248 research outputs found
A model for interacting instabilities and texture dynamics of patterns
A simple model to study interacting instabilities and textures of resulting
patterns for thermal convection is presented. The model consisting of
twelve-mode dynamical system derived for periodic square lattice describes
convective patterns in the form of stripes and patchwork quilt. The interaction
between stationary zig-zag stripes and standing patchwork quilt pattern leads
to spatiotemporal patterns of twisted patchwork quilt. Textures of these
patterns, which depend strongly on Prandtl number, are investigated numerically
using the model. The model also shows an interesting possibility of a
multicritical point, where stability boundaries of four different structures
meet.Comment: 4 pages including 4 figures, page width revise
Bayesian Analysis and Constraints on Kinematic Models from Union SNIa
The kinematic expansion history of the universe is investigated by using the
307 supernovae type Ia from the Union Compilation set. Three simple model
parameterizations for the deceleration parameter (constant, linear and abrupt
transition) and two different models that are explicitly parametrized by the
cosmic jerk parameter (constant and variable) are considered. Likelihood and
Bayesian analyses are employed to find best fit parameters and compare models
among themselves and with the flat CDM model. Analytical expressions
and estimates for the deceleration and cosmic jerk parameters today ( and
) and for the transition redshift () between a past phase of cosmic
deceleration to a current phase of acceleration are given. All models
characterize an accelerated expansion for the universe today and largely
indicate that it was decelerating in the past, having a transition redshift
around 0.5. The cosmic jerk is not strongly constrained by the present
supernovae data. For the most realistic kinematic models the
confidence limits imply the following ranges of values: ,
and , which are compatible with the
CDM predictions, , and .
We find that even very simple kinematic models are equally good to describe the
data compared to the concordance CDM model, and that the current
observations are not powerful enough to discriminate among all of them.Comment: 13 pages. Matches published versio
Cost-effectiveness analysis of sacubitril/valsartan vs enalapril in patients with heart failure and reduced ejection fraction
Importance The angiotensin receptor neprilysin inhibitor sacubitril/valsartan was associated with a reduction in cardiovascular mortality, all-cause mortality, and hospitalizations compared with enalapril. Sacubitril/valsartan has been approved for use in heart failure (HF) with reduced ejection fraction in the United States and cost has been suggested as 1 factor that will influence the use of this agent.
Objective To estimate the cost-effectiveness of sacubitril/valsartan vs enalapril in the United States.
Design, Setting, and Participants Data from US adults (mean [SD] age, 63.8 [11.5] years) with HF with reduced ejection fraction and characteristics similar to those in the PARADIGM-HF trial were used as inputs for a 2-state Markov model simulated HF. Risks of all-cause mortality and hospitalization from HF or other reasons were estimated with a 30-year time horizon. Quality of life was based on trial EQ-5D scores. Hospital costs combined Medicare and private insurance reimbursement rates; medication costs included the wholesale acquisition cost for sacubitril/valsartan and enalapril. A discount rate of 3% was used. Sensitivity analyses were performed on key inputs including: hospital costs, mortality benefit, hazard ratio for hospitalization reduction, drug costs, and quality-of-life estimates.
Main Outcomes and Measures Hospitalizations, quality-adjusted life-years (QALYs), costs, and incremental costs per QALY gained.
Results The 2-state Markov model of US adult patients (mean age, 63.8 years) calculated that there would be 220 fewer hospital admissions per 1000 patients with HF treated with sacubitril/valsartan vs enalapril over 30 years. The incremental costs and QALYs gained with sacubitril/valsartan treatment were estimated at 45 017 per QALY for the base-case. Sensitivity analyses demonstrated ICERs ranging from 75 301 per QALY.
Conclusions and Relevance For eligible patients with HF with reduced ejection fraction, the Markov model calculated that sacubitril/valsartan would increase life expectancy at an ICER consistent with other high-value accepted cardiovascular interventions. Sensitivity analyses demonstrated sacubitril/valsartan would remain cost-effective vs enalapril
NK1 antagonists attenuate tau phosphorylation after blast and repeated concussive injury
Exposure to repeated concussive traumatic brain injury (TBI) and to blast-induced TBI has been associated with the potential development of the neurodegenerative condition known as chronic traumatic encephalopathy (CTE). CTE is characterized by the accumulation of hyperphosphorylated tau protein, with the resultant tau tangles thought to initiate the cognitive and behavioral manifestations that appear as the condition progresses. However, the mechanisms linking concussive and blast TBI with tau hyperphosphorylation are unknown. Here we show that single moderate TBI, repeated concussive TBI and blast-induced mild TBI all result in hyperphosphorylation of tau via a substance P mediated mechanism. Post-injury administration of a substance P, NK1 receptor antagonist attenuated the injury-induced phosphorylation of tau by modulating the activity of several key kinases including Akt, ERK1/2 and JNK, and was associated with improvement in neurological outcome. We also demonstrate that inhibition of the TRPV1 mechanoreceptor, which is linked to substance P release, attenuated injury-associated tau hyperphosphorylation, but only when it was administered prior to injury. Our results demonstrate that TBI-mediated stimulation of brain mechanoreceptors is associated with substance P release and consequent tau hyperphosphorylation, with administration of an NK1 receptor antagonist attenuating tau phosphorylation and associated neurological deficits. NK1 antagonists may thus represent a pharmacological approach to attenuate the potential development of CTE following concussive and blast TBI.Frances Corrigan, Ibolja Cernak, Kelly McAteer, Sarah C. Hellewell, JefreyV. Rosenfeld ... et al
Endothelial miR-30c suppresses tumor growth via inhibition of TGF-β–induced Serpine1
In tumors, extravascular fibrin forms provisional scaffolds for endothelial cell (EC) growth and motility during angiogenesis. We report that fibrin-mediated angiogenesis was inhibited and tumor growth delayed following postnatal deletion of Tgfbr2 in the endothelium of Cdh5-CreERT2 Tgfbr2fl/fl mice (Tgfbr2iECKOmice). ECs from Tgfbr2iECKO mice failed to upregulate the fibrinolysis inhibitor plasminogen activator inhibitor 1 (Serpine1, also known as PAI-1), due in part to uncoupled TGF-β–mediated suppression of miR-30c. Bypassing TGF-β signaling with vascular tropic nanoparticles that deliver miR-30c antagomiRs promoted PAI-1–dependent tumor growth and increased fibrin abundance, whereas miR-30c mimics inhibited tumor growth and promoted vascular-directed fibrinolysis in vivo. Using single-cell RNA-Seq and a NanoString miRNA array, we also found that subtypes of ECs in tumors showed spectrums of Serpine1 and miR-30c expression levels, suggesting functional diversity in ECs at the level of individual cells; indeed, fresh EC isolates from lung and mammary tumor models had differential abilities to degrade fibrin and launch new vessel sprouts, a finding that was linked to their inverse expression patterns of miR-30c and Serpine1 (i.e., miR-30chi Serpine1lo ECs were poorly angiogenic and miR-30clo Serpine1hi ECs were highly angiogenic). Thus, by balancing Serpine1 expression in ECs downstream of TGF-β, miR-30c functions as a tumor suppressor in the tumor microenvironment through its ability to promote fibrin degradation and inhibit blood vessel formation
The Middle Way: East Asian masters students’ perceptions of critical argumentation in U.K. universities.
The paper explores the learning experiences of East Asian masters students in dealing with Western academic norms of critical thinking in classroom debate and assignment writing. The research takes a cultural approach, and employs grounded theory and case study methodology, the aims being for students to explain their perceptions of their personal learning journeys. The data suggest that the majority of students interviewed rejected full academic acculturation into Western norms of argumentation. They instead opted for a ‘Middle Way’ that synergizes the traditional cultural academic values held by many East Asian students with those elements of Western academic norms that are perceived to be aligned with these. This is a relatively new area of research which represents a challenge for British lecturers and students
Constraining the dark energy with galaxy clusters X-ray data
The equation of state characterizing the dark energy component is constrained
by combining Chandra observations of the X-ray luminosity of galaxy clusters
with independent measurements of the baryonic matter density and the latest
measurements of the Hubble parameter as given by the HST key project. By
assuming a spatially flat scenario driven by a "quintessence" component with an
equation of state we place the following limits on the
cosmological parameters and : (i) and (1) if the
equation of state of the dark energy is restricted to the interval (\emph{usual} quintessence) and (ii) and
() if violates the null energy condition and assume values (\emph{extended} quintessence or ``phantom'' energy). These results are in
good agreement with independent studies based on supernovae observations,
large-scale structure and the anisotropies of the cosmic background radiation.Comment: 6 pages, 4 figures, LaTe
Plane-symmetric inhomogeneous magnetized viscous fluid universe with a variable
The behavior of magnetic field in plane symmetric inhomogeneous cosmological
models for bulk viscous distribution is investigated. The coefficient of bulk
viscosity is assumed to be a power function of mass density . The values of cosmological constant for these models are
found to be small and positive which are supported by the results from recent
supernovae Ia observations. Some physical and geometric aspects of the models
are also discussed.Comment: 18 pages, LaTex, no figur
Cosmological consequences of a Chaplygin gas dark energy
A combination of recent observational results has given rise to what is
currently known as the dark energy problem. Although several possible
candidates have been extensively discussed in the literature to date the nature
of this dark energy component is not well understood at present. In this paper
we investigate some cosmological implications of another dark energy candidate:
an exotic fluid known as the Chaplygin gas, which is characterized by an
equation of state , where is a positive constant. By assuming
a flat scenario driven by non-relativistic matter plus a Chaplygin gas dark
energy we study the influence of such a component on the statistical properties
of gravitational lenses. A comparison between the predicted age of the universe
and the latest age estimates of globular clusters is also included and the
results briefly discussed. In general, we find that the behavior of this class
of models may be interpreted as an intermediary case between the standard and
CDM scenarios.Comment: 7 pages, 5 figures, to appear in Phys. Rev.
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