Sample records for wrong dntp substrates
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Bao, Jie; Ryu, Dewey D Y
2007-09-01
Polymerase chain reaction (PCR) and other PCR applications for DNA synthesis require deoxynucleoside triphosphates (dNTP) as the essential precursors and substrates. Currently, the dNTP is commercially produced by a chemical method which is environmentally hazardous and costly due to its low yields in both the synthetic reaction and purification processes. In this study, a enzyme technology for the total integrated biosynthesis of all dNTP components is presented. The bioprocess technology developed and reported here involves two sequential enzymatic phosphorylation reactions coupled with the cofactor regeneration starting from deoxynucleoside monophosphates (dNMP) to deoxynucleoside diphosphates (dNDP) in the first reaction step and to dNTP in the second reaction step in the same bioreactor. The four genes encoding these deoxynucleoside monophosphate kinases were cloned into the recombinant E. coli and expressed using the recombinant E. coli strains. The reaction mechanisms and kinetics of the four kinase enzymes are studied and reported. The total enzymatic syntheses of the four dNTP products were carried out in four separate operations under the high substrate concentrations which emulate the practical application. The optimal process conditions were carefully investigated and complete conversion of dNMP to dNTP at high substrate concentration have been achieved. The purity and quality of dNTP products obtained from this work were analyzed and found to be at least equivalent or better than the commercially available dNTP products. The PCR application of dNTP products obtained from this work were also evaluated for isolating and amplifying genes of different sizes from different organisms. The PCR performance test also showed an equivalent quality as compared to the commercially available dNTP. The bioprocess technology developed and reported here for production of dNTP will provide economically competitive and environmentally friendly viable technology for the industry and research community as compared to the chemical technology currently in use.
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Capella, Cristina; Beltejar, Michael-John; Brown, Caitlin; Fong, Vincent; Daddacha, Waaqo; Kim, Baek
2012-01-01
Mutations that reduce the efficiency of deoxynucleoside (dN) triphosphate (dNTP) substrate utilization by the HIV-1 DNA polymerase prevent viral replication in resting cells, which contain low dNTP concentrations, but not in rapidly dividing cells such as cancer cells, which contain high levels of dNTPs. We therefore tested whether mutations in regions of the adenovirus type 5 (Ad5) DNA polymerase that interact with the dNTP substrate or DNA template could alter virus replication. The majority of the mutations created, including conservative substitutions, were incompatible with virus replication. Five replication-competent mutants were recovered from 293 cells, but four of these mutants failed to replicate in A549 lung carcinoma cells and Wi38 normal lung cells. Purified polymerase proteins from these viruses exhibited only a 2- to 4-fold reduction in their dNTP utilization efficiency but nonetheless could not be rescued, even when intracellular dNTP concentrations were artificially raised by the addition of exogenous dNs to virus-infected A549 cells. The fifth mutation (I664V) reduced biochemical dNTP utilization by the viral polymerase by 2.5-fold. The corresponding virus replicated to wild-type levels in three different cancer cell lines but was significantly impaired in all normal cell lines in which it was tested. Efficient replication and virus-mediated cell killing were rescued by the addition of exogenous dNs to normal lung fibroblasts (MRC5 cells), confirming the dNTP-dependent nature of the polymerase defect. Collectively, these data provide proof-of-concept support for the notion that conditionally replicating, tumor-selective adenovirus vectors can be created by modifying the efficiency with which the viral DNA polymerase utilizes dNTP substrates. PMID:22811532
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Dahl, Joseph M; Wang, Hongyun; Lázaro, José M; Salas, Margarita; Lieberman, Kate R
2014-03-07
The Φ29 DNA polymerase (DNAP) is a processive B-family replicative DNAP. Fluctuations between the pre-translocation and post-translocation states can be quantified from ionic current traces, when individual Φ29 DNAP-DNA complexes are held atop a nanopore in an electric field. Based upon crystal structures of the Φ29 DNAP-DNA binary complex and the Φ29 DNAP-DNA-dNTP ternary complex, residues Tyr-226 and Tyr-390 in the polymerase active site were implicated in the structural basis of translocation. Here, we have examined the dynamics of translocation and substrate binding in complexes formed with the Y226F and Y390F mutants. The Y226F mutation diminished the forward and reverse rates of translocation, increased the affinity for dNTP in the post-translocation state by decreasing the dNTP dissociation rate, and increased the affinity for pyrophosphate in the pre-translocation state. The Y390F mutation significantly decreased the affinity for dNTP in the post-translocation state by decreasing the association rate ∼2-fold and increasing the dissociation rate ∼10-fold, implicating this as a mechanism by which this mutation impedes DNA synthesis. The Y390F dissociation rate increase is suppressed when complexes are examined in the presence of Mn(2+) rather than Mg(2+). The same effects of the Y226F or Y390F mutations were observed in the background of the D12A/D66A mutations, located in the exonuclease active site, ∼30 Å from the polymerase active site. Although translocation rates were unaffected in the D12A/D66A mutant, these exonuclease site mutations caused a decrease in the dNTP dissociation rate, suggesting that they perturb Φ29 DNAP interdomain architecture.
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Baldauf, Hanna-Mari; Stegmann, Lena; Schwarz, Sarah-Marie; Ambiel, Ina; Trotard, Maud; Martin, Margarethe; Burggraf, Manja; Lenzi, Gina M; Lejk, Helena; Pan, Xiaoyu; Fregoso, Oliver I; Lim, Efrem S; Abraham, Libin; Nguyen, Laura A; Rutsch, Frank; König, Renate; Kim, Baek; Emerman, Michael; Fackler, Oliver T; Keppler, Oliver T
2017-03-07
Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis. We find that virion-packaged Vpx proteins from a second SIV lineage, SIV of red-capped mangabeys or mandrills (SIVrcm/mnd-2), increased HIV infection in resting CD4 T cells, but not in macrophages, and, unexpectedly, acted in the absence of SAMHD1 degradation, dNTP pool elevation, or changes in SAMHD1 phosphorylation. Vpx rcm/mnd-2 virion incorporation resulted in a dramatic increase of HIV-1 RT intermediates and viral cDNA in infected resting CD4 T cells. These analyses also revealed a barrier limiting HIV-1 infection of resting CD4 T cells at the level of nuclear import. Single amino acid changes in the SAMHD1-degrading Vpx mac239 allowed it to enhance early postentry steps in a Vpx rcm/mnd-2-like fashion. Moreover, Vpx enhanced HIV-1 infection of SAMHD1-deficient resting CD4 T cells of a patient with Aicardi-Goutières syndrome. These results indicate that Vpx, in addition to SAMHD1, overcomes a previously unappreciated restriction for lentiviruses at the level of RT that acts independently of dNTP concentrations and is specific to resting CD4 T cells.
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Molecular Dynamics Study of the Opening Mechanism for DNA Polymerase I
Miller, Bill R.; Parish, Carol A.; Wu, Eugene Y.
2014-01-01
During DNA replication, DNA polymerases follow an induced fit mechanism in order to rapidly distinguish between correct and incorrect dNTP substrates. The dynamics of this process are crucial to the overall effectiveness of catalysis. Although X-ray crystal structures of DNA polymerase I with substrate dNTPs have revealed key structural states along the catalytic pathway, solution fluorescence studies indicate that those key states are populated in the absence of substrate. Herein, we report the first atomistic simulations showing the conformational changes between the closed, open, and ajar conformations of DNA polymerase I in the binary (enzyme∶DNA) state to better understand its dynamics. We have applied long time-scale, unbiased molecular dynamics to investigate the opening process of the fingers domain in the absence of substrate for B. stearothermophilis DNA polymerase in silico. These simulations are biologically and/or physiologically relevant as they shed light on the transitions between states in this important enzyme. All closed and ajar simulations successfully transitioned into the fully open conformation, which is known to be the dominant binary enzyme-DNA conformation from solution and crystallographic studies. Furthermore, we have detailed the key stages in the opening process starting from the open and ajar crystal structures, including the observation of a previously unknown key intermediate structure. Four backbone dihedrals were identified as important during the opening process, and their movements provide insight into the recognition of dNTP substrate molecules by the polymerase binary state. In addition to revealing the opening mechanism, this study also demonstrates our ability to study biological events of DNA polymerase using current computational methods without biasing the dynamics. PMID:25474643
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dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants.
Williams, Lindsey N; Marjavaara, Lisette; Knowels, Gary M; Schultz, Eric M; Fox, Edward J; Chabes, Andrei; Herr, Alan J
2015-05-12
Mutator phenotypes create genetic diversity that fuels tumor evolution. DNA polymerase (Pol) ε mediates leading strand DNA replication. Proofreading defects in this enzyme drive a number of human malignancies. Here, using budding yeast, we show that mutator variants of Pol ε depend on damage uninducible (Dun)1, an S-phase checkpoint kinase that maintains dNTP levels during a normal cell cycle and up-regulates dNTP synthesis upon checkpoint activation. Deletion of DUN1 (dun1Δ) suppresses the mutator phenotype of pol2-4 (encoding Pol ε proofreading deficiency) and is synthetically lethal with pol2-M644G (encoding altered Pol ε base selectivity). Although pol2-4 cells cycle normally, pol2-M644G cells progress slowly through S-phase. The pol2-M644G cells tolerate deletions of mediator of the replication checkpoint (MRC) 1 (mrc1Δ) and radiation sensitive (Rad) 9 (rad9Δ), which encode mediators of checkpoint responses to replication stress and DNA damage, respectively. The pol2-M644G mutator phenotype is partially suppressed by mrc1Δ but not rad9Δ; neither deletion suppresses the pol2-4 mutator phenotype. Thus, checkpoint activation augments the Dun1 effect on replication fidelity but is not required for it. Deletions of genes encoding key Dun1 targets that negatively regulate dNTP synthesis, suppress the dun1Δ pol2-M644G synthetic lethality and restore the mutator phenotype of pol2-4 in dun1Δ cells. DUN1 pol2-M644G cells have constitutively high dNTP levels, consistent with checkpoint activation. In contrast, pol2-4 and POL2 cells have similar dNTP levels, which decline in the absence of Dun1 and rise in the absence of the negative regulators of dNTP synthesis. Thus, dNTP pool levels correlate with Pol ε mutator severity, suggesting that treatments targeting dNTP pools could modulate mutator phenotypes for therapy.
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Synthesis of Mitochondrial DNA Precursors during Myogenesis, an Analysis in Purified C2C12 Myotubes*
Frangini, Miriam; Franzolin, Elisa; Chemello, Francesco; Laveder, Paolo; Romualdi, Chiara; Bianchi, Vera; Rampazzo, Chiara
2013-01-01
During myogenesis, myoblasts fuse into multinucleated myotubes that acquire the contractile fibrils and accessory structures typical of striated skeletal muscle fibers. To support the high energy requirements of muscle contraction, myogenesis entails an increase in mitochondrial (mt) mass with stimulation of mtDNA synthesis and consumption of DNA precursors (dNTPs). Myotubes are quiescent cells and as such down-regulate dNTP production despite a high demand for dNTPs. Although myogenesis has been studied extensively, changes in dNTP metabolism have not been examined specifically. In differentiating cultures of C2C12 myoblasts and purified myotubes, we analyzed expression and activities of enzymes of dNTP biosynthesis, dNTP pools, and the expansion of mtDNA. Myotubes exibited pronounced post-mitotic modifications of dNTP synthesis with a particularly marked down-regulation of de novo thymidylate synthesis. Expression profiling revealed the same pattern of enzyme down-regulation in adult murine muscles. The mtDNA increased steadily after myoblast fusion, turning over rapidly, as revealed after treatment with ethidium bromide. We individually down-regulated p53R2 ribonucleotide reductase, thymidine kinase 2, and deoxyguanosine kinase by siRNA transfection to examine how a further reduction of these synthetic enzymes impacted myotube development. Silencing of p53R2 had little effect, but silencing of either mt kinase caused 50% mtDNA depletion and an unexpected decrease of all four dNTP pools independently of the kinase specificity. We suggest that during development of myotubes the shortage of even a single dNTP may affect all four pools through dysregulation of ribonucleotide reduction and/or dissipation of the non-limiting dNTPs during unproductive elongation of new DNA chains. PMID:23297407
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Franzolin, Elisa; Salata, Cristiano; Bianchi, Vera; Rampazzo, Chiara
2015-01-01
The dNTP triphosphohydrolase SAMHD1 is a nuclear antiviral host restriction factor limiting HIV-1 infection in macrophages and a major regulator of dNTP concentrations in human cells. In normal human fibroblasts its expression increases during quiescence, contributing to the small dNTP pool sizes of these cells. Down-regulation of SAMHD1 by siRNA expands all four dNTP pools, with dGTP undergoing the largest relative increase. The deoxyguanosine released by SAMHD1 from dGTP can be phosphorylated inside mitochondria by deoxyguanosine kinase (dGK) or degraded in the cytosol by purine nucleoside phosphorylase. Genetic mutations of dGK cause mitochondrial (mt) DNA depletion in noncycling cells and hepato-cerebral mtDNA depletion syndrome in humans. We studied if SAMHD1 and dGK interact in the regulation of the dGTP pool during quiescence employing dGK-mutated skin fibroblasts derived from three unrelated patients. In the presence of SAMHD1 quiescent mutant fibroblasts manifested mt dNTP pool imbalance and mtDNA depletion. When SAMHD1 was silenced by siRNA transfection the composition of the mt dNTP pool approached that of the controls, and mtDNA copy number increased, compensating the depletion to various degrees in the different mutant fibroblasts. Chemical inhibition of purine nucleoside phosphorylase did not improve deoxyguanosine recycling by dGK in WT cells. We conclude that the activity of SAMHD1 contributes to the pathological phenotype of dGK deficiency. Our results prove the importance of SAMHD1 in the regulation of all dNTP pools and suggest that dGK inside mitochondria has the function of recycling the deoxyguanosine derived from endogenous dGTP degraded by SAMHD1 in the nucleus. PMID:26342080
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Targeting Nucleotide Biosynthesis: A Strategy for Improving the Oncolytic Potential of DNA Viruses
Irwin, Chad R.; Hitt, Mary M.; Evans, David H.
2017-01-01
The rapid growth of tumors depends upon elevated levels of dNTPs, and while dNTP concentrations are tightly regulated in normal cells, this control is often lost in transformed cells. This feature of cancer cells has been used to advantage to develop oncolytic DNA viruses. DNA viruses employ many different mechanisms to increase dNTP levels in infected cells, because the low concentration of dNTPs found in non-cycling cells can inhibit virus replication. By disrupting the virus-encoded gene(s) that normally promote dNTP biosynthesis, one can assemble oncolytic versions of these agents that replicate selectively in cancer cells. This review covers the pathways involved in dNTP production, how they are dysregulated in cancer cells, and the various approaches that have been used to exploit this biology to improve the tumor specificity of oncolytic viruses. In particular, we compare and contrast the ways that the different types of oncolytic virus candidates can directly modulate these processes. We limit our review to the large DNA viruses that naturally encode homologs of the cellular enzymes that catalyze dNTP biogenesis. Lastly, we consider how this knowledge might guide future development of oncolytic viruses. PMID:29018771
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Mitochondrial deoxyribonucleoside triphosphate pools in thymidine kinase 2 deficiency.
Saada, Ann; Ben-Shalom, Efrat; Zyslin, Rivka; Miller, Chaya; Mandel, Hanna; Elpeleg, Orly
2003-10-24
Deficiency of mitochondrial thymidine kinase (TK2) is associated with mitochondrial DNA (mtDNA) depletion and manifests by severe skeletal myopathy in infancy. In order to elucidate the pathophysiology of this condition, mitochondrial deoxyribonucleoside triphosphate (dNTP) pools were determined in patients' fibroblasts. Despite normal mtDNA content and cytochrome c oxidase (COX) activity, mitochondrial dNTP pools were imbalanced. Specifically, deoxythymidine triphosphate (dTTP) content was markedly decreased, resulting in reduced dTTP:deoxycytidine triphosphate ratio. These findings underline the importance of balanced mitochondrial dNTP pools for mtDNA synthesis and may serve as the basis for future therapeutic interventions.
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-17
... Dr. Ruth Lunn, Director, ORoC, DNTP, NIEHS, P.O. Box 12233, MD K2-14, Research Triangle Park, NC..., ORoC, DNTP, NIEHS, P.O. Box 12233, MD K2-14, Research Triangle Park, NC 27709; telephone (919) 316...
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MPV17 Loss Causes Deoxynucleotide Insufficiency and Slow DNA Replication in Mitochondria
Dalla Rosa, Ilaria; Cámara, Yolanda; Durigon, Romina; Moss, Chloe F.; Vidoni, Sara; Akman, Gokhan; Hunt, Lilian; Johnson, Mark A.; Grocott, Sarah; Wang, Liya; Thorburn, David R.; Hirano, Michio; Poulton, Joanna; Taylor, Robert W.; Elgar, Greg; Martí, Ramon; Voshol, Peter; Holt, Ian J.; Spinazzola, Antonella
2016-01-01
MPV17 is a mitochondrial inner membrane protein whose dysfunction causes mitochondrial DNA abnormalities and disease by an unknown mechanism. Perturbations of deoxynucleoside triphosphate (dNTP) pools are a recognized cause of mitochondrial genomic instability; therefore, we determined DNA copy number and dNTP levels in mitochondria of two models of MPV17 deficiency. In Mpv17 ablated mice, liver mitochondria showed substantial decreases in the levels of dGTP and dTTP and severe mitochondrial DNA depletion, whereas the dNTP pool was not significantly altered in kidney and brain mitochondria that had near normal levels of DNA. The shortage of mitochondrial dNTPs in Mpv17-/- liver slows the DNA replication in the organelle, as evidenced by the elevated level of replication intermediates. Quiescent fibroblasts of MPV17-mutant patients recapitulate key features of the primary affected tissue of the Mpv17-/- mice, displaying virtual absence of the protein, decreased dNTP levels and mitochondrial DNA depletion. Notably, the mitochondrial DNA loss in the patients’ quiescent fibroblasts was prevented and rescued by deoxynucleoside supplementation. Thus, our study establishes dNTP insufficiency in the mitochondria as the cause of mitochondrial DNA depletion in MPV17 deficiency, and identifies deoxynucleoside supplementation as a potential therapeutic strategy for MPV17-related disease. Moreover, changes in the expression of factors involved in mitochondrial deoxynucleotide homeostasis indicate a remodeling of nucleotide metabolism in MPV17 disease models, which suggests mitochondria lacking functional MPV17 have a restricted purine mitochondrial salvage pathway. PMID:26760297
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Wilson, Peter M.; LaBonte, Melissa J.; Russell, Jared; Louie, Stan; Ghobrial, Andrew A.; Ladner, Robert D.
2011-01-01
Current methods for measuring deoxyribonucleoside triphosphates (dNTPs) employ reagent and labor-intensive assays utilizing radioisotopes in DNA polymerase-based assays and/or chromatography-based approaches. We have developed a rapid and sensitive 96-well fluorescence-based assay to quantify cellular dNTPs utilizing a standard real-time PCR thermocycler. This assay relies on the principle that incorporation of a limiting dNTP is required for primer-extension and Taq polymerase-mediated 5–3′ exonuclease hydrolysis of a dual-quenched fluorophore-labeled probe resulting in fluorescence. The concentration of limiting dNTP is directly proportional to the fluorescence generated. The assay demonstrated excellent linearity (R2 > 0.99) and can be modified to detect between ∼0.5 and 100 pmol of dNTP. The limits of detection (LOD) and quantification (LOQ) for all dNTPs were defined as <0.77 and <1.3 pmol, respectively. The intra-assay and inter-assay variation coefficients were determined to be <4.6% and <10%, respectively with an accuracy of 100 ± 15% for all dNTPs. The assay quantified intracellular dNTPs with similar results obtained from a validated LC–MS/MS approach and successfully measured quantitative differences in dNTP pools in human cancer cells treated with inhibitors of thymidylate metabolism. This assay has important application in research that investigates the influence of pathological conditions or pharmacological agents on dNTP biosynthesis and regulation. PMID:21576234
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The mechano-chemistry of a monomeric reverse transcriptase
Malik, Omri; Khamis, Hadeel; Rudnizky, Sergei
2017-01-01
Abstract Retroviral reverse transcriptase catalyses the synthesis of an integration-competent dsDNA molecule, using as a substrate the viral RNA. Using optical tweezers, we follow the Murine Leukemia Virus reverse transcriptase as it performs strand-displacement polymerization on a template under mechanical force. Our results indicate that reverse transcriptase functions as a Brownian ratchet, with dNTP binding as the rectifying reaction of the ratchet. We also found that reverse transcriptase is a relatively passive enzyme, able to polymerize on structured templates by exploiting their thermal breathing. Finally, our results indicate that the enzyme enters the recently characterized backtracking state from the pre-translocation complex. PMID:29165701
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Bradshaw, Elliot; Yoshida, Minoru; Ling, Feng
2017-01-01
Small mitochondrial genomes can behave as selfish elements by displacing wild-type genomes regardless of their detriment to the host organism. In the budding yeast Saccharomyces cerevisiae, small hypersuppressive mtDNA transiently coexist with wild-type in a state of heteroplasmy, wherein the replicative advantage of the small mtDNA outcompetes wild-type and produces offspring without respiratory capacity in >95% of colonies. The cytosolic enzyme ribonucleotide reductase (RNR) catalyzes the rate-limiting step in dNTP synthesis and its inhibition has been correlated with increased petite colony formation, reflecting loss of respiratory function. Here, we used heteroplasmic diploids containing wild-type (rho+) and suppressive (rho−) or hypersuppressive (HS rho−) mitochondrial genomes to explore the effects of RNR activity on mtDNA heteroplasmy in offspring. We found that the proportion of rho+ offspring was significantly increased by RNR overexpression or deletion of its inhibitor, SML1, while reducing RNR activity via SML1 overexpression produced the opposite effects. In addition, using Ex Taq and KOD Dash polymerases, we observed a replicative advantage for small over large template DNA in vitro, but only at low dNTP concentrations. These results suggest that dNTP insufficiency contributes to the replicative advantage of small mtDNA over wild-type and cytosolic dNTP synthesis by RNR is an important regulator of heteroplasmy involving small mtDNA molecules in yeast. PMID:28717049
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Suppression of the E. coli SOS response by dNTP pool changes.
Maslowska, Katarzyna H; Makiela-Dzbenska, Karolina; Fijalkowska, Iwona J; Schaaper, Roel M
2015-04-30
The Escherichia coli SOS system is a well-established model for the cellular response to DNA damage. Control of SOS depends largely on the RecA protein. When RecA is activated by single-stranded DNA in the presence of a nucleotide triphosphate cofactor, it mediates cleavage of the LexA repressor, leading to expression of the 30(+)-member SOS regulon. RecA activation generally requires the introduction of DNA damage. However, certain recA mutants, like recA730, bypass this requirement and display constitutive SOS expression as well as a spontaneous (SOS) mutator effect. Presently, we investigated the possible interaction between SOS and the cellular deoxynucleoside triphosphate (dNTP) pools. We found that dNTP pool changes caused by deficiencies in the ndk or dcd genes, encoding nucleoside diphosphate kinase and dCTP deaminase, respectively, had a strongly suppressive effect on constitutive SOS expression in recA730 strains. The suppression of the recA730 mutator effect was alleviated in a lexA-deficient background. Overall, the findings suggest a model in which the dNTP alterations in the ndk and dcd strains interfere with the activation of RecA, thereby preventing LexA cleavage and SOS induction. Published by Oxford University Press on behalf of Nucleic Acids Research 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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SAMHD1 enhances nucleoside-analogue efficacy against HIV-1 in myeloid cells
Ordonez, Paula; Kunzelmann, Simone; Groom, Harriet C. T.; Yap, Melvyn W.; Weising, Simon; Meier, Chris; Bishop, Kate N.; Taylor, Ian A.; Stoye, Jonathan P.
2017-01-01
SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level that cannot support productive reverse transcription. We now show that, in addition to this direct effect on virus replication, manipulating cellular SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotide analogue reverse transcription inhibitors presumably as a result of modulating dNTP pools that compete for recruitment by viral polymerases. Further, a variety of other nucleotide-based analogues, not normally considered antiretrovirals, such as the anti-herpes drugs Aciclovir and Ganciclovir and the anti-cancer drug Clofarabine are now revealed as potent anti-HIV-1 agents, under conditions of low dNTPs. This in turn suggests novel uses for nucleotide analogues to inhibit HIV-1 in differentiated cells low in dNTPs. PMID:28220857
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Hinge residue I174 is critical for proper dNTP selection by DNA polymerase beta.
Yamtich, Jen; Starcevic, Daniela; Lauper, Julia; Smith, Elenoe; Shi, Idina; Rangarajan, Sneha; Jaeger, Joachim; Sweasy, Joann B
2010-03-23
DNA polymerase beta (pol beta) is the key gap-filling polymerase in base excision repair, the DNA repair pathway responsible for repairing up to 20000 endogenous lesions per cell per day. Pol beta is also widely used as a model polymerase for structure and function studies, and several structural regions have been identified as being critical for the fidelity of the enzyme. One of these regions is the hydrophobic hinge, a network of hydrophobic residues located between the palm and fingers subdomains. Previous work by our lab has shown that hinge residues Y265, I260, and F272 are critical for polymerase fidelity by functioning in discrimination of the correct from incorrect dNTP during ground state binding. Our work aimed to elucidate the role of hinge residue I174 in polymerase fidelity. To study this residue, we conducted a genetic screen to identify mutants with a substitution at residue I174 that resulted in a mutator polymerase. We then chose the mutator mutant I174S for further study and found that it follows the same general kinetic pathway as and has an overall protein folding similar to that of wild-type (WT) pol beta. Using single-turnover kinetic analysis, we found that I174S exhibits decreased fidelity when inserting a nucleotide opposite a template base G, and this loss of fidelity is due primarily to a loss of discrimination during ground state dNTP binding. Molecular dynamics simulations show that mutation of residue I174 to serine results in an overall tightening of the hinge region, resulting in aberrant protein dynamics and fidelity. These results point to the hinge region as being critical in the maintenance of the proper geometry of the dNTP binding pocket.
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Masaoka, Takashi; Chung, Suhman; Caboni, Pierluigi; Rausch, Jason W.; Wilson, Jennifer A.; Taskent-Sezgin, Humeyra; Beutler, John A.; Tocco, Graziella; Le Grice, Stuart F. J.
2013-01-01
The thienopyrimidinone 5,6-dimethyl-2-(4-nitrophenyl)thieno[2,3-d]pyrimidin-4(3H)-one (DNTP) occupies the interface between the p66 ribonuclease H (RNase H) domain and p51 thumb of human immunodeficiency virus reverse transcriptase (HIV RT), thereby inducing a conformational change incompatible with catalysis. Here, we combined biochemical characterization of 39 DNTP derivatives with antiviral testing of selected compounds. In addition to wild-type HIV-1 RT, derivatives were evaluated with rationally-designed, p66/p51 heterodimers exhibiting high-level DNTP sensitivity or resistance. This strategy identified 3′,4′-dihydroxyphenyl (catechol)-substituted thienopyrimidinones with sub-micromolar in vitro activity against both wild type HIV-1 RT and drug-resistant variants. Thermal shift analysis indicates that, in contrast to active site RNase H inhibitors, these thienopyrimidinones destabilize the enzyme, in some instances reducing the Tm by 5°C. Importantly, catechol-containing thienopyrimidinones also inhibit HIV-1 replication in cells. Our data strengthens the case for allosteric inhibition of HIV RNase H activity, providing a platform for designing improved antagonists for use in combination antiviral therapy. PMID:23631411
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Allosteric dynamics of SAMHD1 studied by molecular dynamics simulations
NASA Astrophysics Data System (ADS)
Patra, K. K.; Bhattacharya, A.; Bhattacharya, S.
2016-10-01
SAMHD1 is a human cellular enzyme that blocks HIV-1 infection in myeloid cells and non-cycling CD4+T cells. The enzyme is an allosterically regulated triphosphohydrolase that modulates the level of cellular dNTP. The virus restriction is attributed to the lowering of the pool of dNTP in the cell to a point where reverse-transcription is impaired. Mutations in SAMHD1 are also implicated in Aicardi-Goutieres syndrome. A mechanistic understanding of the allosteric activation of the enzyme is still elusive. We have performed molecular dynamics simulations to examine the allosteric site dynamics of the protein and to examine the connection between the stability of the tetrameric complex and the Allosite occupancy.
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Gandhi, Vishal V.; Samuels, David C.
2011-01-01
Using a computational model, we simulated mitochondrial deoxynucleotide metabolism and mitochondrial DNA replication. Our results indicate that the output from the mitochondrial salvage enzymes alone is inadequate to support a mitochondrial DNA replication duration of as long as 10 hours. We find that an external source of deoxyribonucleoside diphosphates or triphosphates (dNTPs), in addition to those supplied by mitochondrial salvage, is essential for the replication of mitochondrial DNA to complete in the experimentally observed duration of approximately 1 to 2 hours. For meeting a relatively fast replication target of 2 hours, almost two-thirds of the dNTP requirements had to be externally supplied as either deoxyribonucleoside di- or triphosphates, at about equal rates for all four dNTPs. Added monophosphates did not suffice. However, for a replication target of 10 hours, mitochondrial salvage was able to provide for most, but not all, of the total substrate requirements. Still, additional dGTPs and dATPs had to be supplied. Our analysis of the enzyme kinetics also revealed that the majority of enzymes of this pathway prefer substrates that are not precursors (canonical deoxyribonucleosides and deoxyribonucleotides) for mitochondrial DNA replication, such as phosphorylated ribonucleotides, instead of the corresponding deoxyribonucleotides. The kinetic constants for reactions between mitochondrial salvage enzymes and deoxyribonucleotide substrates are physiologically unreasonable for achieving efficient catalysis with the expected in situ concentrations of deoxyribonucleotides. PMID:21829339
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SAMHD1 knockout mice: modeling retrovirus restriction in vivo.
Wu, Li
2013-11-20
The host dNTP hydrolase SAMHD1 acts as a viral restriction factor to inhibit the replication of several retroviruses and DNA viruses in non-cycling human immune cells. However, understanding the physiological role of mammalian SAMHD1 has been elusive due to the lack of an animal model. Two recent studies reported the generation of samhd1 knockout mouse models for investigating the restriction of HIV-1 vectors and endogenous retroviruses in vivo. Both studies suggest that SAMHD1 is important for regulating the intracellular dNTP pool and the intrinsic immunity against retroviral infection, despite different outcomes of HIV-1 vector transduction in these mouse models. Here I discuss the significance of these new findings and the future directions in studying SAMHD1-mediated retroviral restriction.
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Oz-Gleenberg, Iris; Herzig, Eytan; Hizi, Amnon
2012-01-01
Reverse transcriptases (RTs) possess a non-templated addition (NTA) activity while synthesizing DNA with blunt-ended DNA primer/templates. Interestingly, the RT of the long terminal repeat retrotransposon Tf1 has an NTA activity that is substantially higher than that of HIV-1 or murine leukemia virus RTs. By performing steady state kinetics, we found that the differences between the NTA activities of Tf1 and HIV-1 RTs can be explained by the substantially lower K(M) value for the incoming dNTP of Tf1 RT (while the differences between the apparent k(cat) values of these two RTs are relatively small). Furthermore, the K(M) values, calculated for both RTs with the same dNTP, are much lower for the template-dependent synthesis (TDS) than those of NTA. However, TDS of HIV-1 RT is higher than that of Tf1 RT. The overall relative order of the apparent k(cat)/K(M) values for dATP is: HIV-1 RT (TDS) > Tf1 RT (TDS) > Tf1 RT (NTA) > HIV-1 RT (NTA). Under the employed conditions, Tf1 RT can add up to seven nucleotides to the blunt-ended substrate, while the other RTs add mostly a single nucleotide. The NTA activity of Tf1 RT is restricted to DNA primers. Furthermore, the NTA activity of Tf1 and HIV-1 RTs is suppressed by ATP, as it competes with the incoming dATP (although ATP is not incorporated by the NTA activity of the RTs). The unusually high NTA activity of Tf1 RT can explain why, after completing cDNA synthesis, the in vivo generated Tf1 cDNA has relatively long extra sequences beyond the highly conserved CA at its 3'-ends. © 2011 The Authors Journal compilation © 2011 FEBS.
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A time to be stressed? Time perspectives and cortisol dynamics among healthy adults.
Olivera-Figueroa, Lening A; Juster, Robert-Paul; Morin-Major, Julie Katia; Marin, Marie-France; Lupien, Sonia J
2015-10-01
Perceptions of past, present, and future events may be related to stress pathophysiology. We assessed whether Time Perspective (TP) is associated with cortisol dynamics among healthy adults (N=61, Ages=18-35, M=22.9, SD=4.1) exposed to the Trier Social Stress Test (TSST). TP was measured according to two profiles: maladaptive Deviation from Balanced TP (DBTP) and adaptive Deviation from Negative TP (DNTP). Eight salivary cortisol samples were analyzed using area under the curve with respect to ground (AUCg) and to increase (AUCi). Statistic analyses involved partial correlations controlling for depressive symptoms. Results for both sexes showed that higher DBTP scores were associated with lower cortisol AUCg scores, while higher DNTP scores were associated with higher cortisol AUCg scores. These novel findings suggest that maladaptive TP profiles influence hypocortisolism, whereas adaptive TP profiles influence hypercortisolism. Thus, TP profiles may impact conditions characterized by altered cortisol concentrations. Published by Elsevier B.V.
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Krishnan, Shuba; Paredes, João A.; Zhou, Xiaoshan; Kuiper, Raoul V.; Hultenby, Kjell; Curbo, Sophie; Karlsson, Anna
2014-01-01
Mitochondrial DNA depletion caused by thymidine kinase 2 (TK2) deficiency can be compensated by a nucleoside kinase from Drosophila melanogaster (Dm-dNK) in mice. We show that transgene expression of Dm-dNK in Tk2 knock-out (Tk2−/−) mice extended the life span of Tk2−/− mice from 3 weeks to at least 20 months. The Dm-dNK+/−Tk2−/− mice maintained normal mitochondrial DNA levels throughout the observation time. A significant difference in total body weight due to the reduction of subcutaneous and visceral fat in the Dm-dNK+/−Tk2−/− mice was the only visible difference compared with control mice. This indicates an effect on fat metabolism mediated through residual Tk2 deficiency because Dm-dNK expression was low in both liver and fat tissues. Dm-dNK expression led to increased dNTP pools and an increase in the catabolism of purine and pyrimidine nucleotides but these alterations did not apparently affect the mice during the 20 months of observation. In conclusion, Dm-dNK expression in the cell nucleus expanded the total dNTP pools to levels required for efficient mitochondrial DNA synthesis, thereby compensated the Tk2 deficiency, during a normal life span of the mice. The Dm-dNK+/− mouse serves as a model for nucleoside gene or enzyme substitutions, nucleotide imbalances, and dNTP alterations in different tissues. PMID:25296759
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Krishnan, Shuba; Paredes, João A; Zhou, Xiaoshan; Kuiper, Raoul V; Hultenby, Kjell; Curbo, Sophie; Karlsson, Anna
2014-11-21
Mitochondrial DNA depletion caused by thymidine kinase 2 (TK2) deficiency can be compensated by a nucleoside kinase from Drosophila melanogaster (Dm-dNK) in mice. We show that transgene expression of Dm-dNK in Tk2 knock-out (Tk2(-/-)) mice extended the life span of Tk2(-/-) mice from 3 weeks to at least 20 months. The Dm-dNK(+/-)Tk2(-/-) mice maintained normal mitochondrial DNA levels throughout the observation time. A significant difference in total body weight due to the reduction of subcutaneous and visceral fat in the Dm-dNK(+/-)Tk2(-/-) mice was the only visible difference compared with control mice. This indicates an effect on fat metabolism mediated through residual Tk2 deficiency because Dm-dNK expression was low in both liver and fat tissues. Dm-dNK expression led to increased dNTP pools and an increase in the catabolism of purine and pyrimidine nucleotides but these alterations did not apparently affect the mice during the 20 months of observation. In conclusion, Dm-dNK expression in the cell nucleus expanded the total dNTP pools to levels required for efficient mitochondrial DNA synthesis, thereby compensated the Tk2 deficiency, during a normal life span of the mice. The Dm-dNK(+/-) mouse serves as a model for nucleoside gene or enzyme substitutions, nucleotide imbalances, and dNTP alterations in different tissues. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
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Mechanism of Ribonucleotide Incorporation by Human DNA Polymerase η*
Su, Yan; Egli, Martin; Guengerich, F. Peter
2016-01-01
Ribonucleotides and 2′-deoxyribonucleotides are the basic units for RNA and DNA, respectively, and the only difference is the extra 2′-OH group on the ribonucleotide sugar. Cellular rNTP concentrations are much higher than those of dNTP. When copying DNA, DNA polymerases not only select the base of the incoming dNTP to form a Watson-Crick pair with the template base but also distinguish the sugar moiety. Some DNA polymerases use a steric gate residue to prevent rNTP incorporation by creating a clash with the 2′-OH group. Y-family human DNA polymerase η (hpol η) is of interest because of its spacious active site (especially in the major groove) and tolerance of DNA lesions. Here, we show that hpol η maintains base selectivity when incorporating rNTPs opposite undamaged DNA and the DNA lesions 7,8-dihydro-8-oxo-2′-deoxyguanosine and cyclobutane pyrimidine dimer but with rates that are 103-fold lower than for inserting the corresponding dNTPs. X-ray crystal structures show that the hpol η scaffolds the incoming rNTP to pair with the template base (dG) or 7,8-dihydro-8-oxo-2′-deoxyguanosine with a significant propeller twist. As a result, the 2′-OH group avoids a clash with the steric gate, Phe-18, but the distance between primer end and Pα of the incoming rNTP increases by 1 Å, elevating the energy barrier and slowing polymerization compared with dNTP. In addition, Tyr-92 was identified as a second line of defense to maintain the position of Phe-18. This is the first crystal structure of a DNA polymerase with an incoming rNTP opposite a DNA lesion. PMID:26740629
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Mixtures Research at NIEHS: An Evolving Program
Rider, Cynthia V; Carlin, Danielle J; DeVito, Micheal J; Thompson, Claudia L; Walker, Nigel J
2014-01-01
The National Institute of Environmental Health Sciences (NIEHS) has a rich history in evaluating the toxicity of mixtures. The types of mixtures assessed by the Division of the National Toxicology Program (DNTP) and the extramural community (through the Division of Extramural Research and Training (DERT)) have included a broad range of chemicals and toxicants, with each study having a unique set of questions and design considerations. Some examples of the types of mixtures studied include: groundwater contaminants, pesticides/fertilizers, dioxin-like chemicals (assessing the toxic equivalency approach), drug combinations, air pollution, metals, polycyclic aromatic hydrocarbons, technical mixtures (e.g. pentachlorophenol, flame retardants), and mixed entities (e.g. herbals, asbestos). These endeavors have provided excellent data on the toxicity of specific mixtures and have been informative to the human health risk assessment process in general (e.g. providing data on low dose exposures to environmental chemicals). However, the mixtures research effort at NIEHS, to date, has been driven by test article nominations to the DNTP or by investigator-initiated research through DERT. Recently, the NIEHS has embarked upon an effort to coordinate mixtures research across both intramural and extramural divisions in order to maximize mixtures research results. A path forward for NIEHS mixtures research will be based on feedback from a Request for Information (RFI) designed to gather up-to-date views on the knowledge gaps and roadblocks to evaluating mixtures and performing cumulative risk assessment, and a workshop organized to bring together mixtures experts from risk assessment, exposure science, biology, epidemiology, and statistics. The future of mixtures research at NIEHS will include projects from nominations to DNTP, studies by extramural investigators, and collaborations across government agencies that address high-priority questions in the field of mixtures research. PMID:23146757
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Badia, Roger; Angulo, Guillem; Riveira-Muñoz, Eva; Pujantell, Maria; Puig, Teresa; Ramirez, Cristina; Torres-Torronteras, Javier; Martí, Ramón; Pauls, Eduardo; Clotet, Bonaventura; Ballana, Ester; Esté, José A
2016-02-01
Sterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) has been shown to restrict retroviruses and DNA viruses by decreasing the pool of intracellular deoxynucleotides. In turn, SAMHD1 is controlled by cyclin-dependent kinases (CDK) that regulate the cell cycle and cell proliferation. Here, we explore the effect of CDK6 inhibitors on the replication of herpes simplex virus type 1 (HSV-1) in primary monocyte-derived macrophages (MDM). MDM were treated with palbociclib, a selective CDK4/6 inhibitor, and then infected with a GFP-expressing HSV-1. Intracellular deoxynucleotide triphosphate (dNTP) content was determined using a polymerase-based method. CDK6 inhibitor palbociclib blocked SAMHD1 phosphorylation, intracellular dNTP levels and HSV-1 replication in MDM at subtoxic concentrations. Treatment of MDM with palbociclib reduced CDK2 activation, measured as the phosphorylation of the T-loop at Thr160. The antiviral activity of palbociclib was lost when SAMHD1 was degraded by viral protein X. Similarly, palbociclib did not block HSV-1 replication in SAMHD1-negative Vero cells at subtoxic concentrations, providing further evidence for a role of SAMHD1 in mediating the antiviral effect. SAMHD1-mediated HSV-1 restriction is controlled by CDK and points to a preferential role for CDK6 and CDK2 as mediators of SAMHD1 activation. Similarly, the restricting activity of SAMHD1 against DNA viruses suggests that control of dNTP availability is the major determinant of its antiviral activity. This is the first study describing the anti-HSV-1 activity of palbociclib. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Rutvisuttinunt, Wiriya; Meyer, Peter R.; Scott, Walter A.
2008-01-01
Background Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) forms stable ternary complexes in which RT is bound tightly at fixed positions on the primer-template (P/T). We have probed downstream interactions between RT and the template strand in the complex containing the incoming dNTP (+1 dNTP•RT•P/T complex) and in the complex containing the pyrophosphate analog, foscarnet (foscarnet•RT•P/T complex). Methods and Results UV-induced cross-linking between RT and the DNA template strand was most efficient when a bromodeoxyuridine residue was placed in the +2 position (the first template position downstream from the incoming dNTP). Furthermore, formation of the +1 dNTP•RT•P/T complex on a biotin-containing template inhibited binding of streptavidin when biotin was in the +2 position on the template but not when the biotin was in the +3 position. Streptavidin pre-bound to a biotin residue in the template caused RT to stall two to three nucleotides upstream from the biotin residue. The downstream border of the complex formed by the stalled RT was mapped by digestion with exonuclease RecJF. UV-induced cross-linking of the complex formed by the pyrophosphate analog, foscarnet, with RT and P/T occurred preferentially with bromodeoxyuridine in the +1 position on the template in keeping with the location of RT one base upstream in the foscarnet•RT•P/T complex (i.e., in the pre-translocation position). Conclusions For +1 dNTP•RT•P/T and foscarnet•RT•P/T stable complexes, tight interactions were observed between RT and the first unpaired template nucleotide following the bound dNTP or the primer terminus, respectively. PMID:18974785
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-07-09
... Alternative Toxicological Methods (SACATM) AGENCY: Division of the National Toxicology Program (DNTP.../live ). SACATM advises the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM...
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Selvaraj, Shanmugapriya; Ghebremichael, Musie; Li, Min; Foli, Yram; Langs-Barlow, Allison; Ogbuagu, Arit; Barakat, Lydia; Tubridy, Elizabeth; Edifor, Regina; Lam, Wing; Cheng, Yung-Chi; Paintsil, Elijah
2014-01-01
We hypothesized that competition between NRTI-triphosphate and endogenous deoxyribonucleoside triphosphate (dNTP) may lead to depletion of dNTP pools and mitochondrial dysfunction independent of Pol-γ inhibition. We collected peripheral blood mononuclear cells from 75 adults (25 cases: HIV-infected with mitochondrial toxicity, 25 HIV-infected positive controls, and 25 HIV-negative controls). We observed statistically significant individual and group differences in ribonucleotide (RN) and deoxyribonucleotide (dRN) pools. The median RN pool was 10062 (IQR, 7090 – 12590), 4360 (IQR, 3058 –6838), and 2968 (IQR, 2538 – 4436) pmol/106 cells for negative controls, positive controls, and cases, respectively. Cases had significantly higher absolute mtDNA copy number compared to negative controls (p<0.05). Cases had significantly higher expression of Pol-γ, nucleoside transporters, cellular kinases, and ABC compared to controls. Antiretroviral therapy perturbs ribonucleotide and deoxyribonucleotide pools. Depletion of RN and dRN pools may be associated with ART-induced mitochondrial toxicity independent of Pol-γ inhibition. PMID:24637942
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Nilforoushan, Arman; Furrer, Antonia; Wyss, Laura A; van Loon, Barbara; Sturla, Shana J
2015-04-15
Human DNA polymerase η (hPol η) contributes to anticancer drug resistance by catalyzing the replicative bypass of DNA adducts formed by the widely used chemotherapeutic agent cis-diamminedichloroplatinum (cisplatin). A chemical basis for overcoming bypass-associated resistance requires greater knowledge of how small molecules influence the hPol η-catalyzed bypass of DNA adducts. In this study, we demonstrated how synthetic nucleoside triphosphates act as hPol η substrates and characterized their influence on hPol η-mediated DNA synthesis over unmodified and platinated DNA. The single nucleotide incorporation efficiency of the altered nucleotides varied by more than 10-fold and the higher incorporation rates appeared to be attributable to the presence of an additional hydrogen bond between incoming dNTP and templating base. Finally, full-length DNA synthesis in the presence of increasing concentrations of synthetic nucleotides reduced the amount of DNA product independent of the template, representing the first example of hPol η inhibition in the presence of a platinated DNA template.
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Anacker, Daniel C.; Aloor, Heather L.; Shepard, Caitlin N.; Lenzi, Gina M.; Johnson, Bryan A.; Kim, Baek; Moody, Cary A.
2016-01-01
Productive replication of human papillomaviruses (HPV) is restricted to the uppermost layers of the differentiating epithelia. How HPV ensures an adequate supply of cellular substrates for viral DNA synthesis in a differentiating environment is unclear. Here, we demonstrate that HPV31 positive cells exhibit increased dNTP pools and levels of RRM2, a component of the ribonucleotide reductase (RNR) complex, which is required for de novo synthesis of dNTPs. RRM2 depletion blocks productive replication, suggesting RRM2 provides dNTPs for viral DNA synthesis in differentiating cells. We demonstrate that HPV31 regulates RRM2 levels through expression of E7 and activation of the ATR-Chk1-E2F1 DNA damage response, which is essential to combat replication stress upon entry into S-phase, as well as for productive replication. Our findings suggest a novel way in which viral DNA synthesis is regulated through activation of ATR and Chk1 and highlight an intriguing new virus/host interaction utilized for viral replication. PMID:27764728
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-07
... and Translation Evaluation of the State of the Science for Transgenerational Inheritance of Health Effects; Request for Information SUMMARY: The Office of Health Assessment and Translation (OHAT) of the Division of the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences...
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Vorontsov, Ivan I.; Minasov, George; Kiryukhina, Olga
2012-06-19
The EF1143 protein from Enterococcus faecalis is a distant homolog of deoxynucleotide triphosphate triphosphohydrolases (dNTPases) from Escherichia coli and Thermus thermophilus. These dNTPases are important components in the regulation of the dNTP pool in bacteria. Biochemical assays of the EF1143 dNTPase activity demonstrated nonspecific hydrolysis of all canonical dNTPs in the presence of Mn{sup 2+}. In contrast, with Mg{sup 2+} hydrolysis required the presence of dGTP as an effector, activating the degradation of dATP and dCTP with dGTP also being consumed in the reaction with dATP. The crystal structure of EF1143 and dynamic light scattering measurements in solution revealed amore » tetrameric oligomer as the most probable biologically active unit. The tetramer contains four dGTP specific allosteric regulatory sites and four active sites. Examination of the active site with the dATP substrate suggests an in-line nucleophilic attack on the {alpha}-phosphate center as a possible mechanism of the hydrolysis and two highly conserved residues, His-129 and Glu-122, as an acid-base catalytic dyad. Structural differences between EF1143 apo and holo forms revealed mobility of the {alpha}3 helix that can regulate the size of the active site binding pocket and could be stabilized in the open conformation upon formation of the tetramer and dGTP effector binding.« less
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-28
... Contact Dermatitis in Humans AGENCY: Division of the National Toxicology Program (DNTP), National... categorizing the potency of substances with the potential to cause allergic contact dermatitis (ACD) as strong... Contact Dermatitis in Humans (NIH Publication No. 11-7709), describes ICCVAM's recommendations for using...
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Berglund, Anna-Karin; Navarrete, Clara; Engqvist, Martin K M; Hoberg, Emily; Szilagyi, Zsolt; Taylor, Robert W; Gustafsson, Claes M; Falkenberg, Maria; Clausen, Anders R
2017-02-01
Previous work has demonstrated the presence of ribonucleotides in human mitochondrial DNA (mtDNA) and in the present study we use a genome-wide approach to precisely map the location of these. We find that ribonucleotides are distributed evenly between the heavy- and light-strand of mtDNA. The relative levels of incorporated ribonucleotides reflect that DNA polymerase γ discriminates the four ribonucleotides differentially during DNA synthesis. The observed pattern is also dependent on the mitochondrial deoxyribonucleotide (dNTP) pools and disease-causing mutations that change these pools alter both the absolute and relative levels of incorporated ribonucleotides. Our analyses strongly suggest that DNA polymerase γ-dependent incorporation is the main source of ribonucleotides in mtDNA and argues against the existence of a mitochondrial ribonucleotide excision repair pathway in human cells. Furthermore, we clearly demonstrate that when dNTP pools are limiting, ribonucleotides serve as a source of building blocks to maintain DNA replication. Increased levels of embedded ribonucleotides in patient cells with disturbed nucleotide pools may contribute to a pathogenic mechanism that affects mtDNA stability and impair new rounds of mtDNA replication.
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Delagoutte, Emmanuelle; Baldacci, Giuseppe
2011-01-01
Instability of repetitive sequences originates from strand misalignment during repair or replicative DNA synthesis. To investigate the activity of reconstituted T4 replisomes across trinucleotide repeats (TNRs) during leading strand DNA synthesis, we developed a method to build replication miniforks containing a TNR unit of defined sequence and length. Each minifork consists of three strands, primer, leading strand template, and lagging strand template with a 5′ single-stranded (ss) tail. Each strand is prepared independently, and the minifork is assembled by hybridization of the three strands. Using these miniforks and a minimal reconstituted T4 replisome, we show that during leading strand DNA synthesis, the dNTP concentration dictates which strand of the structure-forming 5′CAG/5′CTG repeat creates the strongest impediment to the minimal replication complex. We discuss this result in the light of the known fluctuation of dNTP concentration during the cell cycle and cell growth and the known concentration balance among individual dNTPs. PMID:22096622
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SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bonifati, Serena; Daly, Michele B.; St Gelais, Corine
SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G{sub 1}/G{sub 0} phase and reduces apoptosis. These alterationsmore » correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.« less
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Pai, Chen-Chun; Kishkevich, Anastasiya; Deegan, Rachel S; Keszthelyi, Andrea; Folkes, Lisa; Kearsey, Stephen E; De León, Nagore; Soriano, Ignacio; de Bruin, Robertus Antonius Maria; Carr, Antony M; Humphrey, Timothy C
2017-09-12
Chromatin modification through histone H3 lysine 36 methylation by the SETD2 tumor suppressor plays a key role in maintaining genome stability. Here, we describe a role for Set2-dependent H3K36 methylation in facilitating DNA replication and the transcriptional responses to both replication stress and DNA damage through promoting MluI cell-cycle box (MCB) binding factor (MBF)-complex-dependent transcription in fission yeast. Set2 loss leads to reduced MBF-dependent ribonucleotide reductase (RNR) expression, reduced deoxyribonucleoside triphosphate (dNTP) synthesis, altered replication origin firing, and a checkpoint-dependent S-phase delay. Accordingly, prolonged S phase in the absence of Set2 is suppressed by increasing dNTP synthesis. Furthermore, H3K36 is di- and tri-methylated at these MBF gene promoters, and Set2 loss leads to reduced MBF binding and transcription in response to genotoxic stress. Together, these findings provide new insights into how H3K36 methylation facilitates DNA replication and promotes genotoxic stress responses in fission yeast. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Tai, Akiko; Kamei, Yuka; Mukai, Yukio
In eukaryotes, numerous genetic factors contribute to the lifespan including metabolic enzymes, signal transducers, and transcription factors. As previously reported, the forkhead-like transcription factor (FHL1) gene was required for yeast replicative lifespan and cell proliferation. To determine how Fhl1p regulates the lifespan, we performed a DNA microarray analysis of a heterozygous diploid strain deleted for FHL1. We discovered numerous Fhl1p-target genes, which were then screened for lifespan-regulating activity. We identified the ribonucleotide reductase (RNR) 1 gene (RNR1) as a regulator of replicative lifespan. RNR1 encodes a large subunit of the RNR complex, which consists of two large (Rnr1p/Rnr3p) and twomore » small (Rnr2p/Rnr4p) subunits. Heterozygous deletion of FHL1 reduced transcription of RNR1 and RNR3, but not RNR2 and RNR4. Chromatin immunoprecipitation showed that Fhl1p binds to the promoter regions of RNR1 and RNR3. Cells harboring an RNR1 deletion or an rnr1-C428A mutation, which abolishes RNR catalytic activity, exhibited a short lifespan. In contrast, cells with a deletion of the other RNR genes had a normal lifespan. Overexpression of RNR1, but not RNR3, restored the lifespan of the heterozygous FHL1 mutant to the wild-type (WT) level. The Δfhl1/FHL1 mutant conferred a decrease in dNTP levels and an increase in hydroxyurea (HU) sensitivity. These findings reveal that Fhl1p regulates RNR1 gene transcription to maintain dNTP levels, thus modulating longevity by protection against replication stress. - Highlights: • Fhl1p regulates replicative lifespan and transcription of RNR large subunit genes. • Rnr1p uniquely acts as a lifespan regulator independent of the RNR complex. • dNTP levels modulate longevity by protection against replication stress.« less
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Deoxyribonucleoside kinases in mitochondrial DNA depletion.
Saada-Reisch, Ann
2004-10-01
Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a heterogeneous group of mitochondrial disorders, manifested by a decreased mtDNA copy number and respiratory chain dysfunction. Primary MDS are inherited autosomally and may affect a single organ or multiple tissues. Mutated mitochondrial deoxyribonucleoside kinases; deoxyguanosine kinase (dGK) and thymidine kinase 2 (TK2), were associated with the hepatocerebral and myopathic forms of MDS respectively. dGK and TK2 are key enzymes in the mitochondrial nucleotide salvage pathway, providing the mitochondria with deoxyribonucleotides (dNP) essential for mtDNA synthesis. Although the mitochondrial dNP pool is physically separated from the cytosolic one, dNP's may still be imported through specific transport. Non-replicating tissues, where cytosolic dNP supply is down regulated, are thus particularly vulnerable to dGK and TK2 deficiency. The overlapping substrate specificity of deoxycytidine kinase (dCK) may explain the relative sparing of muscle in dGK deficiency, while low basal TK2 activity render this tissue susceptible to TK2 deficiency. The precise pathophysiological mechanisms of mtDNA depletion due to dGK and TK2 deficiencies remain to be determined, though recent findings confirm that it is attributed to imbalanced dNTP pools.
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Kinetic Basis of Nucleotide Selection Employed by a Protein Template-Dependent DNA Polymerase†
Brown, Jessica A.; Fowler, Jason D.; Suo, Zucai
2010-01-01
Rev1, a Y-family DNA polymerase, contributes to spontaneous and DNA damage-induced mutagenic events. In this paper, we have employed pre-steady state kinetic methodology to establish a kinetic basis for nucleotide selection by human Rev1, a unique nucleotidyl transferase that uses a protein template-directed mechanism to preferentially instruct dCTP incorporation. This work demonstrated that the high incorporation efficiency of dCTP is dependent on both substrates: an incoming dCTP and a templating base dG. The extremely low base substitution fidelity of human Rev1 (100 to 10-5) was due to the preferred misincorporation of dCTP with templating bases dA, dT, and dC over correct dNTPs. Using non-natural nucleotide analogs, we showed that hydrogen bonding interactions between residue R357 of human Rev1 and an incoming dNTP are not essential for DNA synthesis. Lastly, human Rev1 discriminates between ribonucleotides and deoxyribonucleotides mainly by reducing the rate of incorporation, and the sugar selectivity of human Rev1 is sensitive to both the size and orientation of the 2′-substituent of a ribonucleotide. PMID:20518555
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Metabolic Recruitment and Directed Evolution of Nucleoside Triphosphate Uptake in Escherichia coli.
Pezo, Valérie; Hassan, Camille; Louis, Dominique; Sargueil, Bruno; Herdewijn, Piet; Marlière, Philippe
2018-05-18
We report the design and elaboration of a selection protocol for importing a canonical substrate of DNA polymerase, thymidine triphosphate (dTTP) in Escherichia coli. Bacterial strains whose growth depend on dTTP uptake, through the action of an algal plastid transporter expressed from a synthetic gene inserted in the chromosome, were constructed and shown to withstand the simultaneous loss of thymidylate synthase and thymidine kinase. Such thyA tdk dual deletant strains provide an experimental model of tight nutritional containment for preventing dissemination of microbial GMOs. Our strains transported the four canonical dNTPs, in the following order of preference: dCTP > dATP ≥ dGTP > dTTP. Prolonged cultivation under limitation of exogenous dTTP led to the enhancement of dNTP transport by adaptive evolution. We investigated the uptake of dCTP analogues with altered sugar or nucleobase moieties, which were found to cause a loss of cell viability and an increase of mutant frequency, respectively. E. coli strains equipped with nucleoside triphosphate transporters should be instrumental for evolving organisms whose DNA genome is morphed chemically by fully substituting its canonical nucleotide components.
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Structure of human DNA polymerase iota and the mechanism of DNA synthesis.
Makarova, A V; Kulbachinskiy, A V
2012-06-01
Cellular DNA polymerases belong to several families and carry out different functions. Highly accurate replicative DNA polymerases play the major role in cell genome replication. A number of new specialized DNA polymerases were discovered at the turn of XX-XXI centuries and have been intensively studied during the last decade. Due to the special structure of the active site, these enzymes efficiently perform synthesis on damaged DNA but are characterized by low fidelity. Human DNA polymerase iota (Pol ι) belongs to the Y-family of specialized DNA polymerases and is one of the most error-prone enzymes involved in DNA synthesis. In contrast to other DNA polymerases, Pol ι is able to use noncanonical Hoogsteen interactions for nucleotide base pairing. This allows it to incorporate nucleotides opposite various lesions in the DNA template that impair Watson-Crick interactions. Based on the data of X-ray structural analysis of Pol ι in complexes with various DNA templates and dNTP substrates, we consider the structural peculiarities of the Pol ι active site and discuss possible mechanisms that ensure the unique behavior of the enzyme on damaged and undamaged DNA.
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-10-31
... announcement of listening session. SUMMARY: The NTP invites written public comment on the proposed Report on... proposed process. DATES: The deadline for submission of written comments is November 30, 2011, and the...: Written comments should be sent to Dr. Ruth Lunn, Director, Office of the Report on Carcinogens, DNTP...
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Structural basis of lentiviral subversion of a cellular protein degradation pathway
NASA Astrophysics Data System (ADS)
Schwefel, David; Groom, Harriet C. T.; Boucherit, Virginie C.; Christodoulou, Evangelos; Walker, Philip A.; Stoye, Jonathan P.; Bishop, Kate N.; Taylor, Ian A.
2014-01-01
Lentiviruses contain accessory genes that have evolved to counteract the effects of host cellular defence proteins that inhibit productive infection. One such restriction factor, SAMHD1, inhibits human immunodeficiency virus (HIV)-1 infection of myeloid-lineage cells as well as resting CD4+ T cells by reducing the cellular deoxynucleoside 5'-triphosphate (dNTP) concentration to a level at which the viral reverse transcriptase cannot function. In other lentiviruses, including HIV-2 and related simian immunodeficiency viruses (SIVs), SAMHD1 restriction is overcome by the action of viral accessory protein x (Vpx) or the related viral protein r (Vpr) that target and recruit SAMHD1 for proteasomal degradation. The molecular mechanism by which these viral proteins are able to usurp the host cell's ubiquitination machinery to destroy the cell's protection against these viruses has not been defined. Here we present the crystal structure of a ternary complex of Vpx with the human E3 ligase substrate adaptor DCAF1 and the carboxy-terminal region of human SAMHD1. Vpx is made up of a three-helical bundle stabilized by a zinc finger motif, and wraps tightly around the disc-shaped DCAF1 molecule to present a new molecular surface. This adapted surface is then able to recruit SAMHD1 via its C terminus, making it a competent substrate for the E3 ligase to mark for proteasomal degradation. The structure reported here provides a molecular description of how a lentiviral accessory protein is able to subvert the cell's normal protein degradation pathway to inactivate the cellular viral defence system.
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Dong, Jiantong; Wu, Tongbo; Xiao, Yu; Xu, Lei; Fang, Simin; Zhao, Meiping
2016-09-29
A fuel-limited isothermal DNA machine has been built for the sensitive fluorescence detection of cellular deoxyribonucleoside triphosphates (dNTPs) at the fmol level, which greatly reduces the required sample cell number. Upon the input of the limiting target dNTP, the machine runs automatically at 37 °C without the need for higher temperature.
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Hoberg, Emily; Szilagyi, Zsolt; Taylor, Robert W.; Gustafsson, Claes M.; Falkenberg, Maria
2017-01-01
Previous work has demonstrated the presence of ribonucleotides in human mitochondrial DNA (mtDNA) and in the present study we use a genome-wide approach to precisely map the location of these. We find that ribonucleotides are distributed evenly between the heavy- and light-strand of mtDNA. The relative levels of incorporated ribonucleotides reflect that DNA polymerase γ discriminates the four ribonucleotides differentially during DNA synthesis. The observed pattern is also dependent on the mitochondrial deoxyribonucleotide (dNTP) pools and disease-causing mutations that change these pools alter both the absolute and relative levels of incorporated ribonucleotides. Our analyses strongly suggest that DNA polymerase γ-dependent incorporation is the main source of ribonucleotides in mtDNA and argues against the existence of a mitochondrial ribonucleotide excision repair pathway in human cells. Furthermore, we clearly demonstrate that when dNTP pools are limiting, ribonucleotides serve as a source of building blocks to maintain DNA replication. Increased levels of embedded ribonucleotides in patient cells with disturbed nucleotide pools may contribute to a pathogenic mechanism that affects mtDNA stability and impair new rounds of mtDNA replication. PMID:28207748
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Selvaraj, S; Ghebremichael, M; Li, M; Foli, Y; Langs-Barlow, A; Ogbuagu, A; Barakat, L; Tubridy, E; Edifor, R; Lam, W; Cheng, Y-C; Paintsil, E
2014-07-01
We hypothesized that competition between nucleotide reverse-transcriptase inhibitor triphosphate and endogenous deoxyribonucleotide triphosphate (dNTP) may lead to depletion of dNTP pools and mitochondrial dysfunction independent of polymerase-γ (pol-γ) inhibition. We collected peripheral blood mononuclear cells from 75 adults (25 cases: HIV-infected patients with mitochondrial toxicity, 25 HIV-infected positive controls, and 25 HIV-negative controls). We observed statistically significant individual and group differences in ribonucleotide (RN) and deoxyribonucleotide (dRN) pools. The median values for the RN pools were 10,062 (interquartile range (IQR): 7,090-12,590), 4,360 (IQR: 3,058-6,838), and 2,968 (IQR: 2,538-4,436) pmol/10(6) cells for negative controls, positive controls, and cases, respectively. Cases had significantly higher absolute mitochondrial DNA copy number as compared with negative controls (P < 0.05). Moreover, cases had significantly higher expression levels of pol-γ, nucleotide transporters, cellular kinases, and adenosine triphosphate (ATP)-binding cassette (ABC) proteins as compared with controls. Antiretroviral therapy (ART) perturbs RN and dRN pools. Depletion of RN and dRN pools may be associated with ART-induced mitochondrial toxicity independent of pol-γ inhibition.
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Efficiency and Fidelity of Human DNA Polymerases λ and β during Gap-Filling DNA Synthesis
Brown, Jessica A.; Pack, Lindsey R.; Sanman, Laura E.; Suo, Zucai
2010-01-01
The base excision repair (BER) pathway coordinates the replacement of 1 to 10 nucleotides at sites of single-base lesions. This process generates DNA substrates with various gap sizes which can alter the catalytic efficiency and fidelity of a DNA polymerase during gap-filling DNA synthesis. Here, we quantitatively determined the substrate specificity and base substitution fidelity of human DNA polymerase λ (Pol λ), an enzyme proposed to support the known BER DNA polymerase β (Pol β), as it filled 1- to 10-nucleotide gaps at 1-nucleotide intervals. Pol λ incorporated a correct nucleotide with relatively high efficiency until the gap size exceeded 9 nucleotides. Unlike Pol λ, Pol β did not have an absolute threshold on gap size as the catalytic efficiency for a correct dNTP gradually decreased as the gap size increased from 2 to 10 nucleotides and then recovered for non-gapped DNA. Surprisingly, an increase in gap size resulted in lower polymerase fidelity for Pol λ, and this downregulation of fidelity was controlled by its non-enzymatic N-terminal domains. Overall, Pol λ was up to 160-fold more error-prone than Pol β, thereby suggesting Pol λ would be more mutagenic during long gap-filling DNA synthesis. In addition, dCTP was the preferred misincorporation for Pol λ and its N-terminal domain truncation mutants. This nucleotide preference was shown to be dependent upon the identity of the adjacent 5′-template base. Our results suggested that both Pol λ and Pol β would catalyze nucleotide incorporation with the highest combination of efficiency and accuracy when the DNA substrate contains a single-nucleotide gap. Thus, Pol λ, like Pol β, is better suited to catalyze gap-filling DNA synthesis during short-patch BER in vivo, although, Pol λ may play a role in long-patch BER. PMID:20961817
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Editing disulphide bonds: error correction using redox currencies.
Ito, Koreaki
2010-01-01
The disulphide bond-introducing enzyme of bacteria, DsbA, sometimes oxidizes non-native cysteine pairs. DsbC should rearrange the resulting incorrect disulphide bonds into those with correct connectivity. DsbA and DsbC receive oxidizing and reducing equivalents, respectively, from respective redox components (quinones and NADPH) of the cell. Two mechanisms of disulphide bond rearrangement have been proposed. In the redox-neutral 'shuffling' mechanism, the nucleophilic cysteine in the DsbC active site forms a mixed disulphide with a substrate and induces disulphide shuffling within the substrate part of the enzyme-substrate complex, followed by resolution into a reduced enzyme and a disulphide-rearranged substrate. In the 'reduction-oxidation' mechanism, DsbC reduces those substrates with wrong disulphides so that DsbA can oxidize them again. In this issue of Molecular Microbiology, Berkmen and his collaborators show that a disulphide reductase, TrxP, from an anaerobic bacterium can substitute for DsbC in Escherichia coli. They propose that the reduction-oxidation mechanism of disulphide rearrangement can indeed operate in vivo. An implication of this work is that correcting errors in disulphide bonds can be coupled to cellular metabolism and is conceptually similar to the proofreading processes observed with numerous synthesis and maturation reactions of biological macromolecules.
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DNA Precursor Metabolism and Mitochondrial Genome Stability
2003-04-01
mitochondrial DNA replication , to learn how the pool sizes are regulated, and to understand how perturbations of normal dNTP metabolism within the...mitochondria raises the possibility, however unlikely, that it is serving a function in addition to its role in DNA replication . The literature on non-DNA...is below since many authors do not follow the 200 word limit 14. SUBJECT TERMS Mitochondria, Genome stability, DNA precursors, Mitochondrial DNA
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Pyrosequencing for Microbial Identification and Characterization
Cummings, Patrick J.; Ahmed, Ray; Durocher, Jeffrey A.; Jessen, Adam; Vardi, Tamar; Obom, Kristina M.
2013-01-01
Pyrosequencing is a versatile technique that facilitates microbial genome sequencing that can be used to identify bacterial species, discriminate bacterial strains and detect genetic mutations that confer resistance to anti-microbial agents. The advantages of pyrosequencing for microbiology applications include rapid and reliable high-throughput screening and accurate identification of microbes and microbial genome mutations. Pyrosequencing involves sequencing of DNA by synthesizing the complementary strand a single base at a time, while determining the specific nucleotide being incorporated during the synthesis reaction. The reaction occurs on immobilized single stranded template DNA where the four deoxyribonucleotides (dNTP) are added sequentially and the unincorporated dNTPs are enzymatically degraded before addition of the next dNTP to the synthesis reaction. Detection of the specific base incorporated into the template is monitored by generation of chemiluminescent signals. The order of dNTPs that produce the chemiluminescent signals determines the DNA sequence of the template. The real-time sequencing capability of pyrosequencing technology enables rapid microbial identification in a single assay. In addition, the pyrosequencing instrument, can analyze the full genetic diversity of anti-microbial drug resistance, including typing of SNPs, point mutations, insertions, and deletions, as well as quantification of multiple gene copies that may occur in some anti-microbial resistance patterns. PMID:23995536
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Pyrosequencing for microbial identification and characterization.
Cummings, Patrick J; Ahmed, Ray; Durocher, Jeffrey A; Jessen, Adam; Vardi, Tamar; Obom, Kristina M
2013-08-22
Pyrosequencing is a versatile technique that facilitates microbial genome sequencing that can be used to identify bacterial species, discriminate bacterial strains and detect genetic mutations that confer resistance to anti-microbial agents. The advantages of pyrosequencing for microbiology applications include rapid and reliable high-throughput screening and accurate identification of microbes and microbial genome mutations. Pyrosequencing involves sequencing of DNA by synthesizing the complementary strand a single base at a time, while determining the specific nucleotide being incorporated during the synthesis reaction. The reaction occurs on immobilized single stranded template DNA where the four deoxyribonucleotides (dNTP) are added sequentially and the unincorporated dNTPs are enzymatically degraded before addition of the next dNTP to the synthesis reaction. Detection of the specific base incorporated into the template is monitored by generation of chemiluminescent signals. The order of dNTPs that produce the chemiluminescent signals determines the DNA sequence of the template. The real-time sequencing capability of pyrosequencing technology enables rapid microbial identification in a single assay. In addition, the pyrosequencing instrument, can analyze the full genetic diversity of anti-microbial drug resistance, including typing of SNPs, point mutations, insertions, and deletions, as well as quantification of multiple gene copies that may occur in some anti-microbial resistance patterns.
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Potent Inhibition of HIV-1 Replication in Resting CD4 T Cells by Resveratrol and Pterostilbene
Chan, Chi N.; Trinité, Benjamin
2017-01-01
ABSTRACT HIV-1 infection of resting CD4 T cells plays a crucial and numerically dominant role during virus transmission at mucosal sites and during subsequent acute replication and T cell depletion. Resveratrol and pterostilbene are plant stilbenoids associated with several health-promoting benefits. Resveratrol has been shown to inhibit the replication of several viruses, including herpes simplex viruses 1 and 2, papillomaviruses, severe acute respiratory syndrome virus, and influenza virus. Alone, resveratrol does not inhibit HIV-1 infection of activated T cells, but it does synergize with nucleoside reverse transcriptase inhibitors in these cells to inhibit reverse transcription. Here, we demonstrate that resveratrol and pterostilbene completely block HIV-1 infection at a low micromolar dose in resting CD4 T cells, primarily at the reverse transcription step. The anti-HIV effect was fully reversed by exogenous deoxynucleosides and Vpx, an HIV-1 and simian immunodeficiency virus protein that increases deoxynucleoside triphosphate (dNTP) levels. These findings are consistent with the reported ability of resveratrol to inhibit ribonucleotide reductase and to lower dNTP levels in cells. This study supports the potential use of resveratrol, pterostilbene, or related compounds as adjuvants in anti-HIV preexposure prophylaxis (PrEP) formulations. PMID:28652233
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Potent Inhibition of HIV-1 Replication in Resting CD4 T Cells by Resveratrol and Pterostilbene.
Chan, Chi N; Trinité, Benjamin; Levy, David N
2017-09-01
HIV-1 infection of resting CD4 T cells plays a crucial and numerically dominant role during virus transmission at mucosal sites and during subsequent acute replication and T cell depletion. Resveratrol and pterostilbene are plant stilbenoids associated with several health-promoting benefits. Resveratrol has been shown to inhibit the replication of several viruses, including herpes simplex viruses 1 and 2, papillomaviruses, severe acute respiratory syndrome virus, and influenza virus. Alone, resveratrol does not inhibit HIV-1 infection of activated T cells, but it does synergize with nucleoside reverse transcriptase inhibitors in these cells to inhibit reverse transcription. Here, we demonstrate that resveratrol and pterostilbene completely block HIV-1 infection at a low micromolar dose in resting CD4 T cells, primarily at the reverse transcription step. The anti-HIV effect was fully reversed by exogenous deoxynucleosides and Vpx, an HIV-1 and simian immunodeficiency virus protein that increases deoxynucleoside triphosphate (dNTP) levels. These findings are consistent with the reported ability of resveratrol to inhibit ribonucleotide reductase and to lower dNTP levels in cells. This study supports the potential use of resveratrol, pterostilbene, or related compounds as adjuvants in anti-HIV preexposure prophylaxis (PrEP) formulations. Copyright © 2017 American Society for Microbiology.
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NASA Astrophysics Data System (ADS)
Mermin, N. David
2016-03-01
Part I. Reference Frame Columns, Physics Today, 1988-2009: 1. What's wrong with this Lagrangean? April 1988; 2. What's wrong with this library? August 1988; 3. What's wrong with these prizes? January 1989; 4. What's wrong with this pillow? April 1989; 5. What's wrong with this prose? May 1989; 6. What's wrong with these equations? October 1989; 7. What's wrong with these elements of reality? June 1990; 8. What's wrong with these reviews? August 1990; 9. What's wrong with those epochs? November 1990; 10. Publishing in computopia, May 1991; 11. What's wrong with those grants, June 1991; 12. What's wrong in computopia, April 1992; 13. What's wrong with those talks? November 1992; 14. Two lectures on the wave-particle duality, January 1993; 15. A quarrel we can settle, December 1993; 16. What's wrong with this temptation, June 1994; 17. What's wrong with this sustaining myth, March 1996; 18. The golemization of relativity, April 1996; 19. Diary of a Nobel guest, March 1997; 20. What's wrong with this reading, October 1997; 21. How not to create tigers, August 1999; 22. What's wrong with this elegance? March 2000; 23. The contemplation of quantum computation, July 2000; 24. What's wrong with these questions? February 2001; 25. What's wrong with this quantum world? February 2004; 26. Could Feynman have said this? May 2004; 27. My life with Einstein, December 2005; 28. What has quantum mechanics to do with factoring? April 2007; 29. Some curious facts about quantum factoring, October 2007; 30. What's bad about this habit, May 2009; Part II. Shedding Bad Habits: 31. Fixing the shifty split, Physics Today, July 2012; 32. What I think about Now, Physics Today, March 2014; 33. Why QBism is not the Copenhagen interpretation, lecture, Vienna, June 2014; Part III. More from Professor Mozart: 34. What's wrong with this book? Unpublished, 1992; 35. What's wrong with these stanzas? Physics Today, July 2007; Part IV. More to be said: 36. The complete diary of a Nobel guest, unpublished, 1996; 37. Elegance in physics, unpublished lecture, Minneapolis, 1999; 38. Questions for 2105, unpublished lecture, Zurich, 2005; Part V. Some People I've Known: 39. My life with Fisher, lecture, Rutgers University, 2001; 40. My life with Kohn, 2003, updated 2013; 41. My life with Wilson, lecture, Cornell University, 2014; 42. My life with Peierls, unpublished lecture, Santa Barbara, 1997; Part VI. Summing It Up: 43. Writing physics, lecture, Cornell University, 1999.
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An, Changlong; Beard, William A; Chen, Desheng; Wilson, Samuel H; Makridakis, Nick M
2013-10-01
Human DNA polymerase (pol) β is essential for base excision repair. We previously reported a triple somatic mutant of pol β (p.P261L/T292A/I298T) found in an early onset prostate tumor. This mutation abolishes polymerase activity, and the wild-type allele was not present in the tumor, indicating a complete deficiency in pol β function. The effect on polymerase activity is unexpected because the point mutations that comprise the triple mutant are not part of the active site. Herein, we demonstrate the mechanism of this loss-of-function. In order to understand the effect of the individual point mutations we biochemically analyzed all single and double mutants that comprise the triple mutant. We found that the p.I298T mutation is responsible for a marked instability of the triple mutant protein at 37˚C. At room temperature the triple mutant's low efficiency is also due to a decrease in the apparent binding affinity for the dNTP substrate, which is due to the p.T292A mutation. Furthermore, the triple mutant displays lower fidelity for transversions in vitro, due to the p.T292A mutation. We conclude that distinct mutations of the triple pol β mutant are responsible for the loss of activity, lower fidelity, and instability observed in vitro.
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Pyrophosphorolytic dismutation of oligodeoxy-nucleotides by terminal deoxynucleotidyltransferase.
Anderson, R S; Bollum, F J; Beattie, K L
1999-01-01
Terminal transferase (TdT), when incubated with a purified(32)P-5"-end-labeled oligonucleotide of defined length in the presence of Co(2+), Mn(2+)or Mg(2+)and 2-mercaptoethanol in cacodylate or HEPES buffer, pH 7.2, exhibits the ability to remove a 3"-nucleotide from one oligonucleotide and add it to the 3"-end of another. When analyzed by urea-PAGE, this activity is observed as a disproportionation of the starting oligonucleotide into a ladder of shorter and longer oligonucleotides distributed around the starting material. Optimal metal ion concentration is 1-2 mM. All three metal ions support this activity with Co(2+)> Mn(2+) congruent with Mg(2+). Oligonucleotides p(dT) and p(dA) are more efficient substrates than p(dG) and p(dC) because the latter may form secondary structures. The dismutase activity is significant even in the presence of dNTP concentrations comparable to those that exist in the nucleus during the G(1)phase of the cell cycle. Using BetaScope image analysis the rate of pyrophosphorolytic dismutase activity was found to be only moderately slower than the poly-merization activity. These results may help explain the GC-richness of immunoglobulin gene segment joins (N regions) and the loss of bases that occur during gene rearrangements in pre-B and pre-T cells. PMID:10454617
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Kinoshita, Kenji; Fujimoto, Kentaro; Yakabe, Toru; Saito, Shin; Hamaguchi, Yuzo; Kikuchi, Takayuki; Nonaka, Ken; Murata, Shigenori; Masuda, Daisuke; Takada, Wataru; Funaoka, Sohei; Arai, Susumu; Nakanishi, Hisao; Yokoyama, Kanehisa; Fujiwara, Kazuhiko; Matsubara, Kenichi
2007-01-01
DNA microarrays are routinely used to monitor gene expression profiling and single nucleotide polymorphisms (SNPs). However, for practically useful high performance, the detection sensitivity is still not adequate, leaving low expression genes undetected. To resolve this issue, we have developed a new plastic S-BIO® PrimeSurface® with a biocompatible polymer; its surface chemistry offers an extraordinarily stable thermal property for a lack of pre-activated glass slide surface. The oligonucleotides immobilized on this substrate are robust in boiling water and show no significant loss of hybridization activity during dissociation treatment. This allowed us to hybridize the templates, extend the 3′ end of the immobilized DNA primers on the S-Bio® by DNA polymerase using deoxynucleotidyl triphosphates (dNTP) as extender units, release the templates by denaturalization and use the same templates for a second round of reactions similar to that of the PCR method. By repeating this cycle, the picomolar concentration range of the template oligonucleotide can be detected as stable signals via the incorporation of labeled dUTP into primers. This method of Multiple Primer EXtension (MPEX) could be further extended as an alternative route for producing DNA microarrays for SNP analyses via simple template preparation such as reverse transcript cDNA or restriction enzyme treatment of genome DNA. PMID:17135189
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Conformational Dynamics of Thermus aquaticus DNA Polymerase I during Catalysis
Suo, Zucai
2014-01-01
Despite the fact that DNA polymerases have been investigated for many years and are commonly used as tools in a number of molecular biology assays, many details of the kinetic mechanism they use to catalyze DNA synthesis remain unclear. Structural and kinetic studies have characterized a rapid, pre-catalytic open-to-close conformational change of the Finger domain during nucleotide binding for many DNA polymerases including Thermus aquaticus DNA polymerase I (Taq Pol), a thermostable enzyme commonly used for DNA amplification in PCR. However, little has been done to characterize the motions of other structural domains of Taq Pol or any other DNA polymerase during catalysis. Here, we used stopped-flow Förster resonance energy transfer (FRET) to investigate the conformational dynamics of all five structural domains of the full-length Taq Pol relative to the DNA substrate during nucleotide binding and incorporation. Our study provides evidence for a rapid conformational change step induced by dNTP binding and a subsequent global conformational transition involving all domains of Taq Pol during catalysis. Additionally, our study shows that the rate of the global transition was greatly increased with the truncated form of Taq Pol lacking the N-terminal domain. Finally, we utilized a mutant of Taq Pol containing a de novo disulfide bond to demonstrate that limiting protein conformational flexibility greatly reduced the polymerization activity of Taq Pol. PMID:24931550
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Aptamer Selection Express: A Novel Method for Rapid Single-Step Selection and Sensing of Aptamers
2008-12-01
sample) was as follows: 5 µL buffer, 2 µL MgCl2, 2.5 µL DMSO, 1 µL betaine , 1 µL each dNTP, 2.5 µL F primer, 2.5 µL R primer, 0.54 µL taq polymerase...and 25.1 µL H2O. Betaine and increased DMSO were added to the master mix to eliminate polymerase jumping during PCR ampli- fication.10 Using the
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Concept analysis: wrong-site surgery.
Watson, Donna S
2015-06-01
A concept analysis was conducted on the concept of wrong-site surgery (WSS) using the principle-based method by Penrod and Hupcey. It included analysis of WSS within the context of epistemological, pragmatic, linguistic, and logical principles. The analysis found that WSS is an important concept that is universally accepted, but the definition could be improved with inclusion of comprehensive labeling for types of WSS that may occur, such as wrong patient, wrong site, wrong level/part, wrong procedure, and wrong side. Wrong-site surgery falls into the domains of both nursing and medicine, and there is limited research on the topic specific to nursing interventions, perceptions, and contributions to prevent WSS. Copyright © 2015 AORN, Inc. Published by Elsevier Inc. All rights reserved.
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1988-05-17
The Supreme Court of Missouri affirmed the Circuit Court's dismissal of wrongful life and wrongful birth claims brought against a physician who failed to advise a pregnant woman of the availability of the amniocentesis test for Down's syndrome. The Supreme Court ruled that the Missouri statute precluding actions for wrongful life and wrongful birth does not apply retroactively. However, the Court refused to recognize the validity of wrongful life or wrongful death actions. The wrongful life action brought by or on behalf of a child is improper because of the difficulty in assessing damages, and the wrongful birth action brought by the child's parents is invalid because of the absence of traditional tort causation, the derivative nature of the cause of action, and the uncertainty in determining whether the mother would have chosen to abort.
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Singlet Oxygen-Mediated Oxidation during UVA Radiation Alters the Dynamic of Genomic DNA Replication
Graindorge, Dany; Martineau, Sylvain; Machon, Christelle; Arnoux, Philippe; Guitton, Jérôme; Francesconi, Stefania; Frochot, Céline; Sage, Evelyne; Girard, Pierre-Marie
2015-01-01
UVA radiation (320–400 nm) is a major environmental agent that can exert its deleterious action on living organisms through absorption of the UVA photons by endogenous or exogenous photosensitizers. This leads to the production of reactive oxygen species (ROS), such as singlet oxygen (1O2) and hydrogen peroxide (H2O2), which in turn can modify reversibly or irreversibly biomolecules, such as lipids, proteins and nucleic acids. We have previously reported that UVA-induced ROS strongly inhibit DNA replication in a dose-dependent manner, but independently of the cell cycle checkpoints activation. Here, we report that the production of 1O2 by UVA radiation leads to a transient inhibition of replication fork velocity, a transient decrease in the dNTP pool, a quickly reversible GSH-dependent oxidation of the RRM1 subunit of ribonucleotide reductase and sustained inhibition of origin firing. The time of recovery post irradiation for each of these events can last from few minutes (reduction of oxidized RRM1) to several hours (replication fork velocity and origin firing). The quenching of 1O2 by sodium azide prevents the delay of DNA replication, the decrease in the dNTP pool and the oxidation of RRM1, while inhibition of Chk1 does not prevent the inhibition of origin firing. Although the molecular mechanism remains elusive, our data demonstrate that the dynamic of replication is altered by UVA photosensitization of vitamins via the production of singlet oxygen. PMID:26485711
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Seamon, Kyle J; Bumpus, Namandjé N; Stivers, James T
2016-11-08
Sterile alpha motif and HD domain protein 1 (SAMHD1) is a unique enzyme that plays important roles in nucleic acid metabolism, viral restriction, and the pathogenesis of autoimmune diseases and cancer. Although much attention has been focused on its dNTP triphosphohydrolase activity in viral restriction and disease, SAMHD1 also binds to single-stranded RNA and DNA. Here we utilize a UV cross-linking method using 5-bromodeoxyuridine-substituted oligonucleotides coupled with high-resolution mass spectrometry to identify the binding site for single-stranded nucleic acids (ssNAs) on SAMHD1. Mapping cross-linked amino acids on the surface of existing crystal structures demonstrated that the ssNA binding site lies largely along the dimer-dimer interface, sterically blocking the formation of the homotetramer required for dNTPase activity. Surprisingly, the disordered C-terminus of SAMHD1 (residues 583-626) was also implicated in ssNA binding. An interaction between this region and ssNA was confirmed in binding studies using the purified SAMHD1 583-626 peptide. Despite a recent report that SAMHD1 possesses polyribonucleotide phosphorylase activity, we did not detect any such activity in the presence of inorganic phosphate, indicating that nucleic acid binding is unrelated to this proposed activity. These data suggest an antagonistic regulatory mechanism in which the mutually exclusive oligomeric state requirements for ssNA binding and dNTP hydrolase activity modulate these two functions of SAMHD1 within the cell.
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Valle-Casuso, Jose Carlos; Allouch, Awatef; David, Annie; Lenzi, Gina M; Studdard, Lydia; Barré-Sinoussi, Françoise; Müller-Trutwin, Michaela; Kim, Baek; Pancino, Gianfranco; Sáez-Cirión, Asier
2017-12-01
HIV-1 infection of noncycling cells, such as dendritic cells (DCs), is impaired due to limited availability of deoxynucleoside triphosphates (dNTPs), which are needed for HIV-1 reverse transcription. The levels of dNTPs are tightly regulated during the cell cycle and depend on the balance between dNTP biosynthesis and degradation. SAMHD1 potently blocks HIV-1 replication in DCs, although the underlying mechanism is still unclear. SAMHD1 has been reported to be able to degrade dNTPs and viral nucleic acids, which may both hamper HIV-1 reverse transcription. The relative contribution of these activities may differ in cycling and noncycling cells. Here, we show that inhibition of HIV-1 replication in monocyte-derived DCs (MDDCs) is associated with an increased expression of p21cip1/waf, a cell cycle regulator that is involved in the differentiation and maturation of DCs. Induction of p21 in MDDCs decreases the pool of dNTPs and increases the antiviral active isoform of SAMHD1. Although both processes are complementary in inhibiting HIV-1 replication, the antiviral activity of SAMHD1 in our primary cell model appears to be, at least partially, independent of its dNTPase activity. The reduction in the pool of dNTPs in MDDCs appears rather mostly due to a p21-mediated suppression of several enzymes involved in dNTP synthesis (i.e., RNR2, TYMS, and TK-1). These results are important to better understand the interplay between HIV-1 and DCs and may inform the design of new therapeutic approaches to decrease viral dissemination and improve immune responses against HIV-1. IMPORTANCE DCs play a key role in the induction of immune responses against HIV. However, HIV has evolved ways to exploit these cells, facilitating immune evasion and virus dissemination. We have found that the expression of p21, a cyclin-dependent kinase inhibitor involved in cell cycle regulation and monocyte differentiation and maturation, potentially can contribute to the inhibition of HIV-1 replication in monocyte-derived DCs through multiple mechanisms. p21 decreased the size of the intracellular dNTP pool. In parallel, p21 prevented SAMHD1 phosphorylation and promoted SAMHD1 dNTPase-independent antiviral activity. Thus, induction of p21 resulted in conditions that allowed the effective inhibition of HIV-1 replication through complementary mechanisms. Overall, p21 appears to be a key regulator of HIV infection in myeloid cells. Copyright © 2017 American Society for Microbiology.
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Engineering measures for reducing wrong-way driving.
DOT National Transportation Integrated Search
1975-01-01
Presented is an evaluation of engineering measures instituted in Virginia to reduce incidences of wrong-way driving. Also discussed are the data collected in a survey of wrong-way driving incidents, the causes of wrong-way entries determined through ...
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What We Know Currently about Mirror Neurons
Kilner, J.M.; Lemon, R.N.
2013-01-01
Mirror neurons were discovered over twenty years ago in the ventral premotor region F5 of the macaque monkey. Since their discovery much has been written about these neurons, both in the scientific literature and in the popular press. They have been proposed to be the neuronal substrate underlying a vast array of different functions. Indeed so much has been written about mirror neurons that last year they were referred to, rightly or wrongly, as “The most hyped concept in neuroscience”. Here we try to cut through some of this hyperbole and review what is currently known (and not known) about mirror neurons. PMID:24309286
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Wrong Signs in Regression Coefficients
NASA Technical Reports Server (NTRS)
McGee, Holly
1999-01-01
When using parametric cost estimation, it is important to note the possibility of the regression coefficients having the wrong sign. A wrong sign is defined as a sign on the regression coefficient opposite to the researcher's intuition and experience. Some possible causes for the wrong sign discussed in this paper are a small range of x's, leverage points, missing variables, multicollinearity, and computational error. Additionally, techniques for determining the cause of the wrong sign are given.
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Sandberg, Warren S; Häkkinen, Matti; Egan, Marie; Curran, Paige K; Fairbrother, Pamela; Choquette, Ken; Daily, Bethany; Sarkka, Jukka-Pekka; Rattner, David
2005-09-01
When procedures and processes to assure patient location based on human performance do not work as expected, patients are brought incrementally closer to a possible "wrong patient-wrong procedure'' error. We developed a system for automated patient location monitoring and management. Real-time data from an active infrared/radio frequency identification tracking system provides patient location data that are robust and can be compared with an "expected process'' model to automatically flag wrong-location events as soon as they occur. The system also generates messages that are automatically sent to process managers via the hospital paging system, thus creating an active alerting function to annunciate errors. We deployed the system to detect and annunciate "patient-in-wrong-OR'' events. The system detected all "wrong-operating room (OR)'' events, and all "wrong-OR'' locations were correctly assigned within 0.50+/-0.28 minutes (mean+/-SD). This corresponded to the measured latency of the tracking system. All wrong-OR events were correctly annunciated via the paging function. This experiment demonstrates that current technology can automatically collect sufficient data to remotely monitor patient flow through a hospital, provide decision support based on predefined rules, and automatically notify stakeholders of errors.
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Fowler, Jason D.; Brown, Jessica A.; Kvaratskhelia, Mamuka; Suo, Zucai
2009-01-01
SUMMARY Crystallographic studies of the C-terminal, DNA polymerase β-like domain of human DNA polymerase lambda (fPolλ) suggested that the catalytic cycle might not involve a large protein domain rearrangement as observed with several replicative DNA polymerases and DNA polymerase β. To examine solution-phase protein conformation changes in fPolλ, which also contains a breast cancer susceptibility gene 1 C-terminal domain and a Proline-rich domain at its N-terminus, we used a mass spectrometry - based protein footprinting approach. In parallel experiments, surface accessibility maps for Arg residues were compared for the free fPolλ versus the binary complex of enzyme•gapped DNA and the ternary complex of enzyme•gapped DNA•dNTP. These experiments suggested that fPolλ does not undergo major conformational changes during the catalysis in the solution phase. Furthermore, the mass spectrometry-based protein footprinting experiments revealed that active site residue R386 was shielded from the surface only in the presence of both a gapped DNA substrate and an incoming nucleotide dNTP. Site-directed mutagenesis and pre-steady state kinetic studies confirmed the importance of R386 for the enzyme activity, and indicated the key role for its guanidino group in stabilizing the negative charges of an incoming nucleotide and the leaving pyrophosphate product. We suggest that such interactions could be shared by and important for catalytic functions of other DNA polymerases. PMID:19467241
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The ribonuclease activity of SAMHD1 is required for HIV-1 restriction
Ryoo, Jeongmin; Choi, Jongsu; Oh, Changhoon; Kim, Sungchul; Seo, Minji; Kim, Seokyoung; Seo, Daekwan; Kim, Jongkyu; White, Tommy E.; Brandariz-Nunez, Alberto; Diaz-Griffero, Felipe; Yun, Cheol-Heui; Hollenbaugh, Joseph A.; Kim, Baek; Baek, Daehyun
2015-01-01
The HIV-1 restriction factor SAMHD11,2 is proposed to inhibit HIV-1 replication by depleting the intracellular dNTP pool3-5. However, the phosphorylation of SAMHD1 regulates its ability to restrict HIV-1 without decreasing cellular dNTP levels6-8, which is not consistent with a role for SAMHD1 dNTPase activity in HIV-1 restriction. Here, we show that SAMHD1 possesses RNase activity and that the RNase but not the dNTPase function is essential for HIV-1 restriction. By enzymatically characterizing Aicardi-Goutières syndrome (AGS)-associated SAMHD1 mutations and mutations in the allosteric dGTP-binding site of SAMHD1, we identify SAMHD1 mutants that are RNase-positive but dNTPase-negative (SAMHD1D137N) or RNase-negative but dNTPase-positive (SAMHD1Q548A). The allosteric mutant SAMHD1D137N is able to restrict HIV-1 infection, whereas the AGS mutant SAMHD1Q548A is defective for HIV-1 restriction. SAMHD1 associates with HIV-1 RNA and degrades it during the early phases of infection. SAMHD1 silencing in macrophages and CD4+ T cells from healthy donors increases HIV-1 RNA stability, rendering the cells permissive for HIV-1 infection. Furthermore, the phosphorylation of SAMHD1 at T592 negatively regulates its RNase activity in vivo and impedes HIV-1 restriction. Our results reveal that the RNase activity of SAMHD1 is responsible for preventing HIV-1 infection by directly degrading the HIV-1 RNA. PMID:25038827
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Voluntary euthanasia, physician-assisted suicide, and the right to do wrong.
Varelius, Jukka
2013-09-01
It has been argued that voluntary euthanasia (VE) and physician-assisted suicide (PAS) are morally wrong. Yet, a gravely suffering patient might insist that he has a moral right to the procedures even if they were morally wrong. There are also philosophers who maintain that an agent can have a moral right to do something that is morally wrong. In this article, I assess the view that a suffering patient can have a moral right to VE and PAS despite the moral wrongness of the procedures in light of the main argument for a moral right to do wrong found in recent philosophical literature. I maintain that the argument does not provide adequate support for such a right to VE and PAS.
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Frati, Paola; Fineschi, Vittorio; Di Sanzo, Mariantonia; La Russa, Raffaele; Scopetti, Matteo; Severi, Filiberto M; Turillazzi, Emanuela
2017-05-01
Prenatal diagnosis based on different technologies is increasingly used in developed countries and has become a common strategy in obstetric practice. The tests are crucial in enabling mothers to make informed decisions about the possibility of terminating pregnancy. They have generated numerous bioethical and legal controversies in the field of 'wrongful life' claims (action brought by or on behalf of a child against the mother or other people, claiming that he or she has to endure a not-worth-living existence) and 'wrongful birth' claims (action brought by the mother or parents against the physician for being burdened with an unwanted, often disabled child, which could have been avoided). The possibility which exists nowadays to intervene actively by programming and deciding the phases linked to procreation and birth has raised several questions worldwide. The mother's right to self-determination could be an end but whether or not this right is absolute is debatable. Freedom could, with time, act as a barrier that obstructs intrusion into other people's lives and their personal choices. Therapeutic choices may be manageable in a liberal sense, and the sanctity of life can be inflected in a secular sense. These sensitive issues and the various points of view to be considered have motivated this review. Literature searches were conducted on relevant demographic, social science and medical science databases (SocINDEX, Econlit, PopLine, Medline, Embase and Current Contents) and via other sources. Searches focused on subjects related to bioethical and legal controversies in the field of preimplantation and prenatal diagnosis, wrongful birth and wrongful life. A review of the international state of law was carried out, focusing attention on the peculiar issue of wrongful life and investigating the different jurisdictional solutions of wrongful life claims in a comparative survey. Courts around the world are generally reluctant to acknowledge wrongful life claims due to their ethical and legal implications, such as existence as an injury, the right not to be born, the nature of the harm suffered and non-existence as an alternative to a disabled life. Most countries have rejected such actions while at the same time approving those for wrongful birth. Some countries, such as France with a law passed in March 2002, have definitively excluded Wrongful Life action. Only in the Netherlands and in three states of the USA (California, Washington and New Jersey) Wrongful Life actions are allowed. In other countries, such as Belgium, legislation is unclear because, despite a first decision of the Court allowing Wrongful Life action, the case is still in progress. There is a complete lack of case law regarding wrongful conception, wrongful birth and wrongful life in a few countries, such as Estonia. The themes of 'wrongful birth' and 'wrongful life' are charged with perplexing ethical dilemmas and raise delicate legal questions. These have met, in various countries and on certain occasions, with different solutions and have triggered ethical and juridical debate. The damage case scenarios result from a lack of information or diagnosis prior to the birth, which deprives the mother of the chance to terminate the pregnancy. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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A Rapid and Inexpensive PCR-Based STR Genotyping Method for Identifying Forensic Specimens
2006-06-01
this report) 20. Security Classif. (of this page) 21 . No. of Pages 22. Price Unclassified Unclassified 18 Form DOT F 1700.7 (8-72) Reproduction of...Promega PowerPlex 2.1 system (7) except that the buffer was 1x Amplitaq gold reaction buffer, 0.1% TritonX-100, and 0.2mM each dNTP in a 25µl final...electrophoresis were done using the PowerPlex 16 System (Promega Corp.; Madison, WI). rEsulTs ANd dIsCussION The goal of this study was to develop a simple DNA
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Enhanced Time Out: An Improved Communication Process.
Nelson, Patricia E
2017-06-01
An enhanced time out is an improved communication process initiated to prevent such surgical errors as wrong-site, wrong-procedure, or wrong-patient surgery. The enhanced time out at my facility mandates participation from all members of the surgical team and requires designated members to respond to specified time out elements on the surgical safety checklist. The enhanced time out incorporated at my facility expands upon the safety measures from the World Health Organization's surgical safety checklist and ensures that all personnel involved in a surgical intervention perform a final check of relevant information. Initiating the enhanced time out at my facility was intended to improve communication and teamwork among surgical team members and provide a highly reliable safety process to prevent wrong-site, wrong-procedure, and wrong-patient surgery. Copyright © 2017 AORN, Inc. Published by Elsevier Inc. All rights reserved.
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Distinct neuronal patterns of positive and negative moral processing in psychopathy.
Fede, Samantha J; Borg, Jana Schaich; Nyalakanti, Prashanth K; Harenski, Carla L; Cope, Lora M; Sinnott-Armstrong, Walter; Koenigs, Mike; Calhoun, Vince D; Kiehl, Kent A
2016-12-01
Psychopathy is a disorder characterized by severe and frequent moral violations in multiple domains of life. Numerous studies have shown psychopathy-related limbic brain abnormalities during moral processing; however, these studies only examined negatively valenced moral stimuli. Here, we aimed to replicate prior psychopathy research on negative moral judgments and to extend this work by examining psychopathy-related abnormalities in the processing of controversial moral stimuli and positive moral processing. Incarcerated adult males (N = 245) completed a functional magnetic resonance imaging protocol on a mobile imaging system stationed at the prison. Psychopathy was assessed using the Hare Psychopathy Checklist-Revised (PCL-R). Participants were then shown words describing three types of moral stimuli: wrong (e.g., stealing), not wrong (e.g., charity), and controversial (e.g., euthanasia). Participants rated each stimulus as either wrong or not wrong. PCL-R total scores were correlated with not wrong behavioral responses to wrong moral stimuli, and were inversely related to hemodynamic activity in the anterior cingulate cortex in the contrast of wrong > not wrong. In the controversial > noncontroversial comparison, psychopathy was inversely associated with activity in the temporal parietal junction and dorsolateral prefrontal cortex. These results indicate that psychopathy-related abnormalities are observed during the processing of complex, negative, and positive moral stimuli.
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Broadening the future of value account of the wrongness of killing.
Di Nucci, Ezio
2015-11-01
On Don Marquis's future of value account of the wrongness of killing, 'what makes it wrong to kill those individuals we all believe it is wrong to kill, is that killing them deprives them of their future of value'. Marquis has recently argued for a narrow interpretation of his future of value account of the wrongness of killing and against the broad interpretation that I had put forward in response to Carson Strong. In this article I argue that the narrow view is problematic because it violates some basic principles of equality and because it allows for some of the very killing that Marquis sets out to condemn; further, I argue that the chief reason why Marquis chooses the narrow view over the broad view-namely that the broad view would take the killing of some non-human animals to be also wrong-should rather be considered a welcome upshot of the broad view.
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Kinetic analysis of bypass of abasic site by the catalytic core of yeast DNA polymerase eta.
Yang, Juntang; Wang, Rong; Liu, Binyan; Xue, Qizhen; Zhong, Mengyu; Zeng, Hao; Zhang, Huidong
2015-09-01
Abasic sites (Apurinic/apyrimidinic (AP) sites), produced ∼ 50,000 times/cell/day, are very blocking and miscoding. To better understand miscoding mechanisms of abasic site for yeast DNA polymerase η, pre-steady-state nucleotide incorporation and LC-MS/MS sequence analysis of extension product were studied using pol η(core) (catalytic core, residues 1-513), which can completely eliminate the potential effects of the C-terminal C2H2 motif of pol η on dNTP incorporation. The extension beyond the abasic site was very inefficient. Compared with incorporation of dCTP opposite G, the incorporation efficiencies opposite abasic site were greatly reduced according to the order of dGTP > dATP > dCTP and dTTP. Pol η(core) showed no fast burst phase for any incorporation opposite G or abasic site, suggesting that the catalytic step is not faster than the dissociation of polymerase from DNA. LC-MS/MS sequence analysis of extension products showed that 53% products were dGTP misincorporation, 33% were dATP and 14% were -1 frameshift, indicating that Pol η(core) bypasses abasic site by a combined G-rule, A-rule and -1 frameshift deletions. Compared with full-length pol η, pol η(core) relatively reduced the efficiency of incorporation of dCTP opposite G, increased the efficiencies of dNTP incorporation opposite abasic site and the exclusive incorporation of dGTP opposite abasic site, but inhibited the extension beyond abasic site, and increased the priority in extension of A: abasic site relative to G: abasic site. This study provides further understanding in the mutation mechanism of abasic sites for yeast DNA polymerase η. Copyright © 2015 Elsevier B.V. All rights reserved.
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How a low-fidelity DNA polymerase chooses non-Watson-Crick from Watson-Crick incorporation.
Wu, Wen-Jin; Su, Mei-I; Wu, Jian-Li; Kumar, Sandeep; Lim, Liang-Hin; Wang, Chun-Wei Eric; Nelissen, Frank H T; Chen, Ming-Chuan Chad; Doreleijers, Jurgen F; Wijmenga, Sybren S; Tsai, Ming-Daw
2014-04-02
A dogma for DNA polymerase catalysis is that the enzyme binds DNA first, followed by MgdNTP. This mechanism contributes to the selection of correct dNTP by Watson-Crick base pairing, but it cannot explain how low-fidelity DNA polymerases overcome Watson-Crick base pairing to catalyze non-Watson-Crick dNTP incorporation. DNA polymerase X from the deadly African swine fever virus (Pol X) is a half-sized repair polymerase that catalyzes efficient dG:dGTP incorporation in addition to correct repair. Here we report the use of solution structures of Pol X in the free, binary (Pol X:MgdGTP), and ternary (Pol X:DNA:MgdGTP with dG:dGTP non-Watson-Crick pairing) forms, along with functional analyses, to show that Pol X uses multiple unprecedented strategies to achieve the mutagenic dG:dGTP incorporation. Unlike high fidelity polymerases, Pol X can prebind purine MgdNTP tightly and undergo a specific conformational change in the absence of DNA. The prebound MgdGTP assumes an unusual syn conformation stabilized by partial ring stacking with His115. Upon binding of a gapped DNA, also with a unique mechanism involving primarily helix αE, the prebound syn-dGTP forms a Hoogsteen base pair with the template anti-dG. Interestingly, while Pol X prebinds MgdCTP weakly, the correct dG:dCTP ternary complex is readily formed in the presence of DNA. H115A mutation disrupted MgdGTP binding and dG:dGTP ternary complex formation but not dG:dCTP ternary complex formation. The results demonstrate the first solution structural view of DNA polymerase catalysis, a unique DNA binding mode, and a novel mechanism for non-Watson-Crick incorporation by a low-fidelity DNA polymerase.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Xia, Shuangluo; Beckman, Jeff; Wang, Jimin
2012-10-10
Residues in the nascent base pair binding pocket (NBP) of bacteriophage RB69 DNA polymerase (RB69pol) are responsible for base discrimination. Replacing Tyr567 with Ala leads to greater flexibility in the NBP, increasing the probability of misincorporation. We used the fluorescent cytosine analogue, 1,3-diaza-2-oxophenoxazine (tC{sup o}), to identify preinsertion step(s) altered by NBP flexibility. When tC{sup o} is the templating base in a wild-type (wt) RB69pol ternary complex, its fluorescence is quenched only in the presence of dGTP. However, with the RB69pol Y567A mutant, the fluorescence of tC{sup o} is also quenched in the presence of dATP. We determined the crystalmore » structure of the dATP/tC{sup o}-containing ternary complex of the RB69pol Y567A mutant at 1.9 {angstrom} resolution and found that the incoming dATP formed two hydrogen bonds with an imino-tautomerized form of tC{sup o}. Stabilization of the dATP/tC{sup o} base pair involved movement of the tC{sup o} backbone sugar into the DNA minor groove and required tilting of the tC{sup o} tricyclic ring to prevent a steric clash with L561. This structure, together with the pre-steady-state kinetic parameters and dNTP binding affinity, estimated from equilibrium fluorescence titrations, suggested that the flexibility of the NBP, provided by the Y567 to Ala substitution, led to a more favorable forward isomerization step resulting in an increase in dNTP binding affinity.« less
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Uncovering allostery and regulation in SAMHD1 through molecular dynamics simulations.
Patra, Kajwal Kumar; Bhattacharya, Akash; Bhattacharya, Swati
2017-07-01
The human sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a retroviral restriction factor in myeloid cells and non-cycling CD4+ T cells, a feature imputed to its phosphohydrolase activity-the enzyme depletes the cellular dNTP levels inhibiting reverse transcription. The functionally active form of SAMHD1 is an allosterically triggered tetramer which utilizes GTP-Mg +2 -dNTP cross bridges to link and stabilize adjacent monomers. However, very little is known about how it assembles into a tetramer and how long the tetramer stays intact. In this computational study, we provide a molecular dynamics based analysis of the structural stability and allosteric site dynamics in SAMHD1. We have investigated the allosteric links which assemble and hold the tetramer together. We have also extended this analysis to a regulatory mutant of SAMHD1. Experimental studies have indicated that phosphorylation of T592 downregulates HIV-1 restriction. A similar result is also achieved by a phosphomimetic mutation T592E. While a mechanistic understanding of the process is still elusive, the loss of structural integrity of the enzyme is conjectured to be the cause of the impaired dNTPase activity of the T592E mutant. MD simulations show that the T592E mutation causes slightly elevated local motions which remain confined to the short helix (residues 591-595), which contains the phosphorylation site and do not cause long-range destabilization of the SAMHD1 tetramer within the timeframe of the simulations. Thus, the regulatory mechanism of SAMHD1 is a more subtle mechanism than has been previously suspected. Proteins 2017; 85:1266-1275. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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Inculcating Quality Concepts in the US Air Force: Right Music, Wrong Step
1994-04-01
CONCEPTS IN THE US AIR FORCE: RIGHT MUSIC , WRONG STEP Acceslon For NTIS CRA&J DTIC TAB Unannounced fJ by Justification Barbara A. Kucharczyk By. Lieutenant...TITLE: Inculcating Quality Concepts in the US Air Force: Right Music , Wrong Step AUTHOR: Barbara A. Kucharczyk, Lieutenant Colonel, USAF In its...perceived attitudinal backlash.4 While basic quality concepts are certainly the right music , many Air Force members are dancing the wrong step. Why? This
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McNamara, Adam
2011-01-01
Memes are the fundamental unit of cultural evolution and have been left upon the periphery of cognitive neuroscience due to their inexact definition and the consequent presumption that they are impossible to measure. Here it is argued that although a precise definition of memes is rather difficult it does not preclude highly controlled experiments studying the neural substrates of their initiation and replication. In this paper, memes are termed as either internally or externally represented (i-memes/e-memes) in relation to whether they are represented as a neural substrate within the central nervous system or in some other form within our environment. It is argued that neuroimaging technology is now sufficiently advanced to image the connectivity profiles of i-memes and critically, to measure changes to i-memes over time, i.e., as they evolve. It is argued that it is wrong to simply pass off memes as an alternative term for "stimulus" and "learnt associations" as it does not accurately account for the way in which natural stimuli may dynamically "evolve" as clearly observed in our cultural lives.
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McNamara, Adam
2011-01-01
Memes are the fundamental unit of cultural evolution and have been left upon the periphery of cognitive neuroscience due to their inexact definition and the consequent presumption that they are impossible to measure. Here it is argued that although a precise definition of memes is rather difficult it does not preclude highly controlled experiments studying the neural substrates of their initiation and replication. In this paper, memes are termed as either internally or externally represented (i-memes/e-memes) in relation to whether they are represented as a neural substrate within the central nervous system or in some other form within our environment. It is argued that neuroimaging technology is now sufficiently advanced to image the connectivity profiles of i-memes and critically, to measure changes to i-memes over time, i.e., as they evolve. It is argued that it is wrong to simply pass off memes as an alternative term for “stimulus” and “learnt associations” as it does not accurately account for the way in which natural stimuli may dynamically “evolve” as clearly observed in our cultural lives. PMID:21720531
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Assessment of the effectiveness of wrong way driving countermeasures and mitigation methods.
DOT National Transportation Integrated Search
2014-12-01
This report describes the methodology and results of tasks performed to evaluate the effectiveness of : wrong way driving countermeasures and mitigation methods. Researchers reviewed the state of the practice : regarding wrong way driving in the Unit...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-01-02
...\\ thereunder so that the proposal was effective upon filing with the Commission. The Commission is publishing... initial Delivery Orders (``DO'') for a variety of reasons (e.g., DK, wrong quantity, wrong security, wrong...
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Guidelines for reducing wrong-way crashes on freeways.
DOT National Transportation Integrated Search
2014-05-01
Each year, hundreds of fatal wrong-way driving (WWD) crashes occur across the United States, and thousands : of injuries are reported in traffic crashes caused by wrong-way drivers. Although WWD crashes have been a : concern since the advent of acces...
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Surgical confusions in ophthalmology.
Simon, John W; Ngo, Yen; Khan, Samira; Strogatz, David
2007-11-01
To investigate the hypothesis that surgical confusions rarely occur but are unacceptable to the public; occur in predictable circumstances; involve a wrong lens implant more often than a wrong eye, procedure, or patient; and can be prevented using the Universal Protocol. A retrospective series of 106 cases, including 42 from the Ophthalmic Mutual Insurance Company and 64 from the New York State Health Department. We investigated how the error occurred; when and by whom it was recognized; who was responsible; whether the patient was informed; what treatment was given; what the outcome and liability was; what policy changes or sanctions resulted; and whether the error was preventable using the Universal Protocol. The most common confusion was wrong lens implants, accounting for 67 cases (63%). Wrong-eye operations occurred in 15 cases, wrong-eye block in 14, wrong patient or procedure in 8, and wrong corneal transplant in 2. Use of the Universal Protocol would have prevented the confusion in 90 cases (85%). Surgical confusions occur infrequently. Although they usually cause little or no permanent injury, consequences for the patient, the physician, and the profession may be serious. Measures to prevent such confusions deserve the acceptance, support, and active participation of ophthalmologists.
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Investigation of contributing factors regarding wrong-way driving on freeways.
DOT National Transportation Integrated Search
2012-10-01
In Illinois, there were 217 wrong-way crashes on freeways from 2004 to 2009, resulting in 44 killed and : 248 injured. This research project sought to determine the contributing factors to wrong-way crashes on : freeways and to develop promising, cos...
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Lynøe, Niels; Wessel, Maja; Olsson, Daniel; Alexanderson, Kristina; Tännsjö, Torbjörn; Juth, Niklas
2013-10-01
The aim of this study was to examine if it is plausible to interpret the appearance of shame in a Swedish healthcare setting as a reaction to having one's honour wronged. Using a questionnaire, we studied answers from a sample of long-term sick-listed patients who had experienced negative encounters (n=1628) and of these 64% also felt wronged. We used feeling wronged to examine emotional reactions such as feeling ashamed and made the assumption that feeling shame could be associated with having one's honour wronged. In statistical analyses relative risks (RRs) were computed, adjusting for age, sex, disease-labelling, educational levels, as well as their 95% CI. Approximately half of those who had been wronged stated that they also felt shame and of those who felt shame, 93% (CI 91 to 95) felt that they had been wronged. The RR was 4.5 (CI 3.0 to 6.8) for shame when wronged. This can be compared with the other emotional reactions where the RRs were between 1.1 (CI 0.9 to 1.3)-1.4 (CI 1.2 to 1.7). We found no association between country of birth and feeling shame after having experienced negative encounters. We found that the RR of feeling shame when wronged was significantly higher compared with other feelings. Along with theoretical considerations, and the specific types of negative encounters associated with shame, the results indicate that our research hypothesis might be plausible. We think that the results deserve to be used as point of departure for future research.
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Poor visibility : a common cause of wrong-way driving.
DOT National Transportation Integrated Search
1975-01-01
On-site investigations were made of interchanges in Virginia, some of which had been the site of wrong-way entries and some of which had not, and of intersections that had experienced wrong-way incidents. From the observations made on-site it has bee...
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Comparing countermeasures for mitigating wrong-way entries onto limited access facilities.
DOT National Transportation Integrated Search
2017-03-01
Wrong-way crashes are a major cause for safety concerns along freeways and limited-access facilities. Although wrong-way crashes account for a relatively small portion of total crashes, the impact between two cars crashing into each other at high spe...
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The myth of harmless wrongs in moral cognition: Automatic dyadic completion from sin to suffering.
Gray, Kurt; Schein, Chelsea; Ward, Adrian F
2014-08-01
When something is wrong, someone is harmed. This hypothesis derives from the theory of dyadic morality, which suggests a moral cognitive template of wrongdoing agent and suffering patient (i.e., victim). This dyadic template means that victimless wrongs (e.g., masturbation) are psychologically incomplete, compelling the mind to perceive victims even when they are objectively absent. Five studies reveal that dyadic completion occurs automatically and implicitly: Ostensibly harmless wrongs are perceived to have victims (Study 1), activate concepts of harm (Studies 2 and 3), and increase perceptions of suffering (Studies 4 and 5). These results suggest that perceiving harm in immorality is intuitive and does not require effortful rationalization. This interpretation argues against both standard interpretations of moral dumbfounding and domain-specific theories of morality that assume the psychological existence of harmless wrongs. Dyadic completion also suggests that moral dilemmas in which wrongness (deontology) and harm (utilitarianism) conflict are unrepresentative of typical moral cognition. PsycINFO Database Record (c) 2014 APA, all rights reserved.
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Time trend of injection drug errors before and after implementation of bar-code verification system.
Sakushima, Ken; Umeki, Reona; Endoh, Akira; Ito, Yoichi M; Nasuhara, Yasuyuki
2015-01-01
Bar-code technology, used for verification of patients and their medication, could prevent medication errors in clinical practice. Retrospective analysis of electronically stored medical error reports was conducted in a university hospital. The number of reported medication errors of injected drugs, including wrong drug administration and administration to the wrong patient, was compared before and after implementation of the bar-code verification system for inpatient care. A total of 2867 error reports associated with injection drugs were extracted. Wrong patient errors decreased significantly after implementation of the bar-code verification system (17.4/year vs. 4.5/year, p< 0.05), although wrong drug errors did not decrease sufficiently (24.2/year vs. 20.3/year). The source of medication errors due to wrong drugs was drug preparation in hospital wards. Bar-code medication administration is effective for prevention of wrong patient errors. However, ordinary bar-code verification systems are limited in their ability to prevent incorrect drug preparation in hospital wards.
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Mock jury trials in Taiwan--paving the ground for introducing lay participation.
Huang, Kuo-Chang; Lin, Chang-Ching
2014-08-01
The first mock jury study in Taiwan, in which 279 community members watched a videotaped trial, investigated how jurors' estimates of the relative undesirability of wrongful conviction versus wrongful acquittal predicted individual decisions and how decision rules affected outcomes. The percentage of jurors who viewed wrongful conviction as more undesirable increased from 50.9% to 60.9% after deliberation and jurors' postdeliberation acquittal rate (71.7%) was higher than predeliberation acquittal rate (58.8%). Jurors' estimates of the undesirability of wrongful conviction were not correlated with their predeliberation votes but became positively correlated with their postdeliberation decisions. The unanimous rule facilitated jurors' change of vote, predominantly from conviction to acquittal, than the simple majority rule. Jurors reaching a verdict under the unanimous rule viewed deliberation and the verdict more positively. This study indicates that deliberation can ameliorate the problem of most Taiwanese citizens not viewing wrongful conviction as more undesirable than wrongful acquittal. It also suggests that Taiwan should adopt a unanimous rule for its proposed lay participation system.
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Experiencing Wrongful and Unlawful Conviction
ERIC Educational Resources Information Center
Wildeman, Jennifer; Costelloe, Michael; Schehr, Robert
2011-01-01
This study examines how those wrongfully convicted and punished experience life after exoneration. Using data from intensive individual, in-person interviews with 55 exonerees, we measure both the short- and long-term psychological effects associated with wrongful conviction. The results of this research demonstrate that a substantial portion of…
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How Justice System Officials View Wrongful Convictions
ERIC Educational Resources Information Center
Smith, Brad; Zalman, Marvin; Kiger, Angie
2011-01-01
The wrongful conviction of factually innocent people is a growing concern within the United States. Reforms generated by this concern are predicated in part on the views of justice system participants. The authors surveyed judges, police officials, prosecutors, and defense lawyers in Michigan regarding their views of why wrongful convictions…
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Reproductive autonomy, the non-identity problem, and the non-person problem.
DiSilvestro, Russell
2009-01-01
The Non-Identity Problem is the problem of explaining the apparent wrongness of a decision that does not harm people, especially since some of the people affected by the decision would not exist at all were it not for the decision. One approach to this problem, in the context of reproductive decisions, is to focus on wronging, rather than harming, one's offspring. But a Non-Person Problem emerges for any view that claims (1) that only persons can be wronged and (2) that the person-making properties allow for there to be human non-persons. Consider an individual human organism that is prevented from ever possessing the person-making properties. On person-only accounts of the victims of wronging, this organism cannot be wronged by anyone. Hence even individuals whose decisions prevent it from ever possessing the person-making properties cannot wrong it. But this is counter-intuitive. We can think of examples where a human organism is wronged by precisely those decisions that prevent it from possessing the person-making properties. The best solution to this problem, in the case where the person-making property is rational self-governance in pursuit of a meaningful life, is to adjust the concept of a person so that it refers, not merely to those with the immediate capacity for rational self-governance in pursuit of a meaningful life, but also to those with a higher-order capacity for such self-governance. Any solution to the Non-Identity Problem that focuses on wronging rather than harming should incorporate this sort of solution to the Non-Person Problem.
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ERIC Educational Resources Information Center
Ribble, Mike S.; Bailey,Gerald D.
2005-01-01
When you read or hear an unethical suggestion, such as "Steal this article and sell it to another magazine," we're guessing that your internal compass indicates "wrong direction." In other words, your internal voice says, "No, that would be wrong!" Your internal compass tells you when something is right and something is wrong. In our example, your…
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7 CFR 1.51 - Claims based on negligence, wrongful act or omission.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 1 2010-01-01 2010-01-01 false Claims based on negligence, wrongful act or omission. 1.51 Section 1.51 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Claims § 1.51 Claims based on negligence, wrongful act or omission. (a) Authority of the Department...
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The Moral Problem of Health Disparities
2010-01-01
Health disparities exist along lines of race/ethnicity and socioeconomic class in US society. I argue that we should work to eliminate these health disparities because their existence is a moral wrong that needs to be addressed. Health disparities are morally wrong because they exemplify historical injustices. Contractarian ethics, Kantian ethics, and utilitarian ethics all provide theoretical justification for viewing health disparities as a moral wrong, as do several ethical principles of primary importance in bioethics. The moral consequences of health disparities are also troubling and further support the claim that these disparities are a moral wrong. The Universal Declaration of Human Rights provides additional support that health disparities are a moral wrong, as does an analogy with the generally accepted duty to provide equal access to education. In this article, I also consider and respond to 3 objections to my thesis. PMID:20147677
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Statistical Characteristics of Wrong-Way Driving Crashes on Illinois Freeways.
Zhou, Huaguo; Zhao, Jiguang; Pour-Rouholamin, Mahdi; Tobias, Priscilla A
2015-01-01
Driving the wrong way on freeways, namely wrong-way driving (WWD), has been found to be a major concern for more than 6 decades. The purpose of this study was to identify characteristics of this type of crash as well as to rank the locations/interchanges according to their vulnerability to WWD entries. The WWD crash data on Illinois freeways were statistically analyzed for a 6-year time period (2004 to 2009) from 3 aspects: crash, vehicle, and person. The temporal distributions, geographical distributions, roadway characteristics, and crash locations were analyzed for WWD crashes. The driver demographic information, physical condition, and injury severity were analyzed for wrong-way drivers. The vehicle characteristics, vehicle operation, and collision results were analyzed for WWD vehicles. A method was brought about to identify wrong-way entry points that was then used to develop a relative-importance technique and rank different interchange types in terms of potential WWD incidents. The findings revealed that a large proportion of WWD crashes occurred during the weekend from midnight to 5 a.m. Approximately 80% of WWD crashes were located in urban areas and nearly 70% of wrong-way vehicles were passenger cars. Approximately 58% of wrong-way drivers were driving under the influence (DUI). Of those, nearly 50% were confirmed to be impaired by alcohol, about 4% were impaired by drugs, and more than 3% had been drinking. The analysis of interchange ranking found that compressed diamond interchanges, single point diamond interchanges (SPDIs), partial cloverleaf interchanges, and freeway feeders had the highest wrong-way crash rates (wrong-way crashes per 100 interchanges per year). The findings of this study call for more attention to WWD crashes from different aspects such as driver age group, time of day, day of week, and DUI drivers. Based on the analysis results of WWD distance, the study explained why a 5-mile radius of WWD crash location should be studied for WWD fatal crashes with unknown entry points.
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Experience of wrong site surgery and surgical marking practices among clinicians in the UK
Giles, Sally J; Rhodes, Penny; Clements, Gill; Cook, Gary A; Hayton, Ruth; Maxwell, Melanie J; Sheldon, Trevor A; Wright, John
2006-01-01
Background Little is known about the incidence of “wrong site surgery”, but the consequences of this type of medical error can be severe. Guidance from both the USA and more recently the UK has highlighted the importance of preventing error by marking patients before surgery. Objective To investigate the experiences of wrong site surgery and current marking practices among clinicians in the UK before the release of a national Correct Site Surgery Alert. Methods 38 telephone or face‐to‐face interviews were conducted with consultant surgeons in ophthalmology, orthopaedics and urology in 14 National Health Service hospitals in the UK. The interviews were coded and analysed thematically using the software package QSR Nud*ist 6. Results Most surgeons had experience of wrong site surgery, but there was no clear pattern of underlying causes. Marking practices varied considerably. Surgeons were divided on the value of marking and varied in their practices. Orthopaedic surgeons reported that they marked before surgery; however, some urologists and ophthalmologists reported that they did not. There seemed to be no formal hospital policies in place specifically relating to wrong site surgery, and there were problems associated with implementing a system of marking in some cases. The methods used to mark patients also varied. Some surgeons believed that marking was a limited method of preventing wrong site surgery and may even increase the risk of wrong site surgery. Conclusion Marking practices are variable and marking is not always used. Introducing standard guidance on marking may reduce the overall risk of wrong site surgery, especially as clinicians work at different hospital sites. However, the more specific needs of people and specialties must also be considered. PMID:17074875
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Wrong-way driving crashes on French divided roads.
Kemel, Emmanuel
2015-02-01
The objective of divided roads is to increase users' safety by posting unidirectional traffic flows. It happens however that drivers proceed in the wrong direction, endangering themselves as well as other users. The crashes caused by wrong-way drivers are generally spotlighted by the media and call for public intervention. This paper proposes a characterization of wrong-way driving crashes occurring on French divided road on the 2008-2012 period. The objective is to identify the factors that delineate between wrong-way driving crashes and other crashes. Building on the national injury road crash database, 266 crashes involving a wrong-way driver were identified. Their characteristics (related to timing, location, vehicle and driver) are compared to those of the 22,120 other crashes that occurred on the same roads over the same period. The comparison relies on descriptive statistics, completed by a logistic regression. Wrong-way driving crashes are rare but severe. They are more likely to occur during night hours and on non-freeway roads than other crashes. Wrong-way drivers are older, more likely to be intoxicated, to be locals, to drive older vehicles, mainly passenger cars without passengers, than other drivers. The differences observed across networks can help prioritizing public intervention. Most of the identified WW-driving factors deal with cognitive impairment. Therefore, the specific countermeasures such as alternative road signs should be designed for and tested on cognitively impaired drivers. Nevertheless, WW-driving factors are also risk factors for other types of crashes (e.g. elderly driving, drunk driving and age of the vehicle). This suggests that, instead of (or in addition to) developing WW-driving specific countermeasures, managing these risk factors would help reducing a larger number of crashes. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Vitale, Michael; Minkara, Anas; Matsumoto, Hiroko; Albert, Todd; Anderson, Richard; Angevine, Peter; Buckland, Aaron; Cho, Samuel; Cunningham, Matthew; Errico, Thomas; Fischer, Charla; Kim, Han Jo; Lehman, Ronald; Lonner, Baron; Passias, Peter; Protopsaltis, Themistocles; Schwab, Frank; Lenke, Lawrence
Consensus-building using the Delphi and nominal group technique. To establish best practice guidelines using formal techniques of consensus building among a group of experienced spinal deformity surgeons to avert wrong-level spinal deformity surgery. Numerous previous studies have demonstrated that wrong-level spinal deformity occurs at a substantial rate, with more than half of all spine surgeons reporting direct or indirect experience operating on the wrong levels. Nevertheless, currently, guidelines to avert wrong-level spinal deformity surgery have not been developed. The Delphi process and nominal group technique were used to formally derive consensus among 16 fellowship-trained spine surgeons. Surgeons were surveyed for current practices, presented with the results of a systematic review, and asked to vote anonymously for or against item inclusion during three iterative rounds. Agreement of 80% or higher was considered consensus. Items near consensus (70% to 80% agreement) were probed in detail using the nominal group technique in a facilitated group meeting. Participants had a mean of 13.4 years of practice (range: 2-32 years) and 103.1 (range: 50-250) annual spinal deformity surgeries, with a combined total of 24,200 procedures. Consensus was reached for the creation of best practice guidelines (BPGs) consisting of 17 interventions to avert wrong-level surgery. A final checklist consisting of preoperative and intraoperative methods, including standardized vertebral-level counting and optimal imaging criteria, was supported by 100% of participants. We developed consensus-based best practice guidelines for the prevention of wrong-vertebral-level surgery. This can serve as a tool to reduce the variability in preoperative and intraoperative practices and guide research regarding the effectiveness of such interventions on the incidence of wrong-level surgery. Level V. Copyright © 2017 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.
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Why wrongful birth actions are right.
Dimopoulos, Penny; Bagaric, Mirko
2003-11-01
A wrongful birth action is a claim in negligence brought by parents of a child against a doctor who has "wrongfully" caused their child to be born. These claims can be divided into two categories: those where a doctor performs a failed sterilisation procedure that leads to a healthy child being born; and those where a doctor fails to provide sufficient information to allow parents to choose to abort a handicapped child. The recent decision of the High Court of Australia in Cattanach v Melchior (2003) 77 ALJR 1312 falls into the former category. The decision to allow the parents to receive damages for the costs of raising and maintaining their child has generated much public debate. Despite the endorsement of this "wrongful birth" action, there are indications that the legislature will overturn the decision. This article examines whether there is a sound doctrinal basis for recognising wrongful birth actions.
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Birth, meaningful viability and abortion.
Jensen, David
2015-06-01
What role does birth play in the debate about elective abortion? Does the wrongness of infanticide imply the wrongness of late-term abortion? In this paper, I argue that the same or similar factors that make birth morally significant with regard to abortion make meaningful viability morally significant due to the relatively arbitrary time of birth. I do this by considering the positions of Mary Anne Warren and José Luis Bermúdez who argue that birth is significant enough that the wrongness of infanticide does not imply the wrongness of late-term abortion. On the basis of the relatively arbitrary timing of birth, I argue that meaningful viability is the point at which elective abortion is prima facie morally wrong. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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Omissions and Byproducts across Moral Domains
DeScioli, Peter; Asao, Kelly; Kurzban, Robert
2012-01-01
Research indicates that moral violations are judged less wrong when the violation results from omission as opposed to commission, and when the violation is a byproduct as opposed to a means to an end. Previous work examined these effects mainly for violent offenses such as killing. Here we investigate the generality of these effects across a range of moral violations including sexuality, food, property, and group loyalty. In Experiment 1, we observed omission effects in wrongness ratings for all of the twelve offenses investigated. In Experiments 2 and 3, we observed byproduct effects in wrongness ratings for seven and eight offenses (out of twelve), respectively, and we observed byproduct effects in forced-choice responses for all twelve offenses. Our results address an ongoing debate about whether different cognitive systems compute moral wrongness for different types of behaviors (surrounding violence, sexuality, food, etc.), or, alternatively, a common cognitive architecture computes wrongness for a variety of behaviors. PMID:23071678
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Industrial Arts: Call It What You Want, the Need Still Exists
ERIC Educational Resources Information Center
Howlett, James
2008-01-01
In this article, the author argues that teaching "technological literacy" at the expense of hands-on skills training is wrong for the students, wrong for the economy, and wrong for the nation. Students need not only the opportunity to explore a variety of trade skills but also the opportunity to learn a skill well. It is in the teaching…
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Smacked by the Invisible Hand: The Wrong Debate at the Wrong Time with the Wrong People
ERIC Educational Resources Information Center
Laitsch, Daniel
2013-01-01
Over the past three decades, educators have faced an increasing variety of reform proposals that can best be contextualized as efforts to commodify and privatize public education. While supporters of market-based reforms attempt to place these proposals within education theory, they are in reality firmly entrenched in neoliberal economic theory.…
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Kinetic selection vs. free energy of DNA base pairing in control of polymerase fidelity.
Oertell, Keriann; Harcourt, Emily M; Mohsen, Michael G; Petruska, John; Kool, Eric T; Goodman, Myron F
2016-04-19
What is the free energy source enabling high-fidelity DNA polymerases (pols) to favor incorporation of correct over incorrect base pairs by 10(3)- to 10(4)-fold, corresponding to free energy differences of ΔΔGinc∼ 5.5-7 kcal/mol? Standard ΔΔG° values (∼0.3 kcal/mol) calculated from melting temperature measurements comparing matched vs. mismatched base pairs at duplex DNA termini are far too low to explain pol accuracy. Earlier analyses suggested that pol active-site steric constraints can amplify DNA free energy differences at the transition state (kinetic selection). A recent paper [Olson et al. (2013)J Am Chem Soc135:1205-1208] used Vent pol to catalyze incorporations in the presence of inorganic pyrophosphate intended to equilibrate forward (polymerization) and backward (pyrophosphorolysis) reactions. A steady-state leveling off of incorporation profiles at long reaction times was interpreted as reaching equilibrium between polymerization and pyrophosphorolysis, yielding apparent ΔG° = -RTlnKeq, indicating ΔΔG° of 3.5-7 kcal/mol, sufficient to account for pol accuracy without need of kinetic selection. Here we perform experiments to measure and account for pyrophosphorolysis explicitly. We show that forward and reverse reactions attain steady states far from equilibrium for wrong incorporations such as G opposite T. Therefore,[Formula: see text]values obtained from such steady-state evaluations ofKeqare not dependent on DNA properties alone, but depend largely on constraints imposed on right and wrong substrates in the polymerase active site.
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ERIC Educational Resources Information Center
Olson, Kristina R.; Shaw, Alex
2011-01-01
Adults believe that plagiarizing ideas is wrong, which requires an understanding that others can have ideas and that it is wrong to copy them. In order to test when this understanding emerges, we investigated when children begin to think plagiarism is wrong. In Study 1, children aged 7, 9 and 11 years old, as well as adults, disliked someone who…
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ERIC Educational Resources Information Center
Khaksefidi, Saman
2017-01-01
This study investigates the psychological effect of a wrong question with wrong items on answering to the next question in a test of structure. Forty students selected through stratified random sampling are given 15 questions of a standardized test namely a TOEFL structure test in which questions number 7 and number 11 are wrong and their answers…
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Sada, Oumer; Melkie, Addisu; Shibeshi, Workineh
2015-09-16
Medication errors (MEs) are important problems in all hospitalized populations, especially in intensive care unit (ICU). Little is known about the prevalence of medication prescribing errors in the ICU of hospitals in Ethiopia. The aim of this study was to assess medication prescribing errors in the ICU of Tikur Anbessa Specialized Hospital using retrospective cross-sectional analysis of patient cards and medication charts. About 220 patient charts were reviewed with a total of 1311 patient-days, and 882 prescription episodes. 359 MEs were detected; with prevalence of 40 per 100 orders. Common prescribing errors were omission errors 154 (42.89%), 101 (28.13%) wrong combination, 48 (13.37%) wrong abbreviation, 30 (8.36%) wrong dose, wrong frequency 18 (5.01%) and wrong indications 8 (2.23%). The present study shows that medication errors are common in medical ICU of Tikur Anbessa Specialized Hospital. These results suggest future targets of prevention strategies to reduce the rate of medication error.
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-08-05
... on negligence, wrongful act or omission. Authority: 12 U.S.C. 5492(a)(1), (11); 28 U.S.C. 2672; 28 CFR 14.11. Sec. 1076.101 Claims against a Bureau employee based on negligence, wrongful act or... representative may present a claim against a Bureau employee based on negligence, or wrongful act or omission, as...
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ERIC Educational Resources Information Center
Ladson-Billings, Gloria
2004-01-01
The first part of the title of this lecture is taken from Ajay Heble's (2000) book "Landing on the Wrong Note: Jazz, Dissonance, and Critical Practice." The author chose this musical image to convey the problem of good intentions gone awry. No musician plans to play the wrong note. The plaintiffs, litigators, Supreme Court Justices, and civil…
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ERIC Educational Resources Information Center
Gauderat-Bagault, Laurence; Lehalle, Henri
Children, ages 5 to 8 years (n=71), were required to listen and detect errors out of a partly wrong sequence of tape-recorded French number words from 1 to 100. Children (from several schools near Montpellier, France) were from preschool, grade 1, and grade 2. Results show that wrong syntactic rules were better detected than omissions, whereas…
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Neily, Julia; Chomsky, Amy; Orcutt, James; Paull, Douglas E; Mills, Peter D; Gilbert, Christina; Hemphill, Robin R; Gunnar, William
2018-03-01
The study goals were to examine wrong intraocular lens (IOL) implant adverse events in the Veterans Health Administration (VHA), identify root causes and contributing factors, and describe system changes that have been implemented to address this challenge. This study represents collaboration between the VHA's National Center for Patient Safety (NCPS) and the National Surgery Office (NSO). This report includes 45 wrong IOL implant surgery adverse events reported to established VHA NCPS and NSO databases between July 1, 2006, and June 31, 2014. There are approximately 50,000 eye implant procedures performed each year in the VHA. Wrong IOL implant surgery adverse events are reported by VHA facilities to the NCPS and the NSO. Two authors (A.C. and J.N.) coded the reports for event type (wrong lens or expired lens) and identified the primary contributing factor (coefficient κ = 0.837). A descriptive analysis was conducted, which included the reported yearly event rate. The main outcome measure was the reported wrong IOL implant surgery adverse events. There were 45 reported wrong IOL implant surgery adverse events. Between 2011 and June 30, 2014, there was a significant downward trend (P = 0.02, R = 99.7%) at a pace of -0.08 (per 10,000 cases) every year. The most frequently coded primary contributing factor was incomplete preprocedure time-out (n = 12) followed by failure to perform double check of preprocedural calculations based upon original data and implant read-back at the time the surgical eye implant was performed (n = 10). Preventing wrong IOL implant adverse events requires diligence beyond performance of the preprocedural time-out. In 2013, the VHA has modified policy to ensure double check of preprocedural calculations and implant read-back with positive impact. Continued analysis of contributing human factors and improved surgical team communication are warranted.
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Gadkari, Varun V.; Tokarsky, E. John; Malik, Chanchal K.; Basu, Ashis K.; Suo, Zucai
2014-01-01
3-Nitrobenzanthrone (3-NBA), a nitropolyaromatic hydrocarbon (NitroPAH) pollutant in diesel exhaust, is a potent mutagen and carcinogen. After metabolic activation, the primary metabolites of 3-NBA react with DNA to form dG and dA adducts. One of the three major adducts identified is N-(2’-deoxyguanosin-8-yl)-3-aminobenzanthrone (dGC8-N-ABA). This bulky adduct likely stalls replicative DNA polymerases but can be traversed by lesion bypass polymerases in vivo. Here, we employed running start assays to show that a site-specifically placed dGC8-N-ABA is bypassed in vitro by Sulfolobus solfataricus DNA polymerase IV (Dpo4), a model Y-family DNA polymerase. However, the nucleotide incorporation rate of Dpo4 was significantly reduced opposite both the lesion and the template position immediately downstream from the lesion site, leading to two strong pause sites. To investigate the kinetic effect of dGC8-N-ABA on polymerization, we utilized pre-steady-state kinetic methods to determine the kinetic parameters for individual nucleotide incorporations upstream, opposite, and downstream from the dGC8-N-ABA lesion. Relative to the replication of the corresponding undamaged DNA template, both nucleotide incorporation efficiency and fidelity of Dpo4 were considerably decreased during dGC8-N-ABA lesion bypass and the subsequent extension step. The lower nucleotide incorporation efficiency caused by the lesion is a result of a significantly reduced dNTP incorporation rate constant and modestly weaker dNTP binding affinity. At both pause sites, nucleotide incorporation followed biphasic kinetics with a fast and a slow phase and their rates varied with nucleotide concentration. In contrast, only the fast phase was observed with undamaged DNA. A kinetic mechanism was proposed for the bypass of dGC8-N-ABA bypass catalyzed by Dpo4. PMID:25048879
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Gadkari, Varun V; Tokarsky, E John; Malik, Chanchal K; Basu, Ashis K; Suo, Zucai
2014-09-01
3-Nitrobenzanthrone (3-NBA), a nitropolyaromatic hydrocarbon (NitroPAH) pollutant in diesel exhaust, is a potent mutagen and carcinogen. After metabolic activation, the primary metabolites of 3-NBA react with DNA to form dG and dA adducts. One of the three major adducts identified is N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (dG(C8-N-ABA)). This bulky adduct likely stalls replicative DNA polymerases but can be traversed by lesion bypass polymerases in vivo. Here, we employed running start assays to show that a site-specifically placed dG(C8-N-ABA) is bypassed in vitro by Sulfolobus solfataricus DNA polymerase IV (Dpo4), a model Y-family DNA polymerase. However, the nucleotide incorporation rate of Dpo4 was significantly reduced opposite both the lesion and the template position immediately downstream from the lesion site, leading to two strong pause sites. To investigate the kinetic effect of dG(C8-N-ABA) on polymerization, we utilized pre-steady-state kinetic methods to determine the kinetic parameters for individual nucleotide incorporations upstream, opposite, and downstream from the dG(C8-N-ABA) lesion. Relative to the replication of the corresponding undamaged DNA template, both nucleotide incorporation efficiency and fidelity of Dpo4 were considerably decreased during dG(C8-N-ABA) lesion bypass and the subsequent extension step. The lower nucleotide incorporation efficiency caused by the lesion is a result of a significantly reduced dNTP incorporation rate constant and modestly weaker dNTP binding affinity. At both pause sites, nucleotide incorporation followed biphasic kinetics with a fast and a slow phase and their rates varied with nucleotide concentration. In contrast, only the fast phase was observed with undamaged DNA. A kinetic mechanism was proposed for the bypass of dG(C8-N-ABA) bypass catalyzed by Dpo4. Copyright © 2014 Elsevier B.V. All rights reserved.
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What are the Limitations of Enzymes in Synthetic Organic Chemistry?
Reetz, Manfred T
2016-12-01
Enzymes have been used in organic chemistry and biotechnology for 100 years, but their widespread application has been prevented by a number of limitations, including the often-observed limited thermostability, narrow substrate scope, and low or wrong stereo- and/or regioselectivity. Directed evolution provides a means to address and generally solve these problems, especially since recent methodology development has made this protein engineering method faster, more efficient, and more reliable than in the past. This Darwinian approach to asymmetric catalysis has led to a number of industrial applications. Metabolic-pathway engineering, mutasynthesis, and fermentation are likewise enzyme-based techniques that enrich chemistry. This account outlines the scope, and particularly, the limitations, of biocatalysis. The complementary nature of enzymes and man-made catalysts is emphasized. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Wrongful Convictions: Understanding the Experiences of the Original Crime Victims.
Williamson, Erin J; Stricker, Julie M; Irazola, Seri P; Niedzwiecki, Emily
2016-01-01
Over the past 3 decades, significant strides have been made to identify and assist wrongfully convicted individuals in gaining their freedom and transitioning to life after exoneration. However, little is known about the experiences of the original crime victims during this process. The impact of wrongful convictions on victims has not been empirically researched; most of what is known has been provided anecdotally by stakeholders working with victims, and in a few instances, by victims themselves (e.g., Jenkins, 2009; Levey, 2004; Thompson-Cannino, Cotton, & Torneo, 2009). In an effort to begin to fill this gap in knowledge, ICF International conducted in-depth studies of 11 cases to identify the shared experiences and service needs of victims across cases of wrongful conviction.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Banerjee, Surajit; Christov, Plamen P.; Kozekova, Albena
trans-4-Hydroxynonenal (HNE) is the major peroxidation product of {omega}-6 polyunsaturated fatty acids in vivo. Michael addition of the N{sub 2}-amino group of dGuo to HNE followed by ring closure of N1 onto the aldehyde results in four diastereomeric 1,N{sub 2}-dGuo (1,N{sub 2}-HNE-dGuo) adducts. The (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct was incorporated into the 18-mer templates 5'-d(TCATXGAATCCTTCCCCC)-3' and d(TCACXGAATCCTTCCCCC)-3', where X = (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct. These differed in the identity of the template 5'-neighbor base, which was either Thy or Cyt, respectively. Each of these templates was annealed with either a 13-mer primer 5'-d(GGGGGAAGGATTC)-3' or a 14-mer primer 5'-d(GGGGGAAGGATTCC)-3'. The addition of dNTPsmore » to the 13-mer primer allowed analysis of dNTP insertion opposite to the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct, whereas the 14-mer primer allowed analysis of dNTP extension past a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair. The Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) belongs to the Y-family of error-prone polymerases. Replication bypass studies in vitro reveal that this polymerase inserted dNTPs opposite the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct in a sequence-specific manner. If the template 5'-neighbor base was dCyt, the polymerase inserted primarily dGTP, whereas if the template 5'-neighbor base was dThy, the polymerase inserted primarily dATP. The latter event would predict low levels of Gua {yields} Thy mutations during replication bypass when the template 5'-neighbor base is dThy. When presented with a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair, the polymerase conducted full-length primer extension. Structures for ternary (Dpo4-DNA-dNTP) complexes with all four template-primers were obtained. For the 18-mer:13-mer template-primers in which the polymerase was confronted with the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo adduct, the (6S,8R,11S)-1,N{sub 2}-dGuo lesion remained in the ring-closed conformation at the active site. The incoming dNTP, either dGTP or dATP, was positioned with Watson-Crick pairing opposite the template 5'-neighbor base, dCyt or dThy, respectively. In contrast, for the 18-mer:14-mer template-primers with a primed (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair, ring opening of the adduct to the corresponding N{sub 2}-dGuo aldehyde species occurred. This allowed Watson-Crick base pairing at the (6S,8R,11S)-HNE-1,N{sub 2}-dGuo:dCyd pair.« less
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Operating room briefings and wrong-site surgery.
Makary, Martin A; Mukherjee, Arnab; Sexton, J Bryan; Syin, Dora; Goodrich, Emmanuelle; Hartmann, Emily; Rowen, Lisa; Behrens, Drew C; Marohn, Michael; Pronovost, Peter J
2007-02-01
Wrong-site surgery can be a catastrophic event for a patient, caregiver, and institution. Although communication breakdowns have been identified as the leading cause of wrong-site surgery, the efficacy of preventive strategies remains unknown. This study evaluated the impact of operating room briefings on coordination of care and risk for wrong-site surgery. We administered a case-based version of the Safety Attitudes Questionnaire (SAQ) to operating room (OR) staff at an academic medical center, before and after initiation of an OR briefing program. Items questioned overall coordination and awareness of the surgical site. Response options ranged from 1 (disagree strongly) to 5 (agree strongly). MANOVA was used to compare caregiver assessments before and after the implementation of briefings, and the percentage of OR staff agreeing or disagreeing with each question was reported. The prebriefing response rate was 85% (306 of 360 respondents), and the postbriefing response rate was 75% (116 of 154). Respondents included surgeons (34.9%), anesthesiologists (14.0%), and nurses (44.4%). Briefings were associated with caregiver perceptions of reduced risk for wrong-site surgery and improved collaboration [F (6,390)=10.15, p < 0.001]. Operating room caregiver assessments of briefing and wrong-site surgery issues improved for 5 of 6 items, eg, "Surgery and anesthesia worked together as a well-coordinated team" (67.9% agreed prebriefing, 91.5% agreed postbriefing, p < 0.0001), and "A preoperative discussion increased my awareness of the surgical site and side being operated on" (52.4% agreed prebriefing, 64.4% agreed postbriefing, p < 0.001). OR briefings significantly reduce perceived risk for wrong-site surgery and improve perceived collaboration among OR personnel.
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What’s Wrong with the Survivor Benefit Plan?
1986-04-01
Found aspects of the program confusing. Most often mentioned were the benefit adjustment mechanism and the special tax advantage Features. Not...WHAT’S WRONG WITH THE SURVIVOR BENEFIT PLAN? AUTHOR(S) MAJOR RALPH A. BLA1ELOCK, USAF FACULTY ADVISOR MAJOR MACK FOSTER, ACSC/EDCM SPONSOR LT COLONEL...Include.ecurslty Ckwaaicationl WHAT’S WRONG WITH THE SURVIVOR BENEFIT , PERSONAL AUTHORST Blakelock, ph A., Major, USAF 13a. TYPE OF REPORT 13t. TIME
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What's Wrong with Economics Textbooks?
ERIC Educational Resources Information Center
Culyer, A. J.
1985-01-01
Many things are wrong with college level economics textbooks. For example, they are too ahistorical, too particularist, or unsystematically eclectic. The requirements of a good college economics textbook are examined. (RM)
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Wrongful life: the problem of causation.
Mason, J K
2004-01-01
The paper considers the status of the wrongful life action particularly in the light of the recent acceptance of such actions in continental Europe. It is considered that the hurdle of causation is still not adequately overcome in these cases and, in a search for an answer to the difficulty, the author re-examines the Canadian case of Cherry v Borsman. This case was originally thought of as one of wrongful life associated with a negligently performed abortion and the paper attempts to overcome the problems of causation by comparing and contrasting the roles of the genetic counsellor and the abortionist. While the attempt is by no means wholly successful, it also serves to draw attention to some significant differences between wrongful life actions based on physical and mental disability in the neonate.
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49 CFR Appendix A to Part 231 - Schedule of Civil Penalties 1
Code of Federal Regulations, 2011 CFR
2011-10-01
... 120.B1Brake Step or Brace Bent 2,500 5,000 120.B2Brake Step or Wrong Dimensions 2,500 5,000 120...,000 124.B1Running Board Bent to the Extent that It is Unsafe 2,500 5,000 124.B2Running Board Wrong... 126.B1End Platform or Brace Bent 2,500 5,000 126.B2End Platform Wrong Dimensions 2,500 5,000 126.C1End...
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Evgenia, Smyrnaki
2012-03-01
The main scope of the article is the bioethical and legal issues of wrongful birth and wrongful life with reference to doctors' medical liability. Nowadays, prenatal tests tend to substitute the eugenic practice of Spartan inspection to raise a strong and healthy child. Should the doctor misinform the parents that the child is healthy and the parents do not exercise the right to abort the pregnancy, the doctor can be held liable and claims on wrongful life or birth are raised against him. "Wrongful life" is an oxymoron itself since "life" which has an intrinsic value and sanctity is attributed a negative aspect and is regarded as damage. Courts around the world have awarded parents compensation on that legal ground. In the Perruche affair (2000), where the mother was wrongly diagnosed and gave birth to Nicholas, who had serious neurological problems, the court conferred the right on the child itself, causing an uproar in France. The decision was criticized for encouraging eugenics and diminishing the value of handicapped people. The different approaches to the above issues by different courts around the world (US, EU) with reference to (bio) ethical concerns are going to be examined. We will try to give an answer on whether it is possible for courts to support on legal and bioethical grounds that a child with disabilities should not have been born as a result of the doctor's negligent conduct. In such cases, the limits of normality and the value of life are challenged
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Li, Guangyue; Wang, Jian-Bo; Reetz, Manfred T
2018-04-01
Enzymes have been used for a long time as catalysts in the asymmetric synthesis of chiral intermediates needed in the production of therapeutic drugs. However, this alternative to man-made catalysts has suffered traditionally from distinct limitations, namely the often observed wrong or insufficient enantio- and/or regioselectivity, low activity, narrow substrate range, and insufficient thermostability. With the advent of directed evolution, these problems can be generally solved. The challenge is to develop and apply the most efficient mutagenesis methods which lead to highest-quality mutant libraries requiring minimal screening. Structure-guided saturation mutagenesis and its iterative form have emerged as the method of choice for evolving stereo- and regioselective mutant enzymes needed in the asymmetric synthesis of chiral intermediates. The number of (industrial) applications in the preparation of chiral pharmaceuticals is rapidly increasing. This review features and analyzes typical case studies. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Nwosu, Arinze
2015-01-01
Wrong- site surgeries are iatrogenic errors encountered in the course of surgical patient management. Despite the 'never do harm' pledge in the 'Hippocratic Oath' drafted in 5(th) century BC, man is after all human, with this limitation manifesting in the physician's art despite his best intention. Beyond the catastrophic consequences of wrong- site surgery on the patient and surgeon, and the opprobrium on the art of medicine, the incidents have come to be regarded as a quality-of-care indicator. Orthopaedic surgery is a specialty with a preponderance of this phenomenon and the attendant medico-legal issues relating to malpractice claims. Consequently the specialty had pioneered institutional initiatives at preventing these 'friendly-fires'. Awareness and implementation of these initiatives however remain low in many parts of the world, hampered by a culture of denial and shame. This report presents two cases of wrong-site surgery following trauma from road-traffic accident. The first case was a closed reduction of the 'wrong' dislocated hip in the trauma/emergency unit under the care of senior residents, while the second case was attempted wrong-site surgery on the right leg in a patient with fracture of the left tibia, in conjunction with bilateral femoral fracture and right radio-ulnar fracture; by an experienced Chief Consultant Orthopaedic Surgeon operating elective list. Both are orthopaedic cases, each with some trauma to both lower extremeties. Neither of the cases was formally mentioned anywhere in clinical discourse in the hospital, much less a formal report or audit. There was no formal, institutionalized process to prevent wrong-site surgery in the health institution and this could have been largely responsible for these incidents. An open, mandatory process of reporting such incidents for relevant audit and awareness is necessary, as a mechanism for prevention rather than blame or punishment.
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DOT National Transportation Integrated Search
2018-01-01
Connected vehicles (CVs) and their integration with transportation infrastructure provide new approaches to wrong-way driving (WWD) detection, warning, verification, and intervention that will help practitioners further reduce the occurrence and seve...
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p p →A →Z h and the wrong-sign limit of the two-Higgs-doublet model
NASA Astrophysics Data System (ADS)
Ferreira, Pedro M.; Liebler, Stefan; Wittbrodt, Jonas
2018-03-01
We point out the importance of the decay channels A →Z h and H →V V in the wrong-sign limit of the two-Higgs-doublet model (2HDM) of type II. They can be the dominant decay modes at moderate values of tan β , even if the (pseudo)scalar mass is above the threshold where the decay into a pair of top quarks is kinematically open. Accordingly, large cross sections p p →A →Z h and p p →H →V V are obtained and currently probed by the LHC experiments, yielding conclusive statements about the remaining parameter space of the wrong-sign limit. In addition, mild excesses—as recently found in the ATLAS analysis b b ¯→A →Z h —could be explained. The wrong-sign limit makes other important testable predictions for the light Higgs boson couplings.
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Simkulet, William
2018-01-01
Don Marquis is well known for his future like ours theory (FLO), according to which the killing beings like us is seriously morally wrong because it deprives us of a future we can value. According to Marquis, human fetuses possess a future they can come to value, and thus according to FLO have a right to life. Recently Mark Brown has argued that even if FLO shows fetuses have a right to life, it fails to show that fetuses have a right to use their mother's body, evoking Judith Jarvis Thomson's famous violinist case. In the wake of Brown's conclusion, Marquis presents a new argument-the parenthood argument (PA)-which he believes shows that abortion is seriously morally wrong. Here I argue that the PA fails to show abortion is seriously morally wrong for the same reasons FLO fails to show abortion is seriously morally wrong. © 2017 John Wiley & Sons Ltd.
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Effects of a direct refill program for automated dispensing cabinets on medication-refill errors.
Helmons, Pieter J; Dalton, Ashley J; Daniels, Charles E
2012-10-01
The effects of a direct refill program for automated dispensing cabinets (ADCs) on medication-refill errors were studied. This study was conducted in designated acute care areas of a 386-bed academic medical center. A wholesaler-to-ADC direct refill program, consisting of prepackaged delivery of medications and bar-code-assisted ADC refilling, was implemented in the inpatient pharmacy of the medical center in September 2009. Medication-refill errors in 26 ADCs from the general medicine units, the infant special care unit, the surgical and burn intensive care units, and intermediate units were assessed before and after the implementation of this program. Medication-refill errors were defined as an ADC pocket containing the wrong drug, wrong strength, or wrong dosage form. ADC refill errors decreased by 77%, from 62 errors per 6829 refilled pockets (0.91%) to 8 errors per 3855 refilled pockets (0.21%) (p < 0.0001). The predominant error type detected before the intervention was the incorrect medication (wrong drug, wrong strength, or wrong dosage form) in the ADC pocket. Of the 54 incorrect medications found before the intervention, 38 (70%) were loaded in a multiple-drug drawer. After the implementation of the new refill process, 3 of the 5 incorrect medications were loaded in a multiple-drug drawer. There were 3 instances of expired medications before and only 1 expired medication after implementation of the program. A redesign of the ADC refill process using a wholesaler-to-ADC direct refill program that included delivery of prepackaged medication and bar-code-assisted refill significantly decreased the occurrence of ADC refill errors.
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Sequence Learning Under Uncertainty in Children: Self-Reflection vs. Self-Assertion
Lange-Küttner, Christiane; Averbeck, Bruno B.; Hirsch, Silvia V.; Wießner, Isabel; Lamba, Nishtha
2012-01-01
We know that stochastic feedback impairs children’s associative stimulus–response (S–R) learning (Crone et al., 2004a; Eppinger et al., 2009), but the impact of stochastic feedback on sequence learning that involves deductive reasoning has not been not tested so far. In the current study, 8- to 11-year-old children (N = 171) learned a sequence of four left and right button presses, LLRR, RRLL, LRLR, RLRL, LRRL, and RLLR, which needed to be deduced from feedback because no directional cues were given. One group of children experienced consistent feedback only (deterministic feedback, 100% correct). In this condition, green feedback on the screen indicated that the children had been right when they were right, and red feedback indicated that the children had been wrong when they were wrong. Another group of children experienced inconsistent feedback (stochastic feedback, 85% correct, 15% false), where in some trials, green feedback on the screen could signal that children were right when in fact they were wrong, and red feedback could indicate that they were wrong when in fact they had been right. Independently of age, children’s sequence learning in the stochastic condition was initially much lower than in the deterministic condition, but increased gradually and improved with practice. Responses toward positive vs. negative feedback varied with age. Children were increasingly able to understand that they could have been wrong when feedback indicated they were right (self-reflection), but they remained unable to understand that they could have been right when feedback indicated they were wrong (self-assertion). PMID:22563324
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Sequence Learning Under Uncertainty in Children: Self-Reflection vs. Self-Assertion.
Lange-Küttner, Christiane; Averbeck, Bruno B; Hirsch, Silvia V; Wießner, Isabel; Lamba, Nishtha
2012-01-01
We know that stochastic feedback impairs children's associative stimulus-response (S-R) learning (Crone et al., 2004a; Eppinger et al., 2009), but the impact of stochastic feedback on sequence learning that involves deductive reasoning has not been not tested so far. In the current study, 8- to 11-year-old children (N = 171) learned a sequence of four left and right button presses, LLRR, RRLL, LRLR, RLRL, LRRL, and RLLR, which needed to be deduced from feedback because no directional cues were given. One group of children experienced consistent feedback only (deterministic feedback, 100% correct). In this condition, green feedback on the screen indicated that the children had been right when they were right, and red feedback indicated that the children had been wrong when they were wrong. Another group of children experienced inconsistent feedback (stochastic feedback, 85% correct, 15% false), where in some trials, green feedback on the screen could signal that children were right when in fact they were wrong, and red feedback could indicate that they were wrong when in fact they had been right. Independently of age, children's sequence learning in the stochastic condition was initially much lower than in the deterministic condition, but increased gradually and improved with practice. Responses toward positive vs. negative feedback varied with age. Children were increasingly able to understand that they could have been wrong when feedback indicated they were right (self-reflection), but they remained unable to understand that they could have been right when feedback indicated they were wrong (self-assertion).
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A Quality Improvement Project to Decrease Human Milk Errors in the NICU.
Oza-Frank, Reena; Kachoria, Rashmi; Dail, James; Green, Jasmine; Walls, Krista; McClead, Richard E
2017-02-01
Ensuring safe human milk in the NICU is a complex process with many potential points for error, of which one of the most serious is administration of the wrong milk to the wrong infant. Our objective was to describe a quality improvement initiative that was associated with a reduction in human milk administration errors identified over a 6-year period in a typical, large NICU setting. We employed a quasi-experimental time series quality improvement initiative by using tools from the model for improvement, Six Sigma methodology, and evidence-based interventions. Scanned errors were identified from the human milk barcode medication administration system. Scanned errors of interest were wrong-milk-to-wrong-infant, expired-milk, or preparation errors. The scanned error rate and the impact of additional improvement interventions from 2009 to 2015 were monitored by using statistical process control charts. From 2009 to 2015, the total number of errors scanned declined from 97.1 per 1000 bottles to 10.8. Specifically, the number of expired milk error scans declined from 84.0 per 1000 bottles to 8.9. The number of preparation errors (4.8 per 1000 bottles to 2.2) and wrong-milk-to-wrong-infant errors scanned (8.3 per 1000 bottles to 2.0) also declined. By reducing the number of errors scanned, the number of opportunities for errors also decreased. Interventions that likely had the greatest impact on reducing the number of scanned errors included installation of bedside (versus centralized) scanners and dedicated staff to handle milk. Copyright © 2017 by the American Academy of Pediatrics.
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Physicians’ Beliefs About Conscience in Medicine: A National Survey
Lawrence, Ryan E.; Curlin, Farr A.
2010-01-01
Purpose To explore physicians’ beliefs about whether physicians sometimes have a professional obligation to provide medical services even if doing so goes against their conscience, and to examine associations between physicians’ opinions and their religious and ethical commitments. Method A survey was mailed in 2007 to a stratified random sample of 1,000 U.S. primary care physicians, selected from the American Medical Association Physician Masterfile. Participants were classified into three groups according to agreement or disagreement with two statements: “A physician should never do what he or she believes is morally wrong, no matter what experts say,” and “Sometimes physicians have a professional ethical obligation to provide medical services even if they personally believe it would be morally wrong to do so.” Results The response rate was 51% (446/879 delivered questionnaires). Forty-two percent and 22% believed they are never and sometimes, respectively, obligated to do what they personally believe is wrong, and 36% agreed with both statements. Physicians who are more religious are more likely to believe that physicians are never obligated to do what they believe is wrong (58% and 31% of those with high and low intrinsic religiosity, respectively; multivariate odds ratio, 2.9; 95% CI, 1.2–7.2). Those with moral objections to any of three controversial practices were more likely to hold that physicians should never do what they believe is wrong. Conclusion A substantial minority of physicians do not believe there is ever a professional obligation to do something they personally believe is wrong. PMID:19707071
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Crash test and evaluation of 3-ft mounting height sign support system.
DOT National Transportation Integrated Search
2016-07-01
The Texas Department of Transportation (TxDOT) and other transportation agencies continue to : research potential countermeasure for mitigating wrong-way crashes. Because many drivers involved in : wrong-way crashes are impaired, some highway safety ...
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Wrong-way driving at selected interstate off-ramps.
DOT National Transportation Integrated Search
1980-01-01
This study was designed to evaluate, on interstate roadways in Virginia, the use of a technique developed in California for estimating or determining incidences of wrong-way driving at off-ramps. Also, information gained from a survey of the availabl...
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ABC's of HOV : the Texas experience
DOT National Transportation Integrated Search
1999-09-01
The implementation of High Occupancy Vehicle (HOV) lanes is a very important decision. Done right they offer a great opportunity for improving person-movement in a corridor. Done the wrong way or in the wrong place, they can be a significant public r...
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Liability for wrongful terminations: are hospitals at risk?
Hames, D S
1991-01-01
This article examines the extent to which the three principal exceptions to the common-law doctrine of employment-at-will--namely the public policy, implied contract, and good faith and fair dealing exceptions--have been recognized in hospital termination cases. State supreme court and appellate court cases are analyzed to illustrate the type of conduct that precipitated wrongful termination claims against hospitals during the 1980s, how the courts disposed of these claims, and the rationale underlying their decisions. Suggestions, based on these and related cases, for avoiding or at least minimizing liability for wrongfully terminating hospital employees, are presented.
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Measures for preventing wrong-way entries on highways.
DOT National Transportation Integrated Search
1973-01-01
An evaluation of the results of a two-year survey of incidents of wrong-way driving on Virginia highways revealed that the majority of them originated at diamond type interchanges. On-site investigations of a number of the interchanges at which insta...
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Wrong-way vehicle detection : proof of concept.
DOT National Transportation Integrated Search
2013-03-01
Vehicles that enter freeway exit ramps going the wrong way present one of the most serious traffic hazards on : Arizonas urban freeways. Moler cites a study that finds on average 350 people are killed annually in the United : States as a result of...
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Conceptual design of a connected vehicle wrong-way driving detection and management system.
DOT National Transportation Integrated Search
2016-04-01
This report describes the tasks completed to develop a concept of operations, functional requirements, and : high-level system design for a Connected Vehicle (CV) Wrong-Way Driving (WWD) Detection and Management : System. This system was designed to ...
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ERIC Educational Resources Information Center
Update on the Courts, 1996
1996-01-01
This serial issue concerns itself with several conflicts between individual rights and allegedly wrongful acts that the Supreme Court has not considered previously. The articles on these topics illuminate the constitutional issues of equal protection, due process, and freedom of expression. Specific issues addressed include: (1) equal educational…
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31 CFR 100.18 - Counterfeit notes to be marked; “redemption” of notes wrongfully so marked.
Code of Federal Regulations, 2010 CFR
2010-07-01
... moneys, and all officers of national banks, shall stamp or write in plain letters the word “counterfeit... money, which shall be presented at their places of business; and if such officers shall wrongfully stamp...
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The Abc's Of Hov: The Texas Experience
DOT National Transportation Integrated Search
1999-09-01
The implementation of High Occupancy Vehicle (HOV) lanes is a very important decision. Done right they offer a great opportunity for improving person-movement in a corridor. Done the wrong way or in the wrong place, they can be a significant public r...
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kalapurakal, John A., E-mail: j-kalapurakal@northwestern.edu; Zafirovski, Aleksandar; Smith, Jeffery
Purpose: This report describes the value of a voluntary error reporting system and the impact of a series of quality assurance (QA) measures including checklists and timeouts on reported error rates in patients receiving radiation therapy. Methods and Materials: A voluntary error reporting system was instituted with the goal of recording errors, analyzing their clinical impact, and guiding the implementation of targeted QA measures. In response to errors committed in relation to treatment of the wrong patient, wrong treatment site, and wrong dose, a novel initiative involving the use of checklists and timeouts for all staff was implemented. The impactmore » of these and other QA initiatives was analyzed. Results: From 2001 to 2011, a total of 256 errors in 139 patients after 284,810 external radiation treatments (0.09% per treatment) were recorded in our voluntary error database. The incidence of errors related to patient/tumor site, treatment planning/data transfer, and patient setup/treatment delivery was 9%, 40.2%, and 50.8%, respectively. The compliance rate for the checklists and timeouts initiative was 97% (P<.001). These and other QA measures resulted in a significant reduction in many categories of errors. The introduction of checklists and timeouts has been successful in eliminating errors related to wrong patient, wrong site, and wrong dose. Conclusions: A comprehensive QA program that regularly monitors staff compliance together with a robust voluntary error reporting system can reduce or eliminate errors that could result in serious patient injury. We recommend the adoption of these relatively simple QA initiatives including the use of checklists and timeouts for all staff to improve the safety of patients undergoing radiation therapy in the modern era.« less
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Investigation of contributing factors regarding wrong-way driving on freeways, phase II.
DOT National Transportation Integrated Search
2015-09-01
In the second phase of this project, two major tasks were completed: (1) organizing a national wrong-way driving : (WWD) summit and (2) developing guidelines for reducing WWD on freeways. The first national WWD summit was : held in Edwardsville, Illi...
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Teacher Professionalism: The Wrong Conversation.
ERIC Educational Resources Information Center
Coulter, David; Orme, Liz
2000-01-01
Defining teachers as professionals in the same way that doctors or engineers are professionals is reductionist because such definition generally distorts the moral dimensions of teaching by using the wrong language (clients, customers), focusing on limited forms of knowledge, and ignoring the fundamental democratic character of education.…
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DOT National Transportation Integrated Search
2018-02-01
The primary objective of Phase II was to develop a prototype connected vehicle wrong-way driving detection and management system at the Texas A&M University Respect, Excellence, Leadership, Loyalty, Integrity, Selfless Service (RELLIS) campus. The pu...
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Prevention of 3 "never events" in the operating room: fires, gossypiboma, and wrong-site surgery.
Zahiri, Hamid R; Stromberg, Jeffrey; Skupsky, Hadas; Knepp, Erin K; Folstein, Matthew; Silverman, Ronald; Singh, Devinder
2011-03-01
This study sought to identify and provide preventative recommendations for potentially devastating safety violations in the operating room. A Medline database search from 1950 to current using the terms patient safety and operating room was conducted. All topics identified were reviewed. Three patient safety violations with potential for immediate and devastating outcomes were selected for discussion using evidence-based literature. The search identified 2851 articles, 807 of which were directly related to patient safety in the operating room. Topics addressed by these 807 included infectious complications (26%), fires (11%), communication/teamwork (6%), retained foreign objects (3%), safety checklists (1%), and wrong-site surgery (1%). Fires, gossypiboma, and wrong-site surgery were selected for discussion. Although fire, gossypiboma, and wrong-site surgery should be "never events" in the operating room, they continue to persist as 3 common patient safety violations. This study provides the epidemiology, common etiologies, and evidence-based preventative recommendations for each.
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Park, Ji-Sang; Kang, Joongoo; Yang, Ji-Hui; ...
2015-01-15
Using first-principles density functional calculations, we investigate the relative stability and electronic structure of the grain boundaries (GBs) in zinc-blende CdTe. Among the low-Σ-value symmetric tilt Σ3 (111), Σ3 (112), Σ5 (120), and Σ5 (130) GBs, we show that the Σ3 (111)GB is always the most stable due to the absence of dangling bonds and wrong bonds. The Σ5 (120) GBs, however, are shown to be more stable than the Σ3 (112) GBs, even though the former has a higher Σ value, and the latter is often used as a model system to study GB effects in zinc-blende semiconductors. Furthermore,more » we find that although containing wrong bonds, the Σ5 (120) GBs are electrically benign due to the short wrong bond lengths, and thus are not as harmful as the Σ3 (112) GBs also having wrong bonds but with longer bond lengths.« less
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Nair-Collins, Michael
2017-01-01
The majority of transplantable human organs are retrieved from patients declared dead by neurological criteria, or "brain-dead." Since brain death is considered to be sufficient for death, the procurement of vital organs is not considered to harm or wrong such patients. In this essay I argue that this is not the case. After distinguishing welfare, experiential, and investment interests, and defining precedent autonomy and surviving interests, I argue that brain-dead patients can be, and many are, harmed and wronged by organ procurement as currently practiced. Indeed, with respect to precedent autonomy and surviving investment interests, the brain-dead are morally equivalent to patients with severe dementia, and thus can be harmed and wronged if and only if, and to the extent that, patients with severe dementia can. The "bright line" that separates brain death from all other conditions for clinical and legal purposes is not justified by any morally relevant distinctions.
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The mitochondrial death squad: hardened killers or innocent bystanders?
Ekert, Paul G; Vaux, David L
2005-12-01
Since the discovery that formation of the apoptosome in mammalian cells is triggered by cytochrome c released from the mitochondria, many other mitochondrial proteins have been suspected to be part of a conspiracy to cause cell death. AIF, EndoG, ANT, cyclophilin D, Bit1, p53AIP, GRIM-19, DAP3, Nur77/TR3/NGFB-1, HtrA2/Omi and Smac/Diablo have all been convicted as killers, but new genetic technology is raising questions about their guilt. Gene knockout experiments suggest that many were wrongly convicted on circumstantial evidence, and just happened to be in the wrong place at the wrong time.
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DOT National Transportation Integrated Search
1979-01-01
Recently completed research had proven the feasibility of using raised pavement markers to alert wrong-way drivers to their errors. In that research, however, the raised markers had been placed only in areas where-snowplowing was not a problem; there...
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Cassidy, Nicola; Duggan, Edel; Williams, David J P; Tracey, Joseph A
2011-07-01
Medication errors are widely reported for hospitalised patients, but limited data are available for medication errors that occur in community-based and clinical settings. Epidemiological data from poisons information centres enable characterisation of trends in medication errors occurring across the healthcare spectrum. The objective of this study was to characterise the epidemiology and type of medication errors reported to the National Poisons Information Centre (NPIC) of Ireland. A 3-year prospective study on medication errors reported to the NPIC was conducted from 1 January 2007 to 31 December 2009 inclusive. Data on patient demographics, enquiry source, location, pharmaceutical agent(s), type of medication error, and treatment advice were collated from standardised call report forms. Medication errors were categorised as (i) prescribing error (i.e. physician error), (ii) dispensing error (i.e. pharmacy error), and (iii) administration error involving the wrong medication, the wrong dose, wrong route, or the wrong time. Medication errors were reported for 2348 individuals, representing 9.56% of total enquiries to the NPIC over 3 years. In total, 1220 children and adolescents under 18 years of age and 1128 adults (≥ 18 years old) experienced a medication error. The majority of enquiries were received from healthcare professionals, but members of the public accounted for 31.3% (n = 736) of enquiries. Most medication errors occurred in a domestic setting (n = 2135), but a small number occurred in healthcare facilities: nursing homes (n = 110, 4.68%), hospitals (n = 53, 2.26%), and general practitioner surgeries (n = 32, 1.36%). In children, medication errors with non-prescription pharmaceuticals predominated (n = 722) and anti-pyretics and non-opioid analgesics, anti-bacterials, and cough and cold preparations were the main pharmaceutical classes involved. Medication errors with prescription medication predominated for adults (n = 866) and the major medication classes included anti-pyretics and non-opioid analgesics, psychoanaleptics, and psychleptic agents. Approximately 97% (n = 2279) of medication errors were as a result of drug administration errors (comprising a double dose [n = 1040], wrong dose [n = 395], wrong medication [n = 597], wrong route [n = 133], and wrong time [n = 110]). Prescribing and dispensing errors accounted for 0.68% (n = 16) and 2.26% (n = 53) of errors, respectively. Empirical data from poisons information centres facilitate the characterisation of medication errors occurring in the community and across the healthcare spectrum. Poison centre data facilitate the detection of subtle trends in medication errors and can contribute to pharmacovigilance. Collaboration between pharmaceutical manufacturers, consumers, medical, and regulatory communities is needed to advance patient safety and reduce medication errors.
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Present self-represented futures of value are a reason for the wrongness of killing.
Parsons, S J
2002-06-01
In Marquis's recent paper he has not satisfactorily shown that killing does not adversely affect the victim's present self-represented desires for their future. Marquis is correct in believing life and death are distinct, but living and dying are not. In fact, to use a well-known saying, "the second we are born we start to die". During the process of dying, whether it be long as in over our lifetime or short as in as we are being killed, there comes a point when the present realistic desires we have we know will never be satisfied. This is why killing can be wrong. This would imply killing an unconscious person, infant, or fetus cannot be wrong. But such killing can be wrong, despite the person killed not experiencing the desire not to be killed as he was dying. Killing can be wrong because others can have a present self-represented desire for that person not to be killed to have been killed. If this line of reasoning is correct, then the "best interests" principle often applied to life and death considerations regarding unconscious persons, infants, and fetuses, is invalid, as such human beings do not have present desires. All that matters is what relevant others rationally desire, after being informed of the facts and the consequences, for that unconscious person, infant or fetus.
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Malthus is still wrong: we can feed a world of 9-10 billion, but only by reducing food demand.
Smith, Pete
2015-08-01
In 1798, Thomas Robert Malthus published 'An essay on the principle of population' in which he concluded that: 'The power of population is so superior to the power of the earth to produce subsistence for man, that premature death must in some shape or other visit the human race.' Over the following century he was criticised for underestimating the potential for scientific and technological innovation to provide positive change. Since then, he has been proved wrong, with a number of papers published during the past few decades pointing out why he has been proved wrong so many times. In the present paper, I briefly review the main changes in food production in the past that have allowed us to continue to meet ever growing demand for food, and I examine the possibility of these same innovations delivering food security in the future. On the basis of recent studies, I conclude that technological innovation can no longer be relied upon to prove Malthus wrong as we strive to feed 9-10 billion people by 2050. Unless we are prepared to accept a wide range of significant, undesirable environmental consequences, technology alone cannot provide food security in 2050. Food demand, particularly the demand for livestock products, will need to be managed if we are to continue to prove Malthus wrong into the future.
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What's Really Wrong with Ethnography?
ERIC Educational Resources Information Center
Banfield, Grant
2004-01-01
In asking the provocative question: "What's wrong with ethnography?" Hammersley draws attention to what he sees as the conceptual and methodological confusion arising from two competing strands of practice: "naive realism" and "relativism". As a solution, he offers "subtle realism" to steer a path through and beyond the confusion. This paper…
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When Billionaires Become Educational Experts
ERIC Educational Resources Information Center
Kumashiro, Kevin K.
2012-01-01
For years, critics have pointed to the decreasing ability of health-care professionals to make decisions and provide services because of the demands of insurance companies and health-management organizations to sustain profits. Health-care decisions are increasingly being made by the wrong people and for the wrong reasons. So, too, with public…
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Are the Textbook Writers Wrong about Capacitors?
ERIC Educational Resources Information Center
French, A. P.
1993-01-01
Refutes a recent article which stated that the standard textbook treatment of two capacitors in series is wrong. States that the calculated capacitance is correct if measured immediately after a dc voltage is applied and that perhaps the effect is due to the choice of materials making up the capacitor. (MVL)
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We're Assigning the Wrong Freud
ERIC Educational Resources Information Center
Shusterman, Noah
2007-01-01
In this article, the author, a lecturer in Temple University's intellectual-heritage program, explains why colleges are teaching undergraduates the wrong Freud. Though the book "Civilization and Its Discontents" (1930), which most professors use, is Freud's most consistent and most convincing attempt to apply psychoanalytic theory to society as a…
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Holistic pest management [Chapter 15
Thomas D. Landis; Tara Luna; R. Kasten Dumroese
2009-01-01
As any experienced grower knows only too well, nursery management is a continuous process of solving problems. Murphy's Law of "anything that can go wrong, will go wrong" sounds as if it were meant for native plant production. One recurring problem is pests. Nursery managers have traditionally talked about "controlling" a pest. This approach...
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hanson, Christina J.; Spencer, Khalil J.
This document summarizes an incident where a large volume of explosive gas was detonated at the UH-Manoa's School of Ocean and Earth Science and Technology. This description is used as an example to teach lab safety.
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Medical Errors: Tips to Help Prevent Them
... consider A study by the Massachusetts College of Pharmacy and Allied Health Sciences found that 88% of medical errors involve the wrong drug or the wrong dose. This is one more reason why you should be a ... up refills at the pharmacy. In the hospital, have in writing the medicine ...
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ERIC Educational Resources Information Center
Pittman, Keith A.
1997-01-01
Briefly reviews the historical developments of tort law and identifies some of its main component. Tort law concerns wrongful acts (not involving a breach of contract) that may result in a civil action. Major areas include personal injury and wrongful death, intentional torts, negligence, professional malpractice, misrepresentation, and libel.…
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Underachievers, How They Can Be Helped.
ERIC Educational Resources Information Center
Fine, Benjamin
Addressed to parents and teachers, the book considers the problem of underachievers. After a review of the problem, tests, and what they show, overinvolved and involved parents, self esteem and self image, and childhood rebellion are treated. Also considered are the following: the wrong school and wrong teacher, reading instruction, the…
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ahmad, Md. Faiz; Kaushal, Prem Singh; Wan, Qun
2012-11-01
Ribonucleotide reductases (RRs) catalyze the rate-limiting step of de novo deoxynucleotide (dNTP) synthesis. Eukaryotic RRs consist of two proteins, RR1 ({alpha}) that contains the catalytic site and RR2 ({beta}) that houses a diferric-tyrosyl radical essential for ribonucleoside diphosphate reduction. Biochemical analysis has been combined with isothermal titration calorimetry (ITC), X-ray crystallography and yeast genetics to elucidate the roles of two loop 2 mutations R293A and Q288A in Saccharomyces cerevisiae RR1 (ScRR1). These mutations, R293A and Q288A, cause lethality and severe S phase defects, respectively, in cells that use ScRR1 as the sole source of RR1 activity. Compared to the wild-typemore » enzyme activity, R293A and Q288A mutants show 4% and 15%, respectively, for ADP reduction, whereas they are 20% and 23%, respectively, for CDP reduction. ITC data showed that R293A ScRR1 is unable to bind ADP and binds CDP with 2-fold lower affinity compared to wild-type ScRR1. With the Q288A ScRR1 mutant, there is a 6-fold loss of affinity for ADP binding and a 2-fold loss of affinity for CDP compared to the wild type. X-ray structures of R293A ScRR1 complexed with dGTP and AMPPNP-CDP [AMPPNP, adenosine 5-({beta},{gamma}-imido)triphosphate tetralithium salt] reveal that ADP is not bound at the catalytic site, and CDP binds farther from the catalytic site compared to wild type. Our in vivo functional analyses demonstrated that R293A cannot support mitotic growth, whereas Q288A can, albeit with a severe S phase defect. Taken together, our structure, activity, ITC and in vivo data reveal that the arginine 293 and glutamine 288 residues of ScRR1 are crucial in facilitating ADP and CDP substrate selection.« less
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Shin, Hye Jin; Kim, Chonsaeng; Cho, Sungchan
2018-04-20
Nucleoside analogs have been frequently identified as antiviral agents. In recent years, gemcitabine, a cytidine analog in clinical use for the treatment of many solid tumors, was also shown to have antiviral activity against a broad range of viruses. Nucleoside analogs generally interfere with cellular nucleos(t)ide synthesis pathways, resulting in the depletion or imbalance of (d)NTP pools. Intriguingly, a few recent reports have shown that some nucleoside analogs, including gemcitabine, activated innate immunity, inducing the expression of interferon-stimulated genes, through nucleos(t)ide synthesis inhibition. The precise crosstalk between these two independent processes remains to be determined. Nonetheless, we summarize the current knowledge of nucleos(t)ide synthesis inhibition-related innate immunity and propose it as a newly emerging antiviral mechanism of nucleoside analogs.
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Preparation of 13C/15N-labeled oligomers using the polymerase chain reaction
Chen, Xian; Gupta, Goutam; Bradbury, E. Morton
2001-01-01
Preparation of .sup.13 C/.sup.15 N-labeled DNA oligomers using the polymerase chain reaction (PCR). A PCR based method for uniform (.sup.13 C/.sup.15 N)-labeling of DNA duplexes is described. Multiple copies of a blunt-ended duplex are cloned into a plasmid, each copy containing the sequence of interest and restriction Hinc II sequences at both the 5' and 3' ends. PCR using bi-directional primers and uniformly .sup.13 C/.sup.15 N-labeled dNTP precursors generates labeled DNA duplexes containing multiple copies of the sequence of interest. Twenty-four cycles of PCR, followed by restriction and purification, gave the uniformly .sup.13 C/.sup.15 N-labeled duplex sequence with a 30% yield. Such labeled duplexes find significant applications in multinuclear magnetic resonance spectroscopy.
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The Do It Wrong Approach to Writing.
ERIC Educational Resources Information Center
Grow, Gerald
Deliberately writing badly can be an effective way to learn to write better because knowing when writing is bad is an essential element in knowing when it's good. There are distinct advantages to encouraging students to learn the rules by breaking them. Deliberately doing it wrong removes the threat of failure. Students are playing; they are…
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7 CFR 1.51 - Claims based on negligence, wrongful act or omission.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 1 2013-01-01 2013-01-01 false Claims based on negligence, wrongful act or omission. 1.51 Section 1.51 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS... Department of Agriculture (USDA) may, subject to the provisions of the FTCA and DOJ regulations, consider...
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24 CFR 983.259 - Overcrowded, under-occupied, and accessible units.
Code of Federal Regulations, 2010 CFR
2010-04-01
...-occupied, and accessible units. (a) Family occupancy of wrong-size or accessible unit. The PHA subsidy standards determine the appropriate unit size for the family size and composition. If the PHA determines that a family is occupying a: (1) Wrong-size unit, or (2) Unit with accessibility features that the...
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The Teacher Shortage: A Case of Wrong Diagnosis and Wrong Prescription.
ERIC Educational Resources Information Center
Ingersoll, Richard M.
2002-01-01
Investigates the possibility that the organizational characteristics and conditions of schools are driving teacher turnover. Analysis of data from the National Center for Education Statistics (NCES) indicates that the amount of turnover accounted for by retirement is relatively minor when compared with that associated with other factors such as…
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Teaching about Tort Law--My Actions, My Actions, Somebody Got Hurt!
ERIC Educational Resources Information Center
Rose, Stephen A.
1997-01-01
Presents a lesson plan that uses cases to teach students about three types of torts: intentional wrongs, negligence, and strict liability. Torts are wrongful actions (not involving a breech of contract) that may result in a civic action. Includes lesson procedures, objectives, and student handouts on torts and negligence cases. (MJP)
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2011-12-01
the data we feel that it is less a failure of the exotendon technology and more a failure of the wrong tests with the wrong types of subjects...from incomplete spinal cord injuries. Additionally, a proposal to the National Institutes of Health seeking to develop an exotendon prosthesis for
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When Rewards Go Wrong: A Tale of Five Motivational Misdirects
ERIC Educational Resources Information Center
Steel, Piers; MacDonnell, Rhiannon
2012-01-01
At the heart of most performance management systems is a reward program. However, even when we are doing everything else right, rewards can go wrong. Here, we explore five ways that external incentives can damage performance, from destroying altruistic behavior to distracting people from the task. Fortunately, most of these downfalls are…
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Shame: Does It Have a Place in an Education for Democratic Citizenship?
ERIC Educational Resources Information Center
Benade, Leon
2015-01-01
Shame, shame management and reintegrative shaming feature in some restorative justice literature, and may have implications for schools. Restorative justice in schools is effective when perpetrators of wrong-doing can accept and take ownership of their wrongful acts, are appropriately remorseful, and seek to make amends. Shame may be understood as…
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Abortion: Strong's counterexamples fail.
Di Nucci, E
2009-05-01
This paper shows that the counterexamples proposed by Strong in 2008 in the Journal of Medical Ethics to Marquis's argument against abortion fail. Strong's basic idea is that there are cases--for example, terminally ill patients--where killing an adult human being is prima facie seriously morally wrong even though that human being is not being deprived of a "valuable future". So Marquis would be wrong in thinking that what is essential about the wrongness of killing an adult human being is that they are being deprived of a valuable future. This paper shows that whichever way the concept of "valuable future" is interpreted, the proposed counterexamples fail: if it is interpreted as "future like ours", the proposed counterexamples have no bearing on Marquis's argument. If the concept is interpreted as referring to the patient's preferences, it must be either conceded that the patients in Strong's scenarios have some valuable future or admitted that killing them is not seriously morally wrong. Finally, if "valuable future" is interpreted as referring to objective standards, one ends up with implausible and unpalatable moral claims.
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Anwar, H; Waring, D
2017-07-07
Introduction With an increasing demand to improve patient safety within the NHS, it is important to ensure that measures are undertaken to continually improve patient care. Wrong site surgery has been defined as a 'never event'. This article highlights the importance of preventing wrong tooth extraction within orthodontics through an audit spiral over five years investigating the accuracy and clarity of orthodontic extraction letters at the University Dental Hospital of Manchester.Aims To examine compliance with the standards for accuracy and clarity of extraction letters and the incidence of wrong tooth extractions, and to increase awareness of the errors that can occur with extraction letters and of the current guidelines.Method A retrospective audit was conducted examining extraction letters sent to clinicians outside the department.Results It can be seen there has been no occurrence of a wrong site tooth extraction. The initial audit highlighted issues in conformity, with it falling below expected standards. Cycle two generally demonstrated a further reduction in compliance. Cycle three appeared to result in an increase in levels of compliance. Cycles 4 and 5 have demonstrated gradual improvements. However, it is noteworthy that in all cycles the audit standards were still not achieved, with the exception of no incidences of the incorrect tooth being extracted.Conclusion This audit spiral demonstrates the importance of long term re-audit to aim to achieve excellence in clinical care. There has been a gradual increase in standards through each audit.
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Comparison of existing models to simulate anaerobic digestion of lipid-rich waste.
Béline, F; Rodriguez-Mendez, R; Girault, R; Bihan, Y Le; Lessard, P
2017-02-01
Models for anaerobic digestion of lipid-rich waste taking inhibition into account were reviewed and, if necessary, adjusted to the ADM1 model framework in order to compare them. Experimental data from anaerobic digestion of slaughterhouse waste at an organic loading rate (OLR) ranging from 0.3 to 1.9kgVSm -3 d -1 were used to compare and evaluate models. Experimental data obtained at low OLRs were accurately modeled whatever the model thereby validating the stoichiometric parameters used and influent fractionation. However, at higher OLRs, although inhibition parameters were optimized to reduce differences between experimental and simulated data, no model was able to accurately simulate accumulation of substrates and intermediates, mainly due to the wrong simulation of pH. A simulation using pH based on experimental data showed that acetogenesis and methanogenesis were the most sensitive steps to LCFA inhibition and enabled identification of the inhibition parameters of both steps. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Hempel, Susanne; Maggard-Gibbons, Melinda; Nguyen, David K; Dawes, Aaron J; Miake-Lye, Isomi; Beroes, Jessica M; Booth, Marika J; Miles, Jeremy N V; Shanman, Roberta; Shekelle, Paul G
2015-08-01
Serious, preventable surgical events, termed never events, continue to occur despite considerable patient safety efforts. To examine the incidence and root causes of and interventions to prevent wrong-site surgery, retained surgical items, and surgical fires in the era after the implementation of the Universal Protocol in 2004. We searched 9 electronic databases for entries from 2004 through June 30, 2014, screened references, and consulted experts. Two independent reviewers identified relevant publications in June 2014. One reviewer used a standardized form to extract data and a second reviewer checked the data. Strength of evidence was established by the review team. Data extraction was completed in January 2015. Incidence of wrong-site surgery, retained surgical items, and surgical fires. We found 138 empirical studies that met our inclusion criteria. Incidence estimates for wrong-site surgery in US settings varied by data source and procedure (median estimate, 0.09 events per 10,000 surgical procedures). The median estimate for retained surgical items was 1.32 events per 10,000 procedures, but estimates varied by item and procedure. The per-procedure surgical fire incidence is unknown. A frequently reported root cause was inadequate communication. Methodologic challenges associated with investigating changes in rare events limit the conclusions of 78 intervention evaluations. Limited evidence supported the Universal Protocol (5 studies), education (4 studies), and team training (4 studies) interventions to prevent wrong-site surgery. Limited evidence exists to prevent retained surgical items by using data-matrix-coded sponge-counting systems (5 pertinent studies). Evidence for preventing surgical fires was insufficient, and intervention effects were not estimable. Current estimates for wrong-site surgery and retained surgical items are 1 event per 100,000 and 1 event per 10,000 procedures, respectively, but the precision is uncertain, and the per-procedure prevalence of surgical fires is not known. Root-cause analyses suggest the need for improved communication. Despite promising approaches and global Universal Protocol evaluations, empirical evidence for interventions is limited.
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Beer, Idal; Hoppe-Tichy, Torsten; Trbovich, Patricia
2017-01-01
Objective To examine published evidence on intravenous admixture preparation errors (IAPEs) in healthcare settings. Methods Searches were conducted in three electronic databases (January 2005 to April 2017). Publications reporting rates of IAPEs and error types were reviewed and categorised into the following groups: component errors, dose/calculation errors, aseptic technique errors and composite errors. The methodological rigour of each study was assessed using the Hawker method. Results Of the 34 articles that met inclusion criteria, 28 reported the site of IAPEs: central pharmacies (n=8), nursing wards (n=14), both settings (n=4) and other sites (n=3). Using the Hawker criteria, 14% of the articles were of good quality, 74% were of fair quality and 12% were of poor quality. Error types and reported rates varied substantially, including wrong drug (~0% to 4.7%), wrong diluent solution (0% to 49.0%), wrong label (0% to 99.0%), wrong dose (0% to 32.6%), wrong concentration (0.3% to 88.6%), wrong diluent volume (0.06% to 49.0%) and inadequate aseptic technique (0% to 92.7%)%). Four studies directly compared incidence by preparation site and/or method, finding error incidence to be lower for doses prepared within a central pharmacy versus the nursing ward and lower for automated preparation versus manual preparation. Although eight studies (24%) reported ≥1 errors with the potential to cause patient harm, no study directly linked IAPE occurrences to specific adverse patient outcomes. Conclusions The available data suggest a need to continue to optimise the intravenous preparation process, focus on improving preparation workflow, design and implement preventive strategies, train staff on optimal admixture protocols and implement standardisation. Future research should focus on the development of consistent error subtype definitions, standardised reporting methodology and reliable, reproducible methods to track and link risk factors with the burden of harm associated with these errors. PMID:29288174
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What's Wrong with Our Schools and How We Can Fix Them
ERIC Educational Resources Information Center
Zwaagstra, Michael C.; Clifton, Rodney A.; Long, John C.
2010-01-01
"What's Wrong with Our Schools and How We Can Fix Them" examines the status of public education in North America and exposes many of the absurd instructional practices found in all-too-many schools. Written by three experienced educators, this book provides readers with a direct window into public education. The language is straightforward, the…
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Dystopian Schools: Recovering Dewey's Radical Aesthetics in an Age of Utopia-Gone-Wrong
ERIC Educational Resources Information Center
Heybach, Jessica A.; Sheffield, Eric C.
2014-01-01
In this article, we first suggest that contemporary school policies and practices represent a utopia-gone-wrong. In striving for an unattainable educational utopia--that is, all students will be proficient in math and reading by 2014--current polices and their resulting practices have brought a classic dystopian turn--the dehumanization of…
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Survivability Extensions for Dynamic Ultralog Environments
2004-12-07
8217 on line number 2018 doDo: Wrong number of tokens for ’Do’ on line number 2049 doDo: Wrong number of tokens for ’Do’ on line number 2069 doDo...discuss survivability as defined in the " bible of computational complexity", namely, the book "Computers and Intractability, a Guide to the Theory of
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Classrooms as Safe Places To Be Wrong.
ERIC Educational Resources Information Center
Sankey, Derek
This paper contends that classrooms should be safe places for students and their teachers to be wrong, suggesting that this concept should provide the mainspring for educational reform in Hong Kong and in other places in the world. It notes that education in Hong Kong is harsh and has a tendency to label students; for the majority of students,…
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Item Type and Gender Differences on the Mental Rotations Test
ERIC Educational Resources Information Center
Voyer, Daniel; Doyle, Randi A.
2010-01-01
This study investigated gender differences on the Mental Rotations Test (MRT) as a function of item and response types. Accordingly, 86 male and 109 female undergraduate students completed the MRT without time limits. Responses were coded as reflecting two correct (CC), one correct and one wrong (CW), two wrong (WW), one correct and one blank…
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Using the Euclid RTP11.13 Repository in the SEC Environment
2006-03-01
of wrong user, passwd combination. We found out that the user and password are hard coded in the FCT software. It uses defaultEditor@ rtp I I 13.INETI...The FCT will start, but when connecting to the Repository it fails because of wrong user, passwd combination: It uses defaultEditor@rtpl I 13.INETI
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Moving Past "Right" or "Wrong" toward a Continuum of Young Children's Semantic Knowledge
ERIC Educational Resources Information Center
Christ, Tanya
2011-01-01
Vocabulary development is a critical goal for early childhood education. However, it is difficult for researchers and teachers to determine whether this goal is being met, given the limitations of current assessment tools. These tools tend to view word knowledge dichotomously--as right or wrong. A clear sense of children's depth of semantic…
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Set the Wrong Tuition and You'll Pay a Price
ERIC Educational Resources Information Center
Strauss, David W.
2006-01-01
For all of the attention rising college costs continue to receive, it is striking how poorly informed many decision makers are when it comes to setting tuition and fees. And it's equally astounding that so many institutions are learning the consequences of pricing decisions undertaken solely by trial and error when a wrong judgment can affect…
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Rationality in the Academy: Why Responsibility Center Budgeting Is a Wrong Step Down the Wrong Road.
ERIC Educational Resources Information Center
Adams, E. M.
1997-01-01
Responsibility Center Budgeting/Management in higher education places at the heart of the university a mode of rationality in decision making that subverts educational policy and weakens the institution's ability for corrective cultural criticism. Academic leaders should make academic and research decisions based on students' and society's…
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The Use of Information from Wrong Responses in Measuring Students' Achievement.
ERIC Educational Resources Information Center
Birenbaum, Menucha; Tatsuoka, Kikumi K.
Much valuable information can be gained by analyzing the students' wrong responses. When a student answers a free response item she/he gives the response which she/he considers to be the correct one. Therefore, diagnosing the algorithm that led the student to his/her answer provides an important source of information for assessing his/her…
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In a Secret Classroom in Georgia, Immigrants Learn to Hope
ERIC Educational Resources Information Center
Sander, Libby
2012-01-01
Young immigrants--about 1.4 million of them nationally--are often in the wrong place at the wrong time. Across the country, a patchwork of state laws and policies governs their access to higher education. The inconsistency stems, in part, from disagreement over whether undocumented immigrants are entitled to go to college. While states must…
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The AFT Charter School Study: Not News. Point of View Essay
ERIC Educational Resources Information Center
Bracey, Gerald
2004-01-01
The recent flap over the American Federation of Teachers' (AFT) charter school report is surprising, not because the study used the wrong methods or reached the wrong conclusions, it didn't, but because AFT's conclusions are nothing new. The AFT study "is" the first to use the National Assessment of Educational Progress (NAEP) as its…
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Designing Efficient Self-Diagnosis Activities in the Physics Classroom
ERIC Educational Resources Information Center
Safadi, Rafi'
2017-01-01
Self-diagnosis (SD) activities require students to self-diagnose their solutions to problems that they solved on their own. This involves identifying where they went wrong and then explaining the nature of their errors--why they went wrong--aided by some form of support. Worked examples (WEs) are often used to support students in SD activities. A…
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ERIC Educational Resources Information Center
Loewen, James W.
2011-01-01
William Faulkner famously wrote, "The past is never dead. It's not even past." He would not be surprised to learn that Americans, 150 years after the Civil War began, are still getting it wrong. Did America's most divisive war start over slavery or states' rights? The author says that too many people--including educators--get it wrong. The author…
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Identification of Non-nucleoside Human Ribonucleotide Reductase Modulators
Ahmad, Md. Faiz; Huff, Sarah E.; Pink, John; ...
2015-10-21
Ribonucleotide reductase (RR) catalyzes the rate-limiting step of dNTP synthesis and is an established cancer target. Drugs targeting RR are mainly nucleoside in nature. In this study, we sought to identify non-nucleoside small-molecule inhibitors of RR. Using virtual screening, binding affinity, inhibition, and cell toxicity, we have discovered a class of small molecules that alter the equilibrium of inactive hexamers of RR, leading to its inhibition. Several unique chemical categories, including a phthalimide derivative, show micromolar IC 50s and K Ds while demonstrating cytotoxicity. A crystal structure of an active phthalimide binding at the targeted interface supports the noncompetitive modemore » of inhibition determined by kinetic studies. Furthermore, the phthalimide shifts the equilibrium from dimer to hexamer. Finally, together, these data identify several novel non-nucleoside inhibitors of human RR which act by stabilizing the inactive form of the enzyme.« less
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Heinmets, F; Leary, R H
1991-06-01
A model system (1) was established to analyze purine and pyrimidine metabolism. This system has been expanded to include macrosimulation of DNA synthesis and the study of its regulation by terminal deoxynucleoside triphosphates (dNTPs) via a complex set of interactions. Computer experiments reveal that our model exhibits adequate and reasonable sensitivity in terms of dNTP pool levels and rates of DNA synthesis when inputs to the system are varied. These simulation experiments reveal that in order to achieve maximum DNA synthesis (in terms of purine metabolism), a proper balance is required in guanine and adenine input into this metabolic system. Excessive inputs will become inhibitory to DNA synthesis. In addition, studies are carried out on rates of DNA synthesis when various parameters are changed quantitatively. The current system is formulated by 110 differential equations.
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Cytotoxicity and Antineoplastic Activities of Alkylamines and Their Borane Derivatives
Tse, Elaine Y.; Muhammad, Rosallah A.
1996-01-01
The alkylamines and their related boron derivatives demonstrated potent cytotoxicity against the growth of murine and human tissue cultured cells. These agents did not necessarily require the boron atom to possess potent cytotoxic action in certain tumor lines. Their ability to suppress tumor cell growth was based on their inhibition of DNA and protein syntheses. DNA synthesis was reduced because purine synthesis was blocked at the enzyme site of IMP dehydrogenase by the agents. In addition ribonucleotide reductase and nucleoside kinase activities were reduced by the agents which would account for the reduced d[NTP] pools. The DNA template or molecule may be a target of the drugs with regard to binding of the drug to nucleoside bases or intercalaction of the drug between DNA base pairs. Only some Of the agents caused DNA fragmentation with reduced DNA viscosity. These effects would contribute to overall cell death afforded by the agents. PMID:18472803
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Shang, Ying; Xu, Wentao; Wang, Yong; Xu, Yuancong; Huang, Kunlun
2017-12-15
This study described a novel multiplex qualitative detection method using pyrosequencing. Based on the principle of the universal primer-multiplex-PCR, only one sequencing primer was employed to realize the detection of the multiple targets. Samples containing three genetically modified (GM) crops in different proportions were used to validate the method. The dNTP dispensing order was designed based on the product sequences. Only 12 rounds (ATCTGATCGACT) of dNTPs addition and, often, as few as three rounds (CAT) under ideal conditions, were required to detect the GM events qualitatively, and sensitivity was as low as 1% of a mixture. However, when considering a mixture, calculating signal values allowed the proportion of each GM to be estimated. Based on these results, we concluded that our novel method not only realized detection but also allowed semi-quantitative detection of individual events. Copyright © 2017. Published by Elsevier Ltd.
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ERIC Educational Resources Information Center
Battin, David B.; Ceci, Stephen J.; Lust, Barbara C.
2012-01-01
This study compared younger (M = 53 months) and older (M = 90 months) children's use of linguistic referential devices to make a positive identification. Children were shown a 4-minute video that concluded with a wrongful act. They were interviewed 24 hours later and asked to identify the perpetrator of the wrongful act with open-ended and…
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ERIC Educational Resources Information Center
Reardon, A. W.; And Others
1993-01-01
Instructional materials on hypoglycemia, foot care, and exercise were developed and field tested with 98 diabetes patients who had low vision and/or low literacy. A pretest and posttest revealed an 81% reduction in wrong answers overall and a 72% reduction in wrong answers by a subset with low vision. (Author/DB)
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Following Reading Primers the Wrong Way: Pedagogical Nonsense in Dr. Seuss
ERIC Educational Resources Information Center
Yang, Lichung
2017-01-01
A well-versed writer on the limitations and possibilities of the English language, Seuss follows the conventional primers the wrong way, not by retracing the tradition of the genre, but by working his way against the current. Drawing upon Jean-Jacques Lecercle's notion of nonsense, this essay is a small attempt to examine three of Dr. Seuss's…
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ERIC Educational Resources Information Center
Johnson, Terry L.
2013-01-01
Wrongful criminal convictions have come to the attention of the public and the criminal justice community in recent decades as a result of DNA evidence that has proven innocence after conviction. Research has suggested that as many as 3% to 5% of people currently imprisoned did not, in fact, commit the crimes for which they were convicted. A…
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Promoting Honesty and Truthfulness When Things Go Wrong During Care Delivery for Sick Children.
Glasper, Edward Alan
2018-06-01
Emeritus Professor and Editor-in-Chief Edward Alan Glasper discusses why children's nurses must fully adopt the duty of candour in care delivery, which in some countries is a legal obligation, to ensure that consumers of healthcare and their families are apologized to, and communicated with, openly and honestly when things have gone wrong in their care.
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31 CFR 100.18 - Counterfeit notes to be marked; “redemption” of notes wrongfully so marked.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Counterfeit notes to be marked; âredemptionâ of notes wrongfully so marked. 100.18 Section 100.18 Money and Finance: Treasury Regulations Relating to Money and Finance MONETARY OFFICES, DEPARTMENT OF THE TREASURY EXCHANGE OF PAPER CURRENCY AND...
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31 CFR 100.18 - Counterfeit notes to be marked; “redemption” of notes wrongfully so marked.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 31 Money and Finance: Treasury 1 2014-07-01 2014-07-01 false Counterfeit notes to be marked; âredemptionâ of notes wrongfully so marked. 100.18 Section 100.18 Money and Finance: Treasury Regulations Relating to Money and Finance MONETARY OFFICES, DEPARTMENT OF THE TREASURY EXCHANGE OF PAPER CURRENCY AND...
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Code of Federal Regulations, 2011 CFR
2011-04-01
... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Suspension of running of period of limitation... and Collection § 301.6503(f)-1 Suspension of running of period of limitation; wrongful seizure of... running of the period of limitations on collection after assessment prescribed in section 6502 (relating...
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Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Suspension of running of period of limitation... and Collection § 301.6503(f)-1 Suspension of running of period of limitation; wrongful seizure of... running of the period of limitations on collection after assessment prescribed in section 6502 (relating...
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Social Studies for an Empire: Thoughts on Where Did Social Studies Go Wrong?
ERIC Educational Resources Information Center
Fleury, Stephen C.
2005-01-01
In this article, the author discusses viewpoints on civic education reforms postulated in "Where Did Social Studies Go Wrong?," a book published by the Thomas B. Fordham Institute. The book begins with a legitimate concern about the need to educate youth to care about political life; a noble mission, dating at least to the Greeks.…
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Preanalytical Errors in Hematology Laboratory- an Avoidable Incompetence.
HarsimranKaur, Vikram Narang; Selhi, Pavneet Kaur; Sood, Neena; Singh, Aminder
2016-01-01
Quality assurance in the hematology laboratory is a must to ensure laboratory users of reliable test results with high degree of precision and accuracy. Even after so many advances in hematology laboratory practice, pre-analytical errors remain a challenge for practicing pathologists. This study was undertaken with an objective to evaluate the types and frequency of preanalytical errors in hematology laboratory of our center. All the samples received in the Hematology Laboratory of Dayanand Medical College and Hospital, Ludhiana, India over a period of one year (July 2013-July 2014) were included in the study and preanalytical variables like clotted samples, quantity not sufficient, wrong sample, without label, wrong label were studied. Of 471,006 samples received in the laboratory, preanalytical errors, as per the above mentioned categories was found in 1802 samples. The most common error was clotted samples (1332 samples, 0.28% of the total samples) followed by quantity not sufficient (328 sample, 0.06%), wrong sample (96 samples, 0.02%), without label (24 samples, 0.005%) and wrong label (22 samples, 0.005%). Preanalytical errors are frequent in laboratories and can be corrected by regular analysis of the variables involved. Rectification can be done by regular education of the staff.
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Criminal Prohibition of Wrongful Re‑identification: Legal Solution or Minefield for Big Data?
Phillips, Mark; Dove, Edward S; Knoppers, Bartha M
2017-12-01
The collapse of confidence in anonymization (sometimes also known as de-identification) as a robust approach for preserving the privacy of personal data has incited an outpouring of new approaches that aim to fill the resulting trifecta of technical, organizational, and regulatory privacy gaps left in its wake. In the latter category, and in large part due to the growth of Big Data-driven biomedical research, falls a growing chorus of calls for criminal and penal offences to sanction wrongful re-identification of "anonymized" data. This chorus cuts across the fault lines of polarized privacy law scholarship that at times seems to advocate privacy protection at the expense of Big Data research or vice versa. Focusing on Big Data in the context of biomedicine, this article surveys the approaches that criminal or penal law might take toward wrongful re-identification of health data. It contextualizes the strategies within their respective legal regimes as well as in relation to emerging privacy debates focusing on personal data use and data linkage and assesses the relative merit of criminalization. We conclude that this approach suffers from several flaws and that alternative social and legal strategies to deter wrongful re-identification may be preferable.
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Psychopaths know right from wrong but don’t care
Tonnaer, Franca; Hauser, Marc D.
2010-01-01
Adult psychopaths have deficits in emotional processing and inhibitory control, engage in morally inappropriate behavior, and generally fail to distinguish moral from conventional violations. These observations, together with a dominant tradition in the discipline which sees emotional processes as causally necessary for moral judgment, have led to the conclusion that psychopaths lack an understanding of moral rights and wrongs. We test an alternative explanation: psychopaths have normal understanding of right and wrong, but abnormal regulation of morally appropriate behavior. We presented psychopaths with moral dilemmas, contrasting their judgments with age- and sex-matched (i) healthy subjects and (ii) non-psychopathic, delinquents. Subjects in each group judged cases of personal harms (i.e. requiring physical contact) as less permissible than impersonal harms, even though both types of harms led to utilitarian gains. Importantly, however, psychopaths’ pattern of judgments on different dilemmas was the same as those of the other subjects. These results force a rejection of the strong hypothesis that emotional processes are causally necessary for judgments of moral dilemmas, suggesting instead that psychopaths understand the distinction between right and wrong, but do not care about such knowledge, or the consequences that ensue from their morally inappropriate behavior. PMID:20053752
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Quantum mechanics of neutrino oscillations - hand waving for pedestrians.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lipkin, H. J.
1998-12-22
Why Hand Waving? All calculations in books describe oscillations in time. But real experiments don't measure time. Hand waving is used to convert the results of a ''gedanken time experiment'' to the result of a real experiment measuring oscillations in space. Right hand waving gives the right answer; wrong hand waving gives the wrong answer. Many papers use wrong handwaving to get wrong answers. This talk explains how to do it right and also answers the following questions: (1) A neutrino which is a mixture of two mass eigenstates is emitted with muon in the decay of a pion atmore » rest. This is a ''missing mass experiment'' where the muon energy determines the neutrino mass. Why are the two mass states coherent? (2) A neutrino which is a mixture of two mass eigenstates is emitted at time t=0. The two mass eigenstates move with different velocities and arrive at the detector at different times. Why are the two mass states coherent? (3) A neutrino is a mixture of two overlapping wave packets with different masses moving with different velocities. Will the wave packets eventually separate? If yes, when?« less
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To clone or not to clone--a Jewish perspective.
Lipschutz, J H
1999-01-01
Many new reproductive methods such as artificial insemination, in vitro fertilisation, freezing of human embryos, and surrogate motherhood were at first widely condemned but are now seen in Western society as not just ethically and morally acceptable, but beneficial in that they allow otherwise infertile couples to have children. The idea of human cloning was also quickly condemned but debate is now emerging. This article examines cloning from a Jewish perspective and finds evidence to support the view that there is nothing inherently wrong with the idea of human cloning. A hypothesis is also advanced suggesting that even if a body was cloned, the brain, which is the essence of humanity, would remain unique. This author suggests that the debate should be changed from "Is cloning wrong?" to "When is cloning wrong?". PMID:10226913
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Frontal negativity: An electrophysiological index of interpersonal guilt.
Leng, Bingbing; Wang, Xiangling; Cao, Bihua; Li, Fuhong
2017-12-01
The present study aimed to reveal the temporal course and electrophysiological correlates of interpersonal guilt. Human participants were asked to perform multiple rounds of a dot-estimation task with their partners, while event-related potential being recorded. The paired participants were informed that they would win money if both responded correctly; otherwise, both of them would lose money. The feeling of guilt in Self-Wrong condition (SW) was significantly higher than that in Both-Wrong and Partner-Wrong conditions. At approximately 350 ms after the onset of feedback presentation, greater negativities were observed in the frontal regions in the guilt condition (i.e., SW) than those in the non-guilt condition. The guilt-modulated frontal negativity might reflect the interactions of self-reflection, condemnation, and negative emotion.
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How to Choose the Right Dean for Your University: Remembering the Five P's of Deanship
ERIC Educational Resources Information Center
Maghroori, Ray; Powers, Charles
2004-01-01
Given the number of times schools recruit deans who have short lives as administrators, it seems reasonable to ask if there is something wrong with the usual selection and recruitment process. The authors feel that there is something wrong with this process and after meeting with some deans, they were given some clues about the nature of the…
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ERIC Educational Resources Information Center
Mouritzen, Gaye S.
A practicum was designed to deal with the problem of cheating in a public alternative high school for at-risk students. Questionnaires completed by the teachers and the student body indicated that students had a deficiency in understanding and applying principles of accepted right and wrong to situations involving the possibility of cheating.…
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ERIC Educational Resources Information Center
Stephens, Jason M.
2017-01-01
The belief that cheating is wrong doesn't prevent its enactment. For example, many students cheat despite believing that is wrong or unjustifiable. The question taken up in this article concerns how the resulting cognitive dissonance is ameliorated; that is, how do students cheat and not feel guilty? This article will describe two "good"…
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ERIC Educational Resources Information Center
Rakoczy, Hannes; Tomasello, Michael
2009-01-01
Young children use and comprehend different kinds of speech acts from the beginning of their communicative development. But it is not clear how they understand the conventional and normative structure of such speech acts. In particular, imperative speech acts have a world-to-word direction of fit, such that their fulfillment means that the world…
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ERIC Educational Resources Information Center
Graney, Christopher M.
2012-01-01
What can physics students learn about science from those scientists who got the answers wrong? Your students probably have encountered little science history. What they have encountered probably has portrayed scientists as "The People with the Right Answers." But those who got the wrong answers can teach students that in science, answers are often…
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ERIC Educational Resources Information Center
Posada, Roberto; Wainryb, Cecilia
2008-01-01
Ninety-six Colombian children (mean age = 7.7 years) and adolescents (mean age = 14.6 years) made judgments about stealing and physical harm in the abstract and in the context of survival and revenge. All participants judged it wrong to steal or hurt others because of considerations with justice and welfare, and most also judged it wrong to engage…
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A Metabolic Murder Mystery: A Case-Based Experiment for the Undergraduate Biochemistry Laboratory
ERIC Educational Resources Information Center
Childs-Disney, Jessica L.; Kauffmann, Andrew D.; Poplawski, Shane G.; Lysiak, Daniel R.; Stewart, Robert J.; Arcadi, Jane K.; Dinan, Frank J.
2010-01-01
In 1990, a woman was wrongly convicted of poisoning her infant son and was sentenced to life in prison. Her conviction was based on laboratory work that wrongly identified ethylene glycol as present in her son's blood and in the formula he drank prior to his death. The actual cause of the infant's death, a metabolic disease, was eventually…
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Hedlund, Nancy; Beer, Idal; Hoppe-Tichy, Torsten; Trbovich, Patricia
2017-12-28
To examine published evidence on intravenous admixture preparation errors (IAPEs) in healthcare settings. Searches were conducted in three electronic databases (January 2005 to April 2017). Publications reporting rates of IAPEs and error types were reviewed and categorised into the following groups: component errors, dose/calculation errors, aseptic technique errors and composite errors. The methodological rigour of each study was assessed using the Hawker method. Of the 34 articles that met inclusion criteria, 28 reported the site of IAPEs: central pharmacies (n=8), nursing wards (n=14), both settings (n=4) and other sites (n=3). Using the Hawker criteria, 14% of the articles were of good quality, 74% were of fair quality and 12% were of poor quality. Error types and reported rates varied substantially, including wrong drug (~0% to 4.7%), wrong diluent solution (0% to 49.0%), wrong label (0% to 99.0%), wrong dose (0% to 32.6%), wrong concentration (0.3% to 88.6%), wrong diluent volume (0.06% to 49.0%) and inadequate aseptic technique (0% to 92.7%)%). Four studies directly compared incidence by preparation site and/or method, finding error incidence to be lower for doses prepared within a central pharmacy versus the nursing ward and lower for automated preparation versus manual preparation. Although eight studies (24%) reported ≥1 errors with the potential to cause patient harm, no study directly linked IAPE occurrences to specific adverse patient outcomes. The available data suggest a need to continue to optimise the intravenous preparation process, focus on improving preparation workflow, design and implement preventive strategies, train staff on optimal admixture protocols and implement standardisation. Future research should focus on the development of consistent error subtype definitions, standardised reporting methodology and reliable, reproducible methods to track and link risk factors with the burden of harm associated with these errors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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Koriat, Asher
2018-05-01
Can we tell whether our beliefs and judgments are correct or wrong? Results across many domains indicate that people are skilled at discriminating between correct and wrong answers, endorsing the former with greater confidence than the latter. However, it has not been realized that because of people's adaptation to reality, representative samples of items tend to favor the correct answer, yielding object-level accuracy (OLA) that is considerably better than chance. Across 16 experiments that used 2-alternative forced-choice items from several domains, the confidence/accuracy (C/A) relationship was positive for items with OLA >50%, but consistently negative across items with OLA <50%. A systematic sampling of items that covered the full range of OLA (0-100%) yielded a U-function relating confidence to OLA. The results imply that the positive C/A relationship that has been reported in many studies is an artifact of OLA being better than chance rather than representing a general ability to discriminate between correct and wrong responses. However, the results also support the ecological approach, suggesting that confidence is based on a frugal, "bounded" heuristic that has been specifically tailored to the ecological structure of the natural environment. This heuristic is used despite the fact that for items with OLA <50%, it yields confidence judgments that are counterdiagnostic of accuracy. Our ability to tell between correct and wrong judgments is confined to the probability structure of the world we live in. The results were discussed in terms of the contrast between systematic design and representative design. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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Kantian condemnation of commerce in organs.
Kerstein, Samuel J
2009-06-01
Opponents of commerce in organs sometimes appeal to Kant's Formula of Humanity to justify their position. Kant implies that anyone who sells an integral part of his body violates this principle and thereby acts wrongly. Although appeals to Kant's Formula are apt, they are less helpful than they might be because they invoke the necessity of respecting the dignity of ends in themselves without specifying in detail what dignity is or what it means to respect it, and they cite the wrongness of an agent's treating another merely as a means without clarifying conditions under which this occurs. This paper crystallizes two different approaches to the Formula of Humanity and probes when, according to them, the principle would imply that it is wrong to engage in "live donor" transactions, in which someone chooses to undergo a kidney extraction in exchange for money.
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Lessons learned: wrong intraocular lens.
Schein, Oliver D; Banta, James T; Chen, Teresa C; Pritzker, Scott; Schachat, Andrew P
2012-10-01
To report cases involving the placement of the wrong intraocular lens (IOL) at the time of cataract surgery where human error occurred. Retrospective small case series, convenience sample. Seven surgical cases. Institutional review of errors committed and subsequent improvements to clinical protocols. Lessons learned and changes in procedures adapted. The pathways to a wrong IOL are many but largely reflect some combination of poor surgical team communication, transcription error, lack of preoperative clarity in surgical planning or failure to match the patient, and IOL calculation sheet with 2 unique identifiers. Safety in surgery involving IOLs is enhanced both by strict procedures, such as an IOL-specific "time-out," and the fostering of a surgical team culture in which all members are encouraged to voice questions and concerns. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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Yang, Ruijie; Wang, Junjie; Zhang, Xile; Sun, Haitao; Gao, Yang; Liu, Lu; Lin, Lei
2014-01-01
Objective. To explore the implementation of incident learning for quality management of radiotherapy in a new established radiotherapy program. Materials and Methods. With reference to the consensus recommendations by American Association of Physicist in Medicine, an incident learning system was specifically established for reporting, investigating, and learning of individual incidents. The incidents that occurred in external beam radiotherapy from February, 2012, to February, 2014, were reported. Results. A total of 28 near misses and 5 incidents were reported. Among them, 5 originated in imaging for planning, 25 in planning, and 1 in plan transfer, commissioning, and delivery, respectively. One near miss/incident was classified as wrong patient, 7 wrong sites, 6 wrong laterality, and 5 wrong dose. Five reported incidents were all classified as grade 1/2 of dosimetric severity, 1 as grade 0, and the other 4 as grade 1 of medical severity. For the causes/contributory factors, negligence, policy not followed, and inadequate training contributed to 19, 15, and 12 near misses/incidents, respectively. The average incident rate per 100 patients treated was 0.4. Conclusion. Effective implementation of incident learning can reduce the occurrence of near misses/incidents and enhance the culture of safety. PMID:25140309
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NASA Astrophysics Data System (ADS)
White, Gary D.
2014-01-01
"I would never teach the Bohr model!" he exclaimed. "I don't believe in teaching things that are just wrong." He was a respected teacher, and I knew I should listen to what he had to say, but in the end I wasn't convinced that his view was right for me and my classes. In fact, I do believe in teaching things that are "just wrong"—selectively. For example, I like my introductory physics students to learn the planetary model of Hydrogen, and not only so that we can discuss why it is deficient. It's a great opportunity to "spiral back" to Newton's second law, circular motion, conservation of energy, and the origin of electromagnetic radiation—and it does get the ionization energy right if you assume an empirically determined radius for the atom! In addition, knowing specifically when, why, and how a model is wrong is one of the hallmarks that distinguishes science from other endeavors. Furthermore, one might argue that there really are no perfect models (models that successfully incorporate gravitational and quantum effects in one philosophically cohesive whole, for example), so every model is "just wrong" in some sense. Finally, even if there was a "perfect" model of the atom to teach, it does not follow that good pedagogy involves teaching it. Let me explain.
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The concept of wrongful life in the law.
Kasper, A S
1983-01-01
In the history of the law the concept of wrongful life is not new, but it has become of interest recently due to changing social attitudes and advances in contraceptive and genetic technologies. This discussion tries to assess the effects of wrongful life as a legal concept on the rights of childbearing women and their offspring. An unborn child had no rights under common law, which held that a fetus in utero had no existence separate from its mother. Consequently, a child had no right of action for personal harm brought upon it by another person. On occasion early courts disagreed with this view, but the majority of courts maintained that a child had no existence as a human being during gestation. The effect that this concept of common law would have on current abortion laws would be to make it considerably easier to argue for a woman's right to choose an abortion. The notion of wrongful life initially appeared in cases of illegitimate births. In Zepeda v. Zepeda, 1963, and Williams v. State of New York, 1966, the plaintiffs maintained that the children's births and existence were wrongful because they were unintended and illegitimate. In Williams the court ruled that birth under 1 set of circumstances and not another is not a recoverable injury. These cases failed to meet the requirements of tort law, and the court rejected the notion of children finding legal recourse for being born to a poor family or being born to a less desired race or class. A series of cases followed in which recovery for physical injury or birth deformities were claimed by parents for themselves and their children. In June 1980 a California appeals court reversed the decision of a lower court, addressing the fundamental principles of wrongful life as a legal concept. In Curlender v. Bio-Science Laboratories an infant brought suit alleging that the laboratories failed to correctly inform her parents of their status as carriers of Tay-Sachs disease during the mother's pregnancy. The infant was born with Tay-Sachs. This was the 1st case in which a court established that a child has a cause of action, separate from its parents, for a claim of wrongful life. In recognizing the child as an independent plaintiff the court established the child's right to allege that its life is wrongful, i.e., it should never have been born. The court in Curlender affirmed that the child's life, on its own, is of legitimate concern to the courts. A most forceful social issue raised here is the concept of quality of life and whether or not a life is worth living if burdened by debilitating injury. The court did not address the problems inherent in measuring quality of life from individual to individual, nor did it decide how a child must show injury to warrant recovery in court. The Curlender decision referred to the Roe v. Wade decision as a woman's legal right not to have a child, and by inference, as a child's legal right to be free of damage. By extension, Roe v. Wade could be interpreted as a legal right not to be born.
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de Angel Yágüez, Ricardo
2005-01-01
Chamber number 1 of the Spanish Supreme Court of Justice has announced its fourth wrongful birth case decision dated December 18, 2003. The issue is whether we can state that with these four rulings there is a genuine law of precedent, that is, reiterated doctrine of the Supreme Court of Justice on this matter (Article 1.6 of the Civil Code).
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Tanker Recapitalization: Lessons From the Past
2010-04-01
compliant and; that the effort is conducted with the utmost integrity. Nothing less will suffice. If the AF gets this wrong again it will strike a blow to...guidance compliant and; that the effort is conducted with the utmost integrity. Nothing less will suffice. If the AF gets this wrong again it will strike a...Recapitalization Gets Serious 30 The New Tanker Recapitalization Effort 30 Congressional Concerns 36 Analysis of Alternatives 41 The DOD
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Code of Federal Regulations, 2010 CFR
2010-01-01
... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Can I cancel my FERS election if I was in the wrong retirement plan at the time I elected FERS coverage and I have an election opportunity under... ERRONEOUS RETIREMENT COVERAGE CORRECTIONS ACT Making an Election Fers Elections § 839.621 Can I cancel my...
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Modeling Being "Lost": Imperfect Situation Awareness
NASA Technical Reports Server (NTRS)
Middleton, Victor E.
2011-01-01
Being "lost" is an exemplar of imperfect Situation Awareness/Situation Understanding (SA/SU) -- information/knowledge that is uncertain, incomplete, and/or just wrong. Being "lost" may be a geo-spatial condition - not knowing/being wrong about where to go or how to get there. More broadly, being "lost" can serve as a metaphor for uncertainty and/or inaccuracy - not knowing/being wrong about how one fits into a larger world view, what one wants to do, or how to do it. This paper discusses using agent based modeling (ABM) to explore imperfect SA/SU, simulating geo-spatially "lost" intelligent agents trying to navigate in a virtual world. Each agent has a unique "mental map" -- its idiosyncratic view of its geo-spatial environment. Its decisions are based on this idiosyncratic view, but behavior outcomes are based on ground truth. Consequently, the rate and degree to which an agent's expectations diverge from ground truth provide measures of that agent's SA/SU.
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Collins, Susan J; Newhouse, Robin; Porter, Jody; Talsma, AkkeNeel
2014-07-01
Approximately 2,700 patients are harmed by wrong-site surgery each year. The World Health Organization created the surgical safety checklist to reduce the incidence of wrong-site surgery. A project team conducted a narrative review of the literature to determine the effectiveness of the surgical safety checklist in correcting and preventing errors in the OR. Team members used Swiss cheese model of error by Reason to analyze the findings. Analysis of results indicated the effectiveness of the surgical checklist in reducing the incidence of wrong-site surgeries and other medical errors; however, checklists alone will not prevent all errors. Successful implementation requires perioperative stakeholders to understand the nature of errors, recognize the complex dynamic between systems and individuals, and create a just culture that encourages a shared vision of patient safety. Copyright © 2014 AORN, Inc. Published by Elsevier Inc. All rights reserved.
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Killing people: what Kant could have said about suicide and euthanasia but did not.
Brassington, I
2006-10-01
An agent who takes his own life acts in violation of the moral law, according to Kant; suicide, and, by extension, assisted suicide are therefore wrong. By a similar argument, and with a few important exceptions, killing is wrong; implicitly, then, voluntary euthanasia is also wrong. Kant's conclusions are uncompelling and his argument in these matters is undermined on considering other areas of his thought. Kant, in forbidding suicide and euthanasia, is conflating respect for persons and respect for people, and assuming that, in killing a person (either oneself or another), we are thereby undermining personhood. But an argument along these lines is faulty according to Kant's own standards. There is no reason why Kantians have to accept that self-killing and euthanasia are contrary to the moral law. Even if some Kantians adhere to this doctrine, others can reject it.
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Killing people: what Kant could have said about suicide and euthanasia but did not
Brassington, I
2006-01-01
An agent who takes his own life acts in violation of the moral law, according to Kant; suicide, and, by extension, assisted suicide are therefore wrong. By a similar argument, and with a few important exceptions, killing is wrong; implicitly, then, voluntary euthanasia is also wrong. Kant's conclusions are uncompelling and his argument in these matters is undermined on considering other areas of his thought. Kant, in forbidding suicide and euthanasia, is conflating respect for persons and respect for people, and assuming that, in killing a person (either oneself or another), we are thereby undermining personhood. But an argument along these lines is faulty according to Kant's own standards. There is no reason why Kantians have to accept that self‐killing and euthanasia are contrary to the moral law. Even if some Kantians adhere to this doctrine, others can reject it. PMID:17012496
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Kent, Stephanie L; Carmichael, Jason T
2015-07-01
The number of discovered wrongful criminal convictions (and resulting exonerations) has increased over the past decade. These cases erode public confidence in the criminal justice system and trust in the rule of law. Many states have adopted laws that aim to reduce system errors but no study has examined why some states appear more willing to provide due process protections against wrongful convictions than others. Findings from regression estimates suggest that states with a Republican controlled legislature or more Republican voters are less likely to pass these laws while the presence of advocacy organizations that are part of the 'innocence movement' make legislative change more likely. We thus identify important differences in the political and social context between U.S. states that influence the adoption of criminal justice policies. Copyright © 2015 Elsevier Inc. All rights reserved.
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Benefiting from 'evil': an incipient moral problem in human stem cell research.
Green, Ronald M
2002-11-01
When does benefiting from others' wrongdoing effectively make one a moral accomplice in their evil deeds? If stem cell research lives up to its therapeutic promise, this question (which has previously cropped up in debates over fetal tissue research or the use of Nazi research data) is likely to become a central one for opponents of embryo destruction. I argue that benefiting from wrongdoing is prima facie morally wrong under any of three conditions: (1) when the wrongdoing is one's agent; (2) when acceptance of benefit directly encourages the repetition of the wrongful deed (even though no agency relationship is involved); and (3) when acceptance of a benefit legitimates a wrongful practice. I conclude by showing that, because of the ways in which most embryonic stem cell lines come into being, people who oppose embryo destruction may use human embryonic stem cells without incurring moral blame.
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Doctors, lies and the addiction bureaucracy.
Dalrymple, Theodore
2008-04-01
Almost everything you know about heroin addiction is wrong. Not only is it wrong, but it is obviously wrong. Heroin is not highly addictive; withdrawal from it is not medically serious; addicts do not become criminals to feed their habit; addicts do not need any medical assistance to stop taking heroin; and contrary to received wisdom, heroin addiction most certainly is a moral or spiritual problem. A literary tradition dating back to De Quincey and Coleridge, and continuing up to the deeply sociopathic William Burroughs and beyond, has misled all Western societies for generations about the nature of heroin addiction. These writers' self-dramatizing and dishonest accounts of their own addiction have been accepted uncritically, and have been more influential by far in forming public attitudes than the whole of pharmacological science. As a result, a self-serving, self-perpetuating and completely useless medical bureaucracy has been set up to deal with the problem.
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Air Force Command and Control: The Path Ahead. Volume 2: Panel Reports
2003-03-01
third case, the most destructive result could occur when the wrong information is passed, or sent to the wrong people. This could mean disaster to an...recommendations. This volume, Volume 2, presents the panel reports, including detailed findings and recommendations. The study results are the product of...Force. The lessons learned from DESERT STORM and ALLIED FORCE and the results of every SAB and Defense Science Board study have determined that U.S
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An Examination of Overt Offensive Military Operations Outside of Combat Zones
2006-12-01
Robinson, John Arquilla, Jennifer Duncan and Edwin R. Micewski. The staff and research librarians of the Dudley Knox Library deserve special recognition...militants with the trainees and resources necessary for a terrorist attack like 9/11. John Arquilla writes that a protracted war is the wrong strategy...2004). 10 John Arquilla, “In the Fight Against Terrorism, The Long War is the Wrong War,” San Francisco Chronicle, 16 July 2006. 11 For a
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Shapira, A
1998-01-01
A "wrongful life" suit is based on the purported tortious liability of a genetic counsellor towards an infant with hereditary defects, with the latter asserting that he or she would not have been born at all if not for the counsellor's negligence. This negligence allegedly lies in the failure on the part of the defendant adequately to advice the parents or to conduct properly the relevant testing and thereby prevent the child's conception or birth (where unimpaired life was not possible). This paper will offer support for the thesis that it would be both feasible and desirable to endorse "wrongful life" compensation actions. The genetic counsellor owed a duty of due professional care to the impaired newborn who now claims that but for the counsellor's negligence, he or she would not have been born at all. The plaintiff's defective life (where healthy life was never an option) constitutes a compensable injury. A sufficient causal link may exist between the plaintiff's injury and the defendant's breach of duty of due professional care and an appropriate measure of damages can be allocated to the disabled newborn. Sanctioning a "wrongful life" cause of action does not necessarily entail abandoning valuable constraints with regard to abortion and euthanasia. Nor does it inevitably lead to an uncontrolled slide down a "slippery slope". PMID:9873975
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, R; Wang, J
2014-06-15
Purpose: To explore the implementation and effectiveness of incident learning for the safety and quality of radiotherapy in a new established radiotherapy program with advanced technology. Methods: Reference to the consensus recommendations by American Association of Physicist in Medicine, an incident learning system was specifically designed for reporting, investigating, and learning of individual radiotherapy incidents in a new established radiotherapy program, with 4D CBCT, Ultrasound guided radiotherapy, VMAT, gated treatment delivered on two new installed linacs. The incidents occurring in external beam radiotherapy from February, 2012 to January, 2014 were reported. Results: A total of 33 reports were analyzed, includingmore » 28 near misses and 5 incidents. Among them, 5 originated in imaging for planning, 25 in planning, 1 in plan transfer, 1 in commissioning and 1 in treatment delivery. Among them, three near misses originated in the safety barrier of the radiotherapy process. In terms of error type, 1 incident was classified as wrong patient, 7 near misses/incidents as wrong site, 6 as wrong laterality, 5 as wrong dose, 7 as wrong prescription, and 7 as suboptimal plan quality. 5 incidents were all classified as grade 1/2 of dosimetric severity, 1 as grade 0, and the other 4 as grade 1 of medical severity. For the causes/contributory factors, negligence, policy not followed, inadequate training, failure to develop an effective plan, and communication contributed to 19, 15, 12, 5 and 3 near misses/incidents, respectively. The average incident rate per 100 patients treated was 0.4; this rate fell to 0.28% in the second year from 0.56% in the first year. The rate of near miss fell to 1.24% from 2.22%. Conclusion: Effective incident learning can reduce the occurrence of near miss/incidents, enhance the culture of safety. Incident learning is an effective proactive method for improving the quality and safety of radiotherapy.« less
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Preoperative Safety Briefing Project
DeFontes, James; Surbida, Stephanie
2004-01-01
Context: Increased media attention on surgical procedures that were performed on the wrong anatomic site or wrong patient has prompted the health care industry to identify and address human factors that lead to medical errors. Objective: To increase patient safety in the perioperative setting, our objective was to create a climate of improved communication, collaboration, team-work, and situational awareness while the surgical team reviewed pertinent information about the patient and the pending procedure. Methods: A team of doctors, nurses, and technicians used human factors principles to develop the Preoperative Safety Briefing for use by surgical teams, a briefing similar to the preflight checklist used by the airline industry. A six-month pilot of the briefing began in the Kaiser Permanente (KP) Anaheim Medical Center in February 2002. Four indicators of safety culture were used to measure success of the pilot: occurrence of wrong-site/wrong procedures, attitudinal survey data, near-miss reports, and nursing personnel turnover data. Results: Wrong-site surgeries decreased from 3 to 0 (300%) per year; employee satisfaction increased 19%; nursing personnel turnover decreased 16%; and perception of the safety climate in the operating room improved from “good” to “outstanding.” Operating suite personnel perception of teamwork quality improved substantially. Operating suite personnel perception of patient safety as a priority, of personnel communication, of their taking responsibility for patient safety, of nurse input being well received, of overall morale, and of medical errors being handled appropriately also improved substantially. Conclusions: Team members who work together and communicate well can quickly detect and more easily avoid errors. The Preoperative Safety Briefing is now standard in many operating suites in the KP Orange County Service Area. The concepts and design of this project are transferable, and similar projects are underway in the Departments of Radiology and of Labor and Delivery at KP Anaheim Medical Center. PMID:26704913
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The SAMHD1 dNTP Triphosphohydrolase Is Controlled by a Redox Switch.
Mauney, Christopher H; Rogers, LeAnn C; Harris, Reuben S; Daniel, Larry W; Devarie-Baez, Nelmi O; Wu, Hanzhi; Furdui, Cristina M; Poole, Leslie B; Perrino, Fred W; Hollis, Thomas
2017-12-01
Proliferative signaling involves reversible posttranslational oxidation of proteins. However, relatively few molecular targets of these modifications have been identified. We investigate the role of protein oxidation in regulation of SAMHD1 catalysis. Here we report that SAMHD1 is a major target for redox regulation of nucleotide metabolism and cell cycle control. SAMHD1 is a triphosphate hydrolase, whose function involves regulation of deoxynucleotide triphosphate pools. We demonstrate that the redox state of SAMHD1 regulates its catalytic activity. We have identified three cysteine residues that constitute an intrachain disulfide bond "redox switch" that reversibly inhibits protein tetramerization and catalysis. We show that proliferative signals lead to SAMHD1 oxidation in cells and oxidized SAMHD1 is localized outside of the nucleus. Innovation and Conclusions: SAMHD1 catalytic activity is reversibly regulated by protein oxidation. These data identify a previously unknown mechanism for regulation of nucleotide metabolism by SAMHD1. Antioxid. Redox Signal. 27, 1317-1331.
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Leshinsky-Silver, E; Michelson, M; Cohen, S; Ginsberg, M; Sadeh, M; Barash, V; Lerman-Sagie, T; Lev, D
2008-07-01
Isolated mitochondrial myopathies (IMM) are either due to primary defects in mtDNA, in nuclear genes that control mtDNA abundance and structure such as thymidine kinase 2 (TK2), or due to CoQ deficiency. Defects in the TK2 gene have been found to be associated with mtDNA depletion attributed to a depleted mitochondrial dNTP pool in non-dividing cells. We report an unusual case of IMM, homozygous for the H90N mutation in the TK2 gene but unlike other cases with the same mutation, does not demonstrate mtDNA depletion. The patient's clinical course is relatively mild and a muscle biopsy showed ragged red muscle fibers with a mild decrease in complexes I and an increase in complexes IV and II activities. This report extends the phenotypic expression of TK2 defects and suggests that all patients who present with an IMM even with normal quantities of mtDNA should be screened for TK2 mutations.
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Fatty acid carbon is essential for dNTP synthesis in endothelial cells
Missiaen, Rindert; Queiroz, Karla CS; Borgers, Gitte; Elia, Ilaria; Zecchin, Annalisa; Cantelmo, Anna Rita; Christen, Stefan; Goveia, Jermaine; Heggermont, Ward; Goddé, Lucica; Vinckier, Stefan; Van Veldhoven, Paul P.; Eelen, Guy; Schoonjans, Luc; Gerhardt, Holger; Dewerchin, Mieke; Baes, Myriam; De Bock, Katrien; Ghesquière, Bart; Lunt, Sophia Y.; Fendt, Sarah-Maria; Carmeliet, Peter
2015-01-01
The metabolism of endothelial cells (ECs) during vessel sprouting remains poorly studied. Here, we report that endothelial loss of CPT1a, a rate-limiting enzyme of fatty acid oxidation (FAO), caused vascular sprouting defects due to impaired proliferation, not migration of ECs. Reduction of FAO in ECs did not cause energy depletion or disturb redox homeostasis, but impaired de novo nucleotide synthesis for DNA replication. Isotope labeling studies in control ECs showed that fatty acid carbons substantially replenished the Krebs cycle, and were incorporated into aspartate (a nucleotide precursor), uridine monophosphate (a precursor of pyrimidine nucleoside triphosphates) and DNA. CPT1a silencing reduced these processes and depleted EC stores of aspartate and deoxyribonucleoside triphosphates. Acetate (metabolized to acetyl-CoA, thereby substituting for the depleted FAO-derived acetyl-CoA) or a nucleoside mix rescued the phenotype of CPT1a-silenced ECs. Finally, CPT1 blockade inhibited pathological ocular angiogenesis, suggesting a novel strategy for blocking angiogenesis. PMID:25830893
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Lebovka, I Iu; Kozhina, T N; Fedorova, I V; Peshekhonov, V T; Evstiukhina, T A; Chernenkov, A Iu; Korolev, V G
2014-01-01
SIN3 gene product operates as a repressor for a huge amount of genes in Saccharomyces cerevisiae. Sin3 protein with a mass of about 175 kDa is a member of the RPD3 protein complex with an assessed mass of greater than 2 million Da. It was previously shownthat RPD3 gene mutations influence recombination and repair processes in S. cerevisiae yeasts. We studied the impacts of the sin3 mutation on UV-light sensitivity and UV-induced mutagenesis in budding yeast cells. The deletion ofthe SIN3 gene causes weak UV-sensitivity of mutant budding cells as compared to the wild-type strain. These results show that the sin3 mutation decreases both spontaneous and UV-induced levels of levels. This fact is hypothetically related to themalfunction of ribonucleotide reductase activity regulation, which leads to a decrease in the dNTP pool and the inaccurate error-prone damage bypass postreplication repair pathway, which in turn provokes a reduction in the incidence of mutations.
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Developing an After Action Review System for a 3D Interactive Training Simulation Using XML
2004-03-01
Implementation. Addison Wesley © 1999 ISBN 0-201-32557-8 [2] H. M. Deitel and P. J. Deitel , Deitel and Associates Inc.(2001). C++ How to Program 3rd...and how can this technique help the trainer and the trainee? They both now have a common useful tool to discern what happened during the simulation...participants who acted incorrectly but rather to spot any wrong decisions or actions, and analyze why they were wrong, what the consequences were, and how
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Cyber Deterrence: The Wrong Question for the Wrong Problem
2018-04-20
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NASA Astrophysics Data System (ADS)
Graney, Christopher M.
2012-01-01
What can physics students learn about science from those scientists who got the answers wrong? Your students probably have encountered little science history. What they have encountered probably has portrayed scientists as ``The People with the Right Answers.'' But those who got the wrong answers can teach students that in science, answers are often elusive--not found in the back of a book or discovered in a bold stroke of genius.
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Stability Operations: From the Post-Vietnam War Era to Today
2011-12-01
Peacekeeping Doctrine, and Practice after the Cold War (Westport, CT: Praeger, 2004), 88. 14 John D. Waghelstein, “What’s Wrong in Iraq? Or Ruminations of a...stability operations. “I don’t think our troops ought to be used for what’s called nation-building,” Bush contended during the 2000 presidential...Waghelstein John D. “What’s Wrong in Iraq? Or Ruminations of a Pachyderm.” Military Review 86, no. 1 (January-February 2006). Warner, Volney J., and James H
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When experiments go wrong: the U.S. perspective.
Capron, Alexander M
2004-01-01
The view that once prevailed in the U.S.--that research is no more dangerous than the activities of daily life--no longer holds in light of recent experience. Within the past few years, a number of subjects (including normal volunteers) have been seriously injured or killed in research conducted at prestigious institutions. Plainly, when we are talking about research going wrong, we're talking about something very important. We have seen that experiments can go wrong in several ways. Subjects can be injured--physically, mentally, or by having other interests violated. Investigators can commit fraud in data collection or can abuse subjects. And review mechanisms--such as IRBs--don't always work. The two major issues when research goes wrong in any of these ways are, first: What will be done for subjects who have suffered an injury or other wrong? and second: How will future problems be prevented? The present system in the U.S. is better at the second task than the first one. Part of the difficulty in addressing the first lies in knowing what "caused" an apparent injury. Moreover, since until recently the problem of research-related injuries was thought to be a small one, there was considerable resistance to setting up a non-fault compensation system, for fear that it would lead to payment in many cases where such compensation was not deserved. Now, with a further nudge from the NBAC there is renewed interest in developing a formal system to compensate for research injuries. Finally, I have tried to show that our system of local oversight is only partially effective in improving the design of experiments and the consent process in light of "unexpected (adverse) results." As many observers, including the federal General Accounting Office (GAO), have reported, the requirement for "continuing review" of approved research projects is the weak point in the IRB system. The probable solution would be to more strictly apply the requirement that investigators report back any adverse results, de-emphasizing the "screen" introduced by the present language about "unexpected" findings. Yet, despite its weaknesses, there are good aspects to the local basis of our oversight system, and when problems become severe enough, OHRP is likely to evaluate a system and insist on local improvements. Thus, while the U.S. system is far from perfect in responding when research goes wrong, our experience may be useful to others in crafting a system appropriate to their own circumstances. One of the major tasks will be to adequately define what triggers oversight--that is, who reports what to whom and when? The setting of this trigger needs to balance appropriate incentives and penalties. Any system, including our own, will, in my opinion, work much better once an accreditation process is in place, which will offer much more current and detailed information on how each IRB is functioning and what steps are needed to help avoid "experiments going wrong."
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Actual innocence: is death different?
Acker, James R
2009-01-01
Supreme Court jurisprudence relies heavily on the premise that "death is different" from other criminal sanctions, and that capital cases entail commensurately demanding standards of reliability. Although invoked most frequently with respect to sentencing, both precedent and logic suggest that heightened reliability applies as well to guilt determination in capital trials. Nevertheless, recurrent and highly visible wrongful convictions in capital cases have affected public opinion, contributed to a precipitous decline in new death sentences, and led to calls for reforms designed to guard against the risk of executing innocent persons. This article examines the implications of the "death is different" doctrine for the problem of wrongful convictions in both capital and non-capital cases. It argues that innovations designed to enhance reliability in the special context of death-penalty prosecutions are important in their own right, but relevant new safeguards also should extend to criminal cases generally, where innocent people are similarly at risk and wrongful convictions are far more prevalent. (c) 2009 John Wiley & Sons, Ltd.
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Remote Video Auditing in the Surgical Setting.
Pedersen, Anne; Getty Ritter, Elizabeth; Beaton, Megan; Gibbons, David
2017-02-01
Remote video auditing, a method first adopted by the food preparation industry, was later introduced to the health care industry as a novel approach to improving hand hygiene practices. This strategy yielded tremendous and sustained improvement, causing leaders to consider the potential effects of such technology on the complex surgical environment. This article outlines the implementation of remote video auditing and the first year of activity, outcomes, and measurable successes in a busy surgery department in the eastern United States. A team of anesthesia care providers, surgeons, and OR personnel used low-resolution cameras, large-screen displays, and cell phone alerts to make significant progress in three domains: application of the Universal Protocol for preventing wrong site, wrong procedure, wrong person surgery; efficiency metrics; and cleaning compliance. The use of cameras with real-time auditing and results-sharing created an environment of continuous learning, compliance, and synergy, which has resulted in a safer, cleaner, and more efficient OR. Copyright © 2017 AORN, Inc. Published by Elsevier Inc. All rights reserved.
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Eager feelings and vigilant reasons: Regulatory focus differences in judging moral wrongs
Cornwell, James F. M.; Higgins, E. Tory
2015-01-01
For over a decade, moral psychologists have been actively researching the processes underlying moral judgments that are made intuitively without reference to an action’s concrete harms or injustice, such as the well-known case of non-procreative, consensual incest. We suggest that the reason some judge this scenario as wrong (using intuitive feelings) and others do not (using deliberative reasons) is due to an important motivational distinction. Consistent with this view, across seven studies, we demonstrate that negative judgments of such intuitive moral scenarios are more intense when processed in the promotion focus compared to the prevention focus, and that this is due to differences in whether eager (intuitive) versus vigilant (deliberative) means are employed in judging these moral wrongs. By examining various boundary conditions for this phenomenon and foundations for these judgments, we learn about the overall differences between promotion and prevention regarding how proscriptive judgments are processed, and begin to integrate these differences with existing theories in moral psychology. PMID:26726912
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Influences of misprediction costs on solar flare prediction
NASA Astrophysics Data System (ADS)
Huang, Xin; Wang, HuaNing; Dai, XingHua
2012-10-01
The mispredictive costs of flaring and non-flaring samples are different for different applications of solar flare prediction. Hence, solar flare prediction is considered a cost sensitive problem. A cost sensitive solar flare prediction model is built by modifying the basic decision tree algorithm. Inconsistency rate with the exhaustive search strategy is used to determine the optimal combination of magnetic field parameters in an active region. These selected parameters are applied as the inputs of the solar flare prediction model. The performance of the cost sensitive solar flare prediction model is evaluated for the different thresholds of solar flares. It is found that more flaring samples are correctly predicted and more non-flaring samples are wrongly predicted with the increase of the cost for wrongly predicting flaring samples as non-flaring samples, and the larger cost of wrongly predicting flaring samples as non-flaring samples is required for the higher threshold of solar flares. This can be considered as the guide line for choosing proper cost to meet the requirements in different applications.
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Authority dependence and judgments of utilitarian harm.
Piazza, Jared; Sousa, Paulo; Holbrook, Colin
2013-09-01
Three studies tested the conditions under which people judge utilitarian harm to be authority dependent (i.e., whether its right or wrongness depends on the ruling of an authority). In Study 1, participants judged the right or wrongness of physical abuse when used as an interrogation method anticipated to yield useful information for preventing future terrorist attacks. The ruling of the military authority towards the harm was manipulated (prohibited vs. prescribed) and found to significantly influence judgments of the right or wrongness of inflicting harm. Study 2 established a boundary condition with regards to the influence of authority, which was eliminated when the utility of the harm was definitely obtained rather than forecasted. Finally, Study 3 replicated the findings of Studies 1-2 in a completely different context-an expert committee's ruling about the harming of chimpanzees for biomedical research. These results are discussed as they inform ongoing debates regarding the role of authority in moderating judgments of complex and simple harm. Copyright © 2013 Elsevier B.V. All rights reserved.
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The Effects of Bar-coding Technology on Medication Errors: A Systematic Literature Review.
Hutton, Kevin; Ding, Qian; Wellman, Gregory
2017-02-24
The bar-coding technology adoptions have risen drastically in U.S. health systems in the past decade. However, few studies have addressed the impact of bar-coding technology with strong prospective methodologies and the research, which has been conducted from both in-pharmacy and bedside implementations. This systematic literature review is to examine the effectiveness of bar-coding technology on preventing medication errors and what types of medication errors may be prevented in the hospital setting. A systematic search of databases was performed from 1998 to December 2016. Studies measuring the effect of bar-coding technology on medication errors were included in a full-text review. Studies with the outcomes other than medication errors such as efficiency or workarounds were excluded. The outcomes were measured and findings were summarized for each retained study. A total of 2603 articles were initially identified and 10 studies, which used prospective before-and-after study design, were fully reviewed in this article. Of the 10 included studies, 9 took place in the United States, whereas the remaining was conducted in the United Kingdom. One research article focused on bar-coding implementation in a pharmacy setting, whereas the other 9 focused on bar coding within patient care areas. All 10 studies showed overall positive effects associated with bar-coding implementation. The results of this review show that bar-coding technology may reduce medication errors in hospital settings, particularly on preventing targeted wrong dose, wrong drug, wrong patient, unauthorized drug, and wrong route errors.
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Stigma stories: four discourses about teen mothers, welfare, and poverty.
Kelly, D M
1996-06-01
This study uses a pragmatic model of discourse theory to analyze more than 700 articles about adolescent mothers published in the Canadian printed media in 1980-92. The introduction notes that feminist research has challenged the view that adolescent motherhood is caused by and perpetrates poverty and that a strong social stigma is still associated with teen pregnancy. After describing the methodology and theoretical framework used in this analysis, academic research on adolescent mothers, welfare, and poverty is criticized for using teen motherhood as a conventional scapegoat which allows the structural causes of poverty to be ignored. Discourses about teenage mothers are then described as a "stigma contest." Thus, discussion centers on 1) the bureaucratic notion that the "wrong" girls are keeping their babies, 2) the conservative framework which holds that an unwed teenager who relies on welfare and refuses to give her baby up for adoption (having properly rejected abortion) serves as the epitome of a "wrong family," and 3) oppositional discourse which provides a "wrong society" framework and is articulated in the alternative media. A "stigma-is-wrong" framework is then provided by the self-interpretation of the teen mothers who hold that the right to choose is essential and that it is inappropriate to stigmatize any choice. The bureaucratic viewpoint is the most common winner in this media contest and helps to frame the public debate and public policy about teenage motherhood and, thus, profoundly influences the daily lives of young mothers and their children by perpetuating negative stereotypes.
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Accuracy of outpatient service data for activity-based funding in New South Wales, Australia.
Munyisia, Esther N; Reid, David; Yu, Ping
2017-05-01
Despite increasing research on activity-based funding (ABF), there is no empirical evidence on the accuracy of outpatient service data for payment. This study aimed to identify data entry errors affecting ABF in two drug and alcohol outpatient clinic services in Australia. An audit was carried out on healthcare workers' (doctors, nurses, psychologists, social workers, counsellors, and aboriginal health education officers) data entry errors in an outpatient electronic documentation system. Of the 6919 data entries in the electronic documentation system, 7.5% (518) had errors, 68.7% of the errors were related to a wrong primary activity, 14.5% were due to a wrong activity category, 14.5% were as a result of a wrong combination of primary activity and modality of care, 1.9% were due to inaccurate information on a client's presence during service delivery and 0.4% were related to a wrong modality of care. Data entry errors may affect the amount of funding received by a healthcare organisation, which in turn may affect the quality of treatment provided to clients due to the possibility of underfunding the organisation. To reduce errors or achieve an error-free environment, there is a need to improve the naming convention of data elements, their descriptions and alignment with the national standard classification of outpatient services. It is also important to support healthcare workers in their data entry by embedding safeguards in the electronic documentation system such as flags for inaccurate data elements.
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Daurat, A; Boudet, E; Daurat, G; Roger, C; Gris, J-C; Tunez, V; Gaste, M-C; Lefrant, J-Y
2017-06-01
In France, blood group determination requires the completion of two samples collected at two different times to detect identity mistake and "wrong blood in tube". The aims of the present study were: (1) to evaluate the compliance with guidelines and (2) to identify risk factors of non-compliance. Samples for ABO group determination collected between January 1st and December 15th, 2013 in the University hospital of Nîmes, France were analyzed. An ABO group determination demand was considered non-compliant if more than one tube arrived in the laboratory within ten minutes apart. Between May 1st and June 30th 2014, a self-administered questionnaire was offered to the nurses of the hospital on a random day for each service during this period. The aim was to validate the non-compliance criterion and the identification of risk factors using logistic regression. Among the 16,450 analyzed blood samples, the overall compliance rate was 65.1%. Lower compliance rates were found in the surgical services. Independent risk factors for wrong practice were work overload, surgical service and individual intermediate transfusion frequency. More than one third of ABO group determinations did not follow national recommendations, which induces a substantial risk of "wrong blood in tube" and group error. The study revealed major variations among hospital services. Identification of risk factors allows targeted corrective actions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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E-prescribing errors in community pharmacies: exploring consequences and contributing factors.
Odukoya, Olufunmilola K; Stone, Jamie A; Chui, Michelle A
2014-06-01
To explore types of e-prescribing errors in community pharmacies and their potential consequences, as well as the factors that contribute to e-prescribing errors. Data collection involved performing 45 total hours of direct observations in five pharmacies. Follow-up interviews were conducted with 20 study participants. Transcripts from observations and interviews were subjected to content analysis using NVivo 10. Pharmacy staff detected 75 e-prescription errors during the 45 h observation in pharmacies. The most common e-prescribing errors were wrong drug quantity, wrong dosing directions, wrong duration of therapy, and wrong dosage formulation. Participants estimated that 5 in 100 e-prescriptions have errors. Drug classes that were implicated in e-prescribing errors were antiinfectives, inhalers, ophthalmic, and topical agents. The potential consequences of e-prescribing errors included increased likelihood of the patient receiving incorrect drug therapy, poor disease management for patients, additional work for pharmacy personnel, increased cost for pharmacies and patients, and frustrations for patients and pharmacy staff. Factors that contribute to errors included: technology incompatibility between pharmacy and clinic systems, technology design issues such as use of auto-populate features and dropdown menus, and inadvertently entering incorrect information. Study findings suggest that a wide range of e-prescribing errors is encountered in community pharmacies. Pharmacists and technicians perceive that causes of e-prescribing errors are multidisciplinary and multifactorial, that is to say e-prescribing errors can originate from technology used in prescriber offices and pharmacies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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E-Prescribing Errors in Community Pharmacies: Exploring Consequences and Contributing Factors
Stone, Jamie A.; Chui, Michelle A.
2014-01-01
Objective To explore types of e-prescribing errors in community pharmacies and their potential consequences, as well as the factors that contribute to e-prescribing errors. Methods Data collection involved performing 45 total hours of direct observations in five pharmacies. Follow-up interviews were conducted with 20 study participants. Transcripts from observations and interviews were subjected to content analysis using NVivo 10. Results Pharmacy staff detected 75 e-prescription errors during the 45 hour observation in pharmacies. The most common e-prescribing errors were wrong drug quantity, wrong dosing directions, wrong duration of therapy, and wrong dosage formulation. Participants estimated that 5 in 100 e-prescriptions have errors. Drug classes that were implicated in e-prescribing errors were antiinfectives, inhalers, ophthalmic, and topical agents. The potential consequences of e-prescribing errors included increased likelihood of the patient receiving incorrect drug therapy, poor disease management for patients, additional work for pharmacy personnel, increased cost for pharmacies and patients, and frustrations for patients and pharmacy staff. Factors that contribute to errors included: technology incompatibility between pharmacy and clinic systems, technology design issues such as use of auto-populate features and dropdown menus, and inadvertently entering incorrect information. Conclusion Study findings suggest that a wide range of e-prescribing errors are encountered in community pharmacies. Pharmacists and technicians perceive that causes of e-prescribing errors are multidisciplinary and multifactorial, that is to say e-prescribing errors can originate from technology used in prescriber offices and pharmacies. PMID:24657055
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What's Wrong with Early Medieval Medicine?
Horden, Peregrine
2011-01-01
The medical writings of early medieval western Europe c. 700 – c. 1000 have often been derided for their disorganised appearance, poor Latin, nebulous conceptual framework, admixtures of magic and folklore, and general lack of those positive features that historians attribute to ancient or later medieval medicine. This paper attempts to rescue the period from its negative image. It examines a number of superficially bizarre writings so as to place them in an intellectual and sociological context, and to suggest that the presumed contrast between them and their ancient and later medieval counterparts has been wrongly drawn.
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The Ultimate Challenge: Prove B. F. Skinner Wrong
Chance, Paul
2007-01-01
For much of his career, B. F. Skinner displayed the optimism that is often attributed to behaviorists. With time, however, he became less and less sanguine about the power of behavior science to solve the major problems facing humanity. Near the end of his life he concluded that a fair consideration of principles revealed by the scientific analysis of behavior leads to pessimism about our species. In this article I discuss the case for Skinner's pessimism and suggest that the ultimate challenge for behavior analysts today is to prove Skinner wrong. PMID:22478494
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What's wrong with me? Coming to terms with same sex attraction.
Richardson, Brian
2011-10-01
Many, if not all, young people question what is wrong with them when they begin to realise that they are attracted to people of the same sex. This can be because of feelings of confusion, guilt and shame, which can develop in reaction to the society in which they live; feelings that are often mirrored by the families of the young people concerned. This article explains the theories behind sexuality to help nurses provide unprejudiced, appropriate support and information to children and young people seeking help.
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Application of failure mode and effects analysis (FMEA) to pretreatment phases in tomotherapy.
Broggi, Sara; Cantone, Marie Claire; Chiara, Anna; Di Muzio, Nadia; Longobardi, Barbara; Mangili, Paola; Veronese, Ivan
2013-09-06
The aim of this paper was the application of the failure mode and effects analysis (FMEA) approach to assess the risks for patients undergoing radiotherapy treatments performed by means of a helical tomotherapy unit. FMEA was applied to the preplanning imaging, volume determination, and treatment planning stages of the tomotherapy process and consisted of three steps: 1) identification of the involved subprocesses; 2) identification and ranking of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system; and 3) identification of additional safety measures to be proposed for process quality and safety improvement. RPN upper threshold for little concern of risk was set at 125. A total of 74 failure modes were identified: 38 in the stage of preplanning imaging and volume determination, and 36 in the stage of planning. The threshold of 125 for RPN was exceeded in four cases: one case only in the phase of preplanning imaging and volume determination, and three cases in the stage of planning. The most critical failures appeared related to (i) the wrong or missing definition and contouring of the overlapping regions, (ii) the wrong assignment of the overlap priority to each anatomical structure, (iii) the wrong choice of the computed tomography calibration curve for dose calculation, and (iv) the wrong (or not performed) choice of the number of fractions in the planning station. On the basis of these findings, in addition to the safety strategies already adopted in the clinical practice, novel solutions have been proposed for mitigating the risk of these failures and to increase patient safety.
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Neuroanatomical substrates involved in unrelated false facial recognition.
Ronzon-Gonzalez, Eliane; Hernandez-Castillo, Carlos R; Pasaye, Erick H; Vaca-Palomares, Israel; Fernandez-Ruiz, Juan
2017-11-22
Identifying faces is a process central for social interaction and a relevant factor in eyewitness theory. False recognition is a critical mistake during an eyewitness's identification scenario because it can lead to a wrongful conviction. Previous studies have described neural areas related to false facial recognition using the standard Deese/Roediger-McDermott (DRM) paradigm, triggering related false recognition. Nonetheless, misidentification of faces without trying to elicit false memories (unrelated false recognition) in a police lineup could involve different cognitive processes, and distinct neural areas. To delve into the neural circuitry of unrelated false recognition, we evaluated the memory and response confidence of participants while watching faces photographs in an fMRI task. Functional activations of unrelated false recognition were identified by contrasting the activation on this condition vs. the activations related to recognition (hits) and correct rejections. The results identified the right precentral and cingulate gyri as areas with distinctive activations during false recognition events suggesting a conflict resulting in a dysfunction during memory retrieval. High confidence suggested that about 50% of misidentifications may be related to an unconscious process. These findings add to our understanding of the construction of facial memories and its biological basis, and the fallibility of the eyewitness testimony.
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Does the Golem Feel Pain? Moral Instincts and Ethical Dilemmas Concerning Suffering and the Brain.
Devor, Marshall; Rappaport, Isabelle; Rappaport, Z Harry
2015-07-01
Pain has variously been used as a means of punishment, extracting information, or testing commitment, as a tool for education and social control, as a commodity for sacrifice, and as a draw for sport and entertainment. Attitudes concerning these uses have undergone major changes in the modern era. Normative convictions on what is right and wrong are generally attributed to religious tradition or to secular-humanist reasoning. Here, we elaborate the perspective that ethical choices concerning pain have much earlier roots that are based on instincts and brain-seated empathetic responses. They are fundamentally a function of brain circuitry shaped by processes of Darwinian evolution. Social convention and other environmental influences, with their idiosyncrasies, are a more recent, ever-changing overlay. We close with an example in which details on the neurobiology of pain processing, specifically the question of where in the brain the experience of pain is generated, affect decision making in end-of-life situations. By separating innate biological substrates from culturally imposed attitudes (memes), we may arrive at a more reasoned approach to a morality of pain prevention. © 2014 World Institute of Pain.
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Adolescent Misconduct Behaviors: A Cross-Cultural Perspective of Adolescents and Their Parents
Tisak, Marie S.; Tisak, John; Chen, Yiwei; Fang, Qijuan; Baker, Erin R.
2017-01-01
The primary goal of the current study was to examine cultural differences in Chinese and U.S. adolescents’ and parents’ perceptions and evaluations of adolescent misconduct behaviors. A total of 395 U.S. and Chinese adolescents (ages 11-19 years) and 255 parents participated in this study. Each participant generated adolescent misconduct behaviors and rated each misconduct behavior as to the degree of wrongness. The misconduct behaviors were coded into 10 categories across three themes (moral offenses, drugs, and conventions). Results revealed significant cultural differences in a number of adolescent misconduct behaviors. For example, the United States generated more misconduct behaviors in weapon offenses and drug use than did China. These cultural differences were further complicated by an interaction between culture and generation. Chinese adolescents were more likely than U.S. adolescents to use categories of school, home, and social conventional violations, and considered these adolescent misconduct behaviors to be more wrong. However, it was the U.S. parents who considered adolescent misconduct behaviors in these categories to be more wrong than did Chinese parents. PMID:29051630
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Adolescent Misconduct Behaviors: A Cross-Cultural Perspective of Adolescents and Their Parents.
Tisak, Marie S; Tisak, John; Chen, Yiwei; Fang, Qijuan; Baker, Erin R
2017-01-01
The primary goal of the current study was to examine cultural differences in Chinese and U.S. adolescents' and parents' perceptions and evaluations of adolescent misconduct behaviors. A total of 395 U.S. and Chinese adolescents (ages 11-19 years) and 255 parents participated in this study. Each participant generated adolescent misconduct behaviors and rated each misconduct behavior as to the degree of wrongness. The misconduct behaviors were coded into 10 categories across three themes (moral offenses, drugs, and conventions). Results revealed significant cultural differences in a number of adolescent misconduct behaviors. For example, the United States generated more misconduct behaviors in weapon offenses and drug use than did China. These cultural differences were further complicated by an interaction between culture and generation. Chinese adolescents were more likely than U.S. adolescents to use categories of school, home, and social conventional violations, and considered these adolescent misconduct behaviors to be more wrong. However, it was the U.S. parents who considered adolescent misconduct behaviors in these categories to be more wrong than did Chinese parents.
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The Reputational Consequences of Failed Replications and Wrongness Admission among Scientists
Fetterman, Adam K.; Sassenberg, Kai
2015-01-01
Scientists are dedicating more attention to replication efforts. While the scientific utility of replications is unquestionable, the impact of failed replication efforts and the discussions surrounding them deserve more attention. Specifically, the debates about failed replications on social media have led to worry, in some scientists, regarding reputation. In order to gain data-informed insights into these issues, we collected data from 281 published scientists. We assessed whether scientists overestimate the negative reputational effects of a failed replication in a scenario-based study. Second, we assessed the reputational consequences of admitting wrongness (versus not) as an original scientist of an effect that has failed to replicate. Our data suggests that scientists overestimate the negative reputational impact of a hypothetical failed replication effort. We also show that admitting wrongness about a non-replicated finding is less harmful to one’s reputation than not admitting. Finally, we discovered a hint of evidence that feelings about the replication movement can be affected by whether replication efforts are aimed one’s own work versus the work of another. Given these findings, we then present potential ways forward in these discussions. PMID:26650842
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Reacting to Galileo: Introducing a New Approach for Gen Ed Science
NASA Astrophysics Data System (ADS)
Pettersen, Michael
2009-03-01
Either Galileo was right, or he was wrong; either way, why was there ever any debate about it? And why should we care today about the opposing ideas, which proven wrong so long ago? In the ``Reacting to the Past'' series of curricular materials, students engage with key turning points in human intellectual history by taking sides and recreating the original debate. In this way, students personally identify with points of view that they would otherwise find wrong, boring, and incomprehensible --- and they learn how we test ideas by challenging them, and defend them by marshalling evidence, which is the core of critical thinking. Students almost universally report that the ``Reacting'' experience is tremendously engaging. I shall describe an application of the ``Reacting'' format to the case of Galileo. The scientific issues involved are comprehensible to non-science majors, the cultural context of Renaissance Italy is rich and wonderful, and Galileo's personal history is tremendously moving. The materials include labs designed to be taught by non-scientists teaching cross-disciplinary liberal arts courses. Other ``Reacting'' science materials have been published or are under development.
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The Reputational Consequences of Failed Replications and Wrongness Admission among Scientists.
Fetterman, Adam K; Sassenberg, Kai
2015-01-01
Scientists are dedicating more attention to replication efforts. While the scientific utility of replications is unquestionable, the impact of failed replication efforts and the discussions surrounding them deserve more attention. Specifically, the debates about failed replications on social media have led to worry, in some scientists, regarding reputation. In order to gain data-informed insights into these issues, we collected data from 281 published scientists. We assessed whether scientists overestimate the negative reputational effects of a failed replication in a scenario-based study. Second, we assessed the reputational consequences of admitting wrongness (versus not) as an original scientist of an effect that has failed to replicate. Our data suggests that scientists overestimate the negative reputational impact of a hypothetical failed replication effort. We also show that admitting wrongness about a non-replicated finding is less harmful to one's reputation than not admitting. Finally, we discovered a hint of evidence that feelings about the replication movement can be affected by whether replication efforts are aimed one's own work versus the work of another. Given these findings, we then present potential ways forward in these discussions.
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Dissociation between morality and disgust: an event-related potential study.
Yang, Qun; Li, An; Xiao, Xiao; Zhang, Ye; Tian, Xuehong
2014-10-01
This study explored the neural correlates of morality and disgust, particularly, how the mechanisms that mediate our avoidance of physically disgusting and morally abhorrent behaviors are neurologically dissociated during the time-course of processing. Twelve participants were asked to judge the acceptability of different types of behaviors, which varied in their level of moral wrongness and physical disgust, while event-related potentials (ERPs) were recorded. The main results showed that the two morally wrong conditions elicited greater amplitudes of P300-400 at frontal sites than the neutral condition and the physically disgusting, but not morally wrong, condition. The physically disgusting conditions (with and without moral content) elicited significantly more positive deflections in the 500-600 ms timeframe than the neutral condition at central-posterior sites. These findings indicate that our aversion to harmful substances in the physical environment and offensive behaviors in the social environment may be neurologically dissociable in the temporal dimension. Furthermore, the detection of moral violations may be processed earlier in time than that of physical disgust. Copyright © 2014 Elsevier B.V. All rights reserved.
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Delegation and beyond: what happens when things go wrong?
Solon, Mark
2013-01-01
Both midwives and maternity support workers can be confused about who is liable if a task is delegated and something goes wrong. With proper understanding of roles and a knowledge of which tasks can and can't be delegated, however, the midwife should be protected, particularly as in practice the NHS body will have vicarious liability in the event of any claim. Clinical negligence training identifies the risks and responsibilities involved--and, leaving aside issues of delegation, training should also instil common sense safeguards against incurring criminal liability, which is independent from any professional or civil sanction.
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Fully automatic segmentation of arbitrarily shaped fiducial markers in cone-beam CT projections
NASA Astrophysics Data System (ADS)
Bertholet, J.; Wan, H.; Toftegaard, J.; Schmidt, M. L.; Chotard, F.; Parikh, P. J.; Poulsen, P. R.
2017-02-01
Radio-opaque fiducial markers of different shapes are often implanted in or near abdominal or thoracic tumors to act as surrogates for the tumor position during radiotherapy. They can be used for real-time treatment adaptation, but this requires a robust, automatic segmentation method able to handle arbitrarily shaped markers in a rotational imaging geometry such as cone-beam computed tomography (CBCT) projection images and intra-treatment images. In this study, we propose a fully automatic dynamic programming (DP) assisted template-based (TB) segmentation method. Based on an initial DP segmentation, the DPTB algorithm generates and uses a 3D marker model to create 2D templates at any projection angle. The 2D templates are used to segment the marker position as the position with highest normalized cross-correlation in a search area centered at the DP segmented position. The accuracy of the DP algorithm and the new DPTB algorithm was quantified as the 2D segmentation error (pixels) compared to a manual ground truth segmentation for 97 markers in the projection images of CBCT scans of 40 patients. Also the fraction of wrong segmentations, defined as 2D errors larger than 5 pixels, was calculated. The mean 2D segmentation error of DP was reduced from 4.1 pixels to 3.0 pixels by DPTB, while the fraction of wrong segmentations was reduced from 17.4% to 6.8%. DPTB allowed rejection of uncertain segmentations as deemed by a low normalized cross-correlation coefficient and contrast-to-noise ratio. For a rejection rate of 9.97%, the sensitivity in detecting wrong segmentations was 67% and the specificity was 94%. The accepted segmentations had a mean segmentation error of 1.8 pixels and 2.5% wrong segmentations.
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Sauer, Charles W; Marc-Aurele, Krishelle L.
2016-01-01
Patient: Male, 2 month Final Diagnosis: 2 month old 32 weeks’ gestational age preterm infant Symptoms: Prematurity Medication: — Clinical Procedure: Accidental breastfeeding of the wrong baby Specialty: Pediatrics and Neonatology Objective: Diagnostic/therapeutic accidents Background: Because there are clear benefits to breast milk over formula for infants, the goal of the World Health Organization is to increase breastfeeding rates. As more women are breastfeeding and providing breast milk to newborns in hospitals, there is increased risk for administration error. Case Report: A hospitalized preterm infant was breastfed by the wrong mother when the Neonatal Intensive Care Unit Nurse failed to properly identify the mother. An infectious disease workup done on the donor mother was negative, but the recipient infant was positive for cytomegalovirus (CMV). Since the donor mother who accidentally breastfed the wrong infant was CMV-negative, the baby in our case had likely been exposed to CMV from his biological mother. The attending physician apologized to all of the family members involved, but the father of one infant continued to express anger. Conclusions: To our knowledge, this is the first case of accidental breastfeeding in a hospital setting to be described in the literature. Parental misidentification and a language barrier led to the error. An infectious disease workup did not find any evidence of disease transmission from this event. Increased attention to minimize breast milk errors is needed. Despite a long history of wet nursing, unregulated breast milk sharing and cross nursing is not recommended. Instead, if a mother cannot provide breast milk herself, pasteurized donor breast milk from breast milk banks is encouraged. PMID:27515898
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Arslan, Burcu; Taatgen, Niels A; Verbrugge, Rineke
2017-01-01
The focus of studies on second-order false belief reasoning generally was on investigating the roles of executive functions and language with correlational studies. Different from those studies, we focus on the question how 5-year-olds select and revise reasoning strategies in second-order false belief tasks by constructing two computational cognitive models of this process: an instance-based learning model and a reinforcement learning model. Unlike the reinforcement learning model, the instance-based learning model predicted that children who fail second-order false belief tasks would give answers based on first-order theory of mind (ToM) reasoning as opposed to zero-order reasoning. This prediction was confirmed with an empirical study that we conducted with 72 5- to 6-year-old children. The results showed that 17% of the answers were correct and 83% of the answers were wrong. In line with our prediction, 65% of the wrong answers were based on a first-order ToM strategy, while only 29% of them were based on a zero-order strategy (the remaining 6% of subjects did not provide any answer). Based on our instance-based learning model, we propose that when children get feedback "Wrong," they explicitly revise their strategy to a higher level instead of implicitly selecting one of the available ToM strategies. Moreover, we predict that children's failures are due to lack of experience and that with exposure to second-order false belief reasoning, children can revise their wrong first-order reasoning strategy to a correct second-order reasoning strategy.
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Arslan, Burcu; Taatgen, Niels A.; Verbrugge, Rineke
2017-01-01
The focus of studies on second-order false belief reasoning generally was on investigating the roles of executive functions and language with correlational studies. Different from those studies, we focus on the question how 5-year-olds select and revise reasoning strategies in second-order false belief tasks by constructing two computational cognitive models of this process: an instance-based learning model and a reinforcement learning model. Unlike the reinforcement learning model, the instance-based learning model predicted that children who fail second-order false belief tasks would give answers based on first-order theory of mind (ToM) reasoning as opposed to zero-order reasoning. This prediction was confirmed with an empirical study that we conducted with 72 5- to 6-year-old children. The results showed that 17% of the answers were correct and 83% of the answers were wrong. In line with our prediction, 65% of the wrong answers were based on a first-order ToM strategy, while only 29% of them were based on a zero-order strategy (the remaining 6% of subjects did not provide any answer). Based on our instance-based learning model, we propose that when children get feedback “Wrong,” they explicitly revise their strategy to a higher level instead of implicitly selecting one of the available ToM strategies. Moreover, we predict that children’s failures are due to lack of experience and that with exposure to second-order false belief reasoning, children can revise their wrong first-order reasoning strategy to a correct second-order reasoning strategy. PMID:28293206
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The use of collaboration to implement evidence-based safe practices.
Clarke, John R
2013-12-01
The Pennsylvania Patient Safety Authority receives over 235,000 reports of medical error per year. Near miss and serious event reports of common and interesting problems are analysed to identify best practices for preventing harmful errors. Dissemination of this evidence-based information in the peer-reviewed Pennsylvania Patient Safety Advisory and presentations to medical staffs are not sufficient for adoption of best practices. Adoption of best practices has required working with institutions to identify local barriers to and incentives for adopting best practices and redesigning the delivery system to make desired behaviour easy and undesirable behaviour more difficult. Collaborations, where institutions can learn from the experiences of others, have show decreases in harmful events. The Pennsylvania Program to Prevent Wrong-Site Surgery is used as an example. Two collaborations to prevent wrong-site surgery have been completed, one with 30 institutions in eastern Pennsylvania and one with 19 in western Pennsylvania. The first collaboration achieved a 73% decrease in the rolling average of wrong-site events over 18 months. The second collaboration experienced no wrong-site operating room procedures over more than one year. Significance for public healthSince the Institute of Medicine's To Err is Human identified medical errors as a major cause of death, the public has been interested in the recommendations for reporting of medical errors and implementing safe systems for the delivery of healthcare. The Commonwealth of Pennsylvania has followed those recommendations and found that an essential intermediate step between analysing reports and implementing safe systems is collaborative learning among healthcare institutions. The experience in Pennsylvania should be useful to other public organizations wishing to improve safety.
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Reasons for uncontrolled seizures in adults; the impact of pseudointractability.
Asadi-Pooya, Ali A; Emami, Mehrdad; Ashjazadeh, Nahid; Nikseresht, Alireza; Shariat, Abdolhamid; Petramfar, Peyman; Yousefipour, Gholamali; Borhani-Haghighi, Afshin; Izadi, Sadegh; Rahimi-Jaberi, Abbas
2013-05-01
We investigated the various possible reasons for uncontrolled seizures in patients 18 years of age and older to determine the impact of pseudointractability. We also tried to investigate the various forms of pseudointractability. In this cross-sectional study, all patients 18 years of age and older with their first seizure occurring at least six months prior to the referral date, taking at least one antiepileptic drug (AED) and having at least one seizure in the past three months were studied. The presumed reason for uncontrolled seizures was arbitrarily considered to be one of these five categories: Poor compliance; Wrong medication (misclassification); Wrong dose of the correct medication; Diagnosis other than epilepsy; and finally, Medically-refractory epilepsy. Statistical analyses were performed using Chi-square and Fisher's exact tests, and a P value less than 0.05 was considered significant. 350 patients were referred to us due to uncontrolled seizures. One hundred ninety-one (55%) were male and 159 (45%) were female. Twelve percent of the patients had diagnoses other than epilepsy, 40% had indeed medically-refractory epilepsy; 29% were taking the wrong AEDs (misclassified epilepsy); 18% were taking suboptimal doses of AEDs; and 1% had poor drug compliance. The most common reason for uncontrolled seizures among patients with idiopathic generalized epilepsy was taking the wrong AED. However, among patients with focal epilepsy, true medically-refractory epilepsy was the most common reason. Uncontrolled seizures are a commonly encountered problem, especially at epilepsy clinics and one should consider all possible reasons for these uncontrolled seizures. The mainstay for making a correct diagnosis is a detailed clinical history. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
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Primary health workers' knowledge and practices relating to neonatal jaundice in Ibadan, Nigeria.
Orimadegun, Adebola E; Ojebiyi, Adeola O
2017-01-30
Over half of births and newborn care occur in primary healthcare facilities in Nigeria, but information on activities of personnel working there is scarce. To assess the knowledge and practices relating to neonatal jaundice (NNJ) among community health workers (CHWs) and community birth attendants (CBAs) in Nigeria. We conducted a cross-sectional survey of all 227 CHWs and 193 registered CBAs in Ibadan, Nigeria. Knowledge and practices regarding NNJ were measured using a pretested questionnaire. Knowledge and practices were assessed on a 33-point scale and a 13-point scale, respectively. Scores ≤ 17 and ≤ 9 was regarded as poor knowledge and as wrong practice, respectively. Many (64.5%) of the respondents could not correctly describe examination for NNJ (CHWs: 49.4%; CBAs: 50.6%). Of the 200 (47.6%) who treated NNJ 3 months prior to the study, 62.5% (CHWs: 66.9% and CBAs: 53.7%) treated NNJ with orthodox drugs. Drugs prescribed included: antibiotics (93.3%), antimalarials (5.3%), multivitamins (28.0%), paracetamol (6.2%) and phenobarbitone (7.1%). Significantly more CHWs than CBAs practiced exposure to sunlight (33.1% versus 16.4%) and administration of glucose water (28.6% versus 14.9%), while 58.0% of all respondents referred cases to secondary health facilities. Overall, 80.2% had poor knowledge (CHWs: 78.9%; CBAs: 81.9%) and 46.4% engaged in wrong practices (CHWs: 57.3%; CBAs: 33.7%). CHWs were more likely to indulge in wrong practices than CBAs (OR = 2.22, 95% CI = 1.03, 4.79). Primary Health Workers in Ibadan had poor knowledge and engaged in wrong practices about NNJ. The needs to organise regular training programmes were emphasised.
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Avoidance of Wrong-level Thoracic Spine Surgery Using Sterile Spinal Needles: A Technical Report.
Chin, Kingsley R; Seale, Jason; Cumming, Vanessa
2017-02-01
A technical report. The aim of the present study was to present an improvement on localization techniques employed for use in the thoracic spine using sterile spinal needles docked on the transverse process of each vertebra, which can be performed in both percutaneous and open spinal procedures. Wrong-level surgery may have momentous clinical and emotional implications for a patient and surgeon. It is reported that one in every 2 spine surgeons will operate on the wrong level during his or her career. Correctly localizing the specific thoracic level remains a significant challenge during spine surgery. Fluoroscopic anteroposterior and lateral views were obtained starting in the lower lumbar spine, and an 18-G spinal needle was placed in the transverse process of L3 counting up from the sacrum and also at T12. The fluoroscopy was then moved cephalad and counting from the spinal needle at T12, the other spinal needles were placed at the targeted operating thoracic vertebrae. Once this was done, we were able to accurately determine the thoracic levels for surgical intervention. Using this technique, the markers were kept in place even after the incisions were made. This prevented us from losing our location in the thoracic spine. Correctly placed instrumentation was made evident with postoperative imaging. We have described the successful use of a new technique using spinal needles docked against transverse processes to correctly and reliably identify thoracic levels before instrumentation. The technique was reproducible in both open surgeries and for a percutaneous procedure. This technique maintains the correct spinal level during an open procedure. We posit that wrong-level thoracic spine surgery may be preventable.
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Application of failure mode and effects analysis (FMEA) to pretreatment phases in tomotherapy
Broggi, Sara; Cantone, Marie Claire; Chiara, Anna; Muzio, Nadia Di; Longobardi, Barbara; Mangili, Paola
2013-01-01
The aim of this paper was the application of the failure mode and effects analysis (FMEA) approach to assess the risks for patients undergoing radiotherapy treatments performed by means of a helical tomotherapy unit. FMEA was applied to the preplanning imaging, volume determination, and treatment planning stages of the tomotherapy process and consisted of three steps: 1) identification of the involved subprocesses; 2) identification and ranking of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system; and 3) identification of additional safety measures to be proposed for process quality and safety improvement. RPN upper threshold for little concern of risk was set at 125. A total of 74 failure modes were identified: 38 in the stage of preplanning imaging and volume determination, and 36 in the stage of planning. The threshold of 125 for RPN was exceeded in four cases: one case only in the phase of preplanning imaging and volume determination, and three cases in the stage of planning. The most critical failures appeared related to (i) the wrong or missing definition and contouring of the overlapping regions, (ii) the wrong assignment of the overlap priority to each anatomical structure, (iii) the wrong choice of the computed tomography calibration curve for dose calculation, and (iv) the wrong (or not performed) choice of the number of fractions in the planning station. On the basis of these findings, in addition to the safety strategies already adopted in the clinical practice, novel solutions have been proposed for mitigating the risk of these failures and to increase patient safety. PACS number: 87.55.Qr PMID:24036868
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Koppel, Ross; Wetterneck, Tosha; Telles, Joel Leon; Karsh, Ben-Tzion
2008-01-01
The authors develop a typology of clinicians' workarounds when using barcoded medication administration (BCMA) systems. Authors then identify the causes and possible consequences of each workaround. The BCMAs usually consist of handheld devices for scanning machine-readable barcodes on patients and medications. They also interface with electronic medication administration records. Ideally, BCMAs help confirm the five “rights” of medication administration: right patient, drug, dose, route, and time. While BCMAs are reported to reduce medication administration errors—the least likely medication error to be intercepted— these claims have not been clearly demonstrated. The authors studied BCMA use at five hospitals by: (1) observing and shadowing nurses using BCMAs at two hospitals, (2) interviewing staff and hospital leaders at five hospitals, (3) participating in BCMA staff meetings, (4) participating in one hospital's failure-mode-and-effects analyses, (5) analyzing BCMA override log data. The authors identified 15 types of workarounds, including, for example, affixing patient identification barcodes to computer carts, scanners, doorjambs, or nurses' belt rings; carrying several patients' prescanned medications on carts. The authors identified 31 types of causes of workarounds, such as unreadable medication barcodes (crinkled, smudged, torn, missing, covered by another label); malfunctioning scanners; unreadable or missing patient identification wristbands (chewed, soaked, missing); nonbarcoded medications; failing batteries; uncertain wireless connectivity; emergencies. The authors found nurses overrode BCMA alerts for 4.2% of patients charted and for 10.3% of medications charted. Possible consequences of the workarounds include wrong administration of medications, wrong doses, wrong times, and wrong formulations. Shortcomings in BCMAs' design, implementation, and workflow integration encourage workarounds. Integrating BCMAs within real-world clinical workflows requires attention to in situ use to ensure safety features' correct use. PMID:18436903
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Lesko, Nicole; Naess, Karin; Wibom, Rolf; Solaroli, Nicola; Nennesmo, Inger; von Döbeln, Ulrika; Karlsson, Anna; Larsson, Nils-Göran
2010-03-01
Deficiency of thymidine kinase-2 (TK2) has been described in children with early onset fatal skeletal myopathy. TK2 is a mitochondrial deoxyribonucleoside kinase required for the phosphorylation of deoxycytidine and deoxythymidine and hence is vital for the maintenance of a balanced mitochondrial dNTP pool in post-mitotic tissues. We describe a patient with two novel TK2 mutations, which caused disease onset shortly after birth and death at the age of three months. One mutation (219insCG) generated an early stop codon, thus preventing the synthesis of a functional protein. The second mutation (R130W) resulted in an amino acid substitution, which caused a severe reduction (<3%) of TK2 enzyme activity. These two novel TK2 mutations cause an extremely severe phenotype with overwhelming central nervous system symptoms not commonly seen in patients with TK2-deficiency. We conclude that the severe clinical presentation in this patient was due to a virtual lack of mitochondrial TK2 activity. Copyright 2009 Elsevier B.V. All rights reserved.
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SAMHD1 Inhibits LINE-1 Retrotransposition by Promoting Stress Granule Formation
Xu, Fengwen; Mei, Shan; Le Duff, Yann; Yin, Lijuan; Pang, Xiaojing; Cen, Shan; Jin, Qi; Liang, Chen; Guo, Fei
2015-01-01
The SAM domain and HD domain containing protein 1 (SAMHD1) inhibits retroviruses, DNA viruses and long interspersed element 1 (LINE-1). Given that in dividing cells, SAMHD1 loses its antiviral function yet still potently restricts LINE-1, we propose that, instead of blocking viral DNA synthesis by virtue of its dNTP triphosphohydrolase activity, SAMHD1 may exploit a different mechanism to control LINE-1. Here, we report a new activity of SAMHD1 in promoting cellular stress granule assembly, which correlates with increased phosphorylation of eIF2α and diminished eIF4A/eIF4G interaction. This function of SAMHD1 enhances sequestration of LINE-1 RNP in stress granules and consequent blockade to LINE-1 retrotransposition. In support of this new mechanism of action, depletion of stress granule marker proteins G3BP1 or TIA1 abrogates stress granule formation and overcomes SAMHD1 inhibition of LINE-1. Together, these data reveal a new mechanism for SAMHD1 to control LINE-1 by activating cellular stress granule pathway. PMID:26134849
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Lesion bypass by S. cerevisiae Pol ζ alone
Stone, Jana E.; Kumar, Dinesh; Binz, Sara K.; Inase, Aki; Iwai, Shigenori; Chabes, Andrei; Burgers, Peter M.; Kunkel, Thomas A.
2011-01-01
DNA polymerase zeta (Pol ζ) participates in translesion synthesis (TLS) of DNA adducts that stall replication fork progression. Previous studies have led to the suggestion that the primary role of Pol ζ in TLS is to extend primers created when another DNA polymerase inserts nucleotides opposite lesions. Here we test the non-exclusive possibility that Pol ζ can sometimes perform TLS in the absence of any other polymerase. To do so, we quantified the efficiency with which S. cerevisiae Pol ζ bypasses abasic sites, cis-syn cyclobutane pyrimidine dimers and (6-4) photoproducts. In reactions containing dNTP concentrations that mimic those induced by DNA damage, a Pol ζ derivative with phenylalanine substituted for leucine 979 at the polymerase active site bypasses all three lesions at efficiencies between 27–73%. Wild-type Pol ζ also bypasses these lesions, with efficiencies that are lower and depend on the sequence context in which the lesion resides. The results are consistent with the hypothesis that, in addition to extending aberrant termini created by other DNA polymerases, Pol ζ has the potential to be the sole DNA polymerase involved in TLS. PMID:21622032
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Single-stranded nucleic acids promote SAMHD1 complex formation.
Tüngler, Victoria; Staroske, Wolfgang; Kind, Barbara; Dobrick, Manuela; Kretschmer, Stefanie; Schmidt, Franziska; Krug, Claudia; Lorenz, Mike; Chara, Osvaldo; Schwille, Petra; Lee-Kirsch, Min Ae
2013-06-01
SAM domain and HD domain-containing protein 1 (SAMHD1) is a dGTP-dependent triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs) thereby limiting the intracellular dNTP pool. Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), an inflammatory encephalopathy that mimics congenital viral infection and that phenotypically overlaps with the autoimmune disease systemic lupus erythematosus. Both disorders are characterized by activation of the antiviral cytokine interferon-α initiated by immune recognition of self nucleic acids. Here we provide first direct evidence that SAMHD1 associates with endogenous nucleic acids in situ. Using fluorescence cross-correlation spectroscopy, we demonstrate that SAMHD1 specifically interacts with ssRNA and ssDNA and establish that nucleic acid-binding and formation of SAMHD1 complexes are mutually dependent. Interaction with nucleic acids and complex formation do not require the SAM domain, but are dependent on the HD domain and the C-terminal region of SAMHD1. We finally demonstrate that mutations associated with AGS exhibit both impaired nucleic acid-binding and complex formation implicating that interaction with nucleic acids is an integral aspect of SAMHD1 function.
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Liu, Zhongyuan; Dong, Zhijun; Liu, Dongyan
2016-07-01
Blooms of the harmful jellyfish Cyanea nozakii, which are a severe nuisance to fisheries and tourisms, frequently occur in the northern East China Sea, Yellow Sea, and Bohai Sea. To provide early warning of this species, a simple and effective molecular method for identifying C. nozakii was developed using the loop-mediated isothermal amplification method (LAMP). The LAMP assay is highly specific and uses a set of four primers that target six different regions on the mitochondrial cytochrome c oxidase subunit I (COI) gene of C. nozakii. The amplification conditions, including the dNTP and betaine concentrations, the inner primer to outer primer concentration ratio, reaction time and temperature, were optimized. The LAMP assay amplified DNA extracted from tissue samples of C. nozakii but did not amplify DNA from other common scyphozoans and hydrozoans collected in the same region. In addition, the LAMP assay was more sensitive than conventional PCR. Therefore, the established LAMP assay is a sensitive, specific, fast, and easily performed method for detection of C. nozakii at different stages in their life cycle.
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Lin, Dajie; Mei, Chengyang; Liu, Aili; Jin, Huile; Wang, Shun; Wang, Jichang
2015-04-15
A cascade signal amplification strategy through combining surface-initiated enzymatic polymerization (SIEP) and the subsequent deposition of strepavidin functionalized silver nanoparticles (AgNPs) was proposed. The first step of constructing the electrochemical immunosensor involves covalently immobilizing capture antibody on a chitosan modified glass carbon electrode, which then catalyzes DNA addition of deoxynucleotides (dNTP) at the 3'-OH group by terminal deoxynucleotidyl transferase (TdT), leading to the formation of long single-stranded DNAs labeled with numerous biotins. Following the deposition of numerous strepavidin functionalized AgNPs on those long DNA chains, electrochemical stripping signal of silver was used to monitor the immunoreaction in KCl solution. Using α-fetoprotein as a model analyte, this amplification strategy could detect fetoprotein down to 0.046pg/mL with a wide linear range from 0.1pg/mL to 1.0ng/mL. The achieved high sensitivity and good reproducibility suggest that this cascade signal amplification strategy has great potential for detecting biological samples and possibly clinical application. Copyright © 2014 Elsevier B.V. All rights reserved.
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2011-01-01
Y-family DNA polymerases are characterized by low-fidelity synthesis on undamaged DNA and ability to catalyze translesion synthesis over the damaged DNA. Their translocation along the DNA template is an important event during processive DNA synthesis. In this work we present a Brownian ratchet model for this translocation, where the directed translocation is rectified by the nucleotide binding to the polymerase. Using the model, different features of the available structures for Dpo4, Dbh and polymerase ι in binary and ternary forms can be easily explained. Other dynamic properties of the Y-family polymerases such as the fast translocation event upon dNTP binding for Dpo4 and the considerable variations of the processivity among the polymerases can also be well explained by using the model. In addition, some predicted results of the DNA synthesis rate versus the external force acting on Dpo4 and Dbh polymerases are presented. Moreover, we compare the effect of the external force on the DNA synthesis rate of the Y-family polymerase with that of the replicative DNA polymerase. PMID:21699732
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Walsh, Aileen
2010-12-01
In this paper it is argued that moral distress is an emotional response to an ethical dilemma, and that to date, the literature has largely failed to address the fundamental questions that need to be answered in response to this emotional response. Firstly, does moral distress accurately identify a wrong being done to patients? Secondly, if it does, can nurses carry out this 'wrong doing', but not be responsible for the consequences of their actions? A narrative that reflects the emotional nature of moral distress is presented, with the aim of providing some answers to these questions.
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NASA Astrophysics Data System (ADS)
Tu, Zhoudunming
2011-11-01
Physics, an experiment-based science, seems to be the most appropriate subject in how to explain the inner workings of the world. We respect physics because it is based on facts that are perceived by our observations. However, what if we are not seeing the entire truth we seek? What if our observations are founded on sandy foundations? As humans, we desire to know what the truth is. Rene Descartes, a mathematician, philosopher, and physicist asked this question: what is the absolute truth in our universe? I want to solve the same puzzle. Many people believe that physics will reveal the truth of our universe. But, what if physics is wrong?
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[Immortal time bias in pharmacoepidemiological studies: definition, solutions and examples].
Faillie, Jean-Luc; Suissa, Samy
2015-01-01
Among the observational studies of drug effects in chronic diseases, many of them have found effects that were exaggerated or wrong. Among bias responsible for these errors, the immortal time bias, concerning the definition of exposure and exposure periods, is relevantly important as it usually tends to wrongly attribute a significant benefit to the study drug (or exaggerate a real benefit). In this article, we define the mechanism of immortal time bias, we present possible solutions and illustrate its consequences through examples of pharmacoepidemiological studies of drug effects. © 2014 Société Française de Pharmacologie et de Thérapeutique.
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Righting wrongs and reforming rights.
Ivey, Laurie C
2014-03-01
Discusses issues faced by LGBT people, such as a lack of equal civil rights and the need for extra legal and financial protection for families because partners cannot be married. The author notes that, in our society, it is no longer acceptable to be racist, but it is still okay to be homophobic. The many campaigns against gay marriage and efforts in the legislature to prevent change toward equal civil rights and protections are prime examples. In our current political climate, two things are very clear: (a) homophobia is freely tolerated and (b) the times are changing as we inch closer to equal rights every day. We are "righting wrongs and reforming rights."
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Designing (artificial) people to serve - the other side of the coin
NASA Astrophysics Data System (ADS)
Musiał, Maciej
2017-09-01
This paper addresses the issue of the ethical obligations of human beings towards the robots that will achieve the status of persons. In particular the text investigates the ethical status of designing such robot-persons as servants. The author disagrees with Steve Petersen - who claims that we can design robot-persons as servants without wronging them by implementing the desire to serve into them. Following Jürgen Habermas critique of positive liberal eugenics, the author argues that any kind of intentional designing inevitably wrongs the designed beings regarding their freedom, autonomy, equality and identity. Moreover, some unintended consequences of developing robot-person servants are discussed.
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More than words: patients' views on apology and disclosure when things go wrong in cancer care.
Mazor, Kathleen M; Greene, Sarah M; Roblin, Douglas; Lemay, Celeste A; Firneno, Cassandra L; Calvi, Josephine; Prouty, Carolyn D; Horner, Kathryn; Gallagher, Thomas H
2013-03-01
Guidelines on apology and disclosure after adverse events and errors have been in place for over 5 years. This study examines whether patients consider recommended responses to be appropriate and desirable, and whether clinicians' actions after adverse events are consistent with recommendations. Patients who believed that something had gone wrong during their cancer care were identified. During in-depth interviews, patients described the event, clinicians' responses, and their reactions. 78 patients were interviewed. Patients' valued apology and expressions of remorse, empathy and caring, explanation, acknowledgement of responsibility, and efforts to prevent recurrences, but these key elements were often missing. For many patients, actions and evidence of clinician learning were most important. Patients' reports of apology and disclosure when they believe something has gone wrong in their care suggest that clinicians' responses continue to fall short of expectations. Clinicians preparing to talk with patients after an adverse event or medical error should be aware that patients expect their actions to be congruent with their words of apology and caring. Healthcare systems need to support clinicians throughout the disclosure process, and facilitate both system and individual learning to prevent recurrences. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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More Than Words: Patients' Views on Apology and Disclosure When Things Go Wrong in Cancer Care
Mazor, Kathleen M.; Greene, Sarah M.; Roblin, Douglas; Lemay, Celeste A.; Firneno, Cassandra L.; Calvi, Josephine; Prouty, Carolyn D.; Horner, Kathryn; Gallagher, Thomas H.
2011-01-01
Objective Guidelines on apology and disclosure after adverse events and errors have been in place for over five years. This study examines whether patients consider recommended responses to be appropriate and desirable, and whether clinicians' actions after adverse events are consistent with recommendations. Methods Patients who believed that something had gone wrong during their cancer care were identified. During in-depth interviews, patients described the event, clinicians' responses, and their reactions. Results 78 patients were interviewed. Patients' valued apology and expressions of remorse, empathy and caring, explanation, acknowledgement of responsibility, and efforts to prevent recurrences, but these key elements were often missing. For many patients, actions and evidence of clinician learning were most important. Conclusion Patients' reports of apology and disclosure when they believe something has gone wrong in their care suggest that clinicians' responses continue to fall short of expectations. Practice Implications Clinicians preparing to talk with patients after an adverse event or medical error should be aware that patients expect their actions to be congruent with their words of apology and caring. Healthcare systems need to support clinicians throughout the disclosure process, and facilitate both system and individual learning to prevent recurrences. PMID:21824739
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Incidence of wrong-site surgery among foot and ankle surgeons.
Schweitzer, Karl M; Brimmo, Olubusola; May, Ryan; Parekh, Selene G
2011-02-01
In 1998, the American Academy of Orthopaedic Surgeons initiated the "sign your site" campaign to address the issue of wrong-site surgery (WSS). Using a confidential online survey sent to 1094 active members of the American Academy of Foot and Ankle Surgeons, the authors assessed participation in the "sign your site" campaign and the occurrence of WSS encountered during their careers. A total of 319 responses were received (response rate = 29.2%). In all, 41 of 310 respondents (13%) reported performing WSS at least once, with 4 surgeons (1%) reporting the occurrence twice in their careers; 70 of 310 (23%) surgeons reported that they had prepped the wrong surgical site, but the error was recognized prior to making an incision. In all, 302 of 309 respondents (97.7%) reported that they were aware of the "sign your site" initiative. Since the introduction of the campaign, significantly more (89.2% vs 49.2%) foot and ankle surgeons routinely mark the surgical site (P < .001). The Joint Commission revised the universal protocol for surgical site verification requiring an individual directly involved in a surgical procedure to mark the site as of January 1, 2009. The authors believe this revision will lower the incidence of WSS further.
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Time-lapse analysis of gravitropism in Ceratodon protonemata
NASA Technical Reports Server (NTRS)
Young, J. C.; Sack, F. D.
1992-01-01
The tip cell of the protonema of the moss Ceratodon purpureus (Hedw.) Brid. is negatively gravitropic when grown in the dark on supplemented agar. Gravitropism, plastid distribution, and plastid movement were studied in living cells using time-lapse video microscopy and infrared light. A wrong-way (downward) curvature preceded upward curvature and was detected as early as 2 minutes after reorientation. Upward curvature began 30-45 minutes after reorientation to the horizontal. Cell division temporarily reversed upward curvature, but did not inhibit wrong-way curvature. Since significant amyloplast sedimentation always occurred before the start of upward curvature, it is possible that these amyloplasts function as statoliths for upward curvature. However, no significant amyloplast sedimentation occurred before wrong-way curvature. Thus, this early phase of gravitropism cannot require plastid sedimentation for gravity sensing. Most plastids moved within and between zones, and plastid zonation was highly dynamic. Plastids moved toward the apex and toward the base of the cell at rates much slower than cytoplasmic streaming. Despite the dynamic nature of plastid movement and zonation, during upward curvature the distance between sedimented plastids and the apex stayed constant. Time-lapse analysis has revealed intriguing events not readily seen previously using destructive sampling.
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Yang, Ziheng; Zhu, Tianqi
2018-02-20
The Bayesian method is noted to produce spuriously high posterior probabilities for phylogenetic trees in analysis of large datasets, but the precise reasons for this overconfidence are unknown. In general, the performance of Bayesian selection of misspecified models is poorly understood, even though this is of great scientific interest since models are never true in real data analysis. Here we characterize the asymptotic behavior of Bayesian model selection and show that when the competing models are equally wrong, Bayesian model selection exhibits surprising and polarized behaviors in large datasets, supporting one model with full force while rejecting the others. If one model is slightly less wrong than the other, the less wrong model will eventually win when the amount of data increases, but the method may become overconfident before it becomes reliable. We suggest that this extreme behavior may be a major factor for the spuriously high posterior probabilities for evolutionary trees. The philosophical implications of our results to the application of Bayesian model selection to evaluate opposing scientific hypotheses are yet to be explored, as are the behaviors of non-Bayesian methods in similar situations.
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Group navigation and the "many-wrongs principle" in models of animal movement.
Codling, E A; Pitchford, J W; Simpson, S D
2007-07-01
Traditional studies of animal navigation over both long and short distances have usually considered the orientation ability of the individual only, without reference to the implications of group membership. However, recent work has suggested that being in a group can significantly improve the ability of an individual to align toward and reach a target direction or point, even when all group members have limited navigational ability and there are no leaders. This effect is known as the "many-wrongs principle" since the large number of individual navigational errors across the group are suppressed by interactions and group cohesion. In this paper, we simulate the many-wrongs principle using a simple individual-based model of movement based on a biased random walk that includes group interactions. We study the ability of the group as a whole to reach a target given different levels of individual navigation error, group size, interaction radius, and environmental turbulence. In scenarios with low levels of environmental turbulence, simulation results demonstrate a navigational benefit from group membership, particularly for small group sizes. In contrast, when movement takes place in a highly turbulent environment, simulation results suggest that the best strategy is to navigate as individuals rather than as a group.
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Reoperative Cardiac Surgery - Part II.
Tribble, Curtis G
2018-04-10
The preparation for a reoperative cardiac surgical case was covered in Part I of this two part review [Tribble 2018]. Part II will cover primarily intraoperative strategies and techniques. As noted in Part I, there has been surprisingly little written about the strategies and techniques of reoperative cardiac surgery. Thus, the goal of this two-part review is to collect and collate some of the lessons, abjurations, and tenets related to reoperative cardiac surgery that may be valuable to cardiac surgeons, especially those in training or early in their careers.Some time-honored admonitions that can apply to all complex operations, often enunciated by "old salts," bear repeating:• Everything matters. Nothing is neutral.• Some say that a "life or death" decision is made, on average, every 10 seconds during cardiac surgery. • If something can go wrong, presume that it will.• If it seems absolutely impossible for something to go wrong, it will anyway, at least some of the time.• When something does go wrong, it generally does so all at once.• If what you are doing is working, keep on doing it. If it ain't working, do something else.
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Faunce, Thomas; Jefferys, Susannah
2007-05-01
The Australian High Court recently found that the common law could allow parents to claim tortious damages when medical negligence was proven to have led to the birth of an unplanned, but healthy, baby (Cattanach v Melchior (2003) 215 CLR 1). In Harriton v Stephens (2006) 80 ALJR 791; [2006] HCA 15 and Waller v James; Waller v Hoolahan (2006) 80 ALJR 846; [2006] HCA 16 the High Court in a six-to-one decision (Kirby J dissenting) decided that no such claim could be made by a child when medical negligence in failing to order an in utero genetic test caused the child severe disability. In an era when almost all pregnancies will soon require patented fetal genetic tests as part of the professional standard of care, the High Court, by barring so-called "wrongful life" (better termed "wrongful suffering") claims, may have created a partial immunity from suit for their corporate manufacturers and the doctors who administer them. What lessons can be learnt from this case about how the Australian High Court is, or should be, approaching medical negligence cases and its role as guardian of the Australian common law?
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When patients are harmed, but are not wronged: ethics, law, and history.
Klaas, Paul B; Berge, Keith H; Klaas, Kelsey M; Klaas, James P; Larson, Annalise Noelle
2014-09-01
Iatrogenic injury-injury caused unintentionally by medical treatment-breaks the oldest and most famous rule of medical ethics: primum non nocere, or above all, do no harm. Medical malpractice law, however, focuses on whether an injury was caused by negligence, not on whether an injury was iatrogenic. Iatrogenic injury inflicted without negligence is a common pattern in medical malpractice lawsuits; it is likely the pattern of Jacobs v Cross (Minnesota, 1872), in which Dr W. W. Mayo testified as an expert witness. As a matter of law, the doctor defendants should win all those lawsuits, for iatrogenic injury inflicted without negligence is not a legal wrong in the United States and has not been considered a legal wrong for hundreds of years. However, the medical ethics applicable to doctors' duties to report incompetence in colleagues, including those who inflict excessive iatrogenic injury, have developed dramatically over time. In 1872, the ethical codes in the United States exhorted doctors not to criticize another doctor, even if incompetent. Today, doctors in the United States are ethically required to report an incompetent colleague. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
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McCarthy, D
1999-01-01
Is cloning human beings morally wrong? The basis for the one serious objection to cloning is that, because of what a clone is, clones would have much worse lives than non-clones. I sketch a fragment of moral theory to make sense of the objection. I then outline several ways in which it might be claimed that, because of what a clone is, clones would have much worse lives than non-clones. In particular, I look at various ideas connected with autonomy. I conclude that there is no basis to the claim that, because of what a clone is, clones would have much worse lives than non-clones. I therefore reject the claim that cloning human beings is morally wrong. PMID:10226912
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Guilty Feelings, Targeted Actions
Cryder, Cynthia E.; Springer, Stephen; Morewedge, Carey K.
2014-01-01
Early investigations of guilt cast it as an emotion that prompts broad reparative behaviors that help guilty individuals feel better about themselves or about their transgressions. The current investigation found support for a more recent representation of guilt as an emotion designed to identify and correct specific social offenses. Across five experiments, guilt influenced behavior in a targeted and strategic way. Guilt prompted participants to share resources more generously with others, but only did so when those others were persons whom the participant had wronged and only when those wronged individuals could notice the gesture. Rather than trigger broad reparative behaviors that remediate one’s general reputation or self-perception, guilt triggers targeted behaviors intended to remediate specific social transgressions. PMID:22337764
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Guilty feelings, targeted actions.
Cryder, Cynthia E; Springer, Stephen; Morewedge, Carey K
2012-05-01
Early investigations of guilt cast it as an emotion that prompts broad reparative behaviors that help guilty individuals feel better about themselves or about their transgressions. The current investigation found support for a more recent representation of guilt as an emotion designed to identify and correct specific social offenses. Across five experiments, guilt influenced behavior in a targeted and strategic way. Guilt prompted participants to share resources more generously with others, but only did so when those others were persons whom the participant had wronged and only when those wronged individuals could notice the gesture. Rather than trigger broad reparative behaviors that remediate one's general reputation or self-perception, guilt triggers targeted behaviors intended to remediate specific social transgressions.
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[Enterostomy post emergency enterectomy].
Gavrilescu, S; Velicu, D; Gheorghiu, L; Duţescu, S
2002-01-01
This is a clinical approach regarding 43 resection of intestine, performed in emergency condition, terminated as enterostomy, with represent 20% of enterectomyes performed in emergency condition and 1.6% of urgent operations. The decision of enterostomy has been taken in the conditions of peritoneal sepsis, occlusion or the association of the two circumstances. The results are comparatively analyzed between the cases with enterostomy that has been made from the beginning (66% success, 33% gone wrong), and those with enterostomy made at the second intervention (14% success, 86% gone wrong). One discusses problems of leading, technique and post-operating nursing. The intestinal reintegration has been made possible at 16 patients after a timing of three of four weeks.
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Dodds, Susan; Jones, Karen
1989-01-01
The authors respond to Laura Purdy's article, "Surrogate mothering: exploitation or empowerment?," in the same issue of Bioethics. They contend that focusing on what is necessarily wrong with surrogate motherhood contracts allows Purdy to overlook the contingent features of classist, patriarchal society that make such contracts morally wrong and to marginalize feminist concerns. Theoretical fallacies within Purdy's consequentialist framework create too individualistic and narrow a discussion of the possible harms of surrogate contracts, ignoring influences upon women as a group and the psychological risks to the surrogate mother. If surrogacy contracts have the potential to empower women, then we must see some specific changes that would make this a reality, given that Purdy does not mean surrogacy as it is currently practised.
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Biomedical surveillance: rights conflict with rights.
Atherley, G; Johnston, N; Tennassee, M
1986-10-01
Medical screening and biomedical monitoring violate individual rights. Such conflicts of right with right are acted upon synergistically by uncertainty which, in some important respects, increases rather than decreases as a result of research. Issues of rightness and wrongness, ethical issues, arise because the human beings who are subjects of medical screening and biological monitoring often have little or no option whether to be subjected to them. We identify issues of rightness and wrongness of biomedical surveillance for various purposes of occupational health and safety. We distinguish between social validity and scientific validity. We observe that principles are well established for scientific validity, but not for social validity. We support guidelines as a way forward.
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The ethics of self-sacrifice: what's wrong with suicide bombing?
Battin, Margaret P
2004-01-01
What's wrong with suicide bombing? The tactic has been used by the Tamil Tigers, by the Japanese kamikaze, by al-Qaeda, by Palestinian militants against Israel, by Iraqi defenders loyal to Saddam Hussein against the U.S. invasion, and by others; it is typically understood by these groups as martyrdom rather than suicide. Scientific theories of suicide--biological, psychological, and sociological--do not contribute to an understanding. Nor is the claim that it is amoral, the product of psychopathology or mental illness, adequate. The central moral core of the issue of suicide bombing rests, rather, on the violation of a tacit assumption of equality in combat: "they" have a weapon "we" don't.
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Neural markers of errors as endophenotypes in neuropsychiatric disorders
Manoach, Dara S.; Agam, Yigal
2013-01-01
Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach. PMID:23882201
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Tsunoda, Hirosuke; Kudo, Tomomi; Masaki, Yoshiaki; Ohkubo, Akihiro; Seio, Kohji; Sekine, Mitsuo
2011-01-01
To clarify the biochemical behavior of 2′-deoxyribonucleoside 5′-triphosphates and oligodeoxyribonucleotides (ODNs) containing cytosine N-oxide (Co) and adenine N-oxide (Ao), we examined their base recognition ability in DNA duplex formation using melting temperature (Tm) experiments and their substrate specificity in DNA polymerase-mediated replication. As the result, it was found that the Tm values of modified DNA–DNA duplexes incorporating 2′-deoxyribonucleoside N-oxide derivatives significantly decreased compared with those of the unmodified duplexes. However, single insertion reactions by DNA polymerases of Klenow fragment (KF) (exo−) and Vent (exo−) suggested that Co and Ao selectively recognized G and T, respectively. Meanwhile, the kinetic study showed that the incorporation efficiencies of the modified bases were lower than those of natural bases. Ab initio calculations suggest that these modified bases can form the stable base pairs with the original complementary bases. These results indicate that the modified bases usually recognize the original bases as partners for base pairing, except for misrecognition of dATP by the action of KF (exo−) toward Ao on the template, and the primers could be extended on the template DNA. When they misrecognized wrong bases, the chain could not be elongated so that the modified base served as the chain terminator. PMID:21300642
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Tsunoda, Hirosuke; Kudo, Tomomi; Masaki, Yoshiaki; Ohkubo, Akihiro; Seio, Kohji; Sekine, Mitsuo
2011-04-01
To clarify the biochemical behavior of 2'-deoxyribonucleoside 5'-triphosphates and oligodeoxyribonucleotides (ODNs) containing cytosine N-oxide (C(o)) and adenine N-oxide (A(o)), we examined their base recognition ability in DNA duplex formation using melting temperature (T(m)) experiments and their substrate specificity in DNA polymerase-mediated replication. As the result, it was found that the T(m) values of modified DNA-DNA duplexes incorporating 2'-deoxyribonucleoside N-oxide derivatives significantly decreased compared with those of the unmodified duplexes. However, single insertion reactions by DNA polymerases of Klenow fragment (KF) (exo(-)) and Vent (exo(-)) suggested that C(o) and A(o) selectively recognized G and T, respectively. Meanwhile, the kinetic study showed that the incorporation efficiencies of the modified bases were lower than those of natural bases. Ab initio calculations suggest that these modified bases can form the stable base pairs with the original complementary bases. These results indicate that the modified bases usually recognize the original bases as partners for base pairing, except for misrecognition of dATP by the action of KF (exo(-)) toward A(o) on the template, and the primers could be extended on the template DNA. When they misrecognized wrong bases, the chain could not be elongated so that the modified base served as the chain terminator.
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Neural markers of errors as endophenotypes in neuropsychiatric disorders.
Manoach, Dara S; Agam, Yigal
2013-01-01
Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.
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Engelhardt, Benjamin; Kschischo, Maik; Fröhlich, Holger
2017-06-01
Ordinary differential equations (ODEs) are a popular approach to quantitatively model molecular networks based on biological knowledge. However, such knowledge is typically restricted. Wrongly modelled biological mechanisms as well as relevant external influence factors that are not included into the model are likely to manifest in major discrepancies between model predictions and experimental data. Finding the exact reasons for such observed discrepancies can be quite challenging in practice. In order to address this issue, we suggest a Bayesian approach to estimate hidden influences in ODE-based models. The method can distinguish between exogenous and endogenous hidden influences. Thus, we can detect wrongly specified as well as missed molecular interactions in the model. We demonstrate the performance of our Bayesian dynamic elastic-net with several ordinary differential equation models from the literature, such as human JAK-STAT signalling, information processing at the erythropoietin receptor, isomerization of liquid α -Pinene, G protein cycling in yeast and UV-B triggered signalling in plants. Moreover, we investigate a set of commonly known network motifs and a gene-regulatory network. Altogether our method supports the modeller in an algorithmic manner to identify possible sources of errors in ODE-based models on the basis of experimental data. © 2017 The Author(s).
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Implicit moral evaluations: A multinomial modeling approach.
Cameron, C Daryl; Payne, B Keith; Sinnott-Armstrong, Walter; Scheffer, Julian A; Inzlicht, Michael
2017-01-01
Implicit moral evaluations-i.e., immediate, unintentional assessments of the wrongness of actions or persons-play a central role in supporting moral behavior in everyday life. Yet little research has employed methods that rigorously measure individual differences in implicit moral evaluations. In five experiments, we develop a new sequential priming measure-the Moral Categorization Task-and a multinomial model that decomposes judgment on this task into multiple component processes. These include implicit moral evaluations of moral transgression primes (Unintentional Judgment), accurate moral judgments about target actions (Intentional Judgment), and a directional tendency to judge actions as morally wrong (Response Bias). Speeded response deadlines reduced Intentional Judgment but not Unintentional Judgment (Experiment 1). Unintentional Judgment was stronger toward moral transgression primes than non-moral negative primes (Experiments 2-4). Intentional Judgment was associated with increased error-related negativity, a neurophysiological indicator of behavioral control (Experiment 4). Finally, people who voted for an anti-gay marriage amendment had stronger Unintentional Judgment toward gay marriage primes (Experiment 5). Across Experiments 1-4, implicit moral evaluations converged with moral personality: Unintentional Judgment about wrong primes, but not negative primes, was negatively associated with psychopathic tendencies and positively associated with moral identity and guilt proneness. Theoretical and practical applications of formal modeling for moral psychology are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.
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Neural basis of moral verdict and moral deliberation
Borg, Jana Schaich; Sinnott-Armstrong, Walter; Calhoun, Vince D.; Kiehl, Kent A.
2011-01-01
How people judge something to be morally right or wrong is a fundamental question of both the sciences and the humanities. Here we aim to identify the neural processes that underlie the specific conclusion that something is morally wrong. To do this, we introduce a novel distinction between “moral deliberation,” or the weighing of moral considerations, and the formation of a “moral verdict,” or the commitment to one moral conclusion. We predict and identify hemodynamic activity in the bilateral anterior insula and basal ganglia that correlates with committing to the moral verdict “this is morally wrong” as opposed to “this is morally not wrong,” a finding that is consistent with research from economic decision-making. Using comparisons of deliberation-locked vs. verdict-locked analyses, we also demonstrate that hemodynamic activity in high-level cortical regions previously implicated in morality—including the ventromedial prefrontal cortex, posterior cingulate, and temporoparietal junction—correlates primarily with moral deliberation as opposed to moral verdicts. These findings provide new insights into what types of processes comprise the enterprise of moral judgment, and in doing so point to a framework for resolving why some clinical patients, including psychopaths, may have intact moral judgment but impaired moral behavior. PMID:21590588
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The cost of getting CCS wrong: Uncertainty, infrastructure design, and stranded CO 2
Middleton, Richard Stephen; Yaw, Sean Patrick
2018-01-11
Carbon capture, and storage (CCS) infrastructure will require industry—such as fossil-fuel power, ethanol production, and oil and gas extraction—to make massive investment in infrastructure. The cost of getting these investments wrong will be substantial and will impact the success of CCS technology. Multiple factors can and will impact the success of commercial-scale CCS, including significant uncertainties regarding capture, transport, and injection-storage decisions. Uncertainties throughout the CCS supply chain include policy, technology, engineering performance, economics, and market forces. In particular, large uncertainties exist for the injection and storage of CO 2. Even taking into account upfront investment in site characterization, themore » final performance of the storage phase is largely unknown until commercial-scale injection has started. We explore and quantify the impact of getting CCS infrastructure decisions wrong based on uncertain injection rates and uncertain CO 2 storage capacities using a case study managing CO 2 emissions from the Canadian oil sands industry in Alberta. We use SimCCS, a widely used CCS infrastructure design framework, to develop multiple CCS infrastructure scenarios. Each scenario consists of a CCS infrastructure network that connects CO 2 sources (oil sands extraction and processing) with CO 2 storage reservoirs (acid gas storage reservoirs) using a dedicated CO 2 pipeline network. Each scenario is analyzed under a range of uncertain storage estimates and infrastructure performance is assessed and quantified in terms of cost to build additional infrastructure to store all CO 2. We also include the role of stranded CO 2, CO 2 that a source was expecting to but cannot capture due substandard performance in the transport and storage infrastructure. Results show that the cost of getting the original infrastructure design wrong are significant and that comprehensive planning will be required to ensure that CCS becomes a successful climate mitigation technology. Here, we show that the concept of stranded CO 2 can transform a seemingly high-performing infrastructure design into the worst case scenario.« less
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The causal cognition of wrong doing: incest, intentionality, and morality.
Astuti, Rita; Bloch, Maurice
2015-01-01
The paper concerns the role of intentionality in reasoning about wrong doing. Anthropologists have claimed that, in certain non-Western societies, people ignore whether an act of wrong doing is committed intentionally or accidentally. To examine this proposition, we look at the case of Madagascar. We start by analyzing how Malagasy people respond to incest, and we find that in this case they do not seem to take intentionality into account: catastrophic consequences follow even if those who commit incest are not aware that they are related as kin; punishment befalls on innocent people; and the whole community is responsible for repairing the damage. However, by looking at how people reason about other types of wrong doing, we show that the role of intentionality is well understood, and that in fact this is so even in the case of incest. We therefore argue that, when people contemplate incest and its consequences, they simultaneously consider two quite different issues: the issue of intentionality and blame, and the much more troubling and dumbfounding issue of what society would be like if incest were to be permitted. This entails such a fundamental attack on kinship and on the very basis of society that issues of intentionality and blame become irrelevant. Using the insights we derive from this Malagasy case study, we re-examine the results of Haidt's psychological experiment on moral dumbfoundedness, which uses a story about incest between siblings as one of its test scenarios. We suggest that the dumbfoundedness that was documented among North American students may be explained by the same kind of complexity that we found in Madagascar. In light of this, we discuss the methodological limitations of experimental protocols, which are unable to grasp multiple levels of response. We also note the limitations of anthropological methods and the benefits of closer cross-disciplinary collaboration.
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The causal cognition of wrong doing: incest, intentionality, and morality
Astuti, Rita; Bloch, Maurice
2015-01-01
The paper concerns the role of intentionality in reasoning about wrong doing. Anthropologists have claimed that, in certain non-Western societies, people ignore whether an act of wrong doing is committed intentionally or accidentally. To examine this proposition, we look at the case of Madagascar. We start by analyzing how Malagasy people respond to incest, and we find that in this case they do not seem to take intentionality into account: catastrophic consequences follow even if those who commit incest are not aware that they are related as kin; punishment befalls on innocent people; and the whole community is responsible for repairing the damage. However, by looking at how people reason about other types of wrong doing, we show that the role of intentionality is well understood, and that in fact this is so even in the case of incest. We therefore argue that, when people contemplate incest and its consequences, they simultaneously consider two quite different issues: the issue of intentionality and blame, and the much more troubling and dumbfounding issue of what society would be like if incest were to be permitted. This entails such a fundamental attack on kinship and on the very basis of society that issues of intentionality and blame become irrelevant. Using the insights we derive from this Malagasy case study, we re-examine the results of Haidt’s psychological experiment on moral dumbfoundedness, which uses a story about incest between siblings as one of its test scenarios. We suggest that the dumbfoundedness that was documented among North American students may be explained by the same kind of complexity that we found in Madagascar. In light of this, we discuss the methodological limitations of experimental protocols, which are unable to grasp multiple levels of response. We also note the limitations of anthropological methods and the benefits of closer cross-disciplinary collaboration. PMID:25741304
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Leung, Yuk Yee; Chang, Chun Qi; Hung, Yeung Sam
2012-01-01
Using hybrid approach for gene selection and classification is common as results obtained are generally better than performing the two tasks independently. Yet, for some microarray datasets, both classification accuracy and stability of gene sets obtained still have rooms for improvement. This may be due to the presence of samples with wrong class labels (i.e. outliers). Outlier detection algorithms proposed so far are either not suitable for microarray data, or only solve the outlier detection problem on their own. We tackle the outlier detection problem based on a previously proposed Multiple-Filter-Multiple-Wrapper (MFMW) model, which was demonstrated to yield promising results when compared to other hybrid approaches (Leung and Hung, 2010). To incorporate outlier detection and overcome limitations of the existing MFMW model, three new features are introduced in our proposed MFMW-outlier approach: 1) an unbiased external Leave-One-Out Cross-Validation framework is developed to replace internal cross-validation in the previous MFMW model; 2) wrongly labeled samples are identified within the MFMW-outlier model; and 3) a stable set of genes is selected using an L1-norm SVM that removes any redundant genes present. Six binary-class microarray datasets were tested. Comparing with outlier detection studies on the same datasets, MFMW-outlier could detect all the outliers found in the original paper (for which the data was provided for analysis), and the genes selected after outlier removal were proven to have biological relevance. We also compared MFMW-outlier with PRAPIV (Zhang et al., 2006) based on same synthetic datasets. MFMW-outlier gave better average precision and recall values on three different settings. Lastly, artificially flipped microarray datasets were created by removing our detected outliers and flipping some of the remaining samples' labels. Almost all the 'wrong' (artificially flipped) samples were detected, suggesting that MFMW-outlier was sufficiently powerful to detect outliers in high-dimensional microarray datasets.
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The cost of getting CCS wrong: Uncertainty, infrastructure design, and stranded CO 2
DOE Office of Scientific and Technical Information (OSTI.GOV)
Middleton, Richard Stephen; Yaw, Sean Patrick
Carbon capture, and storage (CCS) infrastructure will require industry—such as fossil-fuel power, ethanol production, and oil and gas extraction—to make massive investment in infrastructure. The cost of getting these investments wrong will be substantial and will impact the success of CCS technology. Multiple factors can and will impact the success of commercial-scale CCS, including significant uncertainties regarding capture, transport, and injection-storage decisions. Uncertainties throughout the CCS supply chain include policy, technology, engineering performance, economics, and market forces. In particular, large uncertainties exist for the injection and storage of CO 2. Even taking into account upfront investment in site characterization, themore » final performance of the storage phase is largely unknown until commercial-scale injection has started. We explore and quantify the impact of getting CCS infrastructure decisions wrong based on uncertain injection rates and uncertain CO 2 storage capacities using a case study managing CO 2 emissions from the Canadian oil sands industry in Alberta. We use SimCCS, a widely used CCS infrastructure design framework, to develop multiple CCS infrastructure scenarios. Each scenario consists of a CCS infrastructure network that connects CO 2 sources (oil sands extraction and processing) with CO 2 storage reservoirs (acid gas storage reservoirs) using a dedicated CO 2 pipeline network. Each scenario is analyzed under a range of uncertain storage estimates and infrastructure performance is assessed and quantified in terms of cost to build additional infrastructure to store all CO 2. We also include the role of stranded CO 2, CO 2 that a source was expecting to but cannot capture due substandard performance in the transport and storage infrastructure. Results show that the cost of getting the original infrastructure design wrong are significant and that comprehensive planning will be required to ensure that CCS becomes a successful climate mitigation technology. Here, we show that the concept of stranded CO 2 can transform a seemingly high-performing infrastructure design into the worst case scenario.« less
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Detection and correction of prescription errors by an emergency department pharmacy service.
Stasiak, Philip; Afilalo, Marc; Castelino, Tanya; Xue, Xiaoqing; Colacone, Antoinette; Soucy, Nathalie; Dankoff, Jerrald
2014-05-01
Emergency departments (EDs) are recognized as a high-risk setting for prescription errors. Pharmacist involvement may be important in reviewing prescriptions to identify and correct errors. The objectives of this study were to describe the frequency and type of prescription errors detected by pharmacists in EDs, determine the proportion of errors that could be corrected, and identify factors associated with prescription errors. This prospective observational study was conducted in a tertiary care teaching ED on 25 consecutive weekdays. Pharmacists reviewed all documented prescriptions and flagged and corrected errors for patients in the ED. We collected information on patient demographics, details on prescription errors, and the pharmacists' recommendations. A total of 3,136 ED prescriptions were reviewed. The proportion of prescriptions in which a pharmacist identified an error was 3.2% (99 of 3,136; 95% confidence interval [CI] 2.5-3.8). The types of identified errors were wrong dose (28 of 99, 28.3%), incomplete prescription (27 of 99, 27.3%), wrong frequency (15 of 99, 15.2%), wrong drug (11 of 99, 11.1%), wrong route (1 of 99, 1.0%), and other (17 of 99, 17.2%). The pharmacy service intervened and corrected 78 (78 of 99, 78.8%) errors. Factors associated with prescription errors were patient age over 65 (odds ratio [OR] 2.34; 95% CI 1.32-4.13), prescriptions with more than one medication (OR 5.03; 95% CI 2.54-9.96), and those written by emergency medicine residents compared to attending emergency physicians (OR 2.21, 95% CI 1.18-4.14). Pharmacists in a tertiary ED are able to correct the majority of prescriptions in which they find errors. Errors are more likely to be identified in prescriptions written for older patients, those containing multiple medication orders, and those prescribed by emergency residents.
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Hickman, Thu-Trang T; Quist, Arbor Jessica Lauren; Salazar, Alejandra; Amato, Mary G; Wright, Adam; Volk, Lynn A; Bates, David W; Schiff, Gordon
2018-04-01
Computerised prescriber order entry (CPOE) systems users often discontinue medications because the initial order was erroneous. To elucidate error types by querying prescribers about their reasons for discontinuing outpatient medication orders that they had self-identified as erroneous. During a nearly 3 year retrospective data collection period, we identified 57 972 drugs discontinued with the reason 'Error (erroneous entry)." Because chart reviews revealed limited information about these errors, we prospectively studied consecutive, discontinued erroneous orders by querying prescribers in near-real-time to learn more about the erroneous orders. From January 2014 to April 2014, we prospectively emailed prescribers about outpatient drug orders that they had discontinued due to erroneous initial order entry. Of 2 50 806 medication orders in these 4 months, 1133 (0.45%) of these were discontinued due to error. From these 1133, we emailed 542 unique prescribers to ask about their reason(s) for discontinuing these mediation orders in error. We received 312 responses (58% response rate). We categorised these responses using a previously published taxonomy. The top reasons for these discontinued erroneous orders included: medication ordered for wrong patient (27.8%, n=60); wrong drug ordered (18.5%, n=40); and duplicate order placed (14.4%, n=31). Other common discontinued erroneous orders related to drug dosage and formulation (eg, extended release versus not). Oxycodone (3%) was the most frequent drug discontinued error. Drugs are not infrequently discontinued 'in error.' Wrong patient and wrong drug errors constitute the leading types of erroneous prescriptions recognised and discontinued by prescribers. Data regarding erroneous medication entries represent an important source of intelligence about how CPOE systems are functioning and malfunctioning, providing important insights regarding areas for designing CPOE more safely in the future. © 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.
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Lynöe, Niels; Wessel, Maja; Olsson, Daniel; Alexanderson, Kristina; Helgesson, Gert
2013-03-23
Previous research shows that how patients perceive encounters with healthcare staff may affect their health and self-estimated ability to return to work. The aim of the present study was to explore long-term sick-listed patients' encounters with social insurance office staff and the impact of these encounters on self-estimated ability to return to work. A random sample of long-term sick-listed patients (n = 10,042) received a questionnaire containing questions about their experiences of positive and negative encounters and item lists specifying such experiences. Respondents were also asked whether the encounters made them feel respected or wronged and how they estimated the effect of these encounters on their ability to return to work. Statistical analysis was conducted using 95% confidence intervals (CI) for proportions, and attributable risk (AR) with 95% CI. The response rate was 58%. Encounter items strongly associated with feeling respected were, among others: listened to me, believed me, and answered my questions. Encounter items strongly associated with feeling wronged were, among others: did not believe me, doubted my condition, and questioned my motivation to work. Positive encounters facilitated patients' self-estimated ability to return to work [26.9% (CI: 22.1-31.7)]. This effect was significantly increased if the patients also felt respected [49.3% (CI: 47.5-51.1)]. Negative encounters impeded self-estimated ability to return to work [29.1% (CI: 24.6-33.6)]; when also feeling wronged return to work was significantly further impeded [51.3% (CI: 47.1-55.5)]. Long-term sick-listed patients find that their self-reported ability to return to work is affected by positive and negative encounters with social insurance office staff. This effect is further enhanced by feeling respected or wronged, respectively.
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Tridandapani, Srini; Ramamurthy, Senthil; Provenzale, James; Obuchowski, Nancy A; Evanoff, Michael G; Bhatti, Pamela
2014-08-01
To evaluate whether the presence of facial photographs obtained at the point-of-care of portable radiography leads to increased detection of wrong-patient errors. In this institutional review board-approved study, 166 radiograph-photograph combinations were obtained from 30 patients. Consecutive radiographs from the same patients resulted in 83 unique pairs (ie, a new radiograph and prior, comparison radiograph) for interpretation. To simulate wrong-patient errors, mismatched pairs were generated by pairing radiographs from different patients chosen randomly from the sample. Ninety radiologists each interpreted a unique randomly chosen set of 10 radiographic pairs, containing up to 10% mismatches (ie, error pairs). Radiologists were randomly assigned to interpret radiographs with or without photographs. The number of mismatches was identified, and interpretation times were recorded. Ninety radiologists with 21 ± 10 (mean ± standard deviation) years of experience were recruited to participate in this observer study. With the introduction of photographs, the proportion of errors detected increased from 31% (9 of 29) to 77% (23 of 30; P = .006). The odds ratio for detection of error with photographs to detection without photographs was 7.3 (95% confidence interval: 2.29-23.18). Observer qualifications, training, or practice in cardiothoracic radiology did not influence sensitivity for error detection. There is no significant difference in interpretation time for studies without photographs and those with photographs (60 ± 22 vs. 61 ± 25 seconds; P = .77). In this observer study, facial photographs obtained simultaneously with portable chest radiographs increased the identification of any wrong-patient errors, without substantial increase in interpretation time. This technique offers a potential means to increase patient safety through correct patient identification. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.
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Anomaly Analysis: NASA's Engineering and Safety Center Checks Recurring Shuttle Glitches
NASA Technical Reports Server (NTRS)
Morring, Frank, Jr.
2004-01-01
The NASA Engineering and Safety Center (NESC), set up in the wake of the Columbia accident to backstop engineers in the space shuttle program, is reviewing hundreds of recurring anomalies that the program had determined don't affect flight safety to see if in fact they might. The NESC is expanding its support to other programs across the agency, as well. The effort, which will later extend to the International Space Station (ISS), is a principal part of the attempt to overcome the normalization of deviance--a situation in which organizations proceeded as if nothing was wrong in the face of evidence that something was wrong--cited by sociologist Diane Vaughn as contributing to both space shuttle disasters.
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[Antineutrophil cytoplasmic antibodies associated with infective endocarditis: Literature review].
Langlois, V; Marie, I
2017-07-01
Antineutrophil cytoplasmic antibodies (ANCA) associated with infective endocarditis are a rare disorder. The condition can mimic primary systemic vasculitis (i.e. granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis). Thus, a wrong diagnosis of valvular involvement related to primary systemic vasculitis can be made in patients exhibiting ANCA associated with infective endocarditis. Because treatment of both conditions is different, this wrong diagnosis will lead to dramatic consequences in these latter patients. This review reports the state of knowledge and proposes an algorithm to follow when confronted to a possible case of ANCA associated with infective endocarditis. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.
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Mars Pathfinder Near-Field Rock Distribution Re-Evaluation
NASA Technical Reports Server (NTRS)
Haldemann, A. F. C.; Golombek, M. P.
2003-01-01
We have completed analysis of a new near-field rock count at the Mars Pathfinder landing site and determined that the previously published rock count suggesting 16% cumulative fractional area (CFA) covered by rocks is incorrect. The earlier value is not so much wrong (our new CFA is 20%), as right for the wrong reason: both the old and the new CFA's are consistent with remote sensing data, however the earlier determination incorrectly calculated rock coverage using apparent width rather than average diameter. Here we present details of the new rock database and the new statistics, as well as the importance of using rock average diameter for rock population statistics. The changes to the near-field data do not affect the far-field rock statistics.
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THE ROLE OF THE MICROCOMPUTER IN THE DEMISE OF WESTERN CIVILIZATION
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stevens, David
Every revolutionary: new technology has been accompanied by a host of Cassandras prophesying the end of the world as we know it. Unlike Cassandra, heretofore they have all been wrong. The microcomputer has come into its own as a revolutioary new technology, and the new generation of Cassandras is beginning to appear. They, too, for the most part are wrong, but their error is not in their conclusion--for the microcomputer will bring about the end of Western Civilization--but in their conentration on technological consequences. It is rather a social consequence, the willful dis-integiation of society, which will be the motivatingmore » force. But Cassandra's tragedy was that no-one listened to her.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Vyas, Rajan; Reed, Andrew J.; Tokarsky, E. John
One common oxidative DNA lesion, 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG), is highly mutagenic in vivo due to its anti-conformation forming a Watson–Crick base pair with correct deoxycytidine 5'-triphosphate (dCTP) and its syn-conformation forming a Hoogsteen base pair with incorrect deoxyadenosine 5'-triphosphate (dATP). Here in this article, we utilized time-resolved X-ray crystallography to follow 8-oxoG bypass by human DNA polymerase β (hPolβ). In the 12 solved structures, both Watson–Crick (anti-8-oxoG:anti-dCTP) and Hoogsteen (syn-8-oxoG:anti-dATP) base pairing were clearly visible and were maintained throughout the chemical reaction. Additionally, a third Mg 2+ appeared during the process of phosphodiester bond formation and was located between the reactingmore » α- and β-phosphates of the dNTP, suggesting its role in stabilizing reaction intermediates. After phosphodiester bond formation, hPolβ reopened its conformation, pyrophosphate was released, and the newly incorporated primer 3'-terminal nucleotide stacked, rather than base paired, with 8-oxoG. These structures provide the first real-time pictures, to our knowledge, of how a polymerase correctly and incorrectly bypasses a DNA lesion.« less
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Akman, Hasan O; Dorado, Beatriz; López, Luis C; García-Cazorla, Angeles; Vilà, Maya R; Tanabe, Lauren M; Dauer, William T; Bonilla, Eduardo; Tanji, Kurenai; Hirano, Michio
2008-08-15
Mitochondrial DNA (mtDNA) depletion syndrome (MDS), an autosomal recessive condition, is characterized by variable organ involvement with decreased mtDNA copy number and activities of respiratory chain enzymes in affected tissues. MtDNA depletion has been associated with mutations in nine autosomal genes, including thymidine kinase (TK2), which encodes a ubiquitous mitochondrial protein. To study the pathogenesis of TK2-deficiency, we generated mice harboring an H126N Tk2 mutation. Homozygous Tk2 mutant (Tk2(-/-)) mice developed rapidly progressive weakness after age 10 days and died between ages 2 and 3 weeks. Tk2(-/-) animals showed Tk2 deficiency, unbalanced dNTP pools, mtDNA depletion and defects of respiratory chain enzymes containing mtDNA-encoded subunits that were most prominent in the central nervous system. Histopathology revealed an encephalomyelopathy with prominent vacuolar changes in the anterior horn of the spinal cord. The H126N TK2 mouse is the first knock-in animal model of human MDS and demonstrates that the severity of TK2 deficiency in tissues may determine the organ-specific phenotype.
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Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency
Garone, Caterina; Garcia-Diaz, Beatriz; Emmanuele, Valentina; Lopez, Luis C; Tadesse, Saba; Akman, Hasan O; Tanji, Kurenai; Quinzii, Catarina M; Hirano, Michio
2014-01-01
Autosomal recessive mutations in the thymidine kinase 2 gene (TK2) cause mitochondrial DNA depletion, multiple deletions, or both due to loss of TK2 enzyme activity and ensuing unbalanced deoxynucleotide triphosphate (dNTP) pools. To bypass Tk2 deficiency, we administered deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) to the Tk2 H126N (Tk2−/−) knock-in mouse model from postnatal day 4, when mutant mice are phenotypically normal, but biochemically affected. Assessment of 13-day-old Tk2−/− mice treated with dCMP+dTMP 200 mg/kg/day each (Tk2−/−200dCMP/dTMP) demonstrated that in mutant animals, the compounds raise dTTP concentrations, increase levels of mtDNA, ameliorate defects of mitochondrial respiratory chain enzymes, and significantly prolong their lifespan (34 days with treatment versus 13 days untreated). A second trial of dCMP+dTMP each at 400 mg/kg/day showed even greater phenotypic and biochemical improvements. In conclusion, dCMP/dTMP supplementation is the first effective pharmacologic treatment for Tk2 deficiency. Subject Categories Genetics, Gene Therapy & Genetic Disease; Metabolism PMID:24968719
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Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency.
Garone, Caterina; Garcia-Diaz, Beatriz; Emmanuele, Valentina; Lopez, Luis C; Tadesse, Saba; Akman, Hasan O; Tanji, Kurenai; Quinzii, Catarina M; Hirano, Michio
2014-08-01
Autosomal recessive mutations in the thymidine kinase 2 gene (TK2) cause mitochondrial DNA depletion, multiple deletions, or both due to loss of TK2 enzyme activity and ensuing unbalanced deoxynucleotide triphosphate (dNTP) pools. To bypass Tk2 deficiency, we administered deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) to the Tk2 H126N (Tk2(-/-)) knock-in mouse model from postnatal day 4, when mutant mice are phenotypically normal, but biochemically affected. Assessment of 13-day-old Tk2(-/-) mice treated with dCMP+dTMP 200 mg/kg/day each (Tk2(-/-200dCMP/) (dTMP)) demonstrated that in mutant animals, the compounds raise dTTP concentrations, increase levels of mtDNA, ameliorate defects of mitochondrial respiratory chain enzymes, and significantly prolong their lifespan (34 days with treatment versus 13 days untreated). A second trial of dCMP+dTMP each at 400 mg/kg/day showed even greater phenotypic and biochemical improvements. In conclusion, dCMP/dTMP supplementation is the first effective pharmacologic treatment for Tk2 deficiency. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.
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Akman, Hasan O.; Dorado, Beatriz; López, Luis C.; García-Cazorla, Ángeles; Vilà, Maya R.; Tanabe, Lauren M.; Dauer, William T.; Bonilla, Eduardo; Tanji, Kurenai; Hirano, Michio
2008-01-01
Mitochondrial DNA (mtDNA) depletion syndrome (MDS), an autosomal recessive condition, is characterized by variable organ involvement with decreased mtDNA copy number and activities of respiratory chain enzymes in affected tissues. MtDNA depletion has been associated with mutations in nine autosomal genes, including thymidine kinase (TK2), which encodes a ubiquitous mitochondrial protein. To study the pathogenesis of TK2-deficiency, we generated mice harboring an H126N Tk2 mutation. Homozygous Tk2 mutant (Tk2−/−) mice developed rapidly progressive weakness after age 10 days and died between ages 2 and 3 weeks. Tk2−/− animals showed Tk2 deficiency, unbalanced dNTP pools, mtDNA depletion and defects of respiratory chain enzymes containing mtDNA-encoded subunits that were most prominent in the central nervous system. Histopathology revealed an encephalomyelopathy with prominent vacuolar changes in the anterior horn of the spinal cord. The H126N TK2 mouse is the first knock-in animal model of human MDS and demonstrates that the severity of TK2 deficiency in tissues may determine the organ-specific phenotype. PMID:18467430
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Zhang, Peipei; Liu, Yan; Liu, Wenwen; Massart, Sebastien; Wang, Xifeng
2017-11-01
Wheat dwarf virus (WDV), barley yellow striate mosaic virus (BYSMV), rice black-streaked dwarf virus (RBSDV) and northern cereal mosaic virus (NCMV) are four viruses infecting wheat and causing similar symptoms. In this paper, a multiplex reverse transcription polymerase chain reaction (m-RT-PCR) method has been developed for the simultaneous detection and discrimination of these viruses. The protocol uses specific primer set for each virus and produces four distinct fragments (273, 565, 783 and 1296bp), detecting the presence of RBSDV, BYSMV, WDV and NCMV, respectively. Annealing temperature, concentrations of dNTP, Taq polymerase and Mg 2+ were optimized for the m-RT-PCR. The detection limit of the assay was up to 10 -2 dilution. The amplification specificity of these primers was tested against a range of field samples from different regions of China, where RBSDV, BYSMV, WDV have been detected. This study fulfills the need for a rapid and specific wheat virus detection that also has the potential for investigating the epidemiology of these new viral diseases. Copyright © 2017 Elsevier B.V. All rights reserved.
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Polyphosphate is a key factor for cell survival after DNA damage in eukaryotic cells.
Bru, Samuel; Samper-Martín, Bàrbara; Quandt, Eva; Hernández-Ortega, Sara; Martínez-Laínez, Joan M; Garí, Eloi; Rafel, Marta; Torres-Torronteras, Javier; Martí, Ramón; Ribeiro, Mariana P C; Jiménez, Javier; Clotet, Josep
2017-09-01
Cells require extra amounts of dNTPs to repair DNA after damage. Polyphosphate (polyP) is an evolutionary conserved linear polymer of up to several hundred inorganic phosphate (Pi) residues that is involved in many functions, including Pi storage. In the present article, we report on findings demonstrating that polyP functions as a source of Pi when required to sustain the dNTP increment essential for DNA repair after damage. We show that mutant yeast cells without polyP produce less dNTPs upon DNA damage and that their survival is compromised. In contrast, when polyP levels are ectopically increased, yeast cells become more resistant to DNA damage. More importantly, we show that when polyP is reduced in HEK293 mammalian cell line cells and in human dermal primary fibroblasts (HDFa), these cells become more sensitive to DNA damage, suggesting that the protective role of polyP against DNA damage is evolutionary conserved. In conclusion, we present polyP as a molecule involved in resistance to DNA damage and suggest that polyP may be a putative target for new approaches in cancer treatment or prevention. Copyright © 2017 Elsevier B.V. All rights reserved.
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Pérez-Torrado, Roberto; Llopis, Silvia; Perrone, Benedetta; Gómez-Pastor, Rocío; Hube, Bernhard; Querol, Amparo
2015-01-01
In recent years, the number of human infection cases produced by the food related species Saccharomyces cerevisiae has increased. Whereas many strains of this species are considered safe, other 'opportunistic' strains show a high degree of potential virulence attributes and can cause infections in immunocompromised patients. Here we studied the genetic characteristics of selected opportunistic strains isolated from dietary supplements and also from patients by array comparative genomic hybridization. Our results show increased copy numbers of IMD genes in opportunistic strains, which are implicated in the de novo biosynthesis of the purine nucleotides pathway. The importance of this pathway for virulence of S. cerevisiae was confirmed by infections in immunodeficient murine models using a GUA1 mutant, a key gene of this pathway. We show that exogenous guanine, an end product of this pathway in its triphosphorylated form, increases the survival of yeast strains in ex vivo blood infections. Finally, we show the importance of the DNA damage response that activates dNTP biosynthesis in yeast cells during ex vivo blood infections. We conclude that opportunistic yeasts may use an enhanced de novo biosynthesis of the purine nucleotides pathway to increase survival and favor infections in the host.
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ERIC Educational Resources Information Center
Gillam, Barbara
1980-01-01
Various theories are introduced to explain illusions in which the length, orientation, curvature or direction is wrongly perceived. The role of eye movements in the process of diminution is discussed. (SA)
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Zajicek, G
2001-08-01
Metaphysics, is generally a pleasant, and harmless intellectual endeavor. Even if leading to wrong conclusions, nobody is hurt. Suppose that contrary to general belief, the Big Bang (1) never happened and the world is eternal. No harm is done. Some philosophers, like Kant, enjoyed life despite the fact that, nature, or the thing in itself, eluded their understanding (2). But suppose that the thing in itself is your patient, and you apply metaphysical reasoning for his treatment, metaphysics may occasionally be damaging. This is particularly pertinent to cancer, a disease that is haunted by false metaphysical statements. Since cancer is part of medicine, the present discourse deals with medical metaphysics. Medicine provides a simple way, or rule of thumb, for distinguishing between correct and wrong medical metaphysical statements. If they harm the patient, they are wrong, and if they aid him, they are correct. Statements that do not affect a patient's well being, e.g., 'Big Bang may be hazardous to your health', are of no apparent value and doubtful. Since treatment outcome is generally uncertain, the physician continually searches for new ideas that may aid his patient, even if they are metaphysical. In diseases, like cancer, that elude his understanding, his adherence to metaphysics intensifies, and he is ready to consider even doubtful suggestions for treatment. Yet by relaxing the rules of thumb for evaluating metaphysical concepts, he gradually slips into the irrational domain. Copyright 2001 Harcourt Publishers Ltd.
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Generalized hydromechanical model for stomatal responses to hydraulic perturbations.
Kwon, H W; Choi, M Y
2014-01-07
Stomata respond in a common pattern to various hydraulic perturbations on any part of the 'soil-plant-air' system: initial transient 'wrong-way' responses and final stationary 'right-way' responses. In order to describe this pattern on the basis of statistical physics, we propose a simple model where turgor pressure of a cell is taken to be a power function of its volume, and obtain results in qualitative agreement with experimental data for responses to a variety of hydraulic perturbations: Firstly, stationary stomatal conductance as a function of the vapor pressure deficit divides into three regimes characterized by sensitivities of the stomatal conductance and the transpiration rate with respect to vapor pressure deficit; secondly, for every hydraulic perturbation, the initial transient 'wrong-way' responses always appear; thirdly, on condition that water is supplied insufficiently, stomatal oscillations are often observed; finally, stomatal responses following leaf excision exhibit, after the initial transient wrong-way responses, slow relaxation to stomatal closing. In particular, comparison of areoles having different numbers of stomata demonstrates that areoles with small numbers of stomata tend to provoke lack of water in the soil as well as in the plant. In addition, our model also describes well dependence of the stomatal conductance on temperature. It may be extended further to describe stomatal responses to other environmental factors such as carbon dioxide, light, and temperature. © 2013 Elsevier Ltd. All rights reserved.
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Why Aristotle took so long to die
NASA Astrophysics Data System (ADS)
Danielson, Dennis
2006-04-01
Like young people looking askance at their parents, we often have trouble taking seriously the interests or even the intellects of ``scientists'' from centuries gone by (an attitude already betrayed by the urge to use quotation marks). After all, their theories were wrong. But the greatest wrong physicist of them all was Aristotle. The earliest thinkers we today classify as scientists (Bacon, Galileo, Newton) cut their teeth trying to show how he was wrong--but it wasn't easy. In order to see why it was so hard, we need to transport ourselves mentally back to the period between ancient Greece and seventeenth-century Europe and try to think like Aristotelians. That way we can catch a taste of the intellectual pleasures of Aristotelian physics and cosmology--including Aristotle's concepts of elements, cause, natural motion, and the ``two-storey'' universe. By becoming (temporary) Aristotelians, we'll be able to see better, for example, why Copernicanism took a hundred years to catch on. For the heliocentric ``celestial machine'' demanded a new physics that nobody had yet provided. Finally, to examine Aristotle's long monopoly on physics--based on what had grown to look like simple common sense--is also to stir up questions about how we might gain enough perspective on our present habits of thought to avoid getting stuck in our own orthodoxies. We may even find that those habits, as exemplified by modern astrophysics, still conceal unpurged remnants of Aristotle.
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H4: A challenging system for natural orbital functional approximations
NASA Astrophysics Data System (ADS)
Ramos-Cordoba, Eloy; Lopez, Xabier; Piris, Mario; Matito, Eduard
2015-10-01
The correct description of nondynamic correlation by electronic structure methods not belonging to the multireference family is a challenging issue. The transition of D2h to D4h symmetry in H4 molecule is among the most simple archetypal examples to illustrate the consequences of missing nondynamic correlation effects. The resurgence of interest in density matrix functional methods has brought several new methods including the family of Piris Natural Orbital Functionals (PNOF). In this work, we compare PNOF5 and PNOF6, which include nondynamic electron correlation effects to some extent, with other standard ab initio methods in the H4 D4h/D2h potential energy surface (PES). Thus far, the wrongful behavior of single-reference methods at the D2h-D4h transition of H4 has been attributed to wrong account of nondynamic correlation effects, whereas in geminal-based approaches, it has been assigned to a wrong coupling of spins and the localized nature of the orbitals. We will show that actually interpair nondynamic correlation is the key to a cusp-free qualitatively correct description of H4 PES. By introducing interpair nondynamic correlation, PNOF6 is shown to avoid cusps and provide the correct smooth PES features at distances close to the equilibrium, total and local spin properties along with the correct electron delocalization, as reflected by natural orbitals and multicenter delocalization indices.
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Goal Directed Model Inversion: A Study of Dynamic Behavior
NASA Technical Reports Server (NTRS)
Colombano, Silvano P.; Compton, Michael; Raghavan, Bharathi; Lum, Henry, Jr. (Technical Monitor)
1994-01-01
Goal Directed Model Inversion (GDMI) is an algorithm designed to generalize supervised learning to the case where target outputs are not available to the learning system. The output of the learning system becomes the input to some external device or transformation, and only the output of this device or transformation can be compared to a desired target. The fundamental driving mechanism of GDMI is to learn from success. Given that a wrong outcome is achieved, one notes that the action that produced that outcome 0 "would have been right if the outcome had been the desired one." The algorithm then proceeds as follows: (1) store the action that produced the wrong outcome as a "target" (2) redefine the wrong outcome as a desired goal (3) submit the new desired goal to the system (4) compare the new action with the target action and modify the system by using a suitable algorithm for credit assignment (Back propagation in our example) (5) resubmit the original goal. Prior publications by our group in this area focused on demonstrating empirical results based on the inverse kinematic problem for a simulated robotic arm. In this paper we apply the inversion process to much simpler analytic functions in order to elucidate the dynamic behavior of the system and to determine the sensitivity of the learning process to various parameters. This understanding will be necessary for the acceptance of GDMI as a practical tool.
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Overcoming Murphy`s Law to gain ERP - a case study at Gibbons Creek Lignite Mine, Texas
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lancaster, E.M.; Horbaczewski, J.K.
1997-12-31
As of January 1997, there are 2,586 acres of reclaimed land in the Extended Responsibility Period (ERP) at Gibbons Creek Lignite Mine, Texas. This achievement has taken approximately five years to accomplish - from 1991 to 1996. During this period, there were a number of issues, some of which appeared to follow Murphy`s Law (whatever can go wrong, will go wrong!). For example, the ERP candidate areas were split among three permit areas, which first had to be consolidated to facilitate the ERP process. Minesoil issues, identified as ERP prerequisites, became entangled in an overall renewal/revision of the newly-consolidated Permitmore » 26B. Special-purpose vegetation studies were performed to investigate the effects of different minesoil textures. In the meantime, small depressional areas, wetland/wildlife enhancement areas, reclamation ponds and restored drainages became the subjects of attention from landowners and regulatory agencies. Some of these structures and features were subsequently reclaimed; others were approved via the permitting process. In some cases, the only way out of the impasse was through land acquisition. Finally, after all these issues had been resolved, an unforeseen oil-well drilling program crisscrossed the proposed ERP areas with a network of oil well pads and service roads, requiring a post-mining land use change. Eventually, whatever could go wrong, went right, and entry of lands into ERP was accomplished.« less
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... disorder, something goes wrong with this process. Mitochondrial diseases are a group of metabolic disorders. Mitochondria are ... cells and cause damage. The symptoms of mitochondrial disease can vary. It depends on how many mitochondria ...
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... woman is pregnant. If you have an ectopic pregnancy, the fertilized egg grows in the wrong place, ... tubes. The result is usually a miscarriage. Ectopic pregnancy can be a medical emergency if it ruptures. ...
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The inconvenient truth of failed climate policies
NASA Astrophysics Data System (ADS)
van Renssen, Sonja
2018-05-01
Sometimes policymakers have backed the wrong technologies, lacked ambition or simply not engaged with potential emissions reductions. Sonja van Renssen explores climate policies that have not delivered and why.
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... or not used properly can make for some heavy health problems. How Can Backpacks Cause Problems? Your ... as natural shock absorbers. When you put a heavy weight on your shoulders in the wrong way, ...
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Yau, Jenny; Smetana, Judith G
2003-01-01
Sixty-one Chinese preschoolers from Hong Kong at 2 ages (Ms = 4.36 and 6.00 years) were interviewed about familiar moral, social-conventional, and personal events. Children treated personal events as distinct from moral obligations and conventional regulations. Children judged the child as deciding personal issues, based on personal choice justifications, whereas children judged parents as deciding moral and conventional issues. With age, children granted increased decision-making power to the child. In contrast, children viewed moral transgressions as more serious, generalizably wrong, and wrong independent of authority than other events, based on welfare and fairness. Punishment-avoidance justifications for conventional events decreased with age, whereas conventional justifications increased. Young Chinese preschool children make increasingly differentiated judgments about their social world.
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Reducing Wrong Patient Selection Errors: Exploring the Design Space of User Interface Techniques
Sopan, Awalin; Plaisant, Catherine; Powsner, Seth; Shneiderman, Ben
2014-01-01
Wrong patient selection errors are a major issue for patient safety; from ordering medication to performing surgery, the stakes are high. Widespread adoption of Electronic Health Record (EHR) and Computerized Provider Order Entry (CPOE) systems makes patient selection using a computer screen a frequent task for clinicians. Careful design of the user interface can help mitigate the problem by helping providers recall their patients’ identities, accurately select their names, and spot errors before orders are submitted. We propose a catalog of twenty seven distinct user interface techniques, organized according to a task analysis. An associated video demonstrates eighteen of those techniques. EHR designers who consider a wider range of human-computer interaction techniques could reduce selection errors, but verification of efficacy is still needed. PMID:25954415
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Dumsday, Travis
2016-03-01
If elective abortion is publicly funded, then the government is obligated to take active measures designed to reduce its prevalence. I present two arguments for that conclusion. The first argument is directed at those pro-choice thinkers who hold that while some or all elective abortions are morally wrong, they still ought to be legally permitted and publicly subsidized. The second argument is directed at pro-choice thinkers who hold that there is nothing morally wrong with elective abortion and that it should be both legally permitted and publicly subsidized. The second argument employs premises that generalize beyond the abortion debate and that may serve to shed light on broader questions concerning conscience and the requirements of political compromise in a democracy.
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The transformational power of IT: Experience from patient safety leaders.
May, Ellen Lanser
2005-01-01
Late last year, David J. Brailer, M.D., Ph.D., National Health Information Technology Coordinator for the Department of Health and Human Services, visited Evanston (IL) Northwestern Hospital (ENH) to observe its electronic medical record system. ENH is the first in the nation to put such a system into an acute care setting, including all three of its hospitals and its 70 medical offices and ambulatory sites. "It's been truly transformational for our processes, our delivery of care, our communications, and our way of doing business," says Mark R. Neaman, FACHE, ENH's president and chief executive officer. What's more, ENH has demonstrated at least a 20 percent reduction in medication errors, and the remaining errors have shifted from wrong medication and wrong patient to errors of timing, which are almost always less severe.
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Paull, J D; Morris, G M
2012-07-01
On 16 February 1845 the Reverend W. H. Browne, rector of St John's Church in Launceston, Van Diemen's Land, wrote in his journal, "My dear Wife died very suddenly almost immediately after and in consequence of taking a preparation of Hyd. Cyan. Acid prepared & supplied by Dr Pugh". This journal entry raises a number of questions. Was Dr Pugh treating a condition which he thought merited that treatment or was it a ghastly mistake? Was Caroline Browne suffering from pulmonary tuberculosis? Was hydrocyanic acid an accepted treatment at that time? Did Mrs Browne take the wrong dose? Was an incorrect concentration of the drug prepared by Dr Pugh? Did he use the wrong pharmacopoeia in preparing the hydrocyanic acid? Why was there no inquest? Only some of these questions can be answered.
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Goto, Masami; Kunimatsu, Akira; Shojima, Masaaki; Abe, Osamu; Aoki, Shigeki; Hayashi, Naoto; Mori, Harushi; Ino, Kenji; Yano, Keiichi; Saito, Nobuhito; Ohtomo, Kuni
2013-03-25
We present a case in which the origin of the branching vessel at the aneurysm neck was observed at the wrong place on the volume rendering method (VR) with 3D time-of-flight MRA (3D-TOF-MRA) with 3-Tesla MR system. In 3D-TOF-MRA, it is often difficult to observe the origin of the branching vessel, but it is unusual for it to be observed in the wrong place. In the planning of interventional treatment and surgical procedures, false recognition, as in the unique case in the present report, is a serious problem. Decisions based only on VR with 3D-TOF-MRA can be a cause of suboptimal selection in clinical treatment.
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Reducing wrong patient selection errors: exploring the design space of user interface techniques.
Sopan, Awalin; Plaisant, Catherine; Powsner, Seth; Shneiderman, Ben
2014-01-01
Wrong patient selection errors are a major issue for patient safety; from ordering medication to performing surgery, the stakes are high. Widespread adoption of Electronic Health Record (EHR) and Computerized Provider Order Entry (CPOE) systems makes patient selection using a computer screen a frequent task for clinicians. Careful design of the user interface can help mitigate the problem by helping providers recall their patients' identities, accurately select their names, and spot errors before orders are submitted. We propose a catalog of twenty seven distinct user interface techniques, organized according to a task analysis. An associated video demonstrates eighteen of those techniques. EHR designers who consider a wider range of human-computer interaction techniques could reduce selection errors, but verification of efficacy is still needed.
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[Maturation diagnosis in full term hypotrophic fetuses].
Scharnke, H D; Gartzke, J; Fleischer, G; Isbruch, E
1977-01-01
Foam-Test by Clements is a valuable method for determining the foetus maturity of lungs. We introduce this test along with other parameters for the maturity-diagnosis since one year. In 15% result, the Foam-Test was not applicable because of blood, or meconic amniotic fluid, other wise wrong negative and in 0% wrong positive results. By unmatured child, there was doubtable results with Foam-Test. Since it is important to determine the early delivery of unmatured children, particularly the case of foetus maturity of lungs must be exact, we therefore decided to use the Lecithin/Sphingomyelinquotients in some cases. The results of Lecithin/Sphingomyelinquotient in unmatured children are almost with the approximated date under two. From this, one must deduce from these children, that the intrauterine unmatured lungs lately took place.
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What I got wrong about shelterin.
de Lange, Titia
2018-05-24
The ASBMB 2018 Bert and Natalie Vallee award in Biomedical Sciences honors our work on shelterin, a protein complex that helps cells distinguish the chromosome ends from sites of DNA damage. Shelterin protects telomeres from all aspects of the DNA damage response, including ATM and ATR serine/threonine kinase signaling and several forms of double-strand break repair. Today, this six-subunit protein complex could easily be identified in one single proteomics step. But it took us more than 15 years to piece the entire shelterin complex together, one protein at a time. Although we did a lot of things right, here I tell the story of shelterin's discovery with an emphasis on the things that I got wrong along the way. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.
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Physics on the Bus—How About Physics on Your Bus?
NASA Astrophysics Data System (ADS)
Romer, Robert H.
2004-12-01
Riders on the buses of UMass Transit (here in the "Five-College" area) and of the University of Georgia transit system have something other than the usual "Please don't eat on the bus" placards to read—simple physics questions in the overhead advertising racks, with appealing cats and dogs posing questions, giving partial answers (some flat-out wrong, some partially correct), ending up with "What do you think? … Visit our website." One sample is given below; others can be viewed at http://www.amherst.edu/˜physicsqanda. (More often than not, the dog gets it wrong; I'm a cat person.) This project was begun in collaboration with John King and was inspired by one of the many ideas described in his 2000 Oersted Medal address.
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NASA Astrophysics Data System (ADS)
Mika, J.; Verőci, Zs.; Fülöp, A.; Hirsch, T.; Dúll, A.
2009-04-01
Weather disturbances like fronts, influence human biorhythm, our biological balance becomes manipulated, and adaptation mechanisms are impaired. Our working hypothesis is that even the best chess players of the world are not exceptions from this rule. As their movements on the chess board, as well as the best possible ones, if they missed to make, are already assessed by computers objectively, we can use this game as a model of intellectual performance. By the date of the Abstract edition, 580 wrong chess moves were selected with the threshold of over 1/3 peasant to be lost. I.e. this is the minimum difference between the assessment of the positions after the best possible and the really performed move. (Obviously, all moves both sides in ca. the same number of games were checked, i.e. over 35,000 moves were assessed.) For assessing the moves, the most popular database is MegaDatabase 2006 (ChessBase- Hamburg), Chess Informant Expert from Chess Informant Beograd and the program ChessBase 9.0 together with the engines Fritz 10, Rybka 2.3, Junior 10. First of all the World Chess Champions, Karpov, Kasparov, Kramnik and Anand were examined played in the traditional big chess tournaments, category 19th and more (average rating more the 2701 Elo-points). We further selected the games by the top-ranked players of the world between 2005 and 2008. This selection is explained by the likely fact that they make the less wrong moves for simply the lack of chess understanding, moreover, as full professionals, they allow the minimum of non-weather disturbing circumstances (e.g. imperfect sleeping before the game, etc.). Their moves were selected as (i) very wrong move with more than 3.0 differences, (i.e. unforced loss of a knight, or a bishop, (ii) very weak move with an assessment of 1.0-3.0, (i.e. unforced loss between one peasant and one bishop/knight) and (iii) weak move with less than 1.0 assessment of the passed chance, or unforced loss of less than one peasant. These new data on mental behavior are statistically compared to a common set of diurnal meteorological parameters, including various near-surface and lower troposphere temperature values, sea-level pressures, relative topographies, precipitation amount and existence (duration) and wind speed. The data and the aerologic fields are retrieved from the ECMWF ERA-40 (until 2002) and ECMWF operational analysis (after 2002) for the date and site of the individual mistakes. According to our preliminary results, the wrong moves fall to the lower or higher than average parts of the diurnal mean temperature distribution. Even if we should be careful because of the well known bi-modal distribution of the temperature (if not performing any seasonal correction), but, even after considering these differences the best players make more frequent mistakes in case of higher or lower than normal temperature situations. Another preliminary experience is that decreasing tendency of the RT850/500 hPa relative topography also indicates increase of wrong and very wrong moves. After performing this analysis, the result will be compared to the better known empirical paradigms of medical meteorology and experimental psychology.
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Knowles, D
Managing clinical risk involves all staff with clinical and managerial responsibilities. This article draws attention to some key steps in risk management and ways to deal with the problems when things do go wrong.
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... What Can go Wrong Some people get arthritis (ar-THRY-tis). The term arthritis is often used ... different forms of arthritis: Osteoarthritis (AH-stee-oh-ar-THRY-tis) is the most common type of ...
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Carbohydrate Metabolism Disorders
Metabolism is the process your body uses to make energy from the food you eat. Food is ... disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally ...
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... help figure out what's wrong. A specialist in learning disabilities knows a lot about learning problems that kids ... good grade; it's to spot problems. Discovering a learning disability is the first step toward getting help that ...
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... the wrong times. This damage is called diabetic neuropathy. Over half of people with diabetes get it. ... change positions quickly Your doctor will diagnose diabetic neuropathy with a physical exam and nerve tests. Controlling ...
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... brain, spinal cord, and nerves make up the nervous system. Together they control all the workings of the ... something goes wrong with a part of your nervous system, you can have trouble moving, speaking, swallowing, breathing, ...
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28 CFR 104.4 - Personal Representative.
Code of Federal Regulations, 2014 CFR
2014-07-01
... spouses, children, other dependents, and parents), to the executor, administrator, and beneficiaries of... an award or to have a cause of action to recover damages relating to the wrongful death of the...
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28 CFR 104.4 - Personal Representative.
Code of Federal Regulations, 2011 CFR
2011-07-01
..., children, other dependents, and parents), to the executor, administrator, and beneficiaries of the decedent... to have a cause of action to recover damages relating to the wrongful death of the decedent. Personal...
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28 CFR 104.4 - Personal Representative.
Code of Federal Regulations, 2012 CFR
2012-07-01
... spouses, children, other dependents, and parents), to the executor, administrator, and beneficiaries of... an award or to have a cause of action to recover damages relating to the wrongful death of the...
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28 CFR 104.4 - Personal Representative.
Code of Federal Regulations, 2010 CFR
2010-07-01
..., children, other dependents, and parents), to the executor, administrator, and beneficiaries of the decedent... to have a cause of action to recover damages relating to the wrongful death of the decedent. Personal...
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28 CFR 104.4 - Personal Representative.
Code of Federal Regulations, 2013 CFR
2013-07-01
... spouses, children, other dependents, and parents), to the executor, administrator, and beneficiaries of... an award or to have a cause of action to recover damages relating to the wrongful death of the...
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... during water tank construction. He wore a charcoal filter respirator while sandblasting, but it was the wrong ... properly fitted and selected respirator (e.g. particulate filter or airline supplied air respirator) designated for protection ...
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Otake, Y.; Schafer, S.; Stayman, J. W.; Zbijewski, W.; Kleinszig, G.; Graumann, R.; Khanna, A. J.; Siewerdsen, J. H.
2012-01-01
Surgical targeting of the incorrect vertebral level (“wrong-level” surgery) is among the more common wrong-site surgical errors, attributed primarily to a lack of uniquely identifiable radiographic landmarks in the mid-thoracic spine. Conventional localization method involves manual counting of vertebral bodies under fluoroscopy, is prone to human error, and carries additional time and dose. We propose an image registration and visualization system (referred to as LevelCheck), for decision support in spine surgery by automatically labeling vertebral levels in fluoroscopy using a GPU-accelerated, intensity-based 3D-2D (viz., CT-to-fluoroscopy) registration. A gradient information (GI) similarity metric and CMA-ES optimizer were chosen due to their robustness and inherent suitability for parallelization. Simulation studies involved 10 patient CT datasets from which 50,000 simulated fluoroscopic images were generated from C-arm poses selected to approximate C-arm operator and positioning variability. Physical experiments used an anthropomorphic chest phantom imaged under real fluoroscopy. The registration accuracy was evaluated as the mean projection distance (mPD) between the estimated and true center of vertebral levels. Trials were defined as successful if the estimated position was within the projection of the vertebral body (viz., mPD < 5mm). Simulation studies showed a success rate of 99.998% (1 failure in 50,000 trials) and computation time of 4.7 sec on a midrange GPU. Analysis of failure modes identified cases of false local optima in the search space arising from longitudinal periodicity in vertebral structures. Physical experiments demonstrated robustness of the algorithm against quantum noise and x-ray scatter. The ability to automatically localize target anatomy in fluoroscopy in near-real-time could be valuable in reducing the occurrence of wrong-site surgery while helping to reduce radiation exposure. The method is applicable beyond the specific case of vertebral labeling, since any structure defined in pre-operative (or intra-operative) CT or cone-beam CT can be automatically registered to the fluoroscopic scene. PMID:22864366
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Björkstén, Karin Sparring; Bergqvist, Monica; Andersén-Karlsson, Eva; Benson, Lina; Ulfvarson, Johanna
2016-08-24
Many studies address the prevalence of medication errors but few address medication errors serious enough to be regarded as malpractice. Other studies have analyzed the individual and system contributory factor leading to a medication error. Nurses have a key role in medication administration, and there are contradictory reports on the nurses' work experience in relation to the risk and type for medication errors. All medication errors where a nurse was held responsible for malpractice (n = 585) during 11 years in Sweden were included. A qualitative content analysis and classification according to the type and the individual and system contributory factors was made. In order to test for possible differences between nurses' work experience and associations within and between the errors and contributory factors, Fisher's exact test was used, and Cohen's kappa (k) was performed to estimate the magnitude and direction of the associations. There were a total of 613 medication errors in the 585 cases, the most common being "Wrong dose" (41 %), "Wrong patient" (13 %) and "Omission of drug" (12 %). In 95 % of the cases, an average of 1.4 individual contributory factors was found; the most common being "Negligence, forgetfulness or lack of attentiveness" (68 %), "Proper protocol not followed" (25 %), "Lack of knowledge" (13 %) and "Practice beyond scope" (12 %). In 78 % of the cases, an average of 1.7 system contributory factors was found; the most common being "Role overload" (36 %), "Unclear communication or orders" (30 %) and "Lack of adequate access to guidelines or unclear organisational routines" (30 %). The errors "Wrong patient due to mix-up of patients" and "Wrong route" and the contributory factors "Lack of knowledge" and "Negligence, forgetfulness or lack of attentiveness" were more common in less experienced nurses. The experienced nurses were more prone to "Practice beyond scope of practice" and to make errors in spite of "Lack of adequate access to guidelines or unclear organisational routines". Medication errors regarded as malpractice in Sweden were of the same character as medication errors worldwide. A complex interplay between individual and system factors often contributed to the errors.
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NASA Technical Reports Server (NTRS)
Yee, Helen M. C.; Kotov, D. V.; Wang, Wei; Shu, Chi-Wang
2013-01-01
The goal of this paper is to relate numerical dissipations that are inherited in high order shock-capturing schemes with the onset of wrong propagation speed of discontinuities. For pointwise evaluation of the source term, previous studies indicated that the phenomenon of wrong propagation speed of discontinuities is connected with the smearing of the discontinuity caused by the discretization of the advection term. The smearing introduces a nonequilibrium state into the calculation. Thus as soon as a nonequilibrium value is introduced in this manner, the source term turns on and immediately restores equilibrium, while at the same time shifting the discontinuity to a cell boundary. The present study is to show that the degree of wrong propagation speed of discontinuities is highly dependent on the accuracy of the numerical method. The manner in which the smearing of discontinuities is contained by the numerical method and the overall amount of numerical dissipation being employed play major roles. Moreover, employing finite time steps and grid spacings that are below the standard Courant-Friedrich-Levy (CFL) limit on shockcapturing methods for compressible Euler and Navier-Stokes equations containing stiff reacting source terms and discontinuities reveals surprising counter-intuitive results. Unlike non-reacting flows, for stiff reactions with discontinuities, employing a time step and grid spacing that are below the CFL limit (based on the homogeneous part or non-reacting part of the governing equations) does not guarantee a correct solution of the chosen governing equations. Instead, depending on the numerical method, time step and grid spacing, the numerical simulation may lead to (a) the correct solution (within the truncation error of the scheme), (b) a divergent solution, (c) a wrong propagation speed of discontinuities solution or (d) other spurious solutions that are solutions of the discretized counterparts but are not solutions of the governing equations. The present investigation for three very different stiff system cases confirms some of the findings of Lafon & Yee (1996) and LeVeque & Yee (1990) for a model scalar PDE. The findings might shed some light on the reported difficulties in numerical combustion and problems with stiff nonlinear (homogeneous) source terms and discontinuities in general.
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Cabilan, C J; Hughes, James A; Shannon, Carl
2017-12-01
To describe the contextual, modal and psychological classification of medication errors in the emergency department to know the factors associated with the reported medication errors. The causes of medication errors are unique in every clinical setting; hence, error minimisation strategies are not always effective. For this reason, it is fundamental to understand the causes specific to the emergency department so that targeted strategies can be implemented. Retrospective analysis of reported medication errors in the emergency department. All voluntarily staff-reported medication-related incidents from 2010-2015 from the hospital's electronic incident management system were retrieved for analysis. Contextual classification involved the time, place and the type of medications involved. Modal classification pertained to the stage and issue (e.g. wrong medication, wrong patient). Psychological classification categorised the errors in planning (knowledge-based and rule-based errors) and skill (slips and lapses). There were 405 errors reported. Most errors occurred in the acute care area, short-stay unit and resuscitation area, during the busiest shifts (0800-1559, 1600-2259). Half of the errors involved high-alert medications. Many of the errors occurred during administration (62·7%), prescribing (28·6%) and commonly during both stages (18·5%). Wrong dose, wrong medication and omission were the issues that dominated. Knowledge-based errors characterised the errors that occurred in prescribing and administration. The highest proportion of slips (79·5%) and lapses (76·1%) occurred during medication administration. It is likely that some of the errors occurred due to the lack of adherence to safety protocols. Technology such as computerised prescribing, barcode medication administration and reminder systems could potentially decrease the medication errors in the emergency department. There was a possibility that some of the errors could be prevented if safety protocols were adhered to, which highlights the need to also address clinicians' attitudes towards safety. Technology can be implemented to help minimise errors in the ED, but this must be coupled with efforts to enhance the culture of safety. © 2017 John Wiley & Sons Ltd.
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2014-01-01
Background Honesty and integrity are key attributes of an ethically competent physician. However, academic misconduct, which includes but is not limited to plagiarism, cheating, and falsifying documentation, is common in medical colleges across the world. The purpose of this study is to describe differences in the self-reported attitudes and behaviours of medical students regarding academic misconduct depending on gender, year of study and type of medical institution in Pakistan. Methods A cross sectional study was conducted with medical students from one private and one public sector medical college. A pre-coded questionnaire about attitudes and behaviours regarding plagiarism, lying, cheating and falsifying documentation was completed anonymously by the students. Results A total of 465 medical students filled the questionnaire. 53% of private medical college students reported that they recognize copying an assignment verbatim and listing sources as references as wrong compared to 35% of public medical college students. 26% of private medical college students self-report this behaviour as compared to 42% of public medical college students. 22% of private versus 15% of public medical college students and 21% of students in clinical years compared to 17% in basic science years admit to submitting a fake medical certificate to justify an absence. 87% of students at a private medical college believe that cheating in an examination is wrong as compared to 66% of public medical college students and 24% self-report this behaviour in the former group as compared to 41% in the latter. 63% of clinical year students identify cheating as wrong compared to 89% of their junior colleagues. 71% of male versus 84% of female respondents believe that cheating is wrong and 42% of males compared to 23% of females admit to cheating. Conclusions There are significant differences in medical students’ attitudes and behaviours towards plagiarism, lying, cheating and stealing by gender, seniority status and type of institution. The ability to identify acts of academic misconduct does not deter students from engaging in the behaviour themselves, as evidenced by self-reporting. PMID:24885991
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Ghias, Kulsoom; Lakho, Ghulam Rehmani; Asim, Hamna; Azam, Iqbal Syed; Saeed, Sheikh Abdul
2014-05-29
Honesty and integrity are key attributes of an ethically competent physician. However, academic misconduct, which includes but is not limited to plagiarism, cheating, and falsifying documentation, is common in medical colleges across the world. The purpose of this study is to describe differences in the self-reported attitudes and behaviours of medical students regarding academic misconduct depending on gender, year of study and type of medical institution in Pakistan. A cross sectional study was conducted with medical students from one private and one public sector medical college. A pre-coded questionnaire about attitudes and behaviours regarding plagiarism, lying, cheating and falsifying documentation was completed anonymously by the students. A total of 465 medical students filled the questionnaire. 53% of private medical college students reported that they recognize copying an assignment verbatim and listing sources as references as wrong compared to 35% of public medical college students. 26% of private medical college students self-report this behaviour as compared to 42% of public medical college students. 22% of private versus 15% of public medical college students and 21% of students in clinical years compared to 17% in basic science years admit to submitting a fake medical certificate to justify an absence. 87% of students at a private medical college believe that cheating in an examination is wrong as compared to 66% of public medical college students and 24% self-report this behaviour in the former group as compared to 41% in the latter. 63% of clinical year students identify cheating as wrong compared to 89% of their junior colleagues. 71% of male versus 84% of female respondents believe that cheating is wrong and 42% of males compared to 23% of females admit to cheating. There are significant differences in medical students' attitudes and behaviours towards plagiarism, lying, cheating and stealing by gender, seniority status and type of institution. The ability to identify acts of academic misconduct does not deter students from engaging in the behaviour themselves, as evidenced by self-reporting.
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The Relationships of Nurse Staffing Level and Work Environment With Patient Adverse Events.
Cho, Eunhee; Chin, Dal Lae; Kim, Sinhye; Hong, OiSaeng
2016-01-01
The purpose of this study was to examine the relationships of nurse staffing level and work environment with patient adverse events. This cross-sectional study used a combination of nurse survey data (N = 4,864 nurses), facility data (N = 58 hospitals), and patient hospital discharge data (N = 113,426 patients) in South Korea. The three most commonly nurse-reported adverse events included administration of the wrong medication or dose to a patient, pressure ulcers, and injury from a fall after admission. Multilevel ordinal logistic regression was employed to explore the relationships of nurse staffing level (number of patients assigned to a nurse) and work environment (Practice Environment Scale of the Nursing Work Index) with patient adverse events after controlling for nurse, hospital, and patient characteristics. A larger number of patients per nurse was significantly associated with a greater incidence of administration of the wrong medication or dose (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 1.007-1.016), pressure ulcer (OR = 1.01, 95% CI = 1.007-1.016), and patient falls with injury (OR = 1.02, 95% CI = 1.013-1.022). A better work environment had a significant inverse relationship with adverse events; the odds of reporting a higher incidence of adverse events were 45% lower for administration of the wrong medication or dose (OR = 0.55, 95% CI = 0.400-0.758), followed by 39% lower for pressure ulcer (OR = 0.61, 95% CI = 0.449-0.834) and 32% lower for falls with injury after admission (OR = 0.68, 95% CI = 0.490-0.939). This study found that a larger number of patients per nurse and poor work environment increase the incidence of patient adverse events, such as administration of the wrong medication or dose to a patient, pressure ulcers, and injury from falling after admission. The findings suggest that South Korean hospitals could prevent patient adverse events by improving nurse staffing and work environment. Healthcare strategies and efforts to modify adequate nurse staffing levels and better work environments for nurses are needed to improve patient outcomes. © 2015 Sigma Theta Tau International.
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Evaluative-feedback stimuli selectively activate the self-related brain area: an fMRI study.
Pan, Xiaohong; Hu, Yang; Li, Lei; Li, Jianqi
2009-11-06
Evaluative-feedback, occurring in our daily life, generally contains subjective appraisal of one's specific abilities and personality characteristics besides objective right-or-wrong information. Traditional psychological researches have proved it to be important in building up one's self-concept; however, the neural basis underlying its cognitive processing remains unclear. The present neuroimaging study revealed the mechanism of evaluative-feedback processing at the neural level. 19 healthy Chinese subjects participated in this experiment, and completed the time-estimation task to better their performance according to four types of feedback, namely positive evaluative- and performance-feedback as well as negative evaluative- and performance-feedback. Neuroimaging findings showed that evaluative- rather than performance-feedback can induce increased activities mainly distributed in the cortical midline structures (CMS), including medial prefrontal cortex (BA 8/9)/anterior cigulate cortex (ACC, BA 20), precuneus (BA 7/31) adjacent to posterior cingulate gyrus (PCC, BA 23) of both hemispheres, as well as right inferior lobule (BA 40). This phenomenon can provide evidence that evaluative-feedback may significantly elicit the self-related processing in our brain. In addition, our results also revealed that more brain areas, particularly some self-related neural substrates were activated by the positive evaluative-feedback, in comparative with the negative one. In sum, this study suggested that evaluative-feedback was closely correlated with the self-concept processing, which distinguished it from the performance-feedback.
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5 CFR 890.1020 - Determining length of debarment based on false, wrongful, or deceptive claims.
Code of Federal Regulations, 2011 CFR
2011-01-01
... PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1020...
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5 CFR 890.1020 - Determining length of debarment based on false, wrongful, or deceptive claims.
Code of Federal Regulations, 2014 CFR
2014-01-01
... PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1020...
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Physics that Textbook Writers Usually Get Wrong: III.
ERIC Educational Resources Information Center
Bauman, Robert P.
1992-01-01
Examines inconsistencies in science textbook discussions of vector quantities and force. Provides illustrations of textbook inconsistencies related to Newton's laws of motion and the concepts of centrifugal and coriolis force. (MDH)
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... risk of injury almost as much as playing football without shoulder pads? Using the wrong — or not ... helmets : They're important for sports such as football , hockey, baseball, softball, biking, skateboarding, inline skating, skiing , ...
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... care provider about what's wrong and how to cure it is one of the most important aspects ... you use, such as herbs or supplements. Any allergies you may have, especially to medications. A description ...
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5 CFR 890.1020 - Determining length of debarment based on false, wrongful, or deceptive claims.
Code of Federal Regulations, 2010 CFR
2010-01-01
... PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1020...
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32 CFR 536.63 - Settlement agreements.
Code of Federal Regulations, 2010 CFR
2010-07-01
... required. Court approval is required in a wrongful death claim, or where the claimant is a minor or... citation of the statute will be provided and accompany the payment documents. (2) Attorney representation...
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5 CFR 890.1020 - Determining length of debarment based on false, wrongful, or deceptive claims.
Code of Federal Regulations, 2013 CFR
2013-01-01
... PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1020...
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Mars Terraforming — The Wrong Way
NASA Astrophysics Data System (ADS)
Yakovlev, V. V.
2017-02-01
Because of the damage that will injure the human physiology, the colonies on Mars and satellites are unpromising. The applied scientific elaborations connected with the independent biospheres creation with artificial gravitation should be the priority.
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Forgiveness: Letting Go of Grudges and Bitterness
... Forgiveness can even lead to feelings of understanding, empathy and compassion for the one who hurt you. ... admit wrong. If you find yourself stuck: Practice empathy. Try seeing the situation from the other person's ...
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13 CFR 114.101 - What do these regulations cover?
Code of Federal Regulations, 2010 CFR
2010-01-01
... CLAIMS UNDER THE FEDERAL TORT CLAIMS ACT AND REPRESENTATION AND INDEMNIFICATION OF SBA EMPLOYEES... property, personal injury, or death arising from the negligent or wrongful act or omission of any SBA...
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Return on Investment: Accounting for Training.
ERIC Educational Resources Information Center
Carnevale, Anthony P.; Schulz, Eric R.
1990-01-01
This special report looks at what is wrong with traditional accounting for training and offers a new model--the consensus accounting model--to help measure the costs and benefits of training. (60 references) (Author)
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Building Mathematical Models of Simple Harmonic and Damped Motion.
ERIC Educational Resources Information Center
Edwards, Thomas
1995-01-01
By developing a sequence of mathematical models of harmonic motion, shows that mathematical models are not right or wrong, but instead are better or poorer representations of the problem situation. (MKR)
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... on the head causes brain cancer or that bad people get cancer. This isn't true! Kids don't do anything wrong to get cancer. But some unhealthy habits, especially cigarette smoking or drinking too much alcohol ...
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Comprehensive Psychiatric Evaluation
... wrong? What is the diagnosis? Does my child need additional assessment and/or testing (medical, psychological etc.)? What are your recommendations? How can the family help? Does my child need treatment? Do I need treatment? What will treatment ...
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33 CFR 25.405 - Claims not payable.
Code of Federal Regulations, 2010 CFR
2010-07-01
... wrongful act of the claimant, claimant's agent, or claimant's employee, unless comparative negligence is applicable under local law; (d) Is for death or personal injury of a United States employee for whom benefits...
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Genetics Home Reference: Dent disease
... 20. Review. Citation on PubMed Wrong OM, Norden AG, Feest TG. Dent's disease; a familial proximal renal ... qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Subscribe Customer Support USA. ...
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Anomalous flow deflection at earth's low-Alfvén-Mach-Number bow shock.
Nishino, Masaki N; Fujimoto, Masaki; Phan, Tai-Duc; Mukai, Toshifumi; Saito, Yoshifumi; Kuznetsova, Masha M; Rastätter, Lutz
2008-08-08
Earth's magnetosphere is an obstacle to the supersonic solar wind and the bow shock is formed in the front side of it. In ordinary hydrodynamics, the flow decelerated at the shock is diverted around the obstacle symmetrically about the Earth-Sun line, which is indeed observed in the magnetosheath most of the time. Here we show a case under a very low-density solar wind in which duskward flow was observed in the dawnside magnetosheath. A Rankine-Hugoniot test shows that the magnetic effect is crucial for this "wrong flow" to appear. A full three-dimensional magnetohydrodynamics (MHD) simulation of the situation confirming this interpretation and earlier simulations is also performed. It is illustrated that in addition to the "wrong flow" feature, various peculiar characteristics appear in the global picture of the MHD flow interaction with the obstacle.
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Fıçıcıoğlu, Sezin; Can, Nuray; Tutuğ, Busem
2018-01-01
The differential diagnosis of chronic ulcers covers a wide range of diseases and poses a diagnostic challenge. Subcutaneous ischemic arteriolosclerosis can lead to local ischaemia and ulceration as a result of arteriolar narrowing and reduction of tissue perfusion. This pathophysiological feature can be seen in eutrophication (nonuremic calciphylaxis) in morbid obesity, hypertensive ischemic leg ulcer (Martorell ulcer) and calciphylaxis in chronic renal insufficiency. All of the ulcers happened in this way can be wrongly diagnosed as pyoderma gangrenosum because of clinical similarity and inadequate biopsies. We report a case of chronic ulcer due to subcutaneous arteriolosclerosis in morbid obesity, wrongly diagnosed as pyoderma gangrenosum. It can be detrimental to misdiagnose the ulcers due to subcutaneous arteriolosclerosis as pyoderma gangrenosum since they need a diametrically different approach. PMID:29887980
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Neither aider nor abettor be: attorneys become prosecutorial targets for federal healthcare crimes.
Schmidt, M M
1999-01-01
Attorneys representing healthcare entities are not immune to federal criminal prosecution for the assistance that they give their clients. This Article focuses on potential attorney liability for aiding and abetting a client's violation of law. The author examines the securities, tax, and white-collar crime fields for guidance regarding the interpretation and application of the federal aiding and abetting statute to attorneys practicing in the health law field. Based on these analogous areas, and upon the federal criminal statutes applicable in the healthcare field, he recommends steps that can be taken to minimize the possibility of aiding and abetting liability. In addition, he recommends that the courts require a prosecutorial showing of both actual knowledge of wrong-doing and wrongful intent before imposing aider and abettor liability upon health law practitioners.
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The deprivation argument against abortion.
Stretton, Dean
2004-04-01
The most plausible pro-life argument claims that abortion is seriously wrong because it deprives the foetus of something valuable. This paper examines two recent versions of this argument. Don Marquis's version takes the valuable thing to be a 'future like ours', a future containing valuable experiences and activities. Jim Stone's version takes the valuable thing to be a future containing conscious goods, which it is the foetus's biological nature to make itself have. I give three grounds for rejecting these arguments. First, they lead to unacceptable inequalities in the wrongness of killing. Second, they lead to counterintuitive results in a range of imaginary cases. Third, they ignore the role of psychological connectedness in determining the magnitude or seriousness of deprivation-based harms: because the foetus is only weakly psychologically connected to its own future, it cannot be seriously harmed by being deprived of that future.
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NASA Astrophysics Data System (ADS)
Cummings, Karen; Marx, Jeffrey D.
2010-10-01
We have developed an assessment of students' ability to solve standard textbook style problems and are currently engaged in the validation and revision process. The assessment covers the topics of force and motion, conservation of momentum and conservation of energy at a level consistent with most calculus-based, introductory physics courses. This tool is discussed in more detail in an accompanying paper by Marx and Cummings. [1] Here we present preliminary beta-test data collected at four schools during the 2009/2010 academic year. Data include both pre- and post-instruction results for introductory physics courses as well as results for physics majors in later years. In addition, we present evidence that right/wrong grading may well be a perfectly acceptable grading procedure for a course-level assessment of this type.
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NASA Astrophysics Data System (ADS)
Szent-Györgyi, Andrew
It was always a pleasure to remember your husband Gribov, and how much it meant to spend time with him. Although I am not a physicist, it is clear what a great scientist Volodya was, innovative and deep. At the same time he was an extremely nice person. He was not only a great scientist, but a person who, apart from his great contributions to physics, was also able to clearly see what was right and what was wrong in life. His presence, his opinion about people and science was always a delightful experience. Albert was the only other person I have known well who also clearly knew what was right and what was wrong, and was willing to stand up for his principles. We are lucky to have known and lived with such great individuals. Note from Publisher: This article contains the abstract only.
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"Black art" of thin film coating: why this term is used and how to change this mind-set
NASA Astrophysics Data System (ADS)
Jansen, S. W.; Hatchett, Philip J.; Hughes, S. W.; Jones, D. Paul; Gibson, Desmond R.
1996-08-01
The words 'black art' are often associated with thin film coating. We cast our spell on a coating plant and, as if by magic, the glass is transformed. The problem is that the spell sometimes fails and we end up with stone instead of gold. When we ask the magician (coating technician) what went wrong, the answer is all too often 'I did it exactly the same way as the last time'. This creates the perception that thin film coating is a black art because clearly something different did happen. What we don't know is which of the multitude of parameters went wrong, and often the only way to find out is through a process of elimination. This is very costly to the industry both in monetary value and image.
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Understanding and responding when things go wrong: key principles for primary care educators.
McNab, Duncan; Bowie, Paul; Ross, Alastair; Morrison, Jill
2016-07-01
Learning from events with unwanted outcomes is an important part of workplace based education and providing evidence for medical appraisal and revalidation. It has been suggested that adopting a 'systems approach' could enhance learning and effective change. We believe the following key principles should be understood by all healthcare staff, especially those with a role in developing and delivering educational content for safety and improvement in primary care. When things go wrong, professional accountability involves accepting there has been a problem, apologising if necessary and committing to learn and change. This is easier in a 'Just Culture' where wilful disregard of safe practice is not tolerated but where decisions commensurate with training and experience do not result in blame and punishment. People usually attempt to achieve successful outcomes, but when things go wrong the contribution of hindsight and attribution bias as well as a lack of understanding of conditions and available information (local rationality) can lead to inappropriately blame 'human error'. System complexity makes reduction into component parts difficult; thus attempting to 'find-and-fix' malfunctioning components may not always be a valid approach. Finally, performance variability by staff is often needed to meet demands or cope with resource constraints. We believe understanding these core principles is a necessary precursor to adopting a 'systems approach' that can increase learning and reduce the damaging effects on morale when 'human error' is blamed. This may result in 'human error' becoming the starting point of an investigation and not the endpoint.
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Diffusing aviation innovations in a hospital in The Netherlands.
de Korne, Dirk F; van Wijngaarden, Jeroen D H; Hiddema, U Frans; Bleeker, Fred G; Pronovost, Peter J; Klazinga, Niek S
2010-08-01
Many authors have advocated the diffusion of innovations from other high-risk industries into health care to improve safety. The aviation industry is comparable to health care because of its similarities in (a) the use of technology, (b) the requirement of highly specialized professional teams, and (c) the existence of risk and uncertainties. For almost 20 years, The Rotterdam Eye Hospital (Rotterdam, the Netherlands) has been engaged in diffusing several innovations adapted from aviation. A case-study methodology was used to assess the application of innovations in the hospital, with a focus on the context and the detailed mechanism for each innovation. Data on hospital performance outcomes were abstracted from the hospital information data management system, quality and safety reports, and the incident reporting system. Information on the innovations was obtained from a document search; observations; and semistructured, face-to-face interviews. Aviation industry-based innovations diffused into patient care processes were as follows: patient planning and booking system, taxi service/valet parking, risk analysis (as applied to wrong-site surgery), time-out procedure (also for wrong-site surgery), Crew Resource Management training, and black box. Observations indicated that the innovations had a positive effect on quality and safety in the hospital: Waiting times were reduced, work processes became more standardized, the number of wrong-site surgeries decreased, and awareness of patient safety was heightened. A near-20-year experience with aviation-based innovation suggests that hospitals start with relatively simple innovations and use a systematic approach toward the goal of improving safety.
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How Dental Team Members describe Adverse Events
Maramaldi, Peter; Walji, Muhammad F.; White, Joel; Etoulu, Jini; Kahn, Maria; Vaderhobli, Ram; Kwatra, Japneet; Delattre, Veronique F.; Hebballi, Nutan B.; Stewart, Denice; Kent, Karla; Yansane, Alfa; Ramoni, Rachel B.; Kalenderian, Elsbeth
2016-01-01
Background There is increased recognition that patients suffer adverse events (AEs) or harm caused by treatments in dentistry, and little is known about how dental providers describe these events. Understanding how providers view AEs is essential to building a safer environment in dental practice. Methods Dental providers and domain experts were interviewed through focus groups and in-depth interviews and asked to identify the types of AEs that may occur in dental settings. Results The first order listing of the interview and focus group findings yielded 1,514 items that included both causes and AEs. 632 causes were coded into one of the eight categories of the Eindhoven classification. 882 AEs were coded into 12 categories of a newly developed dental AE classification. Inter-rater reliability was moderate among coders. The list was reanalyzed and duplicate items were removed leaving a total of 747 unique AEs and 540 causes. The most frequently identified AE types were “Aspiration/ingestion” at 14% (n=142), “Wrong-site, wrong-procedure, wrong-patient errors” at 13%, “Hard tissue damage” at 13%, and “Soft tissue damage” at 12%. Conclusions Dental providers identified a large and diverse list of AEs. These events ranged from “death due to cardiac arrest” to “jaw fatigue from lengthy procedures”. Practical Implications Identifying threats to patient safety is a key element of improving dental patient safety. An inventory of dental AEs underpins efforts to track, prevent, and mitigate these events. PMID:27269376
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Complacency and Automation Bias in the Use of Imperfect Automation.
Wickens, Christopher D; Clegg, Benjamin A; Vieane, Alex Z; Sebok, Angelia L
2015-08-01
We examine the effects of two different kinds of decision-aiding automation errors on human-automation interaction (HAI), occurring at the first failure following repeated exposure to correctly functioning automation. The two errors are incorrect advice, triggering the automation bias, and missing advice, reflecting complacency. Contrasts between analogous automation errors in alerting systems, rather than decision aiding, have revealed that alerting false alarms are more problematic to HAI than alerting misses are. Prior research in decision aiding, although contrasting the two aiding errors (incorrect vs. missing), has confounded error expectancy. Participants performed an environmental process control simulation with and without decision aiding. For those with the aid, automation dependence was created through several trials of perfect aiding performance, and an unexpected automation error was then imposed in which automation was either gone (one group) or wrong (a second group). A control group received no automation support. The correct aid supported faster and more accurate diagnosis and lower workload. The aid failure degraded all three variables, but "automation wrong" had a much greater effect on accuracy, reflecting the automation bias, than did "automation gone," reflecting the impact of complacency. Some complacency was manifested for automation gone, by a longer latency and more modest reduction in accuracy. Automation wrong, creating the automation bias, appears to be a more problematic form of automation error than automation gone, reflecting complacency. Decision-aiding automation should indicate its lower degree of confidence in uncertain environments to avoid the automation bias. © 2015, Human Factors and Ergonomics Society.
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Does a normal foetus really have a future of value? A reply to Marquis.
Lovering, Robert P
2005-04-01
The traditional approach to the abortion debate revolves around numerous issues, such as whether the foetus is a person, whether the foetus has rights, and more. Don Marquis suggests that this traditional approach leads to a standoff and that the abortion debate 'requires a different strategy.' Hence his 'future of value' strategy, which is summarized as follows: (1) A normal foetus has a future of value. (2) Depriving a normal foetus of a future of value imposes a misfortune on it. (3) Imposing a misfortune on a normal foetus is prima facie wrong. (4) Therefore, depriving a normal foetus of a future of value is prima facie wrong. (5) Killing a normal foetus deprives it of a future value. (6) Therefore, killing a normal foetus is prima facie wrong. In this paper, I argue that Marquis's strategy is not different since it involves the concept of person--a concept deeply rooted in the traditional approach. Specifically, I argue that futures are valuable insofar as they are not only dominated by goods of consciousness, but are experienced by psychologically continuous persons. Moreover, I argue that his strategy is not sound since premise (1) is false. Specifically, I argue that a normal foetus, at least during the first trimester, is not a person. Thus, during that stage of development it is not capable of experiencing its future as a psychologically continuous person and, hence, it does not have a future of value.
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44 CFR 11.15 - Authority to adjust, determine, compromise and settle.
Code of Federal Regulations, 2010 CFR
2010-10-01
... MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL CLAIMS Administrative Claims Under Federal Tort... this part, any claim for $200 or less which is based on alleged negligence or wrongful act or omission...
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Sutton, Julie; Macey, Nicola
2017-01-04
I feel sad for the nurse who was sacked for praying for a patient. Whatever happened to freedom of speech? What is wrong with offering to pray with patients? I pray this nurse finds a job where people appreciate her.
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Fitness and Your 4-to 5-Year Old
... their child run the wrong way during a game knows. And starting too young can be frustrating ... a group of preschoolers to enjoy, include: playing games such as "Duck, Duck, Goose" or "Follow the ...
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Compound Words: A Problem in Post-Coordinate Retrieval Systems
ERIC Educational Resources Information Center
Jones, Kevin P.
1971-01-01
Compound words cause some difficulty in post-coordinate indexing systems: if too many are fractured, or the wrong categories are selected for fracturing noise will be produced at unacceptable levels on retrieval. (Author/MM)
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What's Wrong with Plastic Trees?
ERIC Educational Resources Information Center
Krieger, Martin H.
1973-01-01
Analyzes several reasons for conservation of natural resources. Environmentalists and profit-making groups should decide together what needs preservation. Author points out that everything rare is not worth preservation. Priorities for preserving the environment are discussed. (PS)
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24 CFR 5.360 - Housing programs: Additional lease provisions.
Code of Federal Regulations, 2013 CFR
2013-04-01
... remove a pet that becomes vicious, displays symptoms of severe illness, or demonstrates other behavior... relieving the project owner from liability for wrongful removal of a pet. The cost of the animal care...
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24 CFR 5.360 - Housing programs: Additional lease provisions.
Code of Federal Regulations, 2011 CFR
2011-04-01
... remove a pet that becomes vicious, displays symptoms of severe illness, or demonstrates other behavior... relieving the project owner from liability for wrongful removal of a pet. The cost of the animal care...
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24 CFR 5.360 - Housing programs: Additional lease provisions.
Code of Federal Regulations, 2012 CFR
2012-04-01
... remove a pet that becomes vicious, displays symptoms of severe illness, or demonstrates other behavior... relieving the project owner from liability for wrongful removal of a pet. The cost of the animal care...
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24 CFR 5.360 - Housing programs: Additional lease provisions.
Code of Federal Regulations, 2014 CFR
2014-04-01
... remove a pet that becomes vicious, displays symptoms of severe illness, or demonstrates other behavior... relieving the project owner from liability for wrongful removal of a pet. The cost of the animal care...
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24 CFR 5.360 - Housing programs: Additional lease provisions.
Code of Federal Regulations, 2010 CFR
2010-04-01
... remove a pet that becomes vicious, displays symptoms of severe illness, or demonstrates other behavior... relieving the project owner from liability for wrongful removal of a pet. The cost of the animal care...
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Termites and Forest Management in Australia
Don McG Ewart
1991-01-01
Termites have long been regarded as major pests of Australian forests. Drawing together research on termite ecology and mammal conservation, this paper argues that this perception is wrong; termites are a vital component of native forests.
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Infant Formula Not Linked to Diabetes
... or may have given the wrong impression. Related Stories Building Social Bonds Sound Health Managing Diabetes Reducing Children’s Chances of Asthma Links Managing Diabetes: New Technologies Can Make It Easier Diabetes Increases in Children ...
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Mutagenic cost of ribonucleotides in bacterial DNA
Schroeder, Jeremy W.; Randall, Justin R.; Hirst, William G.; O’Donnell, Michael E.; Simmons, Lyle A.
2017-01-01
Replicative DNA polymerases misincorporate ribonucleoside triphosphates (rNTPs) into DNA approximately once every 2,000 base pairs synthesized. Ribonucleotide excision repair (RER) removes ribonucleoside monophosphates (rNMPs) from genomic DNA, replacing the error with the appropriate deoxyribonucleoside triphosphate (dNTP). Ribonucleotides represent a major threat to genome integrity with the potential to cause strand breaks. Furthermore, it has been shown in the bacterium Bacillus subtilis that loss of RER increases spontaneous mutagenesis. Despite the high rNTP error rate and the effect on genome integrity, the mechanism underlying mutagenesis in RER-deficient bacterial cells remains unknown. We performed mutation accumulation lines and genome-wide mutational profiling of B. subtilis lacking RNase HII, the enzyme that incises at single rNMP residues initiating RER. We show that loss of RER in B. subtilis causes strand- and sequence-context–dependent GC → AT transitions. Using purified proteins, we show that the replicative polymerase DnaE is mutagenic within the sequence context identified in RER-deficient cells. We also found that DnaE does not perform strand displacement synthesis. Given the use of nucleotide excision repair (NER) as a backup pathway for RER in RNase HII-deficient cells and the known mutagenic profile of DnaE, we propose that misincorporated ribonucleotides are removed by NER followed by error-prone resynthesis with DnaE. PMID:29078353
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Detection of cystic fibrosis mutations in a GeneChip{trademark} assay format
DOE Office of Scientific and Technical Information (OSTI.GOV)
Miyada, C.G.; Cronin, M.T.; Kim, S.M.
1994-09-01
We are developing assays for the detection of cystic fibrosis mutations based on DNA hybridization. A DNA sample is amplified by PCR, labeled by incorporating a fluorescein-tagged dNTP, enzymatically treated to produce smaller fragments and hybridized to a series of short (13-16 bases) oligonucleotides synthesized on a glass surface via photolithography. The hybrids are detected by eqifluorescence and mutations are identified by the specific pattern of hybridization. In a GeneChip assay, the chip surface is composed of a series of subarrays, each being specific for a particular mutation. Each subarray is further subdivided into a series of probes (40 total),more » half based on the mutant sequence and the remainder based on the wild-type sequence. For each of the subarrays, there is a redundancy in the number of probes that should hybridize to either a wild-type or a mutant target. The multiple probe strategy provides sequence information for a short five base region overlapping the mutation site. In addition, homozygous wild-type and mutant as well as heterozygous samples are each identified by a specific pattern of hybridization. The small size of each probe feature (250 x 250 {mu}m{sup 2}) permits the inclusion of additional probes required to generate sequence information by hybridization.« less
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Wendelsdorf, Katherine V.; Song, Zhuo; Cao, Yang; Samuels, David C.
2009-01-01
Nucleoside analogs used in antiretroviral treatment have been associated with mitochondrial toxicity. The polymerase-γ hypothesis states that this toxicity stems from the analogs' inhibition of the mitochondrial DNA polymerase (polymerase-γ) leading to mitochondrial DNA (mtDNA) depletion. We have constructed a computational model of the interaction of polymerase-γ with activated nucleoside and nucleotide analog drugs, based on experimentally measured reaction rates and base excision rates, together with the mtDNA genome size, the human mtDNA sequence, and mitochondrial dNTP concentrations. The model predicts an approximately 1000-fold difference in the activated drug concentration required for a 50% probability of mtDNA strand termination between the activated di-deoxy analogs d4T, ddC, and ddI (activated to ddA) and the activated forms of the analogs 3TC, TDF, AZT, FTC, and ABC. These predictions are supported by experimental and clinical data showing significantly greater mtDNA depletion in cell culture and patient samples caused by the di-deoxy analog drugs. For zidovudine (AZT) we calculated a very low mtDNA replication termination probability, in contrast to its reported mitochondrial toxicity in vitro and clinically. Therefore AZT mitochondrial toxicity is likely due to a mechanism that does not involve strand termination of mtDNA replication. PMID:19132079
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Vyas, Rajan; Reed, Andrew J.; Tokarsky, E. John; ...
2015-03-31
One common oxidative DNA lesion, 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG), is highly mutagenic in vivo due to its anti-conformation forming a Watson–Crick base pair with correct deoxycytidine 5'-triphosphate (dCTP) and its syn-conformation forming a Hoogsteen base pair with incorrect deoxyadenosine 5'-triphosphate (dATP). Here in this article, we utilized time-resolved X-ray crystallography to follow 8-oxoG bypass by human DNA polymerase β (hPolβ). In the 12 solved structures, both Watson–Crick (anti-8-oxoG:anti-dCTP) and Hoogsteen (syn-8-oxoG:anti-dATP) base pairing were clearly visible and were maintained throughout the chemical reaction. Additionally, a third Mg 2+ appeared during the process of phosphodiester bond formation and was located between the reactingmore » α- and β-phosphates of the dNTP, suggesting its role in stabilizing reaction intermediates. After phosphodiester bond formation, hPolβ reopened its conformation, pyrophosphate was released, and the newly incorporated primer 3'-terminal nucleotide stacked, rather than base paired, with 8-oxoG. These structures provide the first real-time pictures, to our knowledge, of how a polymerase correctly and incorrectly bypasses a DNA lesion.« less
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Ribonucleotide reductase activity is regulated by proliferating cell nuclear antigen (PCNA)
Salguero, Israel; Guarino, Estrella; Shepherd, Marianne; Deegan, Tom; Havens, Courtney G.; MacNeill, Stuart A.; Walter, Johannes C.; Kearsey, Stephen E.
2014-01-01
Summary Synthesis of dNTPs is required for both DNA replication and DNA repair and is catalyzed by ribonucleotide reductases (RNR), which convert ribonucleotides to their deoxy forms [1, 2]. Maintaining the correct levels of dNTPs for DNA synthesis is important for minimising the mutation rate [3-7], and this is achieved by tight regulation of ribonucleotide reductase [2, 8, 9]. In fission yeast, ribonucleotide reductase is regulated in part by a small protein inhibitor, Spd1, which is degraded in S phase and after DNA damage to allow up-regulation of dNTP supply [10-12]. Spd1 degradation is mediated by the activity of the CRL4Cdt2 ubiquitin ligase complex [5, 13, 14]. This has been reported to be dependent on modulation of Cdt2 levels which are cell cycle regulated, peaking in S phase, and which also increase after DNA damage in a checkpoint-dependent manner [7, 13]. We show here that Cdt2 levels fluctuations are not sufficient to regulate Spd1 proteolysis and that the key step in this event is the interaction of Spd1 with the polymerase processivity factor PCNA, complexed onto DNA. This mechanism thus provides a direct link between DNA synthesis and ribonucleotide reductase regulation. PMID:22464192
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Vyas, Rajan; Reed, Andrew J.; Tokarsky, E. John; Suo, Zucai
2015-01-01
One common oxidative DNA lesion, 8-oxo-7,8-dihydro-2′-deoxyguanine (8-oxoG), is highly mutagenic in vivo due to its anti-conformation forming a Watson–Crick base pair with correct deoxycytidine 5′-triphosphate (dCTP) and its syn-conformation forming a Hoogsteen base pair with incorrect deoxyadenosine 5′-triphosphate (dATP). Here, we utilized time-resolved X-ray crystallography to follow 8-oxoG bypass by human DNA polymerase β (hPolβ). In the 12 solved structures, both Watson–Crick (anti-8-oxoG:anti-dCTP) and Hoogsteen (syn-8-oxoG:anti-dATP) base pairing were clearly visible and were maintained throughout the chemical reaction. Additionally, a third Mg2+ appeared during the process of phosphodiester bond formation and was located between the reacting α- and β-phosphates of the dNTP, suggesting its role in stabilizing reaction intermediates. After phosphodiester bond formation, hPolβ reopened its conformation, pyrophosphate was released, and the newly incorporated primer 3′-terminal nucleotide stacked, rather than base paired, with 8-oxoG. These structures provide the first real-time pictures, to our knowledge, of how a polymerase correctly and incorrectly bypasses a DNA lesion. PMID:25825995
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Waddell, D; Ullman, B
1983-04-10
From human CCRF-CEM T-cells growing in continuous culture, we have selected, isolated, and characterized a clonal cell line, APHID-D2, with altered ribonucleotide reductase activity. In comparative growth rate experiments, the APHID-D2 cell line is less sensitive than the parental cell line to growth inhibition by deoxyadenosine in the presence of 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of adenosine deaminase. The APHID-D2 cell line has elevated levels of all four dNTPs. The resistance of the APHID-D2 cell line to growth inhibition by deoxyadenosine and the abnormal dNTP levels can be explained by the fact that the APHID-D2 ribonucleotide reductase, unlike the parental ribonucleotide reductase, is not normally sensitive to inhibition by dATP. These results suggest that the allosteric site of ribonucleotide reductase which binds both dATP and ATP is altered in the APHID-D2 line. The isolation of a mutant clone of human T-cells which contains a ribonucleotide reductase that has lost its normal sensitivity to dATP and which is resistant to deoxyadenosine-mediated growth inhibition suggests that a primary pathogenic target of accumulated dATP in lymphocytes from patients with adenosine deaminase deficiency may be the cellular ribonucleotide reductase.
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Waqar, M A; Evans, M J; Huberman, J A
1978-01-01
We have studied the effects of the nucleotide analogue, 2',3'-dideoxythymidine-5'-triphosphate (ddTTP) on replicative DNA synthesis in HeLa cell lysates. As previously demonstrated (1), such lysates carry out extensive DNA synthesis in vitro, at rates and in a fashion similar to in vivo DNA replication. We report here that all aspects of DNA synthesis in such lysates (total dNTP incorporation, elongation of continuous nascent strands, and the initiation, elongation, and joining of Okazaki pieces) are only slightly inhibited by concentrations of ddTTP as high as 100-500 micrometer when the dTTP concentration is maintained at 10 micrometer. This finding is consistent with the report by Edenberg, Anderson, and DePamphilis (2) that all aspects of replicative in vitro simian virus 40 DNA synthesis are also resistant to ddTTP. We also find, in agreement with Edenberg, Anderson, and DePamphilis (2), that DNA synthesis catalyzed by DNA polymerases beta or gamma is easily inhibited by ddTTP, while synthesis catalyzed by DNA polymerase alpha is very resistant. These observations suggest that DNA polymerase alpha may be the only DNA polymerase required for all aspects of cellular DNA synthesis. PMID:673840
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32 CFR 750.44 - Claims not payable.
Code of Federal Regulations, 2010 CFR
2010-07-01
... death which was proximately caused, in whole or in part, by any negligence or wrongful act on the part... Chapter. (4) Federal Tort Claims Act. 28 U.S.C. 2671, 2672, and 2674-2680. (5) International Agreements...
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40 CFR 1620.2 - Administrative claim; when presented.
Code of Federal Regulations, 2010 CFR
2010-07-01
... ADMINISTRATIVE CLAIMS ARISING UNDER THE FEDERAL TORT CLAIMS ACT § 1620.2 Administrative claim; when presented. (a... negligence or wrongful act or omission of the CSB or its employees must be mailed or delivered to the Office...
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5 CFR 177.106 - Authority to adjust, determine, compromise, and settle.
Code of Federal Regulations, 2010 CFR
2010-01-01
... SERVICE REGULATIONS ADMINISTRATIVE CLAIMS UNDER THE FEDERAL TORT CLAIMS ACT § 177.106 Authority to adjust... alleged negligence or wrongful act or omission of an OPM employee, with the exception of claims involving...
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US students have wrong view of teaching
NASA Astrophysics Data System (ADS)
Kruesi, Liz
2017-04-01
Students taking science, technology, engineering and mathematics (STEM) subjects in the US have a number of misconceptions about teaching that may be leading them to choose other careers, according to a study by the American Physical Society (APS).
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What Ideas Do Students Associate with "Biotechnology" and "Genetic Engineering"?
ERIC Educational Resources Information Center
Hill, Ruaraidh; Stanisstreet, Martin; Boyes, Edward
2000-01-01
Explores the ideas that students aged 16-19 associate with the terms 'biotechnology' and 'genetic engineering'. Indicates that some students see biotechnology as risky whereas genetic engineering was described as ethically wrong. (Author/ASK)
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The big-bang-for-your-buck theory.
Lucas, H C; Weill, P; Cox, S
1993-01-01
Do it right, and your investment in information technology can have all sorts of strategic payoffs. Do it wrong, and you'll be paying, dearly, for nothing. Here's a guide to evaluating IT and measuring its impact.
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... Wrong Print en español El bazo y el sistema linfático The lymphatic system is an extensive drainage ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...
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Effects of Hydrolysis on Determining the Solubility Product of Potassium Bitartrate
ERIC Educational Resources Information Center
McNaught, Ian J.; Peckham, Gavin D.
2009-01-01
The method given in many publications for calculating the solubility product of potassium bitartrate is wrong in principle. A way of modifying the experimental approach and calculations to overcome the problem are presented.
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49 CFR Appendix A to Part 224 - Schedule of Civil Penalties1
Code of Federal Regulations, 2010 CFR
2010-10-01
... § 224.105Sheeting dimensions and quantity: Failure to apply minimum amount of retroreflective sheeting in accordance with Table 2 2,500 5,000 Applying retroreflective sheeting of wrong dimensions 2,500 5...
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About Sexually Transmitted Diseases (STDs)
... wrong. A person can get some STDs, like herpes or genital warts, through skin-to-skin contact with an ... STDs, click on the links below. Chlamydia Genital Herpes (HSV-2) Genital Warts Gonorrhea Hepatitis B (HBV) HIV and AIDS ...
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... all go wrong. According to The Dynamics of Human Communication: A Laboratory Approach , by Gail E. Myers and ... the Author Deborah Shuck has aMaster’sDegree in Communications and Human Relations. She has applied to aPh Dprogram and ...
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NASA Astrophysics Data System (ADS)
Iyer, Gokul; Ledna, Catherine; Clarke, Leon; Edmonds, James; McJeon, Haewon; Kyle, Page; Williams, James H.
2018-03-01
In the version of this Article previously published, technical problems led to the wrong summary appearing on the homepage, and an incorrect Supplementary Information file being uploaded. Both errors have now been corrected.
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32 CFR 536.92 - Claims payable under the Non-Scope Claims Act.
Code of Federal Regulations, 2010 CFR
2010-07-01
... negligent or wrongful acts or omissions of Department of Defense or Department of the Army (DA) military... or regulation available to the DA for the administrative settlement of claims. (b) Personal injury or...
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NASA Astrophysics Data System (ADS)
Sand, D.
2018-05-01
In Atel #11665 we reported the wrong RA coordinate for the transient DLT18x/AT 2018bwo. The correct coordinates for the transient are - RA: 00:14:01.68 DEC: -23:11:35.38. We apologize for any inconvenience.
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Mandatory neurotechnological treatment: ethical issues.
Focquaert, Farah
2014-02-01
What if neurofeedback or other types of neurotechnological treatment, by itself or in combination with behavioral treatment, could achieve a successful "rewiring" of the psychopath's brain? Imagine that such treatments exist and that they provide a better long-term risk-minimizing strategy compared to imprisonment. Would it be ethical to offer such treatments as a condition of probation, parole, or (early) prison release? In this paper, I argue that it can be ethical to offer effective, non-invasive neurotechnological treatments to offenders as a condition of probation, parole, or (early) prison release provided that: (1) the status quo is in no way cruel, inhuman, degrading, or in some other way wrong, (2) the treatment option is in no way cruel, inhuman, degrading, or in some other way wrong, (3) the treatment is in the best interests of the offender, and (4) the offender gives his/her informed consent.
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Earth radiation balance and climate: Why the Moon is the wrong place to observe the Earth
NASA Astrophysics Data System (ADS)
Kandel, Robert S.
1994-06-01
Increasing 'greenhouse' gases in the Earth's atmosphere will perturb the Earth's radiation balance, forcing climate change over coming decades. Climate sensitivity depends critically on cloud-radiation feedback: its evaluation requires continual observation of changing patterns of Earth radiation balance and cloud cover. The Moon is the wrong place for such observations, with many disadvantages compared to an observation system combining platforms in low polar, intermediate-inclination and geostationary orbits. From the Moon, active observations are infeasible; thermal infrared observations require very large instruments to reach spatial resolutions obtained at much lower cost from geostationary or lower orbits. The Earth's polar zones are never well observed from the Moon; other zones are invisible more than half the time. The monthly illumination cycle leads to further bias in radiation budget determinations. The Earth will be a pretty sight from the Earth-side of the Moon, but serious Earth observations will be made elsewhere.
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Ding, Yi; Peng, Kai; Yu, Miao; Lu, Lei; Zhao, Kun
2017-08-01
The performance of the two selected spatial frequency phase unwrapping methods is limited by a phase error bound beyond which errors will occur in the fringe order leading to a significant error in the recovered absolute phase map. In this paper, we propose a method to detect and correct the wrong fringe orders. Two constraints are introduced during the fringe order determination of two selected spatial frequency phase unwrapping methods. A strategy to detect and correct the wrong fringe orders is also described. Compared with the existing methods, we do not need to estimate the threshold associated with absolute phase values to determine the fringe order error, thus making it more reliable and avoiding the procedure of search in detecting and correcting successive fringe order errors. The effectiveness of the proposed method is validated by the experimental results.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Singh, Kunwar Pal, E-mail: k-psingh@yahoo.com; Department of Physics, Shri Venkateshwara University, Gajraula, Amroha, Uttar Pradesh 244236; Arya, Rashmi
2015-09-14
We have investigated the effect of initial phase on error in electron energy obtained using paraxial approximation to study electron acceleration by a focused laser pulse in vacuum using a three dimensional test-particle simulation code. The error is obtained by comparing the energy of the electron for paraxial approximation and seventh-order correction description of the fields of Gaussian laser. The paraxial approximation predicts wrong laser divergence and wrong electron escape time from the pulse which leads to prediction of higher energy. The error shows strong phase dependence for the electrons lying along the axis of the laser for linearly polarizedmore » laser pulse. The relative error may be significant for some specific values of initial phase even at moderate values of laser spot sizes. The error does not show initial phase dependence for a circularly laser pulse.« less
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Meloni, Domenico
2015-05-28
The aim of the present survey was to investigate the correct enforcement of the Community rules on the labelling and marketing of bivalve and gastropod molluscs retailed in Sardinia, Italy between 2009 and 2013. A total of 1500 packages and labels for live bivalve and gastropod molluscs were considered. A total of 375 labels (25%) presented non-compliance concerning the wrong trade name and additional wrong or missing information. The highest percentage of anomalous labels has been detected in small-scale retail shops (35%) and open-air markets (25%) compared with the big retailing chains (20%). The 5% of packages were not in compliance with the European Community rules on packaging of bivalve and gastropod molluscs. The high percentage of non-compliance with the European regulations on labelling results is a strong limitation for the consumers and highlights the need to improve the control system about labelling of seafood products.
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What Was Wrong with Eugenics? Conflicting Narratives and Disputed Interpretations
NASA Astrophysics Data System (ADS)
Paul, Diane B.
2014-02-01
Although it is often taken for granted that eugenics is odious, exactly what makes it so is far from obvious. The existence of considerable interpretative flexibility is evident in the disparate policy lessons for contemporary reproductive genetics (or "reprogenetics") that have been derived from essentially the same set of historical facts. In this paper, I will show how different—indeed, diametrically-opposed—morals have been drawn from the history of eugenics and link these contrasting messages both to different underlying conceptions of what constitutes the central wrong of eugenics and differing degrees of enthusiasm for reprogenetic technologies. I will then argue that, for several reasons, the history of eugenics simply cannot provide the kind of direct guidance that many participants in current debates would like. Although the history does have implications for policy, the insights to be gleaned are both subtle and indirect.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Davis, L.N.
1979-01-01
The use of LNG as a major energy source is opposed on a number of grounds: (1) too much can go wrong with an LNG facility that can cause an accident, (2) a major LNG accident could kill hundreds of thousands of people, (3) safety research on LNG is grossly inadequate, (4) the need for LNG has not yet been proven, (5) LNG will increase the US's dependence on insecure or even hostile foreign sources, and (6) LNG costs too much. Gas companies are gambling that LNG is safe, plentiful, and politically reliable and that they can keep prices downmore » to acceptable levels. If they are right, the importing nations will benefit from a valuable new source of energy. But if they are wrong, the gas consumers and the people living near LNG tanks and terminals have the most to lose: soaring prices and future disruptions from supply cutoffs on the one hand and unimaginable destruction on the other.« less
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"Eugenics talk" and the language of bioethics.
Wilkinson, S
2008-06-01
In bioethical discussions of preimplantation genetic diagnosis and prenatal screening, accusations of eugenics are commonplace, as are counter-claims that talk of eugenics is misleading and unhelpful. This paper asks whether "eugenics talk", in this context, is legitimate and useful or something to be avoided. It also looks at the extent to which this linguistic question can be answered without first answering relevant substantive moral questions. Its main conclusion is that the best and most non-partisan argument for avoiding eugenics talk is the Autonomy Argument. According to this, eugenics talk per se is not wrong, but there is something wrong with using its emotive power as a means of circumventing people's critical-rational faculties. The Autonomy Argument does not, however, tell against eugenics talk when such language is used to shock people into critical-rational thought. These conclusions do not depend on unique features of eugenics: similar considerations apply to emotive language throughout bioethics.
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Benign violations: making immoral behavior funny.
McGraw, A Peter; Warren, Caleb
2010-08-01
Humor is an important, ubiquitous phenomenon; however, seemingly disparate conditions seem to facilitate humor. We integrate these conditions by suggesting that laughter and amusement result from violations that are simultaneously seen as benign. We investigated three conditions that make a violation benign and thus humorous: (a) the presence of an alternative norm suggesting that the situation is acceptable, (b) weak commitment to the violated norm, and (c) psychological distance from the violation. We tested the benign-violation hypothesis in the domain of moral psychology, where there is a strong documented association between moral violations and negative emotions, particularly disgust. Five experimental studies show that benign moral violations tend to elicit laughter and amusement in addition to disgust. Furthermore, seeing a violation as both wrong and not wrong mediates behavioral displays of humor. Our account is consistent with evolutionary accounts of laughter, explains humor across many domains, and suggests that humor can accompany negative emotion.
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Marquis: a defense of abortion?
Gelfand, S D
2001-04-01
This is a reply to Don Marquis' "Why Abortion is Immoral." Marquis, who asserts that abortion is morally wrong, bases his argument on the following premise: Killing a being is morally wrong if that being is the sort of being who has a valuable future. I argue that this premise is false. I then assert that if I am correct about this premise being false, Marquis is faced with a dilemma. If he does not alter the premise in a way that makes it true, his argument is unsound. However, if he does make such an alteration, he must also alter a second premise in his argument, and this second change opens him to the charge of question begging. In addition, I conclude that such an alteration requires Marquis to adopt a position much like that taken by Judith J. Thompson in "A Defense of Abortion," a position he initially states is indefensible.
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A problem with inclusion in learning disability research.
McClimens, Alex; Allmark, Peter
2011-09-01
People with severe learning disability are particularly difficult to include in the research process. As a result, researchers may be tempted to focus on those with learning disability who can be included. The problem is exacerbated in this field as the political agenda of inclusion and involvement is driven by those people with learning disability who are the higher functioning. To overcome this we should first detach the notion of consent from ideas about autonomy and think instead of it as a way to avoid wronging others; this fits the original historical use of consent in research. This allows us to think in terms of including participants to the best of their abilities rather than in terms of a threshold of autonomy. Researchers could then use imaginative ways to include the least able and to ensure they are not wronged in research or by exclusion from it.
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“Eugenics talk” and the language of bioethics
Wilkinson, S
2008-01-01
In bioethical discussions of preimplantation genetic diagnosis and prenatal screening, accusations of eugenics are commonplace, as are counter-claims that talk of eugenics is misleading and unhelpful. This paper asks whether “eugenics talk”, in this context, is legitimate and useful or something to be avoided. It also looks at the extent to which this linguistic question can be answered without first answering relevant substantive moral questions. Its main conclusion is that the best and most non-partisan argument for avoiding eugenics talk is the Autonomy Argument. According to this, eugenics talk per se is not wrong, but there is something wrong with using its emotive power as a means of circumventing people’s critical–rational faculties. The Autonomy Argument does not, however, tell against eugenics talk when such language is used to shock people into critical–rational thought. These conclusions do not depend on unique features of eugenics: similar considerations apply to emotive language throughout bioethics. PMID:18511622
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The regulation of commercial surrogacy: The wrong answers to the wrong questions.
Stuhmcke, Anita
2015-12-01
The criminal ban on commercial surrogacy across Australian jurisdictions is the result of the conflation and confusion of two flawed assumptions. The first being that the criminalisation of commercial surrogacy will discourage a surrogacy "industry" and the second that commercial surrogacy and altruistic surrogacy are two distinguishable "types" of surrogacy arrangements. This article argues that the criminalisation of commercial surrogacy has resulted in unforeseen and undesirable consequences, removing opportunity for evidence-based law reform. Moreover, analysis of both the approach of Australian courts and the operation of surrogacy legislation suggests that the binary regulatory approach which distinguishes "commercial" from "altruistic" surrogacy is a legal fiction. In summary, this article argues that the current Australian regulation of surrogacy is both blunt and ineffectual, surrogacy is a nuanced and complex practice which requires a regulatory response which is principled, holistic and evidence based.
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Troublesome Crystal Structures: Prevention, Detection, and Resolution
Harlow, Richard L.
1996-01-01
A large number of incorrect crystal structures is being published today. These structures are proving to be a particular problem to those of us who are interested in comparing structural moieties found in the databases in order to develop structure-property relationships. Problems can reside in the input data, e.g., wrong unit cell or low quality intensity data, or in the structural model, e.g., wrong space group or atom types. Many of the common mistakes are, however, relatively easy to detect and thus should be preventable; at the very least, suspicious structures can be flagged, if not by the authors then by the referees and, ultimately, the crystallographic databases. This article describes some of the more common mistakes and their effects on the resulting structures, lists a series of tests that can be used to detect incorrect structures, and makes a strong plea for the publication of higher quality structures. PMID:27805169
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On the motion of the centre of mass of a system of particles
NASA Astrophysics Data System (ADS)
Saccomandi, Giuseppe
2010-05-01
We consider the simple and classical theorem of the motion of the centre of mass, pointing out that many textbooks append a wrong corollary to it: that the motion of the centre of mass is always independent from the internal forces. We give an explicit example showing that this corollary is wrong. We discuss using a historical approach the genesis of such a misunderstanding. The contents of the paper may be used at different levels of complexity. The explicit example may be used to discuss the theorem at an undergraduate level in a clearer way than usual, but the paper also contains much for an advanced course on classical mechanics. Moreover, the historical approach may also be of interest in the study of the philosophy and sociology of science. This paper is dedicated to the memory of my great and perspicacious teachers of mechanics: Pietro and Aldo.
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Unfalsifiability of security claims.
Herley, Cormac
2016-06-07
There is an inherent asymmetry in computer security: Things can be declared insecure by observation, but not the reverse. There is no observation that allows us to declare an arbitrary system or technique secure. We show that this implies that claims of necessary conditions for security (and sufficient conditions for insecurity) are unfalsifiable. This in turn implies an asymmetry in self-correction: Whereas the claim that countermeasures are sufficient is always subject to correction, the claim that they are necessary is not. Thus, the response to new information can only be to ratchet upward: Newly observed or speculated attack capabilities can argue a countermeasure in, but no possible observation argues one out. Further, when justifications are unfalsifiable, deciding the relative importance of defensive measures reduces to a subjective comparison of assumptions. Relying on such claims is the source of two problems: once we go wrong we stay wrong and errors accumulate, and we have no systematic way to rank or prioritize measures.
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Villa, Ferdinando; Bagstad, Kenneth J.; Voigt, Brian; Johnson, Gary W.; Athanasiadis, Ioannis N; Balbi, Stefano
2014-01-01
In their recent article, Shapiro and Báldi (2014) build on the long-running narrative of “ecosystem services and disservices” (e.g., Zhang et al., 2007 ; Lyytimäki et al., 2008), describing how nature yields both benefits and harms to society. These harms include crop pests, floods, landslides, wildfires, and zoonotic disease transmission, among others. While we agree with their argument that calculation of these harms is commonplace and corresponding quantification of benefits is needed, we feel the use of the concept of “ecosystem disservices” hampers, rather than helps, the development of an integrative and constructive dialogue about conservation and the complex interrelationships between humans and nature. Estimation of costs and benefits and their balancing as positives or negatives is a principal activity in economics; however, we fear that in this case the term “disservice” carries the wrong message for both science and society.
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Darwin endures, despite disparagement.
Van Den Berg, Hugo A
2018-03-01
Evolution lies at the heart of the life sciences, and Charles Darwin is a towering historical figure within evolutionary science. One testimony to his lasting influence is that declaring Darwin to have been wrong all along remains a provocative way to command attention. The present paper discusses various strands of 'Darwin was wrong' partisans and their divergent views and motives: some are looking to Darwin to justify or condemn the political ideologies that they support or reject; others are concerned with the corrupting influence that the bleak cosmic outlook of evolution is deemed to exert on the moral or religious rectitude of impressionable minds, or regard Darwinism as a direct assault on religion; philosophers question the very coherence of the entire enterprise; and certain biologists aspire to go down in history as even greater than Darwin. It is sobering to reflect that this diverse group is united only by their poor grasp of Darwin's theory of natural selection.
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Nicaise, C; Robert, C; Ancellin, J; Cazalaà, J B
1996-01-01
When plugging the O2, N2O and air hoses into the corresponding wall sockets, the air hose was wrongly inserted into the N2O wall outlet. This was made possible because of faulty retaining clasps of the male coupler of the air probe. French "fail-safe" connections consist of a two-clasp male coupler for air, three clasps for O2 and four clasps for N2O hoses. Additionally the clasps of the air probe are broader then those of the N2O probe. However, the latter difference was lost due to wear. The incident was recognized without delay as the N2O hose could not be inserted into the air outlet. However, it could have remained unnoticed had there been two N2O wall outlets and could have resulted in severe adverse effects.
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[Understanding mistake-proofing].
de Saint Maurice, G; Giraud, N; Ausset, S; Auroy, Y; Lenoir, B; Amalberti, R
2011-01-01
The mistake-proofing concept often refers to physical devices that prevent actors from making a wrong action. In anaesthesiology, one immediately thinks to specific design of outlets for medical gases. More generally, the principle of mistake-proofing is to avoid an error, by placing knowledge in the world rather than knowledge in the head. As it often happens in risk management, healthcare has received information transfers from the industry. Computer is changing the concept of mistake-proofing, initially based on physical design, such as aerospace and automotive industry. The mistake-proofing concept may be applied to prevention, detection, and mitigation of errors. The forcing functions are a specific part of mistake-proofing: they prevent a wrong action or they force a virtuous one. Grout proposes a little shortcut to identify mistake-proofing devices: "If it is not possible to picture it in action, it is probably not a mistake-proofing device". Copyright © 2010 Elsevier Masson SAS. All rights reserved.
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Kaufmann, Paul M
2009-09-01
Psychologists must advocate for more stringent legal protection of psychological test materials because using standardized tests is the most distinguishing and exclusive feature of psychological evaluation practice. With the rapid growth in forensic consulting, unrestrained discovery of raw data and psychological test materials during litigation erodes the reliability and validity of the test procedures. Dissemination of test materials reduces the interpretive value of the tests and promotes cheating, turning our best methods into junk science in the courtroom. This article proposes to reform the law and to revise the professional ethics of psychologists consistent with the strong public policy of test security as described by the U.S. Supreme Court in Detroit Edison v. NLRB (1979). Currently, federal courts and about 20 states protect psychological tests as a unique methodology, with some states enacting a psychologist nondisclosure privilege/duty to safeguard test materials from wrongful disclosure. The record management practices of psychologists vary considerably and are vulnerable to legal attack unless psychologists are aware of legal arguments to protect test materials from wrongful release. Although this article does not offer legal advice, it describes the most common records management problem confronting neuropsychologists and some practical solutions to the raw data problem. Best practice for protecting psychological tests requires the psychologist to understand the law and to assert the psychologist nondisclosure privilege. Other strategies are presented and evaluated. Organized psychology and the legal community should advocate for a uniform rule to protect the objectivity, fairness, and integrity psychological methods in litigation.
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Spontaneous abortion and unexpected death: a critical discussion of Marquis on abortion.
Coleman, Mary Clayton
2013-02-01
In his classic paper, 'Why abortion is immoral', Don Marquis argues that what makes killing an adult seriously immoral is that it deprives the victim of the valuable future he/she would have otherwise had. Moreover, Marquis contends, because abortion deprives a fetus of the very same thing, aborting a fetus is just as seriously wrong as killing an adult. Marquis' argument has received a great deal of critical attention in the two decades since its publication. Nonetheless, there is a potential challenge to it that seems to have gone unnoticed. A significant percentage of fetuses are lost to spontaneous abortion. Once we bring this fact to our attention, it becomes less clear whether Marquis can use his account of the wrongness of killing to show that abortion is the moral equivalent of murder. In this paper, I explore the relevance of the rate of spontaneous abortion to Marquis' classic anti-abortion argument. I introduce a case I call Unexpected Death in which someone is about to commit murder, but, just as the would-be murderer is about to strike, his would-be victim dies unexpectedly. I then ask: what does Marquis' account of killing imply about the moral status of what the would-be murderer was about to do? I consider four responses Marquis could give to this question, and I examine what implications these responses have for Marquis' strategy of using his account of the wrongness of killing an adult to show that abortion is in the same moral category.
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Carrez, Laurent; Bouchoud, Lucie; Fleury-Souverain, Sandrine; Combescure, Christophe; Falaschi, Ludivine; Sadeghipour, Farshid; Bonnabry, Pascal
2017-03-01
Background and objectives Centralized chemotherapy preparation units have established systematic strategies to avoid errors. Our work aimed to evaluate the accuracy of manual preparations associated with different control methods. Method A simulation study in an operational setting used phenylephrine and lidocaine as markers. Each operator prepared syringes that were controlled using a different method during each of three sessions (no control, visual double-checking, and gravimetric control). Eight reconstitutions and dilutions were prepared in each session, with variable doses and volumes, using different concentrations of stock solutions. Results were analyzed according to qualitative (choice of stock solution) and quantitative criteria (accurate, <5% deviation from the target concentration; weakly accurate, 5%-10%; inaccurate, 10%-30%; wrong, >30% deviation). Results Eleven operators carried out 19 sessions. No final preparation (n = 438) contained a wrong drug. The protocol involving no control failed to detect 1 of 3 dose errors made and double-checking failed to detect 3 of 7 dose errors. The gravimetric control method detected all 5 out of 5 dose errors. The accuracy of the doses measured was equivalent across the control methods ( p = 0.63 Kruskal-Wallis). The final preparations ranged from 58% to 60% accurate, 25% to 27% weakly accurate, 14% to 17% inaccurate and 0.9% wrong. A high variability was observed between operators. Discussion Gravimetric control was the only method able to detect all dose errors, but it did not improve dose accuracy. A dose accuracy with <5% deviation cannot always be guaranteed using manual production. Automation should be considered in the future.
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Chiastra, Claudio; Grundeken, Maik J; Collet, Carlos; Wu, Wei; Wykrzykowska, Joanna J; Pennati, Giancarlo; Dubini, Gabriele; Migliavacca, Francesco
2018-05-17
The treatment of coronary bifurcations is challenging for interventional cardiologists. The Tryton stent (Tryton Medical, Inc., USA) is one of the few devices specifically designed for coronary bifurcations that underwent large clinical trials. Although the manufacturer provides specific recommendations to position the stent in the bifurcation side branch (SB) according to four radio-opaque markers under angiographic guidance, wrong device positioning may accidentally occur. In this study, the virtual bench testing approach was used to investigate the impact of wrong positioning of the Tryton stent in coronary bifurcations in terms of geometrical and biomechanical criteria. A finite element model of the left anterior descending/first diagonal coronary bifurcation was created with a 45° distal angle and realistic lumen diameters. A validated model of the Tryton stent mounted on stepped delivery balloon was used. All steps of the Tryton deployment sequence were simulated. Three Tryton positions, namely 'proximal', 'recommended', and 'distal' positions, obtained by progressively implanting the stent more distally in the SB, were compared. The 'recommended' case exhibited the lowest ostial area stenosis (44.8 vs. 74.3% ('proximal') and 51.5% ('distal')), the highest diameter at the SB ostium (2.81 vs. 2.70 mm ('proximal') and 2.54 mm ('distal')), low stent malapposition (9.9 vs. 16.3% ('proximal') and 8.5% ('distal')), and the lowest peak wall stress (0.37 vs. 2.20 MPa ('proximal') and 0.71 MPa ('distal')). In conclusion, the study shows that a 'recommended' Tryton stent positioning may be required for optimal clinical results.
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Elemental misinterpretation in automated analysis of LIBS spectra.
Hübert, Waldemar; Ankerhold, Georg
2011-07-01
In this work, the Stark effect is shown to be mainly responsible for wrong elemental allocation by automated laser-induced breakdown spectroscopy (LIBS) software solutions. Due to broadening and shift of an elemental emission line affected by the Stark effect, its measured spectral position might interfere with the line position of several other elements. The micro-plasma is generated by focusing a frequency-doubled 200 mJ pulsed Nd/YAG laser on an aluminum target and furthermore on a brass sample in air at atmospheric pressure. After laser pulse excitation, we have measured the temporal evolution of the Al(II) ion line at 281.6 nm (4s(1)S-3p(1)P) during the decay of the laser-induced plasma. Depending on laser pulse power, the center of the measured line is red-shifted by 130 pm (490 GHz) with respect to the exact line position. In this case, the well-known spectral line positions of two moderate and strong lines of other elements coincide with the actual shifted position of the Al(II) line. Consequently, a time-resolving software analysis can lead to an elemental misinterpretation. To avoid a wrong interpretation of LIBS spectra in automated analysis software for a given LIBS system, we recommend using larger gate delays incorporating Stark broadening parameters and using a range of tolerance, which is non-symmetric around the measured line center. These suggestions may help to improve time-resolving LIBS software promising a smaller probability of wrong elemental identification and making LIBS more attractive for industrial applications.
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Crew resource management: using aviation techniques to improve operating room safety.
Ricci, Michael A; Brumsted, John R
2012-04-01
Since the publication of the Institute of Medicine report estimating nearly 100,000 deaths per year from medical errors, hospitals and physicians have a renewed focus upon error reduction. We implemented a surgical crew resource management (CRM) program for all operating room (OR) personnel. In our academic medical center, 19,000 procedures per year are performed in 27 operating rooms. Mandatory CRM training was implemented for all peri-operative personnel. Aviation techniques introduced included a pre-operative checklist and brief, post-operative debrief, read and initial files, and various other aviation-based techniques. Compliance with conduct of the brief/debrief was monitored as well as wrong-site surgeries and retained foreign body events. The malpractice insurance database for claims was also queried for the period prior to and after training. Initial training was accomplished for 517 people, including all anesthesiologists, surgeons, nurses, technicians, and OR assistants. Pre-operative briefing increased from 6.7 to 99% within 4 mo. Wrong site surgeries and retained foreign bodies decreased from a high of seven in 2007 to none in 2008, but, after 14 mo without additional training, these rose to five in 2009. Malpractice expenses (payouts and legal fees) totaled $793,000 (2003-2007), but have been zero since 2008. CRM training and implementation had an impact on reducing the incidence of wrong site surgery and retained foreign bodies in our operating rooms. However, constant reinforcement and refresher training is necessary for sustained results. Though no one technique can prevent all errors, CRM can effect culture change, producing a safer environment.
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32 CFR 842.92 - Scope of this subpart.
Code of Federal Regulations, 2010 CFR
2010-07-01
... ADMINISTRATIVE CLAIMS Property Damage Tort Claims in Favor of the United States (31 U.S.C. 3701, 3711-3719) § 842... damage to or loss or destruction of government property through negligence or wrongful act. It does not...
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ERIC Educational Resources Information Center
Hollander, Patricia A.
Recent court cases involving tort liabilities of institutions of higher education are discussed in this chapter. Issues addressed include negligence citations for injuries in physical education classes, a wrongful death suit, medical malpractice cases, and slip and fall accidents. Other cases included fraudulent misrepresentation, defamation of…
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For Parents Particularly: Lessons in Moral Behavior. A Few Heroes.
ERIC Educational Resources Information Center
Cohen, Stewart
1993-01-01
Discusses ways for parents (and educators) to use the life stories of heroes, such as individuals who rescued Jews from the Holocaust, to foster children's moral courage, sense of right and wrong, and commitment to others. (MDM)
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Physics That Textbook Writers Usually Get Wrong: II. Heat and Energy.
ERIC Educational Resources Information Center
Bauman, Robert P.
1992-01-01
Examines problems that occur with the vocabulary used in physics textbooks related to heat and energy. Discusses the concepts of thermal energy and temperature, conservation of energy laws, and the first law of thermodynamics. (MDH)
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Rubella-Caused Deafness: Maintaining Objectivity and a Positive Frame of Reference.
ERIC Educational Resources Information Center
Pimentel, Albert T.
1980-01-01
Scientific inquiry too often focuses on "what's wrong" and not "what's right" with deaf children, including those with maternal rubella. Failure to succeed should not ignore factors other than etiology, including educational and communicative factors. (Author)
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The eating habits of schoolchildren.
Taitz, L
1989-09-22
Food, either too much, too little or the wrong type, has been implicated in a number of physical and psychological disorders. Children are bigger than ever but also less active, so diets may have to change to guard against coronary artery disease.
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Rights and Wrongs of Ethics Training.
ERIC Educational Resources Information Center
Rice, Dan; Dreilinger, Craig
1990-01-01
Ethics initiatives should provide employees with the tools they need to identify, clarify, and resolve ethical issues. Training efforts should focus on defining desired outcomes and considering the company's values and guidelines in working toward solutions to ethical problems. (SK)
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What's Wrong With Conservation Education?
ERIC Educational Resources Information Center
Hobart, Willis L.
1972-01-01
Conservation and conservation education are critically examined, their definitions, foundations, principles, concepts, weaknesses, failures, and successes. It is concluded educators must first educate themselves, or environmental education will fail the same way conservation education has failed to educate Americans to the intricate…
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48 CFR 52.228-8 - Liability and Insurance-Leased Motor Vehicles.
Code of Federal Regulations, 2010 CFR
2010-10-01
... and (ii) loss or damage caused by the negligence of the Contractor, its agents, or employees; and (2..., negligence, or wrongful act or omission of the Contractor, its agents, or employees. (c) The Contractor shall...
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NASA Astrophysics Data System (ADS)
Bracher, Katherine
1994-09-01
Early in this century, astronomers debated whether spiral nebulae were luminous pieces of our own galaxy or independent galaxies, Kant's "island universes." Harlow Shapley championed the former explanation. Although he turned out to be wrong, his arguments illustrate how science tests it ideas.
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Chemistry Teaching: Science or Alchemy?
ERIC Educational Resources Information Center
Johnstone, A. H.
1997-01-01
Suggests that the development of good chemistry teaching and the pursuit of research have essentially the same structure. Similarities include the need for a clear focus, efficiency in time and effort, and a direction that is more often right than wrong. (DDR)
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The Legal Scene to Come: The Gray Nineties.
ERIC Educational Resources Information Center
Kaplan, Rochelle K.
1990-01-01
Reviews legal challenges that employers are likely to face in the 1990s. Issues discussed include discriminatory recruiting, harassment, globalization and equal employment opportunity laws, wrongful discharge and drug testing, disabilities, family/work legislation, and state legislation. (TE)
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76 FR 60754 - Preserving the Open Internet
Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-30
...-201] Preserving the Open Internet AGENCY: Federal Communications Commission. ACTION: Final rule..., 2011, a document establishing rules to preserve the open Internet. Inadvertently the wrong paragraph... alleging violations of the open Internet rules. Federal Communications Commission. Matt Warner, Attorney...
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Gábor M. Kovács; James M. Trappe; Abdulmagid M. Alsheikh; Karen Hansen; Rosanne A. Healy; Pál Vági
2011-01-01
Reexamination and molecular phylogenetic analyses of American Terfezia species and Mattirolomyces tiffanyae revealed that their generic assignments were wrong. Therefore we here propose these combinations: Mattirolomyces spinosus comb. nov. (=Terfezia spinosa), Stouffera...
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NASA Astrophysics Data System (ADS)
Wade, Jess
2017-07-01
In Inferior: How Science Got Women Wrong and the New Research That's Rewriting the Story, author Angela Saini puts forward the idea that bad science has been used to endorse the cultural prejudice that women are both biologically and psychologically second rate to men.
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Ethics Training: Can We Really Teach People Right from Wrong?
ERIC Educational Resources Information Center
Zemke, Ron
1977-01-01
A discussion of the issue of ethics training in business and whether or not ethics is a problem appropriately addressed by training. Includes two case studies taken from a multimedia program by an educational media corporation. (LAS)
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32 CFR 536.75 - Claims payable under the Military Claims Act.
Code of Federal Regulations, 2011 CFR
2011-07-01
..., acting within the scope of their employment, that is determined to be negligent or wrongful; or (2..., chapter 11. (c) Maritime claims. Claims that arise on the high seas or within the territorial waters of a...