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Sample records for error prone pcr

  1. [Directed evolution of aflatoxin detoxifzyme in vitro by error-prone PCR].

    PubMed

    Zhang, Sai; Xing, Keke; Hu, Yadong; Xie, Chunfang; Liu, Daling; Yao, Dongsheng

    2011-07-01

    The experiment was conducted by directed evolution strategy (error-prone PCR) to improve the activity of aflatoxin detoxifzyme with the high-throughput horse radish peroxidas and recessive brilliant green (HRP-RBG) screening system. We built up a mutant library to the order of 10(4). Two rounds of EP-PCR and HRP-RBG screening were used to obtain three optimum mutant strains A1773, A1476 and A2863. We found that mutant A1773 had upper temperature tolerance of 70 degrees C and that its enzyme activity was 6.5 times higher than that of the parent strain. Mutant strains A1476 worked well at pH 4.0 and its enzyme activity was 21 times higher than that of the parent strain. Mutant A2863 worked well at pH 4.0 and pH 7.5, and its enzyme activity was 12.6 times higher than that of the parent strain. With DNA sequencing we found that mutant A1773 revealed two amino acid substitutions, Glu127Lys and Gln613Arg. Mutant A1476 revealed four amino acid substitutions: Ser46Pro, Lys221Gln, Ile307Leu and Asn471lle. Mutant A2863 revealed four amino acid substitutions: Gly73Ser, Ile307Leu, Va1596Ala and Gln613Arg. The results provided a useful illustration for the deep understanding of the relationship between the function and structure of aflatoxin detoxifzyme. PMID:22016995

  2. Error-prone signalling.

    PubMed

    Johnstone, R A; Grafen, A

    1992-06-22

    The handicap principle of Zahavi is potentially of great importance to the study of biological communication. Existing models of the handicap principle, however, make the unrealistic assumption that communication is error free. It seems possible, therefore, that Zahavi's arguments do not apply to real signalling systems, in which some degree of error is inevitable. Here, we present a general evolutionarily stable strategy (ESS) model of the handicap principle which incorporates perceptual error. We show that, for a wide range of error functions, error-prone signalling systems must be honest at equilibrium. Perceptual error is thus unlikely to threaten the validity of the handicap principle. Our model represents a step towards greater realism, and also opens up new possibilities for biological signalling theory. Concurrent displays, direct perception of quality, and the evolution of 'amplifiers' and 'attenuators' are all probable features of real signalling systems, yet handicap models based on the assumption of error-free communication cannot accommodate these possibilities. PMID:1354361

  3. Directed Evolution and Resolution Mechanism of 1, 3-Propanediol Oxidoreductase from Klebsiella pneumoniae toward Higher Activity by Error-Prone PCR and Bioinformatics

    PubMed Central

    Jiang, Wei; Zhuang, Yuan; Wang, Shizhen; Fang, Baishan

    2015-01-01

    1, 3-propanediol oxidoreductase (PDOR) is a key enzyme in glycerol bioconversion to 1,3-propanediol (1, 3-PD) which is a valuable chemical and one of the six new petrochemical products. We used error-prone PCR and activity screening to identify mutants of Klebsiella pneumoniae (K. pneumoniae) PDOR with improved activity. The activity of one of the identified mutants, PDOR’-24, which includes a single mutation, A199S, was 48 U/mg, 4.9 times that of the wild-type enzyme. Molecular docking was performed to analyze the identified mutants; and amino acids S103, H271, N366, D106, N262 and D364 were predicted to bond with NADH. The origins of the improved activity of PDOR’-24, as well as three other mutants were analyzed by simulating the interaction mechanism of the mutants with the substrate and coenzyme, respectively. This research provides useful information about the use of safranine O plate screening for the directed evolution of oxidoreductases, identifies interesting sites for improving PDOR activity, and demonstrates the utility of using molecular docking to analyze the interaction mechanism of the mutants with the substrate and coenzyme, respectively. PMID:26528716

  4. Stepwise error-prone PCR and DNA shuffling changed the pH activity range and product specificity of the cyclodextrin glucanotransferase from an alkaliphilic Bacillus sp.

    PubMed Central

    Melzer, Susanne; Sonnendecker, Christian; Föllner, Christina; Zimmermann, Wolfgang

    2015-01-01

    Cyclodextrin glucanotransferase (EC 2.4.1.19) from the alkaliphilic Bacillus sp. G-825-6 converts starch mainly to γ-cyclodextrin (CD8). A combination of error-prone PCR and DNA shuffling was used to obtain variants of this enzyme with higher product specificity for CD8 and a broad pH activity range. The variant S54 with seven amino acid substitutions showed a 1.2-fold increase in CD8-synthesizing activity and the product ratio of CD7:CD8 was shifted to 1:7 compared to 1:3 of the wild-type enzyme. Nine amino acid substitutions of the cyclodextrin glucanotransferase were performed to generate the variant S35 active in a pH range 4.0–10.0. Compared to the wild-type enzyme which is inactive below pH 6.0, S35 retained 70% of its CD8-synthesizing activity at pH 4.0. PMID:26155461

  5. Inhibiting HER3-Mediated Tumor Cell Growth with Affibody Molecules Engineered to Low Picomolar Affinity by Position-Directed Error-Prone PCR-Like Diversification

    PubMed Central

    Malm, Magdalena; Kronqvist, Nina; Lindberg, Hanna; Gudmundsdotter, Lindvi; Bass, Tarek; Frejd, Fredrik Y.; Höidén-Guthenberg, Ingmarie; Varasteh, Zohreh; Orlova, Anna; Tolmachev, Vladimir; Ståhl, Stefan; Löfblom, John

    2013-01-01

    The HER3 receptor is implicated in the progression of various cancers as well as in resistance to several currently used drugs, and is hence a potential target for development of new therapies. We have previously generated Affibody molecules that inhibit heregulin-induced signaling of the HER3 pathways. The aim of this study was to improve the affinity of the binders to hopefully increase receptor inhibition efficacy and enable a high receptor-mediated uptake in tumors. We explored a novel strategy for affinity maturation of Affibody molecules that is based on alanine scanning followed by design of library diversification to mimic the result from an error-prone PCR reaction, but with full control over mutated positions and thus less biases. Using bacterial surface display and flow-cytometric sorting of the maturation library, the affinity for HER3 was improved more than 30-fold down to 21 pM. The affinity is among the higher that has been reported for Affibody molecules and we believe that the maturation strategy should be generally applicable for improvement of affinity proteins. The new binders also demonstrated an improved thermal stability as well as complete refolding after denaturation. Moreover, inhibition of ligand-induced proliferation of HER3-positive breast cancer cells was improved more than two orders of magnitude compared to the previously best-performing clone. Radiolabeled Affibody molecules showed specific targeting of a number of HER3-positive cell lines in vitro as well as targeting of HER3 in in vivo mouse models and represent promising candidates for future development of targeted therapies and diagnostics. PMID:23675426

  6. Disruption of N terminus long range non covalent interactions shifted temp.opt 25°C to cold: Evolution of point mutant Bacillus lipase by error prone PCR.

    PubMed

    Goomber, Shelly; Kumar, Arbind; Kaur, Jagdeep

    2016-01-15

    Cold adapted enzymes have applications in detergent, textile, food, bioremediation and biotechnology processes. Bacillus lipases are 'generally recognized as safe' (GRAS) and hence are industrially attractive. Bacillus lipase of 1.4 subfamily are of lowest molecular weight and are reversibly unfolded due to absence of disulphide bonds. Therefore these are largely used to study energetic of protein stability that represents unfolding of native protein to fully unfolded state. In present study, metagenomically isolated Bacillus LipJ was laboratory evolved for cold adaptation by error Prone PCR. Library of variants were screened for high relative activity at low temperature of 10°C compared to native protein LipJ. Point mutant sequenced as Phe19→Leu was determined to be active at cold and was selected for extensive biochemical, biophysical characterization. Variant F19L showed its maximum activity at 10°C where parent protein LipJ had 20% relative activity. Psychrophilic nature of F19L was established with about 50% relative active at 5°C where native protein was frozen to act. Variant F19L showed no activity at temperature 40°C and above, establishing its thermolabile nature. Thermostability studies determined mutant to be unstable above 20°C and three fold decrease in its half life at 30°C compared to native protein. Far UV-CD and intrinsic fluorescence study demonstrated unstable tertiary structure of point variant F19L leading to its unfolding at low temperature of 20°C. Cold adaptation of mutant F19L is accompanied with increased specific activity. Mutant was catalytically more efficient with 1.3 fold increase in kcat. Homologue structure modelling predicted disruption of intersecondary hydrophobic core formed by aromatic ring of Phe19 with non polar residues placed at β3, β4, β5, β6, αF. Increased local flexibility of variant F19L explains molecular basis of its psychrophilic nature. PMID:26456196

  7. Size and Shape Analysis of Error-Prone Shape Data

    PubMed Central

    Du, Jiejun; Dryden, Ian L.; Huang, Xianzheng

    2015-01-01

    We consider the problem of comparing sizes and shapes of objects when landmark data are prone to measurement error. We show that naive implementation of ordinary Procrustes analysis that ignores measurement error can compromise inference. To account for measurement error, we propose the conditional score method for matching configurations, which guarantees consistent inference under mild model assumptions. The effects of measurement error on inference from naive Procrustes analysis and the performance of the proposed method are illustrated via simulation and application in three real data examples. Supplementary materials for this article are available online. PMID:26109745

  8. Mismatch-mediated error prone repair at the Immunoglobulin genes

    PubMed Central

    Chahwan, Richard; Edelmann, Winfried; Scharff, Matthew D; Roa, Sergio

    2011-01-01

    The generation of effective antibodies depends upon somatic hypermutation (SHM) and class-switch recombination (CSR) of antibody genes by activation induced cytidine deaminase (AID) and the subsequent recruitment of error prone base excision and mismatch repair. While AID initiates and is required for SHM, more than half of the base changes that accumulate in V regions are not due to the direct deamination of dC to dU by AID, but rather arise through the recruitment of the mismatch repair complex (MMR) to the U:G mismatch created by AID and the subsequent perversion of mismatch repair from a high fidelity process to one that is very error prone. In addition, the generation of double-strand breaks (DSBs) is essential during CSR, and the resolution of AID-generated mismatches by MMR to promote such DSBs is critical for the efficiency of the process. While a great deal has been learned about how AID and MMR cause hypermutations and DSBs, it is still unclear how the error prone aspect of these processes is largely restricted to antibody genes. The use of knockout models and mice expressing mismatch repair proteins with separation-of-function point mutations have been decisive in gaining a better understanding of the roles of each of the major MMR proteins and providing further insight into how mutation and repair are coordinated. Here, we review the cascade of MMR factors and repair signals that are diverted from their canonical error free role and hijacked by B cells to promote genetic diversification of the Ig locus. This error prone process involves AID as the inducer of enzymatically-mediated DNA mismatches, and a plethora of downstream MMR factors acting as sensors, adaptors and effectors of a complex and tightly regulated process from much of which is not yet well understood. PMID:22100214

  9. Error-prone polymerase activity causes multinucleotide mutations in humans.

    PubMed

    Harris, Kelley; Nielsen, Rasmus

    2014-09-01

    About 2% of human genetic polymorphisms have been hypothesized to arise via multinucleotide mutations (MNMs), complex events that generate SNPs at multiple sites in a single generation. MNMs have the potential to accelerate the pace at which single genes evolve and to confound studies of demography and selection that assume all SNPs arise independently. In this paper, we examine clustered mutations that are segregating in a set of 1092 human genomes, demonstrating that the signature of MNM becomes enriched as large numbers of individuals are sampled. We estimate the percentage of linked SNP pairs that were generated by simultaneous mutation as a function of the distance between affected sites and show that MNMs exhibit a high percentage of transversions relative to transitions, findings that are reproducible in data from multiple sequencing platforms and cannot be attributed to sequencing error. Among tandem mutations that occur simultaneously at adjacent sites, we find an especially skewed distribution of ancestral and derived alleles, with GC → AA, GA → TT, and their reverse complements making up 27% of the total. These mutations have been previously shown to dominate the spectrum of the error-prone polymerase Pol ζ, suggesting that low-fidelity DNA replication by Pol ζ is at least partly responsible for the MNMs that are segregating in the human population. We develop statistical estimates of MNM prevalence that can be used to correct phylogenetic and population genetic inferences for the presence of complex mutations. PMID:25079859

  10. Error-prone polymerase activity causes multinucleotide mutations in humans

    PubMed Central

    Nielsen, Rasmus

    2014-01-01

    About 2% of human genetic polymorphisms have been hypothesized to arise via multinucleotide mutations (MNMs), complex events that generate SNPs at multiple sites in a single generation. MNMs have the potential to accelerate the pace at which single genes evolve and to confound studies of demography and selection that assume all SNPs arise independently. In this paper, we examine clustered mutations that are segregating in a set of 1092 human genomes, demonstrating that the signature of MNM becomes enriched as large numbers of individuals are sampled. We estimate the percentage of linked SNP pairs that were generated by simultaneous mutation as a function of the distance between affected sites and show that MNMs exhibit a high percentage of transversions relative to transitions, findings that are reproducible in data from multiple sequencing platforms and cannot be attributed to sequencing error. Among tandem mutations that occur simultaneously at adjacent sites, we find an especially skewed distribution of ancestral and derived alleles, with GC → AA, GA → TT, and their reverse complements making up 27% of the total. These mutations have been previously shown to dominate the spectrum of the error-prone polymerase Pol ζ, suggesting that low-fidelity DNA replication by Pol ζ is at least partly responsible for the MNMs that are segregating in the human population. We develop statistical estimates of MNM prevalence that can be used to correct phylogenetic and population genetic inferences for the presence of complex mutations. PMID:25079859

  11. Designing an Algorithm to Preserve Privacy for Medical Record Linkage With Error-Prone Data

    PubMed Central

    Pal, Doyel; Chen, Tingting; Khethavath, Praveen

    2014-01-01

    Background Linking medical records across different medical service providers is important to the enhancement of health care quality and public health surveillance. In records linkage, protecting the patients’ privacy is a primary requirement. In real-world health care databases, records may well contain errors due to various reasons such as typos. Linking the error-prone data and preserving data privacy at the same time are very difficult. Existing privacy preserving solutions for this problem are only restricted to textual data. Objective To enable different medical service providers to link their error-prone data in a private way, our aim was to provide a holistic solution by designing and developing a medical record linkage system for medical service providers. Methods To initiate a record linkage, one provider selects one of its collaborators in the Connection Management Module, chooses some attributes of the database to be matched, and establishes the connection with the collaborator after the negotiation. In the Data Matching Module, for error-free data, our solution offered two different choices for cryptographic schemes. For error-prone numerical data, we proposed a newly designed privacy preserving linking algorithm named the Error-Tolerant Linking Algorithm, that allows the error-prone data to be correctly matched if the distance between the two records is below a threshold. Results We designed and developed a comprehensive and user-friendly software system that provides privacy preserving record linkage functions for medical service providers, which meets the regulation of Health Insurance Portability and Accountability Act. It does not require a third party and it is secure in that neither entity can learn the records in the other’s database. Moreover, our novel Error-Tolerant Linking Algorithm implemented in this software can work well with error-prone numerical data. We theoretically proved the correctness and security of our Error

  12. A QUANTITATIVE MODEL OF ERROR ACCUMULATION DURING PCR AMPLIFICATION

    PubMed Central

    Pienaar, E; Theron, M; Nelson, M; Viljoen, HJ

    2006-01-01

    The amplification of target DNA by the polymerase chain reaction (PCR) produces copies which may contain errors. Two sources of errors are associated with the PCR process: (1) editing errors that occur during DNA polymerase-catalyzed enzymatic copying and (2) errors due to DNA thermal damage. In this study a quantitative model of error frequencies is proposed and the role of reaction conditions is investigated. The errors which are ascribed to the polymerase depend on the efficiency of its editing function as well as the reaction conditions; specifically the temperature and the dNTP pool composition. Thermally induced errors stem mostly from three sources: A+G depurination, oxidative damage of guanine to 8-oxoG and cytosine deamination to uracil. The post-PCR modifications of sequences are primarily due to exposure of nucleic acids to elevated temperatures, especially if the DNA is in a single-stranded form. The proposed quantitative model predicts the accumulation of errors over the course of a PCR cycle. Thermal damage contributes significantly to the total errors; therefore consideration must be given to thermal management of the PCR process. PMID:16412692

  13. Analysis of error-prone survival data under additive hazards models: measurement error effects and adjustments.

    PubMed

    Yan, Ying; Yi, Grace Y

    2016-07-01

    Covariate measurement error occurs commonly in survival analysis. Under the proportional hazards model, measurement error effects have been well studied, and various inference methods have been developed to correct for error effects under such a model. In contrast, error-contaminated survival data under the additive hazards model have received relatively less attention. In this paper, we investigate this problem by exploring measurement error effects on parameter estimation and the change of the hazard function. New insights of measurement error effects are revealed, as opposed to well-documented results for the Cox proportional hazards model. We propose a class of bias correction estimators that embraces certain existing estimators as special cases. In addition, we exploit the regression calibration method to reduce measurement error effects. Theoretical results for the developed methods are established, and numerical assessments are conducted to illustrate the finite sample performance of our methods. PMID:26328545

  14. Recovery of arrested replication forks by homologous recombination is error-prone.

    PubMed

    Iraqui, Ismail; Chekkal, Yasmina; Jmari, Nada; Pietrobon, Violena; Fréon, Karine; Costes, Audrey; Lambert, Sarah A E

    2012-01-01

    Homologous recombination is a universal mechanism that allows repair of DNA and provides support for DNA replication. Homologous recombination is therefore a major pathway that suppresses non-homology-mediated genome instability. Here, we report that recovery of impeded replication forks by homologous recombination is error-prone. Using a fork-arrest-based assay in fission yeast, we demonstrate that a single collapsed fork can cause mutations and large-scale genomic changes, including deletions and translocations. Fork-arrest-induced gross chromosomal rearrangements are mediated by inappropriate ectopic recombination events at the site of collapsed forks. Inverted repeats near the site of fork collapse stimulate large-scale genomic changes up to 1,500 times over spontaneous events. We also show that the high accuracy of DNA replication during S-phase is impaired by impediments to fork progression, since fork-arrest-induced mutation is due to erroneous DNA synthesis during recovery of replication forks. The mutations caused are small insertions/duplications between short tandem repeats (micro-homology) indicative of replication slippage. Our data establish that collapsed forks, but not stalled forks, recovered by homologous recombination are prone to replication slippage. The inaccuracy of DNA synthesis does not rely on PCNA ubiquitination or trans-lesion-synthesis DNA polymerases, and it is not counteracted by mismatch repair. We propose that deletions/insertions, mediated by micro-homology, leading to copy number variations during replication stress may arise by progression of error-prone replication forks restarted by homologous recombination. PMID:23093942

  15. Is Non-Homologous End-Joining Really an Inherently Error-Prone Process?

    PubMed Central

    Bétermier, Mireille; Bertrand, Pascale; Lopez, Bernard S.

    2014-01-01

    DNA double-strand breaks (DSBs) are harmful lesions leading to genomic instability or diversity. Non-homologous end-joining (NHEJ) is a prominent DSB repair pathway, which has long been considered to be error-prone. However, recent data have pointed to the intrinsic precision of NHEJ. Three reasons can account for the apparent fallibility of NHEJ: 1) the existence of a highly error-prone alternative end-joining process; 2) the adaptability of canonical C-NHEJ (Ku- and Xrcc4/ligase IV–dependent) to imperfect complementary ends; and 3) the requirement to first process chemically incompatible DNA ends that cannot be ligated directly. Thus, C-NHEJ is conservative but adaptable, and the accuracy of the repair is dictated by the structure of the DNA ends rather than by the C-NHEJ machinery. We present data from different organisms that describe the conservative/versatile properties of C-NHEJ. The advantages of the adaptability/versatility of C-NHEJ are discussed for the development of the immune repertoire and the resistance to ionizing radiation, especially at low doses, and for targeted genome manipulation. PMID:24453986

  16. Meiosis I in Xenopus oocytes is not error-prone despite lacking spindle assembly checkpoint.

    PubMed

    Liu, Dandan; Shao, Hua; Wang, Hongmei; Liu, X Johné

    2014-01-01

    The spindle assembly checkpoint, SAC, is a surveillance mechanism to control the onset of anaphase during cell division. SAC prevents anaphase initiation until all chromosome pairs have achieved bipolar attachment and aligned at the metaphase plate of the spindle. In doing so, SAC is thought to be the key mechanism to prevent chromosome nondisjunction in mitosis and meiosis. We have recently demonstrated that Xenopus oocyte meiosis lacks SAC control. This prompted the question of whether Xenopus oocyte meiosis is particularly error-prone. In this study, we have karyotyped a total of 313 Xenopus eggs following in vitro oocyte maturation. We found no hyperploid egg, out of 204 metaphase II eggs with countable chromosome spreads. Therefore, chromosome nondisjunction is very rare during Xenopus oocyte meiosis I, despite the lack of SAC. PMID:24646611

  17. Inducible error-prone repair in B. subtilis. Final report, September 1, 1979-June 30, 1981

    SciTech Connect

    Yasbin, R. E.

    1981-06-01

    The research performed under this contract has been concentrated on the relationship between inducible DNA repair systems, mutagenesis and the competent state in the gram positive bacterium Bacillus subtilis. The following results have been obtained from this research: (1) competent Bacillus subtilis cells have been developed into a sensitive tester system for carcinogens; (2) competent B. subtilis cells have an efficient excision-repair system, however, this system will not function on bacteriophage DNA taken into the cell via the process of transfection; (3) DNA polymerase III is essential in the mechanism of the process of W-reactivation; (4) B. subtilis strains cured of their defective prophages have been isolated and are now being developed for gene cloning systems; (5) protoplasts of B. subtilis have been shown capable of acquiring DNA repair enzymes (i.e., enzyme therapy); and (6) a plasmid was characterized which enhanced inducible error-prone repair in a gram positive organism.

  18. Interactions and Localization of Escherichia coli Error-Prone DNA Polymerase IV after DNA Damage

    PubMed Central

    Mallik, Sarita; Popodi, Ellen M.; Hanson, Andrew J.

    2015-01-01

    ABSTRACT Escherichia coli's DNA polymerase IV (Pol IV/DinB), a member of the Y family of error-prone polymerases, is induced during the SOS response to DNA damage and is responsible for translesion bypass and adaptive (stress-induced) mutation. In this study, the localization of Pol IV after DNA damage was followed using fluorescent fusions. After exposure of E. coli to DNA-damaging agents, fluorescently tagged Pol IV localized to the nucleoid as foci. Stepwise photobleaching indicated ∼60% of the foci consisted of three Pol IV molecules, while ∼40% consisted of six Pol IV molecules. Fluorescently tagged Rep, a replication accessory DNA helicase, was recruited to the Pol IV foci after DNA damage, suggesting that the in vitro interaction between Rep and Pol IV reported previously also occurs in vivo. Fluorescently tagged RecA also formed foci after DNA damage, and Pol IV localized to them. To investigate if Pol IV localizes to double-strand breaks (DSBs), an I-SceI endonuclease-mediated DSB was introduced close to a fluorescently labeled LacO array on the chromosome. After DSB induction, Pol IV localized to the DSB site in ∼70% of SOS-induced cells. RecA also formed foci at the DSB sites, and Pol IV localized to the RecA foci. These results suggest that Pol IV interacts with RecA in vivo and is recruited to sites of DSBs to aid in the restoration of DNA replication. IMPORTANCE DNA polymerase IV (Pol IV/DinB) is an error-prone DNA polymerase capable of bypassing DNA lesions and aiding in the restart of stalled replication forks. In this work, we demonstrate in vivo localization of fluorescently tagged Pol IV to the nucleoid after DNA damage and to DNA double-strand breaks. We show colocalization of Pol IV with two proteins: Rep DNA helicase, which participates in replication, and RecA, which catalyzes recombinational repair of stalled replication forks. Time course experiments suggest that Pol IV recruits Rep and that RecA recruits Pol IV. These findings

  19. Income Verification Pilot Project (IVPP): The Development of an Error-Prone Model for the School Meal Programs. Revised.

    ERIC Educational Resources Information Center

    Applied Management Sciences, Inc., Silver Spring, MD.

    This report describes efforts made in 1981-82 to develop an error-prone model (EPM) to help judge the extent of misreporting of income and family size on applications for government-sponsored school meal benefits. (EPM's are statistical formulas that produce scoring systems used to distinguish applications likely to result in excess benefits from…

  20. Thermoadaptation-Directed Enzyme Evolution in an Error-Prone Thermophile Derived from Geobacillus kaustophilus HTA426

    PubMed Central

    Kobayashi, Jyumpei; Wada, Keisuke; Furukawa, Megumi; Doi, Katsumi

    2014-01-01

    Thermostability is an important property of enzymes utilized for practical applications because it allows long-term storage and use as catalysts. In this study, we constructed an error-prone strain of the thermophile Geobacillus kaustophilus HTA426 and investigated thermoadaptation-directed enzyme evolution using the strain. A mutation frequency assay using the antibiotics rifampin and streptomycin revealed that G. kaustophilus had substantially higher mutability than Escherichia coli and Bacillus subtilis. The predominant mutations in G. kaustophilus were A · T→G · C and C · G→T · A transitions, implying that the high mutability of G. kaustophilus was attributable in part to high-temperature-associated DNA damage during growth. Among the genes that may be involved in DNA repair in G. kaustophilus, deletions of the mutSL, mutY, ung, and mfd genes markedly enhanced mutability. These genes were subsequently deleted to construct an error-prone thermophile that showed much higher (700- to 9,000-fold) mutability than the parent strain. The error-prone strain was auxotrophic for uracil owing to the fact that the strain was deficient in the intrinsic pyrF gene. Although the strain harboring Bacillus subtilis pyrF was also essentially auxotrophic, cells became prototrophic after 2 days of culture under uracil starvation, generating B. subtilis PyrF variants with an enhanced half-denaturation temperature of >10°C. These data suggest that this error-prone strain is a promising host for thermoadaptation-directed evolution to generate thermostable variants from thermolabile enzymes. PMID:25326311

  1. Thermoadaptation-directed enzyme evolution in an error-prone thermophile derived from Geobacillus kaustophilus HTA426.

    PubMed

    Suzuki, Hirokazu; Kobayashi, Jyumpei; Wada, Keisuke; Furukawa, Megumi; Doi, Katsumi

    2015-01-01

    Thermostability is an important property of enzymes utilized for practical applications because it allows long-term storage and use as catalysts. In this study, we constructed an error-prone strain of the thermophile Geobacillus kaustophilus HTA426 and investigated thermoadaptation-directed enzyme evolution using the strain. A mutation frequency assay using the antibiotics rifampin and streptomycin revealed that G. kaustophilus had substantially higher mutability than Escherichia coli and Bacillus subtilis. The predominant mutations in G. kaustophilus were A · T→G · C and C · G→T · A transitions, implying that the high mutability of G. kaustophilus was attributable in part to high-temperature-associated DNA damage during growth. Among the genes that may be involved in DNA repair in G. kaustophilus, deletions of the mutSL, mutY, ung, and mfd genes markedly enhanced mutability. These genes were subsequently deleted to construct an error-prone thermophile that showed much higher (700- to 9,000-fold) mutability than the parent strain. The error-prone strain was auxotrophic for uracil owing to the fact that the strain was deficient in the intrinsic pyrF gene. Although the strain harboring Bacillus subtilis pyrF was also essentially auxotrophic, cells became prototrophic after 2 days of culture under uracil starvation, generating B. subtilis PyrF variants with an enhanced half-denaturation temperature of >10°C. These data suggest that this error-prone strain is a promising host for thermoadaptation-directed evolution to generate thermostable variants from thermolabile enzymes. PMID:25326311

  2. The Error Prone Model and the Basic Grants Validation Selection System. Draft Final Report.

    ERIC Educational Resources Information Center

    System Development Corp., Falls Church, VA.

    An evaluation of existing and proposed mechanisms to ensure data accuracy for the Pell Grant program is reported, and recommendations for efficient detection of fraud and error in the program are offered. One study objective was to examine the existing system of pre-established criteria (PEC), which are validation criteria that select students on…

  3. Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins

    PubMed Central

    Guilliam, Thomas A.; Jozwiakowski, Stanislaw K.; Ehlinger, Aaron; Barnes, Ryan P.; Rudd, Sean G.; Bailey, Laura J.; Skehel, J. Mark; Eckert, Kristin A.; Chazin, Walter J.; Doherty, Aidan J.

    2015-01-01

    PrimPol is a recently identified polymerase involved in eukaryotic DNA damage tolerance, employed in both re-priming and translesion synthesis mechanisms to bypass nuclear and mitochondrial DNA lesions. In this report, we investigate how the enzymatic activities of human PrimPol are regulated. We show that, unlike other TLS polymerases, PrimPol is not stimulated by PCNA and does not interact with it in vivo. We identify that PrimPol interacts with both of the major single-strand binding proteins, RPA and mtSSB in vivo. Using NMR spectroscopy, we characterize the domains responsible for the PrimPol-RPA interaction, revealing that PrimPol binds directly to the N-terminal domain of RPA70. In contrast to the established role of SSBs in stimulating replicative polymerases, we find that SSBs significantly limit the primase and polymerase activities of PrimPol. To identify the requirement for this regulation, we employed two forward mutation assays to characterize PrimPol's replication fidelity. We find that PrimPol is a mutagenic polymerase, with a unique error specificity that is highly biased towards insertion-deletion errors. Given the error-prone disposition of PrimPol, we propose a mechanism whereby SSBs greatly restrict the contribution of this enzyme to DNA replication at stalled forks, thus reducing the mutagenic potential of PrimPol during genome replication. PMID:25550423

  4. A Nucleotide-Analogue-Induced Gain of Function Corrects the Error-Prone Nature of Human DNA Polymerase iota

    SciTech Connect

    Ketkar, Amit; Zafar, Maroof K.; Banerjee, Surajit; Marquez, Victor E.; Egli, Martin; Eoff, Robert L.

    2012-10-25

    Y-family DNA polymerases participate in replication stress and DNA damage tolerance mechanisms. The properties that allow these enzymes to copy past bulky adducts or distorted template DNA can result in a greater propensity for them to make mistakes. Of the four human Y-family members, human DNA polymerase iota (hpol{iota}) is the most error-prone. In the current study, we elucidate the molecular basis for improving the fidelity of hpol{iota} through use of the fixed-conformation nucleotide North-methanocarba-2{prime}-deoxyadenosine triphosphate (N-MC-dATP). Three crystal structures were solved of hpol{iota} in complex with DNA containing a template 2{prime}-deoxythymidine (dT) paired with an incoming dNTP or modified nucleotide triphosphate. The ternary complex of hpol{iota} inserting N-MC-dATP opposite dT reveals that the adenine ring is stabilized in the anti orientation about the pseudo-glycosyl torsion angle, which mimics precisely the mutagenic arrangement of dGTP:dT normally preferred by hpol{iota}. The stabilized anti conformation occurs without notable contacts from the protein but likely results from constraints imposed by the bicyclo[3.1.0]hexane scaffold of the modified nucleotide. Unmodified dATP and South-MC-dATP each adopt syn glycosyl orientations to form Hoogsteen base pairs with dT. The Hoogsteen orientation exhibits weaker base-stacking interactions and is less catalytically favorable than anti N-MC-dATP. Thus, N-MC-dATP corrects the error-prone nature of hpol{iota} by preventing the Hoogsteen base-pairing mode normally observed for hpol{iota}-catalyzed insertion of dATP opposite dT. These results provide a previously unrecognized means of altering the efficiency and the fidelity of a human translesion DNA polymerase.

  5. A nucleotide-analogue-induced gain of function corrects the error-prone nature of human DNA polymerase iota.

    PubMed

    Ketkar, Amit; Zafar, Maroof K; Banerjee, Surajit; Marquez, Victor E; Egli, Martin; Eoff, Robert L

    2012-06-27

    Y-family DNA polymerases participate in replication stress and DNA damage tolerance mechanisms. The properties that allow these enzymes to copy past bulky adducts or distorted template DNA can result in a greater propensity for them to make mistakes. Of the four human Y-family members, human DNA polymerase iota (hpol ι) is the most error-prone. In the current study, we elucidate the molecular basis for improving the fidelity of hpol ι through use of the fixed-conformation nucleotide North-methanocarba-2'-deoxyadenosine triphosphate (N-MC-dATP). Three crystal structures were solved of hpol ι in complex with DNA containing a template 2'-deoxythymidine (dT) paired with an incoming dNTP or modified nucleotide triphosphate. The ternary complex of hpol ι inserting N-MC-dATP opposite dT reveals that the adenine ring is stabilized in the anti orientation about the pseudo-glycosyl torsion angle, which mimics precisely the mutagenic arrangement of dGTP:dT normally preferred by hpol ι. The stabilized anti conformation occurs without notable contacts from the protein but likely results from constraints imposed by the bicyclo[3.1.0]hexane scaffold of the modified nucleotide. Unmodified dATP and South-MC-dATP each adopt syn glycosyl orientations to form Hoogsteen base pairs with dT. The Hoogsteen orientation exhibits weaker base-stacking interactions and is less catalytically favorable than anti N-MC-dATP. Thus, N-MC-dATP corrects the error-prone nature of hpol ι by preventing the Hoogsteen base-pairing mode normally observed for hpol ι-catalyzed insertion of dATP opposite dT. These results provide a previously unrecognized means of altering the efficiency and the fidelity of a human translesion DNA polymerase. PMID:22632140

  6. The DNA Ligase IV Syndrome R278H Mutation Impairs B Lymphopoiesis via Error-Prone Nonhomologous End-Joining.

    PubMed

    Park, Jihye; Welner, Robert S; Chan, Mei-Yee; Troppito, Logan; Staber, Philipp B; Tenen, Daniel G; Yan, Catherine T

    2016-01-01

    Hypomorphic mutations in the nonhomologous end-joining (NHEJ) DNA repair protein DNA ligase IV (LIG4) lead to immunodeficiency with varying severity. In this study, using a murine knock-in model, we investigated the mechanisms underlying abnormalities in class switch recombination (CSR) associated with the human homozygous Lig4 R278H mutation. Previously, we found that despite the near absence of Lig4 end-ligation activity and severely reduced mature B cell numbers, Lig4(R278H/R278H) (Lig4(R/R)) mice exhibit only a partial CSR block, producing near normal IgG1 and IgE but substantially reduced IgG3, IgG2b, and IgA serum levels. In this study, to address the cause of these abnormalities, we assayed CSR in Lig4(R/R) B cells generated via preassembled IgH and IgK V region exons (HL). This revealed that Lig4(R278H) protein levels while intact exhibited a higher turnover rate during activation of switching to IgG3 and IgG2b, as well as delays in CSR kinetics associated with defective proliferation during activation of switching to IgG1 and IgE. Activated Lig4(R/R)HL B cells consistently accumulated high frequencies of activation-induced cytidine deaminase-dependent IgH locus chromosomal breaks and translocations and were more prone to apoptosis, effects that appeared to be p53-independent, as p53 deficiency did not markedly influence these events. Importantly, NHEJ instead of alternative end-joining (A-EJ) was revealed as the predominant mechanism catalyzing robust CSR. Defective CSR was linked to failed NHEJ and residual A-EJ access to unrepaired double-strand breaks. These data firmly demonstrate that Lig4(R278H) activity renders NHEJ to be more error-prone, and they predict increased error-prone NHEJ activity and A-EJ suppression as the cause of the defective B lymphopoiesis in Lig4 patients. PMID:26608917

  7. The Preference for Error-Free or Error-Prone Postreplication Repair in Saccharomyces cerevisiae Exposed to Low-Dose Methyl Methanesulfonate Is Cell Cycle Dependent

    PubMed Central

    Huang, Dongqing; Piening, Brian D.

    2013-01-01

    Cells employ error-free or error-prone postreplication repair (PRR) processes to tolerate DNA damage. Here, we present a genome-wide screen for sensitivity to 0.001% methyl methanesulfonate (MMS). This relatively low dose is of particular interest because wild-type cells exhibit no discernible phenotypes in response to treatment, yet PRR mutants are unique among repair mutants in their exquisite sensitivity to 0.001% MMS; thus, low-dose MMS treatment provides a distinctive opportunity to study postreplication repair processes. We show that upon exposure to low-dose MMS, a PRR-defective rad18Δ mutant stalls into a lengthy G2 arrest associated with the accumulation of single-stranded DNA (ssDNA) gaps. Consistent with previous results following UV-induced damage, reactivation of Rad18, even after prolonged G2 arrest, restores viability and genome integrity. We further show that PRR pathway preference in 0.001% MMS depends on timing and context; cells preferentially employ the error-free pathway in S phase and do not require MEC1-dependent checkpoint activation for survival. However, when PRR is restricted to the G2 phase, cells utilize REV3-dependent translesion synthesis, which requires a MEC1-dependent delay and results in significant hypermutability. PMID:23382077

  8. Gene Loss and Error-Prone RNA Editing in the Mitochondrion of Perkinsela, an Endosymbiotic Kinetoplastid

    PubMed Central

    David, Vojtěch; Flegontov, Pavel; Gerasimov, Evgeny; Tanifuji, Goro; Hashimi, Hassan; Logacheva, Maria D.; Maruyama, Shinichiro; Onodera, Naoko T.; Gray, Michael W.; Archibald, John M.

    2015-01-01

    ABSTRACT Perkinsela is an enigmatic early-branching kinetoplastid protist that lives as an obligate endosymbiont inside Paramoeba (Amoebozoa). We have sequenced the highly reduced mitochondrial genome of Perkinsela, which possesses only six protein-coding genes (cox1, cox2, cox3, cob, atp6, and rps12), despite the fact that the organelle itself contains more DNA than is present in either the host or endosymbiont nuclear genomes. An in silico analysis of two Perkinsela strains showed that mitochondrial RNA editing and processing machineries typical of kinetoplastid flagellates are generally conserved, and all mitochondrial transcripts undergo U-insertion/deletion editing. Canonical kinetoplastid mitochondrial ribosomes are also present. We have developed software tools for accurate and exhaustive mapping of transcriptome sequencing (RNA-seq) reads with extensive U-insertions/deletions, which allows detailed investigation of RNA editing via deep sequencing. With these methods, we show that up to 50% of reads for a given edited region contain errors of the editing system or, less likely, correspond to alternatively edited transcripts. PMID:26628723

  9. UmuDAb: An Error-Prone Polymerase Accessory Homolog Whose N-Terminal Domain Is Required for Repression of DNA Damage Inducible Gene Expression in Acinetobacter baylyi

    PubMed Central

    Stinnett, DeAnna B.; Wells, Whitney K.; Peterson, Megan A.; Hare, Janelle M.

    2016-01-01

    In many bacteria, the DNA damage response induces genes (SOS genes) that were repressed by LexA. LexA represses transcription by binding to SOS promoters via a helix-turn-helix motif in its N-terminal domain (NTD). Upon DNA damage, LexA cleaves itself and allows induction of transcription. In Acinetobacter baumannii and Acinetobacter baylyi, multiple genes are induced by DNA damage, and although the Acinetobacter genus lacks LexA, a homolog of the error-prone polymerase subunit UmuD, called UmuDAb, regulates some DNA damage-induced genes. The mechanism of UmuDAb regulation has not been determined. We constructed UmuDAb mutant strains of A. baylyi to test whether UmuDAb mediates gene regulation through LexA-like repressor actions consisting of relief of repression through self-cleavage after DNA damage. Real-time quantitative PCR experiments in both a null umuDAb mutant and an NTD mutant showed that the DNA damage-inducible, UmuDAb-regulated gene ddrR was highly expressed even in the absence of DNA damage. Protein modeling identified a potential LexA-like helix-turn-helix structure in the UmuDAb NTD, which when disrupted, also relieved ddrR and umuDAb repression under non-inducing conditions. Mutations in a putative SOS box in the shared umuDAb-ddrR promoter region similarly relieved these genes’ repression under non-inducing conditions. Conversely, cells possessing a cleavage-deficient UmuDAb were unable to induce gene expression after MMC-mediated DNA damage. This evidence of a UmuDAb repressor mechanism was contrasted with the failure of umuDAb to complement an Escherichia coli umuD mutant for UmuD error-prone DNA replication activity. Similarly, A. baumannii null umuDAb mutant cells did not have a reduced UmuDˊ2UmuC-mediated mutation rate after DNA damage, suggesting that although this UmuDAb protein may have evolved from a umuDC operon in this genus, it now performs a LexA-like repressor function for a sub-set of DNA damage-induced genes. PMID:27010837

  10. Quality Control Analysis of Selected Aspects of Programs Administered by the Bureau of Student Financial Assistance. Task 1 and Quality Control Sample; Error-Prone Modeling Analysis Plan.

    ERIC Educational Resources Information Center

    Saavedra, Pedro; And Others

    Parameters and procedures for developing an error-prone model (EPM) to predict financial aid applicants who are likely to misreport on Basic Educational Opportunity Grant (BEOG) applications are introduced. Specifications to adapt these general parameters to secondary data analysis of the Validation, Edits, and Applications Processing Systems…

  11. Error-prone replication bypass of the primary aflatoxin B1 DNA adduct, AFB1-N7-Gua.

    PubMed

    Lin, Ying-Chih; Li, Liang; Makarova, Alena V; Burgers, Peter M; Stone, Michael P; Lloyd, R Stephen

    2014-06-27

    Hepatocellular carcinomas (HCCs) are the third leading cause of cancer deaths worldwide. The highest rates of early onset HCCs occur in geographical regions with high aflatoxin B1 (AFB1) exposure, concomitant with hepatitis B infection. Although the carcinogenic basis of AFB1 has been ascribed to its mutagenic effects, the mutagenic property of the primary AFB1-DNA adduct, AFB1-N7-Gua, in mammalian cells has not been studied extensively. Taking advantage of the ability to create vectors containing a site-specific DNA adduct, the mutagenic potential was determined in primate cells. This adduct was highly mutagenic following replication in COS-7 cells, with a mutation frequency of 45%. The spectrum of mutations was predominantly G to T base substitutions, a result that is consistent with previous mutation data derived from aflatoxin-associated HCCs. To assess which DNA polymerases (pol) might contribute to the mutational outcome, in vitro replication studies were performed. Unexpectedly, replicative pol δ and the error-prone translesion synthesis pol ζ were able to accurately bypass AFB1-N7-Gua. In contrast, replication bypass using pol κ was shown to occur with low fidelity and could account for the commonly detected G to T transversions. PMID:24838242

  12. Elevated variant density around SV breakpoints in germline lineage lends support to error-prone replication hypothesis.

    PubMed

    Dhokarh, Dhananjay; Abyzov, Alexej

    2016-07-01

    Copy number variants (CNVs) are a class of structural variants that may involve complex genomic rearrangements (CGRs) and are hypothesized to have additional mutations around their breakpoints. Understanding the mechanisms underlying CNV formation is fundamental for understanding the repair and mutation mechanisms in cells, thereby shedding light on evolution, genomic disorders, cancer, and complex human traits. In this study, we used data from the 1000 Genomes Project to analyze hundreds of loci harboring heterozygous germline deletions in the subjects NA12878 and NA19240. By utilizing synthetic long-read data (longer than 2 kbp) in combination with high coverage short-read data and, in parallel, by comparing with parental genomes, we interrogated the phasing of these deletions with the flanking tens of thousands of heterozygous SNPs and indels. We found that the density of SNPs/indels flanking the breakpoints of deletions (in-phase variants) is approximately twice as high as the corresponding density for the variants on the haplotype without deletion (out-of-phase variants). This fold change was even larger for the subset of deletions with signatures of replication-based mechanism of formation. The allele frequency (AF) spectrum for deletions is enriched for rare events; and the AF spectrum for in-phase SNPs is shifted toward this deletion spectrum, thus offering evidence consistent with the concomitance of the in-phase SNPs/indels with the deletion events. These findings therefore lend support to the hypothesis that the mutational mechanisms underlying CNV formation are error prone. Our results could also be relevant for resolving mutation-rate discrepancies in human and to explain kataegis. PMID:27216746

  13. Removal of PCR Error Products and Unincorporated Primers by Metal-Chelate Affinity Chromatography

    PubMed Central

    Kanakaraj, Indhu; Jewell, David L.; Murphy, Jason C.; Fox, George E.; Willson, Richard C.

    2011-01-01

    Immobilized Metal Affinity Chromatography (IMAC) has been used for decades to purify proteins on the basis of amino acid content, especially surface-exposed histidines and “histidine tags” genetically added to recombinant proteins. We and others have extended the use of IMAC to purification of nucleic acids via interactions with the nucleotide bases, especially purines, of single-stranded RNA and DNA. We also have demonstrated the purification of plasmid DNA from contaminating genomic DNA by IMAC capture of selectively-denatured genomic DNA. Here we describe an efficient method of purifying PCR products by specifically removing error products, excess primers, and unincorporated dNTPs from PCR product mixtures using flow-through metal-chelate affinity adsorption. By flowing a PCR product mixture through a Cu2+-iminodiacetic acid (IDA) agarose spin column, 94–99% of the dNTPs and nearly all the primers can be removed. Many of the error products commonly formed by Taq polymerase also are removed. Sequencing of the IMAC-processed PCR product gave base-calling accuracy comparable to that obtained with a commercial PCR product purification method. The results show that IMAC matrices (specifically Cu2+-IDA agarose) can be used for the purification of PCR products. Due to the generality of the base-specific mechanism of adsorption, IMAC matrices may also be used in the purification of oligonucleotides, cDNA, mRNA and micro RNAs. PMID:21264292

  14. Heterozygous PALB2 c.1592delT mutation channels DNA double-strand break repair into error-prone pathways in breast cancer patients.

    PubMed

    Obermeier, K; Sachsenweger, J; Friedl, T W P; Pospiech, H; Winqvist, R; Wiesmüller, L

    2016-07-21

    Hereditary heterozygous mutations in a variety of DNA double-strand break (DSB) repair genes have been associated with increased breast cancer risk. In the Finnish population, PALB2 (partner and localizer of BRCA2) represents a major susceptibility gene for female breast cancer, and so far, only one mutation has been described, c.1592delT, which leads to a sixfold increased disease risk. PALB2 is thought to participate in homologous recombination (HR). However, the effect of the Finnish founder mutation on DSB repair has not been investigated. In the current study, we used a panel of lymphoblastoid cell lines (LCLs) derived from seven heterozygous female PALB2 c.1592delT mutation carriers with variable health status and six wild-type matched controls. The results of our DSB repair analysis showed that the PALB2 mutation causes specific changes in pathway usage, namely increases in error-prone single-strand annealing (SSA) and microhomology-mediated end-joining (MMEJ) compared with wild-type LCLs. These data indicated haploinsufficiency regarding the suppression of error-prone DSB repair in PALB2 mutation carriers. To the contrary, neither reduced HR activities, nor impaired RAD51 filament assembly, nor sensitization to PARP inhibition were consistently observed. Expression of truncated mutant versus wild-type PALB2 verified a causal role of PALB2 c.1592delT in the shift to error-prone repair. Discrimination between healthy and malignancy-presenting PALB2 mutation carriers revealed a pathway shift particularly in the breast cancer patients, suggesting interaction of PALB2 c.1592delT with additional genomic lesions. Interestingly, the studied PALB2 mutation was associated with 53BP1 accumulation in the healthy mutation carriers but not the patients, and 53BP1 was limiting for error-prone MMEJ in patients but not in healthy carriers. Our study identified a rise in error-prone DSB repair as a potential threat to genomic integrity in heterozygous PALB2 mutation carriers

  15. Heterozygous PALB2 c.1592delT mutation channels DNA double-strand break repair into error-prone pathways in breast cancer patients

    PubMed Central

    Obermeier, K; Sachsenweger, J; Friedl, T W P; Pospiech, H; Winqvist, R; Wiesmüller, L

    2016-01-01

    Hereditary heterozygous mutations in a variety of DNA double-strand break (DSB) repair genes have been associated with increased breast cancer risk. In the Finnish population, PALB2 (partner and localizer of BRCA2) represents a major susceptibility gene for female breast cancer, and so far, only one mutation has been described, c.1592delT, which leads to a sixfold increased disease risk. PALB2 is thought to participate in homologous recombination (HR). However, the effect of the Finnish founder mutation on DSB repair has not been investigated. In the current study, we used a panel of lymphoblastoid cell lines (LCLs) derived from seven heterozygous female PALB2 c.1592delT mutation carriers with variable health status and six wild-type matched controls. The results of our DSB repair analysis showed that the PALB2 mutation causes specific changes in pathway usage, namely increases in error-prone single-strand annealing (SSA) and microhomology-mediated end-joining (MMEJ) compared with wild-type LCLs. These data indicated haploinsufficiency regarding the suppression of error-prone DSB repair in PALB2 mutation carriers. To the contrary, neither reduced HR activities, nor impaired RAD51 filament assembly, nor sensitization to PARP inhibition were consistently observed. Expression of truncated mutant versus wild-type PALB2 verified a causal role of PALB2 c.1592delT in the shift to error-prone repair. Discrimination between healthy and malignancy-presenting PALB2 mutation carriers revealed a pathway shift particularly in the breast cancer patients, suggesting interaction of PALB2 c.1592delT with additional genomic lesions. Interestingly, the studied PALB2 mutation was associated with 53BP1 accumulation in the healthy mutation carriers but not the patients, and 53BP1 was limiting for error-prone MMEJ in patients but not in healthy carriers. Our study identified a rise in error-prone DSB repair as a potential threat to genomic integrity in heterozygous PALB2 mutation carriers

  16. Structural and Functional Elucidation of the Mechanism Promoting Error-prone Synthesis by Human DNA Polymerase [kappa] Opposite the 7,8-Dihydro-8-oxo-2'-deoxyguanosine Adduct

    SciTech Connect

    Irimia, Adriana; Eoff, Robert L.; Guengerich, F.Peter; Egli, Martin

    2009-09-25

    Human polymerase kappa (hPol {kappa}) is one of four eukaryotic Y-class DNA polymerases and may be an important element in the cellular response to polycyclic aromatic hydrocarbons such as benzo[a]pyrene, which can lead to reactive oxygenated metabolite-mediated oxidative stress. Here, we present a detailed analysis of the activity and specificity of hPol {kappa} bypass opposite the major oxidative adduct 7,8-dihydro-8-oxo-2{prime}-deoxyguanosine (8-oxoG). Unlike its archaeal homolog Dpo4, hPol {kappa} bypasses this lesion in an error-prone fashion by inserting mainly dATP. Analysis of transient-state kinetics shows diminished 'bursts' for dATP:8-oxoG and dCTP:8-oxoG incorporation, indicative of non-productive complex formation, but dATP:8-oxoG insertion events that do occur are 2-fold more efficient than dCTP:G insertion events. Crystal structures of ternary hPol {kappa} complexes with adducted template-primer DNA reveal non-productive (dGTP and dATP) alignments of incoming nucleotide and 8-oxoG. Structural limitations placed upon the hPol {kappa} by interactions between the N-clasp and finger domains combined with stabilization of the syn-oriented template 8-oxoG through the side chain of Met-135 both appear to contribute to error-prone bypass. Mutating Leu-508 in the little finger domain of hPol {kappa} to lysine modulates the insertion opposite 8-oxoG toward more accurate bypass, similar to previous findings with Dpo4. Our structural and activity data provide insight into important mechanistic aspects of error-prone bypass of 8-oxoG by hPol {kappa} compared with accurate and efficient bypass of the lesion by Dpo4 and polymerase {eta}.

  17. Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation

    PubMed Central

    Stavnezer, Janet; Linehan, Erin K.; Thompson, Mikayla R.; Habboub, Ghaith; Ucher, Anna J.; Kadungure, Tatenda; Tsuchimoto, Daisuke; Nakabeppu, Yusaku; Schrader, Carol E.

    2014-01-01

    Somatic hypermutation (SHM) of antibody variable region genes is initiated in germinal center B cells during an immune response by activation-induced cytidine deaminase (AID), which converts cytosines to uracils. During accurate repair in nonmutating cells, uracil is excised by uracil DNA glycosylase (UNG), leaving abasic sites that are incised by AP endonuclease (APE) to create single-strand breaks, and the correct nucleotide is reinserted by DNA polymerase β. During SHM, for unknown reasons, repair is error prone. There are two APE homologs in mammals and, surprisingly, APE1, in contrast to its high expression in both resting and in vitro-activated splenic B cells, is expressed at very low levels in mouse germinal center B cells where SHM occurs, and APE1 haploinsufficiency has very little effect on SHM. In contrast, the less efficient homolog, APE2, is highly expressed and contributes not only to the frequency of mutations, but also to the generation of mutations at A:T base pair (bp), insertions, and deletions. In the absence of both UNG and APE2, mutations at A:T bp are dramatically reduced. Single-strand breaks generated by APE2 could provide entry points for exonuclease recruited by the mismatch repair proteins Msh2–Msh6, and the known association of APE2 with proliferating cell nuclear antigen could recruit translesion polymerases to create mutations at AID-induced lesions and also at A:T bp. Our data provide new insight into error-prone repair of AID-induced lesions, which we propose is facilitated by down-regulation of APE1 and up-regulation of APE2 expression in germinal center B cells. PMID:24927551

  18. Structural basis of error-prone replication and stalling at a thymine base by human DNA polymerase

    SciTech Connect

    Kirouac, Kevin N.; Ling, Hong

    2009-06-30

    Human DNA polymerase iota (pol iota) is a unique member of Y-family polymerases, which preferentially misincorporates nucleotides opposite thymines (T) and halts replication at T bases. The structural basis of the high error rates remains elusive. We present three crystal structures of pol complexed with DNA containing a thymine base, paired with correct or incorrect incoming nucleotides. A narrowed active site supports a pyrimidine to pyrimidine mismatch and excludes Watson-Crick base pairing by pol. The template thymine remains in an anti conformation irrespective of incoming nucleotides. Incoming ddATP adopts a syn conformation with reduced base stacking, whereas incorrect dGTP and dTTP maintain anti conformations with normal base stacking. Further stabilization of dGTP by H-bonding with Gln59 of the finger domain explains the preferential T to G mismatch. A template 'U-turn' is stabilized by pol and the methyl group of the thymine template, revealing the structural basis of T stalling. Our structural and domain-swapping experiments indicate that the finger domain is responsible for pol's high error rates on pyrimidines and determines the incorporation specificity.

  19. Rapid and apparently error-prone excision repair of nonreplicating UV-irradiated plasmids in Xenopus laevis oocytes

    SciTech Connect

    Hays, J.B.; Ackerman, E.J.; Pang, Q.S. )

    1990-07-01

    Repair of UV-irradiated plasmid DNA microinjected into frog oocytes was measured by two techniques: transformation of repair-deficient (delta uvrB delta recA delta phr) bacteria, and removal of UV endonuclease-sensitive sites (ESS). Transformation efficiencies relative to unirradiated plasmids were used to estimate the number of lethal lesions; the latter were assumed to be Poisson distributed. These estimates were in good agreement with measurements of ESS. By both criteria, plasmid DNA was efficiently repaired, mostly during the first 2 h, when as many as 2 x 10(10) lethal lesions were removed per oocyte. This rate is about 10(6) times the average for removal of ESS from repair-proficient human cells. Repair was slower but still significant after 2 h, but some lethal lesions usually remained after overnight incubation. Most repair occurred in the absence of light, in marked contrast to differentiated frog cells, previously shown to possess photoreactivating but no excision repair activity. There was no increase in the resistance to DpnI restriction of plasmids (methylated in Escherichia coli at GATC sites) incubated in oocytes; this implies no increase in hemimethylated GATC sites, and hence no semiconservative DNA replication. Plasmid substrates capable of either intramolecular or intermolecular homologous recombination were not recombined, whether UV-irradiated or not. Repair of Lac+ plasmids was accompanied by a significant UV-dependent increase in the frequency of Lac- mutants, corresponding to a repair synthesis error frequency on the order of 10(-4) per nucleotide.

  20. LEMming: A Linear Error Model to Normalize Parallel Quantitative Real-Time PCR (qPCR) Data as an Alternative to Reference Gene Based Methods

    PubMed Central

    Feuer, Ronny; Vlaic, Sebastian; Arlt, Janine; Sawodny, Oliver; Dahmen, Uta; Zanger, Ulrich M.; Thomas, Maria

    2015-01-01

    Background Gene expression analysis is an essential part of biological and medical investigations. Quantitative real-time PCR (qPCR) is characterized with excellent sensitivity, dynamic range, reproducibility and is still regarded to be the gold standard for quantifying transcripts abundance. Parallelization of qPCR such as by microfluidic Taqman Fluidigm Biomark Platform enables evaluation of multiple transcripts in samples treated under various conditions. Despite advanced technologies, correct evaluation of the measurements remains challenging. Most widely used methods for evaluating or calculating gene expression data include geNorm and ΔΔCt, respectively. They rely on one or several stable reference genes (RGs) for normalization, thus potentially causing biased results. We therefore applied multivariable regression with a tailored error model to overcome the necessity of stable RGs. Results We developed a RG independent data normalization approach based on a tailored linear error model for parallel qPCR data, called LEMming. It uses the assumption that the mean Ct values within samples of similarly treated groups are equal. Performance of LEMming was evaluated in three data sets with different stability patterns of RGs and compared to the results of geNorm normalization. Data set 1 showed that both methods gave similar results if stable RGs are available. Data set 2 included RGs which are stable according to geNorm criteria, but became differentially expressed in normalized data evaluated by a t-test. geNorm-normalized data showed an effect of a shifted mean per gene per condition whereas LEMming-normalized data did not. Comparing the decrease of standard deviation from raw data to geNorm and to LEMming, the latter was superior. In data set 3 according to geNorm calculated average expression stability and pairwise variation, stable RGs were available, but t-tests of raw data contradicted this. Normalization with RGs resulted in distorted data contradicting

  1. Quality Control Analysis of Selected Aspects of Programs Administered by the Bureau of Student Financial Assistance. Error-Prone Model Derived from 1978-1979 Quality Control Study. Data Report. [Task 3.

    ERIC Educational Resources Information Center

    Saavedra, Pedro; Kuchak, JoAnn

    An error-prone model (EPM) to predict financial aid applicants who are likely to misreport on Basic Educational Opportunity Grant (BEOG) applications was developed, based on interviews conducted with a quality control sample of 1,791 students during 1978-1979. The model was designed to identify corrective methods appropriate for different types of…

  2. Comparative Error-Free and Error-Prone Translesion Synthesis of N(2)-2'-Deoxyguanosine Adducts Formed by Mitomycin C and Its Metabolite, 2,7-Diaminomitosene, in Human Cells.

    PubMed

    Bose, Arindam; Surugihalli, Chaitra; Pande, Paritosh; Champeil, Elise; Basu, Ashis K

    2016-05-16

    Mitomycin C (MC) is a cytotoxic and mutagenic antitumor agent that alkylates DNA upon reductive activation. 2,7-Diaminomitosene (2,7-DAM) is a major metabolite of MC in tumor cells, which also alkylates DNA. MC forms seven DNA adducts, including monoadducts and inter- and intrastrand cross-links, whereas 2,7-DAM forms two monoadducts. Herein, the biological effects of the dG-N(2) adducts formed by MC and 2,7-DAM have been compared by constructing single-stranded plasmids containing these adducts and replicating them in human embryonic kidney 293T cells. Translesion synthesis (TLS) efficiencies of dG-N(2)-MC and dG-N(2)-2,7-DAM were 38 ± 3 and 27 ± 3%, respectively, compared to that of a control plasmid. This indicates that both adducts block DNA synthesis and that dG-N(2)-2,7-DAM is a stronger replication block than dG-N(2)-MC. TLS of each adducted construct was reduced upon siRNA knockdown of pol η, pol κ, or pol ζ. For both adducts, the most significant reduction occurred with knockdown of pol κ, which suggests that pol κ plays a major role in TLS of these dG-N(2) adducts. Analysis of the progeny showed that both adducts were mutagenic, and the mutation frequencies (MF) of dG-N(2)-MC and dG-N(2)-2,7-DAM were 18 ± 3 and 10 ± 1%, respectively. For both adducts, the major type of mutation was G → T transversions. Knockdown of pol η and pol ζ reduced the MF of dG-N(2)-MC and dG-N(2)-2,7-DAM, whereas knockdown of pol κ increased the MF of these adducts. This suggests that pol κ predominantly carries out error-free TLS, whereas pol η and pol ζ are involved in error-prone TLS. The largest reduction in MF by 78 and 80%, respectively, for dG-N(2)-MC and dG-N(2)-2,7-DAM constructs occurred when pol η, pol ζ, and Rev1 were simultaneously knocked down. This result strongly suggests that, unlike pol κ, these three TLS polymerases cooperatively perform the error-prone TLS of these adducts. PMID:27082015

  3. miR-155 Over-expression Promotes Genomic Instability by Reducing High-fidelity Polymerase Delta Expression and Activating Error-prone DSB Repair

    PubMed Central

    Czochor, Jennifer R.; Sulkowski, Parker; Glazer, Peter M.

    2016-01-01

    miR-155 is an oncogenic microRNA (miR) that is often over-expressed in cancer and is associated with poor prognosis. miR-155 can target several DNA repair factors including RAD51, MLH1, and MSH6, and its over-expression results in an increased mutation frequency in vitro, although the mechanism has yet to be fully understood. Here, we demonstrate that over-expression of miR-155 drives an increased mutation frequency both in vitro and in vivo, promoting genomic instability by affecting multiple DNA repair pathways. miR-155 over-expression causes a decrease in homologous recombination, but yields a concurrent increase in the error-prone non-homologous end-joining (NHEJ) pathway. Despite repressing established targets MLH1 and MSH6, the identified mutation pattern upon miR-155 over-expression does not resemble that of a mismatch repair-deficient background. Further investigation revealed that all four subunits of polymerase delta, a high-fidelity DNA replication and repair polymerase, are down-regulated at the mRNA level in the context of miR-155 over-expression. FOXO3a, a transcription factor and known target of miR-155, has one or more putative binding site(s) in the promoter of all four polymerase delta subunits. Finally, suppression of FOXO3a by miR-155 or by siRNA knockdown is sufficient to repress the expression of the catalytic subunit of polymerase delta, POLD1, at the protein level, indicating that FOXO3a contributes to the regulation of polymerase delta levels. PMID:26850462

  4. Unique plasmids generated via pUC replicon mutagenesis in an error-prone thermophile derived from Geobacillus kaustophilus HTA426.

    PubMed

    Kobayashi, Jyumpei; Tanabiki, Misaki; Doi, Shohei; Kondo, Akihiko; Ohshiro, Takashi; Suzuki, Hirokazu

    2015-11-01

    The plasmid pGKE75-catA138T, which comprises pUC18 and the catA138T gene encoding thermostable chloramphenicol acetyltransferase with an A138T amino acid replacement (CATA138T), serves as an Escherichia coli-Geobacillus kaustophilus shuttle plasmid that confers moderate chloramphenicol resistance on G. kaustophilus HTA426. The present study examined the thermoadaptation-directed mutagenesis of pGKE75-catA138T in an error-prone thermophile, generating the mutant plasmid pGKE75(αβ)-catA138T responsible for substantial chloramphenicol resistance at 65°C. pGKE75(αβ)-catA138T contained no mutation in the catA138T gene but had two mutations in the pUC replicon, even though the replicon has no apparent role in G. kaustophilus. Biochemical characterization suggested that the efficient chloramphenicol resistance conferred by pGKE75(αβ)-catA138T is attributable to increases in intracellular CATA138T and acetyl-coenzyme A following a decrease in incomplete forms of pGKE75(αβ)-catA138T. The decrease in incomplete plasmids may be due to optimization of plasmid replication by RNA species transcribed from the mutant pUC replicon, which were actually produced in G. kaustophilus. It is noteworthy that G. kaustophilus was transformed with pGKE75(αβ)-catA138T using chloramphenicol selection at 60°C. In addition, a pUC18 derivative with the two mutations propagated in E. coli at a high copy number independently of the culture temperature and high plasmid stability. Since these properties have not been observed in known plasmids, the outcomes extend the genetic toolboxes for G. kaustophilus and E. coli. PMID:26319877

  5. Unique Plasmids Generated via pUC Replicon Mutagenesis in an Error-Prone Thermophile Derived from Geobacillus kaustophilus HTA426

    PubMed Central

    Kobayashi, Jyumpei; Tanabiki, Misaki; Doi, Shohei; Kondo, Akihiko; Ohshiro, Takashi

    2015-01-01

    The plasmid pGKE75-catA138T, which comprises pUC18 and the catA138T gene encoding thermostable chloramphenicol acetyltransferase with an A138T amino acid replacement (CATA138T), serves as an Escherichia coli-Geobacillus kaustophilus shuttle plasmid that confers moderate chloramphenicol resistance on G. kaustophilus HTA426. The present study examined the thermoadaptation-directed mutagenesis of pGKE75-catA138T in an error-prone thermophile, generating the mutant plasmid pGKE75αβ-catA138T responsible for substantial chloramphenicol resistance at 65°C. pGKE75αβ-catA138T contained no mutation in the catA138T gene but had two mutations in the pUC replicon, even though the replicon has no apparent role in G. kaustophilus. Biochemical characterization suggested that the efficient chloramphenicol resistance conferred by pGKE75αβ-catA138T is attributable to increases in intracellular CATA138T and acetyl-coenzyme A following a decrease in incomplete forms of pGKE75αβ-catA138T. The decrease in incomplete plasmids may be due to optimization of plasmid replication by RNA species transcribed from the mutant pUC replicon, which were actually produced in G. kaustophilus. It is noteworthy that G. kaustophilus was transformed with pGKE75αβ-catA138T using chloramphenicol selection at 60°C. In addition, a pUC18 derivative with the two mutations propagated in E. coli at a high copy number independently of the culture temperature and high plasmid stability. Since these properties have not been observed in known plasmids, the outcomes extend the genetic toolboxes for G. kaustophilus and E. coli. PMID:26319877

  6. [Mechanisms of targeted frameshift mutations--insertion formation under error-prone or SOS synthesis of DNA containing CIS-SYN cyncyclobutane thymine dimers].

    PubMed

    Grebneva, E A

    2014-01-01

    Up to now the mechanism of formation of frameshift mutations caused by cyclobutane pyrimidine dimers has not been yet explained satisfactorily. Mechanisms of different mutations are usually considered in polymerase model. Here, the alternative polymerase-tautomer model of ultraviolet mutagenesis is developed. The mechanism of targeted insertion formation caused by cis-syn cyclobutane thymine dimers is proposed. Insertions are mutations when one or several DNA bases are inserted.Targeted insertions are mutations of a frameshift type--when one or severalnucleotides are inserted opposite damageswhich may stop synthesis of DNA. Targeted insertions are induced bycyclobutane pyrimidine dimmers. Ultraviolet irradiation may result in a change of tautomer state of DNA bases. A thymine base may form 5 rare tautomer forms that are stable if the base is a part of cyclobutane dimer. As it was shown by structural analysis, one rare tautomeric form of thymine forms hydrogen bonds with no one canonical DNA base. Therefore, under SOS or error-prone synthesis of DNA containing cis-syn cyclobutane thymine dimers with such rare tautomeric_form a specialize or modified DNA polymerase leaves a single nucleotide gap opposite the cis-syn cyclobutane thymine dimer. According to Streisinger model, if the DNA composition within this region is homogeneous, the end of the growing DNA strand can slip and form complementary pairs with a template nucleotide neighboring to the dimer of such type a loop is formed. Further elongation of the daughter strand leads to the appearance of targeted insertion in the daughter strand. Here, it is first shown that cis-syn cyclobutane thymine dimers with one or both bases in the specific tautomer conformation--opposite which it is impossible to insert a canonical base with a hydrogen bond formation--results in targeted insertions. Moreover, the model of forming targeted single--and several-base insertions is developed. The polymerase-tautomer model of

  7. Digital Droplet PCR: CNV Analysis and Other Applications.

    PubMed

    Mazaika, Erica; Homsy, Jason

    2014-01-01

    Digital droplet PCR (ddPCR) is an assay that combines state-of-the-art microfluidics technology with TaqMan-based PCR to achieve precise target DNA quantification at high levels of sensitivity and specificity. Because quantification is achieved without the need for standard assays in an easy to interpret, unambiguous digital readout, ddPCR is far simpler, faster, and less error prone than real-time qPCR. The basic protocol can be modified with minor adjustments to suit a wide range of applications, such as CNV analysis, rare variant detection, SNP genotyping, and transcript quantification. This unit describes the ddPCR workflow in detail for the Bio-Rad QX100 system, but the theory and data interpretation are generalizable to any ddPCR system. PMID:25042719

  8. Groundtruthing Next-Gen Sequencing for Microbial Ecology–Biases and Errors in Community Structure Estimates from PCR Amplicon Pyrosequencing

    PubMed Central

    Polson, Shawn W.; Wommack, K. Eric; Williamson, Shannon J.; McDonald, Ian R.; Cary, S. Craig

    2012-01-01

    Analysis of microbial communities by high-throughput pyrosequencing of SSU rRNA gene PCR amplicons has transformed microbial ecology research and led to the observation that many communities contain a diverse assortment of rare taxa–a phenomenon termed the Rare Biosphere. Multiple studies have investigated the effect of pyrosequencing read quality on operational taxonomic unit (OTU) richness for contrived communities, yet there is limited information on the fidelity of community structure estimates obtained through this approach. Given that PCR biases are widely recognized, and further unknown biases may arise from the sequencing process itself, a priori assumptions about the neutrality of the data generation process are at best unvalidated. Furthermore, post-sequencing quality control algorithms have not been explicitly evaluated for the accuracy of recovered representative sequences and its impact on downstream analyses, reducing useful discussion on pyrosequencing reads to their diversity and abundances. Here we report on community structures and sequences recovered for in vitro-simulated communities consisting of twenty 16S rRNA gene clones tiered at known proportions. PCR amplicon libraries of the V3–V4 and V6 hypervariable regions from the in vitro-simulated communities were sequenced using the Roche 454 GS FLX Titanium platform. Commonly used quality control protocols resulted in the formation of OTUs with >1% abundance composed entirely of erroneous sequences, while over-aggressive clustering approaches obfuscated real, expected OTUs. The pyrosequencing process itself did not appear to impose significant biases on overall community structure estimates, although the detection limit for rare taxa may be affected by PCR amplicon size and quality control approach employed. Meanwhile, PCR biases associated with the initial amplicon generation may impose greater distortions in the observed community structure. PMID:22970184

  9. The Concept of Accident Proneness: A Review

    PubMed Central

    Froggatt, Peter; Smiley, James A.

    1964-01-01

    The term accident proneness was coined by psychological research workers in 1926. Since then its concept—that certain individuals are always more likely than others to sustain accidents, even though exposed to equal risk—has been questioned but seldom seriously challenged. This article describes much of the work and theory on which this concept is based, details the difficulties encountered in obtaining valid information and the interpretative errors that can arise from the examination of imperfect data, and explains why accident proneness became so readily accepted as an explanation of the facts. A recent hypothesis of accident causation, namely that a person's accident liability may vary from time to time, is outlined, and the respective abilities of this and of accident proneness to accord with data from the more reliable literature are examined. The authors conclude that the hypothesis of individual variation in liability is more realistic and in better agreement with the data than is accident proneness. PMID:14106130

  10. A false positive food chain error associated with a generic predator gut content ELISA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Conventional prey-specific gut content ELISA and PCR assays are useful for identifying predators of insect pests in nature. However, these assays are prone to yielding certain types of food chain errors. For instance, it is possible that prey remains can pass through the food chain as the result of ...

  11. Prone positioning for surgery.

    PubMed

    Bowers, Mark

    2012-05-01

    The role of the registered perioperative practitioner (Operating Department Practitioner or Registered Nurse) includes the responsibility for safely positioning patients for surgery. The prone position is in common use for a variety of surgical procedures. The formal term for this surgical position is ventral decubitus (meaning laying face down). PMID:22720505

  12. Boredom proneness and psychosocial development.

    PubMed

    Watt, J D; Vodanovich, S J

    1999-05-01

    The effect of boredom proneness as measured by the Boredom Proneness Scale (R. F. Farmer & N. D. Sundberg, 1986) on college students' psychosocial development was investigated via the Student Developmental Task and Lifestyle Assessment (SDTLA; R. B. Winston, T. K. Miller, & J. S. Prince, 1995). Low boredom-prone students had significantly higher scores on the following SDTLA measures: career planning, lifestyle planning, peer relationships, educational involvement, instrumental autonomy, emotional autonomy, interdependence, academic autonomy, and salubrious lifestyle. Gender differences on boredom proneness and psychosocial development measures are discussed. PMID:10319449

  13. Development of a high-throughput real time PCR based on a hot-start alternative for Pfu mediated by quantum dots

    NASA Astrophysics Data System (ADS)

    Sang, Fuming; Yang, Yang; Yuan, Lin; Ren, Jicun; Zhang, Zhizhou

    2015-09-01

    Hot start (HS) PCR is an excellent alternative for high-throughput real time PCR due to its ability to prevent nonspecific amplification at low temperature. Development of a cost-effective and simple HS PCR technique to guarantee high-throughput PCR specificity and consistency still remains a great challenge. In this study, we systematically investigated the HS characteristics of QDs triggered in real time PCR with EvaGreen and SYBR Green I dyes by the analysis of amplification curves, standard curves and melting curves. Two different kinds of DNA polymerases, Pfu and Taq, were employed. Here we showed that high specificity and efficiency of real time PCR were obtained in a plasmid DNA and an error-prone two-round PCR assay using QD-based HS PCR, even after an hour preincubation at 50 °C before real time PCR. Moreover, the results obtained by QD-based HS PCR were comparable to a commercial Taq antibody DNA polymerase. However, no obvious HS effect of QDs was found in real time PCR using Taq DNA polymerase. The findings of this study demonstrated that a cost-effective high-throughput real time PCR based on QD triggered HS PCR could be established with high consistency, sensitivity and accuracy.Hot start (HS) PCR is an excellent alternative for high-throughput real time PCR due to its ability to prevent nonspecific amplification at low temperature. Development of a cost-effective and simple HS PCR technique to guarantee high-throughput PCR specificity and consistency still remains a great challenge. In this study, we systematically investigated the HS characteristics of QDs triggered in real time PCR with EvaGreen and SYBR Green I dyes by the analysis of amplification curves, standard curves and melting curves. Two different kinds of DNA polymerases, Pfu and Taq, were employed. Here we showed that high specificity and efficiency of real time PCR were obtained in a plasmid DNA and an error-prone two-round PCR assay using QD-based HS PCR, even after an hour

  14. Virtual PCR

    SciTech Connect

    Gardner, S N; Clague, D S; Vandersall, J A; Hon, G; Williams, P L

    2006-02-23

    experiments were tainted by contaminated products received from the manufacturer. Much knowledge has been gained in the development of the code thus far, but without final debugging, increasing its robustness and verifying it against experimental results, the papers which we have drafted to share our findings still require the final data necessary for publication. The following sections summarize our final progress on VPCR as it stands after 1.5 years of effort on an ambitious project scoped for a 3 year period. We have additional details of the methods than are provided here, but would like to have legal protection in place before releasing them. The result of this project, a suite of programs that predict PCR products as a function of reaction conditions and sequences, will be used to address outstanding questions in pathogen detection and forensics at LLNL. VPCR should enable scientists to optimize PCR protocols in terms of time, temperature, ion concentration, and primer sequences and concentrations, and to estimate products and error rates in advance of performing experiments. Our proposed capabilities are well ahead of all currently available technologies, which do not model non-equilibrium kinetics, polymerase extension, or predict multiple or undesired PCR products. We are currently seeking DHS funding to complete the project, at which time licensing opportunities will be explored, an updated patent application will be prepared, and a publication will be submitted. A provisional and a full patent application have already been filed (1).

  15. Peripheral blood antigen presenting cell responses in otitis-prone and non-otitis-prone infants.

    PubMed

    Surendran, Naveen; Nicolosi, Ted; Kaur, Ravinder; Pichichero, Michael E

    2016-01-01

    Stringently defined otitis-prone (sOP) children represent a new classification of the otitis-prone condition. Previous studies showed dysfunction in Ab, B-cell memory and T-cell memory responses. We sought to determine whether there are defects in numbers, phenotype and/or function of professional APC in the peripheral blood of sOP infants. APC phenotypic counts, MHC II expression and intracellular cytokine levels were determined in response to TLR7/8 (R848) stimulation by flow cytometry. Innate immune mRNA expression was measured using RT-PCR and cytokines were measured using Luminex technology. Significant (P < 0.05) increases in the phenotypic counts of monocytes and conventional dendritic cells but not plasmacytoid DCs were observed in sOP compared with non-otitis-prone (NOP) age-matched infants. No significant differences in APC activation or function were observed. Expression of various TLRs, intracellular signaling molecules and downstream cytokines was also not found to be significantly different between sOP and NOP infants. Higher numbers of APCs in sOP infants suggest the possibility of a persistent mucosal inflammatory status. Transcriptional and cytokine profiles of PBMCs among sOP infants suggest their systemic innate responses are not different compared to NOP infants. PMID:26566651

  16. Replicative mechanisms for CNV formation are error prone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated 67 breakpoint junctions of gene copy number gains in 31 unrelated subjects. We observed a strikingly high frequency of small deletions and insertions (29%) apparently originating from polymerase slippage events, in addition to frameshifts and point mutations in homonucleotide runs (1...

  17. Propensity Score Weighting with Error-Prone Covariates

    ERIC Educational Resources Information Center

    McCaffrey, Daniel F.; Lockwood, J. R.; Setodji, Claude M.

    2011-01-01

    Inverse probability weighting (IPW) estimates are widely used in applications where data are missing due to nonresponse or censoring or in observational studies of causal effects where the counterfactuals cannot be observed. This extensive literature has shown the estimators to be consistent and asymptotically normal under very general conditions,…

  18. List of Error-Prone Abbreviations, Symbols, and Dose Designations

    MedlinePlus

    ... unit dose (e.g., diltiazem 125 mg IV infusion “UD” misin- Use “as directed” terpreted as meaning to give the entire infusion as a unit [bolus] dose) Misinterpretation Correction Mistaken ...

  19. Vegetation fire proneness in Europe

    NASA Astrophysics Data System (ADS)

    Pereira, Mário; Aranha, José; Amraoui, Malik

    2015-04-01

    Fire selectivity has been studied for vegetation classes in terms of fire frequency and fire size in a few European regions. This analysis is often performed along with other landscape variables such as topography, distance to roads and towns. These studies aims to assess the landscape sensitivity to forest fires in peri-urban areas and land cover changes, to define landscape management guidelines and policies based on the relationships between landscape and fires in the Mediterranean region. Therefore, the objectives of this study includes the: (i) analysis of the spatial and temporal variability statistics within Europe; and, (ii) the identification and characterization of the vegetated land cover classes affected by fires; and, (iii) to propose a fire proneness index. The datasets used in the present study comprises: Corine Land Cover (CLC) maps for 2000 and 2006 (CLC2000, CLC2006) and burned area (BA) perimeters, from 2000 to 2013 in Europe, provided by the European Forest Fire Information System (EFFIS). The CLC is a part of the European Commission programme to COoRdinate INformation on the Environment (Corine) and it provides consistent, reliable and comparable information on land cover across Europe. Both the CLC and EFFIS datasets were combined using geostatistics and Geographical Information System (GIS) techniques to access the spatial and temporal evolution of the types of shrubs and forest affected by fires. Obtained results confirms the usefulness and efficiency of the land cover classification scheme and fire proneness index which allows to quantify and to compare the propensity of vegetation classes and countries to fire. As expected, differences between northern and southern Europe are notorious in what concern to land cover distribution, fire incidence and fire proneness of vegetation cover classes. This work was supported by national funds by FCT - Portuguese Foundation for Science and Technology, under the project PEst-OE/AGR/UI4033/2014 and by

  20. Prone positioning: is it safe and effective?

    PubMed

    Dirkes, Susan; Dickinson, Sharon; Havey, Renee; O'brien, Denise

    2012-01-01

    Prone positioning has been used as a treatment option for patients with acute lung injury or acute respiratory distress syndrome (ARDS) since the early 1970s. Prone position and extended prone position ventilation have been shown to increase end-expiratory lung volume, alveolar recruitment, and oxygenation in patients with severe hypoxemic and acute respiratory failure. Prone positioning is not a benign procedure, and there are potential risks (complications) that can occur to both the patient and the health care worker. Notable complications that can arise include: unplanned extubation, lines pulled, tubes kinked, and back and other injuries to personnel. Prone positioning is a viable, inexpensive therapy for the treatment of severe ARDS. This maneuver consistently improves systemic oxygenation in 70% to 80% of patients with ARDS. With the utilization of a standardized protocol and a trained and dedicated critical care staff, prone positioning can be performed safely. PMID:22157493

  1. Translationally optimal codons associate with aggregation-prone sites in proteins.

    PubMed

    Lee, Yaelim; Zhou, Tong; Tartaglia, Gian Gaetano; Vendruscolo, Michele; Wilke, Claus O

    2010-12-01

    We analyze the relationship between codon usage bias and residue aggregation propensity in the genomes of four model organisms, Escherichia coli, yeast, fly, and mouse, as well as the archaeon Halobacterium species NRC-1. Using the Mantel-Haenszel procedure, we find that translationally optimal codons associate with aggregation-prone residues. Our results are qualitatively and quantitatively similar to those of an earlier study where we found an association between translationally optimal codons and buried residues. We also combine the aggregation-propensity data with solvent-accessibility data. Although the resulting data set is small, and hence statistical power low, results indicate that the association between optimal codons and aggregation-prone residues exists both at buried and at exposed sites. By comparing codon usage at different combinations of sites (exposed, aggregation-prone sites versus buried, non-aggregation-prone sites; buried, aggregation-prone sites versus exposed, non-aggregation-prone sites), we find that aggregation propensity and solvent accessibility seem to have independent effects of (on average) comparable magnitude on codon usage. Finally, in fly, we assess whether optimal codons associate with sites at which amino acid substitutions lead to an increase in aggregation propensity, and find only a very weak effect. These results suggest that optimal codons may be required to reduce the frequency of translation errors at aggregation-prone sites that coincide with certain functional sites, such as protein-protein interfaces. Alternatively, optimal codons may be required for rapid translation of aggregation-prone regions. PMID:21046618

  2. Statistical approaches to account for false-positive errors in environmental DNA samples.

    PubMed

    Lahoz-Monfort, José J; Guillera-Arroita, Gurutzeta; Tingley, Reid

    2016-05-01

    Environmental DNA (eDNA) sampling is prone to both false-positive and false-negative errors. We review statistical methods to account for such errors in the analysis of eDNA data and use simulations to compare the performance of different modelling approaches. Our simulations illustrate that even low false-positive rates can produce biased estimates of occupancy and detectability. We further show that removing or classifying single PCR detections in an ad hoc manner under the suspicion that such records represent false positives, as sometimes advocated in the eDNA literature, also results in biased estimation of occupancy, detectability and false-positive rates. We advocate alternative approaches to account for false-positive errors that rely on prior information, or the collection of ancillary detection data at a subset of sites using a sampling method that is not prone to false-positive errors. We illustrate the advantages of these approaches over ad hoc classifications of detections and provide practical advice and code for fitting these models in maximum likelihood and Bayesian frameworks. Given the severe bias induced by false-negative and false-positive errors, the methods presented here should be more routinely adopted in eDNA studies. PMID:26558345

  3. Intra- and Interfractional Variations for Prone Breast Irradiation: An Indication for Image-Guided Radiotherapy

    SciTech Connect

    Morrow, Natalya V.; Stepaniak, Christopher; White, Julia; Wilson, J. Frank; Li, X. Allen

    2007-11-01

    Purpose: Intra- and interfractional errors for breast cancer patients undergoing breast irradiation in the prone position were analyzed. Methods and Materials: To assess intrafractional error resulting from respiratory motion, four-dimensional computed tomography scans were acquired for 3 prone and 3 supine patients, and the respiratory motion was compared for the two positions. To assess the interfractional error caused by daily set-up variations, daily electronic portal images of one of the treatment beams were taken for 15 prone-positioned patients. Portal images were then overlaid with images from the planning system that included the breast contour and the isocenter, treatment beam portal, and isocenter. The shift between the planned and actual isocenter was recorded for each portal image, and descriptive statistics were collected for each patient. The margins were calculated using the 2{sigma}+0.7{sigma} recipe, as well as 95% confidence interval based on the pooled standard deviation of the datasets. Results: Respiratory motion of the chest wall is drastically reduced from 2.3 {+-} 0.9 mm in supine position to -0.1 {+-} 0.4 mm in prone position. The daily set-up errors vary in magnitude from 0.0 cm to 1.65 cm and are patient dependent. The margins were defined by considering only the standard deviation to be 1.1 cm, and 2.0 cm when the systematic errors were considered using the 2{sigma}+0.7{sigma} recipe. Conclusions: Prone positioning of patients for breast irradiation significantly reduces the uncertainty introduced by intrafractional respiratory motion. The presence of large systematic error in the interfractional variations necessitates a large clinical target volume-to-planning target volume margin and indicates the importance of image guidance for partial breast irradiation in the prone position, particularly using imaging modality capable of identifying the lumpectomy cavity.

  4. Cyclone hazard proneness of districts of India

    NASA Astrophysics Data System (ADS)

    Mohapatra, M.

    2015-04-01

    Hazards associated with tropical cyclones (TCs) are long-duration rotatory high velocity winds, very heavy rain, and storm tide. India has a coastline of about 7516 km of which 5400 km is along the mainland. The entire coast is affected by cyclones with varying frequency and intensity. Thus classification of TC hazard proneness of the coastal districts is very essential for planning and preparedness aspects of management of TCs. So, an attempt has been made to classify TC hazard proneness of districts by adopting a hazard criteria based on frequency and intensity of cyclone, wind strength, probable maximum precipitation, and probable maximum storm surge. Ninety-six districts including 72 districts touching the coast and 24 districts not touching the coast, but lying within 100 km from the coast have been classified based on their proneness. Out of 96 districts, 12 are very highly prone, 41 are highly prone, 30 are moderately prone, and the remaining 13 districts are less prone. This classification of coastal districts based on hazard may be considered for all the required purposes including coastal zone management and planning. However, the vulnerability of the place has not been taken into consideration. Therefore, composite cyclone risk of a district, which is the product of hazard and vulnerability, needs to be assessed separately through a detailed study.

  5. Ethnic and gender differences in boredom proneness

    SciTech Connect

    Gibson, G.S.; Morales,

    1996-02-01

    Although boredom may exhibit many shared elements, culturally specific attitudes have also been found to exist. The present paper investigated boredom proneness among African-American college students. Data from 120 participants on the Boredom Proneness (BP) Scale was analyzed and compared to cross-cultural participants. African-American females scored significantly higher than African-American males. Scores were presented from two other studies to show a comparative look at boredom proneness in five other ethnic groups. African-American females are the only female ethnic group to score higher on the BP Scale than their male counterparts. Additionally, overall African-Americans, were found to have higher BP scores than their Western counterparts.

  6. Acceptance testing prone stereotactic breast biopsy units.

    PubMed

    Kimme-Smith, C; Solberg, T

    1994-07-01

    When the Mammography Quality Standards Act becomes law in October, 1994, stereotactic breast biopsy units may require yearly physicist calibration. Upright stereotactic units can be easily tested using conventional mammography procedures and a gelatin phantom containing simulated calcifications, but prone units are difficult to assess because of the under-table tube configuration. The two current manufacturers of these units have made different design decisions which affect each unit's calibration. There are a number of important distinctions between screening and prone biopsy units. For the two currently available prone units, a pronounced heel effect makes ion chamber position critical. Focal spot measurements are particularly difficult on one unit because there is no light field. The fixed grid on the other unit must be tested with a flood film. Physicists who inspect these units before their clinical use should be aware of variations needed by this equipment for specific acceptance tests. PMID:7968854

  7. Alternated Prone and Supine Whole-Breast Irradiation Using IMRT: Setup Precision, Respiratory Movement and Treatment Time

    SciTech Connect

    Veldeman, Liv; De Gersem, Werner; Speleers, Bruno; Truyens, Bart; Van Greveling, Annick; Van den Broecke, Rudy; De Neve, Wilfried

    2012-04-01

    Purpose: The objective of this study was to compare setup precision, respiration-related breast movement and treatment time between prone and supine positions for whole-breast irradiation. Methods and Materials: Ten patients with early-stage breast carcinoma after breast-conserving surgery were treated with prone and supine whole breast-irradiation in a daily alternating schedule. Setup precision was monitored using cone-beam computed tomography (CBCT) imaging. Respiration-related breast movement in the vertical direction was assessed by magnetic sensors. The time needed for patient setup and for the CBCT procedure, the beam time, and the length of the whole treatment slot were also recorded. Results: Random and systematic errors were not significantly different between positions in individual patients for each of the three axes (left-right, longitudinal, and vertical). Respiration-related movement was smaller in prone position, but about 80% of observations showed amplitudes <1 mm in both positions. Treatment slots were longer in prone position (21.2 {+-} 2.5 min) than in supine position (19.4 {+-} 0.8 min; p = 0.044). Conclusion: Comparison of setup precision between prone and supine position in the same patient showed no significant differences in random and systematic errors. Respiratory movement was smaller in prone position. The longer treatment slots in prone position can probably be attributed to the higher repositioning need.

  8. PCR thermocycler

    DOEpatents

    Benett, William J.; Richards, James B.

    2003-01-01

    A sleeve-type silicon polymerase chain reaction (PCR) chamber or thermocycler having improved thermal performance. The silicon sleeve reaction chamber is improved in thermal performance by etched features therein that reduce thermal mass and increase the surface area of the sleeve for cooling. This improved thermal performance of the thermocycler enables an increase in speed and efficiency of the reaction chamber. The improvement is accomplished by providing grooves in the faces of the sleeve and a series of grooves on the interior surfaces that connect with grooves on the faces of the sleeve. The grooves can be anisotropically etched in the silicon sleeve simultaneously with formation of the chamber.

  9. PCR thermocycler

    DOEpatents

    Benett, William J.; Richards, James B.

    2005-05-17

    A sleeve-type silicon polymerase chain reaction (PCR) chamber or thermocycler having improved thermal performance. The silicon sleeve reaction chamber is improved in thermal performance by etched features therein that reduce thermal mass and increase the surface area of the sleeve for cooling. This improved thermal performance of the thermocycler enables an increase in speed and efficiency of the reaction chamber. The improvement is accomplished by providing grooves in the faces of the sleeve and a series of grooves on the interior surfaces that connect with grooves on the faces of the sleeve. The grooves can be anisotropically etched in the silicon sleeve simultaneously with formation of the chamber.

  10. Suffocated prone: the iatrogenic tragedy of SIDS.

    PubMed Central

    Högberg, U; Bergström, E

    2000-01-01

    Epidemiologic research has shown that prone sleeping is a major risk factor for sudden infant death syndrome (SIDS). In a public health review from Sweden, we explored the historical background of the SIDS epidemic, starting with the view of the Catholic Church that sudden infant deaths were infanticides and ending with the slowly disseminated recommendation of a prone sleeping position during the 1960s, 1970s, and 1980s. The story of the SIDS epidemic illustrates a pitfall of preventive medicine--the translation of health care routines for patients to general health advice that targets the whole population. False advice, as well as correct advice, may have a profound effect on public health because of the many individuals concerned. Preventive measures must be based on scientific evidence, and systematic supervision and evaluations are necessary to identify the benefits or the harm of the measures. The discovery of the link between prone sleeping and SIDS has been called a success story for epidemiology, but the slow acceptance of the causal relationship between prone sleeping and SIDS illustrates the weak position of epidemiology and public health within the health care system. PMID:10754964

  11. Refractive Errors

    MedlinePlus

    ... and lens of your eye helps you focus. Refractive errors are vision problems that happen when the ... cornea, or aging of the lens. Four common refractive errors are Myopia, or nearsightedness - clear vision close ...

  12. Covariation bias in panic-prone individuals.

    PubMed

    Pauli, P; Montoya, P; Martz, G E

    1996-11-01

    Covariation estimates between fear-relevant (FR; emergency situations) or fear-irrelevant (FI; mushrooms and nudes) stimuli and an aversive outcome (electrical shock) were examined in 10 high-fear (panic-prone) and 10 low-fear respondents. When the relation between slide category and outcome was random (illusory correlation), only high-fear participants markedly overestimated the contingency between FR slides and shocks. However, when there was a high contingency of shocks following FR stimuli (83%) and a low contingency of shocks following FI stimuli (17%), the group difference vanished. Reversal of contingencies back to random induced a covariation bias for FR slides in high- and low-fear respondents. Results indicate that panic-prone respondents show a covariation bias for FR stimuli and that the experience of a high contingency between FR slides and aversive outcomes may foster such a covariation bias even in low-fear respondents. PMID:8952200

  13. Current Suicide Proneness and Past Suicidal Behavior in Adjudicated Adolescents

    ERIC Educational Resources Information Center

    Langhinrichsen-Rohling, Jennifer; Lamis, Dorian A.

    2008-01-01

    Youth recently assigned to probation (n = 233) were assessed for current suicide proneness, depression, and hopelessness, as well as for recent suicide ideation, previous suicide ideation, or suicide attempt(s). The Life Attitudes Schedule-Short Form (LAS-SF) was used to assess suicide proneness. As per the LAS-SF, suicide proneness was defined…

  14. Registration of prone and supine CT colonography scans using correlation optimized warping and canonical correlation analysis

    SciTech Connect

    Wang Shijun; Yao Jianhua; Liu Jiamin; Petrick, Nicholas; Van Uitert, Robert L.; Periaswamy, Senthil; Summers, Ronald M.

    2009-12-15

    Purpose: In computed tomographic colonography (CTC), a patient will be scanned twice--Once supine and once prone--to improve the sensitivity for polyp detection. To assist radiologists in CTC reading, in this paper we propose an automated method for colon registration from supine and prone CTC scans. Methods: We propose a new colon centerline registration method for prone and supine CTC scans using correlation optimized warping (COW) and canonical correlation analysis (CCA) based on the anatomical structure of the colon. Four anatomical salient points on the colon are first automatically distinguished. Then correlation optimized warping is applied to the segments defined by the anatomical landmarks to improve the global registration based on local correlation of segments. The COW method was modified by embedding canonical correlation analysis to allow multiple features along the colon centerline to be used in our implementation. Results: We tested the COW algorithm on a CTC data set of 39 patients with 39 polyps (19 training and 20 test cases) to verify the effectiveness of the proposed COW registration method. Experimental results on the test set show that the COW method significantly reduces the average estimation error in a polyp location between supine and prone scans by 67.6%, from 46.27{+-}52.97 to 14.98 mm{+-}11.41 mm, compared to the normalized distance along the colon centerline algorithm (p<0.01). Conclusions: The proposed COW algorithm is more accurate for the colon centerline registration compared to the normalized distance along the colon centerline method and the dynamic time warping method. Comparison results showed that the feature combination of z-coordinate and curvature achieved lowest registration error compared to the other feature combinations used by COW. The proposed method is tolerant to centerline errors because anatomical landmarks help prevent the propagation of errors across the entire colon centerline.

  15. Action simulation in hallucination-prone adolescents

    PubMed Central

    Dahoun, Tarik; Eliez, Stephan; Chen, Fei; Badoud, Deborah; Schneider, Maude; Larøi, Frank; Debbane, Martin

    2013-01-01

    Theoretical and empirical accounts suggest that impairments in self-other discrimination processes are likely to promote the expression of hallucinations. Studies using a variety of paradigms involving self-performed actions argue in favor of perspective taking confusion in hallucination-prone subjects. However, our understanding of such processes during adolescence is still at an early stage. The present study thus aims (1) to delineate the neural correlates sustaining mental simulation of actions involving self-performed actions (first-person perspective; 1PP) and other-performed actions (third-person perspective; 3PP) during adolescence (2) to identify atypical activation patterns during 1PP/3PP mental simulation of actions in hallucination-prone adolescents (3) to examine whether differential risk for schizophrenia (clinical vs. genetic) is also associated with differential impairments in the 1PP/3PP mental simulation of actions during adolescence. Twenty-two typically developing controls (Control group; 6 females), 12 hallucination-prone adolescents [auditory hallucination (AH) group; 7 females] and 13 adolescents with 22q11.2 Deletion Syndrome (22q11.2DS group; 4 females) were included in the study. During the fMRI task, subjects were presented with a cue (self-other priming cues) indicating to perform the task using either a first person perspective (“you”-1PP) or a third person perspective (“best friend”-3PP) and then they were asked to mentally simulate actions based on the type of cue. Hallucination-proneness was assessed using a self-report questionnaire [Cardiff Anomalous Perception Scale (CAPS)]. Our results indicated that atypical patterns of cerebral activation, particularly in the key areas of self-other distinction, were found in both groups at risk for auditory hallucinations (AHs and 22q11.2DS). More precisely, adolescents in the AH group presented decreased activations in the right middle occipital gyrus BA19, left cingulate gyrus BA31

  16. Immunologic abnormalities in melanoma-prone families.

    PubMed

    Dean, J H; Greene, M H; Reimer, R R; LeSane, F V; McKeen, E A; Mulvihill, J J; Blattner, W A; Herberman, R B; Fraumeni, J F

    1979-11-01

    Sixty members of 4 families prone to cutaneous malignant melanoma (CMM) and a genetically determined precursor nevus syndrome underwent extensive immunologic evaluation. The most consistent finding was a diminished in vitro response to pooled alloantigens in the one-way mixed leukocyte culture (MLC) and a tendency to low T-lymphocyte and B-lymphocyte levels. When compared to controls, low B-lymphocyte levels and reduced MLC responses were found not only in family members with CMM and/or precursor nevi but also in unaffected blood relatives and spouses. The genesis of the immune dysfunction and its possible relationship to melanoma pathogenesis remain to be clarified. PMID:159376

  17. Production of prone-to-aggregate proteins.

    PubMed

    Lebendiker, Mario; Danieli, Tsafi

    2014-01-21

    Expression of recombinant proteins in Escherichia coli (E. coli) remains the most popular and cost-effective method for producing proteins in basic research and for pharmaceutical applications. Despite accumulating experience and methodologies developed over the years, production of recombinant proteins prone to aggregate in E. coli-based systems poses a major challenge in most research applications. The challenge of manufacturing these proteins for pharmaceutical applications is even greater. This review will discuss effective methods to reduce and even prevent the formation of aggregates in the course of recombinant protein production. We will focus on important steps along the production path, which include cloning, expression, purification, concentration, and storage. PMID:24211444

  18. [Ketosis prone type 2 diabetes (KPD)].

    PubMed

    Concha L, Luciana; Durruty A, Pilar; García de Los Ríos A, Manuel

    2015-09-01

    Ketosis prone type 2 diabetes (KPD) is presently a well-defined clinical entity, characterized by a debut with severe hyperglycemia and ketoacidosis similar to the presenting form of Type 1 diabetes mellitus (DM1). However, it appears in subjects with Type 2 diabetes mellitus (DM2) phenotype. This situation is caused by an acute, reversible dysfunction of the beta cell in individuals with insulin resistance. Once the acute stage subsides, patients behave as having a DM2 and do not require insulin treatment. They should be kept on a diet and oral hypoglycemic drugs due to their susceptibility to have recurrent acute ketotic decompensations. PMID:26530207

  19. Empirical evaluation of humpback whale telomere length estimates; quality control and factors causing variability in the singleplex and multiplex qPCR methods

    PubMed Central

    2012-01-01

    Background Telomeres, the protective cap of chromosomes, have emerged as powerful markers of biological age and life history in model and non-model species. The qPCR method for telomere length estimation is one of the most common methods for telomere length estimation, but has received recent critique for being too error-prone and yielding unreliable results. This critique coincides with an increasing awareness of the potentials and limitations of the qPCR technique in general and the proposal of a general set of guidelines (MIQE) for standardization of experimental, analytical, and reporting steps of qPCR. In order to evaluate the utility of the qPCR method for telomere length estimation in non-model species, we carried out four different qPCR assays directed at humpback whale telomeres, and subsequently performed a rigorous quality control to evaluate the performance of each assay. Results Performance differed substantially among assays and only one assay was found useful for telomere length estimation in humpback whales. The most notable factors causing these inter-assay differences were primer design and choice of using singleplex or multiplex assays. Inferred amplification efficiencies differed by up to 40% depending on assay and quantification method, however this variation only affected telomere length estimates in the worst performing assays. Conclusion Our results suggest that seemingly well performing qPCR assays may contain biases that will only be detected by extensive quality control. Moreover, we show that the qPCR method for telomere length estimation can be highly precise and accurate, and thus suitable for telomere measurement in non-model species, if effort is devoted to optimization at all experimental and analytical steps. We conclude by highlighting a set of quality controls which may serve for further standardization of the qPCR method for telomere length estimation, and discuss some of the factors that may cause variation in qPCR experiments

  20. Comparison of Droplet Digital PCR and qPCR for the Quantification of Shiga Toxin-Producing Escherichia coli in Bovine Feces.

    PubMed

    Verhaegen, Bavo; De Reu, Koen; De Zutter, Lieven; Verstraete, Karen; Heyndrickx, Marc; Van Coillie, Els

    2016-01-01

    Cattle are considered to be the main reservoir for Shiga toxin-producing Escherichia coli (STEC) and are often the direct or indirect source of STEC outbreaks in humans. Accurate measurement of the concentration of shed STEC in cattle feces could be a key answer to questions concerning transmission of STEC, contamination sources and efficiency of treatments at farm level. Infected animals can be identified and the contamination level quantified by real-time quantitative PCR (qPCR), which has its specific limitations. Droplet digital PCR (ddPCR) has been proposed as a method to overcome many of the drawbacks of qPCR. This end-point amplification PCR is capable of absolute quantification independent from any reference material and is less prone to PCR inhibition than qPCR. In this study, the qPCR-based protocol described by Verstraete et al. (2014) for Shiga toxin genes stx1 and stx2 and the intimin gene eae quantification was optimized for ddPCR analysis. The properties of ddPCR and qPCR using two different mastermixes (EMM: TaqMan(®) Environmental Master Mix 2.0; UMM: TaqMan(®) Universal PCR Master Mix) were evaluated, using standard curves and both artificial and natural contaminated cattle fecal samples. In addition, the susceptibility of these assays to PCR-inhibitors was investigated. Evaluation of the standard curves and both artificial and natural contaminated cattle fecal samples suggested a very good agreement between qPCR using EMM and ddPCR. Furthermore, similar sensitivities and no PCR inhibition were recorded for both assays. On the other hand, qPCR using UMM was clearly prone to PCR inhibition. In conclusion, the ddPCR technique shows potential for the accurate absolute quantification of STEC on the farms, without relying on standardized reference material. PMID:27213452

  1. Comparison of Droplet Digital PCR and qPCR for the Quantification of Shiga Toxin-Producing Escherichia coli in Bovine Feces

    PubMed Central

    Verhaegen, Bavo; De Reu, Koen; De Zutter, Lieven; Verstraete, Karen; Heyndrickx, Marc; Van Coillie, Els

    2016-01-01

    Cattle are considered to be the main reservoir for Shiga toxin-producing Escherichia coli (STEC) and are often the direct or indirect source of STEC outbreaks in humans. Accurate measurement of the concentration of shed STEC in cattle feces could be a key answer to questions concerning transmission of STEC, contamination sources and efficiency of treatments at farm level. Infected animals can be identified and the contamination level quantified by real-time quantitative PCR (qPCR), which has its specific limitations. Droplet digital PCR (ddPCR) has been proposed as a method to overcome many of the drawbacks of qPCR. This end-point amplification PCR is capable of absolute quantification independent from any reference material and is less prone to PCR inhibition than qPCR. In this study, the qPCR-based protocol described by Verstraete et al. (2014) for Shiga toxin genes stx1 and stx2 and the intimin gene eae quantification was optimized for ddPCR analysis. The properties of ddPCR and qPCR using two different mastermixes (EMM: TaqMan® Environmental Master Mix 2.0; UMM: TaqMan® Universal PCR Master Mix) were evaluated, using standard curves and both artificial and natural contaminated cattle fecal samples. In addition, the susceptibility of these assays to PCR-inhibitors was investigated. Evaluation of the standard curves and both artificial and natural contaminated cattle fecal samples suggested a very good agreement between qPCR using EMM and ddPCR. Furthermore, similar sensitivities and no PCR inhibition were recorded for both assays. On the other hand, qPCR using UMM was clearly prone to PCR inhibition. In conclusion, the ddPCR technique shows potential for the accurate absolute quantification of STEC on the farms, without relying on standardized reference material. PMID:27213452

  2. Medication Errors

    MedlinePlus

    ... to reduce the risk of medication errors to industry and others at FDA. Additionally, DMEPA prospectively reviews ... List of Abbreviations Regulations and Guidances Guidance for Industry: Safety Considerations for Product Design to Minimize Medication ...

  3. Medication Errors

    MedlinePlus

    Medicines cure infectious diseases, prevent problems from chronic diseases, and ease pain. But medicines can also cause harmful reactions if not used ... You can help prevent errors by Knowing your medicines. Keep a list of the names of your ...

  4. Hallucination proneness, schizotypy and meta-cognition.

    PubMed

    Stirling, John; Barkus, Emma; Lewis, Shon

    2007-06-01

    Disordered or maladaptive meta-cognitive processing appears to be a prominent feature for some individuals with a diagnosis of schizophrenia. We sought to establish whether healthy individuals distinguished either in terms hallucination proneness (HP) or level of schizotypy could also be differentiated on the sub-scales of the Meta-cognitions Questionnaire (MCQ), or a modified version of it in which items about worry were replaced with items specifically related to thinking. A total of 106 healthy volunteers completed the Oxford and Liverpool Inventory of Feelings and Experiences and Launay-Slade hallucination scale, the Schizotypal Personality Questionnaire and two versions of the MCQ: the original which assesses five domains of meta-cognition and an adapted version in which items relating to worry had been replaced by items relating to thinking or reflecting on thinking (MCQ-th). ANOVA indicated highly significant differences between three groups of individuals differentiated in terms of high, medium and low proneness to hallucinations on four of the five MCQ sub-scales, and three of the four MCQ-th factors. Regression analyses indicated that the MCQ factors encompassing (1) a sense of uncontrollability of thinking (and the perceived attendant dangers of this) and (2) negative beliefs about thinking related to suspicion and punishment were the strongest predictors of high schizotypy. Individuals who score higher on a measure of HP are more likely to display patterns of meta-cognitive processing that resemble, in certain respects, those reported in individuals with a diagnosis of schizophrenia. High schizotypy predicts a negative appraisal about both the controllability and consequences of thinking. PMID:16934218

  5. Single-molecule PCR: an artifact-free PCR approach for the analysis of somatic mutations.

    PubMed

    Kraytsberg, Yevgenya; Khrapko, Konstantin

    2005-09-01

    A critical review of the clone-by-clone approach to the analysis of complex spectra of somatic mutations is presented. The study of a priori unknown somatic mutations requires painstaking analysis of complex mixtures of multiple mutant and non-mutant DNA molecules. If mutant fractions are sufficiently high, these mixtures can be dissected by the cloning of individual DNA molecules and scanning of the individual clones for mutations (e.g., by sequencing). Currently, the majority of such cloning is performed using PCR fragments. However, post-PCR cloning may result in various PCR artifacts - PCR errors and jumping PCR - and preferential amplification of certain mutations. This review argues that single-molecule PCR is a simple alternative that promises to evade the disadvantages inherent to post-PCR cloning and enhance mutational analysis in the future. PMID:16149882

  6. Sex Determination Using PCR

    ERIC Educational Resources Information Center

    Kima, Peter E.; Rasche, Madeline E.

    2004-01-01

    PCR has revolutionized many aspects of biochemistry and molecular biology research. In the following exercise, students learn PCR by isolating their own DNA, amplifying specific segments of the X and Y chromosomes, and estimating the sizes of the PCR products using agarose gel electrophoresis. Based on the pattern of PCR products, students can…

  7. Neglected Children, Shame-Proneness, and Depressive Symptoms

    PubMed Central

    Bennett, David S.; Sullivan, Margaret Wolan; Lewis, Michael

    2013-01-01

    Neglected children may be at increased risk for depressive symptoms. This study examines shame-proneness as an outcome of child neglect and as a potential explanatory variable in the relation between neglect and depressive symptoms. Participants were 111 children (52 with a Child Protective Services [CPS] allegation of neglect) seen at age 7. Neglected children reported more shame-proneness and more depressive symptoms than comparison children. Guilt-proneness, in contrast, was unrelated to neglect and depressive symptoms, indicating specificity for shame-proneness. The potential role of shame as a process variable that can help explain how some neglected children exhibit depressive symptoms is discussed. PMID:20724372

  8. Error Detection and Error Classification: Failure Awareness in Data Transfer Scheduling

    SciTech Connect

    Louisiana State University; Balman, Mehmet; Kosar, Tevfik

    2010-10-27

    Data transfer in distributed environment is prone to frequent failures resulting from back-end system level problems, like connectivity failure which is technically untraceable by users. Error messages are not logged efficiently, and sometimes are not relevant/useful from users point-of-view. Our study explores the possibility of an efficient error detection and reporting system for such environments. Prior knowledge about the environment and awareness of the actual reason behind a failure would enable higher level planners to make better and accurate decisions. It is necessary to have well defined error detection and error reporting methods to increase the usability and serviceability of existing data transfer protocols and data management systems. We investigate the applicability of early error detection and error classification techniques and propose an error reporting framework and a failure-aware data transfer life cycle to improve arrangement of data transfer operations and to enhance decision making of data transfer schedulers.

  9. Syndromes of Ketosis-Prone Diabetes Mellitus

    PubMed Central

    Balasubramanyam, Ashok; Nalini, Ramaswami; Hampe, Christiane S.; Maldonado, Mario

    2008-01-01

    Ketosis-prone diabetes (KPD) is a widespread, emerging, heterogeneous syndrome characterized by patients who present with diabetic ketoacidosis or unprovoked ketosis but do not necessarily have the typical phenotype of autoimmune type 1 diabetes. Multiple, severe forms of β-cell dysfunction appear to underlie the pathophysiology of KPD. Until recently, the syndrome has lacked an accurate, clinically relevant and etiologically useful classification scheme. We have utilized a large, longitudinally followed, heterogeneous, multiethnic cohort of KPD patients to identify four clinically and pathophysiologically distinct subgroups that are separable by the presence or absence of β-cell autoimmunity and the presence or absence of β-cell functional reserve. The resulting “Aβ” classification system of KPD has proven to be highly accurate and predictive of such clinically important outcomes as glycemic control and insulin dependence, as well as an aid to biochemical and molecular investigations into novel causes of β-cell dysfunction. In this review, we describe the current state of knowledge in regard to the natural history, pathophysiology, and treatment of the subgroups of KPD, with an emphasis on recent advances in understanding their immunological and genetic bases. PMID:18292467

  10. Evening types are prone to depression.

    PubMed

    Merikanto, Ilona; Lahti, Tuuli; Kronholm, Erkki; Peltonen, Markku; Laatikainen, Tiina; Vartiainen, Erkki; Salomaa, Veikko; Partonen, Timo

    2013-06-01

    Certain preferences for the timing of daily activities (chronotype) may predispose an individual to sleep problems and mood disorders. In this study, we have examined the link between chronotypes and depression. Participants (N = 6071) were recruited from a random sample of the general population aged 25 to 74 yrs living in defined geographical areas, as part of the National FINRISK Study in 2007 in Finland. Chronotype assessment was based on six items from the original Horne-Östberg Morningness-Eveningness Questionnaire. Depression was assessed with four self-reported items, including two probes for a diagnosis of a major depressive episode, diagnosed or treated depression, and use of antidepressants. We also analyzed correlations between chronotype and several health indicators, such as systolic and diastolic blood pressures, resting heart rate, weight, and waist circumference. The odds ratios for a range of indicators of depression were higher for evening types (2.7- to 4.1-fold) and intermediate types (1.5- to 1.9-fold) than for morning types. Our results suggest that individuals having a preference for evening hours to carry out their daily activities are prone to depression. PMID:23688117

  11. Parent Proneness to Shame and the Use of Psychological Control

    ERIC Educational Resources Information Center

    Mills, Rosemary S. L.; Freeman, Wendy S.; Clara, Ian P.; Elgar, Frank J.; Walling, Bobbi R.; Mak, Leanne

    2007-01-01

    We examined the link between parent proneness to shame and two forms of psychological control, overprotection and critical/rejecting behavior, in parents of preschoolers. Because shame is self-condemning, proneness to shame affects intrapersonal and interpersonal functioning. We hypothesized that parents' emotion-regulatory responses to shame…

  12. Systematic lossy forward error protection for error-resilient digital video broadcasting

    NASA Astrophysics Data System (ADS)

    Rane, Shantanu D.; Aaron, Anne; Girod, Bernd

    2004-01-01

    We present a novel scheme for error-resilient digital video broadcasting,using the Wyner-Ziv coding paradigm. We apply the general framework of systematic lossy source-channel coding to generate a supplementary bitstream that can correct transmission errors in the decoded video waveform up to a certain residual distortion. The systematic portion consists of a conventional MPEG-coded bitstream, which is transmitted over the error-prone channel without forward error correction.The supplementary bitstream is a low rate representation of the transmitted video sequence generated using Wyner-Ziv encoding. We use the conventionally decoded error-concealed MPEG video sequence as side information to decode the Wyner-Ziv bits. The decoder combines the error-prone side information and the Wyner-Ziv description to yield an improved decoded video signal. Our results indicate that, over a large range of channel error probabilities, this scheme yields superior video quality when compared with traditional forward error correction techniques employed in digital video broadcasting.

  13. Piezoelectric control of structures prone to instabilities

    NASA Astrophysics Data System (ADS)

    Kim, Sunjung

    Thin-walled structures such as stiffened panels fabricated out of high strength materials are ubiquitous in aerospace structures. These are prone to buckle in a variety of modes with strong possibility of adverse interaction under axial compression and/or bending. Optimally designed stiffened panels, at an appropriate combination of axial compression and suddenly applied lateral pressure undergo large amplitude oscillations and may experience divergence. Under aerodynamic loading, they can experience flutter instability with the amplitudes of oscillations attaining a limit (LCO) or escalating without any limit. Control of structures prone to these forms of instability using piezo-electric actuators is the theme of this dissertation. Issues involved in the control of stiffened panels under axial compression and liable to buckle simultaneously in local and overall modes are studied. The analytical approach employs finite elements in which are embedded periodic components of local buckling including the second order effects. It is shown that the adverse effects of mode interaction can be counteracted by simply controlling the overall bending of the stiffener by piezo-electric actuators attached its tips. Control is exercised by self-sensing actuators by direct negative feedback voltages proportional to the bending strains of the stiffener. In a dynamic loading environment, where vibrations are triggered by suddenly applied lateral pressure, negative velocity feedback is employed with voltages proportional to the bending strain-rate. The local plate oscillations are effectively controlled by a piezo-electric actuators placed along the longitudinal center line of the panel. The problem of flutter under aerodynamic pressure of stiffened panels in the linear and post-critical regimes is studied using modal analysis and finite strips. The analysis, control and interpretation of the response are facilitated by identification of two families of characteristic modes of

  14. Cdk1 phosphorylation of the kinetochore protein Nsk1 prevents error-prone chromosome segregation

    PubMed Central

    Chen, Jun-Song; Lu, Lucy X.; Ohi, Melanie D.; Creamer, Kevin M.; English, Chauca; Partridge, Janet F.; Ohi, Ryoma

    2011-01-01

    Cdk1 controls many aspects of mitotic chromosome behavior and spindle microtubule (MT) dynamics to ensure accurate chromosome segregation. In this paper, we characterize a new kinetochore substrate of fission yeast Cdk1, Nsk1, which promotes proper kinetochore–MT (k-MT) interactions and chromosome movements in a phosphoregulated manner. Cdk1 phosphorylation of Nsk1 antagonizes Nsk1 kinetochore and spindle localization during early mitosis. A nonphosphorylatable Nsk1 mutant binds prematurely to kinetochores and spindle, cementing improper k-MT attachments and leading to high rates of lagging chromosomes that missegregate. Accordingly, cells lacking nsk1 exhibit synthetic growth defects with mutations that disturb MT dynamics and/or kinetochore structure, and lack of proper phosphoregulation leads to even more severe defects. Intriguingly, Nsk1 is stabilized by binding directly to the dynein light chain Dlc1 independently of the dynein motor, and Nsk1–Dlc1 forms chainlike structures in vitro. Our findings establish new roles for Cdk1 and the Nsk1–Dlc1 complex in regulating the k-MT interface and chromosome segregation. PMID:22065639

  15. Psychological performance of accident-prone automobile drivers in China: a case-control study.

    PubMed

    Jin, H Q; Araki, S; Wu, X K; Zhang, Y W; Yokoyama, K

    1991-03-01

    To evaluate the role of neurobehavioural factors in the aetiology of recurrent automobile accidents, we administered the Revised Wechsler Adult Intelligence Scale (WAIS-R), the Eysenck Personality Questionnaire (EPQ), and choice and simple reaction time tests to 31 accident-prone automobile drivers. These drivers who had caused three or more traffic accidents during the years 1980-1984, were selected from records of 2723 traffic accidents registered by Hefei Traffic Police Department during the years 1980-1984. The same tests were administered to an equal number of sex- and age-matched control drivers who had no reported involvement in automobile accidents. None of the subjects had suffered from any neuropsychiatric illness or head injury. Comparisons between the two groups indicated that for accident-prone drivers scores on picture completion and block design subtests of the WAIS-R were significantly lowered (p less than 0.05); scores for neurosis extrovert behaviour and psychosis (EPQ) were significantly higher (p less than 0.05); and the number of errors in the choice reaction time test was significantly higher (p less than 0.01). It is suggested that accident-prone drivers have lower psychological performance, poorer judgement and a higher tendency than safe drivers to be neurotic, extrovert and psychotic. PMID:2066226

  16. Effect of Reducing Abdominal Compression during Prone CT Colonography on Ascending Colonic Rotation during Supine-to-Prone Positional Change

    PubMed Central

    Jang, Jong Keon; Lee, Jong Seok; Kim, Hyun Jin; Kim, Ah Young; Ha, Hyun Kwon

    2016-01-01

    Objective To determine the effect of reduced abdominal compression in prone position on ascending colonic movement during supine-to-prone positional change during CT colonography (CTC). Materials and Methods Eighteen consecutive patients who had undergone prone CTC scanning with cushion blocks placed under the chest and hip/thigh to reduce abdominal compression and had confirmed sessile polyps ≥ 6 mm in the well-distended, straight, mid-ascending colon, were included. Radial location along the ascending colonic luminal circumference (°) was measured for 24 polyps and 54 colonic teniae on supine and prone CTC images. The supine-to-prone change ranging between -180° and +180° (- and + for internal and external colonic rotations, respectively), was determined. In addition, possible causes of any ascending colonic rotations were explored. Results Abdominal compression during prone CTC scanning completely disappeared with the use of cushion blocks in 17 of 18 patients. However, some degrees of ascending colonic rotation were still observed, with the radial location changes of -22° to 61° (median, 13.9°) for the polyps and similar degrees for teniae. Fifty-four percent and 56% of polyps and teniae, respectively, showed changes > 10°. The radial location change of the polyps was significantly associated with the degree of anterior shift of the small bowel and mesentery (r = 0.722, p < 0.001) and the degree of posterior displacement of the ascending colon (r = 0.566, p = 0.004) during supine-to-prone positional change. Conclusion Ascending colonic rotation upon supine-to-prone positional change during CTC, mostly in the form of external rotation, is not eliminated by removing abdominal compression in prone position. PMID:26798215

  17. Cancer Survivors More Prone to Obesity, Study Finds

    MedlinePlus

    ... fullstory_160399.html Cancer Survivors More Prone to Obesity, Study Finds Risk appears to be particularly high ... 12, 2016 FRIDAY, Aug. 12, 2016 (HealthDay News) -- Obesity is more common among cancer survivors in the ...

  18. Empathy, Guilt Proneness, and Gender: Relative Contributions to Prosocial Behaviour

    PubMed Central

    Torstveit, Linda; Sütterlin, Stefan; Lugo, Ricardo Gregorio

    2016-01-01

    Guilt is a moral emotion that is often looked upon as a negative trait. However, studies show that some individuals are more predisposed to think, feel and act in a more ethical manner because of a lower threshold to experience guilt. Some theories of helping behaviour emphasize the evolutionary mechanisms, while other theories stress the importance of social variables. This study investigated whether guilt proneness as a dispositional trait can be associated with prosocial behaviour. Five hundred sixty-nine participants reported in an online survey their own levels of guilt proneness, frequency of prosocial behaviour, and related cognitions such as empathy. This study is among the first to demonstrate how guilt proneness combined with empathy can explain additional variance in prosocial behaviour. The findings also indicate gender differences in the precursors of prosocial behaviour, suggesting women are more influenced by the effects of guilt proneness on prosocial behaviour than men. PMID:27298635

  19. Women More Prone to Anxiety Than Men, Review Finds

    MedlinePlus

    ... 159215.html Women More Prone to Anxiety Than Men, Review Finds Westerners also wrestle with the condition ... twice as likely to suffer from anxiety as men. Moreover, people in North America and Western Europe ...

  20. Empathy, Guilt Proneness, and Gender: Relative Contributions to Prosocial Behaviour.

    PubMed

    Torstveit, Linda; Sütterlin, Stefan; Lugo, Ricardo Gregorio

    2016-05-01

    Guilt is a moral emotion that is often looked upon as a negative trait. However, studies show that some individuals are more predisposed to think, feel and act in a more ethical manner because of a lower threshold to experience guilt. Some theories of helping behaviour emphasize the evolutionary mechanisms, while other theories stress the importance of social variables. This study investigated whether guilt proneness as a dispositional trait can be associated with prosocial behaviour. Five hundred sixty-nine participants reported in an online survey their own levels of guilt proneness, frequency of prosocial behaviour, and related cognitions such as empathy. This study is among the first to demonstrate how guilt proneness combined with empathy can explain additional variance in prosocial behaviour. The findings also indicate gender differences in the precursors of prosocial behaviour, suggesting women are more influenced by the effects of guilt proneness on prosocial behaviour than men. PMID:27298635

  1. Understanding and Confronting Our Mistakes: The Epidemiology of Error in Radiology and Strategies for Error Reduction.

    PubMed

    Bruno, Michael A; Walker, Eric A; Abujudeh, Hani H

    2015-10-01

    Arriving at a medical diagnosis is a highly complex process that is extremely error prone. Missed or delayed diagnoses often lead to patient harm and missed opportunities for treatment. Since medical imaging is a major contributor to the overall diagnostic process, it is also a major potential source of diagnostic error. Although some diagnoses may be missed because of the technical or physical limitations of the imaging modality, including image resolution, intrinsic or extrinsic contrast, and signal-to-noise ratio, most missed radiologic diagnoses are attributable to image interpretation errors by radiologists. Radiologic interpretation cannot be mechanized or automated; it is a human enterprise based on complex psychophysiologic and cognitive processes and is itself subject to a wide variety of error types, including perceptual errors (those in which an important abnormality is simply not seen on the images) and cognitive errors (those in which the abnormality is visually detected but the meaning or importance of the finding is not correctly understood or appreciated). The overall prevalence of radiologists' errors in practice does not appear to have changed since it was first estimated in the 1960s. The authors review the epidemiology of errors in diagnostic radiology, including a recently proposed taxonomy of radiologists' errors, as well as research findings, in an attempt to elucidate possible underlying causes of these errors. The authors also propose strategies for error reduction in radiology. On the basis of current understanding, specific suggestions are offered as to how radiologists can improve their performance in practice. PMID:26466178

  2. The Role of a Prone Setup in Breast Radiation Therapy

    PubMed Central

    Huppert, Nelly; Jozsef, Gabor; DeWyngaert, Keith; Formenti, Silvia Chiara

    2011-01-01

    Most patients undergoing breast conservation therapy receive radiotherapy in the supine position. Historically, prone breast irradiation has been advocated for women with large pendulous breasts in order to decrease acute and late toxicities. With the advent of CT planning, the prone technique has become both feasible and reproducible. It was shown to be advantageous not only for women with larger breasts but in most patients since it consistently reduces, if not eliminates, the inclusion of heart and lung within the field. The prone setup has been accepted as the best localizing position for both MRI and stereotactic biopsy, but its adoption has been delayed in radiotherapy. New technological advances including image-modulated radiation therapy and image-guided radiation therapy have made possible the exploration of accelerated fractionation schemes with a concomitant boost to the tumor bed in the prone position, along with better imaging and verification of reproducibility of patient setup. This review describes some of the available techniques for prone breast radiotherapy and the available experience in their application. The NYU prone breast radiotherapy approach is discussed, including a summary of the results from several prospective trials. PMID:22655240

  3. Development and validation of the Adolescent Shame-Proneness Scale.

    PubMed

    Simonds, Laura M; John, Mary; Fife-Schaw, Chris; Willis, Susie; Taylor, Helen; Hand, Heidi; Rahim, Masuma; Winstanley, Harriet; Winton, Holly

    2016-05-01

    Like other self-conscious emotions, shame takes on particular significance during late childhood and adolescence because of a developing capacity for self-reflection, self-other comparisons, and sensitivity to the views of others. Shame is a potentially important variable in adolescent well-being given its established associations with depression, reduced feelings of self-worth, and problematic anger. Three studies are reported that describe the development and validation of the Adolescent Shame-Proneness Scale (ASPS), a novel semi-idiographic measure of shame-proneness. The ASPS is a 19-item measure assessing 3 components of shame-proneness-negative self-evaluation, externalization, and emotional discomfort. Taken together, the studies support the reliability and validity of the ASPS as a semi-idiographic measure of shame-proneness in adolescents aged 11 to 18 years. ASPS scores correlate as expected with scores on existing measure of shame-proneness and with measures of anger, negative affect, and self-esteem. More important, the data suggest that ASPS scores are related to, but distinct from, guilt. Confirmatory factor analysis supported the validity of the ASPS factor structure (RMSEA = .08, SRMR = .05, CFI = .97, NNFI = .97). The ASPS represents a unique contribution to existing options for measuring shame-proneness in research and clinical contexts. Further work is required to assess the ASPS' temporal stability and its viability and psychometric properties in more culturally diverse samples. (PsycINFO Database Record PMID:26302099

  4. Perspective-taking abilities in the balance between autism tendencies and psychosis proneness

    PubMed Central

    Abu-Akel, Ahmad M.; Wood, Stephen J.; Hansen, Peter C.; Apperly, Ian A.

    2015-01-01

    Difficulties with the ability to appreciate the perspective of others (mentalizing) is central to both autism and schizophrenia spectrum disorders. While the disorders are diagnostically independent, they can co-occur in the same individual. The effect of such co-morbidity is hypothesized to worsen mentalizing abilities. The recent influential ‘diametric brain theory’, however, suggests that the disorders are etiologically and phenotypically diametrical, predicting opposing effects on one's mentalizing abilities. To test these contrasting hypotheses, we evaluated the effect of psychosis and autism tendencies on the perspective-taking (PT) abilities of 201 neurotypical adults, on the assumption that autism tendencies and psychosis proneness are heritable dimensions of normal variation. We show that while both autism tendencies and psychosis proneness induce PT errors, their interaction reduced these errors. Our study is, to our knowledge, the first to observe that co-occurring autistic and psychotic traits can exert opposing influences on performance, producing a normalizing effect possibly by way of their diametrical effects on socio-cognitive abilities. This advances the notion that some individuals may, to some extent, be buffered against developing either illness or present fewer symptoms owing to a balanced expression of autistic and psychosis liability. PMID:25972469

  5. DEM-based Approaches for the Identification of Flood Prone Areas

    NASA Astrophysics Data System (ADS)

    Samela, Caterina; Manfreda, Salvatore; Nardi, Fernando; Grimaldi, Salvatore; Roth, Giorgio; Sole, Aurelia

    2013-04-01

    Manfreda et al. (2011) that suggested a modified Topographic Index (TIm) for the identification of flood prone area. 4) The downslope index proposed by Hjerdt et al. (2004) that quantifies the topographic controls on hydrology by evaluating head differences following the (surface) flow path in the steepest direction. The method does not use the exit point at the stream as reference; instead, the algorithm looks at how far a parcel of water has to travel along its flow path to lose a given head potential, d [m]. This last index was not defined with the aim to describe flood prone areas; in fact it represents an interesting alternative descriptor of morphological features that deserve to be tested. Analyses have been carried out for some Italian catchments. The outcomes of the four methods are presented using, for calibration and validation purposes, flood inundation maps made available by River Basin Authorities. The aim is, therefore, to evaluate the reliability and the relative errors in the detection of the areas subject to the flooding hazard. These techniques should not be considered as an alternative of traditional procedures, but additional tool for the identification of flood-prone areas and hazard graduation over large regions or when a preliminary identification is needed. Reference Degiorgis M., G. Gnecco, S. Gorni, G. Roth, M. Sanguineti, A. C. Taramasso, Classifiers for the detection of flood-prone areas using remote sensed elevation data, J. Hydrol., 470-471, 302-315, 2012. Hjerdt, K. N., J. J. McDonnell, J. Seibert, A. Rodhe, A new topographic index to quantify downslope controls on local drainage, Water Resour. Res., 40, W05602, 2004. Manfreda, S., M. Di Leo, A. Sole, Detection of Flood Prone Areas using Digital Elevation Models, Journal of Hydrologic Engineering, Vol. 16, No. 10, 781-790, 2011. Nardi, F., E. R. Vivoni, S. Grimaldi, Investigating a floodplain scaling relation using a hydrogeomorphic delineation method, Water Resour. Res., 42, W09409, 2006.

  6. [Diagnostic Errors in Medicine].

    PubMed

    Buser, Claudia; Bankova, Andriyana

    2015-12-01

    The recognition of diagnostic errors in everyday practice can help improve patient safety. The most common diagnostic errors are the cognitive errors, followed by system-related errors and no fault errors. The cognitive errors often result from mental shortcuts, known as heuristics. The rate of cognitive errors can be reduced by a better understanding of heuristics and the use of checklists. The autopsy as a retrospective quality assessment of clinical diagnosis has a crucial role in learning from diagnostic errors. Diagnostic errors occur more often in primary care in comparison to hospital settings. On the other hand, the inpatient errors are more severe than the outpatient errors. PMID:26649954

  7. A PCR based protocol for detecting indel mutations induced by TALENs and CRISPR/Cas9 in zebrafish.

    PubMed

    Yu, Chuan; Zhang, Yaguang; Yao, Shaohua; Wei, Yuquan

    2014-01-01

    Genome editing techniques such as the zinc-finger nucleases (ZFNs), transcription activator-like effecter nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system Cas9 can induce efficient DNA double strand breaks (DSBs) at the target genomic sequence and result in indel mutations by the error-prone non-homologous end joining (NHEJ) DNA repair system. Several methods including sequence specific endonuclease assay, T7E1 assay and high resolution melting curve assay (HRM) etc have been developed to detect the efficiency of the induced mutations. However, these assays have some limitations in that they either require specific sequences in the target sites or are unable to generate sequencing-ready mutant DNA fragments or unable to distinguish induced mutations from natural nucleotide polymorphism. Here, we developed a simple PCR-based protocol for detecting indel mutations induced by TALEN and Cas9 in zebrafish. We designed 2 pairs of primers for each target locus, with one putative amplicon extending beyond the putative indel site and the other overlapping it. With these primers, we performed a qPCR assay to efficiently detect the frequencies of newly induced mutations, which was accompanied with a T-vector-based colony analysis to generate single-copy mutant fragment clones for subsequent DNA sequencing. Thus, our work has provided a very simple, efficient and fast assay for detecting induced mutations, which we anticipate will be widely used in the area of genome editing. PMID:24901507

  8. ''I'm Sitting Here Feeling Aphasic!'' A Study of Recurrent Perseverative Errors Elicited in Unimpaired Speakers

    ERIC Educational Resources Information Center

    Moses, Melanie S.; Nickels, Lyndsey A.; Sheard, Christine

    2004-01-01

    In this study, the recurrent perseverative errors produced by 44 speakers without impairment were examined in picture naming and reading aloud tasks under a fast response deadline. The proportion of perseverative relative to non-perseverative errors was greater in picture naming, the more error-prone task, than in reading aloud. Additionally,…

  9. Error Rate Comparison during Polymerase Chain Reaction by DNA Polymerase

    PubMed Central

    McInerney, Peter; Adams, Paul; Hadi, Masood Z.

    2014-01-01

    As larger-scale cloning projects become more prevalent, there is an increasing need for comparisons among high fidelity DNA polymerases used for PCR amplification. All polymerases marketed for PCR applications are tested for fidelity properties (i.e., error rate determination) by vendors, and numerous literature reports have addressed PCR enzyme fidelity. Nonetheless, it is often difficult to make direct comparisons among different enzymes due to numerous methodological and analytical differences from study to study. We have measured the error rates for 6 DNA polymerases commonly used in PCR applications, including 3 polymerases typically used for cloning applications requiring high fidelity. Error rate measurement values reported here were obtained by direct sequencing of cloned PCR products. The strategy employed here allows interrogation of error rate across a very large DNA sequence space, since 94 unique DNA targets were used as templates for PCR cloning. The six enzymes included in the study, Taq polymerase, AccuPrime-Taq High Fidelity, KOD Hot Start, cloned Pfu polymerase, Phusion Hot Start, and Pwo polymerase, we find the lowest error rates with Pfu, Phusion, and Pwo polymerases. Error rates are comparable for these 3 enzymes and are >10x lower than the error rate observed with Taq polymerase. Mutation spectra are reported, with the 3 high fidelity enzymes displaying broadly similar types of mutations. For these enzymes, transition mutations predominate, with little bias observed for type of transition. PMID:25197572

  10. Error Rate Comparison during Polymerase Chain Reaction by DNA Polymerase.

    PubMed

    McInerney, Peter; Adams, Paul; Hadi, Masood Z

    2014-01-01

    As larger-scale cloning projects become more prevalent, there is an increasing need for comparisons among high fidelity DNA polymerases used for PCR amplification. All polymerases marketed for PCR applications are tested for fidelity properties (i.e., error rate determination) by vendors, and numerous literature reports have addressed PCR enzyme fidelity. Nonetheless, it is often difficult to make direct comparisons among different enzymes due to numerous methodological and analytical differences from study to study. We have measured the error rates for 6 DNA polymerases commonly used in PCR applications, including 3 polymerases typically used for cloning applications requiring high fidelity. Error rate measurement values reported here were obtained by direct sequencing of cloned PCR products. The strategy employed here allows interrogation of error rate across a very large DNA sequence space, since 94 unique DNA targets were used as templates for PCR cloning. The six enzymes included in the study, Taq polymerase, AccuPrime-Taq High Fidelity, KOD Hot Start, cloned Pfu polymerase, Phusion Hot Start, and Pwo polymerase, we find the lowest error rates with Pfu, Phusion, and Pwo polymerases. Error rates are comparable for these 3 enzymes and are >10x lower than the error rate observed with Taq polymerase. Mutation spectra are reported, with the 3 high fidelity enzymes displaying broadly similar types of mutations. For these enzymes, transition mutations predominate, with little bias observed for type of transition. PMID:25197572

  11. Sound-Color Associations in Psychosis-Prone Individuals.

    PubMed

    Berman, Brady; Serper, Mark

    2016-08-01

    Synesthetic-pseudosynesthetic characteristics have been hypothesized to be a schizophrenia endophenotype, a developmental feature, and/or a symptom of psychosis. Few studies to date, however, have examined whether individuals at risk for psychosis have synesthetic symptoms. We examined the relationship between hue and pitch in high psychosis prone (HP; n = 30) and low psychosis prone individuals (LP; n = 31). Synesthesia was evaluated using self-report and two performance-based tasks. Results revealed that HP subjects experienced more synesthetic experiences than the LP only on the self-report measure. These results suggest that high psychotic prone patients report unusual experiences but are no more likely to exhibit synesthesia than LP individuals. HP individuals, however, were more likely to choose shorter wavelength colors than LP individuals on performance tasks. These results are consistent with the notion that psychosis vulnerability is associated with a preference to light wavelengths associated with increasing emotional valence and negative affect. PMID:27218222

  12. Real-Time PCR

    NASA Astrophysics Data System (ADS)

    Evrard, A.; Boulle, N.; Lutfalla, G. S.

    Over the past few years there has been a considerable development of DNA amplification by polymerase chain reaction (PCR), and real-time PCR has now superseded conventional PCR techniques in many areas, e.g., the quantification of nucleic acids and genotyping. This new approach is based on the detection and quantification of a fluorescent signal proportional to the amount of amplicons generated by PCR. Real-time detection is achieved by coupling a thermocycler with a fluorimeter. This chapter discusses the general principles of quantitative real-time PCR, the different steps involved in implementing the technique, and some examples of applications in medicine. The polymerase chain reaction (PCR) provides a way of obtaining a large number of copies of a double-stranded DNA fragment of known sequence. This DNA amplification technique, developed in 1985 by K. Mullis (Cetus Corporation), saw a spectacular development over the space of a few years, revolutionising the methods used up to then in molecular biology. Indeed, PCR has many applications, such as the detection of small amounts of DNA, cloning, and quantitative analysis (assaying), each of which will be discussed further below.

  13. How to avoid perioperative visual loss following prone spinal surgery

    PubMed Central

    Epstein, Nancy E.

    2016-01-01

    Background: In a prior article, “Perioperative visual loss (POVL) following prone spinal surgery: A review,” Epstein documented that postoperative visual loss (POVL) occurs in from 0.013% to 0.2% of spine procedures performed in the prone position. POVL is largely attributed to ischemic optic neuropathy (ION), central retinal artery occlusion (CRAO), cortical blindness (CB), direct compression (prone pillows/horseshoe, eye protectors), and rarely, acute angle closure glaucoma. Methods: Risk factors for ION include prolonged surgery, extensive fusions, anemia, hypotension, hypovolemia, diabetes, obesity, use of the Wilson frame, male sex, and microvascular pathology. CRAO may result from improper prone positioning (e.g., eye compression or rotation contributing to jugular/venous or carotid compression), while CB more typically results from both direct compression and obesity. Results: Several preventive/prophylactic measures should limit the risk of POVL. The routine use of an arterial line and continuous intraoperative monitoring document intraoperative hypotension/hypovolemia/anemia that can be immediately corrected with appropriate resuscitative measures. Application of a 3-pin head holder completely eliminates direct eye compression and maintains the neck in a neutral posture, thus avoiding rotation that can contribute to jugular/venous obstruction and/or inadvertent carotid compression. In addition, elevating the head 10° from the horizontal directly reduces intraocular pressure. Conclusions: The best way to avoid POVL following prone spine surgery is to prevent it. Routine use of an arterial line, intraoperative monitoring, a 3-pin head holder, and elevation of the head 10° from the horizontal should limit the risk of encountering POVL after spinal procedures performed in the prone position.

  14. [Continuously alternating prone and supine positioning in acute lung failure].

    PubMed

    Walz, M; Muhr, G

    1992-11-01

    Acute respiratory failure is still one the main problems in surgical intensive care. Unknown pathophysiological mechanisms permit only symptomatic therapy. Today ventilatory strategies by using PEEP und IRV are established to improve gas exchange and FRC by recruiting collapsed alveoli, decreasing intrapulmonary shunting and returning V/Q matching to normal. Furthermore different studies have shown the effects of supine and lateral decubitus posture in patients with acute respiratory failure. There are only rare reports on using the prone position, which doesn't require two-lung ventilation in difference to lateral position. We have studied 16 patients with acute respiratory failure by using continuous changing between prone and supine position under mechanical ventilation. All were male, aged 41.3 years in the middle and showed an average "Injury Severity Score" of 30 (13-50). 15 were trauma patients with blunt chest trauma in 11 cases. We have used prone position on threatening or manifest ARDS. In all patients we observed an increment of PaO2 during prone position on to 48 mmHg so that FiO2 could be reduced on an average of 0.2 within the first 48 h since changing patient's position. Posture changing depends on blood gas analysis, specifically on decreasing PaO2 after previous increment. Patients remained in prone and supine position at a mean of 6.3 (4.5-20) h and posture changing was proceeded over a period of 15.4 (7-32) days. No problems recording to blood pressure or mechanical ventilation appeared during prone position. 11 of 16 patients survived (68.8%), 5 died of cardiac (2) and multi organic failure (3) in connection with sepsis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1458988

  15. Interdisciplinary development of an ergonomic prone mobility cart.

    PubMed

    Brose, Steven W; Kilbane, Martin J; Harpster, Elizabeth; Mitchell, Steven J; Ho, Chester; Gustafson, Ken J

    2016-01-01

    Pressure ulcers remain a major source of morbidity and mortality in Veterans with neurologic impairment. Management of pressure ulcers typically involves pressure relief over skin regions containing wounds, but this can lead to loss of mobility and independence when the wounds are located in regions that receive pressure during sitting. An innovative, iterative design process was undertaken to improve prone cart design for persons with spinal cord injury and pressure ulceration. Further investigation of ways to improve prone carts is warranted to enhance the quality of life of persons with pressure ulcers. PMID:27533301

  16. Systematic lossy error protection of video based on H.264/AVC redundant slices

    NASA Astrophysics Data System (ADS)

    Rane, Shantanu; Girod, Bernd

    2006-01-01

    We propose the use of H.264 redundant slices for Systematic Lossy Error Protection (SLEP) of a video signal transmitted over an error-prone channel. In SLEP, the video signal is transmitted to the decoder without channel coding. Additionally, a Wyner-Ziv encoded version of the video signal is transmitted in order to provide error-resilience. In the event of channel errors, the Wyner-Ziv description is decoded as a substitute for the error-prone portions of the primary video signal. Since the Wyner-Ziv description is typically coarser than the primary video signal, SLEP is a lossy error protection technique which trades-off residual quantization distortion for improved error-resilience properties, such as graceful degradation of decoder picture quality. We describe how H.264 redundant slices can be used to generate the Wyner-Ziv description, and present simulation results to demonstrate the advantages of this method over traditional methods such as FEC.

  17. 44 CFR 60.24 - Planning considerations for flood-related erosion-prone areas.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... flood-related erosion-prone areas. 60.24 Section 60.24 Emergency Management and Assistance FEDERAL..., Mudslide (i.e., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.24 Planning considerations for flood-related erosion-prone areas. The planning process for communities identified under part 65 of...

  18. 44 CFR 60.24 - Planning considerations for flood-related erosion-prone areas.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... flood-related erosion-prone areas. 60.24 Section 60.24 Emergency Management and Assistance FEDERAL..., Mudslide (i.e., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.24 Planning considerations for flood-related erosion-prone areas. The planning process for communities identified under part 65 of...

  19. 44 CFR 60.24 - Planning considerations for flood-related erosion-prone areas.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... flood-related erosion-prone areas. 60.24 Section 60.24 Emergency Management and Assistance FEDERAL..., Mudslide (i.e., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.24 Planning considerations for flood-related erosion-prone areas. The planning process for communities identified under part 65 of...

  20. 44 CFR 60.24 - Planning considerations for flood-related erosion-prone areas.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... flood-related erosion-prone areas. 60.24 Section 60.24 Emergency Management and Assistance FEDERAL..., Mudslide (i.e., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.24 Planning considerations for flood-related erosion-prone areas. The planning process for communities identified under part 65 of...

  1. 44 CFR 60.24 - Planning considerations for flood-related erosion-prone areas.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... flood-related erosion-prone areas. 60.24 Section 60.24 Emergency Management and Assistance FEDERAL..., Mudslide (i.e., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.24 Planning considerations for flood-related erosion-prone areas. The planning process for communities identified under part 65 of...

  2. Sun compass error model

    NASA Technical Reports Server (NTRS)

    Blucker, T. J.; Ferry, W. W.

    1971-01-01

    An error model is described for the Apollo 15 sun compass, a contingency navigational device. Field test data are presented along with significant results of the test. The errors reported include a random error resulting from tilt in leveling the sun compass, a random error because of observer sighting inaccuracies, a bias error because of mean tilt in compass leveling, a bias error in the sun compass itself, and a bias error because the device is leveled to the local terrain slope.

  3. The pathophysiology of medication errors: how and where they arise

    PubMed Central

    McDowell, Sarah E; Ferner, Harriet S; Ferner, Robin E

    2009-01-01

    Errors arise when an action is intended but not performed; errors that arise from poor planning or inadequate knowledge are characterized as mistakes; those that arise from imperfect execution of well-formulated plans are called slips when an erroneous act is committed and lapses when a correct act is omitted. Some tasks are intrinsically prone to error. Examples are tasks that are unfamiliar to the operator or performed under pressure. Tasks that require the calculation of a dosage or dilution are especially susceptible to error. The tasks of prescribing, preparation, and administration of medicines are complex, and are carried out within a complex system; errors can occur at each of many steps and the error rate for the overall process is therefore high. The error rate increases when health-care professionals are inexperienced, inattentive, rushed, distracted, fatigued, or depressed; orthopaedic surgeons and nurses may be more likely than other health-care professionals to make medication errors. Medication error rates in hospital are higher in paediatric departments and intensive care units than elsewhere. Rates of medication errors may be higher in very young or very old patients. Intravenous antibiotics are the drugs most commonly involved in medication errors in hospital; antiplatelet agents, diuretics, and non-steroidal anti-inflammatory drugs are most likely to account for ‘preventable admissions’. Computers effectively reduce the rates of easily counted errors. It is not clear whether they can save lives lost through rare but dangerous errors in the medication process. PMID:19594527

  4. Utility of PCR in diagnosing pulmonary tuberculosis.

    PubMed Central

    Bennedsen, J; Thomsen, V O; Pfyffer, G E; Funke, G; Feldmann, K; Beneke, A; Jenkins, P A; Hegginbothom, M; Fahr, A; Hengstler, M; Cleator, G; Klapper, P; Wilkins, E G

    1996-01-01

    At present, the rapid diagnosis of pulmonary tuberculosis rests with microscopy. However, this technique is insensitive and many cases of pulmonary tuberculosis cannot be initially confirmed. Nucleic acid amplification techniques are extremely sensitive, but when they are applied to tuberculosis diagnosis, they have given variable results. Investigators at six centers in Europe compared a standardized PCR system (Amplicor; Roche) against conventional culture methods. Defined clinical information was collected. Discrepant samples were retested, and inhibition assays and backup amplification with a separate primer pair were performed. Mycobacterium tuberculosis complex organisms were recovered from 654 (9.1%) of 7,194 samples and 293 (7.8%) of 3,738 patients. Four hundred fifty-two of the M. tuberculosis isolates from 204 patients were smear positive and culture positive. Among the culture-positive specimens, PCR had a sensitivity of 91.4% for smear-positive specimens and 60.9% for smear-negative specimens, with a specificity of 96.1%. Analysis of 254 PCR-positive, culture-negative specimens with discrepant results revealed that 130 were from patients with recently diagnosed tuberculosis and 94 represented a presumed laboratory error. Similar analysis of 118 PCR-negative, culture-positive specimens demonstrated that 27 discrepancies were due to presumed uneven aliquot distribution and 11 were due to presumed laboratory error; PCR inhibitors were detected in 8 specimens. Amplicor enables laboratories with little previous experience with nucleic acid amplification to perform PCR. Disease in more than 60% of the patients with tuberculosis with smear-negative, culture-positive specimens can be diagnosed at the time of admission, and potentially all patients with smear-positive specimens can immediately be confirmed as being infected with M. tuberculosis, leading to improved clinical management. PMID:8735089

  5. The Social Antecedents of Anger Proneness in Young Adulthood

    ERIC Educational Resources Information Center

    Turner, R. Jay; Russell, David; Glover, Regan; Hutto, Pamela

    2007-01-01

    Anger has been shown to be an important factor in occupational maladjustment, family conflict, physical and sexual assault, criminal behavior, and substance abuse. It has also been linked with such adverse health outcomes as hypertension, heart disease, and cancer. Focusing on anger proneness, conceptualized as a relatively enduring propensity to…

  6. Complications associated with prone positioning in elective spinal surgery

    PubMed Central

    DePasse, J Mason; Palumbo, Mark A; Haque, Maahir; Eberson, Craig P; Daniels, Alan H

    2015-01-01

    Complications associated with prone surgical positioning during elective spine surgery have the potential to cause serious patient morbidity. Although many of these complications remain uncommon, the range of possible morbidities is wide and includes multiple organ systems. Perioperative visual loss (POVL) is a well described, but uncommon complication that may occur due to ischemia to the optic nerve, retina, or cerebral cortex. Closed-angle glaucoma and amaurosis have been reported as additional etiologies for vision loss following spinal surgery. Peripheral nerve injuries, such as those caused by prolonged traction to the brachial plexus, are more commonly encountered postoperative events. Myocutaneous complications including pressure ulcers and compartment syndrome may also occur after prone positioning, albeit rarely. Other uncommon positioning complications such as tongue swelling resulting in airway compromise, femoral artery ischemia, and avascular necrosis of the femoral head have also been reported. Many of these are well-understood and largely avoidable through thoughtful attention to detail. Other complications, such as POVL, remain incompletely understood and thus more difficult to predict or prevent. Here, the current literature on the complications of prone positioning for spine surgery is reviewed to increase awareness of the spectrum of potential complications and to inform spine surgeons of strategies to minimize the risk of prone patient morbidity. PMID:25893178

  7. Prone position craniotomy in pregnancy without fetal heart rate monitoring.

    PubMed

    Jacob, Jean; Alexander, Ashish; Philip, Shoba; Thomas, Anoop

    2016-09-01

    A pregnant patient in second trimester scheduled for posterior fossa craniotomy in prone position is a challenge for the anesthesiologist. Things to consider are physiological changes during pregnancy, non-obstetric surgery in pregnant patients, neuroanesthetic principles, effects of prone positioning, and need for fetal heart rate (FHR) monitoring. We have described the anesthetic management of this case and discussed intra-operative FHR monitoring including controversies about its role, indications, and various options available as per fetal gestational age. In our case we attempted intermittent intra-operative FHR monitoring to optimize maternal positioning and fetal oxygenation even though the fetus was pre-viable. However the attempt was abandoned due to practical difficulties with prone positioning. Patient made good neurological recovery following the procedure and delivered a healthy term baby 4 months later. Decisions regarding fetal monitoring should be individualized based on viability of the fetus and feasibility of emergency cesarean delivery. Good communication between a multidisciplinary team involving neurosurgeon, anesthesiologist, obstetrician, and neonatologist is important for a successful outcome for mother and fetus. We conclude that prone position neurosurgery can safely be carried out in a pregnant patient with pre-viable fetus without FHR monitoring. PMID:27555144

  8. Pathogenesis of A-beta+ ketosis-prone diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A-beta+ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible beta-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. Fasting plasma fatty acids, acylcarnit...

  9. Optical measurement of dimensional parameters of the breast with subjects in prone position

    PubMed Central

    Roessler, Ann-Christin; Althoff, Felix; Jaeger, Florian; Kalender, Willi; Wenkel, Evelyn

    2015-01-01

    Abstract. Various applications require information on breast parameters, such as breast length and volume. An optical system was designed and tested for measuring these parameters with subjects in a prone position. The study results were used for optimizing patient positioning and handling for a future breast computed tomography (BCT) system. Measurements were conducted using an optical measurement system. To test the functionality and accuracy of the system, measurements were performed using reference phantoms. Additionally, 20 women and 5 men were examined to calculate breast parameters in alternative positions and breathing states. The results of the optical measurements were compared with magnetic resonance imaging (MRI) measurements. Volume and length of the reference phantoms were determined with errors below 2%. The patient study demonstrated a mean breast volume of 530.7 ml for women during normal breathing. During an exhalation state, breast volume increased significantly by 17.7 ml in comparison with normal breathing. Differences with MRI measurements were found to be 3% for breast length and 9% for breast volume on average. The proposed optical measurement system was found to be suitable for measuring the dimensional parameters of the breast in a prone position and provides a tool for evaluating breast coverage for BCT. PMID:26240833

  10. Human factors and medication errors: a case study.

    PubMed

    Gluyas, Heather; Morrison, Paul

    2014-12-15

    Human beings are error prone. A significant component of human error is flaws inherent in human cognitive processes, which are exacerbated by situations in which the individual making the error is distracted, stressed or overloaded, or does not have sufficient knowledge to undertake an action correctly. The scientific discipline of human factors deals with environmental, organisational and job factors, as well as human and individual characteristics, which influence behaviour at work in a way that potentially gives rise to human error. This article discusses how cognitive processing is related to medication errors. The case of a coronial inquest into the death of a nursing home resident is used to highlight the way people think and process information, and how such thinking and processing may lead to medication errors. PMID:25492790

  11. Error Rate Comparison during Polymerase Chain Reaction by DNA Polymerase

    DOE PAGESBeta

    McInerney, Peter; Adams, Paul; Hadi, Masood Z.

    2014-01-01

    As larger-scale cloning projects become more prevalent, there is an increasing need for comparisons among high fidelity DNA polymerases used for PCR amplification. All polymerases marketed for PCR applications are tested for fidelity properties (i.e., error rate determination) by vendors, and numerous literature reports have addressed PCR enzyme fidelity. Nonetheless, it is often difficult to make direct comparisons among different enzymes due to numerous methodological and analytical differences from study to study. We have measured the error rates for 6 DNA polymerases commonly used in PCR applications, including 3 polymerases typically used for cloning applications requiring high fidelity. Errormore » rate measurement values reported here were obtained by direct sequencing of cloned PCR products. The strategy employed here allows interrogation of error rate across a very large DNA sequence space, since 94 unique DNA targets were used as templates for PCR cloning. The six enzymes included in the study, Taq polymerase, AccuPrime-Taq High Fidelity, KOD Hot Start, cloned Pfu polymerase, Phusion Hot Start, and Pwo polymerase, we find the lowest error rates with Pfu , Phusion, and Pwo polymerases. Error rates are comparable for these 3 enzymes and are >10x lower than the error rate observed with Taq polymerase. Mutation spectra are reported, with the 3 high fidelity enzymes displaying broadly similar types of mutations. For these enzymes, transition mutations predominate, with little bias observed for type of transition.« less

  12. Perioperative visual loss following prone spinal surgery: A review

    PubMed Central

    Epstein, Nancy E.

    2016-01-01

    Background: Postoperative visual loss (POVL) following prone spine surgery occurs in from 0.013% to 1% of cases and is variously attributed to ischemic optic neuropathy (ION: anterior ION or posterior ION [reported in 1.9/10,000 cases: constitutes 89% of all POVL cases], central retinal artery occlusion [CRAO], central retinal vein occlusion [CRVO], cortical blindness [CB], direct compression [horseshoe, prone pillows, and eye protectors Dupaco Opti-Gard]), and acute angle closure glaucoma (AACG). Methods: Risk factors for ION include prolonged operative times, long-segment spinal instrumentation, anemia, intraoperative hypotension, diabetes, obesity, male sex, using the Wilson frame, microvascular pathology, decreased the percent of colloid administration, and extensive intraoperative blood loss. Risk factors for CRAO more typically include improper positioning during the surgery (e.g., cervical rotation), while those for CB included prone positioning and obesity. Results: POVL may be avoided by greater utilization of crystalloids versus colloids, administration of α-2 agonists (e.g., decreases intraocular pressure), avoidance of catecholamines (e.g., avoid vasoconstrictors), avoiding intraoperative hypotension, and averting anemia. Patients with glaucoma or glaucoma suspects may undergo preoperative evaluation by ophthalmologists to determine whether they require prophylactic treatment prior to prone spinal surgery and whether and if prophylactic treatment is warranted. Conclusions: The best way to avoid POVL is to recognize its multiple etiologies and limit the various risk factors that contribute to this devastating complication of prone spinal surgery. Furthermore, routinely utilizing a 3-pin head holder will completely avoid ophthalmic compression, while maintaining the neck in a neutral posture, largely avoiding the risk of jugular vein and/or carotid artery compromise and thus avoiding increasing IOP. PMID:27274409

  13. Remediating Common Math Errors.

    ERIC Educational Resources Information Center

    Wagner, Rudolph F.

    1981-01-01

    Explanations and remediation suggestions for five types of mathematics errors due either to perceptual or cognitive difficulties are given. Error types include directionality problems, mirror writing, visually misperceived signs, diagnosed directionality problems, and mixed process errors. (CL)

  14. Denoising PCR-amplified metagenome data

    PubMed Central

    2012-01-01

    Background PCR amplification and high-throughput sequencing theoretically enable the characterization of the finest-scale diversity in natural microbial and viral populations, but each of these methods introduces random errors that are difficult to distinguish from genuine biological diversity. Several approaches have been proposed to denoise these data but lack either speed or accuracy. Results We introduce a new denoising algorithm that we call DADA (Divisive Amplicon Denoising Algorithm). Without training data, DADA infers both the sample genotypes and error parameters that produced a metagenome data set. We demonstrate performance on control data sequenced on Roche’s 454 platform, and compare the results to the most accurate denoising software currently available, AmpliconNoise. Conclusions DADA is more accurate and over an order of magnitude faster than AmpliconNoise. It eliminates the need for training data to establish error parameters, fully utilizes sequence-abundance information, and enables inclusion of context-dependent PCR error rates. It should be readily extensible to other sequencing platforms such as Illumina. PMID:23113967

  15. A nonlinear biomechanical model based registration method for aligning prone and supine MR breast images.

    PubMed

    Han, Lianghao; Hipwell, John H; Eiben, Björn; Barratt, Dean; Modat, Marc; Ourselin, Sebastien; Hawkes, David J

    2014-03-01

    Preoperative diagnostic magnetic resonance (MR) breast images can provide good contrast between different tissues and 3-D information about suspicious tissues. Aligning preoperative diagnostic MR images with a patient in the theatre during breast conserving surgery could assist surgeons in achieving the complete excision of cancer with sufficient margins. Typically, preoperative diagnostic MR breast images of a patient are obtained in the prone position, while surgery is performed in the supine position. The significant shape change of breasts between these two positions due to gravity loading, external forces and related constraints makes the alignment task extremely difficult. Our previous studies have shown that either nonrigid intensity-based image registration or biomechanical modelling alone are limited in their ability to capture such a large deformation. To tackle this problem, we proposed in this paper a nonlinear biomechanical model-based image registration method with a simultaneous optimization procedure for both the material parameters of breast tissues and the direction of the gravitational force. First, finite element (FE) based biomechanical modelling is used to estimate a physically plausible deformation of the pectoral muscle and the major deformation of breast tissues due to gravity loading. Then, nonrigid intensity-based image registration is employed to recover the remaining deformation that FE analyses do not capture due to the simplifications and approximations of biomechanical models and the uncertainties of external forces and constraints. We assess the registration performance of the proposed method using the target registration error of skin fiducial markers and the Dice similarity coefficient (DSC) of fibroglandular tissues. The registration results on prone and supine MR image pairs are compared with those from two alternative nonrigid registration methods for five breasts. Overall, the proposed algorithm achieved the best registration

  16. Overlap extension PCR cloning.

    PubMed

    Bryksin, Anton; Matsumura, Ichiro

    2013-01-01

    Rising demand for recombinant proteins has motivated the development of efficient and reliable cloning methods. Here we show how a beginner can clone virtually any DNA insert into a plasmid of choice without the use of restriction endonucleases or T4 DNA ligase. Chimeric primers encoding plasmid sequence at the 5' ends and insert sequence at the 3' ends are designed and synthesized. Phusion(®) DNA polymerase is utilized to amplify the desired insert by PCR. The double-stranded product is subsequently employed as a pair of mega-primers in a PCR-like reaction with circular plasmids. The original plasmids are then destroyed in restriction digests with Dpn I. The product of the overlap extension PCR is used to transform competent Escherichia coli cells. Phusion(®) DNA polymerase is used for both the amplification and fusion reactions, so both steps can be monitored and optimized in the same way. PMID:23996437

  17. Ultrasound-guided central venous catheterization in prone position

    PubMed Central

    Sofi, Khalid; Arab, Samer

    2010-01-01

    Central venous catheterization (CVC) is a commonly performed intraoperative procedure. Traditionally, CVC placement is performed blindly using anatomic landmarks as a guide to vessel position. Real-time ultrasound provides the operator the benefit of visualizing the target vein and the surrounding anatomic structures prior to and during the catheter insertion, thereby minimizing complications and increasing speed of placement. A 22-year-old male underwent open reduction and internal fixation of acetabulum fracture in prone position. Excessive continuous bleeding intraoperatively warranted placement of CVC in right internal jugular vein (IJV), which was not possible in prone position without the help of ultrasound. Best view of right IJV was obtained and CVC was placed using real-time ultrasound without complications. Ultrasound-guided CVC placement can be done in atypical patient positions where traditional anatomic landmark technique has no role. Use of ultrasound not only increases the speed of placement but also reduces complications known with the traditional blind technique. PMID:20668564

  18. Supine and prone colon registration using quasi-conformal mapping.

    PubMed

    Zeng, Wei; Marino, Joseph; Chaitanya Gurijala, Krishna; Gu, Xianfeng; Kaufman, Arie

    2010-01-01

    In virtual colonoscopy, CT scans are typically acquired with the patient in both supine (facing up) and prone (facing down) positions. The registration of these two scans is desirable so that the user can clarify situations or confirm polyp findings at a location in one scan with the same location in the other, thereby improving polyp detection rates and reducing false positives. However, this supine-prone registration is challenging because of the substantial distortions in the colon shape due to the patient's change in position. We present an efficient algorithm and framework for performing this registration through the use of conformal geometry to guarantee that the registration is a diffeomorphism (a one-to-one and onto mapping). The taeniae coli and colon flexures are automatically extracted for each supine and prone surface, employing the colon geometry. The two colon surfaces are then divided into several segments using the flexures, and each segment is cut along a taenia coli and conformally flattened to the rectangular domain using holomorphic differentials. The mean curvature is color encoded as texture images, from which feature points are automatically detected using graph cut segmentation, mathematic morphological operations, and principal component analysis. Corresponding feature points are found between supine and prone and are used to adjust the conformal flattening to be quasi-conformal, such that the features become aligned. We present multiple methods of visualizing our results, including 2D flattened rendering, corresponding 3D endoluminal views, and rendering of distortion measurements. We demonstrate the efficiency and efficacy of our registration method by illustrating matched views on both the 2D flattened colon images and in the 3D volume rendered colon endoluminal view. We analytically evaluate the correctness of the results by measuring the distance between features on the registered colons. PMID:20975175

  19. QUALITY ASSURANCE FOR PCR

    EPA Science Inventory

    The U.S. Environmental Protection Agency (EPA) held a workshop in January 2003 on the detection of viruses in water using polymerase chain reaction (PCR)-based methods. Speakers were asked to address a series of specific questions, including whether a single standard method coul...

  20. QUALITY CONTROLS FOR PCR

    EPA Science Inventory

    The purpose of this presentation is to present an overview of the quality control (QC) sections of a draft EPA document entitled, "Quality Assurance/Quality Control Guidance for Laboratories Performing PCR Analyses on Environmental Samples." This document has been prepared by th...

  1. Taking qPCR to a higher level: Analysis of CNV reveals the power of high throughput qPCR to enhance quantitative resolution.

    PubMed

    Weaver, Suzanne; Dube, Simant; Mir, Alain; Qin, Jian; Sun, Gang; Ramakrishnan, Ramesh; Jones, Robert C; Livak, Kenneth J

    2010-04-01

    This paper assesses the quantitative resolution of qPCR using copy number variation (CNV) as a paradigm. An error model is developed for real-time qPCR data showing how the precision of CNV determination varies with the number of replicates. Using samples with varying numbers of X chromosomes, experimental data demonstrates that real-time qPCR can readily distinguish four copes from five copies, which corresponds to a 1.25-fold difference in relative quantity. Digital PCR is considered as an alternative form of qPCR. For digital PCR, an error model is shown that relates the precision of CNV determination to the number of reaction chambers. The quantitative capability of digital PCR is illustrated with an experiment distinguishing four and five copies of the human gene MRGPRX1. For either real-time qPCR or digital PCR, practical application of these models to achieve enhanced quantitative resolution requires use of a high throughput PCR platform that can simultaneously perform thousands of reactions. Comparing the two methods, real-time qPCR has the advantage of throughput and digital PCR has the advantage of simplicity in terms of the assumptions made for data analysis. PMID:20079846

  2. Anger Proneness, Gender, and the Risk of Heart Failure

    PubMed Central

    Kucharska-Newton, Anna M.; Williams, Janice E.; Chang, Patricia P.; Stearns, Sally C.; Sueta, Carla A.; Blecker, Saul B.; Mosley, Thomas H.

    2014-01-01

    Background Evidence concerning the association of anger-proneness with incidence of heart failure is lacking. Methods Anger proneness was ascertained among 13,171 black and white participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort using the Spielberger Trait Anger Scale. Incident heart failure events, defined as occurrence of ICD-9-CM code 428.x, were ascertained from participants’ medical records during follow-up 1990–2010. Relative hazard of heart failure across categories of trait anger was estimated from Cox proportional hazard models. Results Study participants (mean age 56.9 (SD 5.7) years) experienced 1,985 incident HF events during 18.5 (SD 4.9) years of follow-up. Incidence of HF was greater among those with high, as compared to those with low or moderate trait anger, with higher incidence observed for men as compared to women. The relative hazard of incident HF was modestly high among those with high trait anger, as compared to those with low or moderate trait anger (age-adjusted HR for men=1.44 (95% CI 1.23, 1.69). Adjustment for comorbidities and depressive symptoms attenuated the estimated age-adjusted relative hazard in men to 1.26 (95% CI 1.00, 1.60). Conclusion Assessment of anger proneness may be necessary in successful prevention and clinical management of heart failure, especially in men. PMID:25284390

  3. Numerical error in groundwater flow and solute transport simulation

    NASA Astrophysics Data System (ADS)

    Woods, Juliette A.; Teubner, Michael D.; Simmons, Craig T.; Narayan, Kumar A.

    2003-06-01

    Models of groundwater flow and solute transport may be affected by numerical error, leading to quantitative and qualitative changes in behavior. In this paper we compare and combine three methods of assessing the extent of numerical error: grid refinement, mathematical analysis, and benchmark test problems. In particular, we assess the popular solute transport code SUTRA [Voss, 1984] as being a typical finite element code. Our numerical analysis suggests that SUTRA incorporates a numerical dispersion error and that its mass-lumped numerical scheme increases the numerical error. This is confirmed using a Gaussian test problem. A modified SUTRA code, in which the numerical dispersion is calculated and subtracted, produces better results. The much more challenging Elder problem [Elder, 1967; Voss and Souza, 1987] is then considered. Calculation of its numerical dispersion coefficients and numerical stability show that the Elder problem is prone to error. We confirm that Elder problem results are extremely sensitive to the simulation method used.

  4. Use of Droplet Digital PCR for Estimation of Fish Abundance and Biomass in Environmental DNA Surveys

    PubMed Central

    Doi, Hideyuki; Uchii, Kimiko; Takahara, Teruhiko; Matsuhashi, Saeko; Yamanaka, Hiroki; Minamoto, Toshifumi

    2015-01-01

    An environmental DNA (eDNA) analysis method has been recently developed to estimate the distribution of aquatic animals by quantifying the number of target DNA copies with quantitative real-time PCR (qPCR). A new quantitative PCR technology, droplet digital PCR (ddPCR), partitions PCR reactions into thousands of droplets and detects the amplification in each droplet, thereby allowing direct quantification of target DNA. We evaluated the quantification accuracy of qPCR and ddPCR to estimate species abundance and biomass by using eDNA in mesocosm experiments involving different numbers of common carp. We found that ddPCR quantified the concentration of carp eDNA along with carp abundance and biomass more accurately than qPCR, especially at low eDNA concentrations. In addition, errors in the analysis were smaller in ddPCR than in qPCR. Thus, ddPCR is better suited to measure eDNA concentration in water, and it provides more accurate results for the abundance and biomass of the target species than qPCR. We also found that the relationship between carp abundance and eDNA concentration was stronger than that between biomass and eDNA by using both ddPCR and qPCR; this suggests that abundance can be better estimated by the analysis of eDNA for species with fewer variations in body mass. PMID:25799582

  5. An enriched environment improves cognitive performance in mice from the senescence-accelerated prone mouse 8 strain

    PubMed Central

    Yuan, Zhenyun; Wang, Mingwei; Yan, Baoyong; Gu, Ping; Jiang, Xiangming; Yang, Xiufen; Cui, Dongsheng

    2012-01-01

    In this study, we examined 3-month-old female mice from the senescence-accelerated prone mouse 8 strain and age-matched homologous normal aging female mice from the senescence accelerated- resistant mouse 1 strain. Mice from each strain were housed in an enriched environment (including a platform, running wheels, tunnel, and some toys) or a standard environment for 3 months. The mice housed in the enriched environment exhibited shorter escape latencies and a greater percentage of time in the target quadrant in the Morris water maze test, and they exhibited reduced errors and longer latencies in step-down avoidance experiments compared with mice housed in the standard environment. Correspondently, brain-derived neurotrophic factor mRNA and protein expression in the hippocampus was significantly higher in mice housed in the enriched environment compared with those housed in the standard environment, and the level of hippocampal brain-derived neurotrophic factor protein was positively correlated with the learning and memory abilities of mice from the senescence-accelerated prone mouse 8 strain. These results suggest that an enriched environment improved cognitive performance in mice form the senescence-accelerated prone mouse 8 strain by increasing brain-derived neurotrophic factor expression in the hippocampus. PMID:25624804

  6. 44 CFR 60.23 - Planning considerations for mudslide (i.e., mudflow)-prone areas.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., Mudslide (i.e., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.23 Planning considerations for..., flood plain, mudslide (i.e., mudflow), soil, land, and water regulation in neighboring communities;...

  7. 44 CFR 60.23 - Planning considerations for mudslide (i.e., mudflow)-prone areas.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., Mudslide (i.e., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.23 Planning considerations for..., flood plain, mudslide (i.e., mudflow), soil, land, and water regulation in neighboring communities;...

  8. Automated Forensic Animal Family Identification by Nested PCR and Melt Curve Analysis on an Off-the-Shelf Thermocycler Augmented with a Centrifugal Microfluidic Disk Segment

    PubMed Central

    Zengerle, Roland; von Stetten, Felix; Schmidt, Ulrike

    2015-01-01

    Nested PCR remains a labor-intensive and error-prone biomolecular analysis. Laboratory workflow automation by precise control of minute liquid volumes in centrifugal microfluidic Lab-on-a-Chip systems holds great potential for such applications. However, the majority of these systems require costly custom-made processing devices. Our idea is to augment a standard laboratory device, here a centrifugal real-time PCR thermocycler, with inbuilt liquid handling capabilities for automation. We have developed a microfluidic disk segment enabling an automated nested real-time PCR assay for identification of common European animal groups adapted to forensic standards. For the first time we utilize a novel combination of fluidic elements, including pre-storage of reagents, to automate the assay at constant rotational frequency of an off-the-shelf thermocycler. It provides a universal duplex pre-amplification of short fragments of the mitochondrial 12S rRNA and cytochrome b genes, animal-group-specific main-amplifications, and melting curve analysis for differentiation. The system was characterized with respect to assay sensitivity, specificity, risk of cross-contamination, and detection of minor components in mixtures. 92.2% of the performed tests were recognized as fluidically failure-free sample handling and used for evaluation. Altogether, augmentation of the standard real-time thermocycler with a self-contained centrifugal microfluidic disk segment resulted in an accelerated and automated analysis reducing hands-on time, and circumventing the risk of contamination associated with regular nested PCR protocols. PMID:26147196

  9. 44 CFR 60.22 - Planning considerations for flood-prone areas.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Planning considerations for...., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.22 Planning considerations for flood-prone areas... flood, or to compensate for future urban development; (16) Requirement of consistency between...

  10. 44 CFR 60.22 - Planning considerations for flood-prone areas.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Planning considerations for...., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.22 Planning considerations for flood-prone areas... flood, or to compensate for future urban development; (16) Requirement of consistency between...

  11. 44 CFR 60.22 - Planning considerations for flood-prone areas.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Planning considerations for...., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.22 Planning considerations for flood-prone areas... flood, or to compensate for future urban development; (16) Requirement of consistency between...

  12. Field error lottery

    SciTech Connect

    Elliott, C.J.; McVey, B. ); Quimby, D.C. )

    1990-01-01

    The level of field errors in an FEL is an important determinant of its performance. We have computed 3D performance of a large laser subsystem subjected to field errors of various types. These calculations have been guided by simple models such as SWOOP. The technique of choice is utilization of the FELEX free electron laser code that now possesses extensive engineering capabilities. Modeling includes the ability to establish tolerances of various types: fast and slow scale field bowing, field error level, beam position monitor error level, gap errors, defocusing errors, energy slew, displacement and pointing errors. Many effects of these errors on relative gain and relative power extraction are displayed and are the essential elements of determining an error budget. The random errors also depend on the particular random number seed used in the calculation. The simultaneous display of the performance versus error level of cases with multiple seeds illustrates the variations attributable to stochasticity of this model. All these errors are evaluated numerically for comprehensive engineering of the system. In particular, gap errors are found to place requirements beyond mechanical tolerances of {plus minus}25{mu}m, and amelioration of these may occur by a procedure utilizing direct measurement of the magnetic fields at assembly time. 4 refs., 12 figs.

  13. Inborn errors of metabolism

    MedlinePlus

    Metabolism - inborn errors of ... Bodamer OA. Approach to inborn errors of metabolism. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 205. Rezvani I, Rezvani G. An ...

  14. Programming Errors in APL.

    ERIC Educational Resources Information Center

    Kearsley, Greg P.

    This paper discusses and provides some preliminary data on errors in APL programming. Data were obtained by analyzing listings of 148 complete and partial APL sessions collected from student terminal rooms at the University of Alberta. Frequencies of errors for the various error messages are tabulated. The data, however, are limited because they…

  15. Prone Breast Intensity Modulated Radiation Therapy: 5-Year Results

    SciTech Connect

    Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Fenton Kerimian, Maria; Goldberg, Judith D.; Formenti, Silvia C.

    2014-07-15

    Purpose: To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. Methods and Materials: Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. Results: Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm{sup 3}, mean 19.65 cm{sup 3}. In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm{sup 3}, mean 1.59 cm{sup 3}. There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. Conclusions: Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and

  16. Boredom proneness and emotion regulation predict emotional eating.

    PubMed

    Crockett, Amanda C; Myhre, Samantha K; Rokke, Paul D

    2015-05-01

    Emotional eating is considered a risk factor for eating disorders and an important contributor to obesity and its associated health problems. It has been suggested that boredom may be an important contributor to overeating, but has received relatively little attention. A sample of 552 college students was surveyed. Linear regression analyses found that proneness to boredom and difficulties in emotion regulation simultaneously predicted inappropriate eating behavior, including eating in response to boredom, other negative emotions, and external cues. The unique contributions of these variables to emotional eating were discussed. These findings help to further identify which individuals could be at risk for emotional eating and potentially for unhealthy weight gain. PMID:25903253

  17. Video Error Concealment Using Fidelity Tracking

    NASA Astrophysics Data System (ADS)

    Yoneyama, Akio; Takishima, Yasuhiro; Nakajima, Yasuyuki; Hatori, Yoshinori

    We propose a method to prevent the degradation of decoded MPEG pictures caused by video transmission over error-prone networks. In this paper, we focus on the error concealment that is processed at the decoder without using any backchannels. Though there have been various approaches to this problem, they generally focus on minimizing the degradation measured frame by frame. Although this frame-level approach is effective in evaluating individual frame quality, in the sense of human perception, the most noticeable feature is the spatio-temporal discontinuity of the image feature in the decoded video image. We propose a novel error concealment algorithm comprising the combination of i) A spatio-temporal error recovery function with low processing cost, ii) A MB-based image fidelity tracking scheme, and iii) An adaptive post-filter using the fidelity information. It is demonstrated by experimental results that the proposed algorithm can significantly reduce the subjective degradation of corrupted MPEG video quality with about 30% of additional decoding processing power.

  18. Systematic errors in strong lens modeling

    NASA Astrophysics Data System (ADS)

    Johnson, Traci Lin; Sharon, Keren; Bayliss, Matthew B.

    2015-08-01

    The lensing community has made great strides in quantifying the statistical errors associated with strong lens modeling. However, we are just now beginning to understand the systematic errors. Quantifying these errors is pertinent to Frontier Fields science, as number counts and luminosity functions are highly sensitive to the value of the magnifications of background sources across the entire field of view. We are aware that models can be very different when modelers change their assumptions about the parameterization of the lensing potential (i.e., parametric vs. non-parametric models). However, models built while utilizing a single methodology can lead to inconsistent outcomes for different quantities, distributions, and qualities of redshift information regarding the multiple images used as constraints in the lens model. We investigate how varying the number of multiple image constraints and available redshift information of those constraints (ex., spectroscopic vs. photometric vs. no redshift) can influence the outputs of our parametric strong lens models, specifically, the mass distribution and magnifications of background sources. We make use of the simulated clusters by M. Meneghetti et al. and the first two Frontier Fields clusters, which have a high number of multiply imaged galaxies with spectroscopically-measured redshifts (or input redshifts, in the case of simulated clusters). This work will not only inform upon Frontier Field science, but also for work on the growing collection of strong lensing galaxy clusters, most of which are less massive and are capable of lensing a handful of galaxies, and are more prone to these systematic errors.

  19. MAMMALIAN DNA IN PCR REAGENTS

    EPA Science Inventory

    Ancient DNA analysis is becoming widespread. These studies use polymerase chain reaction (PCR) to amplify minute quantities of heavily damaged template. Unusual steps are taken to achieve the sensitivity necessary to detect ancient DNA, including high- cycle PCR amplification t...

  20. When soft controls get slippery: User interfaces and human error

    SciTech Connect

    Stubler, W.F.; O`Hara, J.M.

    1998-12-01

    Many types of products and systems that have traditionally featured physical control devices are now being designed with soft controls--input formats appearing on computer-based display devices and operated by a variety of input devices. A review of complex human-machine systems found that soft controls are particularly prone to some types of errors and may affect overall system performance and safety. This paper discusses the application of design approaches for reducing the likelihood of these errors and for enhancing usability, user satisfaction, and system performance and safety.

  1. Boredom proneness: its relationship to psychological- and physical-health symptoms.

    PubMed

    Sommers, J; Vodanovich, S J

    2000-01-01

    The relationship between boredom proneness and health-symptom reporting was examined. Undergraduate students (N = 200) completed the Boredom Proneness Scale and the Hopkins Symptom Checklist. A multiple analysis of covariance indicated that individuals with high boredom-proneness total scores reported significantly higher ratings on all five subscales of the Hopkins Symptom Checklist (Obsessive-Compulsive, Somatization, Anxiety, Interpersonal Sensitivity, and Depression). The results suggest that boredom proneness may be an important element to consider when assessing symptom reporting. Implications for determining the effects of boredom proneness on psychological- and physical-health symptoms. as well as the application in clinical settings, are discussed. PMID:10661377

  2. Refractive errors in children.

    PubMed

    Tongue, A C

    1987-12-01

    Optical correction of refractive errors in infants and young children is indicated when the refractive errors are sufficiently large to cause unilateral or bilateral amblyopia, if they are impairing the child's ability to function normally, or if the child has accommodative strabismus. Screening for refractive errors is important and should be performed as part of the annual physical examination in all verbal children. Screening for significant refractive errors in preverbal children is more difficult; however, the red reflex test of Bruckner is useful for the detection of anisometropic refractive errors. The photorefraction test, which is an adaptation of Bruckner's red reflex test, may prove to be a useful screening device for detecting bilateral as well as unilateral refractive errors. Objective testing as well as subjective testing enables ophthalmologists to prescribe proper optical correction for refractive errors for infants and children of any age. PMID:3317238

  3. Coping Mechanisms for Crop Plants in Drought-prone Environments

    PubMed Central

    Neumann, Peter M.

    2008-01-01

    Background Drought is a major limitation to plant productivity. Various options are available for increasing water availability and sustaining growth of crop plants in drought-prone environments. Scope After a general introduction to the problems of water availability, this review focuses on a critical evaluation of recent progress in unravelling mechanisms for modifying plant growth responses to drought. Conclusions Investigations of key regulatory mechanisms integrating plant growth responses to water deficits at the whole-organism, cellular and genomic levels continue to provide novel and exiting research findings. For example, recent reports contradict the widespread conception that root-derived abscisic acid is necessarily involved in signalling for stomatal and shoot-growth responses to soil water deficits. The findings bring into question the theoretical basis for alternate-side root-irrigation techniques. Similarly, recent reports indicate that increased ABA production or increased aquaporin expression did not lead to improved drought resistance. Other reports have concerned key genes and proteins involved in regulation of flowering (FT), vegetative growth (DELLA), leaf senescence (IPT) and desiccation tolerance (LEA). Introgression of such genes, with suitable promoters, can greatly impact on whole-plant responses to drought. Further developments could facilitate the introduction by breeders of new crop varieties with growth physiologies tailored to improved field performance under drought. Parallel efforts to encourage the introduction of supplementary irrigation with water made available by improved conservation measures and by sea- or brackish-water desalination, will probably provide comprehensive solutions to coping with drought-prone environments. PMID:18252764

  4. Study on proneness of spontaneous combustion of macerals

    SciTech Connect

    Zhang, Y.G.; Li, F.; Tang, X.Y.; Xie, K.C.

    1999-07-01

    Pure macerals from brown coal to gas coal were separated from coalfields of Pingzhuang, Liaoyuan, Fuxin, Fushun, Changguang Hunyuan and Tangcun, and effect of macerals on spontaneous combustion was recently investigated with ignition temperature and index gas technique. Three kinds of maceral group with same rank have different ignition temperature and proneness of spontaneous combustion. Vitrinite group has the lowest ignition temperature, it is the most liable to spontaneous combustion, and the proneness of spontaneous combustion of coal increases with the increases of vitrain content, fusinite group has the highest ignition temperature, is least liable; Exinite group is in the middle. Gaseous products of three kinds of maceral group such as CO, C{sub 2}H{sub 4} and C{sub 3}H{sub 6} which are used as index gas have different rates of formation during oxidation; the vitrinite group is higher than others. Vitrinite group with more active site is easy to oxidize at low temperature. Exinite group with the lowest aromaticity and many aliphatic structure present in the aromatic layers is of steady chemical properties, so it is least liable to oxidize at low temperature. Fusinite group with the short CH{sub 3} and/or CH{sub 2} side chain and fewer active sites in the aromatic rings is inert in chemical properties and most difficult to oxidize at low temperature.

  5. Error-resilient method for robust video transmissions

    NASA Astrophysics Data System (ADS)

    Choi, Dong-Hwan; Lim, Tae-Gyun; Lee, Sang-Hak; Hwang, Chan-Sik

    2003-06-01

    In this paper we address the problems of video transmission in error prone environments. A novel error-resilient method is proposed that uses a data embedding scheme for header parameters in video coding standards, such as MPEG-2 and H.263. In case of requiring taking the loss of data information into account except for header errors, the video decoder hides visual degradation as well as possible, employing an error concealment method using an affine transform. Header information is very important because syntax elements, tables, and decoding processes all depend on the values of the header information. Therefore, transmission errors in header information can result in serious visual degradation of the output video and also cause an abnormal decoding process. In the proposed method, the header parameters are embedded into the least significant bits (LSB) of the quantized DCT coefficients. Then, when errors occur in the header field of the compressed bitstream, the decoder can accurately recover the corrupted header parameters if the embedded information is extracted correctly. The error concealment technique employed in this paper uses motion estimation considering actual motions, such as rotation, magnification, reduction, and parallel motion, in moving pictures. Experimental results show that the proposed error-resilient method can effectively reconstruct the original video sequence without any additional bits or modifications to the video coding standard and the error concealment method can produce a higher PSNR value and better subjective video quality, estimating the motion of lost data more accurately.

  6. Skills, rules and knowledge in aircraft maintenance: errors in context

    NASA Technical Reports Server (NTRS)

    Hobbs, Alan; Williamson, Ann

    2002-01-01

    Automatic or skill-based behaviour is generally considered to be less prone to error than behaviour directed by conscious control. However, researchers who have applied Rasmussen's skill-rule-knowledge human error framework to accidents and incidents have sometimes found that skill-based errors appear in significant numbers. It is proposed that this is largely a reflection of the opportunities for error which workplaces present and does not indicate that skill-based behaviour is intrinsically unreliable. In the current study, 99 errors reported by 72 aircraft mechanics were examined in the light of a task analysis based on observations of the work of 25 aircraft mechanics. The task analysis identified the opportunities for error presented at various stages of maintenance work packages and by the job as a whole. Once the frequency of each error type was normalized in terms of the opportunities for error, it became apparent that skill-based performance is more reliable than rule-based performance, which is in turn more reliable than knowledge-based performance. The results reinforce the belief that industrial safety interventions designed to reduce errors would best be directed at those aspects of jobs that involve rule- and knowledge-based performance.

  7. Errors Affect Hypothetical Intertemporal Food Choice in Women

    PubMed Central

    Sellitto, Manuela; di Pellegrino, Giuseppe

    2014-01-01

    Growing evidence suggests that the ability to control behavior is enhanced in contexts in which errors are more frequent. Here we investigated whether pairing desirable food with errors could decrease impulsive choice during hypothetical temporal decisions about food. To this end, healthy women performed a Stop-signal task in which one food cue predicted high-error rate, and another food cue predicted low-error rate. Afterwards, we measured participants’ intertemporal preferences during decisions between smaller-immediate and larger-delayed amounts of food. We expected reduced sensitivity to smaller-immediate amounts of food associated with high-error rate. Moreover, taking into account that deprivational states affect sensitivity for food, we controlled for participants’ hunger. Results showed that pairing food with high-error likelihood decreased temporal discounting. This effect was modulated by hunger, indicating that, the lower the hunger level, the more participants showed reduced impulsive preference for the food previously associated with a high number of errors as compared with the other food. These findings reveal that errors, which are motivationally salient events that recruit cognitive control and drive avoidance learning against error-prone behavior, are effective in reducing impulsive choice for edible outcomes. PMID:25244534

  8. Characterization of genetic deletions in Becker muscular dystrophy using monoclonal antibodies against a deletion-prone region of dystrophin

    SciTech Connect

    Thanh, L.T.; Man, Nguyen Thi; Morris, G.E.

    1995-08-28

    We have produced a new panel of 20 monoclonal antibodies (mAbs) against a region of the dystrophin protein corresponding to a deletion-prone region of the Duchenne muscular dystrophy gene (exons 45-50). We show that immunohistochemistry or Western blotting with these {open_quotes}exon-specific{close_quotes} mAbs can provide a valuable addition to Southern blotting or PCR methods for the accurate identification of genetic deletions in Becker muscular dystrophy patients. The antibodies were mapped to the following exons: exon 45 (2 mAbs), exon 46 (6), exon 47 (1), exons 47/48 (4), exons 48-50 (6), and exon 50 (1). PCR amplification of single exons or groups of exons was used both to produce specific dystrophin immunogens and to map the mAbs obtained. PCR-mediated mutagenesis was also used to identify regions of dystrophin important for mAb binding. Because the mAbs can be used to characterize the dystrophin produced by individual muscle fibres, they will also be useful for studying {open_quotes}revertant{close_quotes} fibres in Duchenne muscle and for monitoring the results of myoblast therapy trials in MD patients with deletions in this region of the dystrophin gene. 27 refs., 7 figs., 3 tabs.

  9. Error resiliency of distributed video coding in wireless video communication

    NASA Astrophysics Data System (ADS)

    Ye, Shuiming; Ouaret, Mourad; Dufaux, Frederic; Ansorge, Michael; Ebrahimi, Touradj

    2008-08-01

    Distributed Video Coding (DVC) is a new paradigm in video coding, based on the Slepian-Wolf and Wyner-Ziv theorems. DVC offers a number of potential advantages: flexible partitioning of the complexity between the encoder and decoder, robustness to channel errors due to intrinsic joint source-channel coding, codec independent scalability, and multi-view coding without communications between the cameras. In this paper, we evaluate the performance of DVC in an error-prone wireless communication environment. We also present a hybrid spatial and temporal error concealment approach for DVC. Finally, we perform a comparison with a state-of-the-art AVC/H.264 video coding scheme in the presence of transmission errors.

  10. Aircraft system modeling error and control error

    NASA Technical Reports Server (NTRS)

    Kulkarni, Nilesh V. (Inventor); Kaneshige, John T. (Inventor); Krishnakumar, Kalmanje S. (Inventor); Burken, John J. (Inventor)

    2012-01-01

    A method for modeling error-driven adaptive control of an aircraft. Normal aircraft plant dynamics is modeled, using an original plant description in which a controller responds to a tracking error e(k) to drive the component to a normal reference value according to an asymptote curve. Where the system senses that (1) at least one aircraft plant component is experiencing an excursion and (2) the return of this component value toward its reference value is not proceeding according to the expected controller characteristics, neural network (NN) modeling of aircraft plant operation may be changed. However, if (1) is satisfied but the error component is returning toward its reference value according to expected controller characteristics, the NN will continue to model operation of the aircraft plant according to an original description.

  11. Simulation of between Repeat Variability in Real Time PCR Reactions

    PubMed Central

    Lievens, Antoon; Van Aelst, Stefan; Van den Bulcke, Marc; Goetghebeur, Els

    2012-01-01

    While many decisions rely on real time quantitative PCR (qPCR) analysis few attempts have hitherto been made to quantify bounds of precision accounting for the various sources of variation involved in the measurement process. Besides influences of more obvious factors such as camera noise and pipetting variation, changing efficiencies within and between reactions affect PCR results to a degree which is not fully recognized. Here, we develop a statistical framework that models measurement error and other sources of variation as they contribute to fluorescence observations during the amplification process and to derived parameter estimates. Evaluation of reproducibility is then based on simulations capable of generating realistic variation patterns. To this end, we start from a relatively simple statistical model for the evolution of efficiency in a single PCR reaction and introduce additional error components, one at a time, to arrive at stochastic data generation capable of simulating the variation patterns witnessed in repeated reactions (technical repeats). Most of the variation in values was adequately captured by the statistical model in terms of foreseen components. To recreate the dispersion of the repeats' plateau levels while keeping the other aspects of the PCR curves within realistic bounds, additional sources of reagent consumption (side reactions) enter into the model. Once an adequate data generating model is available, simulations can serve to evaluate various aspects of PCR under the assumptions of the model and beyond. PMID:23189123

  12. How good is a PCR efficiency estimate: Recommendations for precise and robust qPCR efficiency assessments.

    PubMed

    Svec, David; Tichopad, Ales; Novosadova, Vendula; Pfaffl, Michael W; Kubista, Mikael

    2015-03-01

    We have examined the imprecision in the estimation of PCR efficiency by means of standard curves based on strategic experimental design with large number of technical replicates. In particular, how robust this estimation is in terms of a commonly varying factors: the instrument used, the number of technical replicates performed and the effect of the volume transferred throughout the dilution series. We used six different qPCR instruments, we performed 1-16 qPCR replicates per concentration and we tested 2-10 μl volume of analyte transferred, respectively. We find that the estimated PCR efficiency varies significantly across different instruments. Using a Monte Carlo approach, we find the uncertainty in the PCR efficiency estimation may be as large as 42.5% (95% CI) if standard curve with only one qPCR replicate is used in 16 different plates. Based on our investigation we propose recommendations for the precise estimation of PCR efficiency: (1) one robust standard curve with at least 3-4 qPCR replicates at each concentration shall be generated, (2) the efficiency is instrument dependent, but reproducibly stable on one platform, and (3) using a larger volume when constructing serial dilution series reduces sampling error and enables calibration across a wider dynamic range. PMID:27077029

  13. Comparative analysis of human papillomavirus detection by PCR and non-isotopic in situ hybridisation.

    PubMed Central

    Herrington, C S; Anderson, S M; Bauer, H M; Troncone, B; de Angelis, M L; Noell, H; Chimera, J A; Van Eyck, S L; McGee, J O

    1995-01-01

    AIMS--To assess the relative diagnostic performance of the polymerase chain reaction (PCR) and non-isotopic in situ hybridisation (NISH) and to correlate these data with cytopathological assessment. METHODS--Paired analysis of human papillomavirus (HPV) detection was performed by PCR and NISH on exfoliated cervical cells from 122 women attending a routine gynaecological examination. PCR amplification followed by generic and HPV type specific hybridisation was compared with NISH on a parallel cervical smear. RESULTS--Overall, 32 cases were positive by NISH and 61 positive by PCR. Of the 105 cases in which both PCR and NISH were interpretable, 76 (26%) were normal smears, 20 of which were HPV positive by NISH and 37 (49%) by PCR. Of 17 borderline smears, two were NISH positive and 12 PCR positive. Eight of nine smears containing koilocytes were positive by NISH and seven by PCR. Of three dyskaryotic smears, none were NISH and two were PCR positive. The concordance of NISH and PCR in these samples was 57%. To assess sampling error, NISH and PCR were performed on an additional 50 cases using aliquots from the same sample. This increased the concordance between assays to 74%. Filter hybridisation of PCR products with the cocktail of probes used in NISH (under low and high stringency conditions) demonstrated that several cases of NISH positivity could be accounted for by cross-hybridisation to HPV types identified by PCR but not present in the NISH probe cocktail. CONCLUSIONS--Sampling error and potential cross-hybridisation of probe and target should be considered in interpretation of these techniques. PCR is more sensitive because it provides for the amplification of target DNA sequences. In addition, the PCR assay utilised in this study detects a wider range of HPV types than are contained in the cocktails used for NISH. However, PCR assays detect viral DNA present both within cells and in cervical fluid whereas NISH permits morphological localisation. Images PMID

  14. Comparative analysis of human papillomavirus detection by PCR and non-isotopic in situ hybridisation.

    PubMed

    Herrington, C S; Anderson, S M; Bauer, H M; Troncone, B; de Angelis, M L; Noell, H; Chimera, J A; Van Eyck, S L; McGee, J O

    1995-05-01

    AIMS--To assess the relative diagnostic performance of the polymerase chain reaction (PCR) and non-isotopic in situ hybridisation (NISH) and to correlate these data with cytopathological assessment. METHODS--Paired analysis of human papillomavirus (HPV) detection was performed by PCR and NISH on exfoliated cervical cells from 122 women attending a routine gynaecological examination. PCR amplification followed by generic and HPV type specific hybridisation was compared with NISH on a parallel cervical smear. RESULTS--Overall, 32 cases were positive by NISH and 61 positive by PCR. Of the 105 cases in which both PCR and NISH were interpretable, 76 (26%) were normal smears, 20 of which were HPV positive by NISH and 37 (49%) by PCR. Of 17 borderline smears, two were NISH positive and 12 PCR positive. Eight of nine smears containing koilocytes were positive by NISH and seven by PCR. Of three dyskaryotic smears, none were NISH and two were PCR positive. The concordance of NISH and PCR in these samples was 57%. To assess sampling error, NISH and PCR were performed on an additional 50 cases using aliquots from the same sample. This increased the concordance between assays to 74%. Filter hybridisation of PCR products with the cocktail of probes used in NISH (under low and high stringency conditions) demonstrated that several cases of NISH positivity could be accounted for by cross-hybridisation to HPV types identified by PCR but not present in the NISH probe cocktail. CONCLUSIONS--Sampling error and potential cross-hybridisation of probe and target should be considered in interpretation of these techniques. PCR is more sensitive because it provides for the amplification of target DNA sequences. In addition, the PCR assay utilised in this study detects a wider range of HPV types than are contained in the cocktails used for NISH. However, PCR assays detect viral DNA present both within cells and in cervical fluid whereas NISH permits morphological localisation. PMID:7629286

  15. Error detection method

    DOEpatents

    Olson, Eric J.

    2013-06-11

    An apparatus, program product, and method that run an algorithm on a hardware based processor, generate a hardware error as a result of running the algorithm, generate an algorithm output for the algorithm, compare the algorithm output to another output for the algorithm, and detect the hardware error from the comparison. The algorithm is designed to cause the hardware based processor to heat to a degree that increases the likelihood of hardware errors to manifest, and the hardware error is observable in the algorithm output. As such, electronic components may be sufficiently heated and/or sufficiently stressed to create better conditions for generating hardware errors, and the output of the algorithm may be compared at the end of the run to detect a hardware error that occurred anywhere during the run that may otherwise not be detected by traditional methodologies (e.g., due to cooling, insufficient heat and/or stress, etc.).

  16. The Error in Total Error Reduction

    PubMed Central

    Witnauer, James E.; Urcelay, Gonzalo P.; Miller, Ralph R.

    2013-01-01

    Most models of human and animal learning assume that learning is proportional to the discrepancy between a delivered outcome and the outcome predicted by all cues present during that trial (i.e., total error across a stimulus compound). This total error reduction (TER) view has been implemented in connectionist and artificial neural network models to describe the conditions under which weights between units change. Electrophysiological work has revealed that the activity of dopamine neurons is correlated with the total error signal in models of reward learning. Similar neural mechanisms presumably support fear conditioning, human contingency learning, and other types of learning. Using a computational modelling approach, we compared several TER models of associative learning to an alternative model that rejects the TER assumption in favor of local error reduction (LER), which assumes that learning about each cue is proportional to the discrepancy between the delivered outcome and the outcome predicted by that specific cue on that trial. The LER model provided a better fit to the reviewed data than the TER models. Given the superiority of the LER model with the present data sets, acceptance of TER should be tempered. PMID:23891930

  17. Error coding simulations

    NASA Technical Reports Server (NTRS)

    Noble, Viveca K.

    1993-01-01

    There are various elements such as radio frequency interference (RFI) which may induce errors in data being transmitted via a satellite communication link. When a transmission is affected by interference or other error-causing elements, the transmitted data becomes indecipherable. It becomes necessary to implement techniques to recover from these disturbances. The objective of this research is to develop software which simulates error control circuits and evaluate the performance of these modules in various bit error rate environments. The results of the evaluation provide the engineer with information which helps determine the optimal error control scheme. The Consultative Committee for Space Data Systems (CCSDS) recommends the use of Reed-Solomon (RS) and convolutional encoders and Viterbi and RS decoders for error correction. The use of forward error correction techniques greatly reduces the received signal to noise needed for a certain desired bit error rate. The use of concatenated coding, e.g. inner convolutional code and outer RS code, provides even greater coding gain. The 16-bit cyclic redundancy check (CRC) code is recommended by CCSDS for error detection.

  18. Model Error Budgets

    NASA Technical Reports Server (NTRS)

    Briggs, Hugh C.

    2008-01-01

    An error budget is a commonly used tool in design of complex aerospace systems. It represents system performance requirements in terms of allowable errors and flows these down through a hierarchical structure to lower assemblies and components. The requirements may simply be 'allocated' based upon heuristics or experience, or they may be designed through use of physics-based models. This paper presents a basis for developing an error budget for models of the system, as opposed to the system itself. The need for model error budgets arises when system models are a principle design agent as is increasingly more common for poorly testable high performance space systems.

  19. Error coding simulations

    NASA Astrophysics Data System (ADS)

    Noble, Viveca K.

    1993-11-01

    There are various elements such as radio frequency interference (RFI) which may induce errors in data being transmitted via a satellite communication link. When a transmission is affected by interference or other error-causing elements, the transmitted data becomes indecipherable. It becomes necessary to implement techniques to recover from these disturbances. The objective of this research is to develop software which simulates error control circuits and evaluate the performance of these modules in various bit error rate environments. The results of the evaluation provide the engineer with information which helps determine the optimal error control scheme. The Consultative Committee for Space Data Systems (CCSDS) recommends the use of Reed-Solomon (RS) and convolutional encoders and Viterbi and RS decoders for error correction. The use of forward error correction techniques greatly reduces the received signal to noise needed for a certain desired bit error rate. The use of concatenated coding, e.g. inner convolutional code and outer RS code, provides even greater coding gain. The 16-bit cyclic redundancy check (CRC) code is recommended by CCSDS for error detection.

  20. SU-E-J-21: Setup Variability of Colorectal Cancer Patients Treated in the Prone Position and Dosimetric Comparison with the Supine Position

    SciTech Connect

    Kim, A; Foster, J; Chu, W; Karotki, A

    2015-06-15

    Purpose: Many cancer centers treat colorectal patients in the prone position on a belly board to minimize dose to the small bowel. That may potentially Result in patient setup instability with corresponding impact on dose delivery accuracy for highly conformal techniques such as IMRT/VMAT. Two aims of this work are 1) to investigate setup accuracy of rectum patients treated in the prone position on a belly board using CBCT and 2) to evaluate dosimetric impact on bladder and small bowel of treating rectum patients in supine vs. prone position. Methods: For the setup accuracy study, 10 patients were selected. Weekly CBCTs were acquired and matched to bone. The CBCT-determined shifts were recorded. For the dosimetric study, 7 prone-setup patients and 7 supine-setup patients were randomly selected from our clinical database. Various clinically relevant dose volume histogram values were recorded for the small bowel and bladder. Results: The CBCT-determined rotational shifts had a wide variation. For the dataset acquired at the time of this writing, the ranges of rotational setup errors for pitch, roll, and yaw were [−3.6° 4.7°], [−4.3° 3.2°], and [−1.4° 1.4°]. For the dosimetric study: the small bowel V(45Gy) and mean dose for the prone position was 5.6±12.1% and 18.4±6.2Gy (ranges indicate standard deviations); for the supine position the corresponding dose values were 12.9±15.8% and 24.7±8.8Gy. For the bladder, the V(30Gy) and mean dose for prone position were 68.7±12.7% and 38.4±3.3Gy; for supine position these dose values were 77.1±13.7% and 40.7±3.1Gy. Conclusion: There is evidence of significant rotational instability in the prone position. The OAR dosimetry study indicates that there are some patients that may still benefit from the prone position, though many patients can be safely treated supine.

  1. Sources of PCR-induced distortions in high-throughput sequencing data sets.

    PubMed

    Kebschull, Justus M; Zador, Anthony M

    2015-12-01

    PCR permits the exponential and sequence-specific amplification of DNA, even from minute starting quantities. PCR is a fundamental step in preparing DNA samples for high-throughput sequencing. However, there are errors associated with PCR-mediated amplification. Here we examine the effects of four important sources of error-bias, stochasticity, template switches and polymerase errors-on sequence representation in low-input next-generation sequencing libraries. We designed a pool of diverse PCR amplicons with a defined structure, and then used Illumina sequencing to search for signatures of each process. We further developed quantitative models for each process, and compared predictions of these models to our experimental data. We find that PCR stochasticity is the major force skewing sequence representation after amplification of a pool of unique DNA amplicons. Polymerase errors become very common in later cycles of PCR but have little impact on the overall sequence distribution as they are confined to small copy numbers. PCR template switches are rare and confined to low copy numbers. Our results provide a theoretical basis for removing distortions from high-throughput sequencing data. In addition, our findings on PCR stochasticity will have particular relevance to quantification of results from single cell sequencing, in which sequences are represented by only one or a few molecules. PMID:26187991

  2. Medical error and disclosure.

    PubMed

    White, Andrew A; Gallagher, Thomas H

    2013-01-01

    Errors occur commonly in healthcare and can cause significant harm to patients. Most errors arise from a combination of individual, system, and communication failures. Neurologists may be involved in harmful errors in any practice setting and should familiarize themselves with tools to prevent, report, and examine errors. Although physicians, patients, and ethicists endorse candid disclosure of harmful medical errors to patients, many physicians express uncertainty about how to approach these conversations. A growing body of research indicates physicians often fail to meet patient expectations for timely and open disclosure. Patients desire information about the error, an apology, and a plan for preventing recurrence of the error. To meet these expectations, physicians should participate in event investigations and plan thoroughly for each disclosure conversation, preferably with a disclosure coach. Physicians should also anticipate and attend to the ongoing medical and emotional needs of the patient. A cultural change towards greater transparency following medical errors is in motion. Substantial progress is still required, but neurologists can further this movement by promoting policies and environments conducive to open reporting, respectful disclosure to patients, and support for the healthcare workers involved. PMID:24182370

  3. Everyday Scale Errors

    ERIC Educational Resources Information Center

    Ware, Elizabeth A.; Uttal, David H.; DeLoache, Judy S.

    2010-01-01

    Young children occasionally make "scale errors"--they attempt to fit their bodies into extremely small objects or attempt to fit a larger object into another, tiny, object. For example, a child might try to sit in a dollhouse-sized chair or try to stuff a large doll into it. Scale error research was originally motivated by parents' and…

  4. Error prone translesion synthesis past gamma-hydroxypropano deoxyguanosine, the primary acrolein-derived adduct in mammalian cells.

    PubMed

    Kanuri, Manorama; Minko, Irina G; Nechev, Lubomir V; Harris, Thomas M; Harris, Constance M; Lloyd, R Stephen

    2002-05-24

    8-Hydroxy-5,6,7,8-tetrahydropyrimido[1,2-a]purin- 10(3H)-one,3-(2'-deoxyriboside) (1,N(2)-gamma-hydroxypropano deoxyguanosine, gamma-HOPdG) is a major DNA adduct that forms as a result of exposure to acrolein, an environmental pollutant and a product of endogenous lipid peroxidation. gamma-HOPdG has been shown previously not to be a miscoding lesion when replicated in Escherichia coli. In contrast to those prokaryotic studies, in vivo replication and mutagenesis assays in COS-7 cells using single stranded DNA containing a specific gamma-HOPdG adduct, revealed that the gamma-HOPdG adduct was significantly mutagenic. Analyses revealed both transversion and transition types of mutations at an overall mutagenic frequency of 7.4 x 10(-2)/translesion synthesis. In vitro gamma-HOPdG strongly blocks DNA synthesis by two major polymerases, pol delta and pol epsilon. Replicative blockage of pol delta by gamma-HOPdG could be diminished by the addition of proliferating cell nuclear antigen, leading to highly mutagenic translesion bypass across this adduct. The differential functioning and processing capacities of the mammalian polymerases may be responsible for the higher mutation frequencies observed in this study when compared with the accurate and efficient nonmutagenic bypass observed in the bacterial system. PMID:11889127

  5. The discovery of error-prone DNA polymerase V and its unique regulation by RecA and ATP.

    PubMed

    Goodman, Myron F

    2014-09-26

    My career pathway has taken a circuitous route, beginning with a Ph.D. degree in electrical engineering from The Johns Hopkins University, followed by five postdoctoral years in biology at Hopkins and culminating in a faculty position in biological sciences at the University of Southern California. My startup package in 1973 consisted of $2,500, not to be spent all at once, plus an ancient Packard scintillation counter that had a series of rapidly flashing light bulbs to indicate a radioactive readout in counts/minute. My research pathway has been similarly circuitous. The discovery of Escherichia coli DNA polymerase V (pol V) began with an attempt to identify the mutagenic DNA polymerase responsible for copying damaged DNA as part of the well known SOS regulon. Although we succeeded in identifying a DNA polymerase, one that was induced as part of the SOS response, we actually rediscovered DNA polymerase II, albeit in a new role. A decade later, we discovered a new polymerase, pol V, whose activity turned out to be regulated by bound molecules of RecA protein and ATP. This Reflections article describes our research trajectory, includes a review of key features of DNA damage-induced SOS mutagenesis leading us to pol V, and reflects on some of the principal researchers who have made indispensable contributions to our efforts. PMID:25160630

  6. The Discovery of Error-prone DNA Polymerase V and Its Unique Regulation by RecA and ATP

    PubMed Central

    Goodman, Myron F.

    2014-01-01

    My career pathway has taken a circuitous route, beginning with a Ph.D. degree in electrical engineering from The Johns Hopkins University, followed by five postdoctoral years in biology at Hopkins and culminating in a faculty position in biological sciences at the University of Southern California. My startup package in 1973 consisted of $2,500, not to be spent all at once, plus an ancient Packard scintillation counter that had a series of rapidly flashing light bulbs to indicate a radioactive readout in counts/minute. My research pathway has been similarly circuitous. The discovery of Escherichia coli DNA polymerase V (pol V) began with an attempt to identify the mutagenic DNA polymerase responsible for copying damaged DNA as part of the well known SOS regulon. Although we succeeded in identifying a DNA polymerase, one that was induced as part of the SOS response, we actually rediscovered DNA polymerase II, albeit in a new role. A decade later, we discovered a new polymerase, pol V, whose activity turned out to be regulated by bound molecules of RecA protein and ATP. This Reflections article describes our research trajectory, includes a review of key features of DNA damage-induced SOS mutagenesis leading us to pol V, and reflects on some of the principal researchers who have made indispensable contributions to our efforts. PMID:25160630

  7. TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer

    PubMed Central

    Banerjee, Rajat; Russo, Nickole; Liu, Min; Basrur, Venkatesha; Bellile, Emily; Palanisamy, Nallasivam; Scanlon, Christina S.; van Tubergen, Elizabeth; Inglehart, Ronald C.; Metwally, Tarek; Mani, Ram-Shankar; Yocum, Anastasia; Nyati, Mukesh K.; Castilho, Rogerio M.; Varambally, Sooryanarayana; Chinnaiyan, Arul M.

    2014-01-01

    Head and neck cancer (SCCHN) is a common, aggressive, treatment-resistant cancer with a high recurrence rate and mortality, but the mechanism of treatment-resistance remains unclear. Here we describe a mechanism where the AAA-ATPase TRIP13 promotes treatment-resistance. Overexpression of TRIP13 in non-malignant cells results in malignant transformation. High expression of TRIP13 in SCCHN leads to aggressive, treatment-resistant tumors and enhanced repair of DNA damage. Using mass spectrometry, we identify DNA-PKcs complex proteins that mediate non homologous end joining (NHEJ), as TRIP13 binding partners. Using repair-deficient reporter systems, we show that TRIP13 promotes NHEJ, even when homologous recombination is intact. Importantly, overexpression of TRIP13 sensitizes SCCHN to an inhibitor of DNA-PKcs. Thus, this study defines a new mechanism of treatment resistance in SCCHN and underscores the importance of targeting NHEJ to overcome treatment failure in SCCHN and potentially in other cancers that overexpress TRIP13. PMID:25078033

  8. Digital droplet PCR on disk.

    PubMed

    Schuler, Friedrich; Trotter, Martin; Geltman, Marcel; Schwemmer, Frank; Wadle, Simon; Domínguez-Garrido, Elena; López, María; Cervera-Acedo, Cristina; Santibáñez, Paula; von Stetten, Felix; Zengerle, Roland; Paust, Nils

    2016-01-01

    Existing systems for digital droplet PCR (ddPCR) either suffer from low integration or are difficult to introduce to mass fabrication. Here we present an integrated system that is compatible to mass fabrication and combines emulsification, PCR, and fluorescence readout in a single chamber within a disposable cartridge (disk). Droplets are generated by injecting the sample into fluorinated oil via centrifugal step emulsification. The resulting emulsion is aligned in the PCR and readout zone by capillary action. During thermocycling, gas bubbles generated by degassing are removed by capillary driven transport through tapered regions in the PCR chamber. Thereby, the positioning of the emulsion within the readout zone of the PCR chamber is ensured at any time and no bubbles are present during readout. Manual handling of the disk solely requires pipetting of oil and PCR mix into the inlet structures, placing the disk into the thermocycler and subsequently into a microarray scanner. The functionality of the ddPCR process chain is demonstrated by quantitative detection of the cystic fibrosis causing mutation p.Phe508del, which is of interest for non-invasive prenatal testing (NIPT). The mutation was detected in a concentration range spanning four orders of magnitude. We envision that this work will lay the base for the development of highly integrated sample-to-digital-answer PCR systems that can be employed in routine clinical diagnosis. PMID:26610263

  9. Cross-Cultural Differences and Similarities in Proneness to Shame: An Adaptationist and Ecological Approach

    PubMed Central

    Takemura, Kosuke; Delton, Andrew W.; Sato, Kosuke; Robertson, Theresa; Cosmides, Leda; Tooby, John

    2013-01-01

    People vary in how easily they feel ashamed, that is, in their shame proneness. According to the information threat theory of shame, variation in shame proneness should, in part, be regulated by features of a person’s social ecology. On this view, shame is an emotion program that evolved to mitigate the likelihood or costs of reputation-damaging information spreading to others. In social environments where there are fewer possibilities to form new relationships (i.e., low relational mobility), there are higher costs to damaging or losing existing ones. Therefore, shame proneness toward current relationship partners should increase as perceived relational mobility decreases. In contrast, individuals with whom one has little or no relationship history are easy to replace, and so shame-proneness towards them should not be modulated by relational mobility. We tested these predictions cross-culturally by measuring relational mobility and shame proneness towards friends and strangers in Japan, the United States, and the United Kingdom. Japanese subjects were more shame-prone than their British and American counterparts. Critically, lower relational mobility was associated with greater shame proneness towards friends (but not strangers), and this relationship partially mediated the cultural differences in shame proneness. Shame proneness appears tailored to respond to relevant features of one’s social ecology. PMID:22947644

  10. Supine chest compression: alternative to prone ventilation in acute respiratory distress syndrome.

    PubMed

    Samanta, Sukhen; Samanta, Sujay; Soni, Kapil Dev

    2014-05-01

    Prone ventilation is usually used for severe acute respiratory distress syndrome. We applied an alternative method to prone position. We described 2 cases of trauma where prone position could not be done. Chest wall compression was performed by 2-kg weight in front of the chest wall bilaterally while the patient was in a supine position. Respiratory mechanics work to improve oxygenation almost as same as the mechanism proposed for prone position without any major adverse effects and serious complications. We suggest a larger randomized study to determine the efficacy and also to find out the optimum weight required to compress the chest. PMID:24332252

  11. Procrastination and suicide proneness: A moderated-mediation model for cognitive schemas and gender.

    PubMed

    Klibert, Jeffrey; LeLeux-LaBarge, Kayla; Tarantino, Nicholas; Yancey, Thresa; Lamis, Dorian A

    2016-07-01

    This study examined the direct and indirect paths between procrastination and suicide proneness while considering gender differences. Participants included 547 undergraduates from a southeastern university. Procrastination was positively related to suicide proneness for both genders, although this relation was stronger for women. Moderated-mediation analyses with bootstrapping highlighted insufficient self-control schemas as a mediator in the relation between procrastination and suicide proneness. However, indirect pathways did not vary by gender. Results represent an extension of the Procrastination-Health Model by highlighting the contribution of cognitive factors in explaining the relation between procrastination and suicide proneness. PMID:26766597

  12. Uncorrected refractive errors

    PubMed Central

    Naidoo, Kovin S; Jaggernath, Jyoti

    2012-01-01

    Global estimates indicate that more than 2.3 billion people in the world suffer from poor vision due to refractive error; of which 670 million people are considered visually impaired because they do not have access to corrective treatment. Refractive errors, if uncorrected, results in an impaired quality of life for millions of people worldwide, irrespective of their age, sex and ethnicity. Over the past decade, a series of studies using a survey methodology, referred to as Refractive Error Study in Children (RESC), were performed in populations with different ethnic origins and cultural settings. These studies confirmed that the prevalence of uncorrected refractive errors is considerably high for children in low-and-middle-income countries. Furthermore, uncorrected refractive error has been noted to have extensive social and economic impacts, such as limiting educational and employment opportunities of economically active persons, healthy individuals and communities. The key public health challenges presented by uncorrected refractive errors, the leading cause of vision impairment across the world, require urgent attention. To address these issues, it is critical to focus on the development of human resources and sustainable methods of service delivery. This paper discusses three core pillars to addressing the challenges posed by uncorrected refractive errors: Human Resource (HR) Development, Service Development and Social Entrepreneurship. PMID:22944755

  13. Uncorrected refractive errors.

    PubMed

    Naidoo, Kovin S; Jaggernath, Jyoti

    2012-01-01

    Global estimates indicate that more than 2.3 billion people in the world suffer from poor vision due to refractive error; of which 670 million people are considered visually impaired because they do not have access to corrective treatment. Refractive errors, if uncorrected, results in an impaired quality of life for millions of people worldwide, irrespective of their age, sex and ethnicity. Over the past decade, a series of studies using a survey methodology, referred to as Refractive Error Study in Children (RESC), were performed in populations with different ethnic origins and cultural settings. These studies confirmed that the prevalence of uncorrected refractive errors is considerably high for children in low-and-middle-income countries. Furthermore, uncorrected refractive error has been noted to have extensive social and economic impacts, such as limiting educational and employment opportunities of economically active persons, healthy individuals and communities. The key public health challenges presented by uncorrected refractive errors, the leading cause of vision impairment across the world, require urgent attention. To address these issues, it is critical to focus on the development of human resources and sustainable methods of service delivery. This paper discusses three core pillars to addressing the challenges posed by uncorrected refractive errors: Human Resource (HR) Development, Service Development and Social Entrepreneurship. PMID:22944755

  14. Insulin use: preventable errors.

    PubMed

    2014-01-01

    Insulin is vital for patients with type 1 diabetes and useful for certain patients with type 2 diabetes. The serious consequences of insulin-related medication errors are overdose, resulting in severe hypoglycaemia, causing seizures, coma and even death; or underdose, resulting in hyperglycaemia and sometimes ketoacidosis. Errors associated with the preparation and administration of insulin are often reported, both outside and inside the hospital setting. These errors are preventable. By analysing reports from organisations devoted to medication error prevention and from poison control centres, as well as a few studies and detailed case reports of medication errors, various types of error associated with insulin use have been identified, especially in the hospital setting. Generally, patients know more about the practicalities of their insulin treatment than healthcare professionals with intermittent involvement. Medication errors involving insulin can occur at each step of the medication-use process: prescribing, data entry, preparation, dispensing and administration. When prescribing insulin, wrong-dose errors have been caused by the use of abbreviations, especially "U" instead of the word "units" (often resulting in a 10-fold overdose because the "U" is read as a zero), or by failing to write the drug's name correctly or in full. In electronic prescribing, the sheer number of insulin products is a source of confusion and, ultimately, wrong-dose errors, and often overdose. Prescribing, dispensing or administration software is rarely compatible with insulin prescriptions in which the dose is adjusted on the basis of the patient's subsequent capillary blood glucose readings, and can therefore generate errors. When preparing and dispensing insulin, a tuberculin syringe is sometimes used instead of an insulin syringe, leading to overdose. Other errors arise from confusion created by similar packaging, between different insulin products or between insulin and other

  15. Error Prevention Aid

    NASA Technical Reports Server (NTRS)

    1987-01-01

    In a complex computer environment there is ample opportunity for error, a mistake by a programmer, or a software-induced undesirable side effect. In insurance, errors can cost a company heavily, so protection against inadvertent change is a must for the efficient firm. The data processing center at Transport Life Insurance Company has taken a step to guard against accidental changes by adopting a software package called EQNINT (Equations Interpreter Program). EQNINT cross checks the basic formulas in a program against the formulas that make up the major production system. EQNINT assures that formulas are coded correctly and helps catch errors before they affect the customer service or its profitability.

  16. Impairment of immunological functions in genetically epilepsy-prone rats.

    PubMed

    De Sarro, G; Liberto, M C; Berlinghieri, M C; Focà, A; Aragona, M; Cavaliere, R; Gulletta, E

    1996-06-01

    1. In genetically epilepsy-prone rats (GEPR-9s), which represent a natural genetic model of epilepsy, we observed that the number of peritoneal macrophages was significantly lower with respect to normal rats, and that some functional parameters (i.e. phagocytosis and intracellular killing) of these macrophages were impaired. 2. The count of lymphocyte populations showed a predominance of T-helper over T-cytotoxic/suppressor both in the spleen and lymph nodes. Moreover, an increased T-cell/B-cell ratio was observed in GEPR-9s. Flow cytometry revealed that GEPR-9s spleens possessed a large percentage of T-helper cells in comparison to normal rats. 3. By using concanavalin A-induced proliferation of GEPR-9s cultured lymphocytes, we have shown increased functional activation. 4. We suggest that the alterations in T-cell functions in GEPR-9s could be due to the involvement of the neuroendocrine system in the modulation of immunity, in the shift between Th1 and Th2, and in the activation of stress response. PMID:8853298

  17. Pathogenesis of A−β+ Ketosis-Prone Diabetes

    PubMed Central

    Patel, Sanjeet G.; Hsu, Jean W.; Jahoor, Farook; Coraza, Ivonne; Bain, James R.; Stevens, Robert D.; Iyer, Dinakar; Nalini, Ramaswami; Ozer, Kerem; Hampe, Christiane S.; Newgard, Christopher B.; Balasubramanyam, Ashok

    2013-01-01

    A−β+ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible β-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. Fasting plasma fatty acids, acylcarnitines, and amino acids were quantified in 20 KPD patients compared with 19 nondiabetic control subjects. Unique signatures in KPD—higher glutamate but lower glutamine and citrulline concentrations, increased β-hydroxybutyryl-carnitine, decreased isovaleryl-carnitine (a leucine catabolite), and decreased tricarboxylic acid (TCA) cycle intermediates—generated hypotheses that were tested through stable isotope/mass spectrometry protocols in nine new-onset, stable KPD patients compared with seven nondiabetic control subjects. Free fatty acid flux and acetyl CoA flux and oxidation were similar, but KPD had slower acetyl CoA conversion to β-hydroxybutyrate; higher fasting β-hydroxybutyrate concentration; slower β-hydroxybutyrate oxidation; faster leucine oxidative decarboxylation; accelerated glutamine conversion to glutamate without increase in glutamate carbon oxidation; and slower citrulline flux, with diminished glutamine amide–nitrogen transfer to citrulline. The confluence of metabolomic and kinetic data indicate a distinctive pathogenic sequence: impaired ketone oxidation and fatty acid utilization for energy, leading to accelerated leucine catabolism and transamination of α-ketoglutarate to glutamate, with impaired TCA anaplerosis of glutamate carbon. They highlight a novel process of defective energy production and ketosis in A−β+ KPD. PMID:23160531

  18. Human Enhancers Are Fragile and Prone to Deactivating Mutations

    PubMed Central

    Li, Shan; Ovcharenko, Ivan

    2015-01-01

    To explore the underlying mechanisms whereby noncoding variants affect transcriptional regulation, we identified nucleotides capable of disrupting binding of transcription factors and deactivating enhancers if mutated (dubbed candidate killer mutations or KMs) in HepG2 enhancers. On average, approximately 11% of enhancer positions are prone to KMs. A comparable number of enhancer positions are capable of creating de novo binding sites via a single-nucleotide mutation (dubbed candidate restoration mutations or RSs). Both KM and RS positions are evolutionarily conserved and tend to form clusters within an enhancer. We observed that KMs have the most deleterious effect on enhancer activity. In contrast, RSs have a smaller effect in increasing enhancer activity. Additionally, the KMs are strongly associated with liver-related Genome Wide Association Study traits compared with other HepG2 enhancer regions. By applying our framework to lymphoblastoid cell lines, we found that KMs underlie differential binding of transcription factors and differential local chromatin accessibility. The gene expression quantitative trait loci associated with the tissue-specific genes are strongly enriched in KM positions. In summary, we conclude that the KMs have the greatest impact on the level of gene expression and are likely to be the causal variants of tissue-specific gene expression and disease predisposition. PMID:25976354

  19. Characterization of an alcohol addiction-prone phenotype in mice.

    PubMed

    Radwanska, Kasia; Kaczmarek, Leszek

    2012-05-01

    Human studies indicate that high impulsivity, novelty seeking and anxiety predispose individuals to alcohol abuse. Unclear, however, is whether the same phenotypes can be observed in laboratory animals prone to uncontrolled alcohol drinking. To characterize a novelty-seeking trait, anxiety, impulsivity, compulsivity and the motivation for natural rewards in mice, numerous tests were performed in the automated IntelliCage learning system. The same mice then had extended access to alcohol for 70 days, followed by the evaluation of addiction-like behaviors, including (1) the motivation for alcohol in a progressive-ratio schedule of reinforcement; (2) persistent and compulsive alcohol seeking and taking during signaled 'no alcohol' periods and (3) when subjected to punishment; and (4) the intensity of relapse after alcohol withdrawal. Our data suggest that high levels of anxiety-related traits (i.e. low novelty seeking, low resistance to punishment and a high level of compulsive behaviors) and high impulsivity predict addiction-like alcohol drinking in mice. Future studies are, however, warranted to create a valid model of alcohol addiction in mice in the IntelliCage system. PMID:22017485

  20. Development of Korean Smartphone Addiction Proneness Scale for Youth

    PubMed Central

    Kim, Dongil; Lee, Yunhee; Lee, Juyoung; Nam, JeeEun Karin; Chung, Yeoju

    2014-01-01

    This study developed a Smartphone Addiction Proneness Scale (SAPS) based on the existing internet and cellular phone addiction scales. For the development of this scale, 29 items (1.5 times the final number of items) were initially selected as preliminary items, based on the previous studies on internet/phone addiction as well as the clinical experience of involved experts. The preliminary scale was administered to a nationally representative sample of 795 students in elementary, middle, and high schools across South Korea. Then, final 15 items were selected according to the reliability test results. The final scale consisted of four subdomains: (1) disturbance of adaptive functions, (2) virtual life orientation, (3) withdrawal, and (4) tolerance. The final scale indicated a high reliability with Cronbach's α of .880. Support for the scale's criterion validity has been demonstrated by its relationship to the internet addiction scale, KS-II (r  =  .49). For the analysis of construct validity, we tested the Structural Equation Model. The results showed the four-factor structure to be valid (NFI  =  .943, TLI  =  .902, CFI  =  .902, RMSEA  =  .034). Smartphone addiction is gaining a greater spotlight as possibly a new form of addiction along with internet addiction. The SAPS appears to be a reliable and valid diagnostic scale for screening adolescents who may be at risk of smartphone addiction. Further implications and limitations are discussed. PMID:24848006

  1. Multidisciplinary approach to converting power chair into motorized prone cart.

    PubMed

    Brose, Steven W; Wali, Eisha

    2014-01-01

    Pressure ulcers remain a major source of morbidity and mortality in veterans with neurologic impairment. Management of pressure ulcers typically involves pressure relief over skin regions containing wounds, but this can lead to loss of mobility and independence when the wounds are located in regions that receive pressure from sitting. An innovative, low-cost, multidisciplinary effort was undertaken to maximize quality of life in a veteran with a thoracic-4 level complete spinal cord injury and a stage 4 ischial wound. The person's power wheelchair was converted into a motorized prone cart, allowing navigation of the Department of Veterans Affairs spinal cord injury hospital ward and improved socialization while relieving pressure on the wound. Physical and occupational therapy assisted with the reconfiguration of the power chair and verified safe transfers into the chair and driving of the device. Psychology verified positive psychosocial benefit, while nursing and physician services verified an absence of unwanted pain or skin injury resulting from use of the device. Further investigation of ways to apply this technique is warranted to improve the quality of life of persons with pressure ulcers. PMID:25786192

  2. Development of Korean Smartphone addiction proneness scale for youth.

    PubMed

    Kim, Dongil; Lee, Yunhee; Lee, Juyoung; Nam, JeeEun Karin; Chung, Yeoju

    2014-01-01

    This study developed a Smartphone Addiction Proneness Scale (SAPS) based on the existing internet and cellular phone addiction scales. For the development of this scale, 29 items (1.5 times the final number of items) were initially selected as preliminary items, based on the previous studies on internet/phone addiction as well as the clinical experience of involved experts. The preliminary scale was administered to a nationally representative sample of 795 students in elementary, middle, and high schools across South Korea. Then, final 15 items were selected according to the reliability test results. The final scale consisted of four subdomains: (1) disturbance of adaptive functions, (2) virtual life orientation, (3) withdrawal, and (4) tolerance. The final scale indicated a high reliability with Cronbach's α of .880. Support for the scale's criterion validity has been demonstrated by its relationship to the internet addiction scale, KS-II (r  =  .49). For the analysis of construct validity, we tested the Structural Equation Model. The results showed the four-factor structure to be valid (NFI  =  .943, TLI  =  .902, CFI  =  .902, RMSEA  =  .034). Smartphone addiction is gaining a greater spotlight as possibly a new form of addiction along with internet addiction. The SAPS appears to be a reliable and valid diagnostic scale for screening adolescents who may be at risk of smartphone addiction. Further implications and limitations are discussed. PMID:24848006

  3. Facts about Refractive Errors

    MedlinePlus

    ... the lens can cause refractive errors. What is refraction? Refraction is the bending of light as it passes ... rays entering the eye, causing a more precise refraction or focus. In many cases, contact lenses provide ...

  4. Error mode prediction.

    PubMed

    Hollnagel, E; Kaarstad, M; Lee, H C

    1999-11-01

    The study of accidents ('human errors') has been dominated by efforts to develop 'error' taxonomies and 'error' models that enable the retrospective identification of likely causes. In the field of Human Reliability Analysis (HRA) there is, however, a significant practical need for methods that can predict the occurrence of erroneous actions--qualitatively and quantitatively. The present experiment tested an approach for qualitative performance prediction based on the Cognitive Reliability and Error Analysis Method (CREAM). Predictions of possible erroneous actions were made for operators using different types of alarm systems. The data were collected as part of a large-scale experiment using professional nuclear power plant operators in a full scope simulator. The analysis showed that the predictions were correct in more than 70% of the cases, and also that the coverage of the predictions depended critically on the comprehensiveness of the preceding task analysis. PMID:10582035

  5. Pronominal Case-Errors

    ERIC Educational Resources Information Center

    Kaper, Willem

    1976-01-01

    Contradicts a previous assertion by C. Tanz that children commit substitution errors usually using objective pronoun forms for nominative ones. Examples from Dutch and German provide evidence that substitutions are made in both directions. (CHK)

  6. Errors in prenatal diagnosis.

    PubMed

    Anumba, Dilly O C

    2013-08-01

    Prenatal screening and diagnosis are integral to antenatal care worldwide. Prospective parents are offered screening for common fetal chromosomal and structural congenital malformations. In most developed countries, prenatal screening is routinely offered in a package that includes ultrasound scan of the fetus and the assay in maternal blood of biochemical markers of aneuploidy. Mistakes can arise at any point of the care pathway for fetal screening and diagnosis, and may involve individual or corporate systemic or latent errors. Special clinical circumstances, such as maternal size, fetal position, and multiple pregnancy, contribute to the complexities of prenatal diagnosis and to the chance of error. Clinical interventions may lead to adverse outcomes not caused by operator error. In this review I discuss the scope of the errors in prenatal diagnosis, and highlight strategies for their prevention and diagnosis, as well as identify areas for further research and study to enhance patient safety. PMID:23725900

  7. Estimating Bias Error Distributions

    NASA Technical Reports Server (NTRS)

    Liu, Tian-Shu; Finley, Tom D.

    2001-01-01

    This paper formulates the general methodology for estimating the bias error distribution of a device in a measuring domain from less accurate measurements when a minimal number of standard values (typically two values) are available. A new perspective is that the bias error distribution can be found as a solution of an intrinsic functional equation in a domain. Based on this theory, the scaling- and translation-based methods for determining the bias error distribution arc developed. These methods are virtually applicable to any device as long as the bias error distribution of the device can be sufficiently described by a power series (a polynomial) or a Fourier series in a domain. These methods have been validated through computational simulations and laboratory calibration experiments for a number of different devices.

  8. Regional vulnerability of mesencephalic dopaminergic neurons prone to degenerate in Parkinson's disease: a post-mortem study in human control subjects.

    PubMed

    Lu, Lixia; Neff, Frauke; Fischer, Daniel Alvarez; Henze, Carmen; Hirsch, Etienne C; Oertel, Wolfgang H; Schlegel, Jürgen; Hartmann, Andreas

    2006-08-01

    Parkinson's disease (PD) is characterized by loss of dopaminergic (DA) neurons in the human midbrain, which varies greatly among mesencephalic subregions. The genetic expression profiles of mesencephalic DA neurons particularly prone to degenerate during PD (nigrosome 1 within the substantia nigra pars compacta-SNpc) and those particularly resistant in the disease course (central grey substance-CGS) were compared in five control subjects by immuno-laser capture microdissection followed by RNA arbitrarily primed PCR. 8 ESTs of interest were selected for analysis by real time quantitative reverse transcription PCR. DA neurons in the CGS preferentially expressed implicated in cell survival (7 out of 8 genes selected), whereas SNpc DA neurons preferentially expressed one gene making them potentially susceptible to undergo cell death in PD. We propose that factors making CGS DA neurons more resistant may be helpful in protecting SNpc DA neurons against a pathological insult. PMID:16753304

  9. Are brain and heart tissue prone to the development of thiamine deficiency?

    PubMed

    Klooster, Astrid; Larkin, James R; Wiersema-Buist, Janneke; Gans, Reinold O B; Thornalley, Paul J; Navis, Gerjan; van Goor, Harry; Leuvenink, Henri G D; Bakker, Stephan J L

    2013-05-01

    Thiamine deficiency is a continuing problem leading to beriberi and Wernicke's encephalopathy. The symptoms of thiamine deficiency develop in the heart, brain and neuronal tissue. Yet, it is unclear how rapid thiamine deficiency develops and which organs are prone to development of thiamine deficiency. We investigated these issues in a thiamine deficient animal model. Twenty-four male Lewis rats were fed a thiamine deficient diet, which contained 0.04% of normal thiamine intake. Six control rats were fed 200 μg of thiamine per day. Every week a group of six rats on the thiamine-deficient diet was sacrificed and blood, urine and tissue were stored. Blood and tissue transketolase activity, thiamine and thiamine metabolites were measured and PCR of thiamine transporter-1 (ThTr-1) was performed. Transketolase activity was significantly reduced in red blood cells, liver, lung, kidney and spleen tissue after two weeks of thiamine deficient diet. In brain tissue, transketolase activity was not reduced after up to four weeks of thiamine deficient diet. The amount of thiamine pyrophosphate was also significantly conserved in brain and heart tissue (decrease of 31% and 28% respectively), compared to other tissues (decrease of ~70%) after four weeks of thiamine deficient diet. There was no difference between tissues in ThTr-1 expression after four weeks of thiamine deficient diet. Despite the fact that the heart and the brain are predilection sites for complications from thiamine deficiency, these tissues are protected against thiamine deficiency. Other organs could be suffering from thiamine deficiency without resulting in clinical signs of classic thiamine deficiency in beriberi and Wernicke's encephalopathy. PMID:23357554

  10. Error-Compensated Telescope

    NASA Technical Reports Server (NTRS)

    Meinel, Aden B.; Meinel, Marjorie P.; Stacy, John E.

    1989-01-01

    Proposed reflecting telescope includes large, low-precision primary mirror stage and small, precise correcting mirror. Correcting mirror machined under computer control to compensate for error in primary mirror. Correcting mirror machined by diamond cutting tool. Computer analyzes interferometric measurements of primary mirror to determine shape of surface of correcting mirror needed to compensate for errors in wave front reflected from primary mirror and commands position and movement of cutting tool accordingly.

  11. Thermodynamics of Error Correction

    NASA Astrophysics Data System (ADS)

    Sartori, Pablo; Pigolotti, Simone

    2015-10-01

    Information processing at the molecular scale is limited by thermal fluctuations. This can cause undesired consequences in copying information since thermal noise can lead to errors that can compromise the functionality of the copy. For example, a high error rate during DNA duplication can lead to cell death. Given the importance of accurate copying at the molecular scale, it is fundamental to understand its thermodynamic features. In this paper, we derive a universal expression for the copy error as a function of entropy production and work dissipated by the system during wrong incorporations. Its derivation is based on the second law of thermodynamics; hence, its validity is independent of the details of the molecular machinery, be it any polymerase or artificial copying device. Using this expression, we find that information can be copied in three different regimes. In two of them, work is dissipated to either increase or decrease the error. In the third regime, the protocol extracts work while correcting errors, reminiscent of a Maxwell demon. As a case study, we apply our framework to study a copy protocol assisted by kinetic proofreading, and show that it can operate in any of these three regimes. We finally show that, for any effective proofreading scheme, error reduction is limited by the chemical driving of the proofreading reaction.

  12. Body Image, Self-Esteem, and Depression-Proneness: Closing the Gender Gap.

    ERIC Educational Resources Information Center

    McCaulay, Marci; And Others

    1988-01-01

    Examines gender differences in body image and its relationship to depression-proneness and self-esteem. Findings indicate a preoccupation with body weight and appearance for both men and women, and a relationship between body satisfaction and depression-proneness. (FMW)

  13. A Comparison of Men Who Are Divorce Prone with Those Who Are Marriage Phobic.

    ERIC Educational Resources Information Center

    Counts, Robert M.; Reid, Kelly

    1986-01-01

    Compares two divorce prone men with two marriage phobic men. Marriage phobic men were fearful of getting married and used avoidance as a means of coping. Divorce prone were self-centered, hard driving, and reckless using acting out to manage conflict. Both groups were wary of the opposite sex and needed to be in control of relationships.…

  14. The Relationship of Stress Arousal and Stress Prone Personality Traits to Menstrual Distress.

    ERIC Educational Resources Information Center

    Marini, David C.

    The various relationships of stress arousal and stress-prone personality traits to menstrual distress were investigated in order to quantify psychophysiological arousal differences between high and low menstrual distress symptom reporters and examine differences in stress-prone personality traits between high and low menstrual distress symptom…

  15. Critical Differences between the Type-A Prone and Type-A Personalitites.

    ERIC Educational Resources Information Center

    Cassel, Russell N.; Cassel, Susie L.

    1984-01-01

    Type-A Prone and Type-A personalities were assessed on the basis of the Cassel Type-A Personality Assessment Profile. Statistical data analysis indicated differences in positive lifestyle, blood pressure, and self-control and no differences in negative lifestyle, pulse rate, or peripheral temperature. Type-A Prone and Type-A norm profiles were…

  16. Suicide Proneness in College Students: Relationships with Gender, Procrastination, and Achievement Motivation

    ERIC Educational Resources Information Center

    Klibert, Jeffrey; Langhinrichsen-Rohling, Jennifer; Luna, Amy; Robichaux, Michelle

    2011-01-01

    This study examined the relationships between 2 academic dispositions (i.e., procrastination and achievement motivation) and 2 indices of suicidal proneness in college women and men. The degree these 2 academic dispositions could predict unique variance in suicide proneness scores, above and beyond the influence of depression and self-esteem was…

  17. Rumination, reflection, intrusive thoughts, and hallucination-proneness: towards a new model.

    PubMed

    Jones, Simon R; Fernyhough, Charles

    2009-01-01

    Although rumination has been proposed to play an important role in the creation of hallucinations, direct empirical tests of this proposal have not yet been performed. Employing a distinction between ruminative and reflective self-consciousness, we set out to test a new model of the relations among rumination, reflection, intrusive thoughts, thought suppression, social anxiety, and hallucination-proneness. This model proposed that rumination would be related to hallucination-proneness through the mediating variable of intrusive thoughts, but that reflection would not be related to hallucination-proneness. The model was tested in a student population (N=296) using path analyses. A modified version of the model was found to be a good fit to the data, once a direct path from reflection to hallucination-proneness had been added. As hypothesized, rumination was related to hallucination-proneness only indirectly, through the mediating variable of intrusive thoughts. Implications for interventions and future directions for research are considered. PMID:19013552

  18. Human error in aviation operations

    NASA Technical Reports Server (NTRS)

    Nagel, David C.

    1988-01-01

    The role of human error in commercial and general aviation accidents and the techniques used to evaluate it are reviewed from a human-factors perspective. Topics addressed include the general decline in accidents per million departures since the 1960s, the increase in the proportion of accidents due to human error, methods for studying error, theoretical error models, and the design of error-resistant systems. Consideration is given to information acquisition and processing errors, visually guided flight, disorientation, instrument-assisted guidance, communication errors, decision errors, debiasing, and action errors.

  19. Errata: Papers in Error Analysis.

    ERIC Educational Resources Information Center

    Svartvik, Jan, Ed.

    Papers presented at the symposium of error analysis in Lund, Sweden, in September 1972, approach error analysis specifically in its relation to foreign language teaching and second language learning. Error analysis is defined as having three major aspects: (1) the description of the errors, (2) the explanation of errors by means of contrastive…

  20. Genome-Wide Association Study of Proneness to Anger

    PubMed Central

    Mick, Eric; McGough, James; Deutsch, Curtis K.; Frazier, Jean A.; Kennedy, David; Goldberg, Robert J.

    2014-01-01

    Background Community samples suggest that approximately 1 in 20 children and adults exhibit clinically significant anger, hostility, and aggression. Individuals with dysregulated emotional control have a greater lifetime burden of psychiatric morbidity, severe impairment in role functioning, and premature mortality due to cardiovascular disease. Methods With publically available data secured from dbGaP, we conducted a genome-wide association study of proneness to anger using the Spielberger State-Trait Anger Scale in the Atherosclerosis Risk in Communities (ARIC) study (n = 8,747). Results Subjects were, on average, 54 (range 45–64) years old at baseline enrollment, 47% (n = 4,117) were male, and all were of European descent by self-report. The mean Angry Temperament and Angry Reaction scores were 5.8±1.8 and 7.6±2.2. We observed a nominally significant finding (p = 2.9E-08, λ = 1.027 - corrected pgc = 2.2E-07, λ = 1.0015) on chromosome 6q21 in the gene coding for the non-receptor protein-tyrosine kinase, Fyn. Conclusions Fyn interacts with NDMA receptors and inositol-1,4,5-trisphosphate (IP3)-gated channels to regulate calcium influx and intracellular release in the post-synaptic density. These results suggest that signaling pathways regulating intracellular calcium homeostasis, which are relevant to memory, learning, and neuronal survival, may in part underlie the expression of Angry Temperament. PMID:24489884

  1. A Comprehensive Review of Prone Position in ARDS.

    PubMed

    Kallet, Richard H

    2015-11-01

    Prone position (PP) has been used since the 1970s to treat severe hypoxemia in patients with ARDS because of its effectiveness at improving gas exchange. Compared with the supine position (SP), placing patients in PP effects a more even tidal volume distribution, in part, by reversing the vertical pleural pressure gradient, which becomes more negative in the dorsal regions. PP also improves resting lung volume in the dorsocaudal regions by reducing the superimposed pressure of both the heart and the abdomen. In contrast, pulmonary perfusion remains preferentially distributed to the dorsal lung regions, thus improving overall alveolar ventilation/perfusion relationships. Moreover, the larger tissue mass suspended from a wider dorsal chest wall effects a more homogeneous distribution of pleural pressures throughout the lung that reduces abnormal strain and stress development. This is believed to ameliorate the severity or development of ventilator-induced lung injury and may partly explain why PP reduces mortality in severe ARDS. Over 40 years of clinical trials have consistently reported improved oxygenation in approximately 70% of subjects with ARDS. Early initiation of PP is more likely to improve oxygenation than initiation during the subacute phase. Maximal oxygenation improvement occurs over a wide time frame ranging from several hours to several days. Meta-analyses of randomized controlled trials suggest that PP provides a survival advantage only in patients with relatively severe ARDS (PaO2 /FIO2 < 150 mm Hg). Moreover, survival is enhanced when patients are managed with a smaller tidal volume (≤ 8 mL/kg), higher PEEP (10-13 cm H2O), and longer duration of PP sessions (> 10-12 h/session). Combining adjunctive therapies (high PEEP, recruitment maneuvers, and inhaled vasodilators) with PP has an additive effect in improving oxygenation and may be particularly helpful in stabilizing gas exchange in very severe ARDS. PMID:26493592

  2. Smoothing error pitfalls

    NASA Astrophysics Data System (ADS)

    von Clarmann, T.

    2014-09-01

    The difference due to the content of a priori information between a constrained retrieval and the true atmospheric state is usually represented by a diagnostic quantity called smoothing error. In this paper it is shown that, regardless of the usefulness of the smoothing error as a diagnostic tool in its own right, the concept of the smoothing error as a component of the retrieval error budget is questionable because it is not compliant with Gaussian error propagation. The reason for this is that the smoothing error does not represent the expected deviation of the retrieval from the true state but the expected deviation of the retrieval from the atmospheric state sampled on an arbitrary grid, which is itself a smoothed representation of the true state; in other words, to characterize the full loss of information with respect to the true atmosphere, the effect of the representation of the atmospheric state on a finite grid also needs to be considered. The idea of a sufficiently fine sampling of this reference atmospheric state is problematic because atmospheric variability occurs on all scales, implying that there is no limit beyond which the sampling is fine enough. Even the idealization of infinitesimally fine sampling of the reference state does not help, because the smoothing error is applied to quantities which are only defined in a statistical sense, which implies that a finite volume of sufficient spatial extent is needed to meaningfully discuss temperature or concentration. Smoothing differences, however, which play a role when measurements are compared, are still a useful quantity if the covariance matrix involved has been evaluated on the comparison grid rather than resulting from interpolation and if the averaging kernel matrices have been evaluated on a grid fine enough to capture all atmospheric variations that the instruments are sensitive to. This is, under the assumptions stated, because the undefined component of the smoothing error, which is the

  3. Compact disk error measurements

    NASA Technical Reports Server (NTRS)

    Howe, D.; Harriman, K.; Tehranchi, B.

    1993-01-01

    The objectives of this project are as follows: provide hardware and software that will perform simple, real-time, high resolution (single-byte) measurement of the error burst and good data gap statistics seen by a photoCD player read channel when recorded CD write-once discs of variable quality (i.e., condition) are being read; extend the above system to enable measurement of the hard decision (i.e., 1-bit error flags) and soft decision (i.e., 2-bit error flags) decoding information that is produced/used by the Cross Interleaved - Reed - Solomon - Code (CIRC) block decoder employed in the photoCD player read channel; construct a model that uses data obtained via the systems described above to produce meaningful estimates of output error rates (due to both uncorrected ECC words and misdecoded ECC words) when a CD disc having specific (measured) error statistics is read (completion date to be determined); and check the hypothesis that current adaptive CIRC block decoders are optimized for pressed (DAD/ROM) CD discs. If warranted, do a conceptual design of an adaptive CIRC decoder that is optimized for write-once CD discs.

  4. A simple, universal, efficient PCR-based gene synthesis method: sequential OE-PCR gene synthesis.

    PubMed

    Zhang, Pingping; Ding, Yingying; Liao, Wenting; Chen, Qiuli; Zhang, Huaqun; Qi, Peipei; He, Ting; Wang, Jinhong; Deng, Songhua; Pan, Tianyue; Ren, Hao; Pan, Wei

    2013-07-25

    Herein we present a simple, universal, efficient gene synthesis method based on sequential overlap extension polymerase chain reactions (OE-PCRs). This method involves four key steps: (i) the design of paired complementary 54-mer oligonucleotides with 18 bp overlaps, (ii) the utilisation of sequential OE-PCR to synthesise full-length genes, (iii) the cloning and sequencing of four positive T-clones of the synthesised genes and (iv) the resynthesis of target genes by OE-PCR with correct templates. Mispriming and secondary structure were found to be the principal obstacles preventing successful gene synthesis and were easily identified and solved in this method. Compensating for the disadvantages of being laborious and time-consuming, this method has many attractive advantages, such as the ability to guarantee successful gene synthesis in most cases and good allowance for Taq polymerase, oligonucleotides, PCR conditions and a high error rate. Thus, this method provides an alternative tool for individual gene synthesis without strict needs of the high-specialised experience. PMID:23597923

  5. [Rapid PCR authentication Lonicera japanica].

    PubMed

    Jiang, Chao; Hou, Jing-Yi; Huang, Lu-Qi; Yuan, Yuan; Chen, Min; Jin, Yan

    2014-10-01

    To simply and rapid authenticate Lonicera japanica. Rapid allele-specific PCR primer was designed base on trnL-trnF 625 G/T Single nucleotide polymorphism and the PCR reaction systems including annealing temperature was optimized; optimized results were performed to authenticate L. japanica and its 9 adulterants. When 100 x SYBR Green I was added in the PCR product of 87 degrees C initial denatured 1 min; 87 degrees C denatured 5 s, 68 degrees C annealing 5 s, 30 cycle; L. japanica visualize strong green fluorescence under 365 nm UV lamp whereas adulterants without. The results indicate rapid allele-specific PCR could authenticate L. japanica and its adulterants rapidly and simply. PMID:25612418

  6. The importance of robust error control in data compression applications

    NASA Technical Reports Server (NTRS)

    Woolley, S. I.

    1993-01-01

    Data compression has become an increasingly popular option as advances in information technology have placed further demands on data storage capabilities. With compression ratios as high as 100:1 the benefits are clear; however, the inherent intolerance of many compression formats to error events should be given careful consideration. If we consider that efficiently compressed data will ideally contain no redundancy, then the introduction of a channel error must result in a change of understanding from that of the original source. While the prefix property of codes such as Huffman enables resynchronisation, this is not sufficient to arrest propagating errors in an adaptive environment. Arithmetic, Lempel-Ziv, discrete cosine transform (DCT) and fractal methods are similarly prone to error propagating behaviors. It is, therefore, essential that compression implementations provide sufficient combatant error control in order to maintain data integrity. Ideally, this control should be derived from a full understanding of the prevailing error mechanisms and their interaction with both the system configuration and the compression schemes in use.

  7. Experimental investigation of observation error in anuran call surveys

    USGS Publications Warehouse

    McClintock, B.T.; Bailey, L.L.; Pollock, K.H.; Simons, T.R.

    2010-01-01

    Occupancy models that account for imperfect detection are often used to monitor anuran and songbird species occurrence. However, presenceabsence data arising from auditory detections may be more prone to observation error (e.g., false-positive detections) than are sampling approaches utilizing physical captures or sightings of individuals. We conducted realistic, replicated field experiments using a remote broadcasting system to simulate simple anuran call surveys and to investigate potential factors affecting observation error in these studies. Distance, time, ambient noise, and observer abilities were the most important factors explaining false-negative detections. Distance and observer ability were the best overall predictors of false-positive errors, but ambient noise and competing species also affected error rates for some species. False-positive errors made up 5 of all positive detections, with individual observers exhibiting false-positive rates between 0.5 and 14. Previous research suggests false-positive errors of these magnitudes would induce substantial positive biases in standard estimators of species occurrence, and we recommend practices to mitigate for false positives when developing occupancy monitoring protocols that rely on auditory detections. These recommendations include additional observer training, limiting the number of target species, and establishing distance and ambient noise thresholds during surveys. ?? 2010 The Wildlife Society.

  8. Experimental Quantum Error Detection

    PubMed Central

    Jin, Xian-Min; Yi, Zhen-Huan; Yang, Bin; Zhou, Fei; Yang, Tao; Peng, Cheng-Zhi

    2012-01-01

    Faithful transmission of quantum information is a crucial ingredient in quantum communication networks. To overcome the unavoidable decoherence in a noisy channel, to date, many efforts have been made to transmit one state by consuming large numbers of time-synchronized ancilla states. However, such huge demands of quantum resources are hard to meet with current technology and this restricts practical applications. Here we experimentally demonstrate quantum error detection, an economical approach to reliably protecting a qubit against bit-flip errors. Arbitrary unknown polarization states of single photons and entangled photons are converted into time bins deterministically via a modified Franson interferometer. Noise arising in both 10 m and 0.8 km fiber, which induces associated errors on the reference frame of time bins, is filtered when photons are detected. The demonstrated resource efficiency and state independence make this protocol a promising candidate for implementing a real-world quantum communication network. PMID:22953047

  9. Measurement error revisited

    NASA Astrophysics Data System (ADS)

    Henderson, Robert K.

    1999-12-01

    It is widely accepted in the electronics industry that measurement gauge error variation should be no larger than 10% of the related specification window. In a previous paper, 'What Amount of Measurement Error is Too Much?', the author used a framework from the process industries to evaluate the impact of measurement error variation in terms of both customer and supplier risk (i.e., Non-conformance and Yield Loss). Application of this framework in its simplest form suggested that in many circumstances the 10% criterion might be more stringent than is reasonably necessary. This paper reviews the framework and results of the earlier work, then examines some of the possible extensions to this framework suggested in that paper, including variance component models and sampling plans applicable in the photomask and semiconductor businesses. The potential impact of imperfect process control practices will be examined as well.

  10. Surprise beyond prediction error

    PubMed Central

    Chumbley, Justin R; Burke, Christopher J; Stephan, Klaas E; Friston, Karl J; Tobler, Philippe N; Fehr, Ernst

    2014-01-01

    Surprise drives learning. Various neural “prediction error” signals are believed to underpin surprise-based reinforcement learning. Here, we report a surprise signal that reflects reinforcement learning but is neither un/signed reward prediction error (RPE) nor un/signed state prediction error (SPE). To exclude these alternatives, we measured surprise responses in the absence of RPE and accounted for a host of potential SPE confounds. This new surprise signal was evident in ventral striatum, primary sensory cortex, frontal poles, and amygdala. We interpret these findings via a normative model of surprise. PMID:24700400

  11. Evolution of error diffusion

    NASA Astrophysics Data System (ADS)

    Knox, Keith T.

    1999-10-01

    As we approach the new millennium, error diffusion is approaching the 25th anniversary of its invention. Because of its exceptionally high image quality, it continues to be a popular choice among digital halftoning algorithms. Over the last 24 years, many attempts have been made to modify and improve the algorithm--to eliminate unwanted textures and to extend it to printing media and color. Some of these modifications have been very successful and are in use today. This paper will review the history of the algorithm and its modifications. Three watershed events in the development of error diffusion will be described, together with the lessons learned along the way.

  12. Evolution of error diffusion

    NASA Astrophysics Data System (ADS)

    Knox, Keith T.

    1998-12-01

    As we approach the new millennium, error diffusion is approaching the 25th anniversary of its invention. Because of its exceptionally high image quality, it continues to be a popular choice among digital halftoning algorithms. Over the last 24 years, many attempts have been made to modify and improve the algorithm - to eliminate unwanted textures and to extend it to printing media and color. Some of these modifications have been very successful and are in use today. This paper will review the history of the algorithm and its modifications. Three watershed events in the development of error diffusion will be described, together with the lesions learned along the way.

  13. Error Free Software

    NASA Technical Reports Server (NTRS)

    1985-01-01

    A mathematical theory for development of "higher order" software to catch computer mistakes resulted from a Johnson Space Center contract for Apollo spacecraft navigation. Two women who were involved in the project formed Higher Order Software, Inc. to develop and market the system of error analysis and correction. They designed software which is logically error-free, which, in one instance, was found to increase productivity by 600%. USE.IT defines its objectives using AXES -- a user can write in English and the system converts to computer languages. It is employed by several large corporations.

  14. Regional ventilation-perfusion distribution is more uniform in the prone position

    NASA Technical Reports Server (NTRS)

    Mure, M.; Domino, K. B.; Lindahl, S. G.; Hlastala, M. P.; Altemeier, W. A.; Glenny, R. W.

    2000-01-01

    The arterial blood PO(2) is increased in the prone position in animals and humans because of an improvement in ventilation (VA) and perfusion (Q) matching. However, the mechanism of improved VA/Q is unknown. This experiment measured regional VA/Q heterogeneity and the correlation between VA and Q in supine and prone positions in pigs. Eight ketamine-diazepam-anesthetized, mechanically ventilated pigs were studied in supine and prone positions in random order. Regional VA and Q were measured using fluorescent-labeled aerosols and radioactive-labeled microspheres, respectively. The lungs were dried at total lung capacity and cubed into 603-967 small ( approximately 1.7-cm(3)) pieces. In the prone position the homogeneity of the ventilation distribution increased (P = 0.030) and the correlation between VA and Q increased (correlation coefficient = 0.72 +/- 0.08 and 0.82 +/- 0.06 in supine and prone positions, respectively, P = 0.03). The homogeneity of the VA/Q distribution increased in the prone position (P = 0.028). We conclude that the improvement in VA/Q matching in the prone position is secondary to increased homogeneity of the VA distribution and increased correlation of regional VA and Q.

  15. Is decreased diameter of renal pelvis in prone position an indicator of successful pyeloplasty?

    PubMed Central

    Sharma, Gyanendra; Sharma, Anshu; Leung, Vivian Yee-Fong; Chu, Winnie Chiu-Wing

    2016-01-01

    Objective: To evaluate patients who had undergone pyeloplasty for pelviureteric junction obstruction, by measuring the anteroposterior diameter (APD) of the renal pelvis in supine and prone positions, and determine whether a decrease in APD in prone position can exclude obstruction in dilated renal system. Materials and Methods: From January 2012 to December 2013, patients who had undergone pyeloplasty were evaluated by ultrasound in two centers. The difference of APD of the renal pelvis in supine and prone positions was obtained. Correlation was made with the pre- and post-pyeloplasty renal function by radionuclide renogram. Results: There were 42 patients (31 males, 11 females; age range 5 months to 18 years). Residual hydronephrosis was detected in 41 patients of whom 35 patients (85%) showed decrease in APD by >10% in prone position. These patients and the one without hydronephrosis showed either no deterioration or improvement in renal function. Six patients (15%) showed either no change or increase in APD in prone position. Three patients (7.5%) were confirmed to have decrease in renal function indicating obstruction. Three patients (7.5%) showed no deterioration of renal function, but sluggish drainage on radionuclide renogram. Conclusion: Demonstration of decreased APD of renal pelvis in prone position by ultrasound is useful to differentiate obstructed from non-obstructed dilated renal system, and it correctly identified 85% candidates with successful pyeloplasty. In patients with no decrease or increase in APD at prone position, further follow-up is recommended to rule out obstruction. PMID:27081219

  16. A study of PCR inhibition mechanisms using real time PCR.

    PubMed

    Opel, Kerry L; Chung, Denise; McCord, Bruce R

    2010-01-01

    In this project, real time polymerase chain reaction (PCR) was utilized to study the mechanism of PCR inhibition through examination of the effect of amplicon length, melting temperature, and sequence. Specifically designed primers with three different amplicon lengths and three different melting temperatures were used to target a single homozygous allele in the HUMTH01 locus. The effect on amplification efficiency for each primer pair was determined by adding different concentrations of various PCR inhibitors to the reaction mixture. The results show that a variety of inhibition mechanisms can occur during the PCR process depending on the type of co-extracted inhibitor. These include Taq inhibition, DNA template binding, and effects on reaction efficiency. In addition, some inhibitors appear to affect the reaction in more than one manner. Overall we find that amplicon size and melting temperature are important in some inhibition mechanisms and not in others and the key issue in understanding PCR inhibition is determining the identity of the interfering substance. PMID:20015162

  17. Ligation-independent cloning of PCR products (LIC-PCR).

    PubMed Central

    Aslanidis, C; de Jong, P J

    1990-01-01

    A new procedure has been developed for the efficient cloning of complex PCR mixtures, resulting in libraries exclusively consisting of recombinant clones. Recombinants are generated between PCR products and a PCR-amplified plasmid vector. The procedure does not require the use of restriction enzymes, T4 DNA ligase or alkaline phosphatase. The 5'-ends of the primers used to generate the cloneable PCR fragments contain an additional 12 nucleotide (nt) sequence lacking dCMP. As a result, the amplification products include 12-nt sequences lacking dGMP at their 3'-ends. The 3'-terminal sequence can be removed by the action of the (3'----5') exonuclease activity of T4 DNA polymerase in the presence of dGTP, leading to fragments with 5'-extending single-stranded (ss) tails of a defined sequence and length. Similarly, the entire plasmid vector is amplified with primers homologous to sequences in the multiple cloning site. The vector oligos have additional 12-nt tails complementary to the tails used for fragment amplification, permitting the creation of ss-ends with T4 DNA polymerase in the presence of dCTP. Circularization can occur between vector molecules and PCR fragments as mediated by the 12-nt cohesive ends, but not in mixtures lacking insert fragments. The resulting circular recombinant molecules do not require in vitro ligation for efficient bacterial transformation. We have applied the procedure for the cloning of inter-ALU fragments from hybrid cell-lines and human cosmid clones. Images PMID:2235490

  18. Individual Positioning: A Comparative Study of Adjuvant Breast Radiotherapy in the Prone Versus Supine Position

    SciTech Connect

    Varga, Zoltan; Hideghety, Katalin; Mezo, Tamas; Nikolenyi, Aliz; Thurzo, Laszlo; Kahan, Zsuzsanna

    2009-09-01

    Purpose: To study breast radiotherapy in the prone vs. supine positions through dosimetry and clinical implementation. Methods and Materials: Conformal radiotherapy plans in 61 patients requiring only breast irradiation were developed for both the prone and supine positions. After evaluation of the of the first 20 plan pairs, the patients were irradiated in the prone or supine position in a randomized fashion. These cases were analyzed for repositioning accuracy and skin reactions related to treatment position and patient characteristics. Results: The planning target volume covered with 47.5-53.5 Gy in the prone vs. the supine position was 85.1% {+-} 4.2% vs. 89.2 {+-} 2.2%, respectively (p < 0.0001). Radiation exposure of the ipsilateral lung, expressed in terms of the mean lung dose and the V{sub 20Gy}, was dramatically lower in the prone vs. supine position (p < 0.0001), but the doses to the heart did not differ. There was no difference in the need to correct positioning during radiotherapy, but the extent of displacement was significantly higher in the prone vs. supine position (p = 0.021). The repositioning accuracy in the prone position exhibited an improvement over time and did not depend on any patient-related parameters. Significantly more radiodermatitis of Grade 1-2 developed following prone vs. supine irradiation (p = 0.025). Conclusions: Conformal breast radiotherapy is feasible in the prone position. Its primary advantage is the substantially lower radiation dose to the ipsilateral lung. The higher dose inhomogeneity and increased rate of Grade 1-2 skin toxicity, however, may be of concern.

  19. Help prevent hospital errors

    MedlinePlus

    ... A.D.A.M. Editorial team. Related MedlinePlus Health Topics Medication Errors Patient Safety Browse the Encyclopedia A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission ... for online health information and services. Learn more about A.D. ...

  20. Orwell's Instructive Errors

    ERIC Educational Resources Information Center

    Julian, Liam

    2009-01-01

    In this article, the author talks about George Orwell, his instructive errors, and the manner in which Orwell pierced worthless theory, faced facts and defended decency (with fluctuating success), and largely ignored the tradition of accumulated wisdom that has rendered him a timeless teacher--one whose inadvertent lessons, while infrequently…

  1. Challenge and Error: Critical Events and Attention-Related Errors

    ERIC Educational Resources Information Center

    Cheyne, James Allan; Carriere, Jonathan S. A.; Solman, Grayden J. F.; Smilek, Daniel

    2011-01-01

    Attention lapses resulting from reactivity to task challenges and their consequences constitute a pervasive factor affecting everyday performance errors and accidents. A bidirectional model of attention lapses (error [image omitted] attention-lapse: Cheyne, Solman, Carriere, & Smilek, 2009) argues that errors beget errors by generating attention…

  2. Mapping radon-prone areas using γ-radiation dose rate and geological information.

    PubMed

    García-Talavera, M; García-Pérez, A; Rey, C; Ramos, L

    2013-09-01

    Identifying radon-prone areas is key to policies on the control of this environmental carcinogen. In the current paper, we present the methodology followed to delineate radon-prone areas in Spain. It combines information from indoor radon measurements with γ-radiation and geological maps. The advantage of the proposed approach is that it lessens the requirement for a high density of measurements by making use of commonly available information. It can be applied for an initial definition of radon-prone areas in countries committed to introducing a national radon policy or to improving existing radon maps in low population regions. PMID:23803560

  3. Standing prone positioning in establishing causality between matched ventilation-perfusion defects and pleural effusion.

    PubMed

    Fotos, Joseph S; Tulchinsky, Mark

    2015-01-01

    Ventilation-perfusion scintigraphy is routinely performed in patients with suspected pulmonary thromboembolism. Pleural effusions in such patients are common and can cause matched ventilation-perfusion defects. This is especially true of the posterior projections in the supine patient. Prone positioning has been described as a useful technique to redistribute pleural fluid anteriorly, exposing perfusion in posterior lung fields; however, some patients have a concurrent condition that renders prone positioning difficult. This report discusses a modified technique that allows patients to be imaged in a standing prone position with excellent results. PMID:25247271

  4. Sources of Error in Mammalian Genetic Screens.

    PubMed

    Sack, Laura Magill; Davoli, Teresa; Xu, Qikai; Li, Mamie Z; Elledge, Stephen J

    2016-01-01

    Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. PMID:27402361

  5. Sources of Error in Mammalian Genetic Screens

    PubMed Central

    Sack, Laura Magill; Davoli, Teresa; Xu, Qikai; Li, Mamie Z.; Elledge, Stephen J.

    2016-01-01

    Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc. This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. PMID:27402361

  6. E-prescribing errors identified in a compounding pharmacy: a quality-improvement project.

    PubMed

    Reed-Kane, Dana; Kittell, Katrina; Adkins, Jacquelyn; Flocks, Sarah; Nguyen, Thu

    2014-01-01

    Errors during the prescribing process can cause problems for patients. When the pharmacist intercepts a prescribing error, it can cause a delay, as the patient may not receive the medication until the problem is resolved. Electronic prescriptions are purported to reduce prescribing errors. However, studies have shown that electronic prescriptions can be prone to certain types of errors. Compounding pharmacies may present an additional obstacle for e-prescribing, as the prescribed medications are not commercially available and may not be listed in the e-prescribing software. The objectives of this study were to estimate the electronic prescription error rate in a compounding pharmacy, determine the most common error types, list the most common interventions pharmacists made, and estimate how long it took to resolve these errors. The study design was quality improvement with descriptive data. During the four weeks of data collection, the pharmacists were trained to complete a standardized data collection form when they identified an electronic prescription error. Percentages were calculated for new prescriptions, electronic prescriptions with errors, error types, and error resolution methods. In the four-week period of the study, there were 982 new prescriptions, 111 of which were electronic prescriptions. Of those 111 electronic prescriptions, 70 had errors. The electronic prescriptions error rate was 63%. The most common type of error was wrong entry field (70.3%). For this project, wrong entry field was defined to mean that the drug name was in the wrong field (81%) or that multiple entries were in the wrong field (7%). Pharmacists usually used their own judgment to resolve an error (67%). Many e-prescription errors were identified in this compounding pharmacy. When prescription errors happen, workflow and patient care are disrupted. Our goal is to discuss these findings with Surescripts and e-prescribing software companies to seek systems-based solutions. PMID

  7. The Insufficiency of Error Analysis

    ERIC Educational Resources Information Center

    Hammarberg, B.

    1974-01-01

    The position here is that error analysis is inadequate, particularly from the language-teaching point of view. Non-errors must be considered in specifying the learner's current command of the language, its limits, and his learning tasks. A cyclic procedure of elicitation and analysis, to secure evidence of errors and non-errors, is outlined.…

  8. Imagery of Errors in Typing

    ERIC Educational Resources Information Center

    Rieger, Martina; Martinez, Fanny; Wenke, Dorit

    2011-01-01

    Using a typing task we investigated whether insufficient imagination of errors and error corrections is related to duration differences between execution and imagination. In Experiment 1 spontaneous error imagination was investigated, whereas in Experiment 2 participants were specifically instructed to imagine errors. Further, in Experiment 2 we…

  9. Neural Correlates of Reach Errors

    PubMed Central

    Hashambhoy, Yasmin; Rane, Tushar; Shadmehr, Reza

    2005-01-01

    Reach errors may be broadly classified into errors arising from unpredictable changes in target location, called target errors, and errors arising from miscalibration of internal models, called execution errors. Execution errors may be caused by miscalibration of dynamics (e.g.. when a force field alters limb dynamics) or by miscalibration of kinematics (e.g., when prisms alter visual feedback). While all types of errors lead to similar online corrections, we found that the motor system showed strong trial-by-trial adaptation in response to random execution errors but not in response to random target errors. We used fMRI and a compatible robot to study brain regions involved in processing each kind of error. Both kinematic and dynamic execution errors activated regions along the central and the post-central sulci and in lobules V, VI, and VIII of the cerebellum, making these areas possible sites of plastic changes in internal models for reaching. Only activity related to kinematic errors extended into parietal area 5. These results are inconsistent with the idea that kinematics and dynamics of reaching are computed in separate neural entities. In contrast, only target errors caused increased activity in the striatum and the posterior superior parietal lobule. The cerebellum and motor cortex were as strongly activated as with execution errors. These findings indicate a neural and behavioral dissociation between errors that lead to switching of behavioral goals, and errors that lead to adaptation of internal models of limb dynamics and kinematics. PMID:16251440

  10. [The error, source of learning].

    PubMed

    Joyeux, Stéphanie; Bohic, Valérie

    2016-05-01

    The error itself is not recognised as a fault. It is the intentionality which differentiates between an error and a fault. An error is unintentional while a fault is a failure to respect known rules. The risk of error is omnipresent in health institutions. Public authorities have therefore set out a series of measures to reduce this risk. PMID:27155272