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BASIC BIOSTATISTICS
FOR MEDICAL AND
BIOMEDICAL
PRACTITIONERS
Second Edition
BASIC BIOSTATISTICS
FOR MEDICAL AND
BIOMEDICAL
PRACTITIONERS
Second Edition
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
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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 978-0-12-817084-7
Julien Hoffman was born and educated in Salisbury (now named Harare) in Southern
Rhodesia (now named Zimbabwe) in 1925. He entered the Faculty of Medicine at
the University of the Witwatersrand in Johannesburg, South Africa, and obtained a
B.Sc. Hons in Anatomy and Physiology in 1945 and a medical degree (M.B., B.Ch.)
in 1949. After working for almost 3 years at the Central Middlesex Hospital in London,
England as a house officer and registrar in Medicine he returned to Johannesburg as a
senior registrar in the Department of Medicine for 18 months, and then returned to
England to work for the Medical Research Council. In 1957 he went to Boston
Children’s Hospital to study congenital heart disease, and this was followed by 15 months
as a Fellow in the Cardiovascular Research Institute at the University of California in San
Francisco.
In 1962 he joined the faculty at the Albert Einstein College of Medicine in New York
City as an Assistant Professor of Pediatrics and Internal Medicine, and in 1966 returned to
the University of California in San Francisco as Associate Professor of Pediatrics and
member of the Cardiovascular Research Institute. He was a clinical pediatric cardiologist,
taking care of children with heart disease, but spent about 50% time running a research
laboratory to study the pathophysiology of the coronary circulation.
His interest in statistics began while taking his Science degree. After going to England
he took short courses in Biostatistics from Bradford Hill and his colleagues. On returning
to South Africa, as the only department member to know anything about statistics, he was
assigned to perform statistical analyses for other members of the department. This was a
period of learning by trial and error, helped by Dr. J. Kerrich, head of the University’s
Division of Statistics.
When he went to San Francisco as a Fellow, he was assigned to give statistics lectures
to the Fellows and Residents, and when he returned to San Francisco in 1966 he gave an
officially sanctioned course in Biostatistics to research Fellows and Residents. These lec-
tures were given annually for over 30 years. He was a member of the Biostatistics group, a
semiformal group that supervised statistical teaching and consultation. He also was a sta-
tistical consultant to the journal Circulation Research, and was often assigned manu-
scripts by other journals, mostly from the American Heart Association, to check on
the statistical procedures used.
xiii
PREFACE
xv
xvi Preface
can remember that (a b)2 ¼ a2 2ab + b2 you will be able to follow almost all the
formulas provided.
2. Some chapters include a section on advanced methods that should be ignored on a
first reading but provide information when needed, and others have an appendix
where some simple algebraic proofs are given. As this is not intended to be a math-
ematically rigorous book most mathematical proofs are omitted, but a few are impor-
tant teaching tools in their own right and should be studied. However, knowledge of
mathematics (and differential calculus in particular) beyond elementary algebra is not
required to use the material provided in this book.
3. Scattered throughout the chapters are variations on tests that are often needed but
not frequently found in basic texts. These sections are often labeled “Alternative
Methods,” and they should be read and understood because they often provide
simpler and more effective ways of approaching statistical inference. These
include:
a. Robust statistics for dealing with grossly abnormal distributions, both univariate
and bivariate.
b. Equivalence or noninferiority testing, to determine if a new drug or vaccine is
equivalent to or not inferior to those in standard use.
c. Finding the break point between two regression lines. For example, if the lactate:
pyruvate ratio remains unchanged when systemic oxygen delivery is reduced
below normal until some critical point is reached when the ratio starts to rise,
how do we determine the critical oxygen delivery value?
d. Competing risks analysis used when following the survival of a group of patients
after some treatment, say replacement of the mitral valve, and allowing for deaths
from noncardiac causes.
e. Tolerance and prediction testing to determine if a single new measurement is
compatible with a normative group.
f. Cross-over tests, in which for a group of subjects each person receives two treat-
ments, thus acting as his or her own control.
g. Use of weighted kappa statistics for evaluating how much two observers agree on a
diagnosis.
h. Bowker’s test for evaluating more than two sets of paired data.
4. Some chapters describe more complex inferences and their associated tests. The aver-
age reader will not be able to use these tests without consulting a statistician but does
need to know that these techniques exist and, if even vaguely, what to look for and
how to interpret the results of these tests when they appear in publications. These
subjects include:
a. Poisson regression (Chapter 34), in which a predicted count, for example, the
number of carious teeth, is determined by how many subjects have 0, 1, 2, and
so on carious teeth.
Preface xvii
not described in detail in this book. Finally, some are basically nonmathematical discus-
sions of the subject; reading these will expand your knowledge.
Many people devise and carry out their own experiments, and for them a good
knowledge of statistics is essential. There are many statistical consultants, but not enough
of them to advise every investigator who is designing an experiment. An investigator
should be able to develop efficient experiments in most fields and should reserve consul-
tation only for the more complex of these. But more numerous and important are those
who do not intend to do their own research. Even if the person is not a research worker,
he or she is still responsible for assessing the merit of the articles that they are reading. It is
no longer good enough for such a reader to know technical information only about the
drugs used, the techniques for measuring pressure and flow, or to understand the phys-
iologic and biochemical changes that take place in the disease in question. It is as essential
for the reader to learn to read critically and to know how to evaluate the statistical tests
used. Who has not been impressed by the argument that because Fisher’s exact test
showed a probability of 0.003, the two groups were different, or that because the
probability was 0.08 the two groups were not different? Who has heard of Fisher’s exact
test? Of McNemar’s test? Of the Kolmogorov-Smirnov two-group test? Of Poisson
regression? And if the reader has not heard of them, how can he or she know if they
should have been used, or have been used and interpreted correctly? With the pace at
which new knowledge is appearing and being incorporated into medical practice, every-
one engaged in medical research or practice needs to be well grounded in Statistics.
Statistical thinking is not an addendum to the scientific method but is an
integral component of it.
What can you expect to achieve after studying this book?
1. How to take account of variation in assessing the importance of measured values or
the difference between these values in two or more groups.
2. A better understanding of the role of chance in producing unexpected results, and
how to make decisions about what the next steps should be.
3. An appreciation of Bayes’ theorem, that is, how to improve estimates of probability
by adding in potential explanatory variables, and the importance of the population
prevalence in making clinical predictions.
4. An ability to perform simple statistical tests (e.g., t-tests, chi-square, linear regression
and correlation, McNemar’s test, simple analysis of variance, calculate odds ratios and
their confidence limits, and calculate simple survival tables), as well as understanding
their limitations.
5. Realization that the usual attitude that P< .05 has ruled out the null hypothesis is
open to question and should not be used by itself to reach a final conclusion.
6. Appreciate that there are many statistical techniques that can be used to address spe-
cific problems, such as metaanalysis, bioassay methods, nonlinear and multiple regres-
sion, negative binomial distributions, Poisson regression, and time series analysis.
Preface xix
It is unlikely that after studying this book you will be able to perform these analyses on
your own, but you should know that such methods exist and that a statistical consul-
tant can help you to choose the right analytic method.
If an investigator is not well acquainted with principles of experimental design, for exam-
ple, random selection, sample size, the expenditure of time and money will be wasted.
This is unethical and is even more important in clinical research because subjects may be
submitted to an unreliable experiment.
Statistical procedures are technologies to help investigators interpret their data and are
not ends in themselves. Like most technologies, Statistics is a good servant but a bad mas-
ter. Francis Galton wrote in 1889: “Some people hate the very name of statistics, but I
find them full of beauty and interest. Whenever they are not brutalized but delicately
handled by the higher methods, and are warily interpreted, their power of dealing with
complicated phenomena is extraordinary (Galton, 1889).”
REFERENCES
Galton, F.I., 1889. Natural Inheritance. Macmillan and Company, London, p. 62.
Good, P.I., Hardin, J.W., 2009. Common Errors in Statistics (and How to Avoid Them). John Wiley & Sons,
Hoboken, NJ, p. 274.
ACKNOWLEDGMENTS
Many people have helped me eradicate errors and clumsy phrasing. I owe a debt of
gratitude to Joseph P. Archie, Jr., Stanton Glantz, Gus Vlahakes, Calvin Zippin and
particularly to Raul Domenech. My special thanks to my wife for help with editing.
xxi
CHAPTER 1
Basic Concepts
INTRODUCTION
Statistics is a crucial part of scientific method for testing theories derived from empirical
studies. In most scientific studies the investigator starts with an idea, examines the
literature to determine what is and is not known about the subject, formulates a hypoth-
esis, decides what and how measurements should be made, collects and analyzes the
results, and draws conclusions from them. Excellent introductions to these processes
are provided by Moses (1985), Altman (1992), Hulley et al. (2007), and Easterling (2015).
One of the main aims of scientific study is to elucidate causal relationships between a
stimulus and a response: if A, then B. Because responses to a given stimulus usually vary,
we need to deal with variation and the associated uncertainty. In adult males in the
United States, there is some typical number that characterizes weight, for example,
75 kg, but there is variation around that typical value. Although fasting normal blood
glucose is 100 mg/dL, not every normal person will have this blood sugar concentra-
tion. If we measure the length of 2-in. long 20-gauge needles with great accuracy, there
will be variation in length from needle to needle. It is an essential role of statistical thought
to deal with the uncertainty caused by variability. One of the major ways to assess uncer-
tainty is by doing an appropriate statistical test, but the test is merely the instrument that
produces a result that needs to be interpreted. Performing a statistical test without the
correct interpretation may lead to incorrect conclusions.
Basic Biostatistics for Medical and Biomedical Practitioners © 2019 Elsevier Inc.
https://doi.org/10.1016/B978-0-12-817084-7.00001-2 All rights reserved. 3
4 Basic Biostatistics for Medical and Biomedical Practitioners
lowering medication. It is to guard against this type of error (and many other types) that
we need to think about the role of variability in statistical inference.
The term “parameter” has different meanings in different fields of study. In Statistics, it
is usually used to indicate the numerical characteristic of a population, such as the mean μ
(average), slope of a relationship β, proportion of positive results π, and so on.
the randomly chosen sample of adult males have by chance selected the tallest members of
the population so that the estimate of mean height, instead of being 175 cm, was 185 cm?
Yes, indeed such an aberrant sample could have been chosen, even if it is very unlikely,
and if it had been chosen our estimates of the mean population height would be seriously
in error. That is the uncertainty that we have to live with.
Statistical inference
When we ask whether the mean heights of treated and untreated children with growth
hormone deficiency are different, we invoke the second use of statistics—statistical infer-
ence that is done with hypothesis tests. In general, we generate hypotheses about the pos-
sible effects of treatment and then deploy statistical techniques to test the appropriateness
of these hypotheses. Often the null hypothesis is selected, that is, we test the possibility
that the treatments of the groups (taking growth hormone or a placebo) have not caused a
change in an outcome (mean height). If the tests indicate that the differences observed
would be unlikely to occur by chance, then we may decide to reject the null hypothesis.
One of the advantages of the statistical method is that it can give an approximate prob-
ability of correctly rejecting the null hypothesis. It does so by calculating a P value that
may be defined as the probability of finding an observed difference or even more extreme
differences (say in mean heights) if the null hypothesis is true. This subject is dealt with in
depth in Chapter 10.
Statistical methods also allow us to investigate relationships among variables that may be
either causative (independent) or responsive (dependent). Thus if we give a drug to patients
and observe a fall in blood pressure, we hypothesize that the drug (independent cause)
produced the fall in pressure (dependent response).
We investigate relationships in two main ways. In the survey method, we collect
examples from one or more populations and determine if the independent and depen-
dent variables are related. In the survey, there may or may not be a comparison group.
Without comparison groups it is a descriptive study. With comparison groups it is an
analytical study (Grimes and Schulz, 2002). For example, the role of fluoride in prevent-
ing dental caries was examined in cities that did or did not supplement their water sup-
plies with fluoride; the amount of dental caries was lower in people living in the cities
with higher water fluoride concentrations (Grimes and Schulz, 2002). The advantages
of an analytical study are that large populations can be studied and that individuals do
not have to be manipulated and assigned to groups; the disadvantage is that factors other
than the fluoride might have caused the observed differences in the incidence of dental
caries. Factors extraneous to but related to the factors being studied are termed confound-
ing factors; a factor is a confounder if it differs in the groups and affects the outcome. For
example, the incidence of dental caries might really be due to deficiency of another
factor (X) that is inversely correlated with fluoride. If we do not know about X, or
20 Basic Biostatistics for Medical and Biomedical Practitioners
10%, nonparametric tests increased from 0% to 12% (depending on the journal) to 33%–
49%, and the use of more complex tests increased (Kurichi and Sonnad, 2006).
Today, with computers ubiquitous and software statistical packages freely available,
complex statistical analyses are within the grasp of the nonstatistician. However, this does
not mean that investigators necessarily choose the appropriate analyses or perform them
correctly. As Hofacker (1983) stated “The good news is that statistical analysis is becom-
ing easier and cheaper. The bad news is that statistical analysis is becoming easier and
cheaper.”
STATISTICAL MISUSE
Many investigators have examined the use of statistics in both clinical and basic science bio-
medical publications. Altman reviewed the use and misuse of statistics up to the 1980s
(Altman, 1991); more recent studies as summarized by Glantz (2005), Good and Hardin
(2009), and Kilkenny et al. (2009) are discussed later. The results have been fairly uniform.
Of the published articles in which statistical analyses were used, from 50% to 78%
used incorrect tests; this figure has varied little over the past 60 years (Ross, 1951;
Badgley, 1961; Schor and Karten, 1966; Schoolman et al., 1968; Gore et al., 1977;
Freiman et al., 1978; Glantz, 1980; Sheehan, 1980; Reed and Slaichert, 1981; Emerson
and Colditz, 1983; Sheps and Schechter, 1984; Pocock et al., 1987; Williams et al., 1997;
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But, James Garston was on his knees before her now.
“Our child—Margaret! It can all be made right, now. Trust to me. Let
me take you openly to my heart. Be my wife once more. Be a world’s
queen. I will make you happy.”
Bold as he was, he shuddered, as she sprang to her feet. “You
hound!” she bitterly cried, and then slowly turned, and walked
unsteadily to the door. He had found a way to wring her heart at last,
but her courage had returned. The wrongs of her youth burned in her
bosom again.
“Hear me. You must! You shall!” he pleaded, seizing her in his strong
arms. “I knew not even the horn book of my own nature when we
married as young fools marry.” She had torn herself away from him,
and stood at bay with an unutterable loathing hardening upon her
face. “I am rich, now, a Senator to be, and the friend of your friends.
“You dare not openly defy me. For, I can publicly claim you as mine. I
demand to see our child. I offer you myself—the matured man—a
leader of men. I offer you a secured, honored place in Washington
life. And, you need me, for I can throw down your house of cards.
When Alynton told me of the wonder-worker, the Queen of the
Street, the Lady of Lakemere, I was merely interested. But, when I
saw you, last night, my heart leaped up. For mine you were, mine
you are—mine you shall be.”
The strong man counted upon the physical subjection of the woman
once reduced to be his loving vassal—the girl wife who had lain in
his arms.
And, master of her destiny once, he would now bend her to his will
again.
His eyes were burning, his breath came quickly, and he awaited the
physical revulsion of a weakened womanhood.
“There is always the tie that binds—the child—and, she belongs by
Nature’s bond to me.”
But, the man who coarsely counted upon “a previous condition of
servitude” as establishing a valid claim upon the Lady of Lakemere,
shivered under the cold scorn of her words, for the wife of his youth
seated herself, and, gazing into his eyes with an unutterable
contempt, read the death warrant of his hopes.
“Let me cast up our accounts, here, now, in my home, Arnold
Cranstoun, on this winter day, in a solitude on which you shall never
intrude again save when I call upon you.
“The dead past is buried. Let it rest. Dare not to cry Resurgam! I
dismiss all your sneers as to Alynton, and, I fear not your circle. You
are as yet, but a clumsy neophyte there.
“Know, once for all, that your friends are in my power, but they trust
to me, and, I am more than worthy of their confidence.
“For another circle of men of boundless power also trust me—men
who would not trust them, save through me, and, men who would
resistlessly crush you at my bidding.
“I speak now for the woman who is dead.
“Margaret Cranstoun, the woman heart slain by your cowardice, the
loving and tender girl-wife. Look back nineteen long years to see
yourself the trusted bank-cashier, a rising man of thirty-two.
“I was then your slave, your loving slave, a wearer of self-forced
heart shackles. I, the girl of seventeen, believed you to be my lover
husband—a man among men.”
Senator James Garston’s head was bowed in his hands, as the
accusing voice rang out. He heard the knell of his last hopes.
“A year later, when you basely fled, leaving me, the mother of your
two months’ old helpless girl to face the employers whom you had
robbed in your hidden speculations, then, only then, I learned of your
double life in New York. I knew that I was the innocent hostage of
purity and honor. The screen of your dearest vices.”
Garston groaned as the voice rose high in its scorn and Elaine
Willoughby stood before him, with outstretched arm, an angel with a
flaming sword, at the shut gates of his Lost Paradise.
“Where you fled to I knew not—I cared not, for, with young blood and
a loving heart, I might even have shared the fate of a bold sinner.
“But a sneaking coward must learn that woman’s heart condones not
poltrooning nor meanness!
“You would now hold the dead past over my head—trumpet to the
world your own story!” she cried. “I can easily confirm it. I have kept
all your letters—the story of your crime, the papers and vouchers
which were found in your New York room.
“Your letters of egoistic love, your later whining apologies from your
unknown Western haunt. And armed with these, I could chase
James Garston from the Senate.”
The suffering man sprang up. “Not so. I have a right to my name. I
legally changed it years ago. The bank is long years out of
existence; there is also the limitation of the past years. No one would
believe you.”
His voice was broken with helpless tears now.
“Look at me! look at me!” the splendid woman proudly cried. “Dare
any man say that my life has been a lie? Hear my story.
“Starvation, cold charity or the ignominy of helpless dependence was
all you left me. I put our babe away. I went out a toiler into the world.
As a school teacher I drifted away to the far West, and only changed
my name. I left our home to avoid the honest love of good men who
would have married me for pity’s sake. For men were good to the
shamed widowed Margaret Cranstoun.
“My clean hands were still linked by law to the unpunished fugitive
felon. I am free now, and I know that you never would dare to speak.
I know your coward soul. A judicial decree that you are dead can be
easily had; your eighteen years of absence makes that my legal
right. Widow of the heart, I will be a widow by law. But your coward
silence will continue.
“Where did I gain wealth? I see the question in your eyes. I became
a school teacher at Leadville. A few acres of ground and a cottage
were the first fruits of my savings.
“The kindly mountain gnomes worked for me, with fairy friendship.
“There was a million in carbonates under those rocky slopes where I
tempted the hardy flower to grow.
“Young yet—beautiful then—I became the ardent chase of men in
marriage. My gold gilded my lonely life. Many wished to share it.
“I was made sadly wise, and I reaped my harvest of sorrows. Five
years in Europe made me a woman of the world—an accomplished
world wanderer. I have learned in these lonely years the delicious
power of wealth.
“I followed your secret example. I legally changed my name to Elaine
Willoughby. And my honest title is clearer than yours.
“I have an able lawyer to defend my rights, in whom you would find
an implacable foe.”
She paused and spoke the final doom of his hopes.
“Had you come to me, red-handed, but loving, I might have forgiven
you, followed you—loved you even in your crime—and suffered all to
shield the one beloved head. I did love you once with my whole
soul.”
There was the sound of choking sobs, and in an instant, Garston
was on his knees before her. The silence was broken by her faltering
accents.
“But now, freed by Nature’s reincarnation, loyal even yet to a dead
past, I exult in the unchallenged ownership of my mind, body and
soul. You would take to your bosom the woman you still find fair, rich,
powerful and respected. Never! Nature revolts!
“For the starving outcast of the streets who sells herself for bread to
the first chance comer were white as snow compared to the woman
who would again sink to your level.
“Arnold Cranstoun, any man in the world but you may look on me
with longing eyes.
“Between us there is the gulf of your eternal shame! Now, leave me.
I fear you not! Let all else go on as fate ordains.
“Your silence will be assured, for fear will seal your lips. Let there be
neither approach nor avoidance—simply the oblivion of the absolute
divorce of all laws, God’s, Nature’s, and man’s.
“Go now! If you ever seek to cross my path, beware! You may haunt
the peopled solitudes around me and meet me as a chance
acquaintance.
“Your ‘society drill’ will hold you in your place in the poor parade of
this superficial life.”
She dropped her eyes, and her impassioned voice echoed sadly on
his ears. He was defeated, and an agony rent his heart.
“Let me do something for you, Margaret,” he pleaded.
“I am above your power to aid,” the proud woman replied.
“Let me atone,” he begged.
“Dead beyond awakening is my heart, and you know it. Do not now
add a hideous insult to Nature to your cowardly abandonment of the
past.”
The dull, level coldness of her voice proved to him that she bore a
frozen heart, one never to awaken at his touch. He cast himself
down before her in a last appeal.
And then, on his knees before the woman whom he had sworn to
cherish “till death do us part,” the strong man pleaded for the child
whom fate had robbed from the clinging arms of its mother. Margaret
Cranstoun sobbed:
“The child! Oh, my God! Never! Name not her name. Me, your victim
or your sacrifice. Her name shall never cross your lips. Wherever
God’s mercy takes that innocent one, she shall live and die
fatherless—save for Him above. I swear it, on the memory of a
mother’s natal anguish. And now, Senator James Garston,—”
The stately woman stood before him with the menace of a life in her
eyes.
“This is the end of all! Go! You are safe from my vengeance now. I
care not how you have dragged yourself up on Fortune’s wheel.
“Go! And if you ever break the sorrow-shaded stillness of my life,
then, may God help you. For I will strike you down for the sake of
that same fatherless child.”
A black storm of suddenly aroused jealousy swept over Garston’s
face.
“Your handsome lover Vreeland shall be my prey, my tool, my
confidant. I will creep into your heart through your own pleasant vice.
And, by God! He shall find out the girl for me.”
When James Garston’s passion-blinded eyes cleared, he was
standing there alone, and a sudden fear smote upon him.
The ghastly silence of the splendid deserted halls weighed upon him.
He staggered out into the blinding snows, now falling, and crossed
the park to where a sleigh waited at the garden gate.
He was half mad, as he wandered away under the trees, and he
hurled away his revolver lest he should be tempted to die there
before her windows.
“I have lost a woman upon whose breast a king’s head might proudly
rest,” he said to that ghost of his dead self which rose up to mock the
man of mark, the millionaire. “And—she loved me once. Fool—fool—
and—blind fool!” he muttered.
A mad resolve thrilled him now.
“The child! By God! she would hide her. The world is not wide
enough. There’s my money—and this young fellow Vreeland. I have
a lure for him.”
His busy brain thrilled with plots of the one revenge left to him. “I will
steal away both child and lover!” he swore.
Senator Garston’s face was sternly composed that night as he
indited his invitation to the rising young banker to join him at the
Plaza.
“Katie Norreys can soon twist him around her slim, white fingers—he
is young and rash,” the cold-hearted millionaire mused. “I am safe in
Margaret’s silence. My money will talk. My record is safe. I have
made my calling and election sure. I’ll get Vreeland into the fair
Katie’s hands.
“A little money will help. He shall be turned away from Margaret.
Once that I have the girl, then Margaret will surely soften—for that
child’s sake. By God! I’ll buy the girl’s heart! I have money enough,
and I’ll outbid even Mrs. Elaine Willoughby.”
The Senator-elect felt a new glow in his heart, the ardor of a wolf-like
chase, an untiring chase, for love, passion, and vengeance carried
him on.
“I’ll live to laugh at her heroics yet,” he cried, “for I will bring her into
camp. I am not accustomed to fail.” He was resolute now.
The lights were gleaming golden in the Circassia when a pale-faced
woman crept back to the splendors of the pearl boudoir.
No one had marked Senator James Garston’s visit to Lakemere, and
the two caretakers—man and wife—marveled at their mistress’
agitation when she bade them escort her back to New York City. The
gardener summoned to watch over the lonely mansion grumbled: “I
never saw her look like that.” For the brave woman was now “paying
the price.” It was the reflex swing of the pendulum of Life.
Could the three humble servitors have heard the accusing cry of
Elaine Willoughby’s heart they would have known the anguish of a
stricken woman’s arraignment of Providence.
“And he—oh, my God! He prospers, while my child is taken from me!
Is this the price of my mother’s love, my empty heart, my vacant
home, my death in life!”
It seemed as if God had spared the wrongdoer to smite her quivering
mother heart.
Dr. Hugo Alberg and the stolid-faced Martha Wilmot were busily
whispering in a corner of Mrs. Willoughby’s sick room that night long
after midnight had sounded on the frosty air.
For, relaxed and broken by the enforced bravery of her struggle with
the father of her lost child, the Lady of Lakemere had crept, bruised
and wounded in soul, back to die or live, she cared not, in the
peopled wilderness of the two million souls who envied her the lonely
luxuries of her life.
“She has had one dose,” whispered Alberg. “She is dead safe to
sleep till three o’clock. Give her this chloral carefully then. Get your
work done as soon as you can, and at eight o’clock your expected
telegram will call you away. The French woman will watch till the new
nurse comes. You have seen young Vreeland?”
The Doctor’s eyes glowed like live coals.
“Yes,” she whispered. “It’s all right,” and her fingers tightly closed on
the vial. “I am to meet him at the ferry. The boat sails at eleven. It will
be all right.”
Dr. Alberg passed out of the sick-room, and Justine Duprez followed
him down the stair.
“You have left all where she can do the work?” whispered the miserly
German, who already had the price of his treason in his pocket.
“Yes,” murmured Justine. “I’ll tell you all when we meet down there.”
The hoodwinked physician went out into the night, whispering: “I’ll be
here at seven, on the watch.”
It was but half an hour later that a man seated in August Helms’
darkened basement room opened his arms as Justine Duprez glided
in.
“She is sleeping like a log,” murmured the maid. “Here is what you
want. The nurse will do her part later, and be sure that she clears out
at once. I’ll keep the Doctor with me here till noon. She will get her
‘sudden telegram;’ he will be here on duty; while he is busied with
the new nurse Martha will go and rob the Doctor’s office and rooms,
and be soon on the sea. Then we are all covered.”
The schemer’s eyes gleamed as he pocketed the paper which made
his patroness an involuntary traitor to her dangerous trust. Vreeland
breathed in a happy triumph.
“You must not leave your rooms to-morrow. Keep in sight of the Kelly
girl,” warned the Frenchwoman. “Now I will steal away.”
There were words murmured which bound the two wretches to each
other, and they laughed as they pointed to the janitor’s new
telegraphic instrument and telephone.
“A great convenience to the patrons of the Circassia,” laughed
Vreeland. He alone knew how deftly the crafty August Helms had
seized upon Mrs. Willoughby’s absence of the day to effect the
joining of the skilfully hidden wires tapping the lines which led to the
Hanover Bank building and joined Judge Endicott’s private office to
Mrs. Willoughby’s pearl boudoir.
“When I have the extra instrument in my own room,” he exulted,
“then if Miss Romaine Garland is not approachable I will soon find
another more malleable.
“But the secret firm of Endicott & Willoughby will talk into my ear
when they think that the whole world is theirs. It’s a royal plan,” he
mused.
Justine’s gliding step had died away when Harold Vreeland crept out
like a guilty thief.
“Where shall I hide this original,” he muttered, as he disappeared in
the darkness. “I must find a place in my rooms. I cannot carry it
about me.”
When he had regained the Elmleaf he dared hardly breathe as he
carefully examined the original document which tied up the fate of
the Sugar Syndicate with that of men whose very names he feared
to utter.
“She is in my power at last. Her ruin is in my hands.
“And now to bring her into my arms to be my fond tool and willing
slave.”
There was no “stock plunging” for two long weeks, as the illness of
Mrs. Willoughby dragged on, and Martha Wilmot was well across the
seas before the police of New York City had ceased to blunder
around after the ungrateful nurse who had seemingly robbed her
benefactor’s office and then decamped.
Mr. Harold Vreeland was astounded at the golden sunshine of
Senator James Garston’s favors which followed on that luncheon at
the Plaza Hotel which had made him a sworn knight in the rosy
chains of Miss Katharine VanDyke Norreys.
There was little to do, for the market was quiescent.
Miss Mary Kelly’s desk, too, was vacant, for she lay at home ill with a
fever, and it was at the side of the girl’s sick-bed that Mrs. Elaine
Willoughby, still feeble and shaken in soul, suddenly seized a
photograph from the mantel. “Whose picture is this?” she cried, her
voice trembling in the throes of an emotion which swept her loving
soul with wonderment and a new hope.
BOOK III—On a Lee Shore.
CHAPTER XI.