Factors associated with appropriate inhaler use in patients with COPD - lessons from the REAL survey

The authors thank Clarice Field (PhD) and Paul McKiernan (PhD) of Novartis for providing medical writing support, which was funded by Novartis AG, Basel, Switzerland, in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). Pankaj Goyal and Joao Mendes, Novartis Pharma AG, Basel, contributed to the design and conceptualization of study. The survey was designed by PDD, London, United Kingdom, and GfK Switzerland AG, Basel, Switzerland. The survey was conducted by GfK Switzerland AG, Basel, Switzerland, and sponsored by Novartis Pharma AG, Basel, Switzerland.Peer reviewedPublisher PD

Power counting in baryon chiral perturbation theory including vector mesons

It is demonstrated that using a suitable renormalization condition one obtains a consistent power counting in manifestly Lorentz-invariant baryon chiral perturbation theory including vector mesons as explicit degrees of freedom.Comment: 8 pages, REVTeX 4, 3 figure

Prospective and Retrospective Memory Complaints in Mild Cognitive Impairment and Mild Alzheimer's Disease

Current management attempts for Alzheimer's disease (AD) focus on the identification of individuals in the preclinical stage. This has led to the development of the diagnostic concept of Mild Cognitive Impairment (MCI), which applies to individuals with declining cognitive abilities but largely preserved everyday functioning. Previous findings indicate that prospective memory deficits are a sensitive marker of preclinical AD and that awareness of prospective memory failures is particularly high, based on its dependence on executive functions. Thus, the goal of this study was to evaluate the usefulness of subjective prospective versus retrospective memory complaints for an initial screening for MCI and their respective associations with executive functions. 71 healthy older adults, 27 MCI patients, and 9 patients with mild AD completed the Prospective and Retrospective Memory Questionnaire (PRMQ) and three executive functions tests. The healthy and the MCI group could not be distinguished by their level of subjective prospective or retrospective memory complaints, but the mild AD patients differed from the other groups by complaining more about retrospective than prospective memory failures. For the healthy older adults, the prospective memory complaints were correlated to an inhibition test, whereas they did not correlate with any of the executive function tests in the MCI patients. In contrast, in both groups the retrospective memory complaints were related to a task switching test. The findings are discussed with respect to differences between the three groups in cognitive abilities, attention to failures of, use of mnemonic aids for, and everyday demands of prospective and retrospective memor

Comparison of extraction sites versus artificial defects with xenogenic bone substitute in minipigs

Objectives The preclinical evaluation of bone substitutes is frequently performed in artificially created defects. However, such defects do not reflect the predominant clinical application of bone substitutes for socket preservation. Hence, the goal of this animal study was to compare the performance of a xenogenic bone substitute in extraction sites versus artificial defects. Material and Methods Four study sites each were created in the mandibles of four minipigs in the region of the third premolars and first molars, respectively. On one side, fresh extraction sockets were established while contralaterally trephine defects were created in healed alveolar bone. All sites were augmented using a particulate xenogenic bone substitute, covered by resorbable membranes and allowed to heal for 12 weeks. The amounts of new bone, non-bone tissue and remaining bone substitute granules were quantified through histological and micro-CT analysis. Comparative statistics were based on t-tests for two samples and ANOVA with the level of significance set at α = 0.05. Results Histomorphometric data from only two animals could be quantitatively analyzed due to difficulty with identifying the surgical sites. The percentage of newly formed bone ranged between 53.2% ± 5.6% for artificial defects and 54.9% ± 12.4% for extraction sites. With the exception of ANOVA indicating a greater amount of non-bone tissue in extraction sites as compared to artificial sites (p = 0.047), no statistically significant differences were observed. Micro-CT scans showed patterns similar to the ones observed in histomorphometry. As extraction sites could be identified only in two micro-CT reconstructions, quantitative assessment was not undertaken. Conclusions Despite the comparable performance of bone substitute material in artificial defects and extraction sites found here, the data gathered with this experiment was insufficient for showing equivalence of both approaches

The Rise of Certificate Transparency and Its Implications on the Internet Ecosystem

In this paper, we analyze the evolution of Certificate Transparency (CT) over time and explore the implications of exposing certificate DNS names from the perspective of security and privacy. We find that certificates in CT logs have seen exponential growth. Website support for CT has also constantly increased, with now 33% of established connections supporting CT. With the increasing deployment of CT, there are also concerns of information leakage due to all certificates being visible in CT logs. To understand this threat, we introduce a CT honeypot and show that data from CT logs is being used to identify targets for scanning campaigns only minutes after certificate issuance. We present and evaluate a methodology to learn and validate new subdomains from the vast number of domains extracted from CT logged certificates.Comment: To be published at ACM IMC 201

Constraining the Kpi vector form factor by tau---> K pi nu_tau and K_l3 decay data

A subtracted dispersive representation of the $K\pi$ vector form factor, $F_+^{K\pi}$, is used to fit the Belle spectrum of \tauKpi decays incorporating constraints from results on $K_{l3}$ decays. Through the use of three subtractions, the slope and curvature of $F_+^{K\pi}$ are obtained directly from the data yielding $\lambda_+'=(25.49 \pm 0.31) \times 10^{-3}$ and $\lambda_+"= (12.22 \pm 0.14) \times 10^{-4}$. The phase-space integrals relevant for $K_{l3}$ analyses are calculated. Additionally, from the pole position on the second Riemann sheet the mass and width of the $K^*(892)^\pm$ are found to be $m_{K^*(892)^\pm}= 892.0\pm 0.5$ MeV and $\Gamma_{K^*(892)^\pm}= 46.5 \pm 1.1$ MeV. Finally, we study the $P$-wave isospin-1/2 $K\pi$ phase-shift and its threshold parameters.Comment: Talk presented at 15th International QCD Conference, Montpellier, France. Submitted to Nuc. Phys. (Proc. Suppl.), 4 pages, 1 figur

Atomic mutagenesis of stop codon nucleotides reveals the chemical prerequisites for release factor-mediated peptide release.

Termination of protein synthesis is triggered by the recognition of a stop codon at the ribosomal A site and is mediated by class I release factors (RFs). Whereas in bacteria, RF1 and RF2 promote termination at UAA/UAG and UAA/UGA stop codons, respectively, eukaryotes only depend on one RF (eRF1) to initiate peptide release at all three stop codons. Based on several structural as well as biochemical studies, interactions between mRNA, tRNA, and rRNA have been proposed to be required for stop codon recognition. In this study, the influence of these interactions was investigated by using chemically modified stop codons. Single functional groups within stop codon nucleotides were substituted to weaken or completely eliminate specific interactions between the respective mRNA and RFs. Our findings provide detailed insight into the recognition mode of bacterial and eukaryotic RFs, thereby revealing the chemical groups of nucleotides that define the identity of stop codons and provide the means to discriminate against noncognate stop codons or UGG sense codons

Infrared renormalization of two-loop integrals and the chiral expansion of the nucleon mass

We describe details of the renormalization of two-loop integrals relevant to the calculation of the nucleon mass in the framework of manifestly Lorentz-invariant chiral perturbation theory using infrared renormalization. It is shown that the renormalization can be performed while preserving all relevant symmetries, in particular chiral symmetry, and that renormalized diagrams respect the standard power counting rules. As an application we calculate the chiral expansion of the nucleon mass to order O(q^6).Comment: Version accepted for publication in Nucl. Phys. A, missing one-loop diagram added, minor changes in notation, discussion of results improve

Enlarging the synthetic biology toolbox for Pichia pastoris: Golden Gate cloning and CRISPR/Cas9

State-of-the-art strain engineering techniques for the protein producing yeast host Pichia pastoris include overexpression of homologous and heterologous genes, and deletion of host genes. For this purpose overexpression vectors and gene deletion methods such as the split marker technique have been established. For metabolic and cell engineering purposes, the simultaneous overexpression of more than one gene is often needed. Previous approaches employing subsequent steps of overexpression and marker recycling were time- and labor-consuming. Therefore, efficient systems allowing multiple gene overexpression are required, that can be stably integrated into the P. pastoris genome. To this end, we developed a synthetic biology toolbox based on Golden Gate cloning to enable efficient construction of complex and versatile over-expression vectors. Up to five different expression cassettes, employing a library of promoters and terminators can be combined into one vector, and successfully integrated into the genomic DNA of P. pastoris at targeted loci in one step. Recent trends in synthetic biology, however, go into the direction of building up large and complex reaction networks. To allow for clean and unscarred genetic engineering, a CRISPR/Cas9 based method for gene insertions, deletions and replacements was developed, which paves the way for precise genomic rearrangements in P. pastoris. By using this technique precise genomic integrations were performed efficiently without integrative selection markers. The repertoire of genetic techniques developed so far, will provide a wide variety of possibilities to engineer P. pastoris. Applications for these synthetic biology tools in cell engineering of recombinant P. pastoris will be presented