955 research outputs found
Trends in Occurrence and Phenotypic Resistance of Coagulase-Negative Staphylococci (CoNS) Found in Human Blood in the Northern Netherlands between 2013 and 2019
Background: For years, coagulase-negative staphylococci (CoNS) were not considered a cause of bloodstream infections (BSIs) and were often regarded as contamination. However, the association of CoNS with nosocomial infections is increasingly recognized. The identification of more than 40 different CoNS species has been driven by the introduction of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Yet, treatment guidelines consider CoNS as a whole group, despite increasing antibiotic resistance (ABR) in CoNS. This retrospective study provides an in-depth data analysis of CoNS isolates found in human blood culture isolates between 2013 and 2019 in the entire region of the Northern Netherlands. Methods: In total, 10,796 patients were included that were hospitalized in one of the 15 hospitals in the region, leading to 14,992 CoNS isolates for (ABR) data analysis. CoNS accounted for 27.6% of all available 71,632 blood culture isolates. EUCAST Expert rules were applied to correct for errors in antibiotic test results. Results: A total of 27 different CoNS species were found. Major differences were observed in occurrence and ABR profiles. The top five species covered 97.1% of all included isolates: S. epidermidis, S. hominis, S. capitis, S. haemolyticus, and S. warneri. Regarding ABR, methicillin resistance was most frequently detected in S. haemolyticus (72%), S. cohnii (65%), and S. epidermidis (62%). S. epidermidis and S. haemolyticus showed 50–80% resistance to teicoplanin and macrolides while resistance to these agents remained lower than 10% in most other CoNS species. Conclusion: These differences are often neglected in national guideline development, prompting a focus on ‘ABR-safe’ agents such as glycopeptides. In conclusion, this multi-year, full-region approach to extensively assess the trends in both the occurrence and phenotypic resistance of CoNS species could be used for evaluating treatment policies and understanding more about these important but still too often neglected pathogens
Efficiency improvements for the numerical computation of NLO corrections
In this paper we discuss techniques, which lead to a significant improvement
of the efficiency of the Monte Carlo integration, when one-loop QCD amplitudes
are calculated numerically with the help of the subtraction method and contour
deformation. The techniques discussed are: holomorphic and non-holomorphic
division into sub-channels, optimisation of the integration contour,
improvement of the ultraviolet subtraction terms, importance sampling and
antithetic variates in loop momentum space, recurrence relations.Comment: 34 pages, version to be publishe
Concurrent substitutional and displacive phase transformations in Al-Mg-Si nanoclusters
Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs
The reference annotations made for a genome sequence provide the framework
for all subsequent analyses of the genome. Correct annotation is particularly
important when interpreting the results of RNA-seq experiments where short
sequence reads are mapped against the genome and assigned to genes according to
the annotation. Inconsistencies in annotations between the reference and the
experimental system can lead to incorrect interpretation of the effect on RNA
expression of an experimental treatment or mutation in the system under study.
Until recently, the genome-wide annotation of 3-prime untranslated regions
received less attention than coding regions and the delineation of intron/exon
boundaries. In this paper, data produced for samples in Human, Chicken and A.
thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing
technology from Helicos Biosciences which locates 3-prime polyadenylation sites
to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine
examples are illustrated where this combination of data allowed: (1) gene and
3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb);
(2) disentangling of gene expression in complex regions; (3) clearer
interpretation of small RNA expression and (4) identification of novel genes.
While the specific examples displayed here may become obsolete as genome
sequences and their annotations are refined, the principles laid out in this
paper will be of general use both to those annotating genomes and those seeking
to interpret existing publically available annotations in the context of their
own experimental dataComment: 44 pages, 9 figure
Silica particles with a quercetin–R5 peptide conjugate are taken up into HT-29 cells and translocate into the nucleus
Identification and Functional Validation of the Novel Antimalarial Resistance Locus PF10_0355 in Plasmodium falciparum
The Plasmodium falciparum parasite's ability to adapt to environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden to public health. Understanding the genetic basis of these adaptations is critical to intervening successfully against malaria. To that end, we created a high-density genotyping array that assays over 17,000 single nucleotide polymorphisms (~1 SNP/kb), and applied it to 57 culture-adapted parasites from three continents. We characterized genome-wide genetic diversity within and between populations and identified numerous loci with signals of natural selection, suggesting their role in recent adaptation. In addition, we performed a genome-wide association study (GWAS), searching for loci correlated with resistance to thirteen antimalarials; we detected both known and novel resistance loci, including a new halofantrine resistance locus, PF10_0355. Through functional testing we demonstrated that PF10_0355 overexpression decreases sensitivity to halofantrine, mefloquine, and lumefantrine, but not to structurally unrelated antimalarials, and that increased gene copy number mediates resistance. Our GWAS and follow-on functional validation demonstrate the potential of genome-wide studies to elucidate functionally important loci in the malaria parasite genome.Bill & Melinda Gates FoundationEllison Medical FoundationExxon Mobil FoundationFogarty International CenterNational Institute of Allergy and Infectious Diseases (U.S.)Burroughs Wellcome FundDavid & Lucile Packard FoundationNational Science Foundation (U.S.). Graduate Research Fellowship Progra
Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
We report a quasi-differential upper limit on the extremely-high-energy (EHE)
neutrino flux above GeV based on an analysis of nine years of
IceCube data. The astrophysical neutrino flux measured by IceCube extends to
PeV energies, and it is a background flux when searching for an independent
signal flux at higher energies, such as the cosmogenic neutrino signal. We have
developed a new method to place robust limits on the EHE neutrino flux in the
presence of an astrophysical background, whose spectrum has yet to be
understood with high precision at PeV energies. A distinct event with a
deposited energy above GeV was found in the new two-year sample, in
addition to the one event previously found in the seven-year EHE neutrino
search. These two events represent a neutrino flux that is incompatible with
predictions for a cosmogenic neutrino flux and are considered to be an
astrophysical background in the current study. The obtained limit is the most
stringent to date in the energy range between and GeV. This result constrains neutrino models predicting a three-flavor
neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\
{\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}10^9\ {\rm GeV}$. A significant part
of the parameter-space for EHE neutrino production scenarios assuming a
proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review
Radio Astronomy
Contains table of contents for Section 4 and reports on ten research projects.National Science Foundation Grant AST 90-22501Alfred P. Sloan FellowshipDavid and Lucile Packard Fellowship Award for Science and EngineeringNational Aeronautics and Space AdministrationNational Science Foundation Presidential Young Investigator AwardNational Aeronautics and Space Administration Grant NAGW-2310MIT Lincoln Laboratory Agreement BX-4975National Aeronautics and Space Administration/Goddard Space Flight Center Contract NAS 5-31276MIT Leaders for Manufacturing Progra
Radio Astronomy
Contains table of contents for Section 4 and reports on ten research projects.National Science Foundation Grant AST 90-22501National Aeronautics and Space Administration Grant NAGW 1386National Science Foundation Presidential Young Investigator AwardDavid and Lucile Packard Fellowship for Science and EngineeringNational Aeronautics and Space Administration Grant NAGW-2310MIT Lincoln LaboratorySM Systems and Research CorporationNational Aeronautics and Space Administration/Goddard Space Flight Center Contract NAS 5-30791National Aeronautics and Space Administration/Goddard Space Flight Center Grant NAG 5-10MIT Leaders for Manufacturing Progra
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