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Statistics for Biomedical
Engineers and Scientists
Statistics for Biomedical
Engineers and Scientists
How to Visualize and Analyze Data
Andrew P. King
Robert J. Eckersley
Academic Press is an imprint of Elsevier
125 London Wall, London EC2Y 5AS, United Kingdom
525 B Street, Suite 1650, San Diego, CA 92101, United States
50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States
The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom
Copyright © 2019 Elsevier Ltd. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic
or mechanical, including photocopying, recording, or any information storage and retrieval system,
without permission in writing from the publisher. Details on how to seek permission, further
information about the Publisher’s permissions policies and our arrangements with organizations such
as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website:
www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the
Publisher (other than as may be noted herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical treatment
may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any information, methods, compounds, or experiments described herein. In using such
information or methods they should be mindful of their own safety and the safety of others, including
parties for whom they have a professional responsibility.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume
any liability for any injury and/or damage to persons or property as a matter of products liability,
negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas
contained in the material herein.
ISBN: 978-0-08-102939-8
v
“The quiet statisticians have changed the world, not by discovering new facts
or technical developments but by changing the ways we reason, experiment,
and form our opinions about it.”
Ian Hacking
About the Authors
Together Andrew and Robert run the Computational Statistics module for
Biomedical Engineering students upon which this book was based.
xv
Preface
the methods that you are using (which we hope you do), then you can read
and understand these extra sections.
At the beginning of each chapter, clear learning objectives are provided. In the
chapter bodies a range of practical biomedical examples are used to illustrate
the concepts being presented. We also include Activities in the chapter bodies,
which enable the reader to test how well they have met each of the learning ob-
jectives. Solutions to all activities are available from the book’s web site. We use
MATLAB to illustrate the practical application of the statistical techniques we
describe.1 However, the MATLAB content is included at the end of each chapter
in a separate section, which can then be used by the reader to solve the practi-
cal Exercises that follow (which are also linked to the learning objectives at the
beginning of the chapter). Therefore it is possible to read this book purely as a
book about statistics and not engage with the MATLAB content at all. Having
said this, using an automated tool such as MATLAB makes visualizing and an-
alyzing data a lot easier, so we strongly recommend using one, even if it is not
MATLAB. We have done our best to ensure the realism of the data that we use
in our examples, activities, and exercises, and which are freely accessible to the
reader on the book’s web site. However, all data are completely synthetic, and
we take full responsibility for any lack of realism.
At the end of each chapter, we include a brief pen portrait of a famous figure
from the history of the field of statistics. Statistics is sometimes viewed as a dry
and lifeless subject. We hope that by bringing to life some of these significant
figures and linking their work to the concepts that we present, we can help to
overcome this myth.
Learning Objectives
Instructors
It is our intention that the book can be easily used as a companion to a taught
undergraduate or postgraduate module on statistics. We provide a full set of
teaching materials to instructors, which they are free to make use of and mod-
ify as they see fit. The book consists of eleven chapters, each of which could
reasonably be covered in a week of teaching. Depending on how many weeks
are available, instructors can use all or a selection of the chapters.
In our module at King’s College London we perform all teaching in a computer
laboratory. This allows us to quickly link theoretical concepts to practical appli-
cation and encourages hands-on skill acquisition. The teaching materials are
based upon this approach. However, if instructors prefer to separate the the-
ory and applications, for example, by having dedicated lectures and practical
laboratory sessions, then the materials can be adapted accordingly.
We recommend that the learning objectives included at the beginning of each
chapter should be used as the basis for any assessments. For example, a written
exam could test knowledge of the non-MATLAB learning objectives, and/or
practical courseworks could be used to test the MATLAB learning objectives.
Above all, we would like to express our gratitude to Graeme Penney. Graeme
codeveloped the materials for the original module from which this book was
developed. Much of the material in the book is based on Graeme’s original
notes, and he also wrote early versions of some of the text. We are grateful for
Graeme’s permission to build on this material to produce this book.
We would like to thank Esther Puyol Antón for providing the MR data that was
used in Chapters 10 and 11, and Kawal Rhode for permission to use the im-
age in Fig. 10.3. We also thank all previous King’s College London Biomedical
Engineering students and teaching assistants on the Computational Statistics
module for providing useful and constructive feedback, which has helped to
shape the book.
Finally, from the publishers Elsevier we thank Tim Pitts for his encouragement
and honest feedback on our original proposal and Joshua Mearns for his assis-
tance during the development of the book.
xxiii
CHAPTER 1
LEARNING OBJECTIVES
At the end of this chapter you should be able to:
1.1 INTRODUCTION
We are living in a world in which more and more data are being recorded.
As digital and computing advances are made, more data are generated, and
more sophisticated machines are developed to allow us to record, track and
measure data. Data are recorded in almost every discipline (e.g. economics,
health, business, politics, science and engineering), and extremely important
decisions are taken based upon analyzing these data. Statistics is the study
of how to correctly manipulate data to best inform such decisions. In par-
ticular, it helps us to deal with uncertainty in measurements. Outside of the
world of pure mathematics, data will always contain errors and variation.
Statistics enables us to decide when conclusions can be formed, despite our
data containing variation. It can be thought of as “mathematics meets the real
world.”
Statistics can be defined as the science of collecting and analyzing data. It can be
split into two main categories: 1
Dear little Angel. When I saw you tonight I adored you. You
are far removed from all other beings. If you wish to save a
suffering mortal, meet me in the woods where we last saw each
other. Otherwise my death may be on your hands. Fear nothing,
I will guard you as my own sister. At three tomorrow, but I will
wait till you come.
Your devoted servant and knight,
Hugh Desmond.
My Darling Hugh,
Where have you hidden yourself all this time? I have enquired
everywhere, but no one knows anything about you. I am in
such dreadful trouble, I must see you at once. It is too awful.
My husband knows all about us. When he came back from
Germany the servants told him I had been away, and he found
that we had been stopping at that hotel. He put a lawyer on the
track, and discovered everything. Oh! What are we to do! You
must come and advise me, and you will stand by me won’t you?
You know how much I love you, and you know you made me
unfaithful to my husband. You will not leave me now? He is
getting a divorce and what am I to do? I am staying with my
mother, as he will not have me. Do come to me.
Your broken-hearted
Winnie
There were tear stains, and corrections, and crosses at the end.
The letter was unfair and gross, and as Hugh looked up from reading
it, he contrasted in his mind the fair young girl, now throwing little
stones over the hedge to see them drop far below, and the
flamboyant beauty of the other, to whom now he must go, for so the
twisted honour of his race would have it.
“Come, Daphne, let us go back. It is getting late,” he said, but
there was a solemn note in his voice, which made her ask. “Have
you had bad news?”
“Oh no, just the ordinary worries, but it will probably mean I shall
have to go to England. Business affairs you know, but don’t trouble,
little girl, I shall not be away from you for long.”
A shadow crossed her lovely face. It was the first separation.
“Can’t I come too? I would love to see England properly, London
and the big cities.”
“I am afraid not this time, and besides you would hate the winter.
I must get a villa for you, and you can make everything ready for me
when I come back. It will be quite exciting for you, furnishing.”
And so it was arranged. Everything had to be done in a hurry, but
then he was used to that. He bought a charming little Villa at
Murano, and obtained servants for her, while she was to stay in
Venice till she had furnished it. On the last night she was sad.
“Come back soon,” she said “I shall be so lonely without you, and
…” she stopped.
He was tender with her, but there was a hunted look in his eyes.
He could see only one way out of the mess, and that he could not
tell her.
She faced the parting bravely, and he was proud of her. There was
no scene such as he had been accustomed to with others; she
smiled at him, and waved as the train moved out. Only when she got
home to the hotel, she went to her room and burst into a passionate
flood of tears.
Reckavile found all London talking about the case. The worthy
draper had filed his petition, and only awaited his turn to come to
the courts. Winnie he would not see, and rumour gathered round
the action Reckavile would take. Betting was about even on his
marrying the woman or killing the draper.
Those who knew him were certain he would face the music.
He paid two visits, one to his family lawyer to enter a defence,
and one to an intimate friend, Captain Wynter. He found the latter at
the Club, and with his usual abruptness opened at once.
“You’ve heard of this silly business about the man Wheatland,
eh?” Wynter nodded.
“Well, I want you to take a challenge to him. Tell him I’ll fight him
for the lady.”
“My dear fellow,” said the other, dropping his eyeglass in his
astonishment, “are you joking? That sort of thing is quite out of
date, unfortunately, otherwise one would not have to put up with
the insults one meets with nowadays.”
“I mean it quite seriously, I am in a devil of a mess, and if he can
plug me, all the better. It will end the line, and everyone will be
satisfied.”
Wynter looked at him, and realised he was serious, and in a
dangerous mood. It would be best to pacify him, and rather a joke
to frighten the draper; perhaps even it might stay proceedings.
He drew up the challenge with all the formality of a century ago,
and showed it to Reckavile, who gravely agreed, without apparently
seeing any humour in the situation.
Wynter dressed himself in his best, and hailing a hansom cab,
drove to Wheatland Emporium in Highbury.
He found him, an anxious worried little man, pompous and vain,
with horrible mutton chop whiskers.
He had risen by energy and hard work through the stages of
assistant to shop-walker and manager, until he had obtained a shop
of his own, and his middle aged affection had been lavished on his
cashier Winnie, then a beautiful young girl, and ambitious.
She had married him for his money, hoping to twist him round her
fingers, and found him vain and jealous, and exacting in his ideas
both of marital duty and spending limits.
Wynter he greeted with the artificial smile of the business man
expecting custom, and the latter bowed politely; he was enjoying his
part. “Mr. Wheatland, I believe?” he said.
“The same, sir, at your service,” answered the other.
“May I have a word with you, sir?” said the soldier.
“Certainly, come to my office.”
Seated in Wheatland’s private room, Wynter felt a sudden distaste
at his mission. After all, this poor man had been treated badly, and
he had his rights like anyone else.
“I am afraid I have come on an unpleasant errand,” he said “I
represent Lord Reckavile.”
The draper stiffened. “I do not wish to hear anything from that
man, my lawyer has the matter in hand.”
Wynter waved his hand. “This is not a lawyer’s business, but a
personal one—my friend Reckavile feels that you have a distinct
grievance, in fact that you have the right to demand satisfaction. He
is willing to waive his rank, and will meet you, if you will nominate a
second with whom I may arrange details.”
“A second, I don’t understand,” said the bewildered Wheatland.
“Exactly, a friend who will act for you. You can then fight for the
lady. He feels that as the aggrieved party you have the right to
challenge, but you might feel diffident on account of the disparity in
rank.” He produced his Cartel and spread it out.
The little man’s eyes fairly bulged in his head.
“Either you are playing a very discreditable practical joke, or your
friend is mad. Fight, sir, I never heard such rubbish. Are we back in
the Middle Ages? The Law, sir, will give me protection, and I shall
immediately communicate with my solicitor to stop this murderous
ruffian.”
Then his manner changed, and in a whining tone he said, “Is it
not enough that he has seduced my wife, whom I loved with all my
heart, but he must seek my life as well.”
Wynter felt uncomfortable, and cursed himself for coming.
He rose to his feet, and buttoned up his coat, thrusting his famous
challenge into his pocket.
“Then I may take it, Mr. Wheatland, that you will not fight,” he
said.
“Certainly not, sir, I never heard anything so preposterous in my
life,” said the other.
“Very good, but on one point you are wrong. Reckavile is a
strange creature, and he does not wish to kill you; in fact he was
hoping you would kill him.”
Wheatland gazed at him open-mouthed.
“Kill him, sir, and how much better off should I be if I were
hanged for murder, than if I were murdered myself. And what would
become of my business; I should look ridiculous.”
Wynter felt he had better terminate the interview.
“Good-day, Mr. Wheatland,” he said bowing slightly.
Wheatland laid a hand on his arm.
“He will marry her, won’t he sir, when I have my divorce; I should
not like to think he would desert her.”
There was something in the tone which went to Wynter’s heart.
This stubborn man, who would not forgive, and who was willing to
face publicity for the sake of his personal honour, yet hoped that the
woman would find happiness or at any rate safety by marrying the
man.
“I’ll tell him,” said Wynter hurriedly, and went out.
Reckavile was waiting for him in the Club. He had occupied his
time in tossing a friend for sovereigns, and had liberally attended to
his needs for liquid refreshment.
He listened in scornful silence to Wynter’s recital.
“And so the merchant won’t fight,” he said.
“Not likely,” said Wynter with a loud laugh “and the best of the
joke is he wants you to marry the woman.”
Reckavile sat up straight and Wynter eyed him narrowly.
“Of course, that’s your affair, old man, but it certainly looks as
though you are caught at last,” and he slapped the other on the
back. “We all know about the Reckavile honour. You are all
blackguards of the worst type, but men of honour of a sort—a
curious sort.”
There were several in the group, and they laughed boisterously.
“Damn you, you need not remind me of that,” said Reckavile, his
thoughts were with a little lady with great eyes in Italy, watching for
his coming with a lovelit face, whom this same sense of honour has
compelled him to marry. He shook himself.
“You’ll all dine with me,” he said “and we’ll have a flutter
afterwards, but I’m sorry the merchant would not fight.”
Chapter IV.
The Divorce and After
Wheatland got his divorce. There was no defence, for when
Reckavile considered the matter with his family lawyer, he decided
not to have certain letters read in court, and all the details published
in the papers.
He wandered restlessly between London and his castle at
Portham, not able to leave for Italy till the case was over. He wrote
Carlotta, passionate love letters, but gave no address, for to her he
was Hugh Desmond, and no other.
In spite of all the appeals made to him by Winnie in tearful and
illiterate letters, he made no answer, nor would he see her. He told
his lawyer to look to it that she wanted for nothing, and there the
matter rested.
It was the day after the decree nisi had been pronounced when
Reckavile went to his lawyer, Mr. Curtis, head of Curtis, Figgis and
Brice, for a final interview as he was leaving for Italy the next day.
The thought thrilled him, as he pictured her whose whole longing
was bound up in him, with no aspiration after title, or social position,
and trust—absolute trust—that was the very devil.
Curtis was speaking.
“Of course, I don’t know what you propose to do, Lord Reckavile,
when the decree is made absolute—it is hardly my affair, except—
ahem—as the old family lawyer who knew your father, perhaps …”
he stopped confused.
“Well?”
“What I meant to convey was, that if you made the lady an
allowance as you are doing, it would appear sufficient. In your
position I do not think an alliance would be desirable or even
necessary.”
Reckavile’s face hardened.
“You mean as I have compromised the lady, I should now desert
her—of course, with an allowance,” he added bitingly.
Curtis was uneasy, for he knew the Reckaviles; but the marriage
must be stopped. He tried once more.
“It would never do. You know that the estate is heavily
mortgaged, and you are well—rather careless in money matters. I
had hoped that you would marry some desirable lady of your class,
with sufficient funds to put the family in a satisfactory position. I
think that is very necessary.”
He paused at the look on Reckavile’s face. His eyes were dull
black, like a snake’s, and his mouth was twisted in a fiendish smile.
Curtis knew that look only too well.
“Thank you, Curtis,” he said “I was undecided, and thought of
tossing for it, but you have made up my mind for me. I shall
certainly marry the woman—or at least give her my name for what it
is worth, and that should be sufficient punishment for anyone.”
“But, my Lord …”
Reckavile held up his hand. “There is no need for further
discussion.”
A knock sounded at the door, and the clerk came in.
“A lady wishes to see Lord Reckavile,” he said to Curtis “she would
not wait, sir, and seemed very impatient.”
He was brushed aside, and Winnie swept into the office. Her
colour was high, and she certainly looked a beauty at that moment.
The worry of the last few months instead of marring her looks,
had softened the lines of her face, and her fine eyes were appealing.
She came straight to Reckavile, ignoring the lawyer altogether, but
something in the sternness of his face made her pause.
“Oh Hugh!” she said, not venturing to go to him, “why have you
treated me like this? You have taken no notice of my letters, and
refused to see me. Are you going to desert me after you have ruined
me?” Her voice broke, and there were signs of coming tears.
“You need have no apprehension on that score,” he answered
coldly. “I have already discussed the matter with Mr. Curtis here.
When the time comes, you shall become Lady Reckavile, and have
my honoured name. You have a witness here,” and he smiled like
Satan at Curtis.
“But Hugh, you are so hard, so cold. It is your love I want as well
as to be your wife,” she added hastily.
He was unmoved.
“I have said, Winnie, that you shall become my wife. Anything else
I do not care to discuss, especially before another.” Curtis had
remained in the hope that he could dissuade Reckavile from his
purpose, but he now hastily made to go, when the other stopped
him.
“No, Curtis, don’t go. There is nothing to add. I am leaving
England, and you know where to find me. This lady can
communicate with you, and you will continue her allowance. When
my presence is necessary I will come. You can arrange the details at
a registry office, as quietly as possible. No fuss, please, and above
all keep it out of the papers.”
Winnie turned red with anger and shame. How brutal he was and
callous, it was worse than anything that had gone before. Before she
could collect her thoughts Reckavile had turned on his heel, and
strode from the room.
She would have tried tears, or a passionate appeal, but what was
the good of that with a dry old lawyer, whose face was impassive.
“What a way to treat me after all I have been through for him,”
she blazed out, but Curtis remained silent.
“He said he loved me, and that he would remain true to me,” she
went on.
“I am afraid Lord Reckavile has said that to many,” said Curtis
dryly, drawing a paper towards him, “and as for standing by you,
you are the first who has had the honour of becoming Lady
Reckavile.”
His tone was final, and she felt the futility of talking to a
parchment faced lawyer, whose sympathies were obviously with Lord
Reckavile, and who considered she was getting out of it very well.
With a toss of her head she went, vowing she would never enter the
place again.
And Reckavile paced the deck of the Channel boat, deep in
thought. His mind ran on suicide, which was the common weakness
in his family, and generally the solution of impossible positions.
Then another thought came to him, and the more he turned it
over, the better he liked it. Why not end the Line without violent
means. He would give Winnie his name and the Estate for what it
was worth. As Lord Reckavile he would cease to exist, but in sunny
Italy, Hugh Desmond would bury himself with his little wife, and he
would earn a living by his painting, for he was no mean artist.
The idea pleased him. Flowers and kisses, and lying in the sun,
with not too much work, and perhaps a minor war or so to chase
away boredom. By the time he had reached Italy he had made up
his mind. There was only one more hurdle, the ceremony in London,
and then happiness awaited him. The bigamy did not worry him in
the least, such trifles were nothing to a Reckavile.
At Venice he waited all day, and a strange feeling of apprehension
came to him. Suppose something had happened to Carlotta in his
absence; he had left her, a mere girl—alone, with only servants of
whom he knew nothing. Suppose she were ill, or even dead. A
nervousness never felt before beset him. Impatiently he drove out to
Murano, and came to the Villa San Rocco. Night was falling as he
passed through the lovely garden, and approached the windows
from which a soft light shone. She was sitting inside, a piece of work
had dropped from her hands to the floor, and her great eyes were
gazing at nothing. How sweet she looked and how dainty, but so
sad. He had never seen her thus, and pity filled his heart, and
reproach.
He entered through the open window, and with a great cry she
came to him, holding out both arms. He took her to himself in a
passionate embrace, and with a feeling deeper than the old stirring
of desire. She raised her radiant face to his in perfect happiness.
“Oh, Hugh, I am so happy. You’ve come back to me.”
There was no word of reproach, no shadow of fretfulness at his
long absence.
The past and future were gone, and for the moment the pure bliss
of being together absorbed their beings.
She roused herself with a happy laugh, and kissed him, her face
rosy with delight.
“I must tell the servants about dinner, and you will want to dress
won’t you?”
She looked older, more self assured, but more beautiful than ever,
he thought.
He had left his bag in the carriage, and went for it, and to pay the
driver.
When he returned, she was waiting for him, and led him shyly to
their room, fragrant with flowers, and the odours of the night.
She showed him everything with childish pleasure, all arranged for
his return, and his dressing room on which she had lavished such
care, overlooking the rose garden.
Dinner was laid in the loggia, and he seated himself with a sigh of
contentment. The spotless linen and sparkling glass and silver added
to his sense of happiness. She rose and filled his glass, and he made
her sip from it first, the scent of her hair and the nearness of her
warm body intoxicating him. He would have taken her into his arms,
but that the servants were hovering near.
She was dressed in a soft evening gown, which showed the
perfect lines of her young body, and he wondered at her beauty.
Never once did she ask him where he had been, or what he had
been doing, but listened as he told her of England, and then
recounted the little trifles of her life, so pathetically filled with the
sorrow at his absence though she did not speak of it.
They sat over their coffee while he smoked a cigar from his Club,
which had never seemed so fragrant before.
At last he rose.
“It is getting chilly, darling,” he said in a voice he tried to steady.
“Let’s go to bed.”
A deep blush dyed her neck and face, as she rose and took his
hand.
Chapter V.
The Second Marriage
The summons had come, and Hugh braced himself to meet the
call. Would to God he could have refused to go; to pretend that he
was dead, anything to get out of it. But the perverted honour of the
Curse drove him to play the last scene to the end.
“I shall only be away for a week, Darling,” he told her. “There is a
certain property of mine I must look after.” That was true.
“When I come back this time, I shall not leave you again.”
She smiled at him; the wrench was not so bad this time, and she
had other things to think of. When he came back she would tell him,
and she hid her secret close, nursing the thought in her breast.
She came with him to Venice, careful that he had everything for
the journey, papers and cigars. He watched her with a dull sense of
pain; the deception hurt him as nothing had done before.
He had converted a shed into a studio, and she had posed for
him, as he had said at their first meeting. Already one picture was
finished, and he would have sold it, but could not bear to part with
it. Another was half done, which he would finish when he came
back, he told himself.
In London, summer was at its height, but he had no pleasure in it.
The Club nauseated him, and the old companions found him
changed, dull and uninteresting. He was out of touch with things.
Only Wynter and a few intimates who knew, surmised that the
prospect of marriage had caused the change, and behind his back
betted how long he would retain faithful to his marriage vows.
Winnie he met only at the lawyer’s the day before the wedding.
She found him cold and reserved, but he was startled with the
change in her. She was sweetness itself, her voice subdued and a