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<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>The Method for Describing Changes in the Perception of Stenosis in Blood Vessels Caused by an Additional Drug</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Sylwia Buregwa-Czuma</string-name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Jan G. Bazan</string-name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Lech Zareba</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Stanislawa Bazan-Socha</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Przemyslaw W. Pardel</string-name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Barbara Sokolowska</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Lukasz Dydo</string-name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Faculty of Mathematics and Natural Sciences, University of Rzeszow Pigonia 1</institution>
          ,
          <addr-line>35-310 Rzeszow</addr-line>
          ,
          <country country="PL">Poland</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>II Department of Internal Medicine, Jagiellonian University Medical College Skawinska 8</institution>
          ,
          <addr-line>31-066 Krakow</addr-line>
          ,
          <country country="PL">Poland</country>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>Interdisciplinary Centre for Computational Modelling, University of Rzeszow Pigonia 1</institution>
          ,
          <addr-line>35-310 Rzeszow</addr-line>
          ,
          <country country="PL">Poland</country>
        </aff>
      </contrib-group>
      <fpage>115</fpage>
      <lpage>125</lpage>
      <abstract>
        <p>The decision making depends on the perception of the world and the proper identification of objects. The perception can be modified by various factors, such as drugs or diet. The purpose of this research is to study how the disturbing factors can influence the perception. The idea was to introduce the description of the rules of these changes. We propose a method for evaluating the effect of additional therapy in patients with coronary heart disease based on the tree of the impact. The leaves of the tree provide cross-decision rules of perception changes which could be suggested as a solution to the problem of predicting changes in perception. The problems considered in this paper are associated with the design of classifiers which allow the perception of the object in the context of information related to the decision attribute.</p>
      </abstract>
      <kwd-group>
        <kwd>classification</kwd>
        <kwd>perception interference</kwd>
        <kwd>cross-decision rules</kwd>
        <kwd>tree of impact</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>
        One of the aspects of the data mining is learning about the surrounding world by
assigning meanings to received impressions, i.e. information provided by sensors. The way
in which we perceive and interpret the real world significantly determines the
identification of the objects and their classification, which affects the decision-making. The
classifiers, based on the available features (conditional attributes), describe the value of
the decision attribute and may be treated as approximate descriptions of concepts
(decision classes)[
        <xref ref-type="bibr" rid="ref3">3</xref>
        ],[
        <xref ref-type="bibr" rid="ref10">10</xref>
        ]. Therefore, the classifiers allow the perception of the tested object
in the context of information related to the value of the decision attribute.
      </p>
      <p>
        As a perception we understand a cognitive process that involves assigning the
meanings to the received information [
        <xref ref-type="bibr" rid="ref12">12</xref>
        ]. We consider the perception associated with
medical problems, namely the problem of the coronary artery stenosis in patients with stable
coronary heart disease (CHD, see Section 2).
      </p>
      <p>We study how the disturbing factors can influence the perception of stenoses in
blood vessels. We show that some disturbing factors can be managed using data
mining algorithms based on well-known statistics combined with cross-decision rules. Our
approach is illustrated using data representing medical treatment of the patients with
stable CHD. The dataset, collected by the Second Department of Internal Medicine,
Collegium Medicum, Jagiellonian University, Krakow, Poland, relates to 70 patients
subjected to elective coronary angiography with possible percutaneous angioplasty. The
decision problem, however, requires approximation of especially designed complex
decision attribute, corresponding to the analysis of perception interference.
1.1</p>
    </sec>
    <sec id="sec-2">
      <title>Perception and Classification</title>
      <p>There are a number of factors that can modify the behavior of the tested object and
change the way it is perceived, although generally the state of the object is not changed.
The state is stable in the sense that its affiliation to the concept does not change.
Sometimes we have no influence on the disturbing factor, for example, in the case of the
environment or the weather. But sometimes it may be intentionally introduced or even
managed, if we know how to do it (eg. drugs, type of therapy, diet).</p>
      <p>If we assume that the perception is achieved by the classifier, this means that if a
disturbing factor occurs, the classifier must be redesigned. In this situation, one can
build a classifier using additional conditional attribute, representing the information
about the occurrence of the disturbing factor. As a result, the classifier can be effective
both when the agent is present or when it is not. It is also possible to construct two
classifiers: the first one when there is no disturbing factor and the other one in the
presence of it.</p>
      <p>Another issue is, however, the question how does the disturbing factor change the
perception of test objects using the classifier and whether the change affects all test
subjects in the same way? If we could get to know the rules of these changes, this factor
could be used to control the object perception and indirectly its behavior.</p>
      <p>It is known from practical observations, that disturbing factors may often cause
various changes in the perception of the observed object. For example, consider the
situation when perception refers to the condition of the patient described by four states:
A, B, C, D, associated with the severity of disease which may be life-threatening. The
condition A indicates the lowest severity of the disease, B - slightly more advanced
disease, C - yet slightly more and D - the most advanced disease. Suppose also that
perception is based on the attributes describing the results of symptomatic tests, which
describe the actual level of critical illness (eg. ECG signal). Let the administration of the
Z drug be a factor interfering with perception. Let K1 and K2 are classifiers that have
been constructed based on the training data to predict the A, B, C or D state, without
the interfering factor and with its presence, respectively. If the K1 classifier assignes the
particular patient P1 to state B, it turns out that the K2 classifier may classify P1 to each
state: A, B, C or D.</p>
      <p>This is so, because the distortion of perception causes the misrepresentation of
patient’s image, which sometimes is perceived as if he/she had more advanced disease
than it really is, and sometimes as if he/she had less advanced disease. At the same
time, the misstated picture does not concern the real severity of the disease, but the
current degree of threat to life, which this disease causes. Thus, if one could predict what
kind of change in the disease perception the Z drug will trigger for a given patient, it
could be used to support the acute treatment (eg. on the way to the hospital, awaiting
surgery and so on).</p>
      <p>Note, however, that the standard method of a classifier construction is not useful for
predicting changes in the perception caused by a disturbing factor, because there is no
possibility to construct a decision attribute that represents the changes of the perception
of the disease for a given patient. This would require the experiments involving patients
who had to be treated both without and with the use of the additional drug. Such a
situation appears to be technically difficult and unethical, because it can generate a risk
of less effective treatment (treatment extended in time).</p>
      <p>
        The former work on this issue concerned the influence of two methods of surgical
treatment of the throat and larynx cancers on the survival of patients ([
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]). This work led
to the discovery of a data mining method, which calculates the so-called cross-decision
rules in medical data. Each cross-decision rule, for the group of patients described by
its predecessor, gives the consequent likelihood of success of the treatment (patient
survival) for both studied treatments. However, the method is based on the symbolic
data attributes. This limitation comes from the need to count the specific reducts with
regard to the complex decision, which in [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ] are calculated for symbolic data. However,
in many applications there is a need to analyze data with numerical attributes or mixed
ones (symbolic and numeric). We therefore need rules whose predecessors can have
ranges of values rather than specific attribute values.
      </p>
      <p>Therefore, in this paper we propose a method based on the so-called tree of the
impact, which is a binary tree. The impact tree is constructed so that the leaves contain
descriptions of patient groups (patterns) whose perception of the disease changes in a
similar way after the application of a disturbing factor. In some leaves a large change
in perception is observed, while in some others the small one. Some leaves are
characterized by a beneficial change, while certain other by an adverse one. With the
patterns assigned to the leaves, the perception changes of the test objects can be predicted.
Therefore, each leaf of the tree provides a single cross-decision rule, which in this work
will be called a cross-decision rule of perception changes. The rules could be suggested
as a solution to the problem of predicting changes in perception. For this purpose, the
consequent of the rule would bring the information about the perception both without
and with the disturbing factor.
2</p>
      <sec id="sec-2-1">
        <title>Medical Background</title>
        <p>
          Our considerations apply to the patients with stable coronary heart disease. The disease
is characterized by reduced blood supply to the heart caused by atherosclerosis. The
atherosclerosis is usually present in blood vesells even when their lumens appear normal
in angiography. The CHD touches people all over the world and is one od the leading
cause of deaths ([
          <xref ref-type="bibr" rid="ref7">7</xref>
          ]). Treatment may include medication or invasive revascularization.
Treatment is aimed at reducing or eliminating symptoms and reducing the risk of a heart
attack. The standard pharmocotherapy includes such classes of medications as: beta
blockers, nitrates, calcium channel blockers/calcium antagonists or ACE inhibitors.
        </p>
        <p>
          Recently a heated discussion on the inflammatory theory underlying the coronary
artery disease is conducted ([
          <xref ref-type="bibr" rid="ref4">4</xref>
          ],[
          <xref ref-type="bibr" rid="ref6">6</xref>
          ]). Inflammatory mediators are involved in the
development, progression and destabilization of atherosclerotic plaques ([
          <xref ref-type="bibr" rid="ref1">1</xref>
          ]). Some of
the strongest pro-inflammatory mediators are leukotrienes. Increased generation of
leukotrienes is observed during acute myocardial ischemia, coronary angiography or
angioplasty ([
          <xref ref-type="bibr" rid="ref17">17</xref>
          ]).
        </p>
        <p>
          In this context, the studies on the use of anti-inflammatory drugs in CHD were
conducted (eg. [
          <xref ref-type="bibr" rid="ref13">13</xref>
          ], [
          <xref ref-type="bibr" rid="ref16">16</xref>
          ]). In [
          <xref ref-type="bibr" rid="ref16">16</xref>
          ] the effect of pharmacological inhibition of leukotriene
production on the electrical activity of the heart was assessed using an inhibitor
of 5-lipoxygenase (zileuton). It has been shown that pharmacological inhibition of
leukotriene biosynthesis in patients with stable CHD subjected to intracoronary
interventions causes: reduction of the 24 hours average heart rate, increase in parameters of
rhythm variability, and an improvement in the conduction of electrical impulses in the
conduction system during intracoronary procedures. No effects on either arrhythmias
or ECG patterns of ischemia were noted.
        </p>
        <p>In view of the above results, it would be advantageous to indicate patients with
beneficial effects of anti-inflammatory therapy. Commonly used methods based on global
statistics such as the average or standard deviation, does not allow for selection of
individual patients. Therefore, it is necessary to develop additional methods for evaluating
the effect of treatment in individual patients. So we propose the use of a novelty data
mining method using the tree measuring the impact of the factor interfering the
perception. As a disturbing factor we use here an inflamatory drug - zileuton.
3</p>
      </sec>
      <sec id="sec-2-2">
        <title>Tree Measuring the Impact of the Factor Interfering the</title>
      </sec>
      <sec id="sec-2-3">
        <title>Perception</title>
        <p>The proposed cross-decision rules of perception changes are the kind of decision rules.
A decision rule takes the form of implication, in which the left side consists of
presumptions (conditions) expressed as a logical formula, and the right side contains a
conclusion (thesis). In classical decision rules, the thesis identifies the decision class,
while in the cross-decision rules it is a description of groups of objects from different
decision classes.</p>
        <p>For the problem of the coronary disease, the descriptors represent the expected value
of the number of stenoses for different types of treatment. The Formula 1 presents an
exemplary cross-decison rule of perception changes:
a = v1 ∧ b = v2 ⇒</p>
        <p>E(S after A) = x1
E(S after B) = x2
where a, b ∈ A (the set of attributtes), E designates expected value, S - the number of
significantly narrowed coronary arteries and A, B - therapy with placebo and with the
disturbing factor.</p>
        <p>For example, let the pattern a = 1 and b &gt; 2 indicate a stable condition in ECG
(without the danger). Then the cross-decision rule of perception changes can be as in
Formula 2:
a = 1 ∧ b &gt; 2 ⇒</p>
        <p>E(S after P ) = 0
E(S after Z) = 2
(1)
(2)
where P designates a treatment with placebo and Z - with the disturbing factor
(zileuton). Rule 2 means that the treatment causes a misrepresentation of the real state,
determined by coronary angiography (number of stenoses). Despite two significantly
narrowed coronary arteries, patients receiving zileuton have an ECG indistinguishable
from placebo-treated patients without vascular changes.</p>
        <p>The cross-decision rules are therefore a way of the knowledge presentation in an
intelligible form that facilitates its interpretation. For the case of the CHD, they can
be used to decide on the continuation of pharmacotherapy in a designated group of
patients.</p>
        <p>In order to generate the cross-decision rules of perception changes, we will use
the impact tree. It is a binary tree constructed by the greedy algorithm in a top-down
recursive divide-and-conquer manner. It takes a subset of data as an input and evaluates
all possible splits. The best split is chosen to partition the data into two subsets
(divideand-conquer) and the method is called recursively. The algorithm stops when the stop
conditions are met.
3.1</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>Construction of the Tree of Impact</title>
      <p>
        As a criteria for selecting the best split, we propose a measure based on the distance
between the groups. The measure is calulated using probability theory and statistical
techniques, such as expected value, well-known from the literature [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ],[
        <xref ref-type="bibr" rid="ref14 ref15">14, 15</xref>
        ].
      </p>
      <p>Suppose that a set of objects includes two groups of subjects. One group was treated
with a disturbing factor and the other not (patients received placebo). We are interested
in the behavior of a certain characteristic in both groups. Its assessment is carried out
according to the following steps:
1. Determination of the probability distributions of chosen feature in both groups,
designated as A and B
2. Definition of a variable representing the difference of the feature between the two
groups: X = |A − B|
3. Denotation of the distribution of X variable
4. Determination of the expected value of X.</p>
      <p>The expected value of the difference makes it possible to quantify the variation
of the characteristic in both groups. Such a measure used to construct an impact tree,
allows the assessment of the degree of influence of disturbing factor on the behavior of
objects.</p>
      <p>For the concept of CHD, the chosen characteristic may be the number of
significantly narrowed coronary arteries which accepts four values: 0, 1, 2 and 3. Then, the
distributions of the characteristic in both groups are presented in Tables 1 and 2.</p>
      <p>The distribution of X variable (difference of the characteristics between groups) is
presented in Table 3, where the probability pi, for i = 0, 1, ..3 is calculated using the
fomulas in equations 3-6.</p>
      <p>p0 = P (X = 0) = a0b0 + a1b1 + a2b2 + a3b3
p1 = P (X = 1) = a0b1 + a1b0 + a1b2 + a2b3 + a2b1 + a3b2
p2 = P (X = 2) = a0b2 + a1b3 + a2b0 + a3b1
p3 = P (X = 3) = a0b3 + a3b0
The expected value of X is calculated afterwards according to Formula 7.</p>
      <p>E(X) = 0 ∗ p0 + 1 ∗ p1 + 2 ∗ p2 + 3 ∗ p3</p>
      <p>The stop condition of a tree construction is satisfied when the expected value of X
variable exceeds a certain preset threshold th. In addition, the divisions can be
completed also in a situation where the number of objects in a given node falls below a
certain level. The value of th was set to 1.75 for the impact tree in the figure 1.</p>
      <p>The idea is to separate the groups of patients, with a large change in perception from
those with little change. So the quality of the cut is defined by the Formula 8:</p>
      <p>Q = max|E(Xleft) − E(Xright)|
The construction of the impact tree proceeds according to the algorithm 1.</p>
      <p>In a particular node of the impact tree, we determine the effect of a disturbing factor
on the basis of the relationship between the expected number of stenoses in the untreated
group and that value in treated one. The expected impact of the disruption is calculated
by the Formula 9:
(3)
(4)
(5)
(6)
(7)
(8)
Algorithm 1: Construction of impact tree</p>
      <p>Step 1 Sort the values of the numerical attribute a
Step 2 Browsing the values of a attribute from the smallest to the largest
for each appearing cut c designate</p>
      <p>Euclidean distance between the expected values of X feature
Step 3 Select division among the possible divisions,</p>
      <p>such that |E(Xleft) − E(Xright)| = max
Step 4 Split the table DT into two subtables</p>
      <p>DT(Tp ) i DT(¬Tp ) such that
DT(Tp ) includes objects matching the pattern Tp, and</p>
      <p>DT(¬Tp ) includes objects matching the pattern ¬Tp.</p>
      <p>Step 5 IF the tables DT(Tp ) and DT(¬Tp ) meet the stop conditions,
then terminate tree construction
else repeat 1-4 for all tables which do not meet the stop condition
(9)
δ = E(B) − E(A)</p>
      <p>The factor interfering the perception may be deemed as beneficial, if the value of δ
is greater than or equal to some assumed value x. When the δ value falls below a certain
value y, than the factor can be regarded as an adversely affecting agent. In the case of
CHD, we set the value of x on 1.5, and y on -1.5.</p>
      <p>Due to the necessity of sorting attributes values done in time O(n · log n), the
computational complexity of the algoritm 1 is of the order O(n · m · log n).
4</p>
      <sec id="sec-3-1">
        <title>Experiments and Results</title>
        <p>The experiments have been conducted on dataset obtained from the Second Department
of Internal Medicine, Collegium Medicum, Jagiellonian University, Krakow, Poland.
The baseline and angiographic characteristics of the studied subjects are given in Tables
4 and 5. No significant differences with respect to age, gender or the angiographic
characteristics were found between the study groups.</p>
        <p>Using the proposed methodology we achieved the tree of impact as shown in Fig.
1. The tree contains six leaves. An example of the beneficial effect of the additional
therapy (zileuton) in CHD represents the rule in one of the leaves shown in Formula
10. The parameter AV G_ST _DOW N 3 signifies a daily average of the maximum ST
segment depression in particular hours [mV ], F IRST _V LF - heart rate variability
(HRV) power spectrum [ms2] in the range of very low frequencies (0.0033 − 0.04Hz)
in the first hour of the ECG Holter recording and AV G_QT 2_AV G - a daily average of
the QT interval duration average in particular hours [ms]. The pattern based on Holter
ECG parameters is common to untreated patients without coronary stenoses and the
patients with significant stenoses treated with zileuton. In terms of the ECG features,
they are indistinguishable. Therefore, additional treatment modifies the ECG, such as
found in untreated patients without stenosis.</p>
        <p>Placebo(n=33) Zileuton(n=37)
0-vessel coronary disease
1-vessel coronary disease
2-vessel coronary disease
3-vessel coronary disease</p>
        <p>The opposite case represents, for example, the cross-decision rule given by the
Formula 11. The patients with such parameters do not benefit from the additional treatment.
Despite the additional treatment, their ECG is the same as in untreated patients with
significantly narrowed vessels.</p>
        <p>AV G_ST _DOW N 3 &lt; −0.06 ∧ F IRST _V LF &lt; 373 ⇒
E(S after P ) = 2.17
E(S after Z) = 0.2
(11)
For patients who match the exemplary pattern from the rule presented in Formula 12,
using our method, we have no basis for determining whether the anti-inflammatory
treatment is beneficial. In this rule, AV G_QT 1_ST D signifies a daily average of the
QT interval standard deviation in particular hours [ms].</p>
        <p>AV G_ST _DOW N 3 &lt; −0.06 ∧ F IRST _V LF ≥ 373
∧AV G_QT 2_AV G &lt; 464.2 ∧ AV G_QT 1_ST D ≥ 26.1
⇒</p>
        <p>E(S after P ) = 0.25
E(S after Z) = 1.5
(12)
5</p>
      </sec>
      <sec id="sec-3-2">
        <title>Conclusions</title>
        <p>We discussed the method for describing the effect of a disturbing factor on perception.
We considered the influence of anti-inflammatory therapy on perception of narrowing
in the blood vessels modeled by the tree of impact. The presented solution may be used
in the case of CHD for maintaining momentary stability in the ambulance or in the
preoperative period after myocardial infarction.</p>
        <p>Our method chooses ECG parameters which are of great clinical importance, such
as ST-segment depression associated with myocardial ischemia, very low frequency
(VLF) oscillations in the power spectra of HRV or duration and dispersion of QT
interval.</p>
        <p>
          Interestingly, the method selects the parameters of ST-segment, on which
antiinflammatory treatment had no effect according to previous studies [
          <xref ref-type="bibr" rid="ref13">13</xref>
          ],[
          <xref ref-type="bibr" rid="ref16">16</xref>
          ]. The
reason may lie in the use of global statistics, which do not distinguish between individual
patients.
        </p>
        <p>
          In the literature, HRV turned out to be a predictive factor of a cardiac death related
to myocardial infarction and diabetic angiopathy ([
          <xref ref-type="bibr" rid="ref5">5</xref>
          ],[
          <xref ref-type="bibr" rid="ref8">8</xref>
          ]). Suppressed HRV, especially
within its high frequency component, was found predictive for myocardial infarction or
unstable coronary artery disease. While the prolongation of QT interval can predispose
to a potentially fatal ventricular arrhythmia [
          <xref ref-type="bibr" rid="ref11">11</xref>
          ]. The factor interfering perception could
be administered continuously in the case of proven efficacy for specific cases described
by the proposed rules.
        </p>
        <p>The novelty of our method is the use of well-known statistics as an innovative
measure of a cut quality and the application of the cross-decison rules of perception changes
to represent different behaviours of groups of patients.</p>
        <p>However, this method is not free from disadvantages. One of them is the need to
match a particular type of data, that is diversified within the concept (e.g. different
number of stenoses). Another threat is a manual adjustment of the threshold values,
which is always a risk of a misapplication. The weak point of the experiment is small
data set.</p>
        <p>In future we are going to continue the experiments concerning the considered
medical problem, in purpose of extending the results of this paper. We also intent to
strengthen the reliability of the method for its clinical use. We plan to develop a general
approach to describing the influence of a disturbing factor on the perception.</p>
      </sec>
      <sec id="sec-3-3">
        <title>Acknowledgement</title>
        <p>This work was partially supported by two following grants of the Polish National
Science Centre: DEC-2013/09/B/ST6/01568, DEC-2013/09/B/NZ5/00758, and also by the
Centre for Innovation and Transfer of Natural Sciences and Engineering Knowledge of
University of Rzeszów, Poland.</p>
      </sec>
    </sec>
  </body>
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