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Role of basic biological sciences in clinical

orthodontics: A case series
Zeev Davidovitcha and Vinod Krishnanb
Cleveland, Ohio, and Tamilnadu, India
Introduction: Orthodontic therapy is based on interaction between mechanics and biology. Basic biologic
research aims at developing a better understanding of the mechanism of transformation of mechanical
energy into biologic reactions, and exposing the reasons for iatrogenic tissue damage in orthodontics.
Previous research has shown that inflammation is a major part of the biologic response to orthodontic forces.
In inflammation, signal molecules that originate in remote diseased organs can reach strained paradental
tissues and exacerbate the inflammatory process, leading to tissue damage. Methods: Our case series
includes 3 patients, each having had systemic diseases and malocclusion. One had diabetes mellitus,
Hashimotos thyroiditis, and depression. Concern about the possible effect of these conditions on the
well-being of the teeth and their surrounding tissues compelled the orthodontist to choose not to treat this
patient. The other 2 patients had allergies, and 1 also had bronchial asthma and bruises. Results: Although
these conditions are thought to be risk factors for root resorption, these patients received orthodontic
treatment for 2 and 3.5 years, respectively. At the end of treatment, both had excessive root resorption of
many teeth. In 1 patient, this damage led to the loss of most maxillary teeth. Conclusions: Basic research
should continue to address questions related to the biologic mechanisms of tooth movement on tissue,
cellular, and molecular levels. Moreover, this research should continue to identify risk factors that might
jeopardize the longevity of treated teeth. Such basic research should promote the development of new
tissue-friendly and patient-friendly therapeutic methods. (Am J Orthod Dentofacial Orthop 2009;135:222-31)

n the general population of all countries where the

specialty of orthodontics is practiced, the image of
this therapeutic field is synonymous with braces,
and the orthodontist is perceived as the person who
places braces on teeth, or a person who sells braces.
The fact that teeth are enticed to alter their location as
a result of tissue remodeling around the roots of teeth
subjected to mechanical forces is unknown to most
people, including most orthodontic patients.
People seek orthodontic treatment because they or
their parents recognize, or are made aware by other
people, that they have a malocclusion. These occlusal
irregularities can be rotations, protrusion, crowding,
spacing, overeruptions, and other abnormal positions.
But in every case, the recognition of the abnormality is
limited to the position of the dental crown, not the root.
Once the crowns are brought to a pleasing position,
esthetically and functionally, both patient and orthodontist are satisfied with the outcome, paying little
Clinical professor, Department of Orthodontics, Case Western Reserve University, Cleveland, Ohio.
Assistant professor, Department of Orthodontics, Rajas Dental College,
Tirunelveli District, Tamilnadu, India.
Reprint requests to: Zeev Davidovitch, 327 S Harding Rd, Columbus, OH
43209; e-mail,
Submitted, December 2006; revised and accepted, March 2007.
Copyright 2009 by the American Association of Orthodontists.


attention, if any, to the biologic processes that have

facilitated this correction. If patients have tissues damaged (eg, root resorption) as a result of treatment, many
orthodontists try to avoid assuming the responsibility
for it, claiming that this adverse effect is unpredictable,
and that some people are more susceptible than others
for unknown reasons. To drive this point home, patients
are frequently required to sign an informed consent
form that highlights this claim before treatment.
Before the 20th century, orthodontists could only
guess why teeth move when subjected to mechanical
forces. In the middle of the 18th century, Hunter1
explained this phenomenon on the basis of his observation that tissues, especially bone, are capable of
moving out of the way of pressure. Over a century
later, in 1888, Farrar,2 in his classic textbook, provided
a 2-pronged explanation: teeth move either because
the alveolus is resorbed, or due to bending of the
alveolar bone. Support for the former hypothesis was
derived from the landmark histologic investigation of
Sandstedt,3,4 published at the threshold of the 20th
century. Reitan,5-7 using histology as a research tool,
concluded that tissue responses to orthodontic forces
can differ from person to person, depending on variables such as age, sex, type of alveolar bone, and kind
of tooth movement. The latter (bone bending) hypothesis was verified by Baumrind8 8 decades later.

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During the 1920s, Ketcham9,10 examined jaw radiographs of 385 orthodontic patients and discovered that
some had iatrogenic tissue damage, whereas others had
sailed through treatment unscathed. He found that
patients with and without tissue damage frequently had
similar malocclusions and were treated by the same
techniques. Yet, the outcomes of treatment were significantly different. He concluded that something in
addition to the orthodontic appliance might have played
a role in determining the results of treatment. He
attributed this effect to hormonal and dietary factors.9,10
Those pioneer pathfinders helped to formulate a
biologically oriented explanation of the reasons for
tooth movement in response to applied forces and also
highlighted the finding that responses differ from person to person. This dichotomy emphasizes the difference between a typodont and a real patient. A typodont
is a training device consisting of artificial teeth embedded in dental wax that hardens at room temperature,
enabling the user to freeze the teeth in normal and
many abnormal positions. In the latter case, one can
then bond or cement orthodontic attachments to the
dental crowns and fabricate a simulated orthodontic
appliance. When the typodont is dipped into warm
water, the wax softens, and the roots of the teeth that
had been subjected to mechanical forces move with
ease through the soft wax. Hence, this apparatus might
suggest that orthodontic tooth movement results predominantly from a judicious application of force systems to teeth, which react like free bodies in space, with
a small contribution of biologic processes to this
phenomenon. Thus, an erroneous supposition might be
formulated, magnifying the role of orthodontic mechanics, while not emphasizing sufficiently the role of
biology in tooth movement. Actually, the practice of
orthodontics should depend on equality between 2

Orthodontic Mechanics Biology

However, in reality, contemporary orthodontics contains a marked inequality, seen symbolically as follows:


Mechanics Biology

In this symbolic formula, the interest in mechanics is

immense, whereas it is minuscule in biology. A reflection of this reality can be found at any orthodontic
meetinglocal, national, or internationalwhen elaborate and rich displays of mechanical gadgets are
crowded into huge halls, but no exhibit of biologically

Davidovitch and Krishnan 223

related materials is to be found. This attitude and this

approach toward basic biologic sciences neglect these
aspects of clinical orthodontics that can jeopardize the
patients well-being and the stability of the treatment
Medicine and all its specialties pay close attention
to advances in basic biologic sciences that encompass
all levels of diagnosis and treatment. Physicians who
bridge gaps between basic biology laboratories and the
clinical environment are keenly aware that the organs
and tissue systems that interest them are frequently
affected by pathologic processes elsewhere in the body.
Thus, they recognize that, although details of the
functional mode of cells can be explored in a test tube,
it does not preclude the notion that, in the intact
organism, the same cell type might function differently
due to its interactions with signal molecules derived
from other systems or remote organs. However, in
orthodontics, we seem to diminish the attention to
systemic factors in diagnosis and treatment planning, as
well as the progress and outcome of mechanotherapy.
Most patients with malocclusions are labeled diagnostically as having a malocclusion, as if face, jaws, and
teeth are detached from the rest of the body and
function in isolation.
However, emerging results from experiments in
basic biology have shown information that enables the
orthodontist to consider the patients physiopathologic
profile before addressing clinically the orthodontic
problem. This information can be obtained from a
routine medical examination and related tests.11 Some
of these experiments have shown the response of
various cell types to applied mechanical forces.7-9 Of
particular interest in this regard are the reactions of
bone, nerve, and endothelial cells. The picture is
complicated somewhat by the finding that orthodontic
forces evoke inflammation in paradental tissues.11-14
Elements of the nervous, vascular, and immune systems
contribute to this response by subjecting alveolar bone
and periodontal ligament (PDL) cells to many signal
molecules. Simultaneously, molecules produced by endocrine glands or absorbed in the alimentary system
from the diet travel to the strained PDL through the
vascular system, where they become available for
interaction with target cells. Moreover, drugs and
medications routinely consumed by patients find their
way to the PDL via the same route.15 This acquired
knowledge must join the limited description of a
malocclusion in the process of orthodontic diagnosis.
This broad approach uses an ever-expanding body of
scientific data. Its adoption by the orthodontist increases the probability of crafting an individualized

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Fig 1. Patient 1. A, Panoramic radiograph of patient 1s dentition at age 16 years before orthodontic
treatment aimed at closing her open bite. The open bite extended from the second molars on the
left to the second molars on the right. B, Panoramic radiograph of the same dentition at age 19.5
years, after 3.5 years of orthodontic treatment to close her open bite. The radiograph shows that,
despite the long effort, the bite was not entirely closed, and that many teeth in both jaws were
substantially shortened by root resorption.

treatment plan to address the malocclusion and each

patients biologic characteristics.

To illustrate the importance of assessing biologic

characteristics of orthodontic patients as part of the
pretreatment evaluation, the following case series of 3
patients is presented.
The open bite case of patient 1

Patient 1 was a 16-year-old girl, who had been

referred to an orthodontist by her dentist for evaluation
and possible treatment of an open bite that extended
from the second molars on the right side of the dental
arches to the second molars on the left side (Fig 1, a).
The orthodontic diagnosis was open bite from the right
second molars to the left second molars, and the
treatment plan consisted of an edgewise appliance and
vertical elastics to close the bite. Before treatment, the
patient said that she had had bronchial asthma and
allergies since childhood.
This patient was treated orthodontically for 3.5
years. A panoramic radiograph of her dentition taken
after removal of the braces showed extensive root
resorption in most teeth. It also showed that her bite
was still open (Fig 1, b). A consultation with an author
(Z.D.) showed that, in addition to her respiratory
ailment, patient 1 has also had a history of bruising
easily. Medications she was taking regularly included
antihistamines and corticosteroids. Both asthma and
bruising can be risk factors for root resorption.
Her orthodontist used round stainless steel wires
and vertical elastics in the effort to close her open
bite. However, because her maxillary and mandibular incisors were labially inclined, these teeth were
tipped uncontrollably by the vertical force, and their

root apices approached and probably came into

contact with the labial compact plates of alveolar
bone. This type of movement is the main cause of
incisor root resorption.
The many systemic conditions of patient 2 and his
orthodontists dilemma

Patient 2 was a 39-year-old man, referred by a

dentist for an orthodontic consultation. During the
examination, he stated that he had type 1 diabetes,
diagnosed at 14 years of age, Hashimotos thyroiditis,
and depression. Some his teeth had been extracted
during his teenage years, and he was kicked in the left
side of the face at age 13. He consulted regularly with
a nutritionist and ate 3 balanced meals a day. He
monitored his blood glucose level daily and selfadministered long-term insulin twice a day: before
breakfast and at 5 pm. His Hashimotos thyroiditis
started when he was 34 years old. After a brief course
of hyperthyroidism, he gradually became hypothyroid
and was being managed with a daily dose of 0.15 mg of
levothyroxin. At age 37, he was diagnosed with depression and was treated with daily doses of desipramine,
which caused mild xerostomia.
The oral examination (Fig 2) showed a midline
shift, a bilateral buccal crossbite, missing molars in
each quadrant, and a palatally located right first
premolar. The periapical radiographs (Fig 3) showed
short dental roots, particularly of the maxillary
buccal teeth.
The orthodontists dilemma was whether to treat
him despite his systemic conditions. Although these
diseases were being treated with medications and
seemed to be under control, the short dental roots
suggested that root resorption had occurred in the past
and that it might easily reawaken under the influence of
mechanical forces because of his systemic diseases and

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Davidovitch and Krishnan 225

Fig 2. Patient 2. A, Frontal view of patient 2s dentition in occlusion during the orthodontic
consultation appointment. Note poor oral hygiene, general gingivitis, and gingival recession,
especially in the posterior segments of both dental aches. A right mandibular midline shift and a
bilateral posterior crossbite are visible. B and C, Lateral photographs of the left and right sides of
his occlusion. Note the large extraction spaces in both sides of the arches. The molars in both
arches tipped into the extraction spaces. D, Occlusal view of the maxillary dental arch. A narrow
arch and a high vaulted palate are visible. E, Palatal view of the maxilla shows an ectopically erupted
second premolar (palatally).

some or all of the drugs used to treat these illnesses.

Consequently, the orthodontist decided not to offer
patient 2 a course of mechanotherapy.
The bride who refused orthognathic surgery

Patient 3 was a 25-year-old woman who planned to

get married about 6 months after her visit to the
orthodontic office for a consultation. She had received
orthodontic treatment 10 years previously, but her
occlusion had apparently relapsed, and she sought to
correct it, if possible, before her wedding. Her medical
history consisted of allergies. Her dentofacial examination showed restorations in all molars, root resorption
in both dental arches, a 15-mm overjet, earaches, and

soreness and popping of the temporomandibular joints

(Fig 4).
Patient 3 was diagnosed as having a Class II
Division 1 malocclusion, a retrognathic mandible, a
narrow maxillary arch, slight anterior crowding in both
dental arches, condylar atrophy and wear, and habits
(tongue thrusting and bruxism).
In presenting the proposed treatment plan, the
orthodontist stated that the best way to treat her
malocclusion would be orthognathic surgery. However, she refused surgery, and the orthodontist consented to treat her only with orthodontic appliances.
His plan included extraction of the maxillary first
premolars and the mandibular second premolars,

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Fig 3. Patient 2. A, Periapical radiograph of the maxillary right posterior teeth shows that all teeth,
especially the premolars, have short roots. B, Periapical radiograph of the molar-premolar region of
the maxillary right side shows short roots in the second premolar and the molars (distal roots). C,
Periapical radiograph of the mandibular right side. The premolar roots appear to have normal length,
but their apices are blunted. D, Periapical radiograph of the mandibular left side. The premolars
appear to be of normal length, but the alveolar bone height is reduced.

followed by retraction of the maxillary front teeth

and mesial movement of the mandibular molars. The
treatment plan also contained a promise to move the
teeth carefully, because of the previous root resorption.
Treatment lasted 2 years. Panoramic and periapical
radiographs taken after mechanotherapy (Fig 5) showed
excessive loss of root length (40%-70%) in the maxillary teeth, particularly the incisors and the canines. This
destructive process continued unabated after appliance
removal, resulting in the extraction of these teeth (Fig 6).

In orthodontics, the search for a biologic foundation

stems from a desire to understand the tissue and cellular
response to applied mechanical forces. With a microscope, investigators could describe the appearance of
the paradental tissues during tooth movement. Areas of
compression and tension were discovered in the mechanically loaded PDL, and corresponding sites of
alveolar bone resorption and apposition were visualized. Those pictures presumably formed the biologic
foundation of orthodontic tooth movement.
However, because patients differ at various levels

biologically, it would seem helpful to take these differences into account when considering a malocclusion.
Optimally and ideally, an orthodontic diagnosis should,
therefore, contain biologic information that might impact the treatment outcome. At a minimum, variables
such as age, sex, systemic diseases, diet, and drug
consumption should be included. Basic medical tests
pertaining to the assessment of the patients health
status might shed additional light on their actual biological profile. Genetic tests on the molecular level
might facilitate classification of patients according to
their effectiveness in resorbing bone and their susceptibility to root resorption. For an orthodontist, a malocclusion can be obvious and easy to classify. However,
frequently the degree of success in treating it and the
ability to avoid complications depend on well-defined
biologic entities.
In the intact organism, the sensitivity of PDL and
alveolar bone cells to mechanical force can be overshadowed by cellular interactions with many signal
molecules, derived from local cells, remote organs, the
subjects diet, or consumed drugs. Basic biologic research in orthodontics showed that, when 2 or more
factors interact simultaneously with target cells, they

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Davidovitch and Krishnan 227

Fig 4. Patient 3. A, Frontal view of patient 3s dentition in occlusion, showing an excessive overjet.
B, Lateral view of incisor occlusion, showing a 15-mm overjet. C, Lateral cephalogram before
orthodontic treatment, showing soft- and hard-tissue convex profiles, well-developed chin, excessive overjet, and Class II Division 1 malocclusion. D, Panoramic radiographic view of jaws before
treatment shows a small amount of root resorption, particularly in the frontal zone of both dental
arches; this could be attributed to previous mechanotherapy.

can inhibit each others effects, cause an additive effect,

or evoke a synergistic response.15
Inflammation, an all-encompassing event, often follows orthodontic force application. It is feasible to
localize inflammatory mediators in these tissues by
using specific antibodies in an immunohistochemical
procedure. A study of male cat paradental tissues after
distal movement of the maxillary canines for 1 hour to
56 days found increased cytokines and growth factors
in cells at sites of compression and tension.16 In both
sites, the cellular staining intensified, representing increased concentrations of these signal molecules. This
suggests that monitoring the concentrations of these
signal molecules in the gingival crevicular fluid will
provide useful information to assist the orthodontist in
efforts to determine the nature and extent of the
individual response to applied mechanical loads.17-20
The 3 patients discussed here all went to their
respective orthodontists with malocclusions that de-

served professional attention. However, the orthodontist of patient 2 decided not to treat him, even though
his illnesses (diabetes, thyroiditis, and depression) were
being treated by medications. The orthodontist was
apparently concerned about the short roots of the
maxillary teeth and the 3 diseases, treated or not. On the
other hand, the orthodontists of the other 2 patients
treated them despite the systemic diseases. It can be
argued that the severe maxillary root resorption of the
other 2 patients resulted from the use of round wires in
closing the open bite of patient 1 and in reducing the
anterior maxillary protrusion of patient 3. These wires
inadvertently tipped the teeth uncontrollably, with the
root apex first pushed into contact with the labial plate
of compact bone and then torqued palatally. The
systemic diseases (allergies in patient 3; bruising,
allergies, and asthma in patient 1) apparently did not
faze these orthodontists.
Asthma, an inflammatory disease, is triggered by

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Fig 5. Patient 3. A, Panoramic radiographic view of patient 3s jaws 18 months after the start of
treatment. Excessive root resorption can be seen in many teeth, particularly in the maxillary incisor
region. B, Periapical radiograph of the maxillary front teeth when the orthodontic appliances were
removed after 2 years of treatment. The roots of all teeth were apparently resorbed excessively
during treatment that included retraction of these teeth with Class II elastics from round archwires,
causing the teeth to tip uncontrollably. C, Periapical radiograph of the maxillary right canine region
after orthodontic treatment. The length of the canine root is about 25% of its pretreatment length.

airborne allergens such as cockroaches, dust, mite

feces, pollen, or animal hair. It can also be triggered by
cold air, viral infections, and exercise. Basic research
has shown that patients with asthma have an imbalance
between 2 groups of lymphocytesthe T helper 1 and
the T helper 2 cells. The latter group of cells is
responsible for the synthesis and release in the lung

of many inflammatory mediators, such as interleukin

(IL)-4, IL-5, IL-6, IL-10, and IL-13.21 These cytokines
attract to the lung airways many inflammatory cells,
including eosinophils, which secrete large amounts of
histamines, prostaglandins, and leukotriens, causing
blood vessels to leak, and lung tissues to swell and
secrete large amounts of mucus.22 These signal mole-

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Davidovitch and Krishnan 229

Fig 6. Patient 3. A, Frontal view of patient 3s dentition 1 year after orthodontic treatment. Root
resorption continued unabated during that period, prompting the extraction of all maxillary anterior
teeth. B, Frontal view of her dentition, while she was wearing a temporary prosthetic device, before
the surgical placement of dental implants to replace the lost teeth.

cules can enter the circulation and reach the PDL,

where they can interact with target cells involved in
tissue remodeling and tooth movement.23
A possible link between asthma and orthodontic
root resorption was found by McNab et al.24 In that
study, radiographs of the maxillary premolars and
molars and the mandibular molars were examined for
evidence of root resorption after orthodontic treatment.
Patients with asthma had significantly more molar root
resorption than those without it. In another related
study, panoramic dental radiographs of over 1100
patients showed that patients with asthma were significantly more prone to develop root resorption during
orthodontic treatment than those without it.25 In the
patients with asthma, resorption was not limited to the
molars but was found in all orthodontically treated
teeth, particularly the incisors.
Skin bruises result from contusions caused by a
blunt force that injures small blood vessels and causes
interstitial bleeding, usually without disruption of the
continuity of the tissue. The frequency of bruises is
increased in patients with asthma who use steroids.26
After a local hemorrhage, the erythrocytes are lysed,
and hemoglobin is transformed into hemosiderin by
lysosomal enzymes of macrophages. Macrophages are
attracted to the bruise site by platelets, which synthesize and release large amounts of chemotactic agents
and growth factors, such as ILs and platelet-derived
growth factor. Some of these factors, such as IL-1,
IL-6, and platelet-derived growth factor are potent
stimulators of bone resorption. Patients who bruise
easily and are subjected to orthodontic forces can
develop hemorrhages in the PDL. In these patients,
noticeable amounts of resorption-stimulating factors
can be released in the PDL by platelets and macrophages each time the orthodontic appliance is activated.
Root resorption can begin in the early leveling

stages of orthodontic treatment.27 Some identified risk

factors are deviated root form, long and narrow roots,
and increased treatment duration. Patients with an
anterior open bite are apparently at a higher risk for root
resorption during orthodontic treatment, but treatment
factors associated with the increased risk could not be
elucidated.28 However, we suggest that, for patient 1,
whose teeth were extruded with vertical elastics from
round archwires, the horizontal vector of the applied
force moved the root apices into contact with the labial
or buccal plates of compact bone, a situation associated
with increased risk of root resorption. It is possible that
her orthodontist used heavy forces to close her open
bite. Electron microscopic evidence suggests that heavy
forces cause significantly larger resorption lacunae in
dental roots than do light forces.29,30
Recent basic research has elucidated some details of
the cellular-molecular mechanisms of root resorption.
The extracellular proteins osteopontin and sialoprotein
were localized near resorbing roots and in odontoclasts
proximal to resorptive lacunae, suggesting that these
proteins act as signals for odontoclast adhesion.31 Two
other proteins involved in osteoclast differentiation
receptor activator of nuclear factor kappa beta ligand
(RANKL, a stimulator of osteoclast differentiation) and
osteoprotegrin (OPG, an inhibitor of osteoclast differentiation)were studied in rats treated with orthodontic forces.32 The expression of mRNA for RANKL and
OPG was found to fluctuate in resorbing roots, suggesting a role of these proteins in root resorption.
Patient 2 had several systemic diseases that led the
orthodontist not to offer him orthodontic care because
of concerns about complications. In addition to those
diseases, the initial examination showed poor oral
hygiene and gingival inflammation. To eliminate these
conditions, this patient was referred to a dentist.
Dental radiographs were taken of the 2 treated

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patients only twice: before and after treatment, periods

of 2 years for patient 3 and 3.5 years for patient 1.
Consequently, the tissue damage, because of either
faulty mechanics or the systemic diseases or both, was
allowed to proceed unabated. The biologic aspects of
orthodontic diagnosis and treatment were ignored to
these patients detriment. The logical conclusion from
these brief reports is that a patients biologic background should be considered seriously during orthodontic diagnosis, treatment planning, and the entire
course of mechanotherapy.

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Ongoing investigations in many fields of basic

biology are increasing our understanding of the intricate relationships in clinical orthodontics. In this specialty, mechanical energy evokes a biologic response.
This cellular response is the essence of orthodontic
therapy. The purpose of biologic research in orthodontics is twofold: it enables the orthodontist to better
understand the tissue response to mechanical loading,
and it exposes the mechanisms that cause tissue damage. In either case, the main beneficiary of this growing
body of knowledge is the orthodontic patient. The
patients discussed in this article demonstrate that additional research of biologic questions in orthodontics is
warranted. Such research might ultimately lead to new,
efficient, tissue-friendly and patient-friendly orthodontic methods.
As orthodontists, we must strive to improve the
treatment of our patients and elevate the standard of our
specialty to its biologic science status by paying attention to the biologic aspects of treatment as much as to
its mechanical aspects. To accomplish this, we need not
only to join hands with our colleagues in other biologic
fields and continue to do research toward understanding
the biology of tooth movement, but to start approaching
dentofacial deformities and their treatment as biologists
and as engineers.
1. Hunter J. The natural history of the human teeth: explaining their
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Davidovitch and Krishnan 231

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