Enhancing the spectral gap of networks by node removal

Dynamics on networks are often characterized by the second smallest eigenvalue of the Laplacian matrix of the network, which is called the spectral gap. Examples include the threshold coupling strength for synchronization and the relaxation time of a random walk. A large spectral gap is usually associated with high network performance, such as facilitated synchronization and rapid convergence. In this study, we seek to enhance the spectral gap of undirected and unweighted networks by removing nodes because, practically, the removal of nodes often costs less than the addition of nodes, addition of links, and rewiring of links. In particular, we develop a perturbative method to achieve this goal. The proposed method realizes better performance than other heuristic methods on various model and real networks. The spectral gap increases as we remove up to half the nodes in most of these networks.Comment: 5 figure

‘ An investigation of the nervous control of defecation ’ by Denny-Brown and Robertson: a classic paper revisited

In 1935 two young neurologists, Derek Denny-Brown and E. Graeme Robertson, published an article explaining the mechanisms underlying human defaecation based on a manometric study in patients with sacral root and spinal cord lesions, and normal subjects. This article is still routinely cited in studies of rectal and sphincter ani function. Unfortunately, however, the article itself is not written well, being composed of long convoluted sentences and containing 79 often indecipherable figures. Difficult-to-understand articles were common to the publications of Denny-Brown, who became one of the most prominent neurologists of the twentieth century. In accord with our prior work explaining Denny-Brown and Robertson's earlier paper on micturition, we provide here what we hope is a clear explanation of the methods and results in their study on defaecation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73905/1/j.1463-1318.2004.00636.x.pd

Peristaltic Transport of a Rheological Fluid: Model for Movement of Food Bolus Through Esophagus

Fluid mechanical peristaltic transport through esophagus has been of concern in the paper. A mathematical model has been developed with an aim to study the peristaltic transport of a rheological fluid for arbitrary wave shapes and tube lengths. The Ostwald-de Waele power law of viscous fluid is considered here to depict the non-Newtonian behaviour of the fluid. The model is formulated and analyzed with the specific aim of exploring some important information concerning the movement of food bolus through the esophagus. The analysis has been carried out by using lubrication theory. The study is particularly suitable for cases where the Reynolds number is small. The esophagus is treated as a circular tube through which the transport of food bolus takes places by periodic contraction of the esophageal wall. Variation of different variables concerned with the transport phenomena such as pressure, flow velocity, particle trajectory and reflux are investigated for a single wave as well as for a train of periodic peristaltic waves. Locally variable pressure is seen to be highly sensitive to the flow index `n'. The study clearly shows that continuous fluid transport for Newtonian/rheological fluids by wave train propagation is much more effective than widely spaced single wave propagation in the case of peristaltic movement of food bolus in the esophagus.Comment: Accepted for publication in Applied Mathematics and Mechanics (AMM), Springe

Peristaltic Transport of a Couple Stress Fluid: Some Applications to Hemodynamics

The present paper deals with a theoretical investigation of the peristaltic transport of a couple stress fluid in a porous channel. The study is motivated towards the physiological flow of blood in the micro-circulatory system, by taking account of the particle size effect. The velocity, pressure gradient, stream function and frictional force of blood are investigated, when the Reynolds number is small and the wavelength is large, by using appropriate analytical and numerical methods. Effects of different physical parameters reflecting porosity, Darcy number, couple stress parameter as well as amplitude ratio on velocity profiles, pumping action and frictional force, streamlines pattern and trapping of blood are studied with particular emphasis. The computational results are presented in graphical form. The results are found to be in good agreement with those of Shapiro et. al \cite{r25} that was carried out for a non-porous channel in the absence of couple stress effect. The present study puts forward an important observation that for peristaltic transport of a couple stress fluid during free pumping when the couple stress effect of the fluid/Darcy permeability of the medium, flow reversal can be controlled to a considerable extent. Also by reducing the permeability it is possible to avoid the occurrence of trapping phenomenon

Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study

Background - The PCSK9 antibody alirocumab (75 mg every 2 weeks; Q2W) as monotherapy reduced low-density lipoprotein-cholesterol (LDL-C) levels by 47%. Because the option of a monthly dosing regimen is convenient, ODYSSEY CHOICE II evaluated alirocumab 150 mg Q4W in patients with inadequately controlled hypercholesterolemia and not on statin (majority with statin-associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone. Methods and Results - Patients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment to 150 mg Q2W at week (W) 12 if W8 predefined LDL-C target levels were not met. The primary efficacy endpoint was LDL-C percentage change from baseline to W24. Mean baseline LDL-C levels were 163.9 mg/dL (alirocumab 150 mg Q4W, n= 59), 154.5 mg/dL (alirocumab 75 mg Q2W, n= 116), and 158.5 mg/dL (placebo, n= 58). In the alirocumab 150 mg Q4W and 75 mg Q2W groups (49.1% and 36.0% of patients received dose adjustment, respectively), least-squares mean LDL-C changes from baseline to W24 were -51.7% and -53.5%, respectively (placebo [+ 4.7%]; both groups P< 0.0001 versus placebo). In total, 63.9% and 70.3% of alirocumab-treated patients achieved their LDL-C targets at W24. Treatment-emergent adverse events occurred in 77.6% (alirocumab 150 mg Q4W), 73.0% (alirocumab 75 mg Q2W), and 63.8% (placebo) of patients, with injection-site reactions among the most common treatment-emergent adverse events. Conclusions - Alirocumab 150 mg Q4W can be considered in patients not on statin with inadequately controlled hypercholesterolemia as a convenient option for lowering LDL-C

Pretreatment with phenoxybenzamine attenuates the radial artery's vasoconstrictor response to α-adrenergic stimuli

AbstractBackgroundAlthough the radial artery bypass conduit has excellent intermediate-term patency, it has a proclivity to vasospasm. We tested the hypothesis that brief pretreatment of a radial artery graft with the irreversible adrenergic antagonist phenoxybenzamine attenuates the vasoconstrictor response to the vasopressors phenylephrine and norepinephrine compared with the currently used papaverine/lidocaine.MethodsSegments of human radial artery grafts were obtained after a 30-minute intraoperative pretreatment with a solution containing 20 mL of heparinized blood, 0.4 mL of papaverine (30 mg/mL), and 1.6 mL of lidocaine (1%). The segments were transported to the laboratory and placed into a bath containing Krebs-Henseleit solution and 10, 100, or 1000 μmol/L phenoxybenzamine or vehicle. The segments were tested in organ chambers for contractile responses to increasing concentrations of phenylephrine and norepinephrine (0.5-15 μmol/L).ResultsContractile responses to 15 μmol/L phenylephrine in control radial artery segments averaged 44.2% ± 9.1% of the maximal contractile response to 30 mmol/L KCl. Papaverine/lidocaine modestly attenuated contraction to 15 μmol/L phenylephrine (32.1% ± 5.9%; P = .22), but 1000 μmol/L phenoxybenzamine completely abolished radial artery contraction (−7.2% ± 4.4%; P < .001). The effect of 10 and 100 μmol/L phenoxybenzamine on attenuating vasocontraction was intermediate between 1000 μmol/L phenoxybenzamine and papaverine/lidocaine. Responses to 15 μmol/L norepinephrine in control radial artery segments averaged 54.7% ± 7.5% of maximal contraction to 30 mmol/L KCl. Papaverine/lidocaine modestly attenuated the contraction response of radial artery segments (35.6% ± 5.1%; P = .04). In contrast, 1000 μmol/L phenoxybenzamine showed the greatest attenuation of norepinephrine-induced contraction (−10.5% ± 2.0%; P < .001).ConclusionsA brief pretreatment of the human radial artery bypass conduit with 1000 μmol/L phenoxybenzamine completely attenuates the vasoconstrictor responses to the widely used vasopressors norepinephrine and phenylephrine. Papaverine/lidocaine alone did not block vasoconstriction to these α-adrenergic agonists

Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole-Body Physiology

Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a “virtual population” from which “virtual individuals” can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the “virtual individuals” that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models