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Search Results: 1 - 10 of 288057 matches for " W. Alan C. Mutch "
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Fractal ventilation enhances respiratory sinus arrhythmia
W Alan C Mutch, M Ruth Graham, Linda G Girling, John F Brewster
Respiratory Research , 2005, DOI: 10.1186/1465-9921-6-41
Abstract: Pigs were anaesthetised with propofol/ketamine, paralysed with doxacurium, and ventilated in either control mode (CV) or in fractal mode (FV) at baseline and then following infusion of oleic acid to result in lung injury.Mean RSA and mean positive RSA were nearly double with FV, both at baseline and following oleic acid. At baseline, mean RSA = 18.6 msec with CV and 36.8 msec with FV (n = 10; p = 0.043); post oleic acid, mean RSA = 11.1 msec with CV and 21.8 msec with FV (n = 9, p = 0.028); at baseline, mean positive RSA = 20.8 msec with CV and 38.1 msec with FV (p = 0.047); post oleic acid, mean positive RSA = 13.2 msec with CV and 24.4 msec with FV (p = 0.026). Heart rate variability was also greater with FV. At baseline the coefficient of variation for heart rate was 2.2% during CV and 4.0% during FV. Following oleic acid the variation was 2.1 vs. 5.6% respectively.These findings suggest FV enhances physiological entrainment between respiratory, brain stem and cardiac nonlinear oscillators, further supporting the concept that RSA itself reflects cardiorespiratory interaction. In addition, these results provide another mechanism whereby FV may be superior to conventional CV.Systems or computational biology – the use of mathematical analysis to examine complex biological systems – is becoming increasingly important [1,2]. Biological signals are complex, with fractal or even multi-fractal characteristics, and health is associated with fractal timing sequences [3]. For example, normal sinus rhythm is multi-fractal and the onset of congestive failure significantly attenuates this complex signal[4]. Respiratory sinus arrhythmia (RSA) – the increase in heart rate with inspiration and decrease with expiration – is one component of this complexity. It represents a dynamic interaction between respiratory, brain stem and cardiac oscillators that is physiologically advantageous. Hayano et al.[5]showed in dogs that positive RSA is associated with lower shunt fraction and lowe
Approaches to Brain Stress Testing: BOLD Magnetic Resonance Imaging with Computer-Controlled Delivery of Carbon Dioxide
W. Alan C. Mutch, Daniel M. Mandell, Joseph A. Fisher, David J. Mikulis, Adrian P. Crawley, Olivia Pucci, James Duffin
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047443
Abstract: Background An impaired vascular response in the brain regionally may indicate reduced vascular reserve and vulnerability to ischemic injury. Changing the carbon dioxide (CO2) tension in arterial blood is commonly used as a cerebral vasoactive stimulus to assess the cerebral vascular response, changing cerebral blood flow (CBF) by up to 5–11 percent/mmHg in normal adults. Here we describe two approaches to generating the CO2 challenge using a computer-controlled gas blender to administer: i) a square wave change in CO2 and, ii) a ramp stimulus, consisting of a continuously graded change in CO2 over a range. Responses were assessed regionally by blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI). Methodology/Principal Findings We studied 8 patients with known cerebrovascular disease (carotid stenosis or occlusion) and 2 healthy subjects. The square wave stimulus was used to study the dynamics of the vascular response, while the ramp stimulus assessed the steady-state response to CO2. Cerebrovascular reactivity (CVR) maps were registered by color coding and overlaid on the anatomical scans generated with 3 Tesla MRI to assess the corresponding BOLD signal change/mmHg change in CO2, voxel-by-voxel. Using a fractal temporal approach, detrended fluctuation analysis (DFA) maps of the processed raw BOLD signal per voxel over the same CO2 range were generated. Regions of BOLD signal decrease with increased CO2 (coded blue) were seen in all of these high-risk patients, indicating regions of impaired CVR. All patients also demonstrated regions of altered signal structure on DFA maps (Hurst exponents less than 0.5; coded blue) indicative of anti-persistent noise. While ‘blue’ CVR maps remained essentially stable over the time of analysis, ‘blue’ DFA maps improved. Conclusions/Significance This combined dual stimulus and dual analysis approach may be complementary in identifying vulnerable brain regions and thus constitute a regional as well as global brain stress test.
Dementia and Depression with Ischemic Heart Disease: A Population-Based Longitudinal Study Comparing Interventional Approaches to Medical Management
W. Alan C. Mutch,Randall R. Fransoo,Barry I. Campbell,Dan G. Chateau,Monica Sirski,R. Keith Warrian
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017457
Abstract: We compared the proportion of ischemic heart disease (IHD) patients newly diagnosed with dementia and depression across three treatment groups: percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical management alone (IHD-medical).
Mathematical modelling to centre low tidal volumes following acute lung injury: A study with biologically variable ventilation
M Ruth Graham, Craig J Haberman, John F Brewster, Linda G Girling, Bruce M McManus, W Alan C Mutch
Respiratory Research , 2005, DOI: 10.1186/1465-9921-6-64
Abstract: Pigs (n = 22) received pentothal/midazolam anaesthesia, oleic acid lung injury, then inspiratory P-V curve fitting to the four-parameter logistic Venegas equation F(P) = a + b[1 + e-(P-c)/d]-1 where: a = volume at lower asymptote, b = the vital capacity or the total change in volume between the lower and upper asymptotes, c = pressure at the inflection point and d = index related to linear compliance. Both groups received BVV with gas exchange and respiratory mechanics measured hourly for 5 hrs. Postmortem bronchoalveolar fluid was analysed for interleukin-8 (IL-8).All P-V curves fit the Venegas equation (R2 > 0.995). Control VT averaged 7.4 ± 0.4 mL/kg as compared to Experimental 9.5 ± 1.6 mL/kg (range 6.6 – 10.8 mL/kg; p < 0.05). Variable VTs were within the convex portion of the P-V curve. In such circumstances, Jensen's inequality states "if F(P) is a convex function defined on an interval (r, s), and if P is a random variable taking values in (r, s), then the average or expected value (E) of F(P); E(F(P)) > F(E(P))." In both groups the inequality applied, since F(P) defines volume in the Venegas equation and (P) pressure and the range of VTs varied within the convex interval for individual P-V curves. Over 5 hrs, there were no significant differences between groups in minute ventilation, airway pressure, blood gases, haemodynamics, respiratory compliance or IL-8 concentrations.No difference between groups is a consequence of BVV occurring on the convex interval for individualised Venegas P-V curves in all experiments irrespective of group. Jensen's inequality provides theoretical proof of why a variable ventilatory approach is advantageous under these circumstances. When using BVV, with VT centred by Venegas P-V curve analysis at the point of maximal compliance change, some leeway in low VT settings beyond ARDSNet protocols may be possible in acute lung injury. This study also shows that in this model, the standard ARDSNet algorithm assures ventilation occurs o
Cerebral Oxygen Saturation: Graded Response to Carbon Dioxide with Isoxia and Graded Response to Oxygen with Isocapnia
W. Alan C. Mutch, Sunni R. Patel, Ayda M. Shahidi, Susith I. Kulasekara, Joseph A. Fisher, James Duffin, Christopher Hudson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057881
Abstract: Background Monitoring cerebral saturation is increasingly seen as an aid to management of patients in the operating room and in neurocritical care. How best to manipulate cerebral saturation is not fully known. We examined cerebral saturation with graded changes in carbon dioxide tension while isoxic and with graded changes in oxygen tension while isocapnic. Methodology/Principal Findings The study was approved by the Research Ethics Board of the University Health Network at the University of Toronto. Thirteen studies were undertaken in healthy adults with cerebral oximetry by near infrared spectroscopy. End-tidal gas concentrations were manipulated using a model-based prospective end-tidal targeting device. End-tidal carbon dioxide was altered ±15 mmHg from baseline in 5 mmHg increments with isoxia (clamped at 110±4 mmHg). End-tidal oxygen was changed to 300, 400, 500, 80, 60 and 50 mmHg under isocapnia (37±2 mmHg). Twelve studies were completed. The end-tidal carbon dioxide versus cerebral saturation fit a linear relationship (R2 = 0.92±0.06). The end-tidal oxygen versus cerebral saturation followed log-linear behaviour and best fit a hyperbolic relationship (R2 = 0.85±0.10). Cerebral saturation was maximized in isoxia at end-tidal carbon dioxide of baseline +15 mmHg (77±3 percent). Cerebral saturation was minimal in isocapnia at an end-tidal oxygen tension of 50 mmHg (61±3 percent). The cerebral saturation during normoxic hypocapnia was equivalent to normocapnic hypoxia of 60 mmHg. Conclusions/Significance Hypocapnia reduces cerebral saturation to an extent equivalent to moderate hypoxia.
Brain MRI CO2 Stress Testing: A Pilot Study in Patients with Concussion
W. Alan C. Mutch, Michael J. Ellis, M. Ruth Graham, Vincent Wourms, Roshan Raban, Joseph A. Fisher, David Mikulis, Jeffrey Leiter, Lawrence Ryner
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0102181
Abstract: Background There is a real need for quantifiable neuro-imaging biomarkers in concussion. Here we outline a brain BOLD-MRI CO2 stress test to assess the condition. Methods This study was approved by the REB at the University of Manitoba. A group of volunteers without prior concussion were compared to post-concussion syndrome (PCS) patients – both symptomatic and recovered asymptomatic. Five 3-minute periods of BOLD imaging at 3.0 T were studied – baseline 1 (BL1– at basal CO2 tension), hypocapnia (CO2 decreased ~5 mmHg), BL2, hypercapnia (CO2 increased ~10 mmHg) and BL3. Data were processed using statistical parametric mapping (SPM) for 1st level analysis to compare each subject’s response to the CO2 stress at the p = 0.001 level. A 2nd level analysis compared each PCS patient’s response to the mean response of the control subjects at the p = 0.05 level. Results We report on 5 control subjects, 8 symptomatic and 4 asymptomatic PCS patients. Both increased and decreased response to CO2 was seen in all PCS patients in the 2nd level analysis. The responses were quantified as reactive voxel counts: whole brain voxel counts (2.0±1.6%, p = 0.012 for symptomatic patients for CO2 response < controls and 3.0±5.1%, p = 0.139 for CO2 response > controls: 0.49±0.31%, p = 0.053 for asymptomatic patients for CO2 response < controls and 4.4±6.8%, p = 0.281 for CO2 response > controls). Conclusions Quantifiable alterations in regional cerebrovascular responsiveness are present in concussion patients during provocative CO2 challenge and BOLD MRI and not in healthy controls. Future longitudinal studies must aim to clarify the relationship between CO2 responsiveness and individual patient symptoms and outcomes.
A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury
Duane J Funk, M Ruth Graham, Linda G Girling, James A Thliveris, Bruce M McManus, Elizabeth KY Walker, Edward S Rector, Craig Hillier, J Elliott Scott, W Alan C Mutch
Respiratory Research , 2004, DOI: 10.1186/1465-9921-5-22
Abstract: We compared gas exchange, respiratory mechanics, and measured bronchoalveolar fluid for inflammatory cytokines, cell counts and surfactant function. Lung injury was scored by light microscopy. Pigs received mechanical ventilation (FIO2 = 0.3; PEEP 5 cm H2O) in control mode until PaO2 decreased to 60 mm Hg with oleic acid infusion (PaO2/FIO2 <200 mm Hg). Additional PEEP to 10 cm H2O was added after injury. Animals were randomized to one of the 3 modes of ventilation and followed for 5 hr after injury.PaO2 and respiratory system compliance was significantly greater with biologically variable ventilation compared to the other 2 groups. Mean and mean peak airway pressures were also lower. There were no differences in cell counts in bronchoalveolar fluid by flow cytometry, or interleukin-8 and -10 levels between groups. Lung injury scoring revealed no difference between groups in the regions examined. No differences in surfactant function were seen between groups by capillary surfactometry.In this porcine model of acute lung injury, various indices to measure injury or inflammation did not differ between the 3 approaches to ventilation. However, when using a low tidal volume strategy with moderate levels of PEEP, sustained improvements in arterial oxygen tension and respiratory system compliance were only seen with BVV when compared to CMV or CMV with a recruitment manoeuvre.A negative consequence of mechanical ventilation using lower tidal volumes (VT) in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is alveolar collapse [1-3]. Numerous strategies to recruit these collapsed units have been advocated, but the efficacy of various recruitment manoeuvres for improving and sustaining gas exchange is controversial. Increased PEEP levels have been advocated to maintain patency of the recruited lung, but higher levels of PEEP can cause regional overinflation [4], potentially contributing to ventilator associated lung injury [5]. Moreover, r
Dark-ages reionization and galaxy formation simulation III: Modelling galaxy formation and the Epoch of Reionization
Simon J. Mutch,Paul M. Geil,Gregory B. Poole,Paul W. Angel,Alan R. Duffy,Andrei Mesinger,J. Stuart B. Wyithe
Physics , 2015,
Abstract: We introduce Meraxes, a new, purpose-built semi-analytic galaxy formation model designed for studying galaxy growth during reionization. Meraxes is the first model of its type to include a temporally- and spatially-coupled treatment of reionization and is built upon a custom (100 Mpc)$^3$ N-body simulation with high temporal and mass resolution, allowing us to resolve the galaxy and star formation physics relevant to early galaxy formation. Our fiducial model with supernova feedback reproduces the observed optical depth to electron scattering and evolution of the galaxy stellar mass function between $z$=5-7, predicting that a broad range of halo masses contribute to reionization. Using a constant escape fraction and global recombination rate, our model is unable to simultaneously match the observed ionizing emissivity at $z{\lesssim}6$. However, the use of an evolving escape fraction of 0.05-0.1 at $z{\sim}6$, increasing towards higher redshift, is able to satisfy these three constraints. We also demonstrate that photoionization suppression of low mass galaxy formation during reionization has only a small effect on the ionization history of the inter-galactic medium. This lack of "self-regulation" arises due to the already efficient quenching of star formation by supernova feedback. It is only in models with gas supply limited star formation that reionization feedback is effective at regulating galaxy growth. We similarly find that reionization has only a small effect on the stellar mass function, with no observationally detectable imprint at $M_{\rm *}{>}10^{7.5}\,{\rm M_\odot}$. However, patchy reionization has significant effects on individual galaxy masses, with variations of factors of 2-3 at $z$=5 that correlate with environment.
Dark-ages reionization & galaxy formation simulation IV: UV luminosity functions of high-redshift galaxies
Chuanwu Liu,Simon J. Mutch,P. W. Angel,Alan R. Duffy,Paul M. Geil,Gregory B. Poole,Andrei Mesinger,J. Stuart B. Wyithe
Physics , 2015,
Abstract: In this paper we present calculations of the UV luminosity function predictions from the Dark-ages Reionization And Galaxy-formation Observables from Numerical Simulations (DRAGONS) project, which combines N-body, semi-analytic and semi-numerical modeling designed to study galaxy formation during the Epoch of Reionization. Using galaxy formation physics including supernova feedback, the model naturally reproduces the UV LFs for high-redshift star-forming galaxies from $z{\sim}5$ through to $z{\sim}10$. We investigate the predicted luminosity-star formation rate (SFR) relation, finding that variable SFR histories of galaxies result in a scatter around the mean relation of $0.1$-$0.3$ dex depending on UV luminosity. We find close agreement between the model and observationally derived SFR functions. We use our predicted luminosities to investigate the luminosity function below current detection limits, and the ionizing photon budget for reionization. We predict that the slope of the UV LF remains steep below current detection limits and becomes flat at $M_\mathrm{UV}{\gtrsim}{-14}$. We find that $48$ ($17$) per cent of the total UV flux at $z{\sim}6$ ($10$) has been detected above an observational limit of $M_\mathrm{UV}{\sim}{-17}$, and that galaxies fainter than $M_\mathrm{UV}{\sim}{-17}$ are the main source of ionizing photons for reionzation. We investigate the luminosity-stellar mass relation, and find a correlation for galaxies with $M_\mathrm{UV}{<}{-14}$ that has the form $M_\bigstar{\propto}10^{-0.47M_\mathrm{UV}}$, in good agreement with observations, but which flattens for fainter galaxies. We determine the luminosity-halo mass relation to be $M_\mathrm{vir}{\propto}10^{-0.35M_\mathrm{UV}}$, finding that galaxies with $M_\mathrm{UV}{=}{-20}$ reside in host dark matter haloes of $10^{11.0\pm 0.1}\mathrm{M_\odot}$ at $z{\sim}6$, and that this mass decreases towards high redshift.
Dark-ages Reionization & Galaxy Formation Simulation II: Spin and concentration parameters for dark matter haloes during the Epoch of Reionization
Paul W. Angel,Gregory B. Poole,Aaron D. Ludlow,Alan R. Duffy,Paul M. Geil,Simon J. Mutch,Andrei Mesinger,J. Stuart B. Wyithe
Physics , 2015,
Abstract: We use high resolution N-Body simulations to study the concentration and spin parameters of dark matter haloes in the mass range $10^8\, {\rm M}_{\odot}\, h^{-1} < {\rm M} < 10^{11}\, {\rm M}_{\odot}\, h^{-1}$ and redshifts $5{<}z{<}10$, corresponding to the haloes of galaxies thought to be responsible for reionization. We build a sub-sample of equilibrium haloes and contrast their properties to the full population that also includes unrelaxed systems. Concentrations are calculated by fitting both NFW and Einasto profiles to the spherically-averaged density profiles of individual haloes. After removing haloes that are out-of-equilibrium, we find a $z{>}5$ concentration$-$mass ($c(M)$) relation that is almost flat and well described by a simple power-law for both NFW and Einasto fits. The intrinsic scatter around the mean relation is $\Delta c_{\rm{vir}}{\sim1}$ (or 20 per cent) at $z=5$. We also find that the analytic model proposed by Ludlow et al. reproduces the mass and redshift-dependence of halo concentrations. Our best-fit Einasto shape parameter, $\alpha$, depends on peak height, $\nu$, in a manner that is accurately described by $\alpha {=}0.0070\nu^2{+}0.1839$. The distribution of the spin parameter, $\lambda$, has a weak dependence on equilibrium state; $\lambda$ peaks at roughly ${\sim}0.033$ for our relaxed sample, and at ${\sim}0.04$ for the full population. The spin--virial mass relation has a mild negative correlation at high redshift.
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