Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

Acknowledgements The iHARP database was funded by unrestricted grants from Mundipharma International Ltd and Research in Real-Life Ltd; these analyses were funded by an unrestricted grant from Teva Pharmaceuticals. Mundipharma and Teva played no role in study conduct or analysis and did not modify or approve the manuscript. The authors wish to direct a special appreciation to all the participants of the iHARP group who contributed data to this study and to Mundipharma, sponsors of the iHARP group. In addition, we thank Julie von Ziegenweidt for assistance with data extraction and Anna Gilchrist and Valerie L. Ashton, PhD, for editorial assistance. Elizabeth V. Hillyer, DVM, provided editorial and writing support, funded by Research in Real-Life, Ltd.

Ancient mtDNA sequences in the human nuclear genome: A potential source of errors in identifying pathogenic mutations

Nuclear-localized mtDNA pseudogenes might explain a recent report describing a heteroplasmic mtDNA molecule containing five linked missense mutations dispersed over the contiguous mtDNA CO1 and CO2 genes in Alzheimer’s disease (AD) patients. To test this hypothesis, we have used the PCR primers utilized in the original report to amplify CO1 and CO2 sequences from two independent ρ° (mtDNA-less) cell lines. CO1 and CO2 sequences amplified from both of the ρ° cells, demonstrating that these sequences are also present in the human nuclear DNA. The nuclear pseudogene CO1 and CO2 sequences were then tested for each of the five “AD” missense mutations by restriction endonuclease site variant assays. All five mutations were found in the nuclear CO1 and CO2 PCR products from ρ° cells, but none were found in the PCR products obtained from cells with normal mtDNA. Moreover, when the overlapping nuclear CO1 and CO2 PCR products were cloned and sequenced, all five missense mutations were found, as well as a linked synonymous mutation. Unlike the findings in the original report, an additional 32 base substitutions were found, including two in adjacent tRNAs and a two base pair deletion in the CO2 gene. Phylogenetic analysis of the nuclear CO1 and CO2 sequences revealed that they diverged from modern human mtDNAs early in hominid evolution about 770,000 years before present. These data would be consistent with the interpretation that the missense mutations proposed to cause AD may be the product of ancient mtDNA variants preserved as nuclear pseudogenes.

Complex mtDNA constitutes an approximate 620-kb insertion on Arabidopsis thaliana chromosome 2: Implication of potential sequencing errors caused by large-unit repeats

Previously conducted sequence analysis of Arabidopsis thaliana (ecotype Columbia-0) reported an insertion of 270-kb mtDNA into the pericentric region on the short arm of chromosome 2. DNA fiber-based fluorescence in situ hybridization analyses reveal that the mtDNA insert is 618 ± 42 kb, ≈2.3 times greater than that determined by contig assembly and sequencing analysis. Portions of the mitochondrial genome previously believed to be absent were identified within the insert. Sections of the mtDNA are repeated throughout the insert. The cytological data illustrate that DNA contig assembly by using bacterial artificial chromosomes tends to produce a minimal clone path by skipping over duplicated regions, thereby resulting in sequencing errors. We demonstrate that fiber-fluorescence in situ hybridization is a powerful technique to analyze large repetitive regions in the higher eukaryotic genomes and is a valuable complement to ongoing large genome sequencing projects.

On the forecast accuracy and consistency of exchange rate expectations: The Spanish PwC Survey.

We examine the predictive ability and consistency properties of exchange rate expectations for the dollar/euro using a survey conducted in Spain by PwC among a panel of experts and entrepreneurs. Our results suggest that the PwC panel have some forecasting ability for time horizons from 3 to 9 months, although only for the 3-month ahead expectations we obtain marginal evidence of unbiasedness and efficiency in the forecasts. As for the consistency properties of the exchange rate expectations formation process, we find that survey participants form stabilising expectations in the short-run and destabilising expectations in the long- run and that the expectation formation process is closer to fundamentalists than chartists.

The Climate-system Historical Forecast Project: do stratosphere-resolving models make better seasonal climate predictions in boreal winter?

Using an international, multi-model suite of historical forecasts from the World Climate Research Programme (WCRP) Climate-system Historical Forecast Project (CHFP), we compare the seasonal prediction skill in boreal wintertime between models that resolve the stratosphere and its dynamics (high-top') and models that do not (low-top'). We evaluate hindcasts that are initialized in November, and examine the model biases in the stratosphere and how they relate to boreal wintertime (December-March) seasonal forecast skill. We are unable to detect more skill in the high-top ensemble-mean than the low-top ensemble-mean in forecasting the wintertime North Atlantic Oscillation, but model performance varies widely. Increasing the ensemble size clearly increases the skill for a given model. We then examine two major processes involving stratosphere-troposphere interactions (the El Niño/Southern Oscillation (ENSO) and the Quasi-Biennial Oscillation (QBO)) and how they relate to predictive skill on intraseasonal to seasonal time-scales, particularly over the North Atlantic and Eurasia regions. High-top models tend to have a more realistic stratospheric response to El Niño and the QBO compared to low-top models. Enhanced conditional wintertime skill over high latitudes and the North Atlantic region during winters with El Niño conditions suggests a possible role for a stratospheric pathway.

Reducing visual deficits caused by refractive errors in school and preschool children: results of a pilot school program in the Andean region of Apurimac, Peru

Background: Refractive error is defined as the inability of the eye to bring parallel rays of light into focus on the retina, resulting in nearsightedness (myopia), farsightedness (Hyperopia) or astigmatism. Uncorrected refractive error in children is associated with increased morbidity and reduced educational opportunities. Vision screening (VS) is a method for identifying children with visual impairment or eye conditions likely to lead to visual impairment. Objective: To analyze the utility of vision screening conducted by teachers and to contribute to a better estimation of the prevalence of childhood refractive errors in Apurimac, Peru. Design: A pilot vision screening program in preschool (Group I) and elementary school children (Group II) was conducted with the participation of 26 trained teachers. Children whose visual acuity was<6/9 [20/30] (Group I) and≤6/9 (Group II) in one or both eyes, measured with the Snellen Tumbling E chart at 6 m, were referred for a comprehensive eye exam. Specificity and positive predictive value to detect refractive error were calculated against clinical examination. Program assessment with participants was conducted to evaluate outcomes and procedures. Results: A total sample of 364 children aged 3–11 were screened; 45 children were examined at Centro Oftalmológico Monseñor Enrique Pelach (COMEP) Eye Hospital. Prevalence of refractive error was 6.2% (Group I) and 6.9% (Group II); specificity of teacher vision screening was 95.8% and 93.0%, while positive predictive value was 59.1% and 47.8% for each group, respectively. Aspects highlighted to improve the program included extending training, increasing parental involvement, and helping referred children to attend the hospital. Conclusion: Prevalence of refractive error in children is significant in the region. Vision screening performed by trained teachers is a valid intervention for early detection of refractive error, including screening of preschool children. Program sustainability and improvements in education and quality of life resulting from childhood vision screening require further research.

Efficient Mitigation of Data and Control Flow Errors in Microprocessors

The use of microprocessor-based systems is gaining importance in application domains where safety is a must. For this reason, there is a growing concern about the mitigation of SEU and SET effects. This paper presents a new hybrid technique aimed to protect both the data and the control-flow of embedded applications running on microprocessors. On one hand, the approach is based on software redundancy techniques for correcting errors produced in the data. On the other hand, control-flow errors can be detected by reusing the on-chip debug interface, existing in most modern microprocessors. Experimental results show an important increase in the system reliability even superior to two orders of magnitude, in terms of mitigation of both SEUs and SETs. Furthermore, the overheads incurred by our technique can be perfectly assumable in low-cost systems.

Errors Associated to Keratoconus Grading using Systems based on Corneal Power

Purpose: To analyze and define the possible errors that may be introduced in keratoconus classification when the keratometric corneal power is used in such classification. Materials and methods: Retrospective study including a total of 44 keratoconus eyes. A comprehensive ophthalmologic examination was performed in all cases, which included a corneal analysis with the Pentacam system (Oculus). Classical keratometric corneal power (Pk), Gaussian corneal power (Pc Gauss), True Net Power (TNP) (Gaussian power neglecting the corneal thickness effect), and an adjusted keratometric corneal power (Pkadj) (keratometric power considering a variable keratometric index) were calculated. All cases included in the study were classified according to five different classification systems: Alió-Shabayek, Amsler-Krumeich, Rabinowitz-McDonnell, collaborative longitudinal evaluation of keratoconus (CLEK), and McMahon. Results: When Pk and Pkadj were compared, differences in the type of grading of keratoconus cases was found in 13.6% of eyes when the Alió-Shabayek or the Amsler-Krumeich systems were used. Likewise, grading differences were observed in 22.7% of eyes with the Rabinowitz-McDonnell and McMahon classification systems and in 31.8% of eyes with the CLEK classification system. All reclassified cases using Pkadj were done in a less severe stage, indicating that the use of Pk may lead to the classification of a cornea as keratoconus, being normal. In general, the results obtained using Pkadj, Pc Gauss or the TNP were equivalent. Differences between Pkadj and Pc Gauss were within ± 0.7D. Conclusion: The use of classical keratometric corneal power may lead to incorrect grading of the severity of keratoconus, with a trend to a more severe grading.

Notes of proceedings and cases determined in the high court of errors and appeals, the court of chancery, and the orphans court of the state of Delaware, 1792-1832

Contains summaries of cases heard by the Delaware Supreme Court and the Delaware Appeals Court in the counties of Sussex, Kent, and Newcastle covering a variety of legal topics. Supposedly based on Wilson's Red Book.