Special Article
Accepted: April 30, 2009 Published online: August 27, 2009
Psychosomatic Assessment
Giovanni A. Fava a, d Nicoletta Sonino b–d
a Department of Psychology, University of Bologna, Bologna , and Departments of b Statistical Sciences and
c Mental Health, University of Padova, Padova , Italy; d Department of Psychiatry, State University of New York
Key Words
the pathophysiological links and mechanisms underlying
Psychosomatic medicine ؒ Depressive disorders ؒ
symptom presentation. Pointing to individually targeted
Anxiety disorders ؒ Somatization ؒ Clinimetrics ؒ
methods may improve final outcomes and quality of life.
Stress, psychological ؒ Macroanalysis ؒ Quality of life ؒ
Psychological well-being ؒ Diagnostic Criteria for Psychosomatic Research
A considerable body of evidence has accumulated in
psychosomatic medicine related to concepts such as qual-
Abstract
ity of life, stressful life events, somatization, illness be-
The primary goal of psychosomatic medicine is the incorpo-
havior and personality, but it has not resulted in opera-
ration of its operational strategies into clinical practice. The
tional tools whereby psychosocial aspects of medical dis-
traditional attitude toward disease and the functional/or-
ease could be routinely assessed. This paper is concerned
ganic dichotomy were criticized by George Engel in the ear-
with the psychosomatic assessment, a crucial step toward
ly sixties. Only recently, however, there has been increasing
awareness of the limitations of disease as the primary focus of medical care. It is not that certain disorders lack an organ-ic explanation; it is our assessment that is inadequate in most
Inadequacy of the Concept of Disease
clinical encounters. The research evidence which has accu-mulated in psychosomatic medicine offers unprecedented
In 1960, George Engel [1] sharply criticized the con-
opportunities for the identification and treatment of medi-
cept of disease: ‘The traditional attitude toward disease
cal problems. Taking full advantage of clinimetric methods
tends in practice to restrict what it categorized as disease
(such as the use of Emmelkamp’s two levels of functional
to what can be understood or recognized by the physician
analysis and the Diagnostic Criteria for Psychosomatic Re-
and/or what he notes can be helped by his intervention.
search) may greatly improve the clinical process, including
This attitude has plagued medicine throughout its his-
shared decision making and self-management. Endorse-
tory and still stands in the way of physicians’ fully appre-
ment of the psychosomatic perspective may better clarify
ciating disease as a natural phenomenon.’ Further, ‘many
Department of Psychology, University of Bologna
Tel. +39 051 209 1339, Fax +39 051 243 086, E-Mail [email protected]
kinds of processes or experiences may be thought of in 20] . We thus thought that the process of somatization terms of disease or related to disease even though they are
could be disclosed by more sensitive methods of assess-
not currently so regarded. For example, the experience of
ment and attention to the longitudinal course of distur-
grief as ordinarily follows the loss of a loved person, a val-
bances. In a study we designed, DSM-III-R criteria were
ued possession, or an ideal, fulfils all the requirements of
supplemented by the use of rating scales which had been
a disease process as we have defined it’ (pp. 471–472). En-
found to be particularly sensitive in research on subclin-
gel [2] elaborated this example and his observations have ical symptoms of mood and anxiety disorders [19] , in-not lost their validity [3, 4] . His unified concept of health cluding Paykel’s Clinical Interview for Depression [21] , and disease was subsequently elaborated within the bio-
Kellner’s Symptom Questionnaire [22] , and Kellner’s Ill-
psychosocial model [5–7] . The introduction of structured
ness Attitude Scales [23] . In more than half of the patients
methods of data collection and control groups has al-
who fulfilled the criteria of Kannel et al. [17] , a psychiat-
lowed to substantiate the link between life events and a ric diagnosis (mainly an anxiety disorder) antedated the number of medical disorders, encompassing endocrine, onset of neurocirculatory asthenia, which was defined as cardiovascular, respiratory, gastrointestinal, autoim-
secondary, particularly since cardiorespiratory symp-
mune, cutaneous and neoplastic disease [6, 8–13] .
toms were part of the mental symptomatology [24] . In
Not surprisingly, Engel was very critical of the disease doing so, we were influenced by Robins and Guze’s [25]
concept of functional medical disorder or medically un-
primary/secondary dichotomy, which was based on chro-
explained symptoms. For instance, he regarded the view nology and course of follow-up. The anxiety disturbanc-that irritable bowel syndrome is caused by psychological es were, however, mostly atypical and with close links to influences as an oversimplification [14] . The concept of various manifestations of health anxiety [26] . In about functional medical disorder indeed comprises a spec-
40% of patients, neurocirculatory asthenia was the pri-
trum of disturbances ranging from mild transitory ill-
mary disorder [24] . These patients did not significantly
ness to chronic disorders with severe disability [15] .
differ from healthy control subjects in all the dimension-al variables that were selected, except for observer-rated depression [21] . At 1 year of follow-up, patients with pri-
The Concept of Functional Medical Disorder
mary neurocirculatory asthenia had a much better prog-nosis than those with secondary neurocirculatory asthe-
In the late eighties, our research group became con-
nia [24] . In a subsequent investigation [27] , a sample of
cerned with the psychosomatic aspects of cardiac neuro-
patients meeting the criteria of Kannel et al. [17] for neu-
sis (neurocirculatory asthenia). The starting assumption rocirculatory asthenia and a control group of healthy was that disturbances were mainly the expression of an subjects were studied as to the occurrence of recent life underlying affective disorder. In a preliminary investiga-
events with a very sensitive and accurate method, i.e.
tion [16] , we attempted to apply DSM-III-R criteria to a Paykel’s Interview for Recent Life Events [28] . The results sample of patients who fulfilled the criteria of Kannel et suggested a strong relationship between life stress and al. [17] for neurocirculatory asthenia. We chose these cri-
neurocirculatory asthenia, irrespective of the primary/
teria because they had been validated in the Framingham
study, were above a certain threshold of severity, and were more precise than definitions of atypical chest pain. We were impressed by the fact that associated psychopathol-
Emergence of New Models
ogy departed from the classical descriptions, and had a limited power in explaining cardiac symptomatology.
The term ‘psychosomatic disorder’ was strongly criti-
The classification of somatoform disorders was of little or
cized by several psychosomatic researchers, notably En-
gel and Lipowski [29] . Engel [30] wrote that the term ‘psy-
Lipowski [18] had defined somatization as the tenden-
chosomatic disorder’ was misleading, since it implied a
cy to experience and communicate psychological distress
special class of disorders of psychogenic etiology and, by
in the form of physical symptoms and to seek medical inference, the absence of a psychosomatic interface in help for them. In those years we were also interested in other diseases. On the other hand, he viewed reduction-subclinical symptoms of mood and anxiety disorders, ism, which neglected the impact of nonbiological circum-with special reference to their longitudinal development stances upon biological processes, as a major cause of (prodromal, acute, residual phases) and their staging [19, mistreatment [5] . Lipowski [18] criticized the concept of
psychosomatic disorder since it tended to perpetuate the Table 1. Psychosocial variables affecting illness vulnerability obsolete notion of psychogenesis, which is incompatible with the doctrine of multicausality, a core postulate of Presence of physical and/or sexual abuse at some point in life
current psychosomatic medicine. Kissen [31] clarified
that the relative weight of psychosocial factors may vary Perception of an environment as exceeding personal resources from one individual to another within the same illness
and underscored the basic conceptual flaw of considering
Interpersonal relationships providing a buffering role for stress
It took many years to translate Engel’s unified concept
of health and disease into clinical perspectives. In 2004, Tinetti and Fried [32] suggested that time has come to abandon disease as the primary focus of medical care. Table 2. Psychosocial correlates of medical disease When disease became the focus of medicine in the past two centuries, the average life expectation was 47 years Psychiatric disturbances and most clinical encounters were for acute illness. Today
the life expectancy in Western countries is much high-
er and most of clinical activities are concentrated on chronic disease or non-disease-specific complaints. ‘The changed spectrum of health conditions, the complex in-terplay of biological and nonbiological factors, the aging population, and the interindividual variability in health ful analysis of symptoms, with all the details). This priorities render medical care that is centred primarily on
approach was found to be particularly helpful in the
the diagnosis and treatment of individual diseases at best
sequential treatment of depression, where residual symp-
out of date and at worst harmful. A primary focus on dis-
toms and impairment after pharmacotherapy alone were
ease, given the changed health needs of patients, inadver-
the primary targets of treatment, even though they could
tently leads to undertreatment, overtreatment, or mis-
not be ascribed to discrete diseases [38] . Further, the pur-
treatment’ [ 32 , p. 179]. Disease-specific guidelines pro-
pose of the science of clinimetrics is to provide a home for
vide very limited indicators for patients with multiple a number of clinical phenomena which do not find room conditions [33] . Tinetti and Fried [32] suggest that the in customary clinical taxonomy, such as type, severity goal of treatment should be the attainment of individual and sequence of symptoms, rate of progression of illness goals, and the identification and treatment of all modifi-
(staging), well-being and distress [36] . In recent years,
able biological and nonbiological factors, according to there have been several exemplifications of this approach Engel’s biopsychosocial model [5] .
in research on mood and anxiety disorders [38–44] .
In the same year of Tinetti and Fried’s paper [32] , psy-
chometric theory, the basis for developing assessment in-struments in psychiatric and most medical research, was
Psychosocial Foundations of Clinical Assessment
regarded as an obstacle to the progress of clinical research [34, 35] . Clinimetrics, a term introduced by Alvan R.
A fundamental characteristic of clinical medicine is
Feinstein to indicate a domain concerned with indices, the sensitive and systematic collection of information rating scales and other expressions that are used to de-
from patients in various settings [45] , and the medical
scribe or measure symptoms, physical signs and other interview is most important in this process [46] . Gold-distinctly clinical phenomena in medicine [36] , was re-
berg and Novack [47] developed a psychosocial review of
garded as the conceptual ground for a substantial revi-
systems, which were grouped as follows: smoking/alco-
sion of assessment tools and for linking co-occurring hol/drugs; stress; expectations/fears/meanings; living sit-syndromes [34, 35] . Important innovations were Em-
uation/social support; sexual life; marital status; work/fi-
melkamp’s two levels of functional analysis in psycho-
nances/education; psychiatric history/mood/cognition;
logical assessment [37] : macroanalysis (establishing links
functional status. Fava and Sonino [8] suggested the need
among coexisting syndromes or symptoms to determine for specific evaluations in medical assessment ( tables 1 , which problem should be treated first, taking into ac-
2 ) that may be performed by psychosomatic specialists.
count the patient’s priorities) and microanalysis (a care-
Table 2 displays the main psychosocial correlates of med-
ical disease. They include comorbid psychiatric distur-
for her. As the patient was pointing out, quality of life may
bances, psychological symptoms, illness behavior (the be compromised even though the patient is apparently ways in which individuals experience, perceive and re-
doing fine according to a hormonal viewpoint. In fact, in
spond to their health status) and quality of life (the func-
clinical endocrinology, there is often the tendency to rely
tional status of the individual and his/her appraisal of exclusively on ‘hard data’, preferably expressed in the di-health) [48–52] . This information may be crucial in man-
mensional numbers of laboratory measurements, exclud-
aging patients with unexplained medical symptoms, dif-
ing ‘soft information’, such as disability and well-being
ficult patient-doctor relationships, partial response to [61–63]
. Soft information, however, can now be as-
treatment, suspected psychiatric complications of medi-
cal illness, and abnormal illness behavior [53] . It may re-
The issue is to take full advantage of clinimetric tools
quire expert interviewing, self-rating inventories, and/or in the clinical process. It is not that certain disorders lack techniques of self-observation (self-monitoring of daily an organic explanation; it is our assessment that is inad-activities and recording of the observed findings in a di-
equate in most clinical encounters and this particularly
strikes when ‘hard data’ are missing. As Feinstein [55]
Disturbances are generally translated into diagnostic remarks, ‘even when the morphologic evidence shows the
endpoints, where the clinical process stops. This does not
actual lesion that produces the symptoms of a functional
necessarily explain the mechanisms by which the symp-
disorder, a mere citation of the lesion does not explain the
tom is produced [54, 55] . Not surprisingly, psychological functional process by which the symptom is produced factors are often advocated as an exclusion resource when
(.). Thus, the clinician may make an accurate diagnosis
symptoms cannot be explained by standard medical pro-
of gallstones, but if the diagnosed gallstones do not ac-
cedures, a diagnostic oversimplification which both En-
count for the abdominal pain, a cholecystectomy will not
gel [14] and Lipowski [56] refused. Macroanalysis [34, 37] solve the patient’s problem’ (p. 270). Alvan Feinstein [64] may allow to identify modifiable factors and their inter-
was also the one who warned against the destruction of
actions. Two examples show how clinical assessment and
the pathophysiological bridges from bench to bedside.
management follow similar patterns in case the disorder is either functional or organic. The case which is illus-trated in Appendix 1 exemplifies the use of macroanaly-
Expanding the Spectrum of Psychosocial
sis in the setting of a functional bowel disorder. Recurrent
Assessment
headaches together with additional symptoms of auto-nomic arousal and exaggerated side effects from medical
Replication attempts in psychosomatic studies are of-
therapy, signs of low sensation threshold and high sug-
ten disappointing, as one would expect from characteris-
gestibility indicated a syndrome of persistent somatiza-
tics of modest sensitivity and low specificity in hetero-
tion [48–50] . This category identifies patients in whom geneous medical entities. A different strategy was thus psychophysiological symptoms tend to cluster [57] , as is
attempted: to translate psychosocial characteristics ob-
frequently the case in patients with irritable bowel syn-
served in various medical diseases in Diagnostic Criteria
drome [58] . The clinical psychologist approached the for Psychosomatic Research (DCPR) [65] . The DCPR psychological problems sequentially [38] , starting from have now undergone extensive validation and these stud-lifestyle modification
, proceeding to explanatory ies have been summarized in a monograph [48] . They
therapy [59] and then to exposure, cognitive restructur-
have been found to be more suitable than DSM criteria in
ing and well-being therapy [60] . The treatment team was describing psychological distress in a variety of medical multidisciplinary and involved the collaboration of a pri-
mary care physician who referred the patient to a psy-
Fava and Wise [50] have suggested to modify the DSM-
chiatrist, a gastroenterologist, a clinical psychologist and IV category concerned with psychological factors affect-a nutritionist.
ing medical conditions, that is a poorly defined diagnosis
The case depicted in Appendix 2 is that of an appar-
with virtually no impact on clinical practice. They sug-
ently straightforward hypothyroidism on replacement gested a new section which consists of the 6 most frequent therapy. The endocrinologists the patient had previously DCPR syndromes [49] . The clinical specifiers, listed in consulted only looked at her thyroid hormone levels; they
table 3 , include the DSM diagnosis of hypochondriasis
did not understand what was wrong, since thyroid func-
and its prevalent variant, disease phobia [49] . Both the
tion parameters were satisfactory, and what they could do DSM somatization disorder and undifferentiated so-
matoform disorder are replaced by the DCPR persistent Table 3. New proposed classification for psychological factors somatization, conceptualized as a clustering of function-
affecting either identified or feared medical conditions [20]
al symptoms involving different organ systems [57] . Con-
version may be redefined according to Engel’s stringent Disease phobia (DCPR)
criteria [66] , involving features such as ambivalence, his-
trionic personality, and precipitation of symptoms by Conversion symptoms (DCPR)psychological stress of which the patients is unaware. Illness denial (DCPR)DCPR illness denial, demoralization, and irritable mood Demoralization (DCPR)
offer further specifiers. Persistent denial of having a med-ical disorder and needing treatment (e.g. lack of compli-ance, delay in seeking of medical attention) frequently occurs in the medical setting [67] . Demoralization con-notes the patient’s consciousness of having failed to meet tients with functional gastrointestinal disturbances or his or her own expectations (or those of others) with feel-
cardiac disease [76] . Further, the use of DCPR has dis-
ings of helplessness, hopelessness, or giving up [68] . It can
closed that not all coronary artery disease patients dis-
be found in almost a third of medical patients and can be
play type A behavior, and, vice versa, that type A behavior
differentiated from depressive illness [69] . Irritable mood,
is present in other settings including dermatology, gas-
that may be experienced as brief episodes or be prolonged
troenterology, cancer patients and frequent attenders of
and generalized, has also been associated with the course
of several medical disorders, carrying important clinical
Expanding the spectrum of psychological classifica-
implications [70] . Other DCPR constructs involve func-
tion by the introduction of psychosomatic constructs has
tional somatic symptoms secondary to a psychiatric dis-
allowed a more specific designation of problems in clini-
order, type A behavior, alexithymia, health anxiety and cal medicine. thanatophobia [48, 65] .
The advantage of this classification is that it departs
from the organic/functional dichotomy and from the
Finding Pathophysiological Links
misleading and dangerous assumption that if organic factors cannot be identified, there should be psychiatric
Feinstein [64] remarks that, when making a diagnosis,
reasons which may be able to fully explain the somatic thoughtful clinicians seldom leap from a clinical mani-symptomatology. The psychosomatic literature provides festation to a diagnostic endpoint. The clinical reasoning an endless series of examples where psychological factors
goes through a series of ‘transfer stations’ [54, 55] , where
could only account for part of the unexplained medical potential connections between presenting symptoms and disorders [8, 56] . Similarly, the presence of a nonfunc-
pathophysiological processes are drawn. The lack of a
tional medical disorder does not exclude, but indeed in-
psychosocial perspective, as is generally the case in cur-
creases the likelihood of psychological distress and ab-
rent medicine, deprives the clinical process of a number
normal illness behavior [56, 71] . McKegney [72] found a of important links. coexisting organic disease in about half of patients with
(a) McEwen [9] proposed a formulation of the relation-
conversion symptoms referred for psychiatric consulta-
ship between stress and disease onset based on the con-
tions from the medical and surgical wards. Orchard [73] cept of allostasis, the ability of the organism to achieve has drawn attention to the occurrence of atypical chest stability through change. The concept of allostatic load pain in about 50% of patients who had suffered from refers to the wear and tear that results from either too myocardial infarction. Lishman [74] outlined the range much stress or from insufficient coping, such as not shut-of problems which may be associated with silent or mild ting off response when it is no longer needed. Biological cerebrovascular disorders (including hypochondriasis parameters of allostatic load, such as glycosylated pro-and bodily preoccupations) and may be prodromal to teins, coagulation/fibrinolysis and hormonal markers, cognitive deterioration. Indeed, depression, anxiety, ir-
have been linked to cognitive and physical functioning
ritability and somatic symptoms are often prodromes of and mortality [9, 79, 80] . a medical disorder [74, 75] . Not surprisingly, psychologi-
(b) Prospective population studies have substantiated
cal assessment with DCPR was found to be more suitable
the role of social support in relation to mortality, psychi-
than DSM-IV criteria in identifying somatization in pa-
atric and physical morbidity, and adjustment to and re-
covery from chronic disease [8] . An area that is now called
able pathophysiological insights into the tendency to de-
‘social neuroscience’ is beginning to address the effects of
velop symptoms and abnormal illness behavior in the
the social environment on the brain and the physiology setting of medical disease. it regulates [9] .
(c) Lipowski [56] remarks that ‘once the symptoms of
a somatic disease are perceived by the person, or he has
Conclusions
been told by a doctor that he is ill even if symptoms are absent, then this disease-related information gives rise to
Psychosomatic medicine may be defined as a compre-
psychological responses which influence the patient’s ex-
hensive, interdisciplinary framework [8, 18] for the as-
perience and behavior as well as the course, therapeutic sessment of psychosocial factors affecting individual vul-response and outcome of a given illness episode’ (p. 483). nerability, course and outcome of any type of disease; Recent advances in psychoneuroimmunology offer links holistic consideration of patient care; integration of psy-between endogenous danger signals and the brain cyto-
chological therapies in the prevention, treatment and re-
kine system that organizes the sickness response in its habilitation of medical conditions. Its primary goal is its subjective, behavioral and metabolic components [81] .
incorporation into clinical practice [101] . The interdisci-
The neurobiology of illness behavior, including the pla-
plinary dimension, that includes the psychosocial do-
cebo effect [82] , is beginning to unravel a number of clin-
main, characterizes many rehabilitation units and pain
clinics and is an operational translation of psychosomat-
(d) The autonomic system has been a traditional target
for exploration of psychosomatic research. Autonomic
Psychosomatic assessment may be pursued both at the
imbalance, such as a state of low heart rate variability, level of the individual practicing physician and of health may be associated with a wide range of psychological and
specialists in multidisciplinary settings. The interest in
medical dysfunctions [84] and may affect response to health promotion rather than disease prevention, and the medical treatments [85] .
consideration of patients as partners in managing their
(e) Mood and anxiety disorders have been associated own disease are new emerging concepts to be further de-
with a variety of medical conditions [51] . The neurotrans-
veloped. In particular, the partnership paradigm includes
mitter imbalances which are underlying, such as rein-
collaborative care (a patient-physician relationship in
forcement-reward dysregulation, central pain and psy-
which physicians and patients make health decisions to-
chomotor functioning, may provide pathophysiological gether) [104] and self-management (a plan that provides bridges for a number of clinical phenomena [86] . Similar
patients with problem-solving skills to enhance their self-
considerations apply to the neurobiology of anger and ir-
efficacy) [105] . An interesting holistic method is current-
ly exemplified by functional medicine [106] . It refers to a
(f) Positive health is often regarded as the absence of comprehensive analysis of the manner in which all com-
illness, despite the fact that, half a century ago, the World
ponents of the human biological system interact func-
Health Organization defined health as a ‘state of com-
tionally with the environment over time, with particular
plete physical, mental and social well-being and not emphasis on pathophysiological process. So far therapeu-merely the absence of disease or infirmity’ [90] . Research
tic efforts have been concerned with diseases as homoge-
on psychological well-being has indicated that it derives neous entities, comparing one or more psychosocial in-from the interaction of several related dimensions [91, gredients with treatment as usual, for all patients sharing 92] . A large body of evidence suggests that psychological the same diagnosis. well-being plays a buffering role in coping with stress and
At present, the challenge of psychosomatic research is
has a favorable impact on disease course [93, 94] . Re-
to demonstrate, in randomized controlled trials, that an
search on the neurobiologic correlates of resilience and individually targeted method may improve clinical out-well-being [79, 95] has disclosed how different circuits comes and quality of life, as was found to be the case with may involve the same brain structures, and particularly rehabilitation research [107, 108] . the amygdala, the nucleus accumbens, and the medial prefrontal cortex.
The neurobiology of personality features, such as re-
ward dependence and novelty seeking [96] , alexithymia [97–99] and type A behavior [100] , provides other valu-
Appendix 1. Macroanalysis of a case of irritable bowel syndrome Appendix 2. Macroanalysis of a case of hypothyroidism
Ms. X is a 24-year-old woman who was diagnosed with
Mrs. Y is a 54-year-old woman who was diagnosed with
irritable bowel syndrome (abdominal pain, diarrhea) on the
hypothyroidism. She was prescribed replacement therapy
basis of her symptomatology, after extensive negative medical
which restored thyroid hormone levels within the normal
workup. She was in a situation of chronic stress and suffered
range, but kept feeling miserable, with a very bothersome
from recurrent headache (muscle tension type). Symptom-
globus in the throat. She consulted several endocrinologists,
atic medications that were prescribed yielded very limited
who all stated that her thyroid replacement was fine and
relief. She was then referred for psychiatric consultation.
there was nothing wrong with her, which made her angry
Interviewing did not identify a specific psychiatric disorder,
and dissatisfied. She was then referred by her primary care
but disclosed the presence of a considerable allostatic load
physician to a Psychoneuroendocrinology Service. Care -
(she felt overwhelmed by her job demands as a journalist), a
ful interviewing in this setting disclosed the presence of
tendency to perfectionism, and also phobic avoidance (as to
agoraphobia (fear of public spaces and going out alone) with
certain types of food she thought could worsen her symptoms)
sporadic panic attacks and that she attributed the globus
and lack of assertiveness (both at work and within her family).
sensation and panic to the thyroid. She was adjusting
No psychotropic drugs were prescribed. She was referred to
by herself thyroid replacement in relation to her current
a clinical psychologist who found persistent somatization
feelings. She also reported marital problems. The psycho-
and first introduced some lifestyle modifications as to her
somatic assessment and physical examination led to di-
allostatic load. The psychologist then addressed abnormal
agnosing persistent somatization and explaining that ago-
illness behavior with explanatory therapy for correcting
raphobia is a psychological disorder, her globus sensation was
hypochondriacal fears and beliefs, phobic food avoidance
related to it, not to the thyroid, and that changing herself
with exposure and with the help of a nutritionist, per-
thyroid replacement could only make things worse. A brief
fectionism with cognitive restructuring, and lack of as-
course of cognitive treatment by a psychologist did improve
sertiveness with well-being therapy. After a few months
her agoraphobia and marital problems greatly, with dis-
there was a remarkable general improvement, which was
appearance of panic attacks and only sporadic symptoms
of globus sensation related to anxiety.
The various elements of macroanalysis are highlighted in
The various elements of macroanalysis are highlighted in
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Dynamics of green fluorescent protein mutant2in solution, on spin-coated glasses, and encapsulatedin wet silica gelsGIUSEPPE CHIRICO,1,5 FABIO CANNONE,1,5 SABRINA BERETTA,1,5ALBERTO DIASPRO,2,5 BARBARA CAMPANINI,3,5 STEFANO BETTATI,3,4,5ROBERTA RUOTOLO,3 AND ANDREA MOZZARELLI3,51Department of Physics, University of Milan-Bicocca, 20126 Milan, Italy2Department of Physics, University of Genova, 161
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