398 research outputs found
Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis.
Tuberculous meningitis (TBM) is the most lethal form of tuberculosis, and new treatments that improve outcomes are required. We randomly assigned adults with TBM to treatment with standard antituberculosis treatment alone or in combination with ciprofloxacin (750 mg/12 h), levofloxacin (500 mg/12 h), or gatifloxacin (400 mg/24 h) for the first 60 days of therapy. Fluoroquinolone concentrations were measured with plasma and cerebrospinal fluid (CSF) specimens taken at predetermined, randomly assigned times throughout treatment. We aimed to describe the pharmacokinetics of each fluoroquinolone during TBM treatment and evaluate the relationship between drug exposure and clinical response over 270 days of therapy (Controlled Trials number ISRCTN07062956). Sixty-one patients with TBM were randomly assigned to treatment with no fluoroquinolone (n = 15), ciprofloxacin (n = 16), levofloxacin (n = 15), or gatifloxacin (n = 15). Cerebrospinal fluid penetration, measured by the ratio of the plasma area under the concentration-time curve from 0 to 24 h (AUC0â24) to the cerebrospinal fluid AUC0â24, was greater for levofloxacin (median, 0.74; range, 0.58 to 1.03) than for gatifloxacin (median, 0.48; range, 0.47 to 0.50) or ciprofloxacin (median, 0.26; range, 0.11 to 0.77). Univariable and multivariable analyses of fluoroquinolone exposure against a range of different treatment responses revealed worse outcomes among patients with lower and higher plasma and CSF exposures than for patients with intermediate exposures (a U-shaped exposure-response). TBM patients most likely to benefit from fluoroquinolone therapy were identified, along with exposure-response relationships associated with improved outcomes. Fluoroquinolones add antituberculosis activity to the standard treatment regimen, but to improve outcomes of TBM, they must be started early, before the onset of coma
Routine Pediatric Enterovirus 71 Vaccination in China: a Cost-Effectiveness Analysis
published_or_final_versio
Aidnogenesis via Leptogenesis and Dark Sphalerons
We discuss aidnogenesis, the generation of a dark matter asymmetry via new
sphaleron processes associated to an extra non-abelian gauge symmetry common to
both the visible and the dark sectors. Such a theory can naturally produce an
abundance of asymmetric dark matter which is of the same size as the lepton and
baryon asymmetries, as suggested by the similar sizes of the observed baryonic
and dark matter energy content, and provide a definite prediction for the mass
of the dark matter particle. We discuss in detail a minimal realization in
which the Standard Model is only extended by dark matter fermions which form
"dark baryons" through an SU(3) interaction, and a (broken) horizontal symmetry
that induces the new sphalerons. The dark matter mass is predicted to be
approximately 6 GeV, close to the region favored by DAMA and CoGeNT.
Furthermore, a remnant of the horizontal symmetry should be broken at a lower
scale and can also explain the Tevatron dimuon anomaly.Comment: Minor changes, discussion of present constraints expanded. 16 pages,
2 eps figures, REVTeX
Faster Smith-Waterman database searches with inter-sequence SIMD parallelisation
<p>Abstract</p> <p>Background</p> <p>The Smith-Waterman algorithm for local sequence alignment is more sensitive than heuristic methods for database searching, but also more time-consuming. The fastest approach to parallelisation with SIMD technology has previously been described by Farrar in 2007. The aim of this study was to explore whether further speed could be gained by other approaches to parallelisation.</p> <p>Results</p> <p>A faster approach and implementation is described and benchmarked. In the new tool SWIPE, residues from sixteen different database sequences are compared in parallel to one query residue. Using a 375 residue query sequence a speed of 106 billion cell updates per second (GCUPS) was achieved on a dual Intel Xeon X5650 six-core processor system, which is over six times more rapid than software based on Farrar's 'striped' approach. SWIPE was about 2.5 times faster when the programs used only a single thread. For shorter queries, the increase in speed was larger. SWIPE was about twice as fast as BLAST when using the BLOSUM50 score matrix, while BLAST was about twice as fast as SWIPE for the BLOSUM62 matrix. The software is designed for 64 bit Linux on processors with SSSE3. Source code is available from <url>http://dna.uio.no/swipe/</url> under the GNU Affero General Public License.</p> <p>Conclusions</p> <p>Efficient parallelisation using SIMD on standard hardware makes it possible to run Smith-Waterman database searches more than six times faster than before. The approach described here could significantly widen the potential application of Smith-Waterman searches. Other applications that require optimal local alignment scores could also benefit from improved performance.</p
The Cosmology of Composite Inelastic Dark Matter
Composite dark matter is a natural setting for implementing inelastic dark
matter - the O(100 keV) mass splitting arises from spin-spin interactions of
constituent fermions. In models where the constituents are charged under an
axial U(1) gauge symmetry that also couples to the Standard Model quarks, dark
matter scatters inelastically off Standard Model nuclei and can explain the
DAMA/LIBRA annual modulation signal. This article describes the early Universe
cosmology of a minimal implementation of a composite inelastic dark matter
model where the dark matter is a meson composed of a light and a heavy quark.
The synthesis of the constituent quarks into dark mesons and baryons results in
several qualitatively different configurations of the resulting dark matter
hadrons depending on the relative mass scales in the system.Comment: 31 pages, 4 figures; references added, typos correcte
Electroweak Baryogenesis and Dark Matter with an approximate R-symmetry
It is well known that R-symmetric models dramatically alleviate the SUSY
flavor and CP problems. We study particular modifications of existing
R-symmetric models which share the solution to the above problems, and have
interesting consequences for electroweak baryogenesis and the Dark Matter (DM)
content of the universe. In particular, we find that it is naturally possible
to have a strongly first-order electroweak phase transition while
simultaneously relaxing the tension with EDM experiments. The R-symmetry (and
its small breaking) implies that the gauginos (and the neutralino LSP) are
pseudo-Dirac fermions, which is relevant for both baryogenesis and DM. The
singlet superpartner of the U(1)_Y pseudo-Dirac gaugino plays a prominent role
in making the electroweak phase transition strongly first-order. The
pseudo-Dirac nature of the LSP allows it to behave similarly to a Dirac
particle during freeze-out, but like a Majorana particle for annihilation today
and in scattering against nuclei, thus being consistent with current
constraints. Assuming a standard cosmology, it is possible to simultaneously
have a strongly first-order phase transition conducive to baryogenesis and have
the LSP provide the full DM relic abundance, in part of the allowed parameter
space. However, other possibilities for DM also exist, which are discussed. It
is expected that upcoming direct DM searches as well as neutrino signals from
DM annihilation in the Sun will be sensitive to this class of models.
Interesting collider and Gravity-wave signals are also briefly discussed.Comment: 50 pages, 10 figure
Clues from nearby galaxies to a better theory of cosmic evolution
The great advances in the network of cosmological tests show that the
relativistic Big Bang theory is a good description of our expanding universe.
But the properties of nearby galaxies that can be observed in greatest detail
suggest a still better theory would more rapidly gather matter into galaxies
and groups of galaxies. This happens in theoretical ideas now under discussion.Comment: published in Natur
The Seroprevalence and Seroincidence of Enterovirus71 Infection in Infants and Children in Ho Chi Minh City, Viet Nam
Enterovirus 71 (EV71)-associated hand, foot and mouth disease has emerged as a serious public health problem in South East Asia over the last decade. To better understand the prevalence of EV71 infection, we determined EV71 seroprevalence and seroincidence amongst healthy infants and children in Ho Chi Minh City, Viet Nam. In a cohort of 200 newborns, 55% of cord blood samples contained EV71 neutralizing antibodies and these decayed to undetectable levels by 6 months of age in 98% of infants. The EV71 neutralizing antibody seroconversion rate was 5.6% in the first year and 14% in the second year of life. In children 5â15 yrs of age, seroprevalence of EV71 neutralizing antibodies was 84% and in cord blood it was 55%. Taken together, these data suggest EV71 force of infection is high and highlights the need for more research into its epidemiology and pathogenesis in high disease burden countries
A âquiet revolutionâ? The impact of Training Schools on initial teacher training partnerships
This paper discusses the impact on initial teacher training of a new policy initiative in England: the introduction of Training Schools. First, the Training School project is set in context by exploring the evolution of a partnership approach to initial teacher training in England. Ways in which Training Schools represent a break with established practice are considered together with their implications for the dominant mode of partnership led by higher education institutions (HEIs). The capacity of Training Schools to achieve their own policy objectives is examined, especially their efficacy as a strategy for managing innovation and the dissemination of innovation. The paper
ends by focusing on a particular Training School project which has adopted an unusual approach to its work and enquires whether this alternative approach could offer a more profitable way forward. During the course of the paper, five different models of partnership are considered:
collaborative, complementary, HEI-led, school-led and partnership within a partnership
Spontaneous R-Parity Violation, Flavor Symmetry and Tribimaximal Mixing
We explore the possibility of spontaneous R parity violation in the context
of flavor symmetry. Our model contains singlet matter chiral superfields which are arranged as triplet of
and as well as few additional Higgs chiral superfields which are singlet
under MSSM gauge group and belong to triplet and singlet representation under
the flavor symmetry. R parity is broken spontaneously by the vacuum
expectation values of the different sneutrino fields and hence we have
neutrino-neutralino as well as neutrino-MSSM gauge singlet higgsino mixings in
our model, in addition to the standard model neutrino- gauge singlet neutrino,
gaugino-higgsino and higgsino-higgsino mixings. Because all of these mixings we
have an extended neutral fermion mass matrix. We explore the low energy
neutrino mass matrix for our model and point out that with some specific
constraints between the sneutrino vacuum expectation values as well as the MSSM
gauge singlet Higgs vacuum expectation values, the low energy neutrino mass
matrix will lead to a tribimaximal mixing matrix. We also analyze the potential
minimization for our model and show that one can realize a higher vacuum
expectation value of the singlet
sneutrino fields even when the other sneutrino vacuum expectation values are
extremely small or even zero.Comment: 18 page
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