compared to the untreated control (both P is less than 0.05). After four weeks of twice-daily CRM application among subjects with a history of AD, a significant decrease of itching/stinging scores compared to baseline was reported, as well as an improvement in the quality-of- life and a high level of satisfaction regarding the product. When CRM was used as an adjunctive treatment with topical steroid for four weeks among subjects with mild-to-moderate AD, a more rapid decrease of overall disease severity was observed on days 7, 14 and 21 by the blinded investigator (P is less than 0.05), compared to steroid treatment alone. In summary, CRM is suitable for the specific needs of patients with AD and can be used either alone for long-term management or in adjunction with traditional treatment for both short and long-term disease control.

Rocky milieu: Challenges of effective integration of clinical risk management into hospitals in Iran

PubMed Central

Farokhzadian, Jamileh; Nayeri, Nahid Dehghan; Borhani, Fariba

2015-01-01

Healthcare risks and clinical risks have been recognized as a major challenge in healthcare. Clinical risks can never be eliminated and can have serious adverse effects on patient safety. Thus, a clinical risk management (CRM) system has been introduced in the healthcare system to improve quality services. The aim of this study was to explore nurses’ experiences related to the challenges of implementing CRM in the organizational context. This qualitative study was based on the conventional content analysis of the Lundman and Graneheim approach, and it consisted of 22 interview sessions with 20 nurses. The purposive sampling method was used to choose the participants from three hospitals affiliated with the Kerman University of Medical Sciences. We used semi-structured interviews and review of relevant documents to collect data. The analysis of the data led to the emergence of “rocky milieu” as the main theme, and it consisted of three categories that, along with their subcategories, explain the challenges of implementing CRM. The three categories and their subcategories were (1) organizational culture and leadership challenges (decision and performance of leadership and cultural resistance to change), (2) limitation of resources (financial, human, and physical and equipment resources), and (3) variations and complexities in working conditions (the emotional, psychological, and social atmosphere and the heaviness of workload). Attempts have been made to establish CRM through clinical governance and accreditation, but organizational challenges have created a rocky milieu for implementing CRM. However, from an organizational context concerning the suitability of healthcare in Iran, there are obvious needs to move toward quality improvement and safe practices through the effective implementation of CRM. PMID:25968444

On a wing and a prayer: an assessment of modularized crew resource management training for health care professionals.

PubMed

Clay-Williams, Robyn; Greenfield, David; Stone, Judy; Braithwaite, Jeffrey

2014-01-01

Evidence suggests that Crew Resource Management (CRM), a form of team training, is beneficial. In CRM training, participants learn individual portable team skills such as communication and decision making through group discussion and activities. However, the usual 1-day course format is not always compatible with health care organizational routines. A modular training format, while theoretically sound, is untested for interprofessional team training. The aim of this study was to explore the potential for modularized CRM training to be delivered to a group of interprofessional learners. Modularized CRM training, consisting of two 2-hour workshops, was delivered to health care workers in an Australian tertiary hospital. Kirkpatrick's evaluation model provided a framework for the study. Baseline attitude surveys were conducted prior to each workshop. Participants completed a written questionnaire at the end of each workshop that examined their motivations, reactions to the training, and learner demographics. An additional survey, administered 6 weeks post training, captured self-assessed behavior data. Twenty-three individuals from a range of professions and clinical streams participated. One in 5 participants (22%) reported that they translated teamwork skills to the workplace. While positive about the workshop format and content, many respondents identified personal, team, and organizational barriers to the application of the workshop techniques. CRM training when delivered in a modular format has positive outcomes. Following the training, some respondents overcame workplace barriers to attempt to change negative workplace behavior. This progress provides cautious optimism for the potential for modular CRM training to benefit groups of interprofessional health staff. © 2014 The Alliance for Continuing Education in the Health Professions, the Society for Academic Continuing Medical Education, and the Council on Continuing Medical Education, Association for Hospital Medical Education.

Software Intensive Systems

DTIC Science & Technology

2006-07-01

Architect, Developer and Platform Evangelism • Microsoft Dynamic Systems Initiative-- John Wilson, Architect Windows Management • Windows Lifecycle...Presentations • Aegis--Reuben Pitts & CDR John Ailes, Program Executive Office, Integrated Warfare Systems • Long Term Mine Reconnaissance (LMRS)--CAPT...Paul Imes • Joint Tactical Radio System (JTRS)--Richard North, JPEO JTRS & Leonard Schiavone , MITRE • Single Integrated Air Picture (SIAP)--CAPT

Dynamic Analysis of UTAUT: The Case of Microsoft Project Management Software

ERIC Educational Resources Information Center

Abualbasal, Wejdan; Abu-Shanab, Emad; Al-Quraan, Heba

2016-01-01

The technology adoption domain is rich with studies that utilized a cross-sectional snapshot of subjects' perceptions regarding the adoption of new technology. This research tried to implement a longitudinal study that took three measures within 4 months to estimate the influence of time and experience on students' perceptions. The study adopted a…

Low-dimensional dynamical characterization of human performance of cancer patients using motion data.

PubMed

Hasnain, Zaki; Li, Ming; Dorff, Tanya; Quinn, David; Ueno, Naoto T; Yennu, Sriram; Kolatkar, Anand; Shahabi, Cyrus; Nocera, Luciano; Nieva, Jorge; Kuhn, Peter; Newton, Paul K

2018-05-18

Biomechanical characterization of human performance with respect to fatigue and fitness is relevant in many settings, however is usually limited to either fully qualitative assessments or invasive methods which require a significant experimental setup consisting of numerous sensors, force plates, and motion detectors. Qualitative assessments are difficult to standardize due to their intrinsic subjective nature, on the other hand, invasive methods provide reliable metrics but are not feasible for large scale applications. Presented here is a dynamical toolset for detecting performance groups using a non-invasive system based on the Microsoft Kinect motion capture sensor, and a case study of 37 cancer patients performing two clinically monitored tasks before and after therapy regimens. Dynamical features are extracted from the motion time series data and evaluated based on their ability to i) cluster patients into coherent fitness groups using unsupervised learning algorithms and to ii) predict Eastern Cooperative Oncology Group performance status via supervised learning. The unsupervised patient clustering is comparable to clustering based on physician assigned Eastern Cooperative Oncology Group status in that they both have similar concordance with change in weight before and after therapy as well as unexpected hospitalizations throughout the study. The extracted dynamical features can predict physician, coordinator, and patient Eastern Cooperative Oncology Group status with an accuracy of approximately 80%. The non-invasive Microsoft Kinect sensor and the proposed dynamical toolset comprised of data preprocessing, feature extraction, dimensionality reduction, and machine learning offers a low-cost and general method for performance segregation and can complement existing qualitative clinical assessments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Continual Response Measurement: Design and Validation.

ERIC Educational Resources Information Center

Baggaley, Jon

1987-01-01

Discusses reliability and validity of continual response measurement (CRM), a computer-based measurement technique, and its use in social science research. Highlights include the importance of criterion-referencing the data, guidelines for designing studies using CRM, examples typifying their deductive and inductive functions, and a discussion of…

Australian mental health consumers contributions to the evaluation and improvement of recovery-oriented service provision.

PubMed

Marshal, Sarah L; Oades, Lindsay G; Growe, Trevor P

2010-01-01

One key component of recovery-oriented mental health services, typically overlooked, involves genuine collaboration between researchers and consumers to evaluate and improve services delivered within a recovery framework. Eighteen mental health consumers working with staff who had received training in the Collaborative Recovery Model (CRM) took part in in-depth focus group meetings, of approximately 2.5 hours each, to generate feedback to guide improvement of the CRM and its use in mental health services. Consumers identified clear avenues for improvement for the CRM both specific to the model and broadly applicable to recovery-oriented service provision. Findings suggest consumers want to be more engaged and empowered in the use of the CRM from the outset. Improved sampling procedures may have led to the identification of additional dissatisfied consumers. Collaboration with mental health consumers in the evaluation and improvement of recovery-oriented practice is crucial with an emphasis on rebuilding mental health services that are genuinely oriented to support recovery.

Use of MenACWY-CRM in adolescents in the United States.

PubMed

Black, Steven; Block, Stan L

2013-03-01

Adolescents constitute a high-risk group for invasive meningococcal disease. MenACWY-CRM (Menveo, Novartis Vaccines, Cambridge, MA) is a quadrivalent meningococcal conjugate vaccine indicated to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W-135, and Y. It has been approved for use in persons age 2-55 years. The tolerability and immunogenicity of MenACWY-CRM in adolescents have been ascertained in phase 2 and 3 trials against MPSV4 (Menomune, sanofi pasteur, Swiftwater, PA), an unconjugated quadrivalent meningococcal vaccine, and MenACWY-D (Menactra, sanofi pasteur), another conjugated quadrivalent meningococcal vaccine. Clinical trials also have demonstrated that MenACWY-CRM is well tolerated and immunogenic when administered to adolescents concomitantly with the combined tetanus, diphtheria, and acellular pertussis vaccine (Boostrix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent human papillomavirus vaccine (Gardasil, Merck & Co., Inc., Whitehouse Station, NJ). Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Vi-CRM 197 as a new conjugate vaccine against Salmonella Typhi.

PubMed

Micoli, F; Rondini, S; Pisoni, I; Proietti, D; Berti, F; Costantino, P; Rappuoli, R; Szu, S; Saul, A; Martin, L B

2011-01-17

An efficacious, low cost vaccine against typhoid fever, especially for young children, would make a major impact on disease burden in developing countries. The virulence capsular polysaccharide of Salmonella Typhi (Vi) coupled to recombinant mutant Pseudomonas aeruginosa exoprotein A (Vi-rEPA) has been shown to be highly efficacious. We investigated the use of carrier proteins included in infant vaccines, standardized the conjugation process and developed key assays required for routine lot release at production scale. Vi from a BSL1 organism, Citrobacter freundii, strain WR7011, was used as an alternative to Vi from S. Typhi. We showed that Vi conjugated to CRM(197), a non-toxic mutant of diphtheria toxin, widely used in commercial vaccines, was produced at high yield. Vi-CRM(197) proved immunogenic in animal studies, even without adjuvant. Thus, Vi-CRM(197) appears to be a suitable candidate for the development of a commercially viable, effective typhoid vaccine for developing countries. Copyright © 2010 Elsevier Ltd. All rights reserved.

Data exploration of social client relationship management (CRM 2.0) adoption in the Nigerian construction business.

PubMed

Ojelabi, Rapheal A; Afolabi, Adedeji O; Oyeyipo, Opeyemi O; Tunji-Olayeni, Patience F; Adewale, Bukola A

2018-06-01

Integrating social client relationship management (CRM 2.0) in the built environment can enhance the relationship between construction organizations and client towards sustaining a long and lasting collaboration. The data exploration analyzed the e-readiness of contracting and consulting construction firms in the uptake of CRM 2.0 and the barriers encountered in the adoption of the modern business tool. The targeted organizations consist of seventy five (75) construction businesses operating in Lagos State which were selected from a pool of registered contracting and consulting construction firms using random sampling technique. Descriptive statistics of the e-readiness of contracting and consulting construction firms for CRM 2.0 adoption and barriers limiting its uptake were analyzed. Also, inferential analysis using Mann-Whitney U statistical and independent sample t-test was performed on the dataset obtained. The data generated will support construction firms on the necessity to engage in client social relationship management in ensuring sustainable client relationship management in the built environment.

What Is the Return on Investment for Implementation of a Crew Resource Management Program at an Academic Medical Center?

PubMed

Moffatt-Bruce, Susan D; Hefner, Jennifer L; Mekhjian, Hagop; McAlearney, John S; Latimer, Tina; Ellison, Chris; McAlearney, Ann Scheck

Crew Resource Management (CRM) training has been used successfully within hospital units to improve quality and safety. This article presents a description of a health system-wide implementation of CRM focusing on the return on investment (ROI). The costs included training, programmatic fixed costs, time away from work, and leadership time. Cost savings were calculated based on the reduction in avoidable adverse events and cost estimates from the literature. Between July 2010 and July 2013, roughly 3000 health system employees across 12 areas were trained, costing $3.6 million. The total number of adverse events avoided was 735-a 25.7% reduction in observed relative to expected events. Savings ranged from a conservative estimate of $12.6 million to as much as $28.0 million. Therefore, the overall ROI for CRM training was in the range of $9.1 to $24.4 million. CRM presents a financially viable way to systematically organize for quality improvement.

Remedial training: Will CRM work for everyone

NASA Technical Reports Server (NTRS)

Johnston, A. N.

1987-01-01

The subject of those pilots who seem unresponsive to Cockpit Resource Management (CRM) training is addressed. Attention is directed to the need and opportunity for remedial action. Emphasis is given to the requirement for new perspectives and additional training resources. It is also argued that, contrary to conventional training wisdom, such individuals do not represent a hard core which is beyond assistance. Some evidence is offered that such a new perspective will lend itself to a wider appreciation of certain specific training needs. The role of appropriately trained specialists is briefly outlined, and a selected bibliography is attached. The combined experiences of several Pilot Advisory Groups (PAG's) within IFALPA member association form the basis for this discussion. It does not purport to desribe the activities of any one PAG. While much of the activities of PAG's have no relevance to CRM, there are clearly some very important points of intersection. The relevance of these points to diagnostic skills, and remedial training in the general domain of CRM is made obvious.

Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation.

PubMed

Alejo, Alí; Ruiz-Argüello, M Begoña; Pontejo, Sergio M; Fernández de Marco, María Del Mar; Saraiva, Margarida; Hernáez, Bruno; Alcamí, Antonio

2018-05-03

The role of cytokines and chemokines in anti-viral defense has been demonstrated, but their relative contribution to protective anti-viral responses in vivo is not fully understood. Cytokine response modifier D (CrmD) is a secreted receptor for TNF and lymphotoxin containing the smallpox virus-encoded chemokine receptor (SECRET) domain and is expressed by ectromelia virus, the causative agent of the smallpox-like disease mousepox. Here we show that CrmD is an essential virulence factor that controls natural killer cell activation and allows progression of fatal mousepox, and demonstrate that both SECRET and TNF binding domains are required for full CrmD activity. Vaccination with recombinant CrmD protects animals from lethal mousepox. These results indicate that a specific set of chemokines enhance the inflammatory and protective anti-viral responses mediated by TNF and lymphotoxin, and illustrate how viruses optimize anti-TNF strategies with the addition of a chemokine binding domain as soluble decoy receptors.

Recombinant TNF-binding protein from variola virus as a novel potential TNF antagonist.

PubMed

Gileva, I P; Nepomnyashchikh, T S; Ryazankin, I A; Shchelkunov, S N

2009-12-01

Gel-filtration chromatographic separation of the lysate of Sf21 insect cells infected with recombinant baculovirus BVi67 containing the gene for TNF-binding protein (CrmB) of variola virus (VARV) revealed that hTNF-cytotoxicity neutralization activity is associated with a fraction corresponding mainly to high molecular weight proteins (above 500 kDa) and less with fractions corresponding to proteins of 270 or 90 kDa. The recombinant VARV-CrmB protein has been purified by affinity chromatography. Difference in the experimentally determined and estimated (according to amino acid composition) VARV-CrmB molecular weight is due to glycosylation of the recombinant protein expressed in the insect cells. VARV-CrmB neutralizes in vitro the cytotoxic effect of hTNF and hLTalpha, and its TNF-neutralizing activity is two to three orders of magnitude higher compared to the analogous effects of type I and II soluble TNF receptors, comparable with the activity of mAb MAK195, and somewhat lower than the effect of the commercial drug Remicade.

Investigating the connections between health lean management and clinical risk management.

PubMed

Crema, Maria; Verbano, Chiara

2015-01-01

The purpose of this paper is to investigate connections and overlaps between health lean management (HLM) and clinical risk management (CRM) understanding whether and how these two approaches can be combined together to pursue efficiency and patient safety improvements simultaneously. A systematic literature review has been carried out. Searching in academic databases, papers that focus not only on HLM, but also on clinical errors and risk reduction, were included. The general characteristics of the selected papers were analysed and a content analysis was conducted. In most of the papers, pursing objectives of HLM and CRM and adopting tools and practices of both approaches, results of quality and, particularly, of safety improvements were obtained. A two-way arrow between HLM and CRM emerged but so far, none of the studies has been focused on the relationship between HLM and CRM. Results highlight an emerging research stream, with many useful theoretical and practical implications and opportunities for further research.

Development of C-reactive protein certified reference material NMIJ CRM 6201-b: optimization of a hydrolysis process to improve the accuracy of amino acid analysis.

PubMed

Kato, Megumi; Kinumi, Tomoya; Yoshioka, Mariko; Goto, Mari; Fujii, Shin-Ichiro; Takatsu, Akiko

2015-04-01

To standardize C-reactive protein (CRP) assays, the National Metrology Institute of Japan (NMIJ) has developed a C-reactive protein solution certified reference material, CRM 6201-b, which is intended for use as a primary reference material to enable the SI-traceable measurement of CRP. This study describes the development process of CRM 6201-b. As a candidate material of the CRM, recombinant human CRP solution was selected because of its higher purity and homogeneity than the purified material from human serum. Gel filtration chromatography was used to examine the homogeneity and stability of the present CRM. The total protein concentration of CRP in the present CRM was determined by amino acid analysis coupled to isotope-dilution mass spectrometry (IDMS-AAA). To improve the accuracy of IDMS-AAA, we optimized the hydrolysis process by examining the effect of parameters such as the volume of protein samples taken for hydrolysis, the procedure of sample preparation prior to the hydrolysis, hydrolysis temperature, and hydrolysis time. Under optimized conditions, we conducted two independent approaches in which the following independent hydrolysis and liquid chromatography-isotope dilution mass spectrometry (LC-IDMS) were combined: one was vapor-phase acid hydrolysis (130 °C, 24 h) and hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) method, and the other was microwave-assisted liquid-phase acid hydrolysis (150 °C, 3 h) and pre-column derivatization liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The quantitative values of the two different amino acid analyses were in agreement within their uncertainties. The certified value was the weighted mean of the results of the two methods. Uncertainties from the value-assignment method, between-method variance, homogeneity, long-term stability, and short-term stability were taken into account in evaluating the uncertainty for a certified value. The certified value and the expanded uncertainty (k = 2) of CRM 6201-b are (40.0 ± 1.6) μmol kg(-1).

Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants.

PubMed

Abdelnour, Arturo; Silas, Peter E; Lamas, Marta Raquel Valdés; Aragón, Carlos Fernándo Grazioso; Chiu, Nan-Chang; Chiu, Cheng-Hsun; Acuña, Teobaldo Herrera; Castrejón, Tirza De León; Izu, Allen; Odrljin, Tatjana; Smolenov, Igor; Hohenboken, Matthew; Dull, Peter M

2014-02-12

The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants. Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1-7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%). A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI -0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference -0.1% [95% CI -4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups. In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone. Copyright © 2013 Elsevier Ltd. All rights reserved.

Occupational exposure to asphalt mixture during road paving is related to increased mitochondria DNA copy number: a cross-sectional study.

PubMed

Xu, Yiyi; Lindh, Christian H; Jönsson, Bo A G; Broberg, Karin; Albin, Maria

2018-03-27

Asphalt workers are exposed to polyaromatic hydrocarbons (PAHs) from hot mix asphalt via both inhalation and dermal absorption. The use of crumb rubber modified (CRM) asphalt may result in higher exposure to PAHs and more adverse effects. Our aim is to assess occupational exposure to PAHs from conventional and CRM asphalt paving by measuring PAH metabolites in urine, and to investigate the effects on mitochondrial DNA copy number (mtDNAcn) and telomere length. We recruited 116 workers paving conventional asphalt, 51 workers paving CRM asphalt and 100 controls in Sweden, all males. A repeated-measures analysis included 31 workers paving both types of asphalt. Urine and blood samples were collected pre-working on Monday morning and post-working on Thursday afternoon after 4 days working. PAH metabolites: 1-hydroxypyrene (1-OH-PYR) and 2-hydroxyphenanthrene (2-OH-PH) were measured in urine by LC-MS/MS. Relative mtDNAcn and telomere length were measured by quantitative PCR. Conventional and CRM asphalt workers showed higher 1-OH-PYR and 2-OH-PH than controls (p < 0.001 for all). Relative mtDNAcn were 0.21 units (p < 0.001) higher in conventional asphalt workers and 0.13 units (p = 0.010) higher in CRM asphalt workers compared to controls. Relative telomere length did not differ across occupational groups, but it was positively associated with increment of 2-OH-PH (β = 0.075, p = 0.037) in asphalt workers. The repeated-measures analysis showed no difference in either increment of 1-OH-PYP, or changes in effect biomarkers (mtDNAcn or telomere length) between paving with conventional and CRM asphalt. Increment of 2-OH-PH was smaller after paving with CRM asphalt. Road asphalt paving in open areas resulted in PAHs exposure, as shown by elevation of PAH metabolites in urine. Asphalt workers may experience oxidative stress, evidenced by alternation in mtDNAcn; however the effects could not be fully explained by exposure to PAHs from the asphalt mixture.

[Shuttle Challenger disaster: what lessons can be learned for management of patients in the operating room?].

PubMed

Suva, Domizio; Poizat, Germain

2015-02-04

For many years hospitals have been implementing crew resource management (CRM) programs, inspired by the aviation industry, in order to improve patient safety. However, while contributing to improved patient care, CRM programs are controversial because of their limited impact, a decrease in effectiveness over time, and the underinvestment by some caregivers. By analyzing the space shuttle Challenger accident, the objective of this article is to show the potential impact of the professional culture in decision-making processes. In addition, to present an approach by cultural factors which are an essential complement to current CRM programs in order to enhance the safety of care.

My copilot is a nurse--using crew resource management in the OR.

PubMed

Powell, Stephen M; Hill, Ruth Kimberly

2006-01-01

Crew resource management (CRM) has been used for more than 20 years in the aviation industry to teach individual error countermeasures by developing nontechnical (ie, cognitive, social) skills based on the observed traits of successful individuals and crews. The health care industry began to investigate aviation CRM after the Institute of Medicine's report, To Err is Human: Building a Safer Health System, recommended that medicine adopt aviation's approach to safety and error management. Initial results of implementing CRM in health care arenas have demonstrated reduced adverse outcomes, reduced errors, reduced length of stay, improved nurse retention, and changed attitudes and behaviors toward teamwork.

Lyme Disease Data

MedlinePlus

... County-level Lyme disease data from 2000-2016 Microsoft Excel file [Excel CSV – 209KB] ––Right–click the link ... PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel file Audio/Video file Apple Quicktime file RealPlayer ...

CRM Meets the Campus

ERIC Educational Resources Information Center

Villano, Matt

2007-01-01

In the corporate world, the notion of customer relationship management (CRM) is nothing new. That particular technology sector is now jam-packed with software that enables organizations to monitor and manage every interaction with a customer, from the very first experience on, throughout the lifecycle of the relationship. That relationship spans…

Criterion-Referenced Measurement (CRM) in the Initial Acquisition of a Psychomotor Skill with Exceptional Children

ERIC Educational Resources Information Center

Muhich, Dolores

1976-01-01

Criterion Referenced Measurement (CRM) in the initial acquisition of the psychomotor skill of typewriting demonstrated speed gains from 8 hours of instruction distributed over a 6-week interval for 4 male adolescent underachievers of above- and below-average intelligence. (Author)

Immunogenicity and safety of concomitant administration of meningococcal serogroup B (4CMenB) and serogroup C (MenC-CRM) vaccines in infants: A phase 3b, randomized controlled trial.

PubMed

P Safadi, Marco Aurelio; Martinon-Torres, Federico; Weckx, Lily Yin; Moreira, Edson Duarte; da Fonseca Lima, Eduardo Jorge; Mensi, Ilhem; Calabresi, Marco; Toneatto, Daniela

2017-04-11

After implementation of routine infant MenC vaccination, MenB remains a serious cause of meningococcal disease, yet to be targeted by vaccination programs in several countries. This study (NCT01339923) investigated the immunogenicity and safety of MenC CRM-conjugated vaccine (MenC-CRM) concomitantly administered with MenB vaccine (4CMenB). Infants (N=251) were randomised 1:1 to receive 4CMenB and MenC-CRM (Group 1) or MenC-CRM alone (Group 2) at 3 and 5months (M3, M5) and a booster at 12months of age (M12), and pneumococcal vaccine at M3, M5, M7, M12. Antibody responses to meningococcal vaccines were measured at M3, M6, M12, and M13. Non-inferiority of MenC-CRM response in Group 1 vs Group 2 was demonstrated at M6 and M13, if the lower limit of the 95% confidence interval (LL95%CI) of the difference in percentage of infants with hSBA titres ≥1:8 was >-10%. Sufficiency of MenB response was achieved if LL95%CI of the percentage of infants with hSBA titres ≥1:4 against fHbp, NadA and PorA strains was ≥70% at M6 or ≥75% at M13. Adverse events (AEs) were collected for 7days post-vaccination, and serious AEs (SAEs) and medically attended AEs throughout the study. Non-inferiority of MenC response in Group 1 vs Group 2 (LL95%CI -6.4% [M6]; -5.2% [M13]) and sufficiency of MenB response in Group 1 (LL95%CI 92%, 90%, 89% [M6]; 97%, 92%, 93% [M13] against fHbp, NadA, PorA, respectively) were demonstrated. Higher rates of mild to moderate solicited AEs were reported in Group 1. Unsolicited AEs and SAEs incidences were similar across groups. Concomitant administration of MenC-CRM and 4CMenB in infants was immunogenic, resulting in non-inferior responses against MenC compared to MenC-CRM alone and demonstration of sufficient immune response to MenB, after primary and booster vaccination. Reactogenicity was higher for concomitant vaccines administration, but no safety concerns were identified. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical Assessment of Risk Management: an INtegrated Approach (CARMINA).

PubMed

Tricarico, Pierfrancesco; Tardivo, Stefano; Sotgiu, Giovanni; Moretti, Francesca; Poletti, Piera; Fiore, Alberto; Monturano, Massimo; Mura, Ida; Privitera, Gaetano; Brusaferro, Silvio

2016-08-08

Purpose - The European Union recommendations for patient safety calls for shared clinical risk management (CRM) safety standards able to guide organizations in CRM implementation. The purpose of this paper is to develop a self-evaluation tool to measure healthcare organization performance on CRM and guide improvements over time. Design/methodology/approach - A multi-step approach was implemented including: a systematic literature review; consensus meetings with an expert panel from eight Italian leader organizations to get to an agreement on the first version; field testing to test instrument feasibility and flexibility; Delphi strategy with a second expert panel for content validation and balanced scoring system development. Findings - The self-assessment tool - Clinical Assessment of Risk Management: an INtegrated Approach includes seven areas (governance, communication, knowledge and skills, safe environment, care processes, adverse event management, learning from experience) and 52 standards. Each standard is evaluated according to four performance levels: minimum; monitoring; outcomes; and improvement actions, which resulted in a feasible, flexible and valid instrument to be used throughout different organizations. Practical implications - This tool allows practitioners to assess their CRM activities compared to minimum levels, monitor performance, benchmarking with other institutions and spreading results to different stakeholders. Originality/value - The multi-step approach allowed us to identify core minimum CRM levels in a field where no consensus has been reached. Most standards may be easily adopted in other countries.

Effects of systemic glutamatergic manipulations on conditioned eyeblink responses and hyperarousal in a rabbit model of post-traumatic stress disorder.

PubMed

Burhans, Lauren B; Smith-Bell, Carrie A; Schreurs, Bernard G

2017-10-01

Glutamatergic dysfunction is implicated in many neuropsychiatric conditions, including post-traumatic stress disorder (PTSD). Glutamate antagonists have shown some utility in treating PTSD symptoms, whereas glutamate agonists may facilitate cognitive behavioral therapy outcomes. We have developed an animal model of PTSD, based on conditioning of the rabbit's eyeblink response, that addresses two key features: conditioned responses (CRs) to cues associated with an aversive event and a form of conditioned hyperarousal referred to as conditioning-specific reflex modification (CRM). The optimal treatment to reduce both CRs and CRM is unpaired extinction. The goals of the study were to examine whether treatment with the N-methyl-D-aspartate glutamate receptor antagonist ketamine could reduce CRs and CRM, and whether the N-methyl-D-aspartate agonist D-cycloserine combined with unpaired extinction treatment could enhance the extinction of both. Administration of a single dose of subanesthetic ketamine had no significant immediate or delayed effect on CRs or CRM. Combining D-cycloserine with a single day of unpaired extinction facilitated extinction of CRs in the short term while having no impact on CRM. These results caution that treatments may improve one aspect of the PTSD symptomology while having no significant effects on other symptoms, stressing the importance of a multiple-treatment approach to PTSD and of animal models that address multiple symptoms.

CRM1 plays a nuclear role in transporting snoRNPs to nucleoli in higher eukaryotes.

PubMed

Verheggen, Celine; Bertrand, Edouard

2012-03-01

Here, we review the sn- and sno-RNA transport pathways in S. cerevisiae and humans, aiming at understanding how they evolved and how common factors can have distinct functions depending on the RNA they bind. We give a particular emphasis on Tgs1, the cap hypermethylase that is conserved from yeast to humans and appears to play a central role in both sn- and sno-RNA biogenesis. In yeast, Tgs1 hypermethylates sn- and sno-RNAs in the nucleolus. In humans, Tgs1 occurs in two forms: a long isoform (Tgs1 LF), which locates in the cytoplasm and Cajal bodies, which is predominantly associated with snRNAs and a short isoform (Tgs1 SF), which is nuclear and mainly associates with snoRNAs. We show that Tgs1 LF is exported by CRM1 and that interaction with CRM1 competes for binding with the C-terminal domain of the core protein Nop58, which contains the Nucleolar localization signal of Box C/D snoRNPs (NoLS). Our data suggest a model where CRM1 removes Tgs1 LF from snoRNPs, thereby promoting nucleolar targeting via activation of their NoLS. In this review, we argue that CRM1, while first described as an export receptor, can also control the composition of nucleoplasmic complexes. Thus, it could coordinate the fate of these complexes with the general nucleo-cytoplasmic trafficking.

CHD3 facilitates vRNP nuclear export by interacting with NES1 of influenza A virus NS2.

PubMed

Hu, Yong; Liu, Xiaokun; Zhang, Anding; Zhou, Hongbo; Liu, Ziduo; Chen, Huanchun; Jin, Meilin

2015-03-01

NS2 from influenza A virus mediates Crm1-dependent vRNP nuclear export through interaction with Crm1. However, even though the nuclear export signal 1 (NES1) of NS2 does not play a requisite role in NS2-Crm1 interaction, there is no doubt that NES1 is crucial for vRNP nuclear export. While the mechanism of the NES1 is still unclear, it is speculated that certain host partners might mediate the NES1 function through their interaction with NES1. In the present study, chromodomain-helicase-DNA-binding protein 3 (CHD3) was identified as a novel host nuclear protein for locating NS2 and Crm1 on dense chromatin for NS2 and Crm1-dependent vRNP nuclear export. CHD3 was confirmed to interact with NES1 in NS2, and a disruption to this interaction by mutation in NES1 significantly delayed viral vRNPs export and viral propagation. Further, the knockdown of CHD3 would affect the propagation of the wild-type virus but not the mutant with the weakened NS2-CHD3 interaction. Therefore, this study demonstrates that NES1 is required for maximal binding of NS2 to CHD3, and that the NS2-CHD3 interaction on the dense chromatin contributed to the NS2-mediated vRNP nuclear export.

A methodology for the synthesis of robust feedback systems. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Milich, David Albert

1988-01-01

A new methodology is developed for the synthesis of linear, time-variant (LTI) controllers for multivariable LTI systems. The resulting closed-loop system is nominally stable and exhibits a known level of performance. In addition, robustness of the feedback system is guaranteed, i.e., stability and performance are retained in the presence of multiple unstructured uncertainty blocks located at various points in the feedback loop. The design technique is referred to as the Causality Recovery Methodology (CRM). The CRM relies on the Youla parameterization of all stabilizing compensators to ensure nominal stability of the feedback system. A frequency-domain inequality in terms of the structured singular value mu defines the robustness specification. The optimal compensator, with respect to the mu condition, is shown to be noncausal in general. The aim of the CRM is to find a stable, causal transfer function matrix that approximates the robustness characteristics of the optimal solution. The CRM, via a series of infinite-dimensional convex programs, produces a closed-loop system whose performance robustness is at least as good as that of any initial design. The algorithm is approximated by a finite dimensional process for the purposes of implementation. Two numerical examples confirm the potential viability of the CRM concept; however, the robustness improvement comes at the expense of increased computational burden and compensator complexity.

Modeling aboveground tree woody biomass using national-scale allometric methods and airborne lidar

NASA Astrophysics Data System (ADS)

Chen, Qi

2015-08-01

Estimating tree aboveground biomass (AGB) and carbon (C) stocks using remote sensing is a critical component for understanding the global C cycle and mitigating climate change. However, the importance of allometry for remote sensing of AGB has not been recognized until recently. The overarching goals of this study are to understand the differences and relationships among three national-scale allometric methods (CRM, Jenkins, and the regional models) of the Forest Inventory and Analysis (FIA) program in the U.S. and to examine the impacts of using alternative allometry on the fitting statistics of remote sensing-based woody AGB models. Airborne lidar data from three study sites in the Pacific Northwest, USA were used to predict woody AGB estimated from the different allometric methods. It was found that the CRM and Jenkins estimates of woody AGB are related via the CRM adjustment factor. In terms of lidar-biomass modeling, CRM had the smallest model errors, while the Jenkins method had the largest ones and the regional method was between. The best model fitting from CRM is attributed to its inclusion of tree height in calculating merchantable stem volume and the strong dependence of non-merchantable stem biomass on merchantable stem biomass. This study also argues that it is important to characterize the allometric model errors for gaining a complete understanding of the remotely-sensed AGB prediction errors.

Television: Stuff of Dreams.

ERIC Educational Resources Information Center

Baggaley, Jon

The fluctuating effects of media can be observed by a data collection technique which reveals patterns of audience response similar to those which C.G. Jung observed in his analyses on word association and dreaming. The technique is known as Continuous Response Movement (CRM). A typical CRM training session automates the audience feedback process…

NBS/EPA (NATIONAL BUREAU OF STANDARDS/ENVIRONMENTAL PROTECTION AGENCY) CERTIFIED REFERENCE MATERIAL PERFORMANCE AUDIT PROGRAM: STATUS REPORT 2

EPA Science Inventory

A traceability procedure has been established which allows specialty gas producers to prepare gaseous pollutant Certified Reference Materials (CRM's). The accuracy, stability and homogeneity of the CRM's approach those of NBS Standard Reference Materials (SRM's). As of October 19...

Trends in Operational Fuel Use

DTIC Science & Technology

2016-08-01

Wikipedia, The Free Encyclopedia. Chow Test. Viewed July 18, 2016 at: https://en.wikipedia.org/wiki/Chow_test 8. CNA Research Memorandum CRM 86-178. Ship...Gren Landry and Gregory Suess. May 2006 10. CNA, CRM D0026186.A2/Final. Vessel Traffic in the Hawaii-Southern California and Atlantic Fleet Testing

The Way of the Gun: Applying Lessons of Ground Combat to Pilot Training

DTIC Science & Technology

2016-02-29

actual practice repetitions.7 Current USAF Crew/Cockpit Resource Management ( CRM ) and Aerospace Physiology courses do not include any instruction on...Burke, Clint A. Bowers, and Katherine A. Wilson. Team Training in the Skies: Does Crew Resource Management ( CRM ) Training Work? Orlando, FL

A PROCEDURE FOR ESTABLISHING TRACEABILITY OF GAS MIXTURES TO CERTAIN NATIONAL BUREAU OF STANDARDS STANDARD REFERENCE MATERIALS

EPA Science Inventory

This procedure includes the specifications and requirements that must be followed by gas manufacturers during the preparation of compressed cylinder gas Certified Reference Materials (CRM). A CRM is a certified gas standard prepared at a concentration that does not exceed + or - ...

The Dynamic Interplay between Spatialization of Written Units in Writing Activity and Functions of Tools on the Computer

ERIC Educational Resources Information Center

Huh, Joo Hee

2012-01-01

I criticize the typewriting model and linear writing structure of Microsoft Word software for writing in the computer. I problematize bodily movement in writing that the error of the software disregards. In this research, writing activity is viewed as bodily, spatial and mediated activity under the premise of the unity of consciousness and…

Release of Native-like Gaseous Proteins from Electrospray Droplets via the Charged Residue Mechanism: Insights from Molecular Dynamics Simulations.

PubMed

McAllister, Robert G; Metwally, Haidy; Sun, Yu; Konermann, Lars

2015-10-07

The mechanism whereby gaseous protein ions are released from charged solvent droplets during electrospray ionization (ESI) remains a matter of debate. Also, it is unclear to what extent electrosprayed proteins retain their solution structure. Molecular dynamics (MD) simulations offer insights into the temporal evolution of protein systems. Surprisingly, there have been no all-atom simulations of the protein ESI process to date. The current work closes this gap by investigating the behavior of protein-containing aqueous nanodroplets that carry excess positive charge. We focus on "native ESI", where proteins initially adopt their biologically active solution structures. ESI proceeds while the protein remains entrapped within the droplet. Protein release into the gas phase occurs upon solvent evaporation to dryness. Droplet shrinkage is accompanied by ejection of charge carriers (Na(+) for the conditions chosen here), keeping the droplet at ∼85% of the Rayleigh limit throughout its life cycle. Any remaining charge carriers bind to the protein as the final solvent molecules evaporate. The outcome of these events is largely independent of the initial protein charge and the mode of charge carrier binding. ESI charge states and collision cross sections of the MD structures agree with experimental data. Our results confirm the Rayleigh/charged residue model (CRM). Field emission of excess Na(+) plays an ancillary role by governing the net charge of the shrinking droplet. Models that envision protein ejection from the droplet are not supported. Most nascent CRM ions retain native-like conformations. For unfolded proteins ESI likely proceeds along routes that are different from the native state mechanism explored here.

RFID of next generation network for enhancing customer relationship management in healthcare industries.

PubMed

Alzahrani, Ahmed; Qureshi, Muhammad Shuaib; Thayananthan, Vijey

2017-10-23

This paper aims to analyze possible next generation of networked radio frequency identification (NGN-RFID) system for customer relationship management (CRM) in healthcare industries. Customer relationship and its management techniques in a specific healthcare industry are considered in this development. The key objective of using NGN-RFID scheme is to enhance the handling of patients' data to improve the CRM efficiency in healthcare industries. The proposed NGN-RFID system is one of the valid points to improve the ability of CRM by analyzing different prior and current traditional approaches. The legacy of customer relationship management will be improved by using this modern NGN-RFID technology without affecting the novelty.

The Army National Guard: Part of the Operational Force and Strategic Reserve

DTIC Science & Technology

2016-05-26

avoiding the war. The limited use of the RC in the Vietnam 6 Patrick M. Cronin, The Total Force Policy in Historical Perspective, No. CRM -87-78. Center...Cronin, Patrick M. The Total Force Policy in Historical Perspective. No. CRM -87-78. Center for Naval Analyses, Alexandria, VA: Naval Planning

The Testing of English as a Second/Foreign Language in the Criterion-Referenced Era.

ERIC Educational Resources Information Center

Davidson, Fred

In the assessment of second/foreign language proficiency, we are entering the era of criterion-referenced assessment as language learning is being recognized as an integrative, multifaceted construct. Norm-referenced measurement (NRM) is compared with criterion-referenced measurement (CRM). CRM is characterized by attention to skill, whereas NRM…

Iowa City Reads! The Reading Event Worth Shouting About.

ERIC Educational Resources Information Center

Donham van Deusen, Jean; Langhorne, Mary Jo

1997-01-01

Describes the Community Reading Month (CRM) initiative in Iowa City, Iowa; its goals are to promote the value of reading and to build a sense of community. Topics include the development of CRM, increased reading scores of Iowa City's elementary school students, activities for people of all ages, and planning and evaluation. (AEF)

Sustaining the Knowledge Base of the United States Air Force for Future Operations

DTIC Science & Technology

2015-12-10

Comptroller, 53, no. 1 (Winter 2008), 20. 30 “Lagan Web Self-Service: Knowledge Management,” 19 September 2015, http://www.kana.com/lagan- crm ...2015, http://www.kana.com/lagan- crm /knowledge-management. Madden, Leign. “U.S. Air Force Soaring to the Cloud with Office 365,” http

Modeling Rare and Unique Documents: Using FRBR[subscript OO]/CIDOC CRM

ERIC Educational Resources Information Center

Le Boeuf, Patrick

2012-01-01

Both the library and the museum communities have developed conceptual models for the information they produce about the collections they hold: FRBR (Functional Requirements for Bibliographic Records) and CIDOC CRM (Conceptual Reference Model). But neither proves perfectly adequate when it comes to some specific types of rare and unique materials:…

Teaching Geographic Field Methods to Cultural Resource Management Technicians

ERIC Educational Resources Information Center

Mires, Peter B.

2004-01-01

There are perhaps 10,000 technicians in the United States who work in the field known as cultural resource management (CRM). The typical field technician possesses a bachelor's degree in anthropology, geography, or a closely allied discipline. The author's experience has been that few CRM field technicians receive adequate undergraduate training…

An Analysis of Female Representation and Marines Performance in Aviation and Logistics Occupations

DTIC Science & Technology

2016-02-01

Parcell, Ann D., Apriel K. Hodari, and Robert W. Shuford. 2003. Predictors of Officer Success. CNA Corporation. CRM D0007437.A2/Final. [18] Kraus...Shuford. 2007. Black and Hispanic Marines: Their Accessions, Representation, Success, and Retention in the Corps. CNA Corporation. CRM D0016910.A1/Final

Managing Risk on the Final Frontier

NASA Technical Reports Server (NTRS)

Lengyel, David M.; Newman, J. S.

2009-01-01

The National Aeronautics and Space Administration (NASA). Exploration Systems Mission Directorate (ESMD) has combined the Continuous Risk Management (CRM) discipline with innovative knowledge management (KM) practices to more effectively enable the accomplishment of work. CRM enables proactive problem identification and problem solving in the complex world of rocket science. while KM is used to improve this process.

Preparation and certification of arsenate [As(V)] reference material, NMIJ CRM 7912-a.

PubMed

Narukawa, Tomohiro; Kuroiwa, Takayoshi; Narushima, Izumi; Jimbo, Yasujiro; Suzuki, Toshihiro; Chiba, Koichi

2010-05-01

Arsenate [As(V)] solution reference material, National Metrology Institute of Japan (NMIJ) certified reference material (CRM) 7912-a, for speciation of arsenic species was developed and certified by NMIJ, the National Institute of Advanced Industrial Science and Technology. High-purity As(2)O(3) reagent powder was dissolved in 0.8 M HNO(3) solution and As(III) was oxidized to As(V) with HNO(3) to prepare 100 mg kg(-1) of As(V) candidate CRM solution. The solution was bottled in 400 bottles (50 mL each). The concentration of As(V) was determined by four independent analytical techniques-inductively coupled plasma mass spectrometry, inductively coupled plasma optical emission spectrometry, graphite furnace atomic absorption spectrometry, and liquid chromatography inductively coupled plasma mass spectrometry-according to As(V) calibration solutions, which were prepared from the arsenic standard of the Japan Calibration Service system and whose species was guaranteed to be As(V) by NMIJ. The uncertainties of all the measurements and preparation procedures were evaluated. The certified value of As(V) in the CRM is (99.53 +/- 1.67) mg kg(-1) (k = 2).

Preparation and certification of hijiki reference material, NMIJ CRM 7405-a, from the edible marine algae hijiki (Hizikia fusiforme).

PubMed

Narukawa, Tomohiro; Inagaki, Kazumi; Zhu, Yanbei; Kuroiwa, Takayoshi; Narushima, Izumi; Chiba, Koichi; Hioki, Akiharu

2012-02-01

A certified reference material, NMIJ CRM 7405-a, for the determination of trace elements and As(V) in algae was developed from the edible marine hijiki (Hizikia fusiforme) and certified by the National Metrology Institute of Japan (NMIJ), the National Institute of Advanced Industrial Science and Technology (AIST). Hijiki was collected from the Pacific coast in the Kanto area of Japan, and was washed, dried, powdered, and homogenized. The hijiki powder was placed in 400 bottles (ca. 20 g each). The concentrations of 18 trace elements and As(V) were determined by two to four independent analytical techniques, including (ID)ICP-(HR)MS, ICP-OES, GFAAS, and HPLC-ICP-MS using calibration solutions prepared from the elemental standard solution of Japan calibration service system (JCSS) and the NMIJ CRM As(V) solution, and whose concentrations are certified and SI traceable. The uncertainties of all the measurements and preparation procedures were evaluated. The values of 18 trace elements and As(V) in the CRM were certified with uncertainty (k = 2).

Why do general circulation models overestimate the aerosol cloud lifetime effect? A case study comparing CAM5 and a CRM

NASA Astrophysics Data System (ADS)

Zhou, Cheng; Penner, Joyce E.

2017-01-01

Observation-based studies have shown that the aerosol cloud lifetime effect or the increase of cloud liquid water path (LWP) with increased aerosol loading may have been overestimated in climate models. Here, we simulate shallow warm clouds on 27 May 2011 at the southern Great Plains (SGP) measurement site established by the Department of Energy's (DOE) Atmospheric Radiation Measurement (ARM) program using a single-column version of a global climate model (Community Atmosphere Model or CAM) and a cloud resolving model (CRM). The LWP simulated by CAM increases substantially with aerosol loading while that in the CRM does not. The increase of LWP in CAM is caused by a large decrease of the autoconversion rate when cloud droplet number increases. In the CRM, the autoconversion rate is also reduced, but this is offset or even outweighed by the increased evaporation of cloud droplets near the cloud top, resulting in an overall decrease in LWP. Our results suggest that climate models need to include the dependence of cloud top growth and the evaporation/condensation process on cloud droplet number concentrations.

Development of a Certified Reference Material (NMIJ CRM 7203-a) for Elemental Analysis of Tap Water.

PubMed

Zhu, Yanbei; Narukawa, Tomohiro; Inagaki, Kazumi; Miyashita, Shin-Ichi; Kuroiwa, Takayoshi; Ariga, Tomoko; Kudo, Izumi; Koguchi, Masae; Heo, Sung Woo; Suh, Jung Ki; Lee, Kyoung-Seok; Yim, Yong-Hyeon; Lim, Youngran

2017-01-01

A certified reference material (CRM), NMIJ CRM 7203-a, was developed for the elemental analysis of tap water. At least two independent analytical methods were applied to characterize the certified value of each element. The elements certified in the present CRM were as follows: Al, As, B, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, Pb, Rb, Sb, Se, Sr, and Zn. The certified value for each element was given as the (property value ± expanded uncertainty), with a coverage factor of 2 for the expanded uncertainty. The expanded uncertainties were estimated while considering the contribution of the analytical methods, the method-to-method variance, the sample homogeneity, the long-term stability, and the concentrations of the standard solutions for calibration. The concentration of Hg (0.39 μg kg -1 ) was given as the information value, since loss of Hg was observed when the sample was stored at room temperature and exposed to light. The certified values of selected elements were confirmed by a co-analysis carried out independently by the NMIJ (Japan) and the KRISS (Korea).

Magnetization of the oceanic crust: TRM or CRM?

NASA Technical Reports Server (NTRS)

Raymond, C. A.; Labrecque, J. L.

1987-01-01

A model was proposed in which chemical remanent magnetization (CRM) acquired within the first 20 Ma of crustal evolution may account for 80% of the bulk natural remanent magnetization (NRM) of older basalts. The CRM of the crust is acquired as the original thermoremanent magnetization (TRM) is lost through low temperature alteration. The CRM intensity and direction are controlled by the post-emplacement polarity history. This model explains several independent observations concerning the magnetization of the oceanic crust. The model accounts for amplitude and skewness discrepancies observed in both the intermediate wavelength satellite field and the short wavelength sea surface magnetic anomaly pattern. It also explains the decay of magnetization away from the spreading axis, and the enhanced magnetization of the Cretaceous Quiet Zones while predicting other systematic variations with age in the bulk magnetization of the oceanic crust. The model also explains discrepancies in the anomaly skewness parameter observed for anomalies of Cretaceous age. Further studies indicate varying rates of TRM decay in very young crust which depicts the advance of low temperature alteration through the magnetized layer.

TNF{alpha} release from peripheral blood leukocytes depends on a CRM1-mediated nuclear export

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miskolci, Veronika; Department of Pediatrics, Feinstein Institute for Medical Research at the North Shore-Long Island Jewish Health System, New Hyde Park, NY 11040; Ghosh, Chandra C.

2006-12-15

Tumor necrosis factor-{alpha} (TNF{alpha}) is a potent pro-inflammatory cytokine that plays a major role in the pathogenesis of acute and chronic inflammatory disorders such as septic shock and arthritis, respectively. Leukocytes stimulated with inflammatory signals such as lipopolysaccharide (LPS) are the predominant producers of TNF{alpha}, and thus control of TNF{alpha} release from stimulated leukocytes represents a potential therapeutic target. Here, we report that leptomycin B (LMB), a specific inhibitor of CRM1-dependent nuclear protein export, inhibits TNF{alpha} release from LPS-stimulated human peripheral blood neutrophils and mononuclear cells. In addition, immunofluorescence confocal microscopy and immunoblotting analysis indicate that TNF{alpha} is localized inmore » the nucleus of human neutrophils and mononuclear cells. This study demonstrates that the cellular release of TNF{alpha} from stimulated leukocytes is mediated by the CRM1-dependent nuclear export mechanism. Inhibition of CRM1-dependent cellular release of TNF{alpha} could thus provide a novel therapeutic approach for disorders involving excessive TNF{alpha} release.« less

Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore.

PubMed

Bao, Xun X; Spanos, Christos; Kojidani, Tomoko; Lynch, Eric M; Rappsilber, Juri; Hiraoka, Yasushi; Haraguchi, Tokuko; Sawin, Kenneth E

2018-05-29

Non-centrosomal microtubule organizing centers (MTOCs) are important for microtubule organization in many cell types. In fission yeast Schizosaccharomyces pombe , the protein Mto1, together with partner protein Mto2 (Mto1/2 complex), recruits the g-tubulin complex to multiple non-centrosomal MTOCs, including the nuclear envelope (NE). Here, we develop a comparative-interactome mass spectrometry approach to determine how Mto1 localizes to the NE. Surprisingly, we find that Mto1, a constitutively cytoplasmic protein, docks at nuclear pore complexes (NPCs), via interaction with exportin Crm1 and cytoplasmic FG-nucleoporin Nup146. Although Mto1 is not a nuclear export cargo, it binds Crm1 via a nuclear export signal-like sequence, and docking requires both Ran in the GTP-bound state and Nup146 FG repeats. In addition to determining the mechanism of MTOC formation at the NE, our results reveal a novel role for Crm1 and the nuclear export machinery in the stable docking of a cytoplasmic protein complex at NPCs. © 2018, Bao et al.

Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore

PubMed Central

Bao, Xun X; Spanos, Christos; Kojidani, Tomoko; Lynch, Eric M; Rappsilber, Juri; Hiraoka, Yasushi; Haraguchi, Tokuko

2018-01-01

Non-centrosomal microtubule organizing centers (MTOCs) are important for microtubule organization in many cell types. In fission yeast Schizosaccharomyces pombe, the protein Mto1, together with partner protein Mto2 (Mto1/2 complex), recruits the γ-tubulin complex to multiple non-centrosomal MTOCs, including the nuclear envelope (NE). Here, we develop a comparative-interactome mass spectrometry approach to determine how Mto1 localizes to the NE. Surprisingly, we find that Mto1, a constitutively cytoplasmic protein, docks at nuclear pore complexes (NPCs), via interaction with exportin Crm1 and cytoplasmic FG-nucleoporin Nup146. Although Mto1 is not a nuclear export cargo, it binds Crm1 via a nuclear export signal-like sequence, and docking requires both Ran in the GTP-bound state and Nup146 FG repeats. In addition to determining the mechanism of MTOC formation at the NE, our results reveal a novel role for Crm1 and the nuclear export machinery in the stable docking of a cytoplasmic protein complex at NPCs. PMID:29809148

What's New with MS Office Suites

ERIC Educational Resources Information Center

Goldsborough, Reid

2012-01-01

If one buys a new PC, laptop, or netbook computer today, it probably comes preloaded with Microsoft Office 2010 Starter Edition. This is a significantly limited, advertising-laden version of Microsoft's suite of productivity programs, Microsoft Office. This continues the trend of PC makers providing ever more crippled versions of Microsoft's…

Utilizing Microsoft Mathematics in Teaching and Learning Calculus

ERIC Educational Resources Information Center

Oktaviyanthi, Rina; Supriani, Yani

2015-01-01

The experimental design was conducted to investigate the use of Microsoft Mathematics, free software made by Microsoft Corporation, in teaching and learning Calculus. This paper reports results from experimental study details on implementation of Microsoft Mathematics in Calculus, students' achievement and the effects of the use of Microsoft…

Experimental Design: Utilizing Microsoft Mathematics in Teaching and Learning Calculus

ERIC Educational Resources Information Center

Oktaviyanthi, Rina; Supriani, Yani

2015-01-01

The experimental design was conducted to investigate the use of Microsoft Mathematics, free software made by Microsoft Corporation, in teaching and learning Calculus. This paper reports results from experimental study details on implementation of Microsoft Mathematics in Calculus, students' achievement and the effects of the use of Microsoft…

RDNAnalyzer: A tool for DNA secondary structure prediction and sequence analysis.

PubMed

Afzal, Muhammad; Shahid, Ahmad Ali; Shehzadi, Abida; Nadeem, Shahid; Husnain, Tayyab

2012-01-01

RDNAnalyzer is an innovative computer based tool designed for DNA secondary structure prediction and sequence analysis. It can randomly generate the DNA sequence or user can upload the sequences of their own interest in RAW format. It uses and extends the Nussinov dynamic programming algorithm and has various application for the sequence analysis. It predicts the DNA secondary structure and base pairings. It also provides the tools for routinely performed sequence analysis by the biological scientists such as DNA replication, reverse compliment generation, transcription, translation, sequence specific information as total number of nucleotide bases, ATGC base contents along with their respective percentages and sequence cleaner. RDNAnalyzer is a unique tool developed in Microsoft Visual Studio 2008 using Microsoft Visual C# and Windows Presentation Foundation and provides user friendly environment for sequence analysis. It is freely available. http://www.cemb.edu.pk/sw.html RDNAnalyzer - Random DNA Analyser, GUI - Graphical user interface, XAML - Extensible Application Markup Language.

LTCP 2D Graphical User Interface. Application Description and User's Guide

NASA Technical Reports Server (NTRS)

Ball, Robert; Navaz, Homayun K.

1996-01-01

A graphical user interface (GUI) written for NASA's LTCP (Liquid Thrust Chamber Performance) 2 dimensional computational fluid dynamic code is described. The GUI is written in C++ for a desktop personal computer running under a Microsoft Windows operating environment. Through the use of common and familiar dialog boxes, features, and tools, the user can easily and quickly create and modify input files for the LTCP code. In addition, old input files used with the LTCP code can be opened and modified using the GUI. The application is written in C++ for a desktop personal computer running under a Microsoft Windows operating environment. The program and its capabilities are presented, followed by a detailed description of each menu selection and the method of creating an input file for LTCP. A cross reference is included to help experienced users quickly find the variables which commonly need changes. Finally, the system requirements and installation instructions are provided.

rhBMP-2 (ACS and CRM formulations) overcomes pseudarthrosis in a New Zealand white rabbit posterolateral fusion model.

PubMed

Lawrence, James P; Waked, Walid; Gillon, Thomas J; White, Andrew P; Spock, Christopher R; Biswas, Debdut; Rosenberger, Patricia; Troiano, Nancy; Albert, Todd J; Grauer, Jonathan N

2007-05-15

The study design consisted of a New Zealand white rabbit model of pseudarthrosis repair. Study groups consisting of no graft, autograft, or recombinant human bone morphogenetic protein-2 (rhBMP-2) with absorbable collagen sponge (ACS) or compression resistant matrix (CRM) were evaluated. To evaluate the relative efficacy of bone graft materials (autograft, ACS, and CRM). rhBMP-2 has been shown to have a 100% fusion rate in a primary rabbit fusion model, even in the presence of nicotine, which is known to inhibit fusion. Seventy-two New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. To establish pseudarthroses, nicotine was administered to all animals. At 5 weeks, the spines were explored and all pseudarthroses were redecorticated and implanted with no graft, autograft, rhBMP-2/ACS, or rhBMP-2/CRM. At 10 weeks, fusions were assessed by manual palpation and histology. Eight rabbits (11%) were lost to complications. At 5 weeks, 66 (97%) had pseudarthroses. At 10 weeks, attempted pseudarthrosis repairs were fused in 1 of 16 of no graft rabbits (6%), 5 of 17 autograft rabbits (29%), and 31 of 31 rhBMP-2 rabbits (with ACS or CRM) (100%). Histologic analysis demonstrated more mature bone formation in the rhBMP-2 groups. The 2 rhBMP-2 formulations led to significantly higher fusion rates and histologic bone formation than no graft and autograft controls in this pseudarthrosis repair model.

A nuclear-encoded chloroplast protein harboring a single CRM domain plays an important role in the Arabidopsis growth and stress response.

PubMed

Lee, Kwanuk; Lee, Hwa Jung; Kim, Dong Hyun; Jeon, Young; Pai, Hyun-Sook; Kang, Hunseung

2014-04-16

Although several chloroplast RNA splicing and ribosome maturation (CRM) domain-containing proteins have been characterized for intron splicing and rRNA processing during chloroplast gene expression, the functional role of a majority of CRM domain proteins in plant growth and development as well as chloroplast RNA metabolism remains largely unknown. Here, we characterized the developmental and stress response roles of a nuclear-encoded chloroplast protein harboring a single CRM domain (At4g39040), designated CFM4, in Arabidopsis thaliana. Analysis of CFM4-GFP fusion proteins revealed that CFM4 is localized to chloroplasts. The loss-of-function T-DNA insertion mutants for CFM4 (cfm4) displayed retarded growth and delayed senescence, suggesting that CFM4 plays a role in growth and development of plants under normal growth conditions. In addition, cfm4 mutants showed retarded seed germination and seedling growth under stress conditions. No alteration in the splicing patterns of intron-containing chloroplast genes was observed in the mutant plants, but the processing of 16S and 4.5S rRNAs was abnormal in the mutant plants. Importantly, CFM4 was determined to possess RNA chaperone activity. These results suggest that the chloroplast-targeted CFM4, one of two Arabidopsis genes encoding a single CRM domain-containing protein, harbors RNA chaperone activity and plays a role in the Arabidopsis growth and stress response by affecting rRNA processing in chloroplasts.

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family

PubMed Central

2010-01-01

Background Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. Findings De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Conclusions Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein. PMID:20979600

Selective Inhibitor of Nuclear Export (SINE) Compounds Alter New World Alphavirus Capsid Localization and Reduce Viral Replication in Mammalian Cells.

PubMed

Lundberg, Lindsay; Pinkham, Chelsea; de la Fuente, Cynthia; Brahms, Ashwini; Shafagati, Nazly; Wagstaff, Kylie M; Jans, David A; Tamir, Sharon; Kehn-Hall, Kylene

2016-11-01

The capsid structural protein of the New World alphavirus, Venezuelan equine encephalitis virus (VEEV), interacts with the host nuclear transport proteins importin α/β1 and CRM1. Novel selective inhibitor of nuclear export (SINE) compounds, KPT-185, KPT-335 (verdinexor), and KPT-350, target the host's primary nuclear export protein, CRM1, in a manner similar to the archetypical inhibitor Leptomycin B. One major limitation of Leptomycin B is its irreversible binding to CRM1; which SINE compounds alleviate because they are slowly reversible. Chemically inhibiting CRM1 with these compounds enhanced capsid localization to the nucleus compared to the inactive compound KPT-301, as indicated by immunofluorescent confocal microscopy. Differences in extracellular versus intracellular viral RNA, as well as decreased capsid in cell free supernatants, indicated the inhibitors affected viral assembly, which led to a decrease in viral titers. The decrease in viral replication was confirmed using a luciferase-tagged virus and through plaque assays. SINE compounds had no effect on VEEV TC83_Cm, which encodes a mutated form of capsid that is unable to enter the nucleus. Serially passaging VEEV in the presence of KPT-185 resulted in mutations within the nuclear localization and nuclear export signals of capsid. Finally, SINE compound treatment also reduced the viral titers of the related eastern and western equine encephalitis viruses, suggesting that CRM1 maintains a common interaction with capsid proteins across the New World alphavirus genus.

The CRM domain: an RNA binding module derived from an ancient ribosome-associated protein.

PubMed

Barkan, Alice; Klipcan, Larik; Ostersetzer, Oren; Kawamura, Tetsuya; Asakura, Yukari; Watkins, Kenneth P

2007-01-01

The CRS1-YhbY domain (also called the CRM domain) is represented as a stand-alone protein in Archaea and Bacteria, and in a family of single- and multidomain proteins in plants. The function of this domain is unknown, but structural data and the presence of the domain in several proteins known to interact with RNA have led to the proposal that it binds RNA. Here we describe a phylogenetic analysis of the domain, its incorporation into diverse proteins in plants, and biochemical properties of a prokaryotic and eukaryotic representative of the domain family. We show that a bacterial member of the family, Escherichia coli YhbY, is associated with pre-50S ribosomal subunits, suggesting that YhbY functions in ribosome assembly. GFP fused to a single-domain CRM protein from maize localizes to the nucleolus, suggesting that an analogous activity may have been retained in plants. We show further that an isolated maize CRM domain has RNA binding activity in vitro, and that a small motif shared with KH RNA binding domains, a conserved "GxxG" loop, contributes to its RNA binding activity. These and other results suggest that the CRM domain evolved in the context of ribosome function prior to the divergence of Archaea and Bacteria, that this function has been maintained in extant prokaryotes, and that the domain was recruited to serve as an RNA binding module during the evolution of plant genomes.

A nuclear-encoded chloroplast protein harboring a single CRM domain plays an important role in the Arabidopsis growth and stress response

PubMed Central

2014-01-01

Background Although several chloroplast RNA splicing and ribosome maturation (CRM) domain-containing proteins have been characterized for intron splicing and rRNA processing during chloroplast gene expression, the functional role of a majority of CRM domain proteins in plant growth and development as well as chloroplast RNA metabolism remains largely unknown. Here, we characterized the developmental and stress response roles of a nuclear-encoded chloroplast protein harboring a single CRM domain (At4g39040), designated CFM4, in Arabidopsis thaliana. Results Analysis of CFM4-GFP fusion proteins revealed that CFM4 is localized to chloroplasts. The loss-of-function T-DNA insertion mutants for CFM4 (cfm4) displayed retarded growth and delayed senescence, suggesting that CFM4 plays a role in growth and development of plants under normal growth conditions. In addition, cfm4 mutants showed retarded seed germination and seedling growth under stress conditions. No alteration in the splicing patterns of intron-containing chloroplast genes was observed in the mutant plants, but the processing of 16S and 4.5S rRNAs was abnormal in the mutant plants. Importantly, CFM4 was determined to possess RNA chaperone activity. Conclusions These results suggest that the chloroplast-targeted CFM4, one of two Arabidopsis genes encoding a single CRM domain-containing protein, harbors RNA chaperone activity and plays a role in the Arabidopsis growth and stress response by affecting rRNA processing in chloroplasts. PMID:24739417

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family.

PubMed

Antonets, Denis V; Nepomnyashchikh, Tatyana S; Shchelkunov, Sergei N

2010-10-27

Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.

Beyond crisis resource management: new frontiers in human factors training for acute care medicine.

PubMed

Petrosoniak, Andrew; Hicks, Christopher M

2013-12-01

Error is ubiquitous in medicine, particularly during critical events and resuscitation. A significant proportion of adverse events can be attributed to inadequate team-based skills such as communication, leadership, situation awareness and resource utilization. Aviation-based crisis resource management (CRM) training using high-fidelity simulation has been proposed as a strategy to improve team behaviours. This review will address key considerations in CRM training and outline recommendations for the future of human factors education in healthcare. A critical examination of the current literature yields several important considerations to guide the development and implementation of effective simulation-based CRM training. These include defining a priori domain-specific objectives, creating an immersive environment that encourages deliberate practice and transfer-appropriate processing, and the importance of effective team debriefing. Building on research from high-risk industry, we suggest that traditional CRM training may be augmented with new training techniques that promote the development of shared mental models for team and task processes, address the effect of acute stress on team performance, and integrate strategies to improve clinical reasoning and the detection of cognitive errors. The evolution of CRM training involves a 'Triple Threat' approach that integrates mental model theory for team and task processes, training for stressful situations and metacognition and error theory towards a more comprehensive training paradigm, with roots in high-risk industry and cognitive psychology. Further research is required to evaluate the impact of this approach on patient-oriented outcomes.

Software Re-Engineering of the Human Factors Analysis and Classification System - (Maintenance Extension) Using Object Oriented Methods in a Microsoft Environment

DTIC Science & Technology

2001-09-01

replication) -- all from Visual Basic and VBA . In fact, we found that the SQL Server engine actually had a plethora of options, most formidable of...2002, the new SQL Server 2000 database engine, and Microsoft Visual Basic.NET. This thesis describes our use of the Spiral Development Model to...versions of Microsoft products? Specifically, the pending release of Microsoft Office 2002, the new SQL Server 2000 database engine, and Microsoft

Improved accuracy of supervised CRM discovery with interpolated Markov models and cross-species comparison.

PubMed

Kazemian, Majid; Zhu, Qiyun; Halfon, Marc S; Sinha, Saurabh

2011-12-01

Despite recent advances in experimental approaches for identifying transcriptional cis-regulatory modules (CRMs, 'enhancers'), direct empirical discovery of CRMs for all genes in all cell types and environmental conditions is likely to remain an elusive goal. Effective methods for computational CRM discovery are thus a critically needed complement to empirical approaches. However, existing computational methods that search for clusters of putative binding sites are ineffective if the relevant TFs and/or their binding specificities are unknown. Here, we provide a significantly improved method for 'motif-blind' CRM discovery that does not depend on knowledge or accurate prediction of TF-binding motifs and is effective when limited knowledge of functional CRMs is available to 'supervise' the search. We propose a new statistical method, based on 'Interpolated Markov Models', for motif-blind, genome-wide CRM discovery. It captures the statistical profile of variable length words in known CRMs of a regulatory network and finds candidate CRMs that match this profile. The method also uses orthologs of the known CRMs from closely related genomes. We perform in silico evaluation of predicted CRMs by assessing whether their neighboring genes are enriched for the expected expression patterns. This assessment uses a novel statistical test that extends the widely used Hypergeometric test of gene set enrichment to account for variability in intergenic lengths. We find that the new CRM prediction method is superior to existing methods. Finally, we experimentally validate 12 new CRM predictions by examining their regulatory activity in vivo in Drosophila; 10 of the tested CRMs were found to be functional, while 6 of the top 7 predictions showed the expected activity patterns. We make our program available as downloadable source code, and as a plugin for a genome browser installed on our servers. © The Author(s) 2011. Published by Oxford University Press.

Development of SI-traceable C-peptide certified reference material NMIJ CRM 6901-a using isotope-dilution mass spectrometry-based amino acid analyses.

PubMed

Kinumi, Tomoya; Goto, Mari; Eyama, Sakae; Kato, Megumi; Kasama, Takeshi; Takatsu, Akiko

2012-07-01

A certified reference material (CRM) is a higher-order calibration material used to enable a traceable analysis. This paper describes the development of a C-peptide CRM (NMIJ CRM 6901-a) by the National Metrology Institute of Japan using two independent methods for amino acid analysis based on isotope-dilution mass spectrometry. C-peptide is a 31-mer peptide that is utilized for the evaluation of β-cell function in the pancreas in clinical testing. This CRM is a lyophilized synthetic peptide having the human C-peptide sequence, and contains deamidated and pyroglutamylated forms of C-peptide. By adding water (1.00 ± 0.01) g into the vial containing the CRM, the C-peptide solution in 10 mM phosphate buffer saline (pH 6.6) is reconstituted. We assigned two certified values that represent the concentrations of total C-peptide (mixture of C-peptide, deamidated C-peptide, and pyroglutamylated C-peptide) and C-peptide. The certified concentration of total C-peptide was determined by two amino acid analyses using pre-column derivatization liquid chromatography-mass spectrometry and hydrophilic chromatography-mass spectrometry following acid hydrolysis. The certified concentration of C-peptide was determined by multiplying the concentration of total C-peptide by the ratio of the relative area of C-peptide to that of the total C-peptide measured by liquid chromatography. The certified value of C-peptide (80.7 ± 5.0) mg/L represents the concentration of the specific entity of C-peptide; on the other hand, the certified value of total C-peptide, (81.7 ± 5.1) mg/L can be used for analyses that does not differentiate deamidated and pyroglutamylated C-peptide from C-peptide itself, such as amino acid analyses and immunochemical assays.

Refined AFC-Enabled High-Lift System Integration Study

NASA Technical Reports Server (NTRS)

Hartwich, Peter M.; Shmilovich, Arvin; Lacy, Douglas S.; Dickey, Eric D.; Scalafani, Anthony J.; Sundaram, P.; Yadlin, Yoram

2016-01-01

A prior trade study established the effectiveness of using Active Flow Control (AFC) for reducing the mechanical complexities associated with a modern high-lift system without sacrificing aerodynamic performance at low-speed flight conditions representative of takeoff and landing. The current technical report expands on this prior work in two ways: (1) a refined conventional high-lift system based on the NASA Common Research Model (CRM) is presented that is more representative of modern commercial transport aircraft in terms of stall characteristics and maximum Lift/Drag (L/D) ratios at takeoff and landing-approach flight conditions; and (2) the design trade space for AFC-enabled high-lift systems is expanded to explore a wider range of options for improving their efficiency. The refined conventional high-lift CRM (HL-CRM) concept features leading edge slats and slotted trailing edge flaps with Fowler motion. For the current AFC-enhanced high lift system trade study, the refined conventional high-lift system is simplified by substituting simply-hinged trailing edge flaps for the slotted single-element flaps with Fowler motion. The high-lift performance of these two high-lift CRM variants is established using Computational Fluid Dynamics (CFD) solutions to the Reynolds-Averaged Navier-Stokes (RANS) equations. These CFD assessments identify the high-lift performance that needs to be recovered through AFC to have the CRM variant with the lighter and mechanically simpler high-lift system match the performance of the conventional high-lift system. In parallel to the conventional high-lift concept development, parametric studies using CFD guided the development of an effective and efficient AFC-enabled simplified high-lift system. This included parametric trailing edge flap geometry studies addressing the effects of flap chord length and flap deflection. As for the AFC implementation, scaling effects (i.e., wind-tunnel versus full-scale flight conditions) are addressed, as are AFC architecture aspects such as AFC unit placement, number AFC units, operating pressures, mass flow rates, and steady versus unsteady AFC applications. These efforts led to the development of a novel traversing AFC actuation concept which is efficient in that it reduces the AFC mass flow requirements by as much as an order of magnitude compared to previous AFC technologies, and it is predicted to be effective in driving the aerodynamic performance of a mechanical simplified high-lift system close to that of the reference conventional high-lift system. Conceptual system integration studies were conducted for the AFC-enhanced high-lift concept applied to a NASA Environmentally Responsible Aircraft (ERA) reference configuration, the so-called ERA-0003 concept. The results from these design integration assessments identify overall system performance improvement opportunities over conventional high-lift systems that suggest the viability of further technology maturation efforts for AFC-enabled high lift flap systems. To that end, technical challenges are identified associated with the application of AFC-enabled high-lift systems to modern transonic commercial transports for future technology maturation efforts.

Vaccination of day-care center attendees reduces carriage of Streptococcus pneumoniae among their younger siblings.

PubMed

Givon-Lavi, Noga; Fraser, Drora; Dagan, Ron

2003-06-01

We conducted a study to determine whether administration of a pneumococcal conjugate vaccine to toddlers attending day-care centers (DCCs) could prevent acquisition of Streptococcus pneumoniae of the vaccine serotypes (VT) by their younger siblings. In a double blind study, 262 DCC attendees ages 12 to 35 months were randomized to receive a 9-valent pneumococcal conjugate vaccine (PnCRM9; n = 132), or a control vaccine (meningococcus C vaccine; n = 130). It was planned to follow the groups for 2 years with monthly nasopharyngeal pneumococcal cultures during the first follow-up year and every 2 months during the second year. Forty-six younger siblings of the above described children, age <18 months (23 siblings of the PnCRM9 recipients and 23 of the controls), were also enrolled, and nasopharyngeal cultures were obtained monthly until the children reached the age of 18 months or started to attend DCC, if before the age of 18 months. Pneumococcal isolates were serotyped and tested for antibiotic susceptibility. Of the 3748 cultures obtained from the DCC attendees, 2450 (65%) were positive for S. pneumoniae. Of 306 cultures obtained from the younger siblings, 151 (49%) were positive. Among the PnCRM9 recipients, cultures were significantly less frequently positive for the VT S. pneumoniae than among the controls (13% vs. 21%, respectively; P < 0.001). The same pattern was seen in the younger siblings of PnCRM9 recipients vs. the siblings of controls (21% vs. 34%, respectively; P = 0.017). The reverse trend was seen for non-VT strains in both the DCC attendees (44% vs. 34%, respectively; P < 0.001) and their younger siblings (19% vs. 13%, respectively; P = 0.15). There was a significant decrease in the carriage rate of antibiotic-resistant S. pneumoniae in both the PnCRM9 recipients and their younger siblings. The relative risks (and 95% confidence intervals) to carry S. pneumoniae penicillin-nonsusceptible, resistant to > or =1, > or =2 and > or =3 antibiotic categories among younger siblings of PnCRM9 recipients vs. siblings of controls were 0.47 (0.31 to 0.70), 0.49 (0.33 to 0.71), 0.46 (0.30 to 0.73) and 0.49 (0.21 to 1.17), respectively. When acquired, VT and antibiotic-resistant S. pneumoniae were carried for a significantly shorter period of time among siblings of PnCRM9 recipients than in siblings of controls. The marked effect of PnCRM9 administration to DCC attendees on carriage of VT and antibiotic-resistant S. pneumoniae among their younger household close contacts demonstrates a herd effect of the vaccine.

Microsoft Biology Initiative: .NET Bioinformatics Platform and Tools

PubMed Central

Diaz Acosta, B.

2011-01-01

The Microsoft Biology Initiative (MBI) is an effort in Microsoft Research to bring new technology and tools to the area of bioinformatics and biology. This initiative is comprised of two primary components, the Microsoft Biology Foundation (MBF) and the Microsoft Biology Tools (MBT). MBF is a language-neutral bioinformatics toolkit built as an extension to the Microsoft .NET Framework—initially aimed at the area of Genomics research. Currently, it implements a range of parsers for common bioinformatics file formats; a range of algorithms for manipulating DNA, RNA, and protein sequences; and a set of connectors to biological web services such as NCBI BLAST. MBF is available under an open source license, and executables, source code, demo applications, documentation and training materials are freely downloadable from http://research.microsoft.com/bio. MBT is a collection of tools that enable biology and bioinformatics researchers to be more productive in making scientific discoveries.

Microsoft in Southeast Europe: A Conversation with Goran Radman

ERIC Educational Resources Information Center

Pendergast, William; Frayne, Colette; Kelley, Patricia

2009-01-01

Goran Radman (GR) joined Microsoft in 1996 and served until Fall 2008 as Microsoft Chairman, Southeast Europe (SEE) and Chairman, East and Central Europe (ECEE). Based in Croatia, where he enjoys sailing the Adriatic coast and islands, he spoke with the authors during 2008 and 2009 about his experience launching Microsoft's commercial presence in…

Microsoft's Tom Corddry on Multimedia, the Information Superhighway and the Future of Online.

ERIC Educational Resources Information Center

Herther, Nancy K.

1994-01-01

Tom Corddry, Microsoft Corporation's Creative Director for the Consumer Division, is interviewed about the Microsoft Home line of products and the development of related CD-ROM and multimedia products. Reasons for Microsoft's entry into the content market and its challenges, the market's future, and the company's interest in developing online…

Uncertainty Quantification of the FUN3D-Predicted NASA CRM Flutter Boundary

NASA Technical Reports Server (NTRS)

Stanford, Bret K.; Massey, Steven J.

2017-01-01

A nonintrusive point collocation method is used to propagate parametric uncertainties of the flexible Common Research Model, a generic transport configuration, through the unsteady aeroelastic CFD solver FUN3D. A range of random input variables are considered, including atmospheric flow variables, structural variables, and inertial (lumped mass) variables. UQ results are explored for a range of output metrics (with a focus on dynamic flutter stability), for both subsonic and transonic Mach numbers, for two different CFD mesh refinements. A particular focus is placed on computing failure probabilities: the probability that the wing will flutter within the flight envelope.

An Investigation Into the Use of Criterion-Referenced Measurement in Vocational and Technical Training.

ERIC Educational Resources Information Center

Day, Gerald F.

The paper investigates and analyses the current state of the art of criterion-referenced measurement (CRM), with a view to determining its use in training and instructional programs. It presents a reveiw of the literature pertaining to the following aspects: a brief history of CRM; a definition and comparison of criterion-referenced and…

The Semantic Mapping of Archival Metadata to the CIDOC CRM Ontology

ERIC Educational Resources Information Center

Bountouri, Lina; Gergatsoulis, Manolis

2011-01-01

In this article we analyze the main semantics of archival description, expressed through Encoded Archival Description (EAD). Our main target is to map the semantics of EAD to the CIDOC Conceptual Reference Model (CIDOC CRM) ontology as part of a wider integration architecture of cultural heritage metadata. Through this analysis, it is concluded…

An Evaluation of Available Models for Estimating the Reliability and Validity of Criterion Referenced Measures.

ERIC Educational Resources Information Center

Oakland, Thomas

New strategies for evaluation criterion referenced measures (CRM) are discussed. These strategies examine the following issues: (1) the use of normed referenced measures (NRM) as CRM and then estimating the reliability and validity of such measures in terms of variance from an arbitrarily specified criterion score, (2) estimation of the…

Time-Resolved Emission Spectroscopy of Field Reversed Configuration Thruster

DTIC Science & Technology

2016-08-31

radiation Collection Optics to 600um fiber Source: Scharer Research Group Source: PEARL 1. Acquire Spectrum 2. Compare to Collisional‐Radiative Model ( CRM ...calibration (deuterium lamp) • Obtain Argon FRC data and use Collisional Radiative Model ( CRM ) to extract plasma properties • Apply knowledge to improve FRC

7 Secrets of Lasting Relationships!

ERIC Educational Resources Information Center

Fredette, Michelle

2013-01-01

Do a web search on the phrase "CRM sucks" and one will find scores of articles, webinars, and blog rants dedicated to the theme. Indeed, if one uses constituent relationship management (CRM) software, one is probably familiar with the litany of complaints. But this is not the time to give up. After all, this is one relationship that really needs…

28 CFR 16.91 - Exemption of Criminal Division Systems-limited access, as indicated.

Code of Federal Regulations, 2013 CFR

2013-07-01

...: (1) Central Criminal Division, Index File and Associated Records System of Records (JUSTICE/CRM-001... Security File System of Records(JUSTICE/CRM-002). These exemptions apply to the extent that information in.... The records in these systems contain the names of the subjects of the files in question and the system...

28 CFR 16.91 - Exemption of Criminal Division Systems-limited access, as indicated.

Code of Federal Regulations, 2011 CFR

2011-07-01

...: (1) Central Criminal Division, Index File and Associated Records System of Records (JUSTICE/CRM-001... Security File System of Records(JUSTICE/CRM-002). These exemptions apply to the extent that information in.... The records in these systems contain the names of the subjects of the files in question and the system...

28 CFR 16.91 - Exemption of Criminal Division Systems-limited access, as indicated.

Code of Federal Regulations, 2012 CFR

2012-07-01

...: (1) Central Criminal Division, Index File and Associated Records System of Records (JUSTICE/CRM-001... Security File System of Records(JUSTICE/CRM-002). These exemptions apply to the extent that information in.... The records in these systems contain the names of the subjects of the files in question and the system...

28 CFR 16.91 - Exemption of Criminal Division Systems-limited access, as indicated.

Code of Federal Regulations, 2014 CFR

2014-07-01

...: (1) Central Criminal Division, Index File and Associated Records System of Records (JUSTICE/CRM-001... Security File System of Records(JUSTICE/CRM-002). These exemptions apply to the extent that information in.... The records in these systems contain the names of the subjects of the files in question and the system...

A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

PubMed Central

2017-01-01

The discovery of cis-regulatory modules (CRMs) is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them. PMID:28497059

Crew resource management in the ICU: the need for culture change.

PubMed

Haerkens, Marck Htm; Jenkins, Donald H; van der Hoeven, Johannes G

2012-08-22

Intensive care frequently results in unintentional harm to patients and statistics don't seem to improve. The ICU environment is especially unforgiving for mistakes due to the multidisciplinary, time-critical nature of care and vulnerability of the patients. Human factors account for the majority of adverse events and a sound safety climate is therefore essential. This article reviews the existing literature on aviation-derived training called Crew Resource Management (CRM) and discusses its application in critical care medicine. CRM focuses on teamwork, threat and error management and blame free discussion of human mistakes. Though evidence is still scarce, the authors consider CRM to be a promising tool for culture change in the ICU setting, if supported by leadership and well-designed follow-up.

75 FR 14401 - Amendment of Certain of the Commission's Rules of Practice and Procedure and Rules of Commission...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-25

... were created, such as Microsoft Excel, Microsoft Word, or Microsoft PowerPoint (``native format'')? We... (condensed) or expanded (detailed) format Export search results to Excel or PDF As noted above, system is...., Microsoft Word ``.doc'' format or non-copy protected text- searchable ``.pdf'' format)? Should submissions...

Kinect-based sign language recognition of static and dynamic hand movements

NASA Astrophysics Data System (ADS)

Dalawis, Rando C.; Olayao, Kenneth Deniel R.; Ramos, Evan Geoffrey I.; Samonte, Mary Jane C.

2017-02-01

A different approach of sign language recognition of static and dynamic hand movements was developed in this study using normalized correlation algorithm. The goal of this research was to translate fingerspelling sign language into text using MATLAB and Microsoft Kinect. Digital input image captured by Kinect devices are matched from template samples stored in a database. This Human Computer Interaction (HCI) prototype was developed to help people with communication disability to express their thoughts with ease. Frame segmentation and feature extraction was used to give meaning to the captured images. Sequential and random testing was used to test both static and dynamic fingerspelling gestures. The researchers explained some factors they encountered causing some misclassification of signs.

Using Microsoft Access: A How-To-Do-It Manual for Librarians. How-To-Do-It Manuals for Librarians, Number 76.

ERIC Educational Resources Information Center

Butler, E. Sonny

Much of what librarians do today requires adeptness in creating and manipulating databases. Many new computers bought by libraries every year come packaged with Microsoft Office and include Microsoft Access. This database program features a seamless interface between Microsoft Office's other programs like Word, Excel, and PowerPoint. This book…

Simulation of orographic effects with a Quasi-3-D Multiscale Modeling Framework: Basic algorithm and preliminary results

DOE PAGES

Jung, Joon -Hee

2016-10-11

Here, the global atmospheric models based on the Multi-scale Modeling Framework (MMF) are able to explicitly resolve subgrid-scale processes by using embedded 2-D Cloud-Resolving Models (CRMs). Up to now, however, those models do not include the orographic effects on the CRM grid scale. This study shows that the effects of CRM grid-scale orography can be simulated reasonably well by the Quasi-3-D MMF (Q3D MMF), which has been developed as a second-generation MMF. In the Q3D framework, the surface topography can be included in the CRM component by using a block representation of the mountains, so that no smoothing of themore » topographic height is necessary. To demonstrate the performance of such a model, the orographic effects over a steep mountain are simulated in an idealized experimental setup with each of the Q3D MMF and the full 3-D CRM. The latter is used as a benchmark. Comparison of the results shows that the Q3D MMF is able to reproduce the horizontal distribution of orographic precipitation and the flow changes around mountains as simulated by the 3-D CRM, even though the embedded CRMs of the Q3D MMF recognize only some aspects of the complex 3-D topography. It is also shown that the use of 3-D CRMs in the Q3D framework, rather than 2-D CRMs, has positive impacts on the simulation of wind fields but does not substantially change the simulated precipitation.« less

Simulation of orographic effects with a Quasi-3-D Multiscale Modeling Framework: Basic algorithm and preliminary results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, Joon -Hee

Here, the global atmospheric models based on the Multi-scale Modeling Framework (MMF) are able to explicitly resolve subgrid-scale processes by using embedded 2-D Cloud-Resolving Models (CRMs). Up to now, however, those models do not include the orographic effects on the CRM grid scale. This study shows that the effects of CRM grid-scale orography can be simulated reasonably well by the Quasi-3-D MMF (Q3D MMF), which has been developed as a second-generation MMF. In the Q3D framework, the surface topography can be included in the CRM component by using a block representation of the mountains, so that no smoothing of themore » topographic height is necessary. To demonstrate the performance of such a model, the orographic effects over a steep mountain are simulated in an idealized experimental setup with each of the Q3D MMF and the full 3-D CRM. The latter is used as a benchmark. Comparison of the results shows that the Q3D MMF is able to reproduce the horizontal distribution of orographic precipitation and the flow changes around mountains as simulated by the 3-D CRM, even though the embedded CRMs of the Q3D MMF recognize only some aspects of the complex 3-D topography. It is also shown that the use of 3-D CRMs in the Q3D framework, rather than 2-D CRMs, has positive impacts on the simulation of wind fields but does not substantially change the simulated precipitation.« less

Collagen I Self-Assembly: Revealing the Developing Structures that Generate Turbidity

PubMed Central

Zhu, Jieling; Kaufman, Laura J.

2014-01-01

Type I collagen gels are routinely used in biophysical studies and bioengineering applications. The structural and mechanical properties of these fibrillar matrices depend on the conditions under which collagen fibrillogenesis proceeds, and developing a fuller understanding of this process will enhance control over gel properties. Turbidity measurements have long been the method of choice for monitoring developing gels, whereas imaging methods are regularly used to visualize fully developed gels. In this study, turbidity and confocal reflectance microscopy (CRM) were simultaneously employed to track collagen fibrillogenesis and reconcile the information reported by the two techniques, with confocal fluorescence microscopy (CFM) used to supplement information about early events in fibrillogenesis. Time-lapse images of 0.5 mg/ml, 1.0 mg/ml, and 2.0 mg/ml acid-solubilized collagen I gels forming at 27°C, 32°C, and 37°C were collected. It was found that in situ turbidity measured in a scanning transmittance configuration was interchangeable with traditional turbidity measurements using a spectrophotometer. CRM and CFM were employed to reveal the structures responsible for the turbidity that develops during collagen self-assembly. Information from CRM and transmittance images was collapsed into straightforward single variables; total intensity in CRM images tracked turbidity development closely for all collagen gels investigated, and the two techniques were similarly sensitive to fibril number and dimension. Complementary CRM, CFM, and in situ turbidity measurements revealed that fibril and network formation occurred before substantial turbidity was present, and the majority of increasing turbidity during collagen self-assembly was due to increasing fibril thickness. PMID:24739181

Critical appraisal of a quadrivalent CRM(197) conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo) in the context of treatment and prevention of invasive disease.

PubMed

Bröker, Michael; Cooper, Brian; Detora, Lisa M; Stoddard, Jeffrey J

2011-01-01

Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo(®)) was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need.

Crisis resource management training for an anaesthesia faculty: a new approach to continuing education.

PubMed

Blum, Richard H; Raemer, Daniel B; Carroll, John S; Sunder, Neelakantan; Felstein, David M; Cooper, Jeffrey B

2004-01-01

Human error and system failures continue to play a substantial role in adverse outcomes in health care. Anaesthesia crisis resource management addresses many patient safety issues by teaching behavioural skills for critical events but it has not been systematically utilized to teach experienced faculty. An anaesthesia crisis resource management course was created for the faculty of our medical school's anaesthesia teaching programmes. The course objectives were to understand and improve participants' proficiency in crisis resource management (CRM) skills and to learn skills for debriefing residents after critical events. Through surveys, measurement objectives assessed acceptance, utility and need for recurrent training immediately post-course. These were measured again approximately 1 year later along with self-perceived changes in the management of difficult or critical events. The highly rated course was well received in terms of overall course quality, realism, debriefings and didactic presentation. Course usefulness, CRM principles, debriefing skills and communication were highly rated immediately post-course and 1 year later. Approximately half of the faculty staff reported a difficult or critical event following the course; of nine self-reported CRM performance criteria surveyed all claimed improvement in their CRM non-technical skills. A unique and highly rated anaesthesia faculty course was created; participation made the faculty staff eligible for malpractice premium reductions. Self-reported CRM behaviours in participants' most significant difficult or critical events indicated an improvement in performance. These data provide indirect evidence supporting the contention that this type of training should be more widely promoted, although more definitive measures of improved outcomes are needed.

Simulation of orographic effects with a Quasi-3-D Multiscale Modeling Framework: Basic algorithm and preliminary results

NASA Astrophysics Data System (ADS)

Jung, Joon-Hee

2016-12-01

The global atmospheric models based on the Multi-scale Modeling Framework (MMF) are able to explicitly resolve subgrid-scale processes by using embedded 2-D Cloud-Resolving Models (CRMs). Up to now, however, those models do not include the orographic effects on the CRM grid scale. This study shows that the effects of CRM grid-scale orography can be simulated reasonably well by the Quasi-3-D MMF (Q3D MMF), which has been developed as a second-generation MMF. In the Q3D framework, the surface topography can be included in the CRM component by using a block representation of the mountains, so that no smoothing of the topographic height is necessary. To demonstrate the performance of such a model, the orographic effects over a steep mountain are simulated in an idealized experimental setup with each of the Q3D MMF and the full 3-D CRM. The latter is used as a benchmark. Comparison of the results shows that the Q3D MMF is able to reproduce the horizontal distribution of orographic precipitation and the flow changes around mountains as simulated by the 3-D CRM, even though the embedded CRMs of the Q3D MMF recognize only some aspects of the complex 3-D topography. It is also shown that the use of 3-D CRMs in the Q3D framework, rather than 2-D CRMs, has positive impacts on the simulation of wind fields but does not substantially change the simulated precipitation.

Analysis of point source size on measurement accuracy of lateral point-spread function of confocal Raman microscopy

NASA Astrophysics Data System (ADS)

Fu, Shihang; Zhang, Li; Hu, Yao; Ding, Xiang

2018-01-01

Confocal Raman Microscopy (CRM) has matured to become one of the most powerful instruments in analytical science because of its molecular sensitivity and high spatial resolution. Compared with conventional Raman Microscopy, CRM can perform three dimensions mapping of tiny samples and has the advantage of high spatial resolution thanking to the unique pinhole. With the wide application of the instrument, there is a growing requirement for the evaluation of the imaging performance of the system. Point-spread function (PSF) is an important approach to the evaluation of imaging capability of an optical instrument. Among a variety of measurement methods of PSF, the point source method has been widely used because it is easy to operate and the measurement results are approximate to the true PSF. In the point source method, the point source size has a significant impact on the final measurement accuracy. In this paper, the influence of the point source sizes on the measurement accuracy of PSF is analyzed and verified experimentally. A theoretical model of the lateral PSF for CRM is established and the effect of point source size on full-width at half maximum of lateral PSF is simulated. For long-term preservation and measurement convenience, PSF measurement phantom using polydimethylsiloxane resin, doped with different sizes of polystyrene microspheres is designed. The PSF of CRM with different sizes of microspheres are measured and the results are compared with the simulation results. The results provide a guide for measuring the PSF of the CRM.

Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka

An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 bindsmore » at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. - Highlights: •DP2392-E10 inhibits replication of a broad range of influenza A subtypes. •DP2392-E10 inhibits nuclear exports of NP and NEP via their NP-NES3 and NEP-NES2 domains, respectively. •DP2392-E10 is predicted to directly bind CRM1 in the region near the HEAT9 and HEAT10 repeats.« less

Differential IFN-gamma stimulation of HLA-A gene expression through CRM-1-dependent nuclear RNA export.

PubMed

Browne, Sarah K; Roesser, James R; Zhu, Sheng Zu; Ginder, Gordon D

2006-12-15

IFNs regulate most MHC class I genes by stimulating transcription initiation. As shown previously, IFN-gamma controls HLA-A expression primarily at the posttranscriptional level. We have defined two 8-base sequences in a 39-nucleotide region in the 3'-transcribed region of the HLA-A gene that are required for the posttranscriptional response to IFN-gamma. Stimulation of HLA-A expression by IFN-gamma requires nuclear export of HLA-A mRNA by chromosome maintenance region 1 (CRM-1). Treatment of cells with leptomycin B, a specific inhibitor of CRM-1, completely inhibited IFN-gamma induction of HLA-A. Expression of a truncated, dominant-negative form of the nucleoporin NUP214/CAN, DeltaCAN, that specifically interacts with CRM-1, also prevented IFN-gamma stimulation of HLA-A, providing confirmation of the role of CRM-1. Increased expression of HLA-A induced by IFN-gamma also requires protein methylation, as shown by the fact that treatment of SK-N-MC cells or HeLa cells with the PRMT1 inhibitor 5'-methyl-5'-thioadenosine abolished the cellular response to IFN-gamma. In contrast with HLA-A, IFN-gamma-induced expression of the HLA class Ib gene, HLA-E, was not affected by either 5'-methyl-5'-thioadenosine or leptomycin B. These results provide proof of principle that it is possible to differentially modulate the IFN-gamma-induced expression of the HLA-E and HLA-A genes, whose products often mediate opposing effects on cellular immunity to tumor cells, pathogens, and autoantigens.

A new approach on stress-related depression and anxiety: Neuro-Psycho- Physical-Optimization with Radio Electric Asymmetric-Conveyer.

PubMed

Rinaldi, Salvatore; Fontani, Vania; Moretti, Elena; Rosettani, Barbara; Aravagli, Lucia; Saragò, Giorgio; Collodel, Giulia

2010-08-01

Chronic social stress is an important factor responsible for the worsening of depressive disorders in humans. In this study we present the relational Neuro-Psycho-Physical Optimization (NPPO) with Radio Electric Asymmetric Conveyer (REAC-CRM) as the treatment to tackle the unconscious dysfunction adjustments carried out by the central nervous system as a response to environmental stresses. Psychological stress was measured in a group of 888 patients using the Psychological Stress Measure (PSM) test, a self-administered questionnaire. Data were collected immediately before and after the 4-wk therapy cycle. The detection of anxiety and depression clusters by PSM test has been based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR, APA, 2000) criteria. Six hundred and eighty eight patients (212 males, 476 females, average PSM test total scores 107.9 +/- 23.13) were treated with REAC-CRM therapy; 200 (64 males, 136 females, average PSM test total scores 107.86 +/- 25.80) were treated with "placebo REAC-CRM therapy"and used as control. This study showed a significant reduction in scores measuring subjective perceptions of stress in the patients treated with a cycle of REAC-CRM therapy. At the end-point the number of patients reporting symptoms of stress-related anxiety and depression on the PSM test was significantly reduced (P<0.001); in the placebo group no significant difference was highlighted. NPPO therapy with a cycle of REAC-CRM was shown to reduce subjective perceptions of stress measured by the PSM test and in particular, symptoms of stress-related anxiety and depression.

Crisis Resources for Emergency Workers (CREW II): results of a pilot study and simulation-based crisis resource management course for emergency medicine residents.

PubMed

Hicks, Christopher M; Kiss, Alex; Bandiera, Glen W; Denny, Christopher J

2012-11-01

Emergency department resuscitation requires the coordinated efforts of an interdisciplinary team. Aviation-based crisis resource management (CRM) training can improve safety and performance during complex events. We describe the development, piloting, and multilevel evaluation of "Crisis Resources for Emergency Workers" (CREW), a simulation-based CRM curriculum for emergency medicine (EM) residents. Curriculum development was informed by an a priori needs assessment survey. We constructed a 1-day course using simulated resuscitation scenarios paired with focused debriefing sessions. Attitudinal shifts regarding team behaviours were assessed using the Human Factors Attitude Survey (HFAS). A subset of 10 residents participated in standardized pre- and postcourse simulated resuscitation scenarios to quantify the effect of CREW training on our primary outcome of CRM performance. Pre/post scenarios were videotaped and scored by two blinded reviewers using a validated behavioural rating scale, the Ottawa CRM Global Rating Scale (GRS). Postcourse survey responses were highly favourable, with the majority of participants reporting that CREW training can reduce errors and improve patient safety. There was a nonsignificant trend toward improved team-based attitudes as assessed by the HFAS (p  =  0.210). Postcourse performance demonstrated a similar trend toward improved scores in all categories on the Ottawa GRS (p  =  0.16). EM residents find simulation-based CRM instruction to be useful, effective, and highly relevant to their practice. Trends toward improved performance and attitudes may have arisen because our study was underpowered to detect a difference. Future efforts should focus on interdisciplinary training and recruiting a larger sample size.

Identification of Novel Saccharomyces cerevisiae Proteins with Nuclear Export Activity: Cell Cycle-Regulated Transcription Factor Ace2p Shows Cell Cycle-Independent Nucleocytoplasmic Shuttling

PubMed Central

Jensen, Torben Heick; Neville, Megan; Rain, Jean Christophe; McCarthy, Terri; Legrain, Pierre; Rosbash, Michael

2000-01-01

Nuclear export of proteins containing leucine-rich nuclear export signals (NESs) is mediated by the NES receptor CRM1/Crm1p. We have carried out a yeast two-hybrid screen with Crm1p as a bait. The Crm1p-interacting clones were subscreened for nuclear export activity in a visual assay utilizing the Crm1p-inhibitor leptomycin B (LMB). This approach identified three Saccharomyces cerevisiae proteins not previously known to have nuclear export activity. These proteins are the 5′ RNA triphosphatase Ctl1p, the cell cycle-regulated transcription factor Ace2p, and a protein encoded by the previously uncharacterized open reading frame YDR499W. Mutagenesis analysis show that YDR499Wp contains an NES that conforms to the consensus sequence for leucine-rich NESs. Mutagenesis of Ctl1p and Ace2p were unable to identify specific NES residues. However, a 29-amino-acid region of Ace2p, rich in hydrophobic residues, contains nuclear export activity. Ace2p accumulates in the nucleus at the end of mitosis and activates early-G1-specific genes. We now provide evidence that Ace2p is nuclear not only in late M-early G1 but also during other stages of the cell cycle. This feature of Ace2p localization explains its ability to activate genes such as CUP1, which are not expressed in a cell cycle-dependent manner. PMID:11027275

Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration.

PubMed

Gasparini, Roberto; Tregnaghi, Miguel; Keshavan, Pavitra; Ypma, Ellen; Han, Linda; Smolenov, Igor

2016-01-01

Given the broad age range across which the quadrivalent meningococcal conjugate vaccine MenACWY-CRM is used, coadministration with routine vaccines should be evaluated across age groups for possible immunologic interference and impact on vaccine reactogenicity and safety. We summarize data from a large population of infants, adolescents and international travelers from 10 phase 3 or 4 clinical studies to evaluate coadministration of MenACWY-CRM with commonly administered vaccines. Noninferiority analyses of immune responses were performed across studies and age groups for each vaccine. Reactogenicity and safety were also assessed. In infants, MenACWY-CRM coadministered with routine vaccines did not reduce immune responses to diphtheria, tetanus, poliovirus, hepatitis B, Haemophilus influenzae type b, pneumococcal conjugate, measles-mumps-rubella, varicella or pertussis antigens. Noninferiority criteria were not met for some pneumococcal conjugate serotypes at 7 months of age, but no consistent trends were observed. In adolescents, coadministration did not reduce immune responses to tetanus, diphtheria and human papilloma virus vaccine antigens. Noninferiority criteria for pertussis antigens were not uniformly met in infant and adolescent studies, although the clinical relevance is unclear. In adults, coadministration did not reduce immune responses to hepatitis A/B, typhoid fever, yellow fever, Japanese encephalitis and rabies antigens. Immune responses to MenACWY-CRM were not impacted by coadministration of commonly administered vaccines. Coadministration did not increase frequencies of postvaccination adverse events in any age group. With no clinically relevant vaccine interactions or impact on vaccine reactogenicity or safety, these results support the coadministration of MenACWY-CRM with routine vaccines in all age groups.

Critical appraisal of a quadrivalent CRM197 conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo®) in the context of treatment and prevention of invasive disease

PubMed Central

Bröker, Michael; Cooper, Brian; DeTora, Lisa M; Stoddard, Jeffrey J

2011-01-01

Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo®) was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need. PMID:21904459

Mindful Application of Aviation Practices in Healthcare.

PubMed

Powell-Dunford, Nicole; Brennan, Peter A; Peerally, Mohammad Farhad; Kapur, Narinder; Hynes, Jonny M; Hodkinson, Peter D

2017-12-01

Evidence supports the efficacy of incorporating select recognized aviation practices and procedures into healthcare. Incident analysis, debrief, safety brief, and crew resource management (CRM) have all been assessed for implementation within the UK healthcare system, a world leader in aviation-based patient safety initiatives. Mindful application, in which aviation practices are specifically tailored to the unique healthcare setting, show promise in terms of acceptance and long-term sustainment. In order to establish British healthcare applications of aviation practices, a PubMed search of UK authored manuscripts published between 2005-2016 was undertaken using search terms 'aviation,' 'healthcare,' 'checklist,' and 'CRM.' A convenience sample of UK-authored aviation medical conference presentations and UK-authored patient safety manuscripts were also reviewed. A total of 11 of 94 papers with UK academic affiliations published between 2005-2016 and relevant to aviation modeled healthcare delivery were found. The debrief process, incident analysis, and CRM are the primary practices incorporated into UK healthcare, with success dependent on cultural acceptance and mindful application. CRM training has gained significant acceptance in UK healthcare environments. Aviation modeled incident analysis, debrief, safety brief, and CRM training are increasingly undertaken within the UK healthcare system. Nuanced application, in which the unique aspects of the healthcare setting are addressed as part of a comprehensive safety approach, shows promise for long-term success. The patient safety brief and aviation modeled incident analysis are in earlier phases of implementation, and warrant further analysis.Powell-Dunford N, Brennan PA, Peerally MF, Kapur N, Hynes JM, Hodkinson PD. Mindful application of aviation practices in healthcare. Aerosp Med Hum Perform. 2017; 88(12):1107-1116.

Dose-finding designs using a novel quasi-continuous endpoint for multiple toxicities

PubMed Central

Ezzalfani, Monia; Zohar, Sarah; Qin, Rui; Mandrekar, Sumithra J; Deley, Marie-Cécile Le

2013-01-01

The aim of a phase I oncology trial is to identify a dose with an acceptable safety profile. Most phase I designs use the dose-limiting toxicity, a binary endpoint, to assess the unacceptable level of toxicity. The dose-limiting toxicity might be incomplete for investigating molecularly targeted therapies as much useful toxicity information is discarded. In this work, we propose a quasi-continuous toxicity score, the total toxicity profile (TTP), to measure quantitatively and comprehensively the overall severity of multiple toxicities. We define the TTP as the Euclidean norm of the weights of toxicities experienced by a patient, where the weights reflect the relative clinical importance of each grade and toxicity type. We propose a dose-finding design, the quasi-likelihood continual reassessment method (CRM), incorporating the TTP score into the CRM, with a logistic model for the dose–toxicity relationship in a frequentist framework. Using simulations, we compared our design with three existing designs for quasi-continuous toxicity score (the Bayesian quasi-CRM with an empiric model and two nonparametric designs), all using the TTP score, under eight different scenarios. All designs using the TTP score to identify the recommended dose had good performance characteristics for most scenarios, with good overdosing control. For a sample size of 36, the percentage of correct selection for the quasi-likelihood CRM ranged from 80% to 90%, with similar results for the quasi-CRM design. These designs with TTP score present an appealing alternative to the conventional dose-finding designs, especially in the context of molecularly targeted agents. PMID:23335156

Improving Representation of Convective Transport for Scale-Aware Parameterization, Part II: Analysis of Cloud-Resolving Model Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yi-Chin; Fan, Jiwen; Zhang, Guang J.

2015-04-27

Following Part I, in which 3-D cloud-resolving model (CRM) simulations of a squall line and mesoscale convective complex in the mid-latitude continental and the tropical regions are conducted and evaluated, we examine the scale-dependence of eddy transport of water vapor, evaluate different eddy transport formulations, and improve the representation of convective transport across all scales by proposing a new formulation that more accurately represents the CRM-calculated eddy flux. CRM results show that there are strong grid-spacing dependencies of updraft and downdraft fractions regardless of altitudes, cloud life stage, and geographical location. As for the eddy transport of water vapor, updraftmore » eddy flux is a major contributor to total eddy flux in the lower and middle troposphere. However, downdraft eddy transport can be as large as updraft eddy transport in the lower atmosphere especially at the mature stage of 38 mid-latitude continental convection. We show that the single updraft approach significantly underestimates updraft eddy transport of water vapor because it fails to account for the large internal variability of updrafts, while a single downdraft represents the downdraft eddy transport of water vapor well. We find that using as few as 3 updrafts can account for the internal variability of updrafts well. Based on evaluation with the CRM simulated data, we recommend a simplified eddy transport formulation that considers three updrafts and one downdraft. Such formulation is similar to the conventional one but much more accurately represents CRM-simulated eddy flux across all grid scales.« less

Using Simulation Education With Deliberate Practice to Teach Leadership and Resource Management Skills to Senior Resident Code Leaders.

PubMed

Burden, Amanda R; Pukenas, Erin W; Deal, Edward R; Coursin, Douglas B; Dodson, Gregory M; Staman, Gregory W; Gratz, Irwin; Torjman, Marc C

2014-09-01

Cardiopulmonary arrests are rare, high-stakes events that benefit from using crisis resource management (CRM). Simulation-based education with deliberate practice can promote skill acquisition. We assessed whether using simulation-based education to teach CRM would lead to improved performance, compared to a lecture format. We tested third-year internal medicine residents in simulated code scenarios. Participants were randomly assigned to simulation-based education with deliberate practice (SIM) group or lecture (LEC) group. We created a checklist of CRM critical actions (which includes announcing the diagnosis, asking for help/suggestions, and assigning tasks), and reviewed videotaped performances, using a checklist of skills and communications patterns to identify CRM skills and communication efforts. Subjects were tested in simulated code scenarios 6 months after the initial assessment. At baseline, all 52 subjects recognized distress, and 92% (48 of 52) called for help. Seventy-eight percent (41 of 52) did not succeed in resuscitating the simulated patient or demonstrate the CRM skills. After intervention, both groups (n  =  26 per group) improved. All SIM subjects announced the diagnosis compared to 65% LEC subjects (17 of 26, P  =  .01); 77% (20 of 26) SIM and 19% (5 of 26) LEC subjects asked for suggestions (P < .001); and 100% (26 of 26) SIM and 27% (7 of 26) LEC subjects assigned tasks (P < .001). The SIM intervention resulted in significantly improved team communication and cardiopulmonary arrest management. During debriefing, participants acknowledged the benefit of the SIM sessions.

Argentina-LLNL-LANL Comparative Sample Analysis on UO2 fuel pellet CRM-125A for Nuclear Forensics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kips, R.

The recent workshop on analytical plan development provided context and background for the next step in this engagement, i.e. a comparative sample analysis on CRM 125-A. This is a commercially available certified low-enriched uranium oxide fuel pellet material from New Brunswick National Laboratory (NBL) (see certificate in Annex 1).

Validation of a Self-Efficacy Instrument and Its Relationship to Performance of Crisis Resource Management Skills

ERIC Educational Resources Information Center

Plant, Jennifer L.; van Schaik, Sandrijn M.; Sliwka, Diane C.; Boscardin, Christy K.; O'Sullivan, Patricia S.

2011-01-01

Self-efficacy is thought to be important for resuscitation proficiency in that it influences the development of and access to the associated medical knowledge, procedural skills and crisis resource management (CRM) skills. Since performance assessment of CRM skills is challenging, self-efficacy is often used as a measure of competence in this…

Aviation Accidents: CRM to Maintaining the Share of Airlines. Case Study on Accidents Airlines in China

ERIC Educational Resources Information Center

Alnuaimi, Qussay A. B.

2015-01-01

We present Aviation Cost Risk management (CRM) methodology designed for Airlines Company, who needs to run projects beyond their normal. These airlines are critical to the survival of these organizations, such as the development and performance. The Aviation crisis can have considerable impact upon the value of the firm. Risk managers must focus…

Cockpit design and cross-cultural issues underlying failures in crew resource management.

PubMed

Harris, Don; Li, Wen-Chin

2008-05-01

High power-distance has been implicated in many aircraft accidents involving Southeast Asian carriers where crew resource management (CRM) has been identified as a root cause. However, this commentary argues that the design of modern flight decks and their standard operating procedures have an inherent Western (low power-distance) bias within them which exacerbates these CRM issues.

Real-time Affective Indices of Potential CRM Breakdown: Qualitative Testing of an Operational Hypothesis

NASA Technical Reports Server (NTRS)

Dickerson, Mark

2007-01-01

This viewgraph presentation begins by showing several cases where poor crew resource management (CRM) resulted in aircraft accidents. The presenter reviews the emotional states that are present in a situation that frequently leads to an accident. The operational answer suggested is given as an acronym: PACE, which stand for Probe, Alert, Challenge, Emergency Action.

In silico evolution of the hunchback gene indicates redundancy in cis-regulatory organization and spatial gene expression

PubMed Central

Zagrijchuk, Elizaveta A.; Sabirov, Marat A.; Holloway, David M.; Spirov, Alexander V.

2014-01-01

Biological development depends on the coordinated expression of genes in time and space. Developmental genes have extensive cis-regulatory regions which control their expression. These regions are organized in a modular manner, with different modules controlling expression at different times and locations. Both how modularity evolved and what function it serves are open questions. We present a computational model for the cis-regulation of the hunchback (hb) gene in the fruit fly (Drosophila). We simulate evolution (using an evolutionary computation approach from computer science) to find the optimal cis-regulatory arrangements for fitting experimental hb expression patterns. We find that the cis-regulatory region tends to readily evolve modularity. These cis-regulatory modules (CRMs) do not tend to control single spatial domains, but show a multi-CRM/multi-domain correspondence. We find that the CRM-domain correspondence seen in Drosophila evolves with a high probability in our model, supporting the biological relevance of the approach. The partial redundancy resulting from multi-CRM control may confer some biological robustness against corruption of regulatory sequences. The technique developed on hb could readily be applied to other multi-CRM developmental genes. PMID:24712536

Review of crisis resource management (CRM) principles in the setting of intraoperative malignant hyperthermia.

PubMed

Isaak, Robert Scott; Stiegler, Marjorie Podraza

2016-04-01

The practice of medicine is characterized by routine and typical cases whose management usually goes according to plan. However, the occasional case does arise which involves rare catastrophic emergencies, such as intraoperative malignant hyperthermia (MH), which require a comprehensive, coordinated, and resource-intensive treatment plan. Physicians are expected to provide expert quality care for routine, typical cases, but is it reasonable to expect the same standard of expertise and comprehensive management when the emergency involves a rare entity? Although physicians would like to say yes to this question, the reality is that no physician will ever amass the amount of experience in patient care needed to truly qualify as an expert in the management of a rare emergency entity, such as MH. However, physicians can become expert in the global process of managing emergencies by using the principles of crisis resource management (CRM). In this article, we review the key concepts of CRM, using a real life example of a team who utilized CRM principles to successfully manage an intraoperative MH crisis, despite there being no one on the team who had ever previously encountered a true MH crisis.

Robust EM Continual Reassessment Method in Oncology Dose Finding

PubMed Central

Yuan, Ying; Yin, Guosheng

2012-01-01

The continual reassessment method (CRM) is a commonly used dose-finding design for phase I clinical trials. Practical applications of this method have been restricted by two limitations: (1) the requirement that the toxicity outcome needs to be observed shortly after the initiation of the treatment; and (2) the potential sensitivity to the prespecified toxicity probability at each dose. To overcome these limitations, we naturally treat the unobserved toxicity outcomes as missing data, and use the expectation-maximization (EM) algorithm to estimate the dose toxicity probabilities based on the incomplete data to direct dose assignment. To enhance the robustness of the design, we propose prespecifying multiple sets of toxicity probabilities, each set corresponding to an individual CRM model. We carry out these multiple CRMs in parallel, across which model selection and model averaging procedures are used to make more robust inference. We evaluate the operating characteristics of the proposed robust EM-CRM designs through simulation studies and show that the proposed methods satisfactorily resolve both limitations of the CRM. Besides improving the MTD selection percentage, the new designs dramatically shorten the duration of the trial, and are robust to the prespecification of the toxicity probabilities. PMID:22375092

Accurate determination of arsenic in arsenobetaine standard solutions of BCR-626 and NMIJ CRM 7901-a by neutron activation analysis coupled with internal standard method.

PubMed

Miura, Tsutomu; Chiba, Koichi; Kuroiwa, Takayoshi; Narukawa, Tomohiro; Hioki, Akiharu; Matsue, Hideaki

2010-09-15

Neutron activation analysis (NAA) coupled with an internal standard method was applied for the determination of As in the certified reference material (CRM) of arsenobetaine (AB) standard solutions to verify their certified values. Gold was used as an internal standard to compensate for the difference of the neutron exposure in an irradiation capsule and to improve the sample-to-sample repeatability. Application of the internal standard method significantly improved linearity of the calibration curve up to 1 microg of As, too. The analytical reliability of the proposed method was evaluated by k(0)-standardization NAA. The analytical results of As in AB standard solutions of BCR-626 and NMIJ CRM 7901-a were (499+/-55)mgkg(-1) (k=2) and (10.16+/-0.15)mgkg(-1) (k=2), respectively. These values were found to be 15-20% higher than the certified values. The between-bottle variation of BCR-626 was much larger than the expanded uncertainty of the certified value, although that of NMIJ CRM 7901-a was almost negligible. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Why do general circulation models overestimate the aerosol cloud lifetime effect? A case study comparing CAM5 and a CRM

DOE PAGES

Zhou, Cheng; Penner, Joyce E.

2017-01-02

Observation-based studies have shown that the aerosol cloud lifetime effect or the increase of cloud liquid water path (LWP) with increased aerosol loading may have been overestimated in climate models. Here, we simulate shallow warm clouds on 27 May 2011 at the southern Great Plains (SGP) measurement site established by the Department of Energy's (DOE) Atmospheric Radiation Measurement (ARM) program using a single-column version of a global climate model (Community Atmosphere Model or CAM) and a cloud resolving model (CRM). The LWP simulated by CAM increases substantially with aerosol loading while that in the CRM does not. The increase of LWP inmore » CAM is caused by a large decrease of the autoconversion rate when cloud droplet number increases. In the CRM, the autoconversion rate is also reduced, but this is offset or even outweighed by the increased evaporation of cloud droplets near the cloud top, resulting in an overall decrease in LWP. Lastly, our results suggest that climate models need to include the dependence of cloud top growth and the evaporation/condensation process on cloud droplet number concentrations.« less

Clinical risk management and patient safety education for nurses: a critique.

PubMed

Johnstone, Megan-Jane; Kanitsaki, Olga

2007-04-01

Nurses have a pivotal role to play in clinical risk management (CRM) and promoting patient safety in health care domains. Accordingly, nurses need to be prepared educationally to manage clinical risk effectively when delivering patient care. Just what form the CRM and safety education of nurses should take, however, remains an open question. A recent search of the literature has revealed a surprising lack of evidence substantiating models of effective CRM and safety education for nurses. In this paper, a critical discussion is advanced on the question of CRM and safety education for nurses and the need for nurse education in this area to be reviewed and systematically researched as a strategic priority, nationally and internationally. It is a key contention of this paper that without 'good' safety education research it will not be possible to ensure that the educational programs that are being offered to nurses in this area are evidence-based and designed in a manner that will enable nurses to develop the capabilities they need to respond effectively to the multifaceted and complex demands that are inherent in their ethical and professional responsibilities to promote and protect patient safety and quality care in health care domains.

Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development.

PubMed

Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka; Kondoh, Yasumitsu; Osada, Hiroyuki; Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori; Aida, Yoko

2017-07-01

An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. Copyright © 2017 Elsevier Inc. All rights reserved.

Consensus Induced Fit Docking (cIFD): methodology, validation, and application to the discovery of novel Crm1 inhibitors

NASA Astrophysics Data System (ADS)

Kalid, Ori; Toledo Warshaviak, Dora; Shechter, Sharon; Sherman, Woody; Shacham, Sharon

2012-11-01

We present the Consensus Induced Fit Docking (cIFD) approach for adapting a protein binding site to accommodate multiple diverse ligands for virtual screening. This novel approach results in a single binding site structure that can bind diverse chemotypes and is thus highly useful for efficient structure-based virtual screening. We first describe the cIFD method and its validation on three targets that were previously shown to be challenging for docking programs (COX-2, estrogen receptor, and HIV reverse transcriptase). We then demonstrate the application of cIFD to the challenging discovery of irreversible Crm1 inhibitors. We report the identification of 33 novel Crm1 inhibitors, which resulted from the testing of 402 purchased compounds selected from a screening set containing 261,680 compounds. This corresponds to a hit rate of 8.2 %. The novel Crm1 inhibitors reveal diverse chemical structures, validating the utility of the cIFD method in a real-world drug discovery project. This approach offers a pragmatic way to implicitly account for protein flexibility without the additional computational costs of ensemble docking or including full protein flexibility during virtual screening.

SAFETY OF A CRM197-CONJUGATED HAEMOPHILUS INFLUENZAE TYPE B VACCINE IN KOREAN CHILDREN.

PubMed

Song, Hyoyoung; Bock, Hans; Guadagno, Alana; Costantini, Marco; Baehner, Frank; Kim, Yeon Ho; Ahn, Seung In; Son, Ki Hyuk; Yim, Dong-Seok

2015-07-01

Haemophilus influenzae type b (Hib) is a major cause of meningitis and pneumonia with high morbidity and mortality rates in young children. The introduction of effective and well-tolerated conjugate Hib vaccines, has nearly eradicated this disease in many countries. We investigated the safety of the Hib PRP-CRM197 vaccine in a multi-center post-marketing surveillance (PMS) study. Korean children (N = 764) aged 1-33 months were enrolled when receiving a routine primary immunization or a booster vaccine with Hib PRP-CRM197 and solicited and unsolicited adverse events (AEs) were recorded using a diary card for 7 and 28 days after each vaccination, respectively. In this study, AEs were reported by 66% of subjects but were generally mild, with 42% of subjects reporting solicited AEs and 46% reporting unsolicited AEs. Among the unsolicited AEs, 98% were determined to be unrelated to the study vaccine. The studied Hib PRP-CRM197 vaccine was well tolerated by the study group and found to have a similar safety profile to that reported in other clinical studies. This vaccine is suitable for routine immunization against Hib disease among Korean children. AEs due to this vaccine will continue to be monitored.

Lack of involvement of strand s1'A of the viral serpin CrmA in anti-apoptotic or caspase-inhibitory functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simonovic, Miljan; Denault, Jean-Bernard; Salvesen, Guy S.

2010-11-30

CrmA is a cowpox virus serpin required for full host infectivity and virulence. Residues 51-56 (DKNKDD), the only region that differs significantly from related viral serpins, were investigated for functional importance. A 1.6 {angstrom} X-ray structure reported here showed that this region can adopt either structured or unstructured conformations. Three variants were expressed, one with the region 51-56 deleted, one substituted by alanines, and one in which this region was replaced by the sequence encoded in smallpox virus. NMR showed that the region is an exposed, flexible loop that can be deleted without perturbing the serpin. The region is alsomore » very susceptible to proteolysis. Significantly, inhibition of caspases 1 and 8 was unaffected by the mutations, and each of the variants was as effective as wild-type CrmA in promoting survival from apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Thus, although the 51-56 region of CrmA is unique, and is exposed and highly susceptible to proteolysis, any in vivo role must involve a function other than proteinase inhibition or cell sparing.« less

Why do general circulation models overestimate the aerosol cloud lifetime effect? A case study comparing CAM5 and a CRM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Cheng; Penner, Joyce E.

Observation-based studies have shown that the aerosol cloud lifetime effect or the increase of cloud liquid water path (LWP) with increased aerosol loading may have been overestimated in climate models. Here, we simulate shallow warm clouds on 27 May 2011 at the southern Great Plains (SGP) measurement site established by the Department of Energy's (DOE) Atmospheric Radiation Measurement (ARM) program using a single-column version of a global climate model (Community Atmosphere Model or CAM) and a cloud resolving model (CRM). The LWP simulated by CAM increases substantially with aerosol loading while that in the CRM does not. The increase of LWP inmore » CAM is caused by a large decrease of the autoconversion rate when cloud droplet number increases. In the CRM, the autoconversion rate is also reduced, but this is offset or even outweighed by the increased evaporation of cloud droplets near the cloud top, resulting in an overall decrease in LWP. Lastly, our results suggest that climate models need to include the dependence of cloud top growth and the evaporation/condensation process on cloud droplet number concentrations.« less

Crew resource management in the ICU: the need for culture change

PubMed Central

2012-01-01

Intensive care frequently results in unintentional harm to patients and statistics don’t seem to improve. The ICU environment is especially unforgiving for mistakes due to the multidisciplinary, time-critical nature of care and vulnerability of the patients. Human factors account for the majority of adverse events and a sound safety climate is therefore essential. This article reviews the existing literature on aviation-derived training called Crew Resource Management (CRM) and discusses its application in critical care medicine. CRM focuses on teamwork, threat and error management and blame free discussion of human mistakes. Though evidence is still scarce, the authors consider CRM to be a promising tool for culture change in the ICU setting, if supported by leadership and well-designed follow-up. PMID:22913855

Cockpit Resource Management (CRM) training in the 349th military airlift wing

NASA Technical Reports Server (NTRS)

Halliday, John T.; Biegalski, Conrad S.; Inzana, Anthony

1987-01-01

CRM training can be done on a limited budget. It seems that everyone has a special name for their CRM program. A new program was created and entitled, Aircrew Resource Management (ARM) to emphasize the use of the full resources on our aircraft. That is meant to specifically include the loadmasters. The name also emphasizes the concept that all crewmembers are responsible for safe completion of the trip. The loadmasters have been the brightest students to date. They are a classic under-utilized resource. Together, their crew position has been credited with more ARM saves than the engineers and pilots. The seminar-based program is run by two seminar facilitators that is reinforced by Line Oriented Flight Training sessions run by the active-duty counterparts.

Heavy metal determinations in algae, mussels and clams. Their possible employment for assessing the sea water quality criteria

NASA Astrophysics Data System (ADS)

Locatelli, C.

2003-05-01

An empirical criterion for a possible classification of sea water quality is proposed. It is based on the knowledge of metal content in algae (Ulva Rigida) mussels (Mytilus Galloprovincialis) and clams (Tapes Philippinarum), three species present in marine ecosystems. The elements considered are Hg, Cu, Pb, Cd, Zn, Ni and Cr. The anatytical technique employed is Atomic Absorption Spectroscopy (AAS). The analytical procedure has been verified on three standard reference materials : Sea Water BCR-CRM 403, Ulva Lactuca BCR-CRM 279 and Mussel Tissue BCR-CRM 278. For all the elements, in addition to detection limits, accuracy and precision are given : the former, expressed as retative error (e). and the latter, expressed as relative standard deviation (sr), were in all cases lower than 6%.

A review on using crumb rubber in reinforcement of asphalt pavement.

PubMed

Mashaan, Nuha Salim; Ali, Asim Hassan; Karim, Mohamed Rehan; Abdelaziz, Mahrez

2014-01-01

An immense problem affecting environmental pollution is the increase of waste tyre vehicles. In an attempt to decrease the magnitude of this issue, crumb rubber modifier (CRM) obtained from waste tyre rubber has gained interest in asphalt reinforcement. The use of crumb rubber in the reinforcement of asphalt is considered as a smart solution for sustainable development by reusing waste materials, and it is believed that crumb rubber modifier (CRM) could be an alternative polymer material in improving hot mix asphalt performance properties. In this paper, a critical review on the use of crumb rubber in reinforcement of asphalt pavement will be presented and discussed. It will also include a review on the effects of CRM on the stiffness, rutting, and fatigue resistance of road pavement construction.

A Review on Using Crumb Rubber in Reinforcement of Asphalt Pavement

PubMed Central

Mashaan, Nuha Salim; Ali, Asim Hassan; Karim, Mohamed Rehan; Abdelaziz, Mahrez

2014-01-01

An immense problem affecting environmental pollution is the increase of waste tyre vehicles. In an attempt to decrease the magnitude of this issue, crumb rubber modifier (CRM) obtained from waste tyre rubber has gained interest in asphalt reinforcement. The use of crumb rubber in the reinforcement of asphalt is considered as a smart solution for sustainable development by reusing waste materials, and it is believed that crumb rubber modifier (CRM) could be an alternative polymer material in improving hot mix asphalt performance properties. In this paper, a critical review on the use of crumb rubber in reinforcement of asphalt pavement will be presented and discussed. It will also include a review on the effects of CRM on the stiffness, rutting, and fatigue resistance of road pavement construction. PMID:24688369

Lessons from Crew Resource Management for Cardiac Surgeons.

PubMed

Marvil, Patrick; Tribble, Curt

2017-04-30

Crew resource management (CRM) describes a system developed in the late 1970s in response to a series of deadly commercial aviation crashes. This system has been universally adopted in commercial and military aviation and is now an integral part of aviation culture. CRM is an error mitigation strategy developed to reduce human error in situations in which teams operate in complex, high-stakes environments. Over time, the principles of this system have been applied and utilized in other environments, particularly in medical areas dealing with high-stakes outcomes requiring optimal teamwork and communication. While the data from formal studies on the effectiveness of formal CRM training in medical environments have reported mixed results, it seems clear that some of these principles should have value in the practice of cardiovascular surgery.

Improving Quality Using Architecture Fault Analysis with Confidence Arguments

DTIC Science & Technology

2015-03-01

the same time, T text, diagram, and table-based requirements documentation and the use of Microsoft Word and Dynamic Object - Oriented Requirements...Lamsweerde 2003] Van Lamsweerde, Axel & Letier, Emmanuel. “From Object Orientation to Goal Orientation : A Paradigm Shift for Requirements Engineering,” 4–8...Introduction 1 Approach , Concepts, and Notations 5 2.1 Requirement Specification and Architecture Design 5 2.2 AADL Concepts Supporting Architecture

Intercomparison of two comparative reactivity method instruments inf the Mediterranean basin during summer 2013

NASA Astrophysics Data System (ADS)

Zannoni, N.; Dusanter, S.; Gros, V.; Sarda Esteve, R.; Michoud, V.; Sinha, V.; Locoge, N.; Bonsang, B.

2015-09-01

The hydroxyl radical (OH) plays a key role in the atmosphere, as it initiates most of the oxidation processes of volatile organic compounds (VOCs), and can ultimately lead to the formation of ozone and secondary organic aerosols (SOAs). There are still uncertainties associated with the OH budget assessed using current models of atmospheric chemistry and direct measurements of OH sources and sinks have proved to be valuable tools to improve our understanding of the OH chemistry. The total first order loss rate of OH, or total OH reactivity, can be directly measured using three different methods, such as the following: total OH loss rate measurement, laser-induced pump and probe technique and comparative reactivity method. Observations of total OH reactivity are usually coupled to individual measurements of reactive compounds in the gas phase, which are used to calculate the OH reactivity. Studies using the three methods have highlighted that a significant fraction of OH reactivity is often not explained by individually measured reactive compounds and could be associated to unmeasured or unknown chemical species. Therefore accurate and reproducible measurements of OH reactivity are required. The comparative reactivity method (CRM) has demonstrated to be an advantageous technique with an extensive range of applications, and for this reason it has been adopted by several research groups since its development. However, this method also requires careful corrections to derive ambient OH reactivity. Herein we present an intercomparison exercise of two CRM instruments, CRM-LSCE (Laboratoire des Sciences du Climat et de l'Environnement) and CRM-MD (Mines Douai), conducted during July 2013 at the Mediterranean site of Ersa, Cape Corsica, France. The intercomparison exercise included tests to assess the corrections needed by the two instruments to process the raw data sets as well as OH reactivity observations. The observation was divided in three parts: 2 days of plant emissions (8-9 July), 2 days of ambient measurements (10-11 July) and 2 days (12-13 July) of plant emissions. We discuss in detail the experimental approach adopted and how the data sets were processed for both instruments. Corrections required for the two instruments lead to higher values of reactivity in ambient air; overall 20 % increase for CRM-MD and 49 % for CRM-LSCE compared to the raw data. We show that ambient OH reactivity measured by the two instruments agrees very well (correlation described by a linear least squares fit with a slope of 1 and R2 of 0.75). This study highlights that ambient measurements of OH reactivity with differently configured CRM instruments yield consistent results in a low NOx (NO + NO2), terpene rich environment, despite differential corrections relevant to each instrument. Conducting more intercomparison exercises, involving more CRM instruments operated under different ambient and instrumental settings will help in assessing the variability induced due to instrument-specific corrections further.

CDC Vital Signs: Adult Smoking among People with Mental Illness

MedlinePlus

... PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ... National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health Page maintained by: Office ...

Photos of MRSA Infections

MedlinePlus

... and Team Healthcare Providers Prevention Information and Advice Posters for the Athletic Community General MRSA Information and ... site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel file Audio/Video file Apple ...

Conducting Automated Test Assembly Using the Premium Solver Platform Version 7.0 with Microsoft Excel and the Large-Scale LP/QP Solver Engine Add-In

ERIC Educational Resources Information Center

Cor, Ken; Alves, Cecilia; Gierl, Mark J.

2008-01-01

This review describes and evaluates a software add-in created by Frontline Systems, Inc., that can be used with Microsoft Excel 2007 to solve large, complex test assembly problems. The combination of Microsoft Excel 2007 with the Frontline Systems Premium Solver Platform is significant because Microsoft Excel is the most commonly used spreadsheet…

Governmentality and Social Capital in Tribal/Federal Relations Regarding Heritage Consultation

DTIC Science & Technology

2016-04-08

cultural resource management (CRM) practices for a qualitative study addressing why tensions between tribes and federal agencies arise in heritage... management (CRM) practices for a qualitative study addressing why tensions between tribes and federal agencies arise in heritage discourse, in spite of...Annual Conference, "Collaborative Archaeology and Collections Management on the Stewart Indian School Project", Invited, Nevada Museum Association

Immunogenicity and safety of a single dose of a CRM-conjugated meningococcal ACWY vaccine in children and adolescents aged 2-18 years in Taiwan: results of an open label study.

PubMed

Huang, Li-Min; Chiu, Nan-Chang; Yeh, Shu-Jen; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

2014-09-08

MenACWY-CRM (Menveo®, Novartis Vaccines, Siena, Italy) is a quadrivalent meningococcal conjugate vaccine developed to help prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W, and Y. It is approved within the European Union in persons >2 years of age and in persons from 2 months to 55 years of age in the United States, among other countries. Little is known about the immunogenicity and safety of this vaccine in Taiwanese children >2 years and adolescents. This study assessed the immunogenicity and safety of a single injection of MenACWY-CRM vaccine in Taiwanese subjects aged 2-18 years old. In this phase III, multicentre, open-label study 341 subjects received one dose of MenACWY-CRM. Immunogenicity measures were rates of seroresponse (defined as the proportion of subjects with a postvaccination hSBA ≥1:8 if the prevaccination (baseline) titre was <1:4, or at least a fourfold higher hSBA titre than baseline if the prevaccination titre was ≥1:4), percentages of subjects with serum bactericidal activity (hSBA) ≥1:8 for serogroups A, C, W and Y and hSBA geometric mean titres (GMTs). Local and systemic reactions and all adverse events (AEs) were recorded for 7 days, and medically attended AEs for 1 month post-vaccination. Seroresponse rates after MenACWY-CRM vaccination at Day 29 for the serogroups A, C, W, and Y were 83%, 93%, 50%, and 65%, respectively. At Day 29 the percentages of subjects with hSBA ≥1:8 against all four serogroups A, C, W and Y were: 83%, 96%, 96% and 82%, respectively. GMTs against all serogroups rose by ≥7-fold from baseline to Day 29. The vaccine was well tolerated. A single dose of MenACWY-CRM demonstrated a robust immune response, and an acceptable safety profile in Taiwanese children and adolescents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of cloud-resolving model simulations of midlatitude cirrus with ARM and A-train observations

DOE PAGES

Muhlbauer, A.; Ackerman, T. P.; Lawson, R. P.; ...

2015-07-14

Cirrus clouds are ubiquitous in the upper troposphere and still constitute one of the largest uncertainties in climate predictions. Our paper evaluates cloud-resolving model (CRM) and cloud system-resolving model (CSRM) simulations of a midlatitude cirrus case with comprehensive observations collected under the auspices of the Atmospheric Radiation Measurements (ARM) program and with spaceborne observations from the National Aeronautics and Space Administration A-train satellites. The CRM simulations are driven with periodic boundary conditions and ARM forcing data, whereas the CSRM simulations are driven by the ERA-Interim product. Vertical profiles of temperature, relative humidity, and wind speeds are reasonably well simulated bymore » the CSRM and CRM, but there are remaining biases in the temperature, wind speeds, and relative humidity, which can be mitigated through nudging the model simulations toward the observed radiosonde profiles. Simulated vertical velocities are underestimated in all simulations except in the CRM simulations with grid spacings of 500 m or finer, which suggests that turbulent vertical air motions in cirrus clouds need to be parameterized in general circulation models and in CSRM simulations with horizontal grid spacings on the order of 1 km. The simulated ice water content and ice number concentrations agree with the observations in the CSRM but are underestimated in the CRM simulations. The underestimation of ice number concentrations is consistent with the overestimation of radar reflectivity in the CRM simulations and suggests that the model produces too many large ice particles especially toward the cloud base. Simulated cloud profiles are rather insensitive to perturbations in the initial conditions or the dimensionality of the model domain, but the treatment of the forcing data has a considerable effect on the outcome of the model simulations. Despite considerable progress in observations and microphysical parameterizations, simulating the microphysical, macrophysical, and radiative properties of cirrus remains challenging. Comparing model simulations with observations from multiple instruments and observational platforms is important for revealing model deficiencies and for providing rigorous benchmarks. But, there still is considerable need for reducing observational uncertainties and providing better observations especially for relative humidity and for the size distribution and chemical composition of aerosols in the upper troposphere.« less

Crew resource management training in the intensive care unit. A multisite controlled before-after study.

PubMed

Kemper, Peter F; de Bruijne, Martine; van Dyck, Cathy; So, Ralph L; Tangkau, Peter; Wagner, Cordula

2016-08-01

There is a growing awareness today that adverse events in the intensive care unit (ICU) are more often caused by problems related to non-technical skills than by a lack of technical, or clinical, expertise. Team training, such as crew resource management (CRM), aims to improve these non-technical skills. The present study evaluated the effectiveness of CRM in the ICU. Six ICUs participated in a paired controlled trial, with one pretest and two post-test measurements (after 3 and 12 months). Three ICUs received CRM training and were compared with a matched control unit. The 2-day classroom-based training was delivered to multidisciplinary groups (ie, ICU physicians, nurses, managers). All levels of Kirkpatrick's evaluation framework were assessed using a mixed method design, including questionnaires, observations and routinely administered patient outcome data. Level I-reaction: participants were very positive directly after the training. Level II-learning: attitudes towards behaviour aimed at optimising situational awareness were relatively high at baseline and remained stable. Level III-behaviour: self-reported behaviour aimed at optimising situational awareness improved in the intervention group. No changes were found in observed explicit professional oral communication. Level IV-organisation: patient outcomes were unaffected. Error management culture and job satisfaction improved in the intervention group. Patient safety culture improved in both control and intervention units. We can conclude that CRM, as delivered in the present study, does not change behaviour or patient outcomes by itself, yet changes how participants think about errors and risks. This indicates that CRM requires a combination with other initiatives in order to improve clinical outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Retrospective robustness of the continual reassessment method.

PubMed

O'Quigley, John; Zohar, Sarah

2010-09-01

We study model sensitivity of the continual reassessment method (CRM). The context is that of dose-finding designs where certain design parameters are fixed by the investigator. Although our focus is on the CRM (O'Quigley et al., 1990), the essential ideas can be applied to any sequential dose-finding method. It is expected that different choices of a model family and particular parameterizations will have an impact on performance. Assuming that the constraints outlined in Shen and O'Quigley (1996) are respected, large sample performance is unaffected. However small sample performance will be affected by these choices, which are to some degree arbitrary. This work focuses on the retrospective robustness of the CRM in practice. The question is not of a general theoretical nature where, in the background, we would want to consider large numbers of true potential situations. Instead, the question is raised in the specific context of any actual completed study and is the following: Would we have come to the same conclusion concerning the MTD had we worked with a design specified differently? The sequential nature of the CRM means that this question cannot be answered in any definitive way. We can, though, by appealing to the retrospective CRM (O'Quigley, 2005), provide consistent estimates of the relationships between the MTD and the chosen model. If these estimates suggest that changes in different family model parameters will be accompanied by changes in final recommendation, then we would not be confident in the reliability of the estimated MTD and more work would be needed. Also, of course, at the planning stage, prospective robustness could be studied by simulating trials using particular models and parameterizations.

Implementation of an original approach on the Mines-Douai Comparative Reactivity Method (MD-CRM) instrument to identify part of the missing OH reactivity at an urban site

NASA Astrophysics Data System (ADS)

Dusanter, S.; Michoud, V.; Leonardis, T.; Riffault, V.; Zhang, S.; Locoge, N.

2015-12-01

Due to the large number of Volatile Organic Compounds (VOCs) expected in the atmosphere (104-105) (Goldstein and Galbally, ES&T, 2007), exhaustive measurements of VOCs appear to be currently unfeasible using common analytical techniques. In this context, measurements of the total sink of OH, referred as total OH reactivity, can provide a critical test to assess the completeness of trace gas measurements during field campaigns. This can be done by comparing the measured total OH reactivity to values calculated from trace gas measurements. Indeed, large discrepancies are usually found between measured and calculated OH reactivity values revealing the presence of important unmeasured reactive species, which have yet to be identified. A Comparative Reactivity Method (CRM) instrument has been setup at Mines Douai to allow sequential measurements of VOCs and OH reactivity using the same Proton Transfer Reaction-Time of Flight Mass Spectrometer. This approach aims at identifying unmeasured reactive VOCs based on a method proposed by Kato et al. (Atmos. Environ., 2011), taking advantage of VOC oxidations occurring in the CRM sampling reactor. MD-CRM has been deployed at an urban site in Dunkirk (France) during July 2014 to test this new approach. During this campaign, a large fraction of the OH reactivity was not explained by collocated measurements of trace gases (67% on average). In this presentation, we will first describe the approach that was implemented in the CRM instrument to identify part of the observed missing OH reactivity and we will then discuss the OH reactivity budget regarding the origin of air masses reaching the measurement site.

Nuclear DDX3 expression predicts poor outcome in colorectal and breast cancer

PubMed Central

Heerma van Voss, Marise R; Vesuna, Farhad; Bol, Guus M; Meeldijk, Jan; Raman, Ana; Offerhaus, G Johan; Buerger, Horst; Patel, Arvind H; van der Wall, Elsken; van Diest, Paul J; Raman, Venu

2017-01-01

Purpose DEAD box protein 3 (DDX3) is an RNA helicase with oncogenic properties that shuttles between the cytoplasm and nucleus. The majority of DDX3 is found in the cytoplasm, but a subset of tumors has distinct nuclear DDX3 localization of yet unknown biological significance. This study aimed to evaluate the significance of and mechanisms behind nuclear DDX3 expression in colorectal and breast cancer. Methods Expression of nuclear DDX3 and the nuclear exporter chromosome region maintenance 1 (CRM1) was evaluated by immunohistochemistry in 304 colorectal and 292 breast cancer patient samples. Correlations between the subcellular localization of DDX3 and CRM1 and the difference in overall survival between patients with and without nuclear DDX3 were studied. In addition, DDX3 mutants were created for in vitro evaluation of the mechanism behind nuclear retention of DDX3. Results DDX3 was present in the nucleus of 35% of colorectal and 48% of breast cancer patient samples and was particularly strong in the nucleolus. Nuclear DDX3 correlated with worse overall survival in both colorectal (hazard ratio [HR] 2.34, P<0.001) and breast cancer (HR 2.39, P=0.004) patients. Colorectal cancers with nuclear DDX3 expression more often had cytoplasmic expression of the nuclear exporter CRM1 (relative risk 1.67, P=0.04). In vitro analysis of DDX3 deletion mutants demonstrated that CRM1-mediated export was most dependent on the N-terminal nuclear export signal. Conclusion Overall, we conclude that nuclear DDX3 is partially CRM1-mediated and predicts worse survival in colorectal and breast cancer patients, putting it forward as a target for therapeutic intervention with DDX3 inhibitors under development in these cancer types. PMID:28761359

Antibody persistence 5 years after vaccination at 2 to 10 years of age with Quadrivalent MenACWY-CRM conjugate vaccine, and responses to a booster vaccination.

PubMed

Block, Stan L; Christensen, Shane; Verma, Bikash; Xie, Fang; Keshavan, Pavitra; Dull, Peter M; Smolenov, Igor

2015-04-27

In a multi-center extension study, children 2-10 years of age, initially vaccinated with one or two doses (2-5 year-olds) or one dose (6-10 year-olds) of quadrivalent meningococcal CRM197-conjugate vaccine (MenACWY-CRM), were assessed five years later for antibody persistence and booster response using serum bactericidal assay with human complement (hSBA). Children 7-10 and 11-15 years of age, who received MenACWY-CRM in the original study, and age-matched vaccine-naïve children, were enrolled in this extension study. After an initial blood draw, children received one dose of MenACWY-CRM as booster or primary dose, with a second blood draw 28 days later. hSBA titers decreased five years after primary vaccination, but were higher than in non-vaccinated controls against serogroups C, W and Y, with substantial proportions having titers ≥8: 7-22% for A, 32-57% for C, 74-83% for W, and 48-54% for Y. Previously-vaccinated children demonstrated booster responses to revaccination against all four serogroups. Responses to primary vaccination in vaccine-naïve controls were lower and similar to primary responses observed in the original study. All vaccinations were generally well tolerated, with no safety concern raised. Approximately half the children vaccinated as 2-10 year-olds maintained protective antibodies against serogroups C, W and Y five years later, but fewer did against serogroup A. Declining titers five years after vaccination and robust booster responses suggest that five years may be an appropriate interval to revaccinate children, subject to epidemiology and delivery considerations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular attributes of conjugate antigen influence function of antibodies induced by anti-nicotine vaccine in mice and non-human primates.

PubMed

McCluskie, Michael J; Thorn, Jennifer; Mehelic, Paul R; Kolhe, Parag; Bhattacharya, Keshab; Finneman, Jari I; Stead, David R; Piatchek, Michele Bailey; Zhang, Ningli; Chikh, Ghania; Cartier, Janna; Evans, Dana M; Merson, James R; Davis, Heather L

2015-04-01

Anti-nicotine vaccines aim to prevent nicotine entering the brain, and thus reduce or eliminate the reward that drives nicotine addiction. Those tested in humans to date have failed to improve quit rates over placebo, possibly because antibody (Ab) responses were insufficient to sequester enough nicotine in the blood in the majority of subjects. We have previously shown in mice that the carrier, hapten and linker used in the nicotine conjugate antigen each influence the function (nicotine-binding capacity) of the Ab induced. Herein we have evaluated immunogenicity in mice of 27 lots of NIC7-CRM, a conjugate of 5-aminoethoxy-nicotine (Hapten 7) and a mutant nontoxic form of diphtheria toxin (CRM197), that differed in three antigen attributes, namely hapten load (number of haptens conjugated to each molecule of CRM197), degree of conjugate aggregation and presence of adducts (small molecules attached to CRM197 via a covalent bond during the conjugation process). A range of functional responses (reduced nicotine in the brain of immunized animals relative to non-immunized controls) were obtained with the different conjugates, which were adjuvanted with aluminum hydroxide and CpG TLR9 agonist. Trends for better functional responses in mice were obtained with conjugates having a hapten load of 11 to 18, a low level of high molecular mass species (HMMS) (i.e., not aggregated) and a low level of adducts and a more limited testing in cynomolgus monkeys confirmed these results. Thus hapten load, conjugate aggregation and presence of adducts are key antigen attributes that can influence Ab function induced by NIC7-CRM. Copyright © 2015 Elsevier B.V. All rights reserved.

Nuclear DDX3 expression predicts poor outcome in colorectal and breast cancer.

PubMed

Heerma van Voss, Marise R; Vesuna, Farhad; Bol, Guus M; Meeldijk, Jan; Raman, Ana; Offerhaus, G Johan; Buerger, Horst; Patel, Arvind H; van der Wall, Elsken; van Diest, Paul J; Raman, Venu

2017-01-01

DEAD box protein 3 (DDX3) is an RNA helicase with oncogenic properties that shuttles between the cytoplasm and nucleus. The majority of DDX3 is found in the cytoplasm, but a subset of tumors has distinct nuclear DDX3 localization of yet unknown biological significance. This study aimed to evaluate the significance of and mechanisms behind nuclear DDX3 expression in colorectal and breast cancer. Expression of nuclear DDX3 and the nuclear exporter chromosome region maintenance 1 (CRM1) was evaluated by immunohistochemistry in 304 colorectal and 292 breast cancer patient samples. Correlations between the subcellular localization of DDX3 and CRM1 and the difference in overall survival between patients with and without nuclear DDX3 were studied. In addition, DDX3 mutants were created for in vitro evaluation of the mechanism behind nuclear retention of DDX3. DDX3 was present in the nucleus of 35% of colorectal and 48% of breast cancer patient samples and was particularly strong in the nucleolus. Nuclear DDX3 correlated with worse overall survival in both colorectal (hazard ratio [HR] 2.34, P <0.001) and breast cancer (HR 2.39, P =0.004) patients. Colorectal cancers with nuclear DDX3 expression more often had cytoplasmic expression of the nuclear exporter CRM1 (relative risk 1.67, P =0.04). In vitro analysis of DDX3 deletion mutants demonstrated that CRM1-mediated export was most dependent on the N-terminal nuclear export signal. Overall, we conclude that nuclear DDX3 is partially CRM1-mediated and predicts worse survival in colorectal and breast cancer patients, putting it forward as a target for therapeutic intervention with DDX3 inhibitors under development in these cancer types.

HIV-1 Nef-associated Factor 1 Enhances Viral Production by Interacting with CRM1 to Promote Nuclear Export of Unspliced HIV-1 gag mRNA.

PubMed

Ren, Xiao-Xin; Wang, Hai-Bo; Li, Chuan; Jiang, Jin-Feng; Xiong, Si-Dong; Jin, Xia; Wu, Li; Wang, Jian-Hua

2016-02-26

HIV-1 depends on host-cell-encoded factors to complete its life cycle. A comprehensive understanding of how HIV-1 manipulates host machineries during viral infection can facilitate the identification of host targets for antiviral drugs or gene therapy. The cellular protein Naf1 (HIV-1 Nef-associated factor 1) is a CRM1-dependent nucleo-cytoplasmic shuttling protein, and has been identified to regulate multiple receptor-mediated signal pathways in inflammation. The cytoplasm-located Naf1 can inhibit NF-κB activation through binding to A20, and the loss of Naf1 controlled NF-κB activation is associated with multiple autoimmune diseases. However, the effect of Naf1 on HIV-1 mRNA expression has not been characterized. In this study we found that the nucleus-located Naf1 could promote nuclear export of unspliced HIV-1 gag mRNA. We demonstrated that the association between Naf1 and CRM1 was required for this function as the inhibition or knockdown of CRM1 expression significantly impaired Naf1-promoted HIV-1 production. The mutation of Naf1 nuclear export signals (NESs) that account for CRM1 recruitment for nuclear export decreased Naf1 function. Additionally, the mutation of the nuclear localization signal (NLS) of Naf1 diminished its ability to promote HIV-1 production, demonstrating that the shuttling property of Naf1 is required for this function. Our results reveal a novel role of Naf1 in enhancing HIV-1 production, and provide a potential therapeutic target for controlling HIV-1 infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents

PubMed Central

Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Graña, Maria Gabriela; Heijnen, Esther; Smolenov, Igor; Dull, Peter M

2015-01-01

This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with ≥68% of subjects achieving hSBA titers ≥5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever (≥38.0°C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885] PMID:25969894

Two-phase transformation of lepidocrocite to maghemite

NASA Astrophysics Data System (ADS)

Dekkers, M. J.; Gapeev, A. K.; Gendler, T. S.; Gribov, S. K.; Shcherbakov, V. P.

2003-04-01

A detailed investigation of CRM acquired at different stages of the transformation lepidocrocite -> maghemite -> hematite is carried out. Apparently, at least two-stage lepidocrocite maghemite transformation was revealed from: a) the two-peak Ms(T) curve; b) the observation of constricted hysteresis loops appearing after annealing fresh lepidocrocite samples at elevated temperatures; c) continuous monitoring (for 500 hrs) of CRM acquisition at elevated temperatures. For the latter two sets of CRM acquisition experiments at 12 temperatures from 175C to 550C in the presence of 0.1 mT magnetic field were performed: 1) with fine dispersed natural lepidocrocite grains in a kaolin matrix (about 1 volume % of lepidocrocite), 2) for lepidocrocite peaces 3x3x3 mm in size. In both cases the CRM was detected already at 175C after 1 day of annealing. Note that this temperature is lower than the temperature of the TGA peak of the lepidocrocite -> maghemite transformation. Mossbauer spectra obtained from the peaces after annealing at 225C during 6 and 14 hours, respectively, revealed significantly different patterns. Unexpectadly, fine dispersed maghemite grains formed due the lepidocrocite dehydration in the first peace (6 hrs of annealing) occurred to be more ordered than those of from the second peace. The samples are subjected to the X-ray analysis in an attempt to clarify the observed difference. The observed phenomena can be explained by the two-phase conception of the transformation lepidocrocite -> maghemite. First the precipitation of small superparamagnetic particles of maghemite takes place growing with time. Second, these grains coalesce with each other resulting in appearance of the antiphase boundaries decreasing the susceptibility, slowing down the process of CRM acquisition and generating the constricted hysteresis loops. The work is supported by INTAS 99-1273.

Development of Subunit Vaccines that Provide High Level Protection and Sterilizing Immunity Against Acute Inhalational Melioidosis.

PubMed

Burtnick, Mary N; Shaffer, Teresa L; Ross, Brittany N; Muruato, Laura A; Sbrana, Elena; DeShazer, David; Torres, Alfredo G; Brett, Paul J

2017-11-06

Burkholderia pseudomallei , the etiologic agent of melioidosis, causes severe disease in humans and animals. Diagnosis and treatment of melioidosis can be challenging and no licensed vaccines currently exist. Several studies have shown that this pathogen expresses a variety of structurally conserved protective antigens that include cell-surface polysaccharides and cell-associated/-secreted proteins. Based on this, such antigens have become important components of the subunit vaccine candidates that we are currently developing. In the present study, the 6-deoxyheptan capsular polysaccharide (CPS) from B. pseudomallei was purified, chemically activated and covalently linked to recombinant CRM197 diphtheria toxin mutant (CRM197) to produce CPS-CRM197. Additionally, tandem nickel-cobalt affinity chromatography was used to prepare highly purified recombinant B. pseudomallei Hcp1 and TssM proteins. Immunization of C57BL/6 mice with CPS-CRM197 produced high-titer IgG and opsonizing antibody responses against the CPS component of the glycoconjugate while immunization with Hcp1 and TssM produced high titer IgG and robust IFN-γ secreting T cell responses against the proteins. Extending upon these studies, we found that when vaccinated with a combination of CPS-CRM197 plus Hcp1, 100% of the mice survived a lethal inhalational challenge of B. pseudomallei Remarkably, 70% of the survivors had no culturable bacteria in their lungs, livers or spleens indicating that the vaccine formulation had generated sterilizing immune responses. Collectively, these studies help to better establish surrogates of antigen-induced immunity against B. pseudomallei as well as provide valuable insights towards the development of a safe, affordable and effective melioidosis vaccine. Copyright © 2017 Burtnick et al.

Cloud Properties Simulated by a Single-Column Model. Part II: Evaluation of Cumulus Detrainment and Ice-phase Microphysics Using a Cloud Resolving Model

NASA Technical Reports Server (NTRS)

Luo, Yali; Krueger, Steven K.; Xu, Kuan-Man

2005-01-01

This paper is the second in a series in which kilometer-scale-resolving observations from the Atmospheric Radiation Measurement program and a cloud-resolving model (CRM) are used to evaluate the single-column model (SCM) version of the National Centers for Environmental Prediction Global Forecast System model. Part I demonstrated that kilometer-scale cirrus properties simulated by the SCM significantly differ from the cloud radar observations while the CRM simulation reproduced most of the cirrus properties as revealed by the observations. The present study describes an evaluation, through a comparison with the CRM, of the SCM's representation of detrainment from deep cumulus and ice-phase microphysics in an effort to better understand the findings of Part I. It is found that detrainment occurs too infrequently at a single level at a time in the SCM, although the detrainment rate averaged over the entire simulation period is somewhat comparable to that of the CRM simulation. Relatively too much detrained ice is sublimated when first detrained. Snow falls over too deep of a layer due to the assumption that snow source and sink terms exactly balance within one time step in the SCM. These characteristics in the SCM parameterizations may explain many of the differences in the cirrus properties between the SCM and the observations (or between the SCM and the CRM). A possible improvement for the SCM consists of the inclusion of multiple cumulus cloud types as in the original Arakawa-Schubert scheme, prognostically determining the stratiform cloud fraction and snow mixing ratio. This would allow better representation of the detrainment from deep convection, better coupling of the volume of detrained air with cloud fraction, and better representation of snow field.

Does the age of acute care physicians impact their (1) crisis management performance and (2) learning after simulation-based education? A protocol for a multicentre prospective cohort study in Toronto and Ottawa, Canada.

PubMed

Alam, Fahad; LeBlanc, Vicki R; Baxter, Alan; Tarshis, Jordan; Piquette, Dominique; Gu, Yuqi; Filipkowska, Caroline; Krywenky, Ashley; Kester-Greene, Nicole; Cardinal, Pierre; Au, Shelly; Lam, Sandy; Boet, Sylvain; Clinical Trials Group, Perioperative Anesthesia

2018-04-21

The proportion of older acute care physicians (ACPs) has been steadily increasing. Ageing is associated with physiological changes and prospective research investigating how such age-related physiological changes affect clinical performance, including crisis resource management (CRM) skills, is lacking. There is a gap in the literature on whether physician's age influences baseline CRM performance and also learning from simulation. We aim to investigate whether ageing is associated with baseline CRM skills of ACPs (emergency, critical care and anaesthesia) using simulated crisis scenarios and to assess whether ageing influences learning from simulation-based education. This is a prospective cohort multicentre study recruiting ACPs from the Universities of Toronto and Ottawa, Canada. Each participant will manage an advanced cardiovascular life support crisis-simulated scenario (pretest) and then be debriefed on their CRM skills. They will then manage another simulated crisis scenario (immediate post-test). Three months after, participants will return to manage a third simulated crisis scenario (retention post-test). The relationship between biological age and chronological age will be assessed by measuring the participants CRM skills and their ability to learn from high-fidelity simulation. This protocol was approved by Sunnybrook Health Sciences Centre Research Ethics Board (REB Number 140-2015) and the Ottawa Health Science Network Research Ethics Board (#20150173-01H). The results will be disseminated in a peer-reviewed journal and at scientific meetings. NCT02683447; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Collagen I self-assembly: revealing the developing structures that generate turbidity.

PubMed

Zhu, Jieling; Kaufman, Laura J

2014-04-15

Type I collagen gels are routinely used in biophysical studies and bioengineering applications. The structural and mechanical properties of these fibrillar matrices depend on the conditions under which collagen fibrillogenesis proceeds, and developing a fuller understanding of this process will enhance control over gel properties. Turbidity measurements have long been the method of choice for monitoring developing gels, whereas imaging methods are regularly used to visualize fully developed gels. In this study, turbidity and confocal reflectance microscopy (CRM) were simultaneously employed to track collagen fibrillogenesis and reconcile the information reported by the two techniques, with confocal fluorescence microscopy (CFM) used to supplement information about early events in fibrillogenesis. Time-lapse images of 0.5 mg/ml, 1.0 mg/ml, and 2.0 mg/ml acid-solubilized collagen I gels forming at 27°C, 32°C, and 37°C were collected. It was found that in situ turbidity measured in a scanning transmittance configuration was interchangeable with traditional turbidity measurements using a spectrophotometer. CRM and CFM were employed to reveal the structures responsible for the turbidity that develops during collagen self-assembly. Information from CRM and transmittance images was collapsed into straightforward single variables; total intensity in CRM images tracked turbidity development closely for all collagen gels investigated, and the two techniques were similarly sensitive to fibril number and dimension. Complementary CRM, CFM, and in situ turbidity measurements revealed that fibril and network formation occurred before substantial turbidity was present, and the majority of increasing turbidity during collagen self-assembly was due to increasing fibril thickness. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Safety and immunogenicity of meningococcal ACWY CRM197-conjugate vaccine in children, adolescents and adults in Russia.

PubMed

Ilyina, Natalia; Kharit, Susanna; Namazova-Baranova, Leila; Asatryan, Asmik; Benashvili, Mayya; Tkhostova, Elmira; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

2014-01-01

Neisseria meningitidis is the leading cause of bacterial invasive infections in people aged <15 years in the Russian Federation. The aim of this phase III, multicenter, open-label study was to assess the immunogenicity and safety of the quadrivalent meningococcal CRM197-conjugate vaccine MenACWY when administered to healthy Russian subjects aged 2 years and above. A total of 197 subjects were immunized with a single dose of the vaccine, and serogroup-specific serum bactericidal activity was measured pre and 1-month post-vaccination with human complement (hSBA) serum titers. Regardless of baseline serostatus, 1 month after a single dose of MenACWY-CRM197 85% (95%CI, 79-90%) of subjects showed serologic response against serogroup A, 74% (67-80%) against serogroup C, 60% (53-67%) against serogroup W, and 83% (77-88%) against serogroup Y. The percentage of subjects with hSBA titers ≥ 1:8 1 month after vaccination was 89% (83-93%) against serogroup A, 84% (78-89%) against serogroup C, 97% (93-99%) against serogroup W, and 88% (82-92%) against serogroup Y. Comparable results were obtained across all subjects: children (2 to 10 years), adolescents (11 to 17 years), and adults (≥18 years). The MenACWY-CRM197 vaccine showed an acceptable safety profile and was well tolerated across all age groups, with no serious adverse events or deaths reported during the study. In conclusion, a single dose of meningococcal MenACWY-CRM197 vaccine is immunogenic and has an acceptable safety profile, provides a broad protection against the most frequent epidemic serogroups, and is a suitable alternative to currently available unconjugated monovalent or bivalent polysaccharide vaccines in Russia.

Safety of Quadrivalent Meningococcal Conjugate Vaccine in Children 2-10 Years.

PubMed

Tartof, Sara Yee; Sy, Lina S; Ackerson, Bradley K; Hechter, Rulin C; Haag, Mendel; Slezak, Jeffrey M; Luo, Yi; Fischetti, Christine A; Takhar, Harp S; Miao, Yan; Solano, Zendi; Jacobsen, Steven J; Tseng, Hung-Fu

2017-11-01

Quadrivalent meningococcal conjugate vaccine is recommended for children, adolescents and adults at increased risk of meningococcal disease. In 2011, MenACWY-CRM (Menveo, GSK, Siena, Italy) was approved for children 2-10 years of age in the United States. Although no safety concerns arose from clinical trials, it remains important to monitor its safety in routine clinical settings. Kaiser Permanente Southern California members 2-10 years old who received MenACWY-CRM between September 2011 and September 2014 were included. Electronic health records were searched using a validated algorithm to identify 26 prespecified events of interests (EOIs) and serious medically attended events (SMAEs) from inpatient or emergency settings up to 1 year after MenACWY-CRM vaccination. SMAEs were categorized by International Classification of Diseases, 9th revision diagnostic categories. All events were reviewed to confirm the diagnosis and symptom onset date. The study was descriptive (NCT01452438); no statistical tests were performed. Among 387 vaccinated children, 327 with ≥6 months membership before vaccination were analyzed. Among EOIs, 9 asthma cases and 1 myasthenia gravis case underwent chart review which confirmed 1 incident asthma case occurring 237 days after concomitant vaccination with MenACWY-CRM and typhoid vaccine. Thirty-one children experienced SMAEs, most commonly because of unrelated injury and poisoning. The remaining events occurred sporadically after vaccination and most were unlikely related to vaccination based on medical record review. One incident EOI of asthma late in the 1-year observation period and sporadic distribution of SMAEs were observed. These data do not suggest safety concerns associated with MenACWY-CRM vaccination in children 2-10 years old.

A model of insulin delivery by a controlled release micropump.

PubMed

Allen, D G; Sefton, M V

1986-01-01

A model has been developed to describe the delivery of insulin from a controlled release micropump (CRM). Basal delivery was provided by diffusion due to a concentration difference driving force across the CRM. This was modelled by considering the CRM to be a series of one-dimensional steady-state diffusion resistances. This delivery model was used to size prototypes and identify the piston, foam and the pump outlet as the controlling resistances to basal insulin transport. Augmented delivery by the CRM was achieved by repeated compression of a foam disk by a mild steel piston which was driven by a solenoid (tested voltage range 0-173 V DC; 5 msec "on" time; frequency 20-40 min-1). The increased delivery was attributed to the combination of mixing inside the pump barrel and displacement of barrel contents into the downstream reservoir. This action was approximated by a three-compartment model, which considered the CRM to consist of a well-mixed upstream reservoir and pump barrel (with a downstream reservoir) separated by two resistances: a constant upstream membrane resistance, (KmAm)-1, and a variable downstream mixing rate resistance, (Qd)-1. A least squares fit of the model to experimental data showed Qd to increase with the cube of the force on the piston and linearly with the compression frequency. In agreement with experimental results, the model predicted the upstream membrane to be rate controlling only at augmented pump resistances close to the value (KmAm)-1. These models were used to design an improved prototype (VIII) which is now being evaluated in vivo in pancreatectomized dogs for its efficacy in restoring and sustaining normoglycemia.

Crop residue management and fertilization effects on soil organic matter and associated biological properties.

PubMed

Zhao, Bingzi; Zhang, Jiabao; Yu, Yueyue; Karlen, Douglas L; Hao, Xiying

2016-09-01

Returning crop residue may result in nutrient reduction in soil in the first few years. A two-year field experiment was conducted to assess whether this negative effect is alleviated by improved crop residue management (CRM). Nine treatments (3 CRM and 3 N fertilizer rates) were used. The CRM treatments were (1) R0: 100 % of the N using mineral fertilizer with no crop residues return; (2) R: crop residue plus mineral fertilizer as for the R0; and (3) Rc: crop residue plus 83 % of the N using mineral and 17 % manure fertilizer. Each CRM received N fertilizer rates at 270, 360, and 450 kg N ha(-1) year(-1). At the end of the experiment, soil NO3-N was reduced by 33 % from the R relative to the R0 treatment, while the Rc treatment resulted in a 21 to 44 % increase in occluded particulate organic C and N, and 80 °C extracted dissolved organic N, 19 to 32 % increase in microbial biomass C and protease activity, and higher monounsaturated phospholipid fatty acid (PLFA):saturated PLFA ratio from stimulating growth of indigenous bacteria when compared with the R treatment. Principal component analysis showed that the Biolog and PLFA profiles in the three CRM treatments were different from each other. Overall, these properties were not influenced by the used N fertilizer rates. Our results indicated that application of 17 % of the total N using manure in a field with crop residues return was effective for improving potential plant N availability and labile soil organic matter, primarily due to a shift in the dominant microorganisms.

78 FR 65431 - Notice of Funds Availability (NOFA) Inviting Applications for the Community Development Financial...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... form; (2) a Microsoft Excel Workbook; (3) a Microsoft Word Narrative template; and (4) other mandatory attachments. (Applicants must use the Microsoft Word Narrative template the CDFI Fund provides; alternative...

Adaptive Prior Variance Calibration in the Bayesian Continual Reassessment Method

PubMed Central

Zhang, Jin; Braun, Thomas M.; Taylor, Jeremy M.G.

2012-01-01

Use of the Continual Reassessment Method (CRM) and other model-based approaches to design in Phase I clinical trials has increased due to the ability of the CRM to identify the maximum tolerated dose (MTD) better than the 3+3 method. However, the CRM can be sensitive to the variance selected for the prior distribution of the model parameter, especially when a small number of patients are enrolled. While methods have emerged to adaptively select skeletons and to calibrate the prior variance only at the beginning of a trial, there has not been any approach developed to adaptively calibrate the prior variance throughout a trial. We propose three systematic approaches to adaptively calibrate the prior variance during a trial and compare them via simulation to methods proposed to calibrate the variance at the beginning of a trial. PMID:22987660

Measurement of ²²⁶Ra in soil from oil field: advantages of γ-ray spectrometry and application to the IAEA-448 CRM.

PubMed

Ceccatelli, A; Katona, R; Kis-Benedek, G; Pitois, A

2014-05-01

The analytical performance of gamma-ray spectrometry for the measurement of (226)Ra in TENORM (Technically Enhanced Naturally Occurring Radioactive Material) soil was investigated by the IAEA. Fast results were obtained for characterization and certification of a new TENORM Certified Reference Material (CRM), identified as IAEA-448 (soil from oil field). The combined standard uncertainty of the gamma-ray spectrometry results is of the order of 2-3% for massic activity measurement values ranging from 16500 Bq kg(-1) to 21500 Bq kg(-1). Methodologies used for the production and certification of the IAEA-448 CRM are presented. Analytical results were confirmed by alpha spectrometry. The "t" test showed agreement between alpha and gamma results at 95% confidence level. © 2013 Published by Elsevier Ltd.

Reasons for Staying: A Test of the Chain of Response Model among Community-College Students. AIR 2001 Annual Forum Paper.

ERIC Educational Resources Information Center

Salomonson, Kristen; Moss, Brian G.; Hill, H. Leon

This paper uses the Chain of Response Model (CRM) to help explain retention in the community college population. In the CRM, the student's decision to remain at an educational institution is not an isolated act, but rather the result of a complex chain of responses based on her/his cognitive evaluation of the present situation. The authors applied…

Soviet Development of Gyrotrons

DTIC Science & Technology

1986-05-01

Relationship Type of Device Remarks V, - Vc, anomalous Doppler Capable of 100 percent efficiency, CRM but more cumbersome than Cheren- kov devices V...authors; and discusses inlividual Soviet reseaLc- groups, the basic organizational units responAiLle for the CRM and gyrotron research and development. The...maintained a cCnEistEnt iecord of significant achievements; it has managed to overcome the systenic yeaxness of the Soviet R&C systeg in teimg atle to

Performance assessment and optimisation of a large information system by combined customer relationship management and resilience engineering: a mathematical programming approach

NASA Astrophysics Data System (ADS)

Azadeh, A.; Foroozan, H.; Ashjari, B.; Motevali Haghighi, S.; Yazdanparast, R.; Saberi, M.; Torki Nejad, M.

2017-10-01

ISs and ITs play a critical role in large complex gas corporations. Many factors such as human, organisational and environmental factors affect IS in an organisation. Therefore, investigating ISs success is considered to be a complex problem. Also, because of the competitive business environment and the high amount of information flow in organisations, new issues like resilient ISs and successful customer relationship management (CRM) have emerged. A resilient IS will provide sustainable delivery of information to internal and external customers. This paper presents an integrated approach to enhance and optimise the performance of each component of a large IS based on CRM and resilience engineering (RE) in a gas company. The enhancement of the performance can help ISs to perform business tasks efficiently. The data are collected from standard questionnaires. It is then analysed by data envelopment analysis by selecting the optimal mathematical programming approach. The selected model is validated and verified by principle component analysis method. Finally, CRM and RE factors are identified as influential factors through sensitivity analysis for this particular case study. To the best of our knowledge, this is the first study for performance assessment and optimisation of large IS by combined RE and CRM.

Use of MenACWY-CRM vaccine in children aged 2 through 23 months at increased risk for meningococcal disease: recommendations of the Advisory Committee on Immunization Practices, 2013.

PubMed

MacNeil, Jessica R; Rubin, Lorry; McNamara, Lucy; Briere, Elizabeth C; Clark, Thomas A; Cohn, Amanda C

2014-06-20

During its October 2013 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended use of a third meningococcal conjugate vaccine, MenACWY-CRM (Menveo, Novartis), as an additional option for vaccinating infants aged 2 through 23 months at increased risk for meningococcal disease. MenACWY-CRM is the first quadrivalent meningococcal conjugate vaccine licensed for use in children aged 2 through 8 months. MenACWY-D (Menactra, Sanofi Pasteur) is recommended for use in children aged 9 through 23 months who are at increased risk for meningococcal disease, and Hib-MenCY-TT (MenHibrix, GlaxoSmithKline) is recommended for use in children aged 6 weeks through 18 months at increased risk. This report summarizes information on MenACWY-CRM administration in infants and provides recommendations for vaccine use in infants aged 2 through 23 months who are at increased risk for meningococcal disease. Because the burden of meningococcal disease in infants is low in the United States and the majority of cases that do occur are caused by serogroup B, which is not included in any vaccine licensed in the United States, only those infants who are at increased risk for meningococcal disease are recommended to receive a meningococcal vaccine.

Exploring Use of the Coordinate Response Measure in a Multitalker Babble Paradigm

PubMed Central

Kidd, Gary R.; Fogerty, Daniel

2017-01-01

Purpose Three experiments examined the use of competing coordinate response measure (CRM) sentences as a multitalker babble. Method In Experiment I, young adults with normal hearing listened to a CRM target sentence in the presence of 2, 4, or 6 competing CRM sentences with synchronous or asynchronous onsets. In Experiment II, the condition with 6 competing sentences was explored further. Three stimulus conditions (6 talkers saying same sentence, 1 talker producing 6 different sentences, and 6 talkers each saying a different sentence) were evaluated with different methods of presentation. Experiment III examined the performance of older adults with hearing impairment in a subset of conditions from Experiment II. Results In Experiment I, performance declined with increasing numbers of talkers and improved with asynchronous sentence onsets. Experiment II identified conditions under which an increase in the number of talkers led to better performance. In Experiment III, the relative effects of the number of talkers, messages, and onset asynchrony were the same for young and older listeners. Conclusions Multitalker babble composed of CRM sentences has masking properties similar to other types of multitalker babble. However, when the number of different talkers and messages are varied independently, performance is best with more talkers and fewer messages. PMID:28249093

Intraguild interactions among specialised pollen feeders and generalist phytoseiids and their effect on citrus rust mite suppression.

PubMed

Maoz, Yonatan; Gal, Shira; Argov, Yael; Domeratzky, Sylvie; Coll, Moshe; Palevsky, Eric

2016-05-01

Antagonistic interactions among predators with shared prey are thought to hamper their ability to suppress herbivores. Our aim was to quantify intraguild interactions in omnivorous predatory mite assemblages in the presence of pollen, and assess their effect on pest populations. We focused on the following naturally occurring phytoseiid species in Israeli citrus orchards and their ability to suppress a key pest, the citrus rust mite (CRM) Phyllocoptruta oleivora (Eriophyidae): the generalists Amblyseius swirskii and Typhlodromus athiasae and the specialised pollen feeders Iphiseius degenerans, Euseius scutalis, E. stipulatus and E. victoriensis. Evaluations were performed on two spatial scales, tree seedlings and leaf discs. On seedlings, experiments were conducted to quantify the interactions between predators in the presence of pollen and its effects on CRM suppression. On leaf discs, intraguild interactions were studied between pairs of phytoseiid species in the presence of pollen without CRM. On seedlings, the specialised pollen predators were more effective at suppressing CRM populations than the generalist predators. In most cases, the more aggressive intraguild predator was the specialised pollen feeder. Similarly, leaf-disc experiments suggest that in these interactions the specialised pollen feeders tend to be the intraguild predators more often than the intraguild prey. © 2015 Society of Chemical Industry.

Changing Community Readiness To Prevent The Abuse Of Inhalants And Other Harmful Legal Products In Alaska1

PubMed Central

Ogilvie, Kristen A.; Moore, Roland S.; Ogilvie, Diane C.; Johnson, Knowlton W.; Collins, David A.; Shamblen, Stephen R.

2008-01-01

This paper presents results from an application of the Community Readiness Model (CRM) as part of a multi-stage community mobilization strategy to engage community leaders, retailers, parents, and school personnel in preventing youth use of inhalants and other harmful legal products in rural Alaska. The CRM is designed to assess readiness to address a single social problem, based on a limited set of key informant interviews. In this study, researchers conducted 32 baseline and 34 post-intervention community readiness assessment interviews in four rural Alaskan communities. These interviews with key informants from the communities were coded and analyzed using CRM methods to yield readiness scores for each community. The aggregate results were analyzed using hierarchical linear modeling (HLM), and the individual community scores were analyzed in the context of the overall study. Significant positive changes in community readiness were found across six readiness dimensions as well as for the overall readiness score. Variation in the degree of changes in readiness across the four communities is attributed to differences in the intervention’s implementation. The implications of these results include the potential for CRM assessments to serve as an integral component of a community mobilization strategy and also to offer meaningful feedback to communities participating in prevention research. PMID:18392927

RDNAnalyzer: A tool for DNA secondary structure prediction and sequence analysis

PubMed Central

Afzal, Muhammad; Shahid, Ahmad Ali; Shehzadi, Abida; Nadeem, Shahid; Husnain, Tayyab

2012-01-01

RDNAnalyzer is an innovative computer based tool designed for DNA secondary structure prediction and sequence analysis. It can randomly generate the DNA sequence or user can upload the sequences of their own interest in RAW format. It uses and extends the Nussinov dynamic programming algorithm and has various application for the sequence analysis. It predicts the DNA secondary structure and base pairings. It also provides the tools for routinely performed sequence analysis by the biological scientists such as DNA replication, reverse compliment generation, transcription, translation, sequence specific information as total number of nucleotide bases, ATGC base contents along with their respective percentages and sequence cleaner. RDNAnalyzer is a unique tool developed in Microsoft Visual Studio 2008 using Microsoft Visual C# and Windows Presentation Foundation and provides user friendly environment for sequence analysis. It is freely available. Availability http://www.cemb.edu.pk/sw.html Abbreviations RDNAnalyzer - Random DNA Analyser, GUI - Graphical user interface, XAML - Extensible Application Markup Language. PMID:23055611

Exploratory Visual Analytics of a Dynamically Built Network of Nodes in a WebGL-Enabled Browser

DTIC Science & Technology

2014-01-01

dimensionality reduction, feature extraction, high-dimensional data, t-distributed stochastic neighbor embedding, neighbor retrieval visualizer, visual...WebGL-enabled rendering is supported natively by browsers such as the latest Mozilla Firefox , Google Chrome, and Microsoft Internet Explorer 11. At the...appropriate names. The resultant 26-node network is displayed in a Mozilla Firefox browser in figure 2 (also see appendix B). 3 Figure 1. The

WASP (Write a Scientific Paper) using Excel - 8: t-Tests.

PubMed

Grech, Victor

2018-06-01

t-Testing is a common component of inferential statistics when comparing two means. This paper explains the central limit theorem and the concept of the null hypothesis as well as types of errors. On the practical side, this paper outlines how different t-tests may be performed in Microsoft Excel, for different purposes, both statically as well as dynamically, with Excel's functions. Copyright © 2018 Elsevier B.V. All rights reserved.

FastStats: Kidney Disease

MedlinePlus

... PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel file Audio/Video file Apple Quicktime file RealPlayer file Text file Zip Archive file SAS file ePub file RIS file Page last reviewed: February 18, 2013 Page last updated: March 30, 2017 Content source: ...

Holographic Rovers: Augmented Reality and the Microsoft HoloLens

NASA Technical Reports Server (NTRS)

Toler, Laura

2017-01-01

Augmented Reality is an emerging field in technology, and encompasses Head Mounted Displays, smartphone apps, and even projected images. HMDs include the Meta 2, Magic Leap, Avegant Light Field, and the Microsoft HoloLens, which is evaluated specifically. The Microsoft HoloLens is designed to be used as an AR personal computer, and is being optimized with that goal in mind. Microsoft allied with the Unity3D game engine to create an SDK for interested application developers that can be used in the Unity environment.

Developing movement recognition application with the use of Shimmer sensor and Microsoft Kinect sensor.

PubMed

Guzsvinecz, Tibor; Szucs, Veronika; Sik Lányi, Cecília

2015-01-01

Nowadays the development of virtual reality-based application is one of the most dynamically growing areas. These applications have a wide user base, more and more devices which are providing several kinds of user interactions and are available on the market. In the applications where the not-handheld devices are not necessary, the potential is that these can be used in educational, entertainment and rehabilitation applications. The purpose of this paper is to examine the precision and the efficiency of the not-handheld devices with user interaction in the virtual reality-based applications. The first task of the developed application is to support the rehabilitation process of stroke patients in their homes. A newly developed application will be introduced in this paper, which uses the two popular devices, the Shimmer sensor and the Microsoft Kinect sensor. To identify and to validate the actions of the user these sensors are working together in parallel mode. For the problem solving, the application is available to record an educational pattern, and then the software compares this pattern to the action of the user. The goal of the current research is to examine the extent of the difference in the recognition of the gestures, how precisely the two sensors are identifying the predefined actions. This could affect the rehabilitation process of the stroke patients and influence the efficiency of the rehabilitation. This application was developed in C# programming language and uses the original Shimmer connecting application as a base. During the working of this application it is possible to teach five-five different movements with the use of the Shimmer and the Microsoft Kinect sensors. The application can recognize these actions at any later time. This application uses a file-based database and the runtime memory of the application to store the saved data in order to reach the actions easier. The conclusion is that much more precise data were collected from the Microsoft Kinect sensor than the Shimmer sensors.

Human-Robot Interface Controller Usability for Mission Planning on the Move

DTIC Science & Technology

2012-11-01

5 Figure 3. Microsoft Xbox 360 controller for Windows...6 Figure 5. Microsoft Trackball Explorer. .........................................................................................7 Figure 6...Xbox 360 Controller is a registered trademark of Microsoft Corporation. 4 3.2.1 HMMWV The HMMWV was equipped with a diesel engine

Scabies: Workplace Frequently Asked Questions (FAQs)

MedlinePlus

... PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel file Audio/Video file Apple Quicktime file RealPlayer file Text file Zip Archive file SAS file ePub file RIS file Page last reviewed: July 19, 2013 Page last updated: July 19, 2013 Content source: ...

Whither CRM? Future directions in Crew Resource Management training in the cockpit and elsewhere

NASA Technical Reports Server (NTRS)

Helmreich, Robert L.

1993-01-01

The past decade has shown worldwide adoption of human factors training in civil aviation, now known as Crew Resource Management (CRM). The shift in name from cockpit to crew reflects a growing trend to extend the training to other components of the aviation system including flight attendants, dispatchers, maintenance personnel, and Air Traffic Controllers. The paper reports findings and new directions in research into human factors.

Sailor Relationship Management: The Use of Customer Relationship Management in Sailor Morale and Retention

DTIC Science & Technology

2002-08-16

advances in information technology. Customer Relationship Management ( CRM ) is a concept that has personalized the marketing process over the Internet. An...even newer concept, Employee Relationship Management (ERM), seeks to turn the lessons learned from CRM inwards to a company’s own employees, not to...within the Navy, resulting in Sailor Relationship Management (SRM.) The work included focus group interviews that led to the development of a survey

Southern Alaska Coastal Relief Model

NASA Astrophysics Data System (ADS)

Lim, E.; Eakins, B.; Wigley, R.

2009-12-01

The National Geophysical Data Center (NGDC), an office of the National Oceanic and Atmospheric Administration (NOAA), in conjunction with the Cooperative Institute for Research in Environmental Sciences (CIRES) at the University of Colorado at Boulder, has developed a 24 arc-second integrated bathymetric-topographic digital elevation model of Southern Alaska. This Coastal Relief Model (CRM) was generated from diverse digital datasets that were obtained from NGDC, the United States Geological Survey, and other U.S. and international agencies. The CRM spans 170° to 230° E and 48.5° to 66.5° N, including the Gulf of Alaska, Bering Sea, Aleutian Islands, and Alaska’s largest communities: Anchorage, Fairbanks, and Juneau. The CRM provides a framework for enabling scientists to refine tsunami propagation and ocean circulation modeling through increased resolution of geomorphologic features. It may also be useful for benthic habitat research, weather forecasting, and environmental stewardship. Shaded-relief image of the Southern Alaska Coastal Relief Model.

The Impact of e-Customer Relationship Marketing in Hotel Industry

NASA Astrophysics Data System (ADS)

Samanta, Irene

The present research investigates the extent to which Greek hotels had developed the electronic customer relationship marketing (E-CRM). The study verifies the practices that frequently appear in relationship marketing process within online operations or whether their Internet presence mainly depends on the basic actions of "supplying information" and "reservations". Also, it investigates the effects of e-CRM system on customer loyalty and satisfaction as well as the impact of relationship marketing practices to customer retention and acquisition. They have understood the importance of using electronic channels instead of traditional ones to implement their marketing strategies. Thus, e-crm system has assisted hotel business to manage more effectively their reservations and serve their customers as fast and as effective as possible. They did not seem to apply many of the relationship marketing strategies to emphasize customer retention and continual satisfaction because of difficulties in staff training.

New technology for recyclingmaterials from oily cold rollingmill sludge

NASA Astrophysics Data System (ADS)

Liu, Bo; Zhang, Shen-gen; Tian, Jian-jun; Pan, De-an; Meng, Ling; Liu, Yang

2013-12-01

Oily cold rolling mill (CRM) sludge is one of metallurgical industry solid wastes. The recycle of these wastes can not only protect the environment but also permit their reutilization. In this research, a new process of "hydrometallurgical treatment + hydrothermal synthesis" was investigated for the combined recovery of iron and organic materials from oily CRM sludge. Hydrometallurgical treatment, mainly including acid leaching, centrifugal separation, neutralization reaction, oxidizing, and preparation of hydrothermal reaction precursor, was first utilized for processing the sludge. Then, micaceous iron oxide (MIO) pigment powders were prepared through hydrothermal reaction of the obtained precursor in alkaline media. The separated organic materials can be used for fuel or chemical feedstock. The quality of the prepared MIO pigments is in accordance with the standards of MIO pigments for paints (ISO 10601-2007). This clean, effective, and economical technology offers a new way to recycle oily CRM sludge.

Customer relationship management implementation in the small and medium enterprise

NASA Astrophysics Data System (ADS)

Nugroho, Agus; Suharmanto, Agus; Masugino

2018-03-01

To win the global competition and sustain the business, small and medium enterprise shall implement a reliable information technology application to support their customer data base, production and sales as well as marketing management. This paper addresses the implementation of Customer Relationship Management (CRM) in small and medium enterprise, CV. Densuko Jaya. It is a small and medium enterprises in Semarang, Central Java, Republic of Indonesia deal with rubber processing industry supply chain. ADDIE model utilized in study to setup the CRM functionality at these enterprises. The aim of the authors is to present the benefits resulting from the application of CRM technologies at these enterprises to solve their chronicle issues in the field of integrated customer data base, production management process and sales automation in order to boost their business in the near future. Training and coaching have been delivered to the enterprises staffs and management to ensure that they can execute the system.

CRM as a General Practice of Every Business Organization

NASA Astrophysics Data System (ADS)

Ahmed, TS Ezaz; Prabhakar, D.

2012-11-01

Every business unit emphasizes on spurting a long term relationship with customers to nurture its stability in todayís blooming market. Customerís expectations are now not only limited to get best products and services, they also need a face-to-face business in which they want to receive exactly what they demand and in a quick time. Customer Relationship Management is an upright concept or strategy to solidify relations with customers and at the same time reducing cost and enhancing productivity and profitability in business. An ideal CRM system is a centralized collection all data sources under an organization and provides an atomistic real time vision of customer information. A CRM system is vast and significant, but it be can implemented for small business, as well as large enterprises also as the main goal is to assist the customers efficiently.

Error Detection-Based Model to Assess Educational Outcomes in Crisis Resource Management Training: A Pilot Study.

PubMed

Bouhabel, Sarah; Kay-Rivest, Emily; Nhan, Carol; Bank, Ilana; Nugus, Peter; Fisher, Rachel; Nguyen, Lily Hp

2017-06-01

Otolaryngology-head and neck surgery (OTL-HNS) residents face a variety of difficult, high-stress situations, which may occur early in their training. Since these events occur infrequently, simulation-based learning has become an important part of residents' training and is already well established in fields such as anesthesia and emergency medicine. In the domain of OTL-HNS, it is gradually gaining in popularity. Crisis Resource Management (CRM), a program adapted from the aviation industry, aims to improve outcomes of crisis situations by attempting to mitigate human errors. Some examples of CRM principles include cultivating situational awareness; promoting proper use of available resources; and improving rapid decision making, particularly in high-acuity, low-frequency clinical situations. Our pilot project sought to integrate CRM principles into an airway simulation course for OTL-HNS residents, but most important, it evaluated whether learning objectives were met, through use of a novel error identification model.

Specifications of a continual reassessment method design for phase I trials of combined drugs†

PubMed Central

Wages, Nolan A.; Conaway, Mark R.

2013-01-01

In studies of combinations of agents in phase I oncology trials, the dose–toxicity relationship may not be monotone for all combinations, in which case the toxicity probabilities follow a partial order. The continual reassessment method for partial orders (PO-CRM) is a design for phase I trials of combinations that leans upon identifying possible complete orders associated with the partial order. This article addresses some practical design considerations not previously undertaken when describing the PO-CRM. We describe an approach in choosing a proper subset of possible orderings, formulated according to the known toxicity relationships within a matrix of combination therapies. Other design issues, such as working model selection and stopping rules, are also discussed. We demonstrate the practical ability of PO-CRM as a phase I design for combinations through its use in a recent trial designed at the University of Virginia Cancer Center. PMID:23729323

Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance.

PubMed

Galvan, Elfego; Walker, Dillon K; Simbo, Sunday Y; Dalton, Ryan; Levers, Kyle; O'Connor, Abigail; Goodenough, Chelsea; Barringer, Nicholas D; Greenwood, Mike; Rasmussen, Christopher; Smith, Stephen B; Riechman, Steven E; Fluckey, James D; Murano, Peter S; Earnest, Conrad P; Kreider, Richard B

2016-01-01

Creatine monohydrate (CrM) and nitrate are popular supplements for improving exercise performance; yet have not been investigated in combination. We performed two studies to determine the safety and exercise performance-characteristics of creatine nitrate (CrN) supplementation. Study 1 participants (N = 13) ingested 1.5 g CrN (CrN-Low), 3 g CrN (CrN-High), 5 g CrM or a placebo in a randomized, crossover study (7d washout) to determine supplement safety (hepatorenal and muscle enzymes, heart rate, blood pressure and side effects) measured at time-0 (unsupplemented), 30-min, and then hourly for 5-h post-ingestion. Study 2 participants (N = 48) received the same CrN treatments vs. 3 g CrM in a randomized, double-blind, 28d trial inclusive of a 7-d interim testing period and loading sequence (4 servings/d). Day-7 and d-28 measured Tendo™ bench press performance, Wingate testing and a 6x6-s bicycle ergometer sprint. Data were analyzed using a GLM and results are reported as mean ± SD or mean change ± 95 % CI. In both studies we observed several significant, yet stochastic changes in blood markers that were not indicative of potential harm or consistent for any treatment group. Equally, all treatment groups reported a similar number of minimal side effects. In Study 2, there was a significant increase in plasma nitrates for both CrN groups by d-7, subsequently abating by d-28. Muscle creatine increased significantly by d-7 in the CrM and CrN-High groups, but then decreased by d-28 for CrN-High. By d-28, there were significant increases in bench press lifting volume (kg) for all groups (PLA, 126.6, 95 % CI 26.3, 226.8; CrM, 194.1, 95 % CI 89.0, 299.2; CrN-Low, 118.3, 95 % CI 26.1, 210.5; CrN-High, 267.2, 95 % CI 175.0, 359.4, kg). Only the CrN-High group was significantly greater than PLA (p < 0.05). Similar findings were observed for bench press peak power (PLA, 59.0, 95 % CI 4.5, 113.4; CrM, 68.6, 95 % CI 11.4, 125.8; CrN-Low, 40.9, 95 % CI -9.2, 91.0; CrN-High, 60.9, 95 % CI 10.8, 111.1, W) and average power. Creatine nitrate delivered at 3 g was well-tolerated, demonstrated similar performance benefits to 3 g CrM, in addition, within the confines of this study, there were no safety concerns.

Inclusion in the Microsoft Workforce

ERIC Educational Resources Information Center

Exceptional Parent, 2008

2008-01-01

Since 1975, Microsoft has been a worldwide leader in software, services, and solutions that help people and businesses realize their full potential. Loren Mikola, the Disability Inclusion Program Manager at Microsoft, ensures that this technology also reaches and includes the special needs population and, through the hiring of individuals with…

FastStats: Chronic Liver Disease and Cirrhosis

MedlinePlus

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Repurposing the Microsoft Kinect for Windows v2 for external head motion tracking for brain PET.

PubMed

Noonan, P J; Howard, J; Hallett, W A; Gunn, R N

2015-11-21

Medical imaging systems such as those used in positron emission tomography (PET) are capable of spatial resolutions that enable the imaging of small, functionally important brain structures. However, the quality of data from PET brain studies is often limited by subject motion during acquisition. This is particularly challenging for patients with neurological disorders or with dynamic research studies that can last 90 min or more. Restraining head movement during the scan does not eliminate motion entirely and can be unpleasant for the subject. Head motion can be detected and measured using a variety of techniques that either use the PET data itself or an external tracking system. Advances in computer vision arising from the video gaming industry could offer significant benefits when re-purposed for medical applications. A method for measuring rigid body type head motion using the Microsoft Kinect v2 is described with results presenting  ⩽0.5 mm spatial accuracy. Motion data is measured in real-time at 30 Hz using the KinectFusion algorithm. Non-rigid motion is detected using the residual alignment energy data of the KinectFusion algorithm allowing for unreliable motion to be discarded. Motion data is aligned to PET listmode data using injected pulse sequences into the PET/CT gantry allowing for correction of rigid body motion. Pilot data from a clinical dynamic PET/CT examination is shown.