712 research outputs found
CASSETTEâclindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation: Study protocol for a randomised controlled trial
Background
Exotoxins are important virulence factors in Staphylococcus aureus. Clindamycin, a protein synthesis inhibitor antibiotic, is thought to limit exotoxin production and improve outcomes in severe S. aureus infections. However, randomised prospective data to support this are lacking.
Methods
An open-label, multicentre, randomised controlled trial (RCT) will compare outcome differences in severe S. aureus infection between standard treatment (flucloxacillin/cefazolin in methicillin-susceptible S. aureus; and vancomycin/daptomycin in methicillin-resistant S. aureus) and standard treatment plus an additional clindamycin given for 7âdays. We will include a minimum of 60 participants (both adult and children) in the pilot study. Participants will be enrolled within 72âh of an index culture. Severe infections will include septic shock, necrotising pneumonia, or multifocal and non-contiguous skin and soft tissue/osteoarticular infections. Individuals who are immunosuppressed, moribund, with current severe diarrhoea or Clostridiodes difficile infection, pregnant, and those with anaphylaxis to ÎČ-lactams or lincosamides will be excluded.
The primary outcomes measure is the number of days alive and free (1 or 0) of systemic inflammatory response syndrome (SIRS) within the first 14âdays post randomisation. The secondary outcomes measure will include all-cause mortality at 14, 42, and 90âdays, time to resolution of SIRS, proportion with microbiological treatment failure, and rate of change of C-reactive protein over time. Impacts of inducible clindamycin resistance, strain types, methicillin susceptibility, and presence of various exotoxins will also be analysed.
Discussion
This study will assess the effect of adjunctive clindamycin on patient-centred outcomes in severe, toxin-mediated S. aureus infections. The pilot study will provide feasibility for a much larger RCT.
Trial registration
Australian New Zealand Clinical Trials Registry, ACTRN12617001416381p. Registered on 6 October 2017
Protecting the primordial baryon asymmetry in the seesaw model compatible with WMAP and KamLAND
We require that the primordial baryon asymmetry is not washed out in the
seesaw model compatible with the recent results of WMAP and the neutrino
oscillation experiments including the first results of KamLAND. We find that
only the case of the normal neutrino mass hierarchy with an approximate
-symmetry satisfies the requirement. We further derive, depending on the
signs of neutrino mass eigenvalues, three types of neutrino mass matrixes,
where the values of each element are rather precisely fixed.Comment: 21pages; added reference
Elimination of onchocerciasis in Africa by 2025: an ambitious target requires ambitious interventions
To achieve the elimination of onchocerciasis transmission in all African countries will entail enormous challenges, as has been highlighted by the active discussion around onchocerciasis intervention strategies and evaluation procedures in this journal.Serological thresholds for onchocerciasis elimination, adapted for the African setting, need to be established. The Onchocerciasis Technical Advisory Subgroup of the World Health Organization is currently developing improved guidelines to allow country elimination commi
Quasars and their host galaxies
This review attempts to describe developments in the fields of quasar and
quasar host galaxies in the past five. In this time period, the Sloan and 2dF
quasar surveys have added several tens of thousands of quasars, with Sloan
quasars being found to z>6. Obscured, or partially obscured quasars have begun
to be found in significant numbers. Black hole mass estimates for quasars, and
our confidence in them, have improved significantly, allowing a start on
relating quasar properties such as radio jet power to fundamental parameters of
the quasar such as black hole mass and accretion rate. Quasar host galaxy
studies have allowed us to find and characterize the host galaxies of quasars
to z>2. Despite these developments, many questions remain unresolved, in
particular the origin of the close relationship between black hole mass and
galaxy bulge mass/velocity dispersion seen in local galaxies.Comment: Review article, to appear in Astrophysics Update
Phenomenology of flavor-mediated supersymmetry breaking
The phenomenology of a new economical SUSY model that utilizes dynamical SUSY
breaking and gauge-mediation (GM) for the generation of the sparticle spectrum
and the hierarchy of fermion masses is discussed. Similarities between the
communication of SUSY breaking through a messenger sector, and the generation
of flavor using the Froggatt-Nielsen (FN) mechanism are exploited, leading to
the identification of vector-like messenger fields with FN fields, and the
messenger U(1) as a flavor symmetry. An immediate consequence is that the first
and second generation scalars acquire flavor-dependent masses, but do not
violate FCNC bounds since their mass scale, consistent with effective SUSY, is
of order 10 TeV. We define and advocate a minimal flavor-mediated model (MFMM),
recently introduced in the literature, that successfully accommodates the small
flavor-breaking parameters of the standard model using order one couplings and
ratios of flavon field vevs. The mediation of SUSY breaking occurs via two-loop
log-enhanced GM contributions, as well as several one-loop and two-loop
Yukawa-mediated contributions for which we provide analytical expressions. The
MFMM is parameterized by a small set of masses and couplings, with values
restricted by several model constraints and experimental data. The
next-to-lightest sparticle (NLSP) always has a decay length that is larger than
the scale of a detector, and is either the lightest stau or the lightest
neutralino. Similar to ordinary GM models, the best collider search strategies
are, respectively, inclusive production of at least one highly ionizing track,
or events with many taus plus missing energy. In addition, D^0 - \bar{D}^0
mixing is also a generic low energy signal. Finally, the dynamical generation
of the neutrino masses is briefly discussed.Comment: 54 pages, LaTeX, 8 figure
Formation of superdense hadronic matter in high energy heavy-ion collisions
We present the detail of a newly developed relativistic transport model (ART
1.0) for high energy heavy-ion collisions. Using this model, we first study the
general collision dynamics between heavy ions at the AGS energies. We then show
that in central collisions there exists a large volume of sufficiently
long-lived superdense hadronic matter whose local baryon and energy densities
exceed the critical densities for the hadronic matter to quark-gluon plasma
transition. The size and lifetime of this matter are found to depend strongly
on the equation of state. We also investigate the degree and time scale of
thermalization as well as the radial flow during the expansion of the
superdense hadronic matter. The flow velocity profile and the temperature of
the hadronic matter at freeze-out are extracted. The transverse momentum and
rapidity distributions of protons, pions and kaons calculated with and without
the mean field are compared with each other and also with the preliminary data
from the E866/E802 collaboration to search for experimental observables that
are sensitive to the equation of state. It is found that these inclusive,
single particle observables depend weakly on the equation of state. The
difference between results obtained with and without the nuclear mean field is
only about 20\%. The baryon transverse collective flow in the reaction plane is
also analyzed. It is shown that both the flow parameter and the strength of the
``bounce-off'' effect are very sensitive to the equation of state. In
particular, a soft equation of state with a compressibility of 200 MeV results
in an increase of the flow parameter by a factor of 2.5 compared to the cascade
case without the mean field. This large effect makes it possible to distinguish
the predictions from different theoretical models and to detect the signaturesComment: 55 pages, latex, + 39 figures available upon reques
Top A_FB at the Tevatron vs. charge asymmetry at the LHC in chiral U(1) flavor models with flavored Higgs doublets
We consider the top forward-backward (FB) asymmetry at the Tevatron and top
charge asymmetry at the LHC within chiral U(1)^\prime models with
flavor-dependent U(1)^\prime charges and flavored Higgs fields, which were
introduced in the ref. [65]. The models could enhance not only the top
forward-backward asymmetry at Tevatron, but also the top charge asymmetry at
LHC, without too large same-sign top pair production rates. We identify
parameter spaces for the U(1)^\prime gauge boson and (pseudo)scalar Higgs
bosons where all the experimental data could be accommodated, including the
case with about 125 GeV Higgs boson, as suggested recently by ATLAS and CMS.Comment: 11 pages, 6 figures, figures and discussion adde
Population Structure in the Model Grass Brachypodium distachyon Is Highly Correlated with Flowering Differences across Broad Geographic Areas
The small, annual grass Brachypodium distachyon (L.) Beauv., a close relative of wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.), is a powerful model system for cereals and bioenergy grasses. Genome-wide association studies (GWAS) of natural variation can elucidate the genetic basis of complex traits but have been so far limited in B. distachyon by the lack of large numbers of well-characterized and sufficiently diverse accessions. Here, we report on genotyping-by-sequencing (GBS) of 84 B. distachyon, seven B. hybridum, and three B. stacei accessions with diverse geographic origins including Albania, Armenia, Georgia, Italy, Spain, and Turkey. Over 90,000 high-quality single-nucleotide polymorphisms (SNPs) distributed across the Bd21 reference genome were identified. Our results confirm the hybrid nature of the B. hybridum genome, which appears as a mosaic of B. distachyon-like and B. stacei-like sequences. Analysis of more than 50,000 SNPs for the B. distachyon accessions revealed three distinct, genetically defined populations. Surprisingly, these genomic profiles are associated with differences in flowering time rather than with broad geographic origin. High levels of differentiation in loci associated with floral development support the differences in flowering phenology between B. distachyon populations. Genome-wide association studies combining genotypic and phenotypic data also suggest the presence of one or more photoperiodism, circadian clock, and vernalization genes in loci associated with flowering time variation within B. distachyon populations. Our characterization elucidates genes underlying population differences, expands the germplasm resources available for Brachypodium, and illustrates the feasibility and limitations of GWAS in this model grass
Azimuthal anisotropy and correlations in p+p, d+Au and Au+Au collisions at 200 GeV
We present the first measurement of directed flow () at RHIC. is
found to be consistent with zero at pseudorapidities from -1.2 to 1.2,
then rises to the level of a couple of percent over the range . The latter observation is similar to data from NA49 if the SPS rapidities
are shifted by the difference in beam rapidity between RHIC and SPS.
Back-to-back jets emitted out-of-plane are found to be suppressed more if
compared to those emitted in-plane, which is consistent with {\it jet
quenching}. Using the scalar product method, we systematically compared
azimuthal correlations from p+p, d+Au and Au+Au collisions. Flow and non-flow
from these three different collision systems are discussed.Comment: Quark Matter 2004 proceeding, 4 pages, 3 figure
Azimuthal anisotropy: the higher harmonics
We report the first observations of the fourth harmonic (v_4) in the
azimuthal distribution of particles at RHIC. The measurement was done taking
advantage of the large elliptic flow generated at RHIC. The integrated v_4 is
about a factor of 10 smaller than v_2. For the sixth (v_6) and eighth (v_8)
harmonics upper limits on the magnitudes are reported.Comment: 4 pages, 6 figures, contribution to the Quark Matter 2004 proceeding
- âŠ