Table Of ContentModelling Methodology for Physiology and Medicine
Second Edition
Modelling Methodology for
Physiology and Medicine
Second Edition
Ewart Carson
Centre for Health Informatics
City University London
London, UK
Claudio Cobelli
Department of Information Engineering
University of Padova
Padova, Italy
AMSTERDAM(cid:1)BOSTON(cid:1)HEIDELBERG(cid:1)LONDON(cid:1)NEWYORK(cid:1)OXFORD
PARIS(cid:1)SANDIEGO(cid:1)SANFRANCISCO(cid:1)SINGAPORE(cid:1)SYDNEY(cid:1)TOKYO
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Firstedition2001
Secondedition2014
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Preface
Mathematicalmodelling is now widely adopted inphysiology andmedicine tosup-
port the life scientist and clinical worker. However, good modelling practice must
be based upon sound methodology. This is the focus of this book. It builds upon
the basic idea of an integrated methodology for the development and testing of
mathematical models. It covers many specific areas of methodology in which
important advances have taken place over recent years and illustrates the applica-
tionofgoodmethodologicalpracticeinkeyareasofphysiologyandmedicine.
Over the past few decades, several books have been written on mathematical
modelling in physiology and medicine. Some have focused on methodology, while
others have centred around a specific area of physiology and medicine. Over the
past 20 years, we ourselves have contributed extensively tothis field, including our
volume from the early 1980s entitled Mathematical Modelling of Metabolic and
Endocrine Systems: Model Formulation, Identification and Validation, which com-
bined methodological detail with a demonstration of its applicability in relation to
metabolicsandendocrinology.
This present volume follows suit by combining advances in methodology with
demonstration of its applicability. It is one of two volumes on the theme of model-
ling included in this Biomedical Engineering series. The other one, which is cur-
rently in production, provides an introduction to modelling in physiology. The
essence of our other volume is summarized in the first chapter of this book. This
book serves as both a stand-alone volume and a complementary work. For the
reader who has some experience in modelling, this volume will provide an accessi-
ble account of recent advances in the field. For the reader who has absorbed the
messagesoftheintroductoryvolume,thechaptershereinbuildlogicallyuponthose
insights.
This book has been designed to appeal to all those who wish to advance their
knowledge of good modelling practice. It will be useful to postgraduate students
and those in the final year of study who have chosen modelling specialities as part
of biomedical engineering or medical or health informatics courses. It is equally
designed tomeetthe needs of advanced practitioners and researchers in the field of
modellingasitappliestophysiologyandmedicine.
Although formally an edited text, this volume is the collaborative work of two
teams in London and Padova who together have extensive experience in communi-
catingtheseideasandconceptstoawiderangeofaudiences,includingundergradu-
ate and postgraduate students, and researchers and professionals across a spectrum
of disciplines from engineering and informatics to medicine and related clinical
xviii Preface
professions. Hence, this book has been produced as an integrated work, meant as
tutorialinstyleandcontainingreferences attheendofthevolume.
In writing this volume, we thank those of our colleagues in our teams who have
chosen to work with us on this project. Their support and encouragement has been
greatly appreciated, and without their efforts this volume would not exist. We also
wish tothankourfriends andcolleagues, whoover manyyearshaveencouraged us
todevelopourmodellingideas,whetherfromtheirperspectivesasfellowengineers
and computer scientists or from their invaluable viewpoints as physiologists and
clinicians. There are many that we would wish to recognize, including Riccardo
Bonadonna, Derek Cramp, Ludwik Finkelstein, Antonio Lepschy, and Peter
So¨nksen.
Finally, we thank Joseph Bronzino, Editor-In-Chief of this Biomedical
Engineering Series, and Joel Claypool, Jane Phelan, and colleagues at Academic
Press for their encouragement, support, and tolerance in working with us to see our
ideascometofruition.
July2000
EwartCarsonandClaudioCobelli
London,EnglandandPadova,Italy
Preface to the Second Edition
In the 12 years that have passed since the first edition was published, considerable
progress has occurred in this field of modelling in physiology and medicine.
Advances have taken place in modelling methodology, availability of new data,
and increased application, both in terms of numbers of studies and new areas of
application. In light of this progress we have been invited to produce this second
edition.Accordingly,thisvolumerepresentsasignificantexpansionofthefirstedi-
tion(from13to23chapters)inorderthatcoveragecanbegiventothese important
developments.Inaddition,almostallofthematerialisnew.
We shouldfirstliketothankalloftheauthorswho havechosentoworkwithus
on this project. In addition, we express our appreciation to Sarah Lay, Erin Hill-
Parks, Cari Owen, and Fiona Geraghty of the Elsevier editorial team for their tech-
nicalexpertiseandsupport.
September2013
EwartCarsonandClaudioCobelli
Ludlow,EnglandandPadova,Italy
List of Contributors
Steen Andreassen Center for Model-Based Medical Decision Support (MMDS),
AalborgUniversity,Denmark
James B. Bassingthwaighte Department of Bioengineering, University of
Washington,Seattle,WA,USA
Riccardo Bellazzi Department of Electrical, Computer and Biomedical
Engineering,UniversityofPavia,Pavia,Italy
B. Wayne Bequette Department of Chemical & Biological Engineering,
RensselaerPolytechnicInstitute,Troy,NY,USA
Alessandra Bertoldo Department of Information Engineering, University of
Padova,Padova,Italy
Roberto Burattini Previously at the Department of Information Engineering,
PolytechnicUniversityofMarche,Italy;DepartmentofVeterinaryandComparative
Anatomy, Pharmacology and Physiology, Washington State University, Pullman,
Washington,USA
EwartCarsonCentreforHealthInformatics,CityUniversityLondon,London,UK
Andrea Caumo Dipartimento di Scienze Biomediche per la Salute, Universita´ di
Milano,Milano,Italy
Claudio Cobelli Department of Information Engineering, University of Padova,
Padova,Italy
Filippo Cona Department of Electrical, Electronic, and Information Engineering,
UniversityofBologna
Chiara Dalla Man Department of Information Engineering, University of Padova,
Padova,Italy
Giuseppe De Nicolao Dipartimento di Informatica e Sistemistica, University of
Pavia,Pavia,Italy
xxii ListofContributors
Barbara Di Camillo Department of Information Engineering, University of
Padova,Padova,Italy
Francis J Doyle, III Department of Chemical Engineering, University of
California Santa Barbara, Santa Barbara, CA; Institute for Collaborative
Biotechnologies,UniversityofCaliforniaSantaBarbara,SantaBarbara,CA,USA
Fulvia Ferrazzi Institute of Human Genetics, Friedrich-Alexander-Universita¨t
Erlangen-Nu¨rnberg,Erlangen,Germany
Dan S. Karbing Respiratory and Critical Care Group (rcare), MMDS, Aalborg
University,Denmark
Søren Kjærgaard Anaesthesia and Intensive Care, Aalborg University Hospital,
Denmark
Boris Kovatchev Center for Diabetes Technology, University of Virginia,
Charlottesville, VA; Department of Systems and Information Engineering,
UniversityofVirginia,Charlottesville,VA,USA
Paolo Magni Dipartimento di Ingegneria Industriale e dell’Informazione,
Universita` degliStudidiPavia,Pavia,Italy
Elisa Magosso Department of Electrical, Electronic, and Information Engineering,
UniversityofBologna
Lorenzo Pasotti Dipartimento di Ingegneria Industriale e dell’Informazione,
Universita` degliStudidiPavia,Pavia,Italy
Stephen Patek Center for Diabetes Technology, University of Virginia,
Charlottesville, VA; Department of Systems and Information Engineering,
UniversityofVirginia,Charlottesville,VA,USA
Morten Gram Pedersen Department of Information Engineering, University of
Padova,Padova,Italy
Maria Pia Saccomani Department of Information Engineering, University of
Padova,Padova,Italy
Gianluigi Pillonetto Department of Information Engineering, University of
Padova,Padova,Italy
Italo Poggesi Model-Based Drug Development, Janssen R&D, Via Michelangelo
Buonarroti,ColognoMonzese(MI),Italy
ListofContributors xxiii
Alberto Redaelli Dipartimento di Elettronica, Informazione e Bioingegneria
(DEIB),PolitecnicodiMilano,Milan,Italy
Stephen E. Rees Respiratory and Critical Care Group (rcare), MMDS, Aalborg
University,Denmark
MaurizioRocchettiIndependentConsultant,Rho,Milan,Italy
Maria Rodriguez-Fernandez Department of Chemical Engineering, University
of California Santa Barbara, Santa Barbara, CA; Institute for Collaborative
Biotechnologies, University of California Santa Barbara, Santa Barbara,
CA,USA
Francesco Sambo Department of Information Engineering, University of Padova,
Padova,Italy
Zimi Sawacha Department of Information Engineering, University of Padova,
Padova,Italy
Bernhard Schrefler Department of Civil, Environmental and Architectural
Engineering,UniversityofPadova,Padova,Italy
Monica Simeoni Biopharm and ImmunoInflammation, Clinical Pharmacology,
Quantitative Sciences, GlaxoSmithKline, Stockley Park West, Uxbridge,
Middlesex,UK
Giovanni Sparacino Dipartimento di Ingegneria dell’Informazione, Universita` di
Padova,Padova,Italy
Peter C. St. John Department of Chemical Engineering, University of California
SantaBarbara,SantaBarbara,CA,USA
Gianna Toffolo Department of Information Engineering, University of Padova,
Padova,Italy
Mauro Ursino Department of Electrical, Electronic, and Information Engineering,
UniversityofBologna
Paolo Vicini Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide
Research and Development, San Diego, CA; Pharmacokinetics, Dynamics and
Metabolism, Pfizer Worldwide Research and Development, Science Center Drive,
SanDiego,CA,USA
xxiv ListofContributors
Emiliano Votta Dipartimento di Elettronica, Informazione e Bioingegneria
(DEIB),PolitecnicodiMilano,Milan,Italy
Ruoting Yang Institute for Collaborative Biotechnologies, University of California
SantaBarbara,SantaBarbara,CA,USA
Susanna Zucca Dipartimento di Ingegneria Industriale e dell’Informazione,
Universita` degliStudidiPavia,Pavia,Italy
