6

Advances in Chinese Medicine Diagnosis: From

Traditional Methods to Computational Models
Arthur de S
Ferreira Centro Universitrio
Augusto Motta, Brazil

1. Introduction
Ancient Chinese medicine practitioners deduced about 5,000 years ago
that the exterior appearance of the body was closely related to the
functions of the internal organs and viscera. They sought for explanations
for this interior-exterior connection by establishing relationships between
human beings and Nature. Other natural philosophers also applied such
reasoning, e.g. Aristotle [384-322 BC], Leonardo Da Vinci [1452-1519],
and Ren Descartes [1596-1650]. Although it is not possible to say that
Chinese medicine practitioners were unique in this task, they organized those
relationships in a pioneer manner long before their Western counterparts.
Chinese and Western physicians were not distinct in their conceptual
framework, but their respective medical practices evolved on different cultures
and historical contexts. Therefore, it is expected that the advances on
medical knowledge represent this cultural divergence.
Many efforts have been made to integrate the ancient, traditional
knowledge of Chinese medicine into contemporary, Eastern medical practice.
Diagnosis is a key element in this integration of medical systems since it
links the patients needs to the available therapeutic resources. The art of
Chinese medicine diagnosis was enriched throughout history but it main
traditional aspect remains unchanged: the exclusive use of information available
to the naked senses. Clinical information provided by vision, hearing, smelling,
and touching is interpreted
in a framework of Chinese medicine theories of physiology. No equipment or
instrument was
developed with specifc diagnostic purposes or based on Chinese medicine theories.
However, advances in computation and biomedical instruments allowed more
powerful analysis of
clinical data and quantifcation of parameters otherwise assessed only in a
qualitative fashion. As a consequence, computer models for diagnosis in Chinese
medicine were developed and tested in the last few decades and are promising
tools in the clinical environment.
This chapter introduces the traditional methods of diagnosis in Chinese
medicine and
introduces their evolution into computational models. Current methods for
validation of computational model by the assessment of their diagnostic
accuracy and possible sources of errors are also presented. Finally, perspectives
on the issue of computational diagnosis are discussed.

2. Science and art in Chinese medicine diagnosis

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Science may be understood as the common sense refinement through a

prospective effort to transform sensorial impressions into sequential, logic facts
with intra- and inter-experimental

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Recent Advances in Theories and Practice of Chinese Medicine

relationships subjected to verifcation and reproducibility at a certain level of

confdence. Such
relationships should minimize the quantity of basic principles while maximize the
explained medical events. Such an organized knowledge has been guiding clinical
practice in China since
early times and may have interacted with other cultures on a reciprocal
manner, either by knowledge transmission or acquisition. Ancient textbooks
present extensive details regarding the empirical search for a cause-effect
relationship, as well as the necessary training to become
a physician. As a matter of fact, Chinese medicine practitioners held distinct
positions in old
China (Tao, 1953b). Systematization of Chinese medical knowledge allowed the
accumulation
of positive trial-and-error results, the discussion of negative results
for
therapy improvement, and the transmission of medical knowledge.
Accordingly, new methods for diagnosis and intervention were developed in
consonance with this systematization. In this sense, Chinese medicine is thus
composed of scientifc
knowledge since its wide theoretical framework
differentiates it from the popular knowledge.
Such scientific approach of medical theories is also reflected in the diagnostic
field. From the historical point-of-view, diagnostic methods probably started
with the simple need to answer dichotomous questions, such as Is the
subject dead or alive?. From this starting point, diagnostic methods evolved
into more complex methods capable of identification of several constitutional
aspects, different aetiologies and their relationships, as well as the
differentiation of multiple morbid or comorbid states. Descriptions of
prognosis based on the patients examination reflect this high evolution of
diagnostic methods since accurate prognosis depends on accurate diagnosis
and extensive theory-based practice.
The main approach to scientifc research on Chinese medicine has been to
explain the observed phenomena by means of its experimental verifcation. By
doing this, the validity of
the Chinese medical knowledge is indirectly assessed by observing
physiologic or therapeutic responses to acupuncture or herbs prescriptions.
An interesting, alternative approach is to seek for the scientifc evidence
that corroborate or not data reported by Chinese medicine practitioners
ancient and contemporary ones included. Such an integrative approach is
a very attractive strategy for development of robust methods in the diagnostic
feld.

3. Recognition of morbid states and the concept of pattern

Apparently, the frst group of morbid conditions to be recognized were infections.
As early
as the Chin [221-207 BC] and Han [206 BC-219 AD] dynasties, outbreaks of
epidemics led to the differentiation of infections and classifcation of their
symptoms. In sequence, disorders
of the digestive system were recognized and also named according to keysymptoms.
Neurologic, metabolic, cardiovascular, and ophthalmic disorders are among the
other early- recognized conditions (Tao, 1953a). Progressively, other morbid
conditions were identified
in the feld of nutrition, paediatry, otorhinolaryngology, stomatology,

Recent Advances in Theories and Practice of Chinese Medicine

dermatology, urologic obstetrics and gynaecology (Tao, 1958a; Tao, 1958b).

The recognition of new diseases, as well as the improvement of information
regarding manifestations, diagnosis and prognosis were continuous developed
until nowadays.
The defnition of morbid conditions in Chinese medicine differs from its
counterpart in
Western medicine. A pattern (or syndrome, zheng) is the morbid entity of
Chinese medicine and can be derived from any physiologic theory: Ba-gan,
Zang-fu, Liu-jing, Wei-qi Ying-xue, San-jiao, Bing-yin, Qi-xue, Jin-ye, Wu-xing,
Jing-luo (Zaslawki, 2003). A pattern is a set of manifestations that are
absent or present depending on individual, social and environmental

conditions. This set of manifestations is similar to a cluster of symptoms

in Western medicine (Dodd et al., 2001). Each pattern presents a wide
description of manifestations including its onset, duration, location,
progression and severity, collectively known as pattern dynamism (Zaslawki,
2003). Manifestations are not limited to signs and symptoms, but also body
characteristics and shape, psychological statuses, personality, emotional
conditions,
interaction
with
environmental
climate,
and
behaviours.
The
term manifestation profle describes a subset of all possible
manifestations related to the pattern presented by a patient. Hence, different
patients may present different manifestation profles and yet get the same
pattern as a diagnosis. As a corollary, the same manifestation profle exhibited
by different patients may be related to different patterns.
Several types of patterns are distinguished, namely single, complex and
multiple patterns. Single patterns are those related to a unique affected
internal system (zangfu) or channel (jingmai). For instance, Shen-yin
deficiency and Gan-xue deficiency are both single patterns. Complex patterns
consist of two or more affected internal systems or channels and often
share aetiologies or risk factors, being an example the Gan-Dan damp-heat.
Multi-patterns are those in which several single patterns are observed due to
either to pattern transmission
or exposure to multiple aetiologies. For an example of multi-patterns, consider the
following transmission, Shen-yin defciency leading to Gan-yang rising.
Notice that the concept of pattern is not strictly related to diseases or
syndromes in the Western medicine (Lu & Chen, 2009). In contemporary
Chinese medicine literature, diseases were assigned to patterns based on
matched signs and symptoms to integrate both medical practices (O'Connor &
Bensky, 1987; Auteroche & Navailh, 1992; Maciocia, 1996; Ross, 2003). Indeed,
the scientifc approach has been to assess the pair disease/pattern model.
In this context, the same disease may be related to several patterns as well as
the same pattern may
be observed in several diseases. It is very important to observe this
disease/pattern
interaction because of the implications to statistical analysis and
consequently data interpretation. Very often, a study sample is frstly selected
from individuals with disease already diagnosed and secondly is subjected to
the traditional Chinese medicine diagnostic procedure. Hence, statistical
inference and data interpretation cannot be extrapolated to the overall
population implying limited external validity but is limited to the disease
under investigation.

4. Diagnosis as a pattern differentiation process

Ancient Chinese medicine literature does not to explicitly discuss
diagnostic reasoning (Yang & Li, 1993; Luo, 1995; Yang, 2003; Flaws, 2004;
Yang & Chase, 2004). Contemporary literature
reports
that
Chinese
medicine
practitioners
apply
only
the
differentiation reasoning for
decision-making (Maciocia, 1996; Zaslawki, 2003). The diagnosis in Chinese
medicine is obtained through a process named pattern differentiation or
syndrome differentiation (bian zheng). In such a process, the practitioner
examines the patient to seek for meaningful manifestations that indicate a
single, a complex or an even a multi-pattern condition. Recently, Chinese
medicine diagnosis started to incorporate other strategies from Western
medicine (Zhou & Zhang, 2006; Zhu et al., 2006; N.L. Zhang et al., 2008),
such as the deductive-inductive reasoning, tests that confrm a target

hypothesis,
eliminate
an alternative hypothesis, or discriminate among
competing ones (McSherry, 1999).
Pattern differentiation is performed in a three-stage process, namely: information
gathering, data interpretation, and decision-making:

 Information gathering: refers to the assessment of manifestations present or

absent in
patients using traditional examination, possibly in coadjutant with
contemporary methods. It is highly dependent on the physicians ability to
recognize manifestations
and to consider those reported by the patient.
Data interpretation: involves the understanding of the acquired clinical
information and
its consideration. Also, it encompasses the selection of the best
physiologic theory to
explain the patients manifestation profle. If a particular theory does
not explain the interaction
among
manifestations
(and
possibly
patterns), another theory more general or specifc can be selected in
the next stage.
Decision-making: is the process of identification of a pattern among other
possible ones.
If it was possible, practitioners should rely on pathognomonic
manifestations to perform pattern differentiation. However, not all patterns
exhibit such a feature, and
many patterns share common manifestations. Moreover, patterns
have several manifestations that can be present or not depending on
individual constitution and environmental factors.
It is worth notice that pattern differentiation is always possible due to the wide
concept of manifestation and the diversity of physiologic theories to better
differentiate the true pattern (or patterns) from possible ones.

5. Traditional examination methods in Chinese medicine

In the medical diagnostic context, traditional refers to methods,
knowledge, skills, and beliefs indigenous to different cultures applied to
health obtainment, maintenance and restoration. Often, when adopted by
different cultures it is termed alternative or complimentary medicine
(WHO, 2008). For information gathering, the traditional methods are still
applied nowadays and are essentially similar to those practiced by Western
physicians (Peterson et al., 1992).
The traditional Chinese ontology of examination is named Four
Examinations (sizhen). It consists of the sequential application of inspection
(wang), auscultation and olfaction (wen), inquiry (wen), and palpation (qie)
(Tao, 1958a). Several classic authors discussed detailed information regarding
this sequence of examination and its impact on diagnostic errors and potential
cure rates. For instance, a superior Chinese medicine practitioners collect data
from patients according to the Four Examinations and interpret those
manifestations using medical theories, obtaining a cure rate of 90%; mediocre
and inferior doctors have cure rates of 7080% and 60% patients, respectively (Yang & Li, 1993; Luo, 1995; Yang, 2003;
Flaws, 2004; Yang
& Chase, 2004). Recently, it was shown that individual examination
methods provide
diagnostic accuracies compatible with inferior doctors (Ferreira, 2008) and are
signifcantly improved after cumulative application of all Four Examinations
(Ferreira, 2009).
According to such ontology, the naked senses are considered sufficient to the
trained, skilled practitioner to recognize and label patterns. While elaborated
instrumentation was invented and developed for acupuncture and moxibustion

treatment including different types and shapes

of
needles,
moxa
presentations not an instrument was developed for diagnostic purposes.
This subjective, personal practice inputs an extremely high dependency in
the examiners knowledge and the applied procedures.
Several contemporary textbooks are devoted to the patients examination
following that
ontology and will not be explored here. Some categories worth mention
regarding each
examination method (Zhou et al., 2004; Ferreira, 2008). Inspection is
performed to collect

information regarding the patients: general aspect; face aspect; tongue

body, fur, and movement; body constitution; gait; urine and stools aspect.
Children under 2-3 years old must have their throat, orifices, finger veins,
and luo channels inspected (S.C. Wang et al.,
2002). Auscultation and olfaction are executed to collect information on the
patients: breath; speech; cough; secretion; and excretions. Inquiry is
conducted
to
observe
the
patients preferences;
cold
and
fever;
transpiration; head and body; chest and abdomen; pain; excretions; diet
and appetite; sense organs; sleep; medical history; habits; and quality of life
(present dignity, past obscurity). Palpation is performed to identify:
painful areas; skin temperature; points; cubital skin; and pulse images.
Some criticism may arise from the sequence of the traditional ontology for
examination. As a corollary of the holistic approach of Chinese medicine, the
order in which Examination methods are applied does not change the
pattern differentiation outcome. Assuming that practitioners always use the
Four Examinations and are successful in this task, they conclude their
screening procedure with the same manifestation profle no matter the
applied order. This must not be confused with the timeline of onset of
manifestations because when at screening, the patient presents simultaneously
all manifestations. Although each Examination contributes differently for
reducing pattern differentiation errors, it seems that the order in which the Four
Examinations are used is just a matter of keeping a rigid routine to ensure that
every aspect of screening was performed (Ferreira, 2011).

6. Introduction to computational models for pattern differentiation

With the advance in computing techniques and equipment, the pattern
differentiation process
is
properly
evolving
into
a
computer-based
procedure.
The
rapid
evolution
of mathematical methods based on
computational algorithms allowed the implementation of diagnostic techniques
derived from simple to complex routines. Additionally, study designs,
statistical methods for data analysis, and guideline reports are also
available
for assessment of diagnostic accuracy and epidemiologic
performance of automated methods. However,
the
computerization
of
Chinese
medicine
cannot
overlook
its
theoretical foundation since it
provides the basis for intervention.
6.1 Attributes of computational models for pattern differentiation
It is not difficult to build computational models for diagnostic purposes the
difficulty lies
in making them good and reliable. An idealized pattern differentiation
model should perform as a superior practitioner or even better. Thus, a
computational model of pattern differentiation must present the following
attributes:
Respectful concerning the theoretical framework of Chinese medicine;
Robust performance across a variety of suitable physiologic theories with
minimal
computational cost;
Ability to perform despite having different amounts of manifestations
in the
manifestation profle;
Ability to identify exams composed of single, complex and multi-patterns;

 Ability to merge manifestations that correspond to the same pattern;

Ability to split manifestations that correspond to more than one pattern;
Ability to decompose multiple patterns despite noisy manifestations and
biological
variability;

 Minimal use of arbitrary thresholds and minimal sensitivity to any required

thresholds;
Multi-pass algorithm to allow classification context to grow iteratively;
Valid stopping criteria for iterative process;
Ability to decouple low-assignment rate versus low-error rate trade-off as
much as
possible;
Accuracy and completeness of pattern differentiation;
Ability to supply some measurement of confidence regarding the pattern
differentiation
results.
6.2 Dataset of computational models for pattern differentiation
Despite the use of different approaches to perform pattern differentiation,
some elements are common to those methods, such as the usage of knowledge
datasets, training and testing databases, and questionnaires. As far as the
manual insertion is the most frequent method applied, some discussion is
needed on this topic.
Although many efforts have been made to standardize medical terms, currently
there is no
standard dataset for patterns and manifestations. In general, datasets have been
generated
by manual insertion of terms collected from literature (Ferreira, 2008;
Ferreira, 2009, Ferreira, 2011) or by data mining algorithms (refer to Lukman
et al., 2007 for a revision on mining methods applied to Chinese medicine;
Zhou et al., 2010). Patterns on database must
be mutually exclusive and collectively exhaustive (Harding, 1996),
i.e., for each manifestation there is at least one possible pattern, and
there is no pattern without manifestations. Manual insertion leads datasets
subjected to common errors of:
Typography: typos, case-sensitive letters, and medical synonymous;
Manifestation redundancy: for the same pattern, typing a manifestation twice
or more
in the same examination method or among different methods regarding
the same pattern;
Pattern label redundancy: typing the same patterns label twice in the
dataset, making
such label not unique and possibly with different descriptions;
Pattern description redundancy: typing the same patterns description
twice in the
dataset yet with distinct labels, making their content not mutually
exclusive (in this case, both patterns are indeed the same pattern).
The errors described above can be minimized or even eliminated with the
use of simple routines for intra-pattern and inter-pattern exploratory
analyses using common string search algorithms. It is strongly recommended
running such routines for quality control of manually inserted datasets before
model validation, especially when dealing with large datasets or even
multiple datasets simultaneously. For instance, intra-pattern consistency can
be obtained by excluding any repetitions of manifestations in the same
examination method, as well as among the Four Examinations describing the
respective pattern (Ferreira,

2008). Inter-pattern consistency can be obtained by ensuring that two

patterns were not
described with the same complete manifestation profle (Ferreira, 2008;
Ferreira, 2009). Analysis of dual pattern similarity by means of the Jaccard
coeffcient (Jaccard, 1901) and associated confidence interval (Real, 1999) is
an alternative to check for pattern redundancy (Ferreira, 2011). The use of a
controlled vocabulary from dataset avoids the typos, eliminates language
ambiguity and ensures that every one is using the same terms to mean the
same attribute which limits the use of synonymous.

7. Computational models for pattern differentiation

The application of objective rules for pattern differentiation may help
diminish diagnosis variability (G.G. Zhang et al., 2005; G.G. Zhang et al., 2008)
dependent on the practitioners expertise. A large amount of computational
methods have been published, too many to list them all. Some of them were
developed and tested against simulated and real cases, in different disease
models, and are discussed here. In chronological sequence, this work
includes the Traditional Chinese Medicine Sizheng Integrated Recorder
and
Aided Syndrome Differentiator (TCM-SIRD), modifed Greedy Bayesian
Pattern Search algorithm (GBPS*), Information Management System of
Traditional Chinese Medicine Syndrome Project based on Prior Knowledge
Support Vector Machine (P-SVM), Chinese Medical Diagnostic System
(CMDS), Pattern Differentiation Algorithm (PDA), and Multi-Label k- Nearest
Neighbour (ML-kNN).
7.1 Traditional Chinese Medicine Sizheng Integrated Recorder and Aided Syndrome
Differentiator (TCM-SIRD)
Zheng and Wu (2004) developed the Traditional Chinese Medicine Sizheng
Integrated Recorder and Aided Syndrome Differentiator (TCM-SIRD). This
system
performs information gathering based on sensors (image, pulse and
odor signal acquisition) and text information.
A
computational
routine, namely
Integrated
Sizheng
Information Application, merges the data transferred from
sensors and provides assistant diagnosis service by means of data
interpretation. The provided output (such as type of tongue coating, face
image, and pulse) is used to form a primary differentiation of syndromes by
the Sizheng Expert Decision, the decision-making modulus based on rules
extracted from Chinese
medicine
experts
experience.
The
objective
rules extracted from expert practitioners were not described, neither their
computational implementation.
The authors described methods to be implemented for an objective assessment of
diagnostic with description of a single test case. Although the model for pattern
differentiation was not
detailed described, the authors advocated the use of the Four Examinations. No
description was given on how the information was processed for diagnosis.
No result regarding its diagnostic accuracy was reported.
7.2 Modified Greedy Bayesian Pattern Search algorithm (GBPS*)
X. Wang et al. (2004) designed a self-learning expert system with a novel
hybrid learning algorithm based on Bayesian networks, called the modifed
greedy Bayesian pattern search algorithm (GBPS*). The proposed pattern
differentiation model was based on the GBPS algorithm (Spirtes & Meek,
1995) with a modifed version in the search procedure algorithm. The maximum
accuracy of 88% obtained for pattern differentiation was estimated by
pseudo-random generation of a sample. The authors discussed the high
dimensionality of patient instances represented by multiple manifestations and
diagnostic hypotheses. Their results suggested the use of most frequent
attributes to reduce such dimensionality and consequently increase diagnostic
accuracy.
The authors developed based on the united system of syndrome
differentiation
characterized by two characteristics. The frst characteristic, the key elements
for syndrome differentiation, was abstracted from keywords in medical

theories and grouped in two categories (the place where diseases occur; and
the pathological state of the body or possible causes that make disease break
out). As each key element usually exhibits a variable

strength of association to manifestations, the pattern identifcation could be

performed
according to whether the key element is present or not. The second
characteristic, the standard syndrome-name database, was used to solve the
problem that a pattern could be assigned with different labels by different
practitioners. In the database, a standard pattern label includes at least one of
the key elements described above. A dataset of 800 cases from real patients
was used to train the Bayesian classifier.
The complete system for pattern differentiation is designed in modulus and its
architecture consists of three parts: (1) input of the system, thereof one is sample
database with attributes
of symptoms and key elements, the other two are key-elements database
and database of
clinical observations to be diagnosed; (2) Analysis and diagnosis part, that is, the
kernel part
of the system, including: module for variable selection, module for discovering
dependency relationship, module for learning classifers, module for syndrome
differentiation, module
for mining frequent sets among key elements, and module for modifcation by
experts; and
(3) user interface, through which users and the system can interact with each
other.
The computational model for pattern differentiation proceeds in two phases and its
pseudo- code was provided (X. Wang et al., 2004). During the frst phase, the key
elements present
by a patient are identified. The second phase searches the standard
syndrome-name database, inquiring whether the corresponding patterns
consist of these identifed key elements. The algorithm considers all the
attributes (including manifestations, key elements and patterns) as Boolean
variables that take only two values: absent and present. The module for
syndrome differentiation used the learned classifier to compute the
posterior probability of every key element with Bayes theorem, and output
those elements whose probability exceeds the threshold set by experts. Then
the module queries and outputs the names of those patterns containing
these key elements from standard pattern-name database. Furthermore,
the module computes occurrence probability of each pattern by multiplying
the probabilities of its corresponding key elements, under the assumption that
these key elements are independent. Finally, the module selects the
patterns with the probability excess diagnosis threshold.
7.3 Information Management System of Traditional Chinese Medicine Syndrome
Project based on Prior Knowledge Support Vector Machine (P-SVM)
Yang et al. (2005) developed the Information Management System of
Traditional Chinese Medicine Syndrome Project based on Prior Knowledge
Support
Vector
Machine
(P-SVM). SVM aims to process training and
generalization with limited information provided by the sample data set
without consideration of knowledge from application background. In the
framework of limited sample data set learning, SVM makes maximum
use
of
the information provided by sample data set theoretically
regardless the application related knowledge. The authors reported an
accuracy rate of 95% with the trained P-SVM to classify
a sample set of 2,000 simulated records.
The general principle of the method is described here, and its pseudo-code

was provided (Yang et al., 2005). A pattern dataset is used to train and
test the P-SVM model. The test procedure consists of: a) generation of an
expert knowledge dataset; b) description of the expert knowledge as rules
to train the dataset to create the scale of confdence values; c) input data
with confdence values to the Platt's Sequential Minimal Optimization (P-SMO)
algorithm; d) comparison of the accuracy rates under different amount of
training samples. The pattern dataset included the literature from 1978 to
2004 with approximately 400,000

entries and its ontology was organized with the entries: author, origin, title,
subject heading, subheading, key word, and abstract. In the classifcation
system of SVM with prior knowledge, the classifer will learn the traits of
the certain thematic information from the corresponding prior knowledge.
Therefore, based on the prior knowledge, the classifer is able to fnd out the
appropriate literary information from the massive data.
No description of how the cases were simulated is available; thus, it is not
possible to repeat the simulation procedure and to compare accuracy results.
Moreover, the P-SVM theory was not discussed in light of the mode-of-thinking of
Chinese medicine experts.
7.4 Chinese Medical Diagnostic System (CMDS)
Huang and Chen (2007) developed the Chinese Medical Diagnostic System
(CMDS) for pattern differentiation of diseases related to the digestive system. It
uses a Web interface and expert system technology in diagnosing 50 types of
digestive system diseases. The authors compared the diagnosis of 20 simulated
cases made by CMDS and diagnosticians and found the results satisfactory;
however, they did not report either simulation procedures or statistical
validity. The authors also stated that the Four Examinations were
necessary for achieving a correct diagnosis. The authors reported high
reliable and accurate diagnostic capabilities in 95% of 50 simulated cases
without any description of either how cases were simulated or possible sources
and types of error.
The CMDs departed from an ontology-based model, in which the proposed
ontology was
derived from the traditional one but focused on digestive diseases and patterns.
The whole system is composed by three main components: a) Java Expert
System Shell (JESS); b) Database set; and c) knowledge extractor. The routine
for pattern differentiation in depicted
in the inference engine modulus of the JESS and automatically matches facts
(users entries) against patterns and concludes which rules are fred in CMDS.
Two databases (general and knowledge databases) are used to store all
information and rules necessary for pattern differentiation, respectively.
7.5 Pattern Differentiation Algorithm (PDA)
Ferreira (2008) proposed the pattern differentiation algorithm (PDA) based on
an objective criterion developed to account for pattern holism (Guang,
2001). A second criterion was proposed and provided a signifcant increase in
diagnostic accuracy of the model, being up
to 94.7%(sensitivity = 89.8%; specificity = 99.5%) with the Four
Examinations for Zangfu
patterns (Ferreira, 2009). This method allowed testing the impact of different
combinations
of the Four Examinations and the amount of available information presented by
patients on PDAs statistical performance. Also, its associated method of model
validation uncovered types of diagnostic errors otherwise not assessed by other
computational models (Ferreira,
2011).
Clinically,
PDA
was
applied
to
patients
with
arterial
hypertension and help understand that Zangfu patterns associated to this
disease are indeed evidence of the progression of target-organ damage (Luiz
et al., 2011).
PDA works in a three-stage schema and its pseudo-code was provided elsewhere
(Ferreira,

2009). The first stage data collection and dataset search uses the data entry
from patients exam to search for free terms and quoted phrases, e.g.,
headache and headache. The former term recalls patterns with headache
within its manifestations profle (ocular headache, occipital headache, etc.); the
latter term recalls patterns with the exact term. Combinatorial procedure (Zuzek
et al., 2000) was used after data collection because the diagnosis does not
depend on

the sequence of the results obtained during the exam (Wolff, 2006).
Manifestations were
described as specifically as possible including onset (palpitation in the
morning, palpitation in the evening), duration (acute headache, chronic
headache), location
(occipital headache, ocular headache) and severity (dry tongue,
slight moist tongue, moist tongue), as well as any other characteristic that
may be necessary to allow the pattern differentiation. Manifestations that cooccur in two or more patterns were assigned with the same term to increase
the accuracy of string search algorithm.
At the second stage selection of candidate patterns a pattern is
considered as a
candidate if it presents at least one manifestation collected at the exam.
Patterns with no manifestations recognized were not used for further
analysis. The strength of such indication of the candidate pattern is
calculated as an objective criterion F%,K. This is an important stage since it
recalls any possibility (F%,K>0) within the dataset and increases the sensitivity
of the algorithm. Since patterns maybe described by different quantities
of manifestations, the available information must be normalized to allow
comparison among them and hence was used as a second objective
criterion, N%,K,. It is expected that the occurrence of a successful pattern
differentiation increases with decreasing F%,K. It is also expected that the
occurrence of a successful pattern differentiation increases with increasing N%,K.
However, as the accuracy of a diagnostic test is expected to decrease with
either lower
or higher cutoff values, it is appropriate to subtract a cutoff values from N%,K to
dislocate the
accuracy curve to its optimum operating point. As such, the maximum
accuracy is
associated with the minimum N%-cutoff,K. Hence, the candidate patterns
simultaneously ranked in descending order of F%,K and ascending order of
N%-cutoff,K represent a list of diagnostic hypotheses.
The last stage pattern differentiation identifes the diagnosis. The
diagnostic algorithm receives the manifestation profle and outputs for each
tested profle: a) the identifed diagnosis; b) the list of diagnostic
hypotheses. Pattern differentiation is considered successful in either of two
situations: 1) if PDA founds a unique diagnostic hypothesis that explains
simultaneously all collected manifestations, i.e. F%,K=100%; or 2) if there is
one pattern among all diagnostic hypotheses with a highest, unique F%,K
value and lowest, unique N%-cutoff,K value. Otherwise, if multiple diagnostic
hypothesis were found with equal values of F%,K and not unique values of N%,K
the procedure is considered unsuccessful since differentiation
among
competing patterns was not possible. In this case, physicians have access
to the diagnostic hypotheses list and may want to revise the collected
manifestations, continue examination of the patient to search for other
manifestations, replace the collected symptoms/signs with more specifc ones, or
even subjectively chose a pattern.
PDAs average time for pattern differentiation of each case with the Four
Examinations is estimated in less than 0.1s, which is suitable for clinical
applications. There is no need to train PDA, which is a mathematical process
already subject to bias. PDAs method is simple, and both criteria can be
calculated even manually by a Chinese medicine practitioner (for a low number
of candidate patterns). Its reasoning is entirely based on the actual

process executed by Chinese medicine experts and thus reduces the error
in data collection and analysis. PDA is more stable than other learning
algorithms because the fnal diagnosis does not depend on the initial guess
or sequence of manifestations used during the learning phase (Ferreira,
2009).
However, PDA is dependent on the pattern dataset. PDAs dataset was built in a
form of open base, in which new information can be added (or modifed) to the
knowledge database

to increase statistical performance of the criterion. As a corollary, the proposed

methodology relies on human experts, not only to select the knowledge, but
also to provide the database organization. To reduce the implications of
the
manual
insertion
of
information, computational routines for interpattern and intra-pattern consistency were implemented.
The major limitation of PDA is that it was tested only for Zangfu single patterns
(Ferreira,
2008; Ferreira, 2009; Ferreira, 2011). Such case is the simplest one found in
clinical practice
for Zangfu patterns since the pathological process just begun to promote
changes in
homeostasis. The same subject may present several patterns simultaneously
that are not
mutually exclusive. Additionally, common etiologies and pattern
transmissions among
Zangfu are contributing factors to limit the models performance. Finally, other
theories are often used to perform diagnosis and were not yet evaluated (Maciocia,
1996).
7.6 Multi-Label k-Nearest Neighbour (ML-kNN)
Liu et al. (2010) obtained up to 78% accuracy using only the Inquiry
method (n=185 manifestations) for identification of multi-patterns (based on
6 ZFSPs) related to coronary heart disease obtained from real cases. The
pseudo-code of the ML-kNN was provided by the authors.
The kNN is an algorithm that searches for the nearest point in a training
data set. This theory regards an instance as a point in synthesis space; thus,
the label of a test instance is probably similar to those of several nearest points.
The data set for pattern differentiation of coronary heart disease belongs to
multi-label; whereas kNN only processes single label data sets,
so
the
collected data set should be split into many groups of single label to be
calculated. In the multi-label data, there is much relationship among each
label, so simple splitting inevitably result in data loss. For this reason,
multi-label learning algorithms are developed so as to better reveal the
correlation of the labels, of which multi-label kNN (ML- kNN) is a popular
technique. ML-kNN is a lazy multi-label learning algorithm developed
on the basis of kNN. Based on the theory of kNN, ML-kNN aims to fnd k nearest
instances for each test instance. In ML- kNN, the labels of test instances are
judged directly by nearest instances, which is different from kNN.

8. Validation of computational models for diagnosis in Chinese medicine

For the model to be useful, expert practitioners must have confdence in
the results and predictions that are inferred from it. Verifying or validating
the model can provide such confdence. In principle, model validation is done
by comparing the models behaviour with the patients and evaluating the
difference. In the diagnostic feld, the computational model
is compared to either a gold-standard or a reference-standard method.
8.1 Model validation with gold-standard and reference-standard
The main issue related to diagnostic accuracy tests it he need for a goldstandard method
or at least a reference-standard method to compare the results obtained

with the model being tested. The gold-standard method for diagnosis is the one
that provides the true health status of a person while the reference-standard
method for diagnosis is the one that provide the health status closest to the
true one. Obviously, gold-standard methods are preferred for model validation
and assessment of a models diagnostic accuracy. However, it is almost
impossible to test clinical diagnostic models with gold-standard methods
since the true

health status is unknown a priori. In this case, a diagnostic model with

known statistical
properties is applied to obtain a result that is used as the reference-standard.
Patterns identifed by a panel of expert Chinese medicine practitioners has been
used as the standard for diagnostic accuracy tests of computational models
using data from population samples (Zhou & Zhang, 2006; Zhu et al., 2006;
N.L. Zhang et al., 2008). This method presents a major drawback since the
real diagnosis is not known and samples may be biased (hospital patients,
community subjects, etc.). Moreover, the agreement in diagnosis among
practitioners may be low (31.7%; 27.535%) (G.G. Zhang et al.,
2005),
despite
some improvement after training (73%; 64.385.7%) (G.G.
Zhang et al., 2008). The Standards for Reporting Interventions in Controlled
Trials of Acupuncture (STRICTA) (MacPherson et al.,
2010) recommend that the experience of Chinese medicine practitioners should
be reported
in clinical studies because such experience may influence diagnosis. As such,
new diagnostic tests should not be compared to diagnoses made by Chinese
medicine practitioners but with methods that guarantee correct diagnosis.
For the determination of the accuracy of Chinese medicine diagnostic tests, a
large number
of patients with possible combinations of the manifestations for each
pattern must be generated. Thus, it is virtually impossible to estimate the
diagnostic accuracy without computer methods. Stochastic simulation
models have been used for research in health sciences. A well-known
simulation method is the Monte Carlo (Metropolis & Ulam, 1949), in which the
basic idea is to stochastically generate examples of a numerical variable and
then evaluate the outcome of the model under evaluation. With stochastic
methods, simulated patients can have their health status characterized
by a computational model. The simulation of cases fxes both issues by
randomly selecting manifestations only from the selected single pattern
(Ferreira, 2009). Stochastic method allows a focus on the properties of
manifestation profles instead of individual manifestations. This procedure
generates a large number of examples of any given pattern (stochastic process)
and then examines the relative proportion of successes of the diagnostic test
(deterministic process). Some modifications of the original Monte Carlo
method are needed to enable stochastic methods to process nominal
variables. Because cases are simulated from all possible manifestations of
each pattern in the dataset, the output of the computational model can be
compared to the actual name of the simulated pattern in the dataset. Thus,
simulation of cases can be considered as
a gold-standard method. Moreover, patient simulation models can be
composed of independent algorithmic codes (i.e., there is no code
sharing), so the results of the identifcation are blinded to the simulation
parameters.
Currently, the computational model for simulating patients and testing diagnostic
accuracy
is the Manifestation Profle Simulation Algorithm (MPSA) (Ferreira, 2008;
Ferreira, 2009, Ferreira, 2011). MPSA generates the study population
according to different strategies to create case (true positive) and control
(true negative) groups, as well as a proposal for identifying and handling
missing cases. The inclusion criterion is the simulation of cases
representing a single pattern in the knowledge dataset. For simulation
purposes, MPSA assumes that the probability of each manifestation in the

general population is given from previous studies or, if unknown, it is

suggested to follow a uniform distribution (Ferreira,
2009). The comparison between the simulated pattern and the identifed diagnosis
yields the binary classification of the proposed method for pattern differentiation.
In MPSA, true positive (TP) cases of a pattern K are simulated by selecting from
the dataset
a random quantity of manifestations NR,K. Each sorted manifestation is excluded
from the

set of possible manifestations to prevent multiple occurrences of the same

manifestation at the respective simulated case. This iterative process continued
until the NR,K manifestations were sorted to generate the manifestation profle.
To obtain a true negative (TN) control for the same pattern K, two alternatives
were proposed. In the frst alternative, this respective pattern K is removed
from the dataset and the same quantity NR,K is selected from the entire dataset
and respective examination methods (Ferreira, 2008; Ferreira, 2009). The
second alternative is to sort NR,K manifestations from another pattern pseudorandomly chosen in the dataset after exclusion of pattern K (Ferreira, 2011). In
both alternatives, the procedure allows a quantitative pair-wise comparison
between TP and TN profles with respect to the available information for pattern
K, N%,K. Although the TP pattern was removed from the dataset,
its
manifestations that co-occur in other patterns are still present and could
be selected to compose a TN manifestation profle. Since patterns
may not present manifestations for some of the examination methods, empty
manifestation profles related to these examination methods represent missing
cases and were excluded from analysis.
Despite the main advantage of knowing a priori the true pattern and
methodological blinding, some limitations need to be mentioned. Manifestations
may be sampled multiple times within the same run, resulting in less variation of
manifestations profle than it would be expected to see in real patients. Also,
manifestations may not be chosen at all, resulting in not tested data. However,
large simulated samples from the dataset diminished these limitations
(Ferreira,
2008). To assess the quality of the simulated cases and controls, a routine can be
implemented
to check if all manifestations were used for simulation of manifestations
profles. The
algorithm performs a reverse engineering by recreating the dataset from all
simulated true
positive cases. The algorithm searched among all manifestation profles
simulated for each
pattern and grouped the manifestations present at least once among the simulated
cases into a
temporary dataset. After comparison with the original dataset, the algorithm
reports whether the patterns that were completely simulated (i.e. all
manifestations were used for analysis), partially simulated and not used for
simulation (Ferreira, 2011).
8.2 Detection and classification problems
In general, the diagnostic process is designed to detect if the subject is healthy
or ill. In this case, two groups of subjects with known true conditions are used: a
group of individuals in which the condition to be tested is truly present; and
a group o individuals in which the condition to be tested is truly absent.
Adapted to Chinese medicine framework, a "healthy pattern" diagnosis must be
described in the same manner as the ill patterns. For instance, the "liver-blood
defciency" pattern should have the mutually exclusive counterpart "liver- blood
healthy" pattern. The description of such health-related patterns is possible
because pattern differentiation process is not limited to assessing
presence/absence
of manifestations (e.g. asymptomatic individuals may be
also have their patterns identifed). A completely healthy person will present
all healthy patterns simultaneously. However, in clinical practice it is difficult
to fnd a patient that is completely healthy and thus the pattern differentiation

process must be applied to patients. In this case, the diagnostic model must
recognize the underlying pattern (or patterns) and not the healthy or ill statuses.
8.3 Sample sizes, participant recruitment and sampling
A important issue in diagnostic accuracy studies is the sample sizes
determination, which can be estimated based on equations derived for
detecting differences in accuracy tests

Advances in Chinese Medicine Diagnosis:

From Traditional Methods to Computational Models

29

using receiver operating characteristic (ROC) curves (Hanley & McNeil,

1982). For
calculations, it is necessary the expected difference in accuracy between the
reference and
the index test, the level of signifcance (usually =5%, Z=1.645, one-sided),
and the power
of the test (usually =90%, Z=1.28). The equation designed to real cases
can be used in
simulated ones provided that the absolute consistency between original
and recreated datasets is proved as described before. This is an important
issue related to the quality control in this study and should not be omitted in
other simulations studies were pattern differentiation outcomes are assessed
(Ferreira, 2011).
8.4 Estimating the diagnostic accuracy of a diagnostic model
Diagnostic models present domains of validity, i.e. they should not be
used outside the validation scope since there is no estimation concerning its
performance. The implications range from underestimation to overestimation
of the models diagnostic accuracy. The Standards for Reporting of Diagnostic
Accuracy (STARD) (Bossuyt et al., 2003) summarized the necessary steps for
conducting scientific works to determine diagnostic accuracy of models.
Although not specifed in the STARD, such methodology can be also be adopted
by studies in which computational models perform diagnosis, even in case
of simulated patients. The validity of a new diagnostic model is obtained
by comparison of the new models results with the actual result. However,
very often the actual value is not known most commonly due to absence of
gold-standard diagnostic methods.
Accuracy, sensitivity, specifcity, positive and negative predictive values
are the most common measures of a models performance. Accuracy is
defned as the proportion of true results in the population. Sensitivity is the
probability that the test is positive given that the patient is sick (Altman &
Bland, 1994a), while specificity is the probability that the test is negative
given that the patient is not sick (Altman & Bland, 1994a). Positive and
negative predictive values are proportions of true positives and true
negatives out of all positive
results, respectively (Altman & Bland, 1994b). All those estimators are
obtained from 22
confusion matrices (Table 1) made from classification of simulated and
identifed diagnosis (Jekel, 1999; Altman & Bland, 1994a; Altman & Blend,
1994b). Departing from Table 1 and adapting the epidemiological concepts to
Chinese medicine framework, computational models can be evaluated with
estimations of:
Gold-standard test result
Simulated
Other pattern
pattern
(Control)
(Case)
Identified pattern True positive (TP)
False positive (FP)
New test result
Other pattern
False negative (FN)
True negative (TN)
Table 1. Confusion 22 matrix for assessment of diagnostic accuracy between
the reference test and pattern differentiation algorithm.

30

Recent Advances in Theories and Practice of Chinese Medicine

a. Accuracy:
proportion
of
successful
pattern
differentiation
(true
results) in the population (equation 1). Diagnostic accuracy indicates
the total sum of corrected assigned cases.
TP TN
Accuracy
TP FN TN
FP

100% ;

(1)

b. Sensitivity: proportion of successful pattern differentiations correctly predicted

by PDA
in cases (equation 2).
Sensitivity
TP

(2)

100%;

TP
FN
c. Specificity: proportion of successful pattern differentiations correctly predicted
by PDA
in controls (equation 3);
Specificity TN 100%;
(3)
TN
FP
d. Negative predictive values: proportion of unsuccessful pattern differentiation
correctly predicted by PDA (equation 4).
Negative

predictive

(4)

value 100%;
TN
TN
FN

e. Positive predictive values: proportion of successful pattern differentiation

correctly predicted by PDA (equation 5).
Positive

predictive

value 100% .
TP

(5)

TP
FP
ROC plots are used to visualize and estimate accuracy of the models
classification. Those estimators
are
readily
available
from
2x2
crosstabs
obtained
from
simultaneous classification of the results
regarding the gold-standard and the new model under evaluation. In
ROC plots, the smallest cutoff value is the minimum observed test value
minus 1, and the largest cutoff value is the maximum observed test value
plus 1. All the other tested cutoff values were the averages of two consecutive
ordered observed test values (Hanley & McNeil, 1982; Hanley & McNeil, 1983;
Altman & Bland, 1994c).
8.5 Comparing diagnostic accuracy of two computational models
Consider now the situation where two computational models can be used. It is of
interest to select the best model in terms of diagnostic accuracy. Such a
comparison can be performed
based on a pair of 22 confusion matrices (Table 2) made from classification of
simulated
and identifed diagnosis simultaneously by the two computational models.
True negative
Model 1
Model
2

True positive
+
B

Model
2

Model 1
+

+
a

Table 2. Confusion 22 matrices for comparison of binomial proportions

between the two diagnostic tests. (+) and (-) indicate positive and negative
test results respectively. B is the number of TN cases classifed correctly by
test 2 and falsely by test 1 and conversely for C cases and analogously for the
TP group.

The 95% confdence interval (95%CI) for the binomial proportions p (accuracy,
sensitivity,
specificity, negative predictive value, positive predictive value; equations 15) can be calculated with Wilsons method (Agresti & Coull, 1998). If both models
are to be evaluated
on the same samples of TP and TN cases, an adaptation of McNemars test for
correlated proportions is applied (Linnet & Brandt, 1986). The TP and the TN
profles are divided into four parts according to their test responses (Table
2). Estimations related to ROC curves (AUC and respective 95%CI) can be
obtained with the nonparametric Wilcoxon statistic (Hanley & McNeil, 1982;
Hanley & McNeil, 1983).
Since the Four Examinations provide the basic ontology for pattern
differentiation, it is of interest to study the partial contribution of each
Examination as well as their cumulative, sequential application. Hence, the
diagnostic accuracy may be studied in terms of the following sets of the
Four Examinations:
1. Inspection;
2. Auscultation & Olfaction;
3. Inquiry;
4. Palpation;
5. Inspection, Auscultation & Olfaction;
6. Inspection, Auscultation & Olfaction, Inquiry;
7. Inspection, Auscultation & Olfaction, Inquiry, Palpation.
Indeed, as manifestations are closely related to the interdependent
internal organs,
combined Examination methods are preferable since they cover several
forms of presentation of the same pattern.
8.6 Recognition of diagnostic errors in pattern differentiation
All models have a certain domain of validity. This may determine how exactly they
are able
to describe the systems behavior. It is hazardous to use a model outside the area
it has been
validated for. Reports of errors for Chinese medicine practitioners are available
from ancient
literature (Yang & Li, 1993; Luo, 1995; Yang, 2003; Flaws, 2004; Yang &
Chase, 2004)
including non-skilled practice, misdiagnosis and mistreatment; however, little
contemporary literature is available on this subject. Evidence shows that
subjectivity of
manifestations or limited detection of clinical features is the major causes of
unreliable
pattern differentiation made by Chinese medicine practitioners (Kim et al., 2008;
OBrien et
al., 2009). While diagnostic errors can never be eliminated, they can be
minimised through
understanding factors related to the pattern differentiation process.
Recognition of factors related to the performance of diagnostic methods is
relevant to the development of reliable methods that can be implemented
for clinical and research
purposes. The frst limitation to pattern differentiation algorithms is that
the user must possess a certain level of knowledge to discriminate or
interpret the patients complains (Harding, 1996). Therefore, an implicit
assumption to all current computational models is that the patients are

capable of reporting their symptoms and that the Chinese medicine

practitioners are able to correctly identify manifestations.
Pattern similarity is intrinsic to Chinese medical knowledge. Pattern
similarity introduces errors in the pattern differentiation process, as the
patients true pattern may not be properly assigned. Dual pattern
similarity
has
moderate,
statistically
signifcant
effect
on pattern
differentiation
outcome
but
cumulative
application
of
the
Four
Examinations progressively reduces the strength of signifcant association
between pattern similarity and diagnostic errors (Ferreira, 2011).

Currently three pattern differentiation outcomes can be distinguished,

namely
(a) identifcation of the true pattern (correct diagnosis), (b)
identifcation of a pattern that is not the true pattern (misdiagnosis) and (c) no
identifcation of pattern at all (undiagnosis). For discrimination of those types
of diagnostic errors, 2x3 crosstabs (Table 3) are used to differentiate
among correct diagnosis, misdiagnosis and undiagnosis.

New test
result

Identified pattern
Other pattern
No pattern identifed

Gold-standard test result

Simulated
Other pattern
pattern
(Control)
(Case)
Correct (TP)
Erroneous (FP)
Erroneous (FN)
Correct (TN)
Absent
Absent

Table 3. Crosstabs (2x3) for investigation of diagnostic errors of computational

models.
The distinction of error types in this study is possible if the manifestation
profles of true negative controls are any other true pattern that was not its
true positive counterpart, and not just random manifestations from all
patterns in dataset as in other studies. This modifcation expands the
interpretation of false negative cases from one wide option (it can
be any other pattern, no pattern at all, or it was not possible to uniquely identify
any pattern K) into two separate options (it is pattern K or it was not possible
to uniquely identify any pattern in dataset). With this true condition made
known a priori it is possible to distinguish misidentification from no
identification among unsuccessful outcomes (Ferreira,
2011).

9. Future directions
Although validated diagnostic models are available, several issues limit their
application in patient care. For instance, almost all computational models
deal with single patterns a condition rarely seen in clinical practice or a
single disease. Complex and multiple patterns present additional difficulties in
the diagnostic task since there are several combinations of two
or
more
patterns that could result in the same diagnosis. Multiple patterns
decomposition is then an open feld of research with direct clinical applications
and should
be investigated.
Standardization of treatment prescription is possible since well-defined,
consistent diagnosis can be achieved with computational models. Current
trends focus in computer-aid to perform diagnosis and treatment. It is
believed that the combination of traditional methods and modern resources may
improve the efficacy of Chinese medicine intervention.
Suggested topics for future research on computational models for pattern
differentiation:
Construction of an internationally available Chinese medicine ontology and
web-based
knowledge dataset with patterns and manifestations.
Use of qualitative, fuzzy-like scales developed in Eastern medicine. Ex.:
tongue fur.
Discovery of which subsets of manifestations lead to a more accurate
diagnosis
Determination of the distribution of manifestations in each pattern (and

patterns in the dataset) to improve the simulation of manifestation profles.

Incorporation of common etiologies and pattern transmissions into
computational
models to extend its application in general clinical practice.

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Recent Advances in Theories and Practice of Chinese Medicine

Edited by Prof. Haixue Kuang

ISBN 978-953-307-903-5
Hard cover, 504 pages
Publisher InTech
Published online 18, January, 2012
Published in print edition January, 2012

During the recent years, traditional Chinese medicine (TCM) has attracted the attention of researchers all over
the world. It is looked upon not only as a bright pearl, but also a treasure house of ancient Chinese culture.
Nowadays, TCM has become a subject area with high potential and the possibility for original innovation. This
book titled Recent Advances in Theories and Practice of Chinese Medicine provides an authoritative and
cutting-edge insight into TCM research, including its basic theories, diagnostic approach, current clinical
applications, latest advances, and more. It discusses many often neglected important issues, such as the theory
of TCM property, and how to carry out TCM research in the direction of TCM property theory using modern
scientific technology. The authors of this book comprise an international group of recognized researchers who
possess abundant clinical knowledge and research background due to their years of practicing TCM. Hopefully,
this book will help our readers gain a deeper understanding of the unique characteristics of Chinese medicine.

How to reference
In order to correctly reference this scholarly work, feel free to copy and paste the following:
Arthur de Sa Ferreira (2012). Advances in Chinese Medicine Diagnosis: From Traditional Methods to
Computational Models, Recent Advances in Theories and Practice of Chinese Medicine, Prof. Haixue Kuang (Ed.),
ISBN: 978-953-307-903-5, InTech, Available from: http://www.intechopen.com/books/recent-advancesin-theories-and-practice-of-chinese-medicine/advances-in-chinese-medicine-diagnosis-from-traditionalmethods-to-computational-models

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