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Hemodynamic and metabolic effects of a new pediatric dobutamine formulation in hypoxic newborn pigs
Background: The aim of our study was to measure drug-related changes in hemodynamics and oxygen metabolism in response to different doses of an age-appropriate dobutamine formulation in hypoxic pigs. A secondary aim was to validate superior vena cava flow (SVCF) as a marker of cardiac index (CI) for subsequent clinical trials of this formulation in humans.
Methods: Newborn pigs (n=18) were exposed to 2h-hypoxia (10-15% oxygen) followed by reoxygenation (21-30% oxygen 4h). After 1h-reoxygenation, pigs were randomized to: control group (no treatment), dobutamine infusion at a rate of 10-15μg/kg/min or 15-20μg/kg/min. Dobutamine groups received two dobutamine doses during 30min with a 60min washout period between doses. Cardiovascular profile and oxygen metabolism were monitored. In four animals an ultrasonic perivascular flow probe was placed around superior vena cava to measure SVCF.
Results: Hypoxia significantly decreased CI, systemic-vascular-resistance and mean-arterial-bloodpressure (MABP). Dobutamine doses significantly increased heart-rate, CI and oxygen-delivery without changes in stroke-volume and MABP. Only 10-15μg/kg/min increased oxygen consumption and peripheral tissue oxygenation measured by Near-infrared-spectroscopy. A positive correlation was observed between SVCF and CI.
Conclusion: The new pediatric dobutamine formulation improved hemodynamic status, with dose-specific
differences in metabolic response. SVCF may be a useful surrogate for CI in subsequent clinical trials
The roles of latent heating and dust in the structure and variability of the northern Martian polar vortex
The winter polar vortices on Mars are annular in terms of their potential
vorticity (PV) structure, a phenomenon identified in observations, reanalysis
and some numerical simulations. Some recent modeling studies have proposed that
condensation of atmospheric carbon dioxide at the winter pole is a contributing
factor to maintaining the annulus through the release of latent heat. Dust and
topographic forcing are also known to be causes of internal and interannual
variability in the polar vortices. However, coupling between these factors
remains uncertain, and previous studies of their impact on vortex structure and
variability have been largely limited to a single Martian global climate model
(MGCM). Here, by further developing a novel MGCM, we decompose the relative
roles of latent heat and dust as drivers for the variability and structure of
the northern Martian polar vortex. We also consider how Martian topography
modifies the driving response. By also analyzing a reanalysis dataset we show
that there is significant dependence in the polar vortex structure and
variability on the observations assimilated. In both model and reanalysis, high
atmospheric dust loading (such as that seen during a global dust storm) can
disrupt the vortex, cause the destruction of PV in the low-mid altitudes (> 0.1
hPa), and significantly reduce spatial and temporal vortex variability. Through
our simulations, we find that the combination of dust and topography primarily
drives the eddy activity throughout the Martian year, and that although latent
heat release can produce an annular vortex, it has a relatively minor effect on
vortex variability.Comment: 16 pages, 14 figures, The Planetary Science Journa
111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells
Radiolabelled, drug-loaded nanoparticles may combine the theranostic properties of radionuclides, the controlled release of chemotherapy and cancer cell targeting. Here, we report the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface conjugated to DTPA-hEGF (DTPA = diethylenetriaminepentaacetic acid, hEGF = human epidermal growth factor) and encapsulating the ruthenium-based DNA replication inhibitor and radiosensitizer Ru(phen)2(tpphz)2+ (phen = 1,10-phenanthroline, tpphz = tetrapyridophenazine) Ru1. The functionalized PLGA surface incorporates the metal ion chelator DTPA for radiolabelling and the targeting ligand for EGF receptor (EGFR). Nanoparticles radiolabelled with 111In are taken up preferentially by EGFR-overexpressing oesophageal cancer cells, where they exhibit radiotoxicity through the generation of cellular DNA damage. Moreover, nanoparticle co-delivery of Ru1 alongside 111In results in decreased cell survival compared to single-agent formulations; an effect that occurs through DNA damage enhancement and an additive relationship between 111In and Ru1. Substantially decreased uptake and radiotoxicity of nanoparticles towards normal human fibroblasts and oesophageal cancer cells with normal EGFR levels is observed. This work demonstrates nanoparticle co-delivery of a therapeutic radionuclide plus a ruthenium-based radiosensitizer can achieve combinational and targeted therapeutic effects in cancer cells that overexpress EGFR
General stability criterion of inviscid parallel flow
A more restrictively general stability criterion of two-dimensional inviscid
parallel flow is obtained analytically. First, a sufficient criterion for
stability is found as either or
in the flow, where is the velocity at inflection
point, is the eigenvalue of Poincar\'{e}'s problem. Second, this
criterion is generalized to barotropic geophysical flows in plane.
Based on the criteria, the flows are are divided into different categories of
stable flows, which may simplify the further investigations. And the
connections between present criteria and Arnol'd's nonlinear criteria are
discussed. These results extend the former criteria obtained by Rayleigh,
Tollmien and Fj{\o}rtoft and would intrigue future research on the mechanism of
hydrodynamic instability.Comment: Revtex4, 4 pages, 2 figures, extends the first part of
physics/0512208, Accepted, to be continue
Generation and Structure of Solitary Rossby Vortices in Rotating Fluids
The formation of zonal flows and vortices in the generalized
Charney-Hasegawa-Mima equation is studied. We focus on the regime when the size
of structures is comparable to or larger than the deformation (Rossby) radius.
Numerical simulations show the formation of anticyclonic vortices in unstable
shear flows and ring-like vortices with quiescent cores and vorticity
concentrated in a ring. Physical mechanisms that lead to these phenomena and
their relevance to turbulence in planetary atmospheres are discussed.Comment: 3 pages in REVTeX, 5 postscript figures separately, submitted to
Phys. Rev.
Recent Advances Concerning Certain Class of Geophysical Flows
This paper is devoted to reviewing several recent developments concerning
certain class of geophysical models, including the primitive equations (PEs) of
atmospheric and oceanic dynamics and a tropical atmosphere model. The PEs for
large-scale oceanic and atmospheric dynamics are derived from the Navier-Stokes
equations coupled to the heat convection by adopting the Boussinesq and
hydrostatic approximations, while the tropical atmosphere model considered here
is a nonlinear interaction system between the barotropic mode and the first
baroclinic mode of the tropical atmosphere with moisture.
We are mainly concerned with the global well-posedness of strong solutions to
these systems, with full or partial viscosity, as well as certain singular
perturbation small parameter limits related to these systems, including the
small aspect ratio limit from the Navier-Stokes equations to the PEs, and a
small relaxation-parameter in the tropical atmosphere model. These limits
provide a rigorous justification to the hydrostatic balance in the PEs, and to
the relaxation limit of the tropical atmosphere model, respectively. Some
conditional uniqueness of weak solutions, and the global well-posedness of weak
solutions with certain class of discontinuous initial data, to the PEs are also
presented.Comment: arXiv admin note: text overlap with arXiv:1507.0523
Multi-level Dynamical Systems: Connecting the Ruelle Response Theory and the Mori-Zwanzig Approach
In this paper we consider the problem of deriving approximate autonomous
dynamics for a number of variables of a dynamical system, which are weakly
coupled to the remaining variables. In a previous paper we have used the Ruelle
response theory on such a weakly coupled system to construct a surrogate
dynamics, such that the expectation value of any observable agrees, up to
second order in the coupling strength, to its expectation evaluated on the full
dynamics. We show here that such surrogate dynamics agree up to second order to
an expansion of the Mori-Zwanzig projected dynamics. This implies that the
parametrizations of unresolved processes suited for prediction and for the
representation of long term statistical properties are closely related, if one
takes into account, in addition to the widely adopted stochastic forcing, the
often neglected memory effects.Comment: 14 pages, 1 figur
Training physicians in behavioural change counseling: A systematic review
Background: Poor health behaviours (e.g., smoking, physical inactivity) represent major underlying causes of non-communicable chronic diseases (NCDs). Prescriptive behaviour change interventions employed by physicians show limited effectiveness. Physician training in evidence-based behaviour change counselling (BCC) may improve behavioural risk factor management, but the efficacy and feasibility of current programs remains unclear.
Objective: (1) To systematically review the efficacy of BCC training programs for physicians, and (2) to describe program content, dose and structure, informing better design and dissemination.
Methods: Using PRISMA guidelines, a database search up to January 2018, yielded 1889 unique articles, screened by 2 authors; 9 studies met inclusion criteria and were retained for analysis.
Results: 100% of studies reported significant improvements in BCC skills among physicians, most programs targeting provider-patient collaboration, supporting patient autonomy, and use of open questions to elicit “change-talk”. Limitation included: poor reporting quality, high program heterogeneity, small sample sizes, 78% of studies having no comparison group, and less than 30% of skills taught being formally assessed.
Conclusion: Training programs were efficacious, but methodological weaknesses limit the ability to determine content and delivery. Caution is necessary when interpreting the results
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