Open Journal of Psychiatry, 2011, 1, 98-105
doi:10.4236/ojpsych.2011.13014 Published Online October 2011 (http://www.SciRP.org/journal/OJPsych/
OJPsych
).
Published Online October 2011 in SciRes. http://www.scirp. org/journal/OJPsych
Are premenstrual symptoms associated with health anxiety in
nursing graduates?
Yinghui Xu1*, Russell Noyes Jr.2, Arthur J. Hartz3, Barcey T. Levy1, Jeanette M. Daly1,
Susan R. Johnson4
1Department of Family Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States;
2Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States;
3Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, United States;
4Department of Obstetrics & Gynecology, and Epidemiology, University of Iowa, Iowa City, United States.
Received 25 August 2011; revised 21 September 2011; accepted 29 September 2011.
ABSTRACT
Objective: This study examined retrospectively the
relationship between premenstrual symptoms and
health anxiety. Methods: Premenstrual symptoms of
nursing school graduates were assessed in 1985 and
again in 1991 using the Premenstrual Assessment
Form (PAF). A total of 571 women completed the
survey in 1991, along with items relating to their
physical and mental health. The latter included de-
pression, anxiety, and panic attacks. Health anxiety
was also assessed using the Whiteley Index (WI). Af-
ter women who were amenorrheic for any reason
were excluded, a final sample of 410 women aged 25
to 52 years was obtained. Factor analyses yielded 57
items that were useful for calculating a total PAF
score. A stepwise multivariate linear regression model
was used to find the association of PAF scores with
various participant characteristics. Results: Thirty-
one of the 410 (7.6%) women had WI scores of ≥5
and were considered to have significant health-re-
lated anxiety. The PAF score had statistically signifi-
cant associations with health anxiety, as well as de-
pression and anxiety. Conclusions: Our results sug-
gest that the premenstrual symptoms often coexist
with health anxiety as well as other psychological
symptoms. Clinicians should be alert to the fact that
PMS may be associated with treatable psychiatric
conditions.
Keywords: Premenstrual Symptoms; PMDD; Health
Anxiety; Hypochondriasis
1. INTRODUCTION
Premenstrual syndrome (PMS) is frequently encountered
by primary care and specialist physicians. Although as
many as 80% of women experience one or more symp-
toms [1], clinically significant PMS may occur in 20% to
50% of women [2]. Three to 8% of women are affected
by premenstrual dysphoric disorder (PMDD), a more
severe form of PMS associated with significant impair-
ment of functioning [1,3-6]. Even though extensive re-
search has been conducted on PMS and PMDD, uncer-
tainty about its etiology and its relationship to biological,
psychological and social factors remains.
Psychological factors include stressful life events, per-
sonality dimensions, and psychiatric comorbidity. Studies
have found high psychiatric comorbidity among wo-
men with PMS/PMDD. For instance, 50% of women with
prospectively diagnosed perimenstrual syndromes had
concurrent major depression, 35% had panic disorder, and
20% had generalized anxiety disorder [4]. The lifetime
prevalence of major depression has been found to be
53% - 58% in women with prospectively confirmed
PMDD [5,7,8], and lifetime anxiety disorders have been
observed in 14% - 16% of women with PMDD [9].
Health anxiety (hypochondriasis) is another common
psychiatric disturbance that is notable for adding to the
severity and impairment of other physical and mental
disorders. Health anxiety is fear of serious illness arising
from bodily sensations. Such anxiety falls on a contin-
uum from mild to severe, and when severe, it is given
the designation hypochondriasis [3]. Hypochondriasis is
a disorder characterized by heightened attention to bod-
ily sensations that are misinterpreted as signs of serious
disease (e.g., this headache means I have a brain tumor).
This is a chronic disturbance affecting about 5% of
medical outpatients [10]. Hypochondriasis is associated
with increased symptom reporting, impairment in
physical and work functioning, and increased health care

Y. H. Xu et al. / Open Journal of Psychiatry 1 (2011) 98-105 99
utilization [11]. For instance, recent studies have found
that hypochondriasis adds to symptom severity and qual-
ity of life in patients with irritable bowel syndrome [12,
13]. In addition, hypochondriasis coexists with other
psychiatric disorders. It is found in about 40% of those
with major depression, 10% - 20% with panic disorder,
5% - 10% with obsessive-compulsive disorder, and gen-
eralized anxiety disorder [14].
Despite its importance no research has examined
health anxiety in women with PMS/PMDD. Given the
relationship between PMS and psychiatric disorders ge-
nerally, our aim was to examine retrospectively the rela-
tionship between premenstrual symptoms and health
anxiety.
2. METHODS
2.1. Study Participants
This study had institutional review board approval, and
written informed consent was obtained from all study par-
ticipants. The original sample consisted of 996 graduates
of the University of Iowa College of Nursing, stratified by
year of graduation. It included all female graduates from
the classes of 1963, 1964, 1965, 1969, 1974, and 1979, as
well as sophomore and senior nursing students enrolled in
1984. The first mailing was sent in 1985, and question-
naires were returned by 731 (73%) participants. Those
same 731 participants were re-surveyed in 1991, and 571
(78%) of them responded. Detailed description of two re-
peat mailings and one telephone contact to non-responders
was previously described [15].
Survey participants who were pregnant, postpartum,
post-abortion, postmenopausal, who had had a hysteric-
tomy or were without periods for any reason, such as
breastfeeding, were excluded. Women who were taking
oral contraceptives were not excluded. Final samples con-
sisted of 616 women in 1985 and 410 in 1991.
2.2. Instruments
The 1985 questionnaire consisted of 46-items and in-
cluded information on socio-demographic, menstrual (onset,
regularity, duration of cycle, dysmenorrhea, last menstrual
period, number of days premenstrual symptoms began
before menstrual period, and number of years with PMS),
gynecological (diagnosed medical problems, and medi-
cations), obstetrical (reproductive events, and oral con-
traceptive use) characteristics, and the 95-item Premen-
strual Assessment Form (PAF) [16]. The questionnaire
mailed in 1991 repeated items from 1985 and added 23
items about depression, anxiety, panic attacks, and health
anxiety. The latter were elicited with questions such as:
“Have you ever suffered from a depression lasting a
month or more?”, “Have you ever suffered from a period
of nervousness or anxiety lasting a month or more?”,
“Have you ever suffered from panic attacks?” The pos-
sible responses were yes or no. Health anxiety was as-
sessed by the Whiteley Index (WI) of hypochondriasis
[17].
The Premenstrual Assessment Form (PAF) is a self-
report questionnaire that elicits information about pre-
menstrual changes in mood, behavior, and physical
status. It contains 95 symptoms rated on six-point sever-
ity scales from 1 (no change or not applicable) to 6 (ex-
treme change). In answering questions, participants were
instructed to consider the condition or change they had
experienced during the premenstrual phase of their pre-
vious three menstrual cycles. Because there is a consid-
erable variation in the duration of premenstrual phase
(range 1 - 14 days), the PAF provides guidelines to help
each woman define her premenstrual period and its du-
ration. The PAF can be scored and analyzed in at least
three different ways: unipolar dimensional scales, bipo-
lar continua, and typological categories. The numerical
scales have been validated by measures of internal con-
sistency, and their reliability is acceptable to good [16].
The Whiteley Index (WI) is a 13-item questionnaire
that asks for yes or no responses. In calculating Whiteley
Index scores, individual items are scored as 1 (positive)
or 0 (negative). All items are scored as positive for an
answer of yes except for one, “Is it easy for you to forget
about yourself and think about all sorts of other things?”
which is reversely scored. The Whiteley Index total
score is the sum of all of items with a total possible
range of 0-13. The Whiteley Index has three subscales:
bodily preoccupation, disease fear, and disease convic-
tion [17]. However, the three-factor structure has not
been confirmed in some studies. As a result, many re-
searchers use the total score of the WI. The internal con-
sistency and test-retest reliability of the WI has been
demonstrated to be satisfactory to good, and there is
evidence of good concurrent, convergent, and predictive
validity [18]. In the present study, a Whiteley Index
score of ≥5 was used as the cut-off for health anxiety
disorder or hypochondriasis. When the Whiteley Index
was used to distinguish between hypochondriacal and
non-hypochondriacal patients, as identified by a struc-
tured interview using DSM-III-R criteria for hypochon-
driasis, the sensitivity and specificity were 87% and 72%
for this cut-off, respectively [19].
2.3. Statistical Analysis
PAF data were used for factor analyses to select a subset
of inter-correlated items representing PMS. Analyses were
originally conducted for PAF data for years 1985 and
1991 separately, and factor structures for those years were
similar. The 1985 factor structure was chosen based on
the larger sample. The items retained in this factor struc-
C opyright © 2011 SciRes. OJPsych

Y. H. Xu et al. / Open Journal of Psychiatry 1 (2011) 98-105 100
ture were used to calculate PAF summary scores for year
1991.
To identify symptom clusters, an exploratory principal
component factor analysis was conducted with varimax
rotation. A total of 57 items loading 0.45 or greater were
retained. Four factors were readily interpreted that ac-
counted for 17.3%, 10.4%, 7.7%, and 6.9% of variance.
The first factor, labeled “premenstrual dysphoria”, con-
tained 31 items such as, sadness, irritability, and other
depressive symptoms. The second factor, labeled “func-
tional impairment”, included 12 symptoms, such as avoids
activities, stays at home more, and does less housework.
Factor three, labeled “motor and cognitive dysfunction”,
included 8 items such as decreased coordination, has
accidents, more forgetful and easily distracted, while
factor four labeled, “physical distress”, consisted of 6
symptoms, such as bloating, weight gain, abdominal
heaviness, and breast pain. Pearson correlations were
used to examine the relationships among the four factors.
Intercorrelations ranged from the lowest at 0.51 to the
highest at 0.75.
For this study, a total PAF score in year 1991 was
calculated by summing all 57 items. Independent vari-
ables were also derived from the 1991 questionnaire.
The distribution of the PAF total scores approximated a
normal curve. Univariate analyses were first used to
evaluate the associations between the outcome variable
(PAF total) and each independent variable. Student’s
t-tests or ANOVAs were used to compare scores from
different groups. Pearson correlations were computed to
examine the associations between pairs of variables.
Multivariate regression was used to examine simultane-
ously the independent relationships between outcome
and independent variables. Variables for which univari-
ate analyses indicated p-values of less than 0.10 were
selected for inclusion in the multivariate regression
model. Stepwise regression was used to select variables
using proc REG procedure. A level of 0.05 was specified
for a variable to enter or leave the model, and r-squared
method was used to select the model. All analyses were
performed using SAS (SAS Institute Inc., SAS 9.1.3,
Cary, NC).
3. RESULTS
In 1991, 410 women between the ages of 25 to 52 years,
with a mean age of 39 years (±7.0 SD), were included in
the study. The majority were white (89%) and married or
living as married (77%). Most of them (93%) had gradu-
ated from college and 87% were employed.
The mean duration of premenstrual symptoms was 6.0
days (±3.1 SD) with a range from 1 to 14 days before the
menses. The mean PAF score was 94.4 (±38.9 SD) with
a range from 57 to 258. Younger women had signifi-
cantly higher mean PAF scores than older women (Table
1). Women who had medical problems and were cur-
rently under a doctor’s care as well as those taking
medications had significantly higher PAF scores than did
those without medical problems. Mean PAF scores were
significantly higher among women with endometriosis,
dysmenorrhea, and migraine compared with participants
without these problems. No significant differences were
Table 1. PAF mean scores* according to patient characteristics.
N (%) PAF Mean
Scores p-values
Age (years) 0.023
25 - 29 58 (14.8%) 100.0
30 - 39 173 (44.0%) 98.0
40 - 52 162 (41.2%) 87.8
Marital Status 0.873
With a partner 222 (76.6%) 96.8
Without a partner 68 (23.4%) 97.7
Annual Household Income 0.168
<$34,999 123 (38.1%) 99.4
$35,999 - $99,999 177 (54.8%) 90.0
>$100,000 23 (7.1%) 90.4
Education 0.104
<16 years 27 (7.3%) 105.0
≥16 years 341 (92.7%) 92.6
Smoking
0.414
Current 37 (9.0%) 99.4
Non-smoker 373 (91.0%) 93.9
Current Medical Problems 0.023
Yes 103 (25.1%) 103.0
No 307 (74.9%) 91.6
Number of Current Medications <0.001
None 324 (79.0%) 88.9
One or more 69 (16.8%) 111.6
Regular Menstruation 0.226
Yes 312 (76.8%) 92.7
No 94 (23.2%) 98.3
Tubal Ligation 0.597
Yes 88 (21.5%) 92.5
No 322 (78.5%) 95.0
Taking Birth Control Pill 0.772
Yes 50 (12.2%) 95.9
No 360 (87.8%) 94.2
Ever Pregnant 0.025
Yes 316 (77.1%) 95.6
No 94 (22.9%) 113.4
Endometriosis 0.049
Yes 19 (5.0) 119.1
No 361 (95.0) 93.3
Dysmenorrhea <0.001
Yes 94 (23.0) 110.1
No 314 (77.0) 89.5
Migraine 0.014
Yes 45 (11.8) 110.9
No 335 (88.2) 92.4
*Scores ranged from 57 to 258 with higher scores indicating more PMS
symptoms.

Y. H. Xu et al. / Open Journal of Psychiatry 1 (2011) 98-105 101
OJPsych
observed in PAF scores according to marital status, in-
come, education, smoking status, regularity of menses,
history of tubal ligation, or taking birth control pills.
PAF scores according to the presence or absence of
individual psychiatric conditions were examined (Table
2). Mean PAF scores were significantly higher among
women with histories of depression, anxiety, and panic
attacks, as well as with family histories of anxiety or
depression.
The mean of Whiteley Index total score for the sample
was 1.7 with a range of 0 - 12. Thirty-one of the 410
(7.6%) women had a Whiteley Index score of ≥5 and
were considered to have health anxiety disorder or hypo-
chondriasis [19]. The mean PAF score for this group was
significantly higher than that from those without health
anxiety (119 ± 55.3 (n = 31) vs. 92.4 ± 36.6 (n = 379);
t-test, p = 0.01). Positive responses on some Whiteley
Index items were associated with higher mean PAF
scores (Table 3). For example, women who answered
the following questions positively had significantly high-
er PAF scores: Are you bothered by many different sym-
ptoms? Is it hard for you to believe the doctor when he
tells you that you have nothing to worry about? Do you
worry a lot about your health? Do you worry about the
possibility that you have a serious illness? Are you often
aware of various things happening in your body? PAF
scores were consistently higher among those answering
questions positively compared with those answering
negatively, with the exception of the question: Are you
afraid of illness? Significant correlations were observed
between mean PAF scores and bodily preoccupation (r =
0.2119, p < 0.0001), disease conviction (r = 0.1861, p <
0.001), but not disease phobia (r = 0.0858, p = 0.0829)
subscales of the Whiteley Index.
Variables that showed significant association (p < 0.10)
with PAF scores in the univariate analysis were exam-
ined further using multivariate regression (Table 4).
Variables significantly and independently associated
Table 2. PAF mean scores according to the presence or ab-
sence of psychiatric conditions.
Mean (n)
Variables Presence Absence
p-values
Psychiatric Conditions
History of Depression 108.3 (n = 93) 90.3 (n = 317)0.001
History of Anxiety 116.1 (n = 37) 92.3 (n = 373)0.016
History of Panic Attacks 115.3 (n = 47) 91.7 (n = 363)0.002
Family History of Anxiety or
Depression 105.1 (n = 101) 90.2 (n = 293)0.004
History of Post-partum
epression D98.5 (n = 30) 94.1 (n = 380)0.548
Table 3. PAF mean scores according to the responses to whiteley index questions.
Mean (n)
Questions Positive Negative
p-values
Are you bothered by many different symptoms? 138.3 (n = 24) 92.0 (n = 381) <0.001
Do you get the feeling that people are not taking your illness seriously enough? 134.9 (n = 12) 93.3 (n = 395) 0.065
Is it hard for you to believe doctor when he tells you nothing to worry about? 121.2 (n = 22) 93.1 (n = 384) 0.041
Do you think something serious wrong with your body? 117.3 (n = 21) 93.2 (n = 387) 0.058
Do you worry a lot about your health? 113.8 (n = 48) 91.7 (n = 358) 0.005
Do you worry about the possibility that you got a serious illness? 111.6 (n = 27) 93.3 (n = 381) 0.018
Is it easy for you to forget about yourself? 109.2 (n = 34) 93.0 (n = 374) 0.078
If a disease is brought to your attention, do you worry about getting it yourself? 107.7 (n = 26) 93.5 (n = 383) 0.072
If you feel ill and someone tells you that you are looking better, you become annoyed.103.6 (n = 38) 93.5 (n = 372) 0.128
Do you worry about your health more than other people? 101.9 (n = 20) 94.0 (n = 390) 0.530
Are you bothered by many pains? 98.5 (n = 84) 93.4 (n = 326) 0.282
Are you often aware of various things happening in your body? 98.0 (n = 213) 90.0 (n = 193) 0.036
Are you afraid of illness? 94.4 (n = 114) 94.8 (n = 292) 0.929
Table 4. Final regression model associated with PAF score.
Variables Coefficients t-valuesp-values
History of panic attacks (yes vs. no) 19.8 3.44 0.001
History of depression (yes vs. no) 17.0 3.78 <0.001
Whiteley Index total score 2.9 2.82 0.005
Age (Years) –0.7 –2.57 0.011
with higher PAF scores were history of depression, his-
tory of panic attacks, total Whiteley Index score and age.
The coefficients represented the expected change in PAF
score associated with a one-unit change in each variable,
given the other variables in the model. For example, the
PAF score was 19.8 points higher in women who had a
history of panic attacks than it was in those without a

Y. H. Xu et al. / Open Journal of Psychiatry 1 (2011) 98-105 102
history of panic attacks. The PAF score was 0.7 points
lower for each one year increase in age. The r-squared
for the model was 0.12, thus 12% of the variance of PAF
score was explained by the variables in this model.
4. DISCUSSION
In the current study, we found health anxiety, as meas-
ured by the Whiteley Index, associated with the premen-
strual symptoms. In addition, a history of depression,
anxiety and younger age were also associated with such
symptoms. To our knowledge, this is the first demonstra-
tion of such a link. Given the relationship of health anxiety
with other symptomatic and functional disturbances, this
finding may not seem surprising. It does not, of course,
establish cause. Such anxiety may serve to accentuate
the experience and reporting of premenstrual symptoms,
or premenstrual symptoms may lead to anxiety about one’s
health, especially if they are not as is too often the case
correctly identified and treated. Either way, the presence
of health anxiety was associated with distress and im-
pairment associated with premenstrual symptoms.
Earlier studies have found that health anxiety tends to
be high among medical specialty populations in which
patients with functional and psychiatric disturbances are
frequent. For instance, one survey found hypochondria-
sis (health anxiety) in 13 percent of otolaryngology cli-
nic patients [20]. Also, hypochondriacal symptoms are
higher in patients with functional and psychiatric distur-
bances than in those with organic illnesses. For example,
one study found significantly higher hypochondriasis
scores in patients with irritable bowel syndrome than in
those with organic gastrointestinal disease [21]. Health
anxiety and hypochondriasis tend to be associated with
increased symptom reporting and functional impairment
in clinical populations. One study found hypochondriasis
in 50% of patients in a pain clinic [22], and another
found high health anxiety predictive of abdominal pain a
year later [23]. Still another found hypochondriasis as-
sociated with chronic pain and pain intensity [24]. Of
course, these associations do not establish cause; painful
symptoms may lead to anxiety about health.
Our finding of significant association between pre-
menstrual symptoms and both depression and anxiety
are consistent with earlier studies [4,7,9,25]. However,
as in previous retrospective studies [26,27], we were not
able to determine the temporal relationship between
these disorders and PMS. Consequently, it is difficult to
know which may have contributed to the other. Indeed, a
definitive diagnosis of PMDD requires prospective
charting of mood and somatic symptoms in two con-
secutive menstrual cycles, and it can be challenging to
distinguish the symptoms of PMDD from those of other
psychiatric disorders.
We found that pain syndromes, such as endometriosis,
dysmenorrhea, and migraine, were also significantly as-
sociated with premenstrual symptoms in univariate ana-
lysis. The diagnoses of these conditions were based on
self-report, and thus mis-classification may have oc-
curred. Also, we did not use a standardized instrument to
collect these diagnoses, so this data can not be compared
directly to other studies. Endometriosis is an estro-
gen-dependent disease, the symptoms of which include
chronic pelvic pain, dysmenorrhea and infertility. En-
dometriosis and PMS are both hormonally influenced
conditions with a wide spectrum severity related to the
menstrual cycle. Dysmenorrhea has also been linked to
PMS [28,29] as has migraine in a few studies. For in-
stance, Hutchinson and colleagues [30] reported that
women suffering from migraine also frequently observe
headache during PMS. Most recently, Martin et al. [31]
found that premenstrual symptoms were more severe
when patients were experiencing migraine. The associa-
tion between these pain syndromes and PMS is consis-
tent with the hypothesis that these syndromes maybe
linked to fluctuations in the levels of estrogen and pro-
gesterone [32].
However, it is important to note that endometriosis,
dysmenorrhea, and migraine did not remain in the final
regression model after controlling for psychiatric disor-
ders. Psychiatric disorders are themselves associated
with increased reporting of physical symptoms. For ex-
ample, patients with major depression experience more
pain symptoms than those without depression [33-35].
Conversely, patients with chronic pain frequently de-
velop depressive disorders, and successful treatment of
depression is often associated with improvement in the
pain [36,37]. Thus, pain syndromes and psychiatric dis-
orders interact and this may explain the failure of such
syndromes to appear in the final model.
Although the reliability and validity of the 95-item
PAF have been tested, the instrument has been criticized
for the overlap in its categorical and numerical scales
[38]. We, therefore, sought to find items that most accu-
rately reflected the premenstrual symptoms in this large
and well-educated group of women, and identified four
factors: premenstrual dysphoria, functional impairment,
motor and cognitive dysfunction, and physical distress.
Premenstrual dysphoria was the dominant factor, which
accounted for 17.3 percent of the variance. Symptoms
that loaded most strongly on this factor included sadness,
irritability, depression, inability to cope and loneliness.
The factors identified in our analysis are comparable to
those found in several previous studies [39-41]. Also, the
symptoms of premenstrual dysphoria as well as physical
distress extracted in our study were also very similar to

Y. H. Xu et al. / Open Journal of Psychiatry 1 (2011) 98-105 103
those found in these studies. Premenstrual dysphoria has
consistently been identified as the first factor in these stud-
ies; it appears to be the central or core feature of PMDD.
This study had several strengths as well as limitations.
The strengths included a large group of well-educated
women aware of health issues by virtue of their study of
nursing. In addition, the study was conducted before
selective serotonin re-uptake inhibitors were in wide-
spread use, thereby eliminating a confounding factor that
would complicate such a study if done today. This study
also has several limitations. First, participants were
largely Caucasian, college graduates, and members of
the middle class. Consequently, they may not have been
representative of the general population. Second, this
was a retrospective study, in which the symptoms were
not confirmed by daily symptom ratings that are the
current gold standard for diagnosis of PMS/PMDD.
Therefore, the diagnosis of PMDD based on DSM-IV
criteria was not possible. In a retrospective study of PMS,
women were more likely to exaggerate past symptoms
and negative moods [42]. Our participants may also have
over-reported symptoms. Third, we did not exclude
women with any psychiatric disorders, and these disor-
ders may have inflated premenstrual symptoms. Lastly,
the most important risk factors, such as depression,
anxiety, panic attacks, and health anxiety were only col-
lected in 1991. Therefore, we could not examine covari-
ates of premenstrual symptoms or risk factors over time.
Health anxiety (hypochondriasis) is important because
it is prevalent, is associated with significant impairment
and is treatable. Effective management and treatment,
including psychological therapies and medication, are
relatively recent developments. Clinicians should be
aware of the association of health anxiety with PMS/
PMDD. Such anxiety as well as other psychiatric disor-
ders are often masked by the presentation of premen-
strual and other physical symptoms. However, if inquiry
is directed toward the meaning of symptoms, health
worry and fear of serious illness may be elicited. Health
anxiety may respond to education regarding premen-
strual and psychiatric symptoms, but definitive treat-
ments include cognitive behavioral therapy and serotonin
re-uptake inhibitors. The latter are used in the treatment of
PMS/PMDD but are often used intermittently. For health
anxiety and other psychiatric disorders continuous admi-
nistration is necessary.
Prospective studies will be needed to clarify the rela-
tionship between health anxiety, other psychiatric disor-
ders, and PMS and PMDD.
5. DECLARATION OF INTEREST
The authors declare that they have no competing inter-
ests.
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