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Methods for Improving Screening for Vascular Cognitive Impairment Using the Montreal Cognitive Assessment
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- Khush-Bakht Zaidi, Jill B. Rich, Kelly M. Sunderland, Malcolm A. Binns, Linda Truong, Paula M. McLaughlin, Bradley Pugh, Donna Kwan, Derek Beaton, Brian Levine, Demetrios J. Sahlas, Dariush Dowlatshahi, Ayman Hassan, Jennifer Mandzia, The ONDRI Investigators, Angela K. Troyer, Richard H. Swartz
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 47 / Issue 6 / November 2020
- Published online by Cambridge University Press:
- 11 June 2020, pp. 756-763
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Background:
Vascular cognitive impairment (VCI) post-stroke is frequent but may go undetected, which highlights the need to better screen cognitive functioning following a stroke.
Aim:We examined the clinical utility of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment against a gold-standard neuropsychological battery.
Methods:We assessed cognitive status with a comprehensive battery of neuropsychological tests in 161 individuals who were at least 3-months post-stroke. We used receiver operating characteristic (ROC) curves to identify two cut points for the MoCA to maximize sensitivity and specificity at a minimum 90% threshold. We examined the utility of the Symbol Digit Modalities Test, a processing speed measure, to determine whether this additional metric would improve classification relative to the MoCA total score alone.
Results:Using two cut points, 27% of participants scored ≤ 23 and were classified as high probability of cognitive impairment (sensitivity 92%), and 24% of participants scored ≥ 28 and were classified as low probability of cognitive impairment (specificity 91%). The remaining 48% of participants scored from 24 to 27 and were classified as indeterminate probability of cognitive impairment. The addition of a processing speed measure improved classification for the indeterminate group by correctly identifying 65% of these individuals, for an overall classification accuracy of 79%.
Conclusions:The utility of the MoCA in detecting cognitive impairment post-stroke is improved when using a three-category approach. The addition of a processing speed measure provides a practical and efficient method to increase confidence in the determined outcome while minimally extending the screening routine for VCI.
The Ontario Neurodegenerative Disease Research Initiative (ONDRI)
- Sali M. K. Farhan, Robert Bartha, Sandra E. Black, Dale Corbett, Elizabeth Finger, Morris Freedman, Barry Greenberg, David A. Grimes, Robert A. Hegele, Chris Hudson, Peter W. Kleinstiver, Anthony E. Lang, Mario Masellis, William E. McIlroy, Paula M. McLaughlin, Manuel Montero-Odasso, David G. Munoz, Douglas P. Munoz, Stephen Strother, Richard H. Swartz, Sean Symons, Maria Carmela Tartaglia, Lorne Zinman, ONDRI Investigators, Michael J. Strong
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 44 / Issue 2 / March 2017
- Published online by Cambridge University Press:
- 22 December 2016, pp. 196-202
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Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
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Stratified flows with vertical layering of density: experimental and theoretical study of flow configurations and their stability
- Roberto Camassa, Richard M. McLaughlin, Matthew N. J. Moore, Kuai Yu
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- Journal of Fluid Mechanics / Volume 690 / 10 January 2012
- Published online by Cambridge University Press:
- 25 November 2011, pp. 571-606
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A vertically moving boundary in a stratified fluid can create and maintain a horizontal density gradient, or vertical layering of density, through the mechanism of viscous entrainment. Experiments to study the evolution and stability of axisymmetric flows with vertically layered density are performed by towing a narrow fibre upwards through a stably stratified viscous fluid. The fibre forms a closed loop and thus its effective length is infinite. A layer of denser fluid is entrained and its thickness is measured by implementing tracking analysis of dyed fluid images. Thickness values of up to 70 times that of the fibre are routinely obtained. A lubrication model is developed for both a two-dimensional geometry and the axisymmetric geometry of the experiment, and shown to be in excellent agreement with dynamic experimental measurements once subtleties of the optical tracking are addressed. Linear stability analysis is performed on a family of exact shear solutions, using both asymptotic and numerical methods in both two dimensions and the axisymmetric geometry of the experiment. It is found analytically that the stability properties of the flow depend strongly on the size of the layer of heavy fluid surrounding the moving boundary, and that the flow is neutrally stable to perturbations in the large-wavelength limit. At the first correction of this limit, a critical layer size is identified that separates stable from unstable flow configurations. Surprisingly, in all of the experiments the size of the entrained layer exceeds the threshold for instability, yet no unstable behaviour is observed. This is a reflection of the small amplification rate of the instability, which leads to growth times much longer than the duration of the experiment. This observation illustrates that for finite times the hydrodynamic stability of a flow does not necessarily correspond to whether or not that flow can be realised from an initial-value problem. Similar instabilities that are neutral to leading order with respect to long waves can arise under the different physical mechanism of viscous stratification, as studied by Yih (J. Fluid Mech., vol. 27, 1967, pp. 337–352), and we draw a comparison to that scenario.
Lagrangian blocking in highly viscous shear flows past a sphere
- ROBERTO CAMASSA, RICHARD M. McLAUGHLIN, LONGHUA ZHAO
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- Journal of Fluid Mechanics / Volume 669 / 25 February 2011
- Published online by Cambridge University Press:
- 16 February 2011, pp. 120-166
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An analytical and computational study of Lagrangian trajectories for linear shear flow past a sphere or spheroid at low Reynolds numbers is presented. Using the exact solutions available for the fluid flow in this geometry, we discover and analyse blocking phenomena, local bifurcation structures and their influence on dynamical effects arising in the fluid particle paths. In particular, building on the work by Chwang & Wu, who established an intriguing blocking phenomenon in two-dimensional flows, whereby a cylinder placed in a linear shear prevents an unbounded region of upstream fluid from passing the body, we show that a similar blocking exists in three-dimensional flows. For the special case when the sphere is centred on the zero-velocity plane of the background shear, the separatrix streamline surfaces which bound the blocked region are computable in closed form by quadrature. This allows estimation of the cross-sectional area of the blocked flow showing how the area transitions from finite to infinite values, depending on the cross-section location relative to the body. When the sphere is off-centre, the quadrature appears to be unavailable due to the broken up-down mirror symmetry. In this case, computations provide evidence for the persistence of the blocking region. Furthermore, we document a complex bifurcation structure in the particle trajectories as the sphere centre is moved from the zero-velocity plane of the background flow. We compute analytically the emergence of different fixed points in the flow and characterize the global streamline topology associated with these fixed points, which includes the emergence of a three-dimensional bounded eddy. Similar results for the case of spheroids are considered in Appendix B. Additionally, the broken symmetry offered by a tilted spheroid geometry induces new three-dimensional effects on streamline deflection, which can be viewed as effective positive or negative suction in the horizontal direction orthogonal to the background flow, depending on the tilt orientation. We conclude this study with results on the case of a sphere embedded at a generic position in a rotating background flow, with its own prescribed rotation including fixed and freely rotating. Exact closed-form solutions for fluid particle trajectories are derived.
A first-principle predictive theory for a sphere falling through sharply stratified fluid at low Reynolds number
- ROBERTO CAMASSA, CLAUDIA FALCON, JOYCE LIN, RICHARD M. McLAUGHLIN, NICHOLAS MYKINS
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- Journal of Fluid Mechanics / Volume 664 / 10 December 2010
- Published online by Cambridge University Press:
- 12 October 2010, pp. 436-465
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A sphere exhibits a prolonged residence time when settling through a stable stratification of miscible fluids due to the deformation of the fluid-density field. Using a Green's function formulation, a first-principles numerically assisted theoretical model for the sphere–fluid coupled dynamics at low Reynolds number is derived. Predictions of the model, which uses no adjustable parameters, are compared with data from an experimental investigation with spheres of varying sizes and densities settling in stratified corn syrup. The velocity of the sphere as well as the deformation of the density field are tracked using time-lapse images, then compared with the theoretical predictions. A settling rate comparison with spheres in dense homogeneous fluid additionally quantifies the effect of the enhanced residence time. Analysis of our theory identifies parametric trends, which are also partially explored in the experiments, further confirming the predictive capability of the theoretical model. The limit of infinite fluid domain is considered, showing evidence that the Stokes paradox of infinite fluid volume dragged by a moving sphere can be regularized by density stratifications. Comparisons with other possible models under a hierarchy of additional simplifying assumptions are also presented.
Trajectory and flow properties for a rod spinning in a viscous fluid. Part 1. An exact solution
- ROBERTO CAMASSA, TERRY JO LEITERMAN, RICHARD M. MCLAUGHLIN
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- Journal of Fluid Mechanics / Volume 612 / 10 October 2008
- Published online by Cambridge University Press:
- 10 October 2008, pp. 153-200
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An exact mathematical solution for the low-Reynolds-number quasi-steady hydrodynamic motion induced by a rod in the form of a prolate spheroid sweeping a symmetric double cone is developed, and the influence of the ensuing fluid motion upon passive particles is studied. The resulting fluid motion is fully three-dimensional and time varying. The advected particles are observed to admit slow orbits around the rotating rods and a fast epicyclic motion roughly commensurate with the rod rotation rate. The epicycle amplitudes, vertical fluctuations, arclengths and angle travelled per rotation are mapped as functions of their initial coordinates and rod geometry. These trajectories exhibit a rich spatial structure with greatly varying trajectory properties. Laboratory frame asymmetries of these properties are explored using integer time Poincaré sections and far-field asymptotic analysis. This includes finding a small cone angle invariant in the limit of large spherical radius whereas an invariant for arbitrary cone angles is obtained in the limit of large cylindrical radius. The Eulerian and Lagrangian flow properties of the fluid flow are studied and shown to exhibit complex structures in both space and time. In particular, spatial regions of high speed and Lagrangian velocities possessing multiple extrema per rod rotation are observed. We establish the origin of these complexities via an auxiliary flow in a rotating frame, which provides a generator that defines the epicycles. Finally, an additional spin around the major spheroidal axis is included in the exact hydrodynamic solution resulting in enhanced vertical spatial fluctuation as compared to the spinless counterpart. The connection and relevance of these observations with recent developments in nano-scale fluidics is discussed, where similar epicycle behaviour has been observed. The present study is of direct use to nano-scale actuated fluidics.
Sensitive enhanced diffusivities for flows with fluctuating mean winds: a two-parameter study
- JAMES BONN, RICHARD M. McLAUGHLIN
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- Journal:
- Journal of Fluid Mechanics / Volume 445 / 25 October 2001
- Published online by Cambridge University Press:
- 16 October 2001, pp. 345-375
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Enhanced diffusion coefficients arising from the theory of periodic homogenized averaging for a passive scalar diffusing in the presence of a large-scale, fluctuating mean wind superimposed upon a small-scale, steady flow with non-trivial topology are studied. The purpose of the study is to assess how the extreme sensitivity of enhanced diffusion coefficients to small variations in large-scale flow parameters previously exhibited for steady flows in two spatial dimensions is modified by either the presence of temporal fluctuation, or the consideration of fully three-dimensional steady flow. We observe the various mixing parameters (Péclet, Strouhal and periodic Péclet numbers) and related non-dimensionalizations. We document non-monotonic Péclet number dependence in the enhanced diffusivities, and address how this behaviour is camouflaged with certain non-dimensional groups. For asymptotically large Strouhal number at fixed, bounded Péclet number, we establish that rapid wind fluctuations do not modify the steady theory, whereas for asymptotically small Strouhal number the enhanced diffusion coefficients are shown to be represented as an average over the steady geometry. The more difficult case of large Péclet number is considered numerically through the use of a conjugate gradient algorithm. We consider Péclet-number-dependent Strouhal numbers, S = QPe−(1+γ), and present numerical evidence documenting critical values of γ which distinguish the enhanced diffusivities as arising simply from steady theory (γ < −1) for which fluctuation provides no averaging, fully unsteady theory (γ ∈ (−1, 0)) with closure coefficients plagued by non-monotonic Péclet number dependence, and averaged steady theory (γ > 0). The transitional case with γ = 0 is examined in detail. Steady averaging is observed to agree well with the full simulations in this case for Q [les ] 1, but fails for larger Q. For non-sheared flow, with Q [les ] 1, weak temporal fluctuation in a large-scale wind is shown to reduce the sensitivity arising from the steady flow geometry; however, the degree of this reduction is itself strongly dependent upon the details of the imposed fluctuation. For more intense temporal fluctuation, strongly aligned orthogonal to the steady wind, time variation averages the sensitive scaling existing in the steady geometry, and the present study observes a Pe1 scaling behaviour in the enhanced diffusion coefficients at moderately large Péclet number. Finally, we conclude with the numerical documentation of sensitive scaling behaviour (similar to the two-dimensional steady case) in fully three dimensional ABC flow.