Fusidic acid binds to elongation factor G (EF-G), preventing its release from the ribosome, thus stalling bacterial protein synthesis. In staphylococci, high-level fusidic acid resistance is usually ...caused by mutations in the gene encoding EF-G, fusA, and low-level resistance is generally caused by the horizontally transferable mechanisms fusB and fusC that have a putative protective role on EF-G. In addition, fusD is responsible for intrinsic resistance in Staphylococcus saprophyticus, and alterations in the L6 portion of rplF (fusE) have a role in fusidic acid resistance. Fusidic acid has been used in Europe and Australia for decades. More recently, it has also been used in other countries and regions, but not in the United States. Worldwide fusidic acid resistance has been slow to develop, and the level of resistance and genetic mechanisms responsible generally reflect the time since introduction, indications for treatment, route of administration, and prescribing practices.
In the opening lines of Ruling the Void Peter Mair states that 'the age of party democracy has passed'. In his eyes political parties are failing and with them democracy itself. This paper addresses ...Mair's concerns about the state of democracy. We review the latest evidence on how democracies have been innovating over the past twenty years or more, with particular attention to reforms that seek to bring citizens into the heart of discussions about constitutional and institutional reforms and significant policy issues. We show how deliberative mini-publics are becoming a more common feature of democratic government today, and, in some instances, how they are being embedded into the democratic system. We assess the implications for the state of state of democratic government today.
BACKGROUND:The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in the United States in February 2000. The PROTEKT US study evaluated serotype distribution, PCV7 coverage and ...antimicrobial susceptibility among Streptococcus pneumoniae isolates collected from children aged 0 to 14 years in 2000 through 2001 (year 1; n = 2033), 2002 through 2003 (year 3; n = 1740) and 2003 through 2004 (year 4; n = 1591).
METHODS:Serotyping was performed by Neufeld Quellung reaction. Antimicrobial susceptibilities were determined centrally according to Clinical Laboratory Standards Institute methodology and interpretive breakpoints.
RESULTS:The proportion of isolates covered by PCV7 (vaccine serotypes) decreased from 65.5% (year 1) to 34.7% (year 3) and to 27.0% (year 4) (P < 0.0001) with similar changes seen at regional and state levels. The most common serotypes in year 4 were nonvaccine serotypes (NVS) 19A (19.0% of all isolates), 6A (7.8%), 3 (7.6%), 15 (6.3%) and 35B (5.8%) and vaccine serotype 19F (12.7%). NVS 19A increased relative to vaccine serotype 19F among isolates expressing the erm(B) + mef(A) macrolide-resistant genotype (P < 0.0001) between year 1 (7.8% 19A versus 86.7% 19F) and year 4 (45.5% 19A versus 51.7% 19F). Antimicrobial resistance rates (year 1 versus year 4) among NVS from nonblood (respiratory tract) sources increased for penicillin (resistant12.7–16.1% P = 0.0857; intermediate susceptibility20.1–31.5% P < 0.0001), erythromycin (21.2–31.6% P < 0.0001), amoxicillin–clavulanate (1.4–5.8% P < 0.0001) and multidrug resistance (resistance to ≥2 antimicrobial classes) (24.6–31.6% P = 0.0034).
CONCLUSIONS:The proportion of S. pneumoniae isolates from U.S. pediatric patients covered by PCV7 decreased substantially in the 4 years after vaccine introduction. However, resistance to commonly used antimicrobials, including β-lactams and macrolides, as well as multidrug-resistant strains increased significantly among respiratory tract isolates of NVS.
Advancement in next generation sequencing offers the possibility of routine use of whole genome sequencing (WGS) for
(
) genomes in clinical reference laboratories. To date, the
genome could only be ...sequenced if the mycobacteria were cultured from tissue. This requirement for culture has been due to the overwhelmingly large amount of host DNA present when DNA is prepared directly from a granuloma. To overcome this formidable hurdle, we evaluated the usefulness of an RNA-based targeted enrichment method to sequence
DNA directly from tissue samples without culture. Initial spiking experiments for method development were established by spiking DNA extracted from tissue samples with serially diluted
BCG DNA at the following concentration range: 0.1 ng/μl to 0.1 pg/μl (10
to 10
). Library preparation, hybridization and enrichment was performed using SureSelect custom capture library RNA baits and the SureSelect XT HS2 target enrichment system for Illumina paired-end sequencing. The method validation was then assessed using direct WGS of
DNA extracted from tissue samples from naturally (
= 6) and experimentally (
= 6) infected animals with variable Ct values. Direct WGS of spiked DNA samples achieved 99.1% mean genome coverage (mean depth of coverage: 108×) and 98.8% mean genome coverage (mean depth of coverage: 26.4×) for tissue samples spiked with BCG DNA at 10
(mean Ct value: 20.3) and 10
(mean Ct value: 23.4), respectively. The
genome from the experimentally and naturally infected tissue samples was successfully sequenced with a mean genome coverage of 99.56% and depth of genome coverage ranging from 9.2× to 72.1×. The spoligoyping and
group assignment derived from sequencing DNA directly from the infected tissue samples matched that of the cultured isolates from the same sample. Our results show that direct sequencing of
DNA from tissue samples has the potential to provide accurate sequencing of
genomes significantly faster than WGS from cultures in research and diagnostic settings.
Many claims have been made for the impact of deliberative democracy in generating change in people's opinions, and often in predictable ways. It is claimed that people involved in deliberation change ...their minds on important issues. We also know that political participation and attitudes towards certain issues depend on political knowledge and civic education. To what extent are these linked? Do certain types of people react differently to their involvement in deliberation and is opinion change contingent on the varying capacities and knowledge of participants? Using data from a nationwide exercise in deliberative democracy carried out in Ireland we find some evidence that the 'deliberative' citizen, or at least the citizen most likely to shift opinion following deliberation, is under 65, with median levels of knowledge. We also find that heterogeneous groups are important for deliberation to be effective.
Primetime for γ Farrell, David H.
Blood,
08/2014, Letnik:
124, Številka:
9
Journal Article
Recenzirano
Odprti dostop
In this issue of
Blood
, Omarova et al show that fibrinogen, particularly the γ′ variant, increases the anticoagulant effect of activated protein C in plasma.
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