Prevalence and factors associated with khat use among minibus workers in northern Tanzania

Abstract

BACKGROUND Khat use is a growing public health concern. Chewed for its stimulant effect, khat can have serious negative social, economic, psychological and health consequences. Little is known about the epidemiology of khat use in Tanzania. This study aimed to determine prevalence and factors associated with khat use among minibus workers in Moshi Municipality, northern Tanzania. METHODS A cross-sectional study was conducted among 254 minibus workers between May and July 2015 in Moshi Municipality, Kilimanjaro region, northern Tanzania. Respondents were sampled from commuter bus stations and interviewed. Multivariable logistic regression models were used to determine factors associated with khat use. RESULTS Prevalence of khat use among minibus workers in Moshi Municipality was found to be 46.5%. Age (OR= 4.68, 95% CI 1.47-14.92), hazardous alcohol use (OR=3.39, 95% CI 1.09-10.53), current cigarette smoking (OR=10.41, 95% CI 2.99-36.26) and having multiple sexual partners (OR=1.92, 95% CI 1.04-3.53) were factors associated with khat use. CONCLUSION Nearly half of minibus workers used khat. Age, hazardous alcohol use, cigarette smoking and having multiple sexual partners were associated with khat use. These findings call for awareness creation about health and social consequences of khat use in line with other risk behaviors like alcohol consumption and cigarette smoking, especially when linked with public transportation services.

Full text

Research Article 1
Prevalence and factors associated with khat use
among minibus workers in northern Tanzania
1Department of Epidemiology and Biostatistics, Kilimanjaro Christian Medical University College, Moshi, Tanzania
2Department of Community Health, Kilimanjaro Christian Medical University College, Moshi, Tanzania
3Mwanza Intervention Trials Unit (MITU), Mwanza, Tanzania
*Corresponding author: ib.mboya@hotmail.com
BACKGROUND
Khat use is a growing public health concern. Chewed for its stimulant effect, khat can have serious negative
social, economic, psychological and health consequences. Little is known about the epidemiology of khat use
in Tanzania. This study aimed to determine prevalence and factors associated with khat use among minibus
workers in Moshi Municipality, northern Tanzania.
METHODS
A cross-sectional study was conducted among 254 minibus workers between May and July 2015 in Moshi
Municipality, Kilimanjaro region, northern Tanzania. Respondents were sampled from commuter bus stations
and interviewed. Multivariable logistic regression models were used to determine factors associated with
khat use.
RESULTS
Prevalence of khat use among minibus workers in Moshi Municipality was found to be 46.5%. Age (OR= 4.68,
95% CI 1.47-14.92), hazardous alcohol use (OR=3.39, 95% CI 1.09-10.53), current cigarette smoking (OR=10.41,
95% CI 2.99-36.26) and having multiple sexual partners (OR=1.92, 95% CI 1.04-3.53) were factors associated
with khat use.
CONCLUSION
Nearly half of minibus workers used khat. Age, hazardous alcohol use, cigarette smoking and having multiple
sexual partners were associated with khat use. These findings call for awareness creation about health and
social consequences of khat use in line with other risk behaviors like alcohol consumption and cigarette
smoking, especially when linked with public transportation services.
Key words: Khat use, minibus workers, prevalence, risk factors, Tanzania
BACKGROUND
Khat use is growing as an issue of public health con-
cern. Khat is a green shrub (from Catha edulis plant) com-
monly cultivated and used in Ethiopia, East Africa and
the southern Arabian Peninsula (El-Menyar, Mekkodathil,
Al-Thani, & Al-Motarred, 2015; Mahfouz, Rahim, Solan,
Makeen, & Alsanosy, 2015; Njuguna, Olieva, Muruka, &
Owek, 2013). People chew khat for its stimulant effect (Al-
sanosy, Mahfouz, & Gaffar, 2013). A number of studies on
khat use have been conducted among secondary school
and college students in Saudi Arabia and Ethiopia. Preva-
lence of about 21% was reported in Jazan region in Saudi
Arabia (Alsanosy et al., 2013) while in Ethiopia it ranged
from 9.6% in University of Gondar (Sinshaw, Messele, &
Kssa, 2014) to 24% in Bahir Dar University (Gebrehanna,
Berhane, & Worku, 2014). Almost two-thirds (68%) of
INNOCENT B. MBOYA1,2*, BEATRICE JOHN1, JULIUS CLEMENT2, FADHILI MBONEA2, AND NEEMA R.
MOSHA3

Research Article 2
men in Masalani town, northeastern Kenya chewed khat,
and half of these did so on a daily basis (Njuguna et al.,
2013). In Tanzania, population-based estimates are scarce.
Prevalence among injection drug users aged 18-59 years in
Dar es Salaam, Tanzania, was reported to be 10.4% among
men and 7.2% among women (Ross et al., 2008). However,
these findings may not reflect khat use among the general
population.
Several demographic, sexual and substance use factors
have been found to be associated with khat use. Fac-
tors associated with khat use include: staying alert for
a long time (El-Menyar et al., 2015; Nigussie, Gobena,
& Mossie, 2013), age, sex (i.e. high among males com-
pared to females), alcohol use, cigarette smoking, having
a friend who uses khat, perceived increased academic
performance, having unprotected sex, initiation of sexual
activity and having multiple sexual partners (Alsanosy
et al., 2013; Birhanu, Bisetegn, & Woldeyohannes, 2014;
Haile & Lakew, 2015; Kassim, Rogers, & Leach, 2014; Nju-
guna et al., 2013; Ross et al., 2008; Sinshaw et al., 2014;
Tilahun & Ayele, 2013). Family history of substance use
“(i.e. alcohol or smoking or khat use)” has also been as-
sociated with khat use (Birhanu et al., 2014). A recent
mixed methods study in Ethiopia has associated problem-
atic khat use with the risk of psychoactive substance use,
especially harmful drinking (Mihretu, Teferra, & Fekadu,
2017).
Consumption of khat can have serious health and eco-
nomic consequences (Haile & Lakew, 2015). For instance,
regular khat use has been associated with increased risk of
hypertension, elevated diastolic blood pressure (Getahun,
Gedif, & Tesfaye, 2010; Mateen & Cascino, 2010), acute
coronary syndrome (Mateen & Cascino, 2010), gastroin-
testinal disorders (Nigussie et al., 2013), psychological
dependence on the substance (Dhaifalah & Santavý, 2004;
Kassim et al., 2014), and mental distress (Damena, Mossie,
& Tesfaye, 2011; Njuguna et al., 2013). Mental health is-
sues such as depression, anxiety, and even psychoses have
been associated with habitual use of khat (Reda, Moges,
Biadgilign, & Wondmagegn, 2012).
Driving under the influence of khat is reported to be
one of the major contributors of road fatalities because
of drivers’ impairment (Awadalla & Suwaydi, 2017;
Eckersley, Salmon, & Gebru, 2010; Gebremichael et
al., 2017; Hayley, Downey, Shiferaw, & Stough, 2016).
Despite this evidence, the burden of khat use among
drivers in Tanzania is not known. Furthermore, because
consumption of khat has been associated with the use of
other substances and increase in other risk behaviors, it
is important to document the burden of this problem to
inform appropriate interventions. This study aimed to
determine prevalence and factors associated with khat
chewing among minibus workers in Tanzania.
METHODS
This was an analytical cross-sectional study conducted
from May to July 2015 in Moshi Municipality, northern
Tanzania. Moshi is one of seven districts of Kilimanjaro
Region, with a total population of 184,292 and an area of
59km2 (National Bureau of Statistics (Tanzania) & Office
of Chief Government Statistician (Zanzibar), 2016). Over
90% of the population depends on income-generation
activities in the informal, micro and small-scale enter-
prises, with the major sources of income being from
private, public and self-employment. The municipality
is a business center and a town containing a main bus
stand as well some other small bus stands serving
different routes within and outside the municipality. This
study included minibus workers from the available 8
commuter bus routes within the municipality streets,
i.e. Kiboroloni, Majengo, Pasua, Kilimanjaro Christian
Medical Center (KCMC), Mailisita, Memorial, Soweto
and Bonite. Minibuses are the most common form of
transportation within the Municipality. The population of
minibus workers was selected under the assumption that
they might be engaging in high-risk behaviors.
Study participants and sample size
Sample size was calculated by using the formula for
estimating a single proportion (Lemeshow, Hosmer, Klar,
Lwanga, & WHO, 1990). Assuming the proportion of
khat use of 20% among minibus workers, the margin of
error of 5% and the standard normal value (1.96) under
the 95% confidence limit, the required sample size was
246. Allowing for 5% of non-response, the minimum
required sample size was estimated to be 260 participants.
We excluded minibus workers whose routes were outside
the municipality. An average of 30 minibus workers were
recruited from each of the 8 stations. Minibus workers
included drivers, conductors and touts – individuals
who persistently, repeatedly and competitively persuade
passengers to board a specific minibus. This population
comprises a mixture of adolescents and youths as well as
adults.
Variables
In this study, khat use was the main outcome. Khat
use was defined as ever chewing the khat substance in the
three months preceding the interview. Participants were
asked how many times they chewed khat in the past three
months. Responses were computed as a binary variable.
Independent variables included socio-demographic
variables such as age, education, area of residence, marital
status, current occupation, alcohol use and smoking status.
Education level was categorized into primary, secondary
and above secondary; area of residence as urban and ru-
ral; occupation as driver, conductor and tout; and marital
status as single, married or cohabiting with a partner, and
widowed, separated or divorced. Smoking status was cat-
egorized as never, former smokers, and current smokers
(smoking cigarette in the past three months) and alcohol
use as never drinkers, non-hazardous drinkers, and haz-
ardous drinkers. Hazardous alcohol use was defined as
East African Journal of Applied Health Monitoring and Evaluation

Research Article 3
a pattern of alcohol consumption that increases the risk
of harmful consequences for the user or others (Babor,
Higgins-Biddle, Saunders, & Monteiro, 2001). This was
calculated based on the WHO AUDIT score, which is a
10-item questionnaire with a range of possible scores from
0 to 40 which is used to assess risk drinking (Babor et al.,
2001; Bazargan-Hejazi, Gaines, Bazargan, Seddighzadeh,
& Ahmadi, 2012). A score of 1 or more indicated consump-
tion at a hazardous level.
We also analyzed risky sexual behavior variables such
as age at first sexual intercourse (in years), condom use
during the first sex, condom use during the last sexual
intercourse, multiple sexual partners (defined as having
two or more sexual partners in the past three months
preceding the interview), alcohol use before sexual
intercourse, and khat use before sexual intercourse.
Data collection
Data collection was conducted by two trained doctor of
medicine students at Kilimanjaro Christian Medical Uni-
versity College. Face-to-face interviews were conducted
using a questionnaire. Each questionnaire was assigned
a unique identification number. As the commuter buses
arrived at the stations during the day, respondents
were approached, administered informed consent, and
recruited (if they had consented) consecutively until the
required sample size was reached.
Statistical analysis
Data was entered and cleaned using Statistical Soft-
ware for Social Sciences (SPSS) (SPSS Inc., Chicago,
IL) version 20.0, checked and corrected for any errors
or inconsistencies every day after the interviews, and
analyzed using STATA
®
software (Stata Corp LP)
version 13.1. Frequency and percentages were used
to describe prevalence of khat use. Numeric variables
were summarized using mean (standard deviation) or
median (interquartile range). Odds ratios (ORs) with
95% confidence intervals (CIs) for factors associated
with khat use were estimated using a multivariable
logistic regression model while controlling for potential
confounders. A p-value of less than 0.05 was considered
to be statistically significant. We also tested for interaction
between alcohol consumption and cigarette smoking
on khat use. We found statistical evidence (p<0.05) for
interaction (results not presented here); the final model
took this into consideration.
Ethical clearance
Ethical clearance was obtained from Kilimanjaro
Christian Medical University College Research and
Ethics Review Committee. Permission to carry out the
study was obtained from Moshi Municipal Authority.
Verbal and written informed consent were obtained from
minibus workers prior to the interviews. Confidentiality
and privacy were maintained by using unique identifi-
cation numbers instead of names. Each participant was
interviewed individually in a private location around the
bus station.
RESULTS
Background characteristics of study participants
A total of 254 minibus workers out of 260 participated
in this study. The mean age of participants was 26.9 years
(standard deviation 6.5; Table 1). About two thirds (62.6%)
were aged between 20 and 29 years. Over half (55.9%) of
those interviewed were drivers. The overall prevalence of
khat use was 46.5%. Of all study participants, 115 (45.5%)
drank alcohol at hazardous levels and 125 (49.2%) were
current cigarette smokers.
Table 1. Background characteristics of minibus workers in Moshi
Municipality (N=254)
Characteristics n %
Khat use
Never used 136 53.5
Ever used 118 46.5
Age in years
Mean (SD) 26.9 (6.5)
15 – 19 25 9.8
20 – 29 159 62.6
30+ 70 27.6
Education
Primary 179 70.5
Secondary 58 22.8
Above Secondary 17 6.7
Area of residence
Urban 191 75.2
Rural 63 24.8
Religion
Muslim 92 36.2
Christian 162 63.8
Current occupation
Driver 142 55.9
Conductor 83 32.7
Tout (tin noise maker) 29 11.4
Marital status
Single 126 49.6
Married/Cohabiting 120 47.2
Widowed/Separated/ Divorced 8 3.2
Alcohol use*
Never 89 35.2
Non-hazardous 49 19.4
Hazardous 115 45.5
Smoking status
Never 100 39.4
Ever smokers 29 11.4
Current smokers 125 49.2
East African Journal of Applied Health Monitoring and Evaluation
One person missing alcohol use information
*

Research Article 4
Risky sexual behaviors of the study participants
The median age at first sexual encounter was 17 years
(interquartile range 15 to 19; Table 2). Over half (52.8%) of
participants reported having two or more sexual partners
in the three months preceding the interview. Prevalence of
condom use during first sex was 23.9% while prevalence
of condom use in the last sexual intercourse was 21.9%.
Of all study participants, 37 (14.7%) used khat before last
sex.
Table 2. Sexual behaviors of minibus workers in Moshi Municipality
Sexual behaviors n %
Age at first sex
Median (IQR) 17 (15,19)
Never 3 1.2
12-14 32 12.6
15-19 166 65.4
20+ 28 11.0
Don’t know/when married 25 9.8
Condom use during first sex
No 191 76.1
Yes 60 23.9
Number of partners, past three months
None 16 6.3
1 Partner 104 40.9
2+ Partners 134 52.8
Alcohol use before last sex
No 126 50.2
Yes 125 49.8
Condom use during last sex
No 196 78.1
Yes 55 21.9
Khat use before last sex
No 214 85.3
Yes 37 14.7
Factors associated with khat use
In the crude analysis, age, hazardous alcohol use,
smoking status, and number of sexual partners showed a
statistically significant association (p<0.05) with higher
odds of khat use (Table 3). Significantly higher odds
of khat use were observed among adolescents (aged
15-19 years) (OR=2.78, 95% CI 1.09, 7.89) and among
those aged 20-29 years (OR=2.32, 95% CI 1.28, 4.20)
compared to adults aged 30 years and above. Likewise,
higher odds of khat use were observed among hazardous
alcohol drinkers (OR=1.91, 95% CI 1.09, 3.36) compared
to never drinkers, current smokers (OR=3.08, 95% CI 1.78,
5.35) compared to those who had never smoked, and
among participants who reported having multiple sexual
partners in the past three months (OR=2.14, 95% CI
1.27, 3.62) compared to those with only one sexual partner.
Table 3. Characteristics associated with khat use among minibus
Characteristics Total Ever
use (%) cOR* (95% CI)
aOR**
(95%CI)
Age in years
15-19 25
14 (56.0)
2.78 (1.09, 7.89)
4.68
(1.47,
14.92)†
20-29 159
82 (51.6)
2.32 (1.28, 4.20)
2.01
(1.02,
3.98)†
30+ 70
22 (31.4)
1.00
Education
Primary 179
84 (46.9)
1.26 (0.46, 3.47) -
Secondary 58
27 (46.6)
1.24 (0.42, 3.72) -
Secondary+ 17 7 (41.2) 1.00
Current occupation
Driver 142
66 (46.5)
1.00
Conductor 83
34 (41.0)
0.80 (0.46, 1.38) -
Tout 29
18 (62.1)
1.88 (0.83, 4.28) -
Marital status
Single/never
married
126
65 (51.6)
1.00
Married/
120
49 (40.8)
0.65 (0.39, 1.07) -
Separated
8 4
(50.0) 0.94 (0.22, 3.92) -
Alcohol use
Never 89
36 (40.4)
1.00
Non-hazardous 49
16 (32.7)
0.71 (0.34, 1.48) -
Hazardous 115
65 (56.5)
1.91 (1.09, 3.36) -
Smoking status
Never 100
32 (32.0)
1.00
Ever smokers 29
12 (41.4)
1.50 (0.64, 3.51) -
Current smok-
ers
125
74 (59.2)
3.08 (1.78, 5.35) -
Age at first sex
Never 3 - - -
12-14 32
17 (53.1)
2.64 (0.72, 5.76) -
15-19 166
80 (48.2)
1.67 (0.73, 3.84) -
20+ 28
10 (35.6)
1.00
Don’t know/
when married
25
11 (44.0)
1.41 (0.47, 4.27) -
Number of sexual partners, past 3 months††
1 partner 104
38 (36.5)
1.00
2+ partners 134
74 (55.2)
2.14 (1.27, 3.62)
1.92
(1.04,
3.53)†
Alcohol use
before
last sex
No 126
56 (44.4)
1.00
Yes 125
62 (49.6)
1.23 (0.75, 2.02) -
Condom use
during
last sex
No 196
95 (48.5)
1.00
Yes 55
23 (41.8)
0.76 (0.42, 1.40) -
*cOR – Crude odds ratio; **aOR – Adjusted odds ratio, adjusted for age, alcohol
use, number of sexual partners, and smoking status;
††
excluded those who never
had sex; †p<0.05; ‡p<0.001.
workers in Moshi Municipality
East African Journal of Applied Health Monitoring and Evaluation

Research Article 5
After adjusting for confounding effects, age, hazardous
alcohol use, smoking status and having multiple sexual
partners remained significantly associated with khat use.
Compared to minibus workers aged 30 years and above,
those aged 15-19 years had about 5 times higher odds of
using khat (OR=4.68, 95% CI 1.47, 14.92), while over 2
times higher odds of khat use were observed among those
aged 20-29 years (OR=2.01, 95% CI 1.02 – 3.98). Minibus
workers with multiple sexual partners had 92% higher
odds of khat use (OR=1.92, 95% CI 1.04, 3.53) compared
to those with only one sexual partner (Table 3).
We also performed a test for interaction due to the
documented co-morbidity between alcohol use and
smoking status (Hurley, Taylor, & Tizabi, 2012) and found
a significant interaction effect (p<0.05). The odds of khat
use were over three times higher (OR=3.39, 95% CI 1.09,
10.53) among hazardous alcohol drinkers (but never
smokers) compared to never drinkers. Current smokers
(but never drinkers) had over ten times higher odds of
using khat compared to never smokers (OR=10.41, 95%
CI 2.99, 36.26). On the other hand, participants who were
non-hazardous drinkers but current smokers had lower
odds of khat use (OR=0.18, 95% CI 0.04, 0.76) compared
to never drinkers (Table 4).
Table 4. Results of interactions* between alcohol use and smoking status
Alcohol
use
Never
drinkers
Non-
hazardous
drinkers
Hazardous
drinkers
Smoking
status
Never
smoke
1.0
1.29 (0.39,
4.26)
3.39 (1.09,
10.53)
Ever smok-
ers
3.17 (0.74,
13.70)
1.80 (0.19,
17.12)
0.31 (0.05,
2.03)†
Current
smokers
10.41 (2.99,
36.26)†
0.18 (0.04,
0.76)†
0.50 (0.16,
1.58)
DISCUSSION
Nearly half of the minibus workers included in this
study in Moshi municipality chewed khat. This is much
higher than that reported among injection drug users in
Dar es Salaam (10% among males and 7% among females)
(Ross et al., 2008) and among secondary school and col-
lege students (10% to 24% in Ethiopia and 21% in Saudi
Arabia) (Alsanosy et al., 2013; Gebrehanna et al., 2014; Sin-
shaw et al., 2014). However, prevalence was lower than
that reported among men (68%) in northeastern Kenya
(Njuguna et al., 2013). Adolescents had higher odds of
khat use in this study, which agrees with findings reported
in Ethiopia (Birhanu et al., 2014; Reda et al., 2012). Adoles-
cence is a period when the khat use habit starts, and khat
is often introduced by peers who are also users, possibly
resulting in higher odds of khat use (Alsanosy et al., 2013;
Gebrehanna et al., 2014).
In the current study, the effect of alcohol consumption
on khat use differed by levels of smoking status. Haz-
ardous alcohol users but never smokers had significantly
higher odds of khat use compared to never drinkers, simi-
lar to findings in Ethiopia (Kassa, Wakgari, & Taddesse,
2016; Mihretu et al., 2017; Tilahun & Ayele, 2013; Tsegay
& Esmael, 2013). Minibus workers who were current
cigarette smokers but were never drinkers had higher
odds of khat use compared to never smokers, which
agrees with findings among men in Kenya (Njuguna et al.,
2013) and among school students in Jazan region, Saudi
Arabia (Alsanosy et al., 2013). Participants who were non-
hazardous drinkers but were current smokers had lower
odds of khat use. Other studies have indicated that one
of the most common consequences of khat chewing is
tobacco uptake (Kassim et al., 2014; Mihretu et al., 2017).
This may be true in our study because current smoking
status increased the odds of khat use. The combined effect
of khat, alcohol and tobacco use leads to serious health
consequences (Hurley et al., 2012; Reda et al., 2012).
Minibus workers with multiple sexual partners were
more likely to be khat users in our study. Similar findings
were reported among secondary school youths in Ethiopia
(Menna, Ali, & Worku, 2014). Repeated khat use has been
reported to increase the odds of high-risk sexual behaviors
(Hoffman & Al’Absi, 2010; Kebede et al., 2005), hence
increased risk of sexually transmitted infections including
HIV/AIDS (Malaju & Asale, 2013). The link between
multiple sexual partners and khat use may be explained
by the high proportion of alcohol use, which is reported
to be associated with high-risk sexual behavior (Bello et
al., 2017). Therefore, interventions to address high-risk
sexual behaviors and substance use should go in hand
with addressing khat use.
Khat is recognized as one of the major contributors
to road traffic a ccidents b ecause i t i ncreases a driver ’s
confidence and excessive speed while also making drivers
irritable and impairing their concentration (Awadalla &
Suwaydi, 2017; Eckersley et al., 2010; Gebremichael et al.,
2017; Hayley et al., 2016). Minibus workers who used khat
in this study were likely to be drinking at hazardous levels
and be current smokers, which could explain the influence
of khat use on road traffic a ccidents. Driving under the
influence of psychoactive substances such as alcohol and
khat is likely to have a negative impact on road transport
safety, especially increased road traffic accidents.
Our study had
some limitations which need to be
taken into consideration. Khat use was estimated based
on minibus workers’ ability to recall for the past three
months, hence there was a potential for recall bias. How-
ever, the questions about khat use were detailed enough
to help participants remember how frequent they used
this substance. Furthermore, minibus workers are a dis-
tinct population, so findings from this study may not be
generalizable to the broader population.
In summary, nearly half of the minibus workers in this
study used khat, and age, hazardous alcohol use, current
cigarette smoking and having multiple sexual partners
East African Journal of Applied Health Monitoring and Evaluation
*Odds ratios (95%CI) adjusted for age and number of sexual partners; †p<0.05

Research Article 6
were all associated with khat use. We recommend raising
awareness about the health and social consequences of
khat use in line with other risk behaviors like alcohol
consumption and cigarette smoking, particularly among
those working in public transportation services. Efforts
should be made to reduce substance use including khat
among those directly involved in public transportation
services. More studies should be conducted in Tanzania
to determine the epidemiology of khat use in relation
to other substances of abuse among adolescents, the
general population and other population subgroups.
Also, additional studies should be done to explore the
link between khat use (and its related risk behaviors) and
road traffic accidents.
ACKNOWLEDGMENTS
We thank all minibus workers who participated in this
study for their voluntary participation and provision of
information which enabled this study to be carried out.
The study was part of a Degree Program in Doctor of
Medicine at the Kilimanjaro Christian Medical University
College.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest
related to this manuscript.
AUTHORS' CONTRIBUTIONS
FM designed the study, data collection, data anal-
ysis and interpretation of the results and drafted the
manuscript. JC designed the study, collected the
data, participated in data analysis and reviewed the
manuscript. BJ participated in data analysis and reviewed
the manuscript. NRM participated in designing the study
and reviewed the manuscript. IBM designed the study,
data analysis and interpretation of findings and reviewed
the manuscript. All authors read and approved the final
version of the manuscript.
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