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Comparison of national strategies to reduce methicillin-resistant Staphylococcus aureus (MRSA) infections in Japan and England
Background
National responses to healthcare-associated infections vary between high-income countries but when analysed for contextual comparability, interventions can be assessed for transferability.
Aim
To identify learning from country-level approaches to addressing meticillin-resistant Staphylococcus aureus (MRSA) in Japan and England.
Methods
A longitudinal analysis (2000-17), comparing epidemiological trends and policy interventions. Data from 441 textual sources concerning infection prevention and control (IPC), surveillance, and antimicrobial stewardship interventions were systematically coded for: type - mandatory requirements, recommendations, or national campaigns; method - restrictive, persuasive, structural in nature; level of implementation - macro (national), meso (organisational), micro (individual) levels. Healthcare organisational structures and role of media were also assessed.
Findings
In England significant reduction has been achieved in number of reported MRSA bloodstream infections. In Japan, in spite of reductions, MRSA remains a predominant infection. Both countries face new threats in the emergence of drug-resistant Escherichia coli. England has focused on national mandatory and structural interventions, supported by a combination of outcomes-based incentives and punitive mechanisms, and multidisciplinary IPC hospital teams. Japan has focused on (non-mandatory) recommendations and primarily persuasive interventions, supported by process-based incentives, with voluntary surveillance. Areas for development in Japan include resourcing of dedicated data management support and implementation of national campaigns for healthcare professionals and the public.
Conclusion
Policy interventions need to be relevant to local epidemiological trends, while acceptable within health system cultures and public expectations. Cross-national learning can help inform the right mix of interventions to create sustainable and resilient systems for future infection and economic challenges
Unstable decay and state selection II
The decay of unstable states when several metastable states are available for
occupation is investigated using path-integral techniques. Specifically, a
method is described which allows the probabilities with which the metastable
states are occupied to be calculated by finding optimal paths, and fluctuations
about them, in the weak noise limit. The method is illustrated on a system
described by two coupled Langevin equations, which are found in the study of
instabilities in fluid dynamics and superconductivity. The problem involves a
subtle interplay between non-linearities and noise, and a naive approximation
scheme which does not take this into account is shown to be unsatisfactory. The
use of optimal paths is briefly reviewed and then applied to finding the
conditional probability of ending up in one of the metastable states, having
begun in the unstable state. There are several aspects of the calculation which
distinguish it from most others involving optimal paths: (i) the paths do not
begin and end on an attractor, and moreover, the final point is to a large
extent arbitrary, (ii) the interplay between the fluctuations and the leading
order contribution are at the heart of the method, and (iii) the final result
involves quantities which are not exponentially small in the noise strength.
This final result, which gives the probability of a particular state being
selected in terms of the parameters of the dynamics, is remarkably simple and
agrees well with the results of numerical simulations. The method should be
applicable to similar problems in a number of other areas such as state
selection in lasers, activationless chemical reactions and population dynamics
in fluctuating environments.Comment: 28 pages, 6 figures. Accepted for publication in Phys. Rev.
Genome landscapes and bacteriophage codon usage
Across all kingdoms of biological life, protein-coding genes exhibit unequal
usage of synonmous codons. Although alternative theories abound, translational
selection has been accepted as an important mechanism that shapes the patterns
of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns
of codon usage across 74 diverse bacteriophages that infect E. coli, P.
aeruginosa and L. lactis as their primary host. We introduce the concept of a
`genome landscape,' which helps reveal non-trivial, long-range patterns in
codon usage across a genome. We develop a series of randomization tests that
allow us to interrogate the significance of one aspect of codon usage, such a
GC content, while controlling for another aspect, such as adaptation to
host-preferred codons. We find that 33 phage genomes exhibit highly non-random
patterns in their GC3-content, use of host-preferred codons, or both. We show
that the head and tail proteins of these phages exhibit significant bias
towards host-preferred codons, relative to the non-structural phage proteins.
Our results support the hypothesis of translational selection on viral genes
for host-preferred codons, over a broad range of bacteriophages.Comment: 9 Color Figures, 5 Tables, 53 Reference
A Pivotal Role of Vitamin B9 in the Maintenance of Regulatory T Cells In Vitro and In Vivo
Dietary factors regulate immunological function, but the underlying mechanisms remain elusive. Here we show that vitamin B9 is a survival factor for regulatory T (Treg) cells expressing high levels of vitamin B9 receptor (folate receptor 4). In vitamin B9-reduced condition in vitro, Treg cells could be differentiated from naïve T cells but failed to survive. The impaired survival of Treg cells was associated with decreased expression of anti-apoptotic Bcl2 and independent of IL-2. In vivo depletion of dietary vitamin B9 resulted in the reduction of Treg cells in the small intestine, a site for the absorption of dietary vitamin B9. These findings provide a new link between diet and the immune system, which could maintain the immunological homeostasis in the intestine
CANGAROO-III Observation of TeV Gamma Rays from the vicinity of PSR B1 706-44
Observation by the CANGAROO-III stereoscopic system of the Imaging Cherenkov
Telescope has detected extended emission of TeV gamma rays in the vicinity of
the pulsar PSR B170644. The strength of the signal observed as
gamma-ray-like events varies when we apply different ways of emulating
background events. The reason for such uncertainties is argued in relevance to
gamma-rays embedded in the "off-source data", that is, unknown sources and
diffuse emission in the Galactic plane, namely, the existence of a complex
structure of TeV gamma-ray emission around PSR B170644.Comment: 10 pages, 13 figures, to be published in Ap
A cAMP-binding ectoprotein in the yeast Saccharomyces cerevisiae
tides 10, 593-595
Lipopolysaccharide from Gut-Associated Lymphoid-Tissue-Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A
Alcaligenes faecalis is the predominant Gram-negative bacterium inhabiting gut-associated lymphoid tissues, Peyer's patches. We previously reported that an A. faecalis lipopolysaccharide (LPS) acted as a weak agonist for Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2) receptor as well as a potent inducer of IgA without excessive inflammation, thus suggesting that A. faecalis LPS might be used as a safe adjuvant. In this study, we characterized the structure of both the lipooligosaccharide (LOS) and LPS from A. faecalis. We synthesized three lipid A molecules with different degrees of acylation by an efficient route involving the simultaneous introduction of 1- and 4′-phosphates. Hexaacylated A. faecalis lipid A showed moderate agonistic activity towards TLR4-mediated signaling and the ability to elicit a discrete interleukin-6 release in human cell lines and mice. It was thus found to be the active principle of the LOS/LPS and a promising vaccine adjuvant candidate
CANGAROO-III observation of TeV gamma rays from the unidentified gamma-ray source HESS J1614-518
We report the detection, with the CANGAROO-III imaging atmospheric Cherenkov
telescope array, of a very high energy gamma-ray signal from the unidentified
gamma-ray source HESS J1614-518, which was discovered in the H.E.S.S. Galactic
plane survey. Diffuse gamma-ray emission was detected above 760 GeV at the 8.9
sigma level during an effective exposure of 54 hr from 2008 May to August. The
spectrum can be represented by a power-law:
8.2+-2.2_{stat}+-2.5_{sys}x10^{-12}x (E/1TeV)^{-Gamma} cm^{-2} s^{-1} TeV^{-1}
with a photon index Gamma of 2.4+-0.3_{stat}+-0.2_{sys}, which is compatible
with that of the H.E.S.S. observations. By combining our result with
multi-wavelength data, we discuss the possible counterparts for HESS J1614-518
and consider radiation mechanisms based on hadronic and leptonic processes for
a supernova remnant, stellar winds from massive stars, and a pulsar wind
nebula. Although a leptonic origin from a pulsar wind nebula driven by an
unknown pulsar remains possible, hadronic-origin emission from an unknown
supernova remnant is preferred.Comment: 9 pages, 7 figures, accepted for publication in Ap
The hERG channel is dependent upon the Hsp90α isoform for maturation and trafficking
Heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of cancer. Several Hsp90 inhibitors have entered clinical trials. However, some toxicological detriments have arisen, such as cardiotoxicity resulting from hERG inhibition following the administration of Hsp90 inhibitors. We sought to investigate this toxicity as hERG has been previously reported as a client protein that depends upon Hsp90 for its maturation and functional trafficking. In this study we show that hERG depends upon a single Hsp90 isoform. hERG preferentially co-immunoprecipitated with Hsp90α and genetic knockdown of Hsp90α, but not Hsp90β, resulted in a trafficking-defective hERG channel. This study demonstrates the importance of delineating the isoform dependence of Hsp90 client proteins and provides rationale for the design of isoform-selective Hsp90 inhibitors that avoid detrimental effect
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