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 $-\mu_1<\frac{U''}{U-U_s}<0$ or $0<\frac{U''}{U-U_s}$ in the flow, where $U_s$ is the velocity at inflection point, $\mu_1$ is the eigenvalue of Poincar\'{e}'s problem. Second, this criterion is generalized to barotropic geophysical flows in $\beta$ 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

Comment on the consensus report on the management of hyperglycaemia in Type 2 diabetes by the American Diabetes Association and the European Association for the Study of Diabetes

Letter to the edito