The Journal of Nutrition

Nutritional Epidemiology

The Combination of Healthy Diet and Healthy

Body Weight Is Associated with Lower Risk of
Nuclear Cataract in the Blue Mountains Eye

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Study
Ava Grace Tan,1 Annette Kifley,1 Victoria M Flood,2,3 Joanna Russell,4 George Burlutsky,1
Robert G Cumming,5 Paul Mitchell,1 and Jie Jin Wang1,6

1
Centre for Vision Research, Department of Ophthalmology, The Westmead Institute for Medical Research, The University of Sydney,
Sydney, NSW, Australia; 2 Faculty of Health Sciences, The University of Sydney, Sydney, NSW, Australia; 3 Western Sydney Local Health
District, Westmead Hospital, Westmead, NSW, Australia; 4 School of Health & Society, Faculty of Social Sciences, University of
Wollongong, Wollongong, NSW, Australia; 5 School of Public Health, The University of Sydney, Sydney, NSW, Australia; and 6 Health
Services and Systems Research, Duke-NUS Medical School, Singapore

ABSTRACT
Background: Greater adherence to dietary guidelines has previously been found to be associated with decreased risk
of visual impairment. However, whether or not this association extends to age-related cataract, 1 of the leading causes
of visual impairment, is unknown.
Objectives: The aim of this study was to assess the association between adherence to dietary guidelines, using total
diet score, and incidence of age-related cataract.
Methods: Of 3654 baseline participants of the population-based Blue Mountains Eye Study cohort (1992–1994), 2334
(75.8% survivors) and 1952 (76.7% survivors) were examined after 5 and 10 y, respectively. Cataract was assessed from
lens photographs using the Wisconsin Cataract Grading System. Baseline total diet score was calculated from FFQ data
following a modified version of the Healthy Eating Index for Australians. OR with 95% CI were estimated using discrete
logistic regression analyses, adjusting for age, sex, and other confounders. To test interaction, a cross-product term of
2 factors was included in regression models.
Results: Of 2173 participants (84.7% of those returned for 1 or both follow-ups) with total diet score estimated, 57%
were women, mean baseline age was 63.9 ± 8.4y, and mean baseline BMI was 26.3 ± 4.3 kg/m2 . After multivariable
adjustment, baseline total diet score was not associated with incidence of any cataract. A multiplicative interaction was
observed between total diet score and BMI for incident nuclear cataract (P-interaction = 0.04): increasing baseline total
diet score was associated with decreased risk of nuclear cataract among participants with BMI <25 (per unit increased
total diet score, OR: 0.90; 95% CI: 0.81, 0.99; P = 0.02), but not among participants with BMI ≥25 (OR: 1.00; 95% CI:
0.92, 1.10; P = 0.95).
Conclusions: Adherence to dietary guidelines had no appreciable influence on cataract development overall in this
older Australian population. However, adherence to dietary guidelines combined with healthy BMI is associated with
decreased risk of nuclear cataract, an aging marker. J Nutr 2019;00:1–6.

Keywords: age-related cataract, epidemiology, nutrition, successful aging, total diet score

Worldwide, age-related cataract is 1 of the leading causes
of blindness and visual impairment among persons aged ≥50 y,
responsible for 35% of blindness and 25% of visual impairment
cases (1). There are 3 different types of age-related cataract:
cortical, nuclear, and posterior subcapsular (PSC), affecting
different parts of the lens (2). Although all 3 cataract types
are associated with age, each type has differing etiologies
that are likely multifactorial (2). With continued increase in
the aging population, the socioeconomic and public health
burden of cataract will increase over time. Cataract prevention
or delay in cataract progression may reduce the burden of
cataract and cataract surgery. Evidence from epidemiological
studies indicates that diet and nutrition may influence cataract
development (3), offering a potential cataract prevention
approach.
Previous research involving nutrition and age-related
cataract has mostly focused on the effects of individual nutrients
or combinations of selected nutrients, such as carotenoids and
vitamins C and E (3). Given that individual nutrients are
not consumed in isolation, and therefore, not likely to act in

Copyright  C American Society for Nutrition 2019. All rights reserved.

Manuscript received December 12, 2018. Initial review completed January 10, 2019. Revision accepted April 25, 2019.
First published online 0, 2019; doi: https://doi.org/10.1093/jn/nxz103. 1
isolation, it is important to investigate the influence of overall
healthy diet on cataract development. Summarized scores of
overall dietary consumption provide a more comprehensive
measure of nutrition intake from both healthy and unhealthy
foods and nutrients (4). Towards this goal, our research team
members (JR, VF) had previously developed the total diet score
using a modified Australian diet quality index, and assessed
the association of adherence to both the Dietary Guidelines for
Healthy Adults and the Australian Guide to Healthy Eating with
mortality risk among older Australians (5).
In the Blue Mountains Eye Study (BMES) cohort, we
previously found a decreased risk of visual impairment over 10 y
associated with increasing total diet score measured at baseline
(6), particularly for persons aged ≥65 y. Whether or not this
protective association is a result of associations between healthy
diet and specific causes of visual impairment remains unclear. As
visual impairment can be caused by a number of different eye
diseases, it is important to determine which specific eye diseases
are associated with healthy diet to better understand the disease
etiology, and develop specific disease prevention strategies.
Although there have been studies examining the association
between adherence to dietary guidelines or overall diet quality
and prevalent cataract (7–9), there has been no study examining
the longitudinal associations between adherence to dietary
guidelines and incident cataract. We therefore aimed to
investigate whether greater adherence to dietary guidelines (high
total diet score) is associated with low incidence of age-related
cataract in the BMES cohort.
Methods
Study population
The BMES is a population-based study of vision and common eye
diseases in an Australian population aged ≥49 y, residing in the Blue
Mountains region of Sydney, Australia. Baseline examinations were
conducted during 1992–1994 on 3654 participants (82.4% of eligible).
Follow-up examinations on surviving participants were conducted
5 and 10 y after baseline, where 2334 (75.8% of survivors) and 1952
(76.7% of survivors) participants were followed-up, respectively. The
baseline and follow-up examinations of the BMES were approved by
the Human Research Ethics Committees of the University of Sydney
and the Western Area Health Service. The study adhered to the tenets of
the Declaration of Helsinki and signed informed consent was obtained
from all participants at each examination.
Examination procedures
The same examination procedures were conducted for all examination
visits and have been described in detail previously (10). Briefly, after
pupil dilation, each participant underwent a detailed eye examination
including lens photography. Interviewer-administered questionnaires
were used to collect demographic and medical information.
Cataract assessment
Cataract grading procedures used for all 3 examinations have been
described previously (10). In brief, using retroillumination (Neitz CT-
R, Neitz Instruments) and slitlamp (Topcon SL-7E, Topcon Optical
Co.) lens photographs taken during the eye examination, presence of
Supported by the Australian National Health and Medical Research Council
(grant numbers 974159, 211069, 1031058, and GNT1094094). The funding
organization had no role in the design or conduct of this research.
Author disclosures: AGT, AK, VMF, JR, GB, RGC, PM, and JJW, no conflicts of
interest.
Address correspondence to JJW (e-mail: jiejin.wang@duke-nus.edu.sg).
Abbreviations used: BMES, Blue Mountains Eye Study; PSC, posterior
subcapsular cataract; ROS, reactive oxygen species.
2 Tan et al.
cataract was assessed in a masked manner following the Wisconsin
Cataract Grading System (11). Cortical and posterior subcapsular
(PSC) cataracts were assessed by laying a grid over the anterior and
posterior retroillumination photographs, respectively, and estimating
the percentage of area involved for each type of cataract. Cortical
cataract was defined for those with ≥5% of total area involved.
PSC cataract was defined for those with any such opacity present
(i.e., >0% of total area involved). Nuclear cataract was assessed by
comparing the slitlamp photograph to a standard set of 4 photographs.
Nuclear cataract was defined for those with nuclear opacity greater
than standard photo #3. Inter- and intragrader reliability of the cataract
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grading has been reported previously with good agreement (12).
Participants without a particular type of cataract at baseline were
considered at risk of that particular type in the follow-up and were
included in the assessment of incident cataract. For example, if a
participant had nuclear cataract only at baseline, they would be
considered at risk of both cortical and PSC cataract at follow-up. As
the 3 age-related cataract types have differing etiologies, this analysis
approach provides risk estimations of each cataract type separately
without taking into consideration whether or not other cataract types
are present at baseline.
Dietary assessment
At each visit, participants were asked to complete a validated semi-
quantitative FFQ to assess typical food consumption throughout the
previous year, including portion size estimates and frequency. The FFQ
included 145 items adapted for the Australian diet and vernacular
from the Willett FFQ (13). Validation of the FFQ was conducted in
a subsample of the population (n = 78) and compared against weighed
food records over 1 y (13). Estimates of dietary intakes were determined
using Australian Tables of Food Composition and were analyzed using a
purpose-built software analysis system with Australian nutrition tables
1990 (NUTTAB90) (14) to generate mean daily nutrient intake (15).
Development of the total diet score for BMES has been described
previously (5). Briefly, the total diet score was based on a modified
version of the Australian Healthy Eating Index to assess adherence to
the recommended foods in the Dietary Guidelines for Australian Adults
(16) and the Australian Guide to Healthy Eating (17). The total diet
score was divided into 10 components, with each component given
a score between 0 and 2, for a total score out of 20. Nine of the
10 components assessed dietary recommendations and 1 component
assessed nondietary recommendation for preventing weight gain in the
form of physical activity and energy expenditure. For each of the 10
components, a maximum score of 2 was given to those who met the
recommendations and scores were adjusted accordingly for those with
generally lower intakes of each item (4). Higher total diet scores indicate
high adherence to dietary recommendations.
In this report, we used data from baseline FFQs to determine baseline
total diet score values.
Statistical analysis
SAS 9.4 (SAS Institute) was used for all statistical analyses. Ten-year
incidence of each type of cataract was estimated among participants
without that type of cataract at baseline and who were at risk of
newly developing that type of cataract after baseline. In particular, after
excluding those who had cataract surgery since baseline and those with
missing or ungradable photos at baseline or follow-up visits, there were
1535 participants without cortical cataract at baseline who were at
risk of developing cortical cataract, 1094 without nuclear cataract at
baseline who were at risk of nuclear cataract, and 1724 without PSC at
baseline who were at risk of PSC cataract.
Quartiles of baseline total diet score were created using the baseline
total diet score values of participants who attended the 5-y and/or
10-y follow-up examinations of the BMES (participants included in
this report). Total diet score was assessed as quartiles (lowest quartile
as reference group) and also as a continuous score (per unit increase).
Potential confounding variables adjusted for in the analyses included
the following: baseline age, sex, education levels (defined as attainment
of trade certificate or higher degree), smoking status (past, current, and
 TABLE 1 Comparison of baseline characteristics in participants and nonparticipants of the 5-y
and/or 10-y follow-up examination of the Blue Mountains Eye Study1

Participants Nonparticipants
Baseline characteristics n = 2564 n = 1090 P2
Age, y 64.3 ± 8.6 70.7 ± 10.8 <0.0001
Female, % 57.9 53.9 0.03
Current smoker, % 13.4 19.4 <0.0001
Diabetes, % 6.5 10.8 <0.0001
Hypertension, % 42.6 52.0 <0.0001
Education, %3 <0.0001

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60.4 52.2
Myopia, % 15.4 19.4 0.003
BMI, kg/m2 26.3 ± 4.4 25.6 ± 4.8 <0.0001
Total diet score, unit 9.4 ± 2.2 8.9 ± 2.2 <0.0001
1
Values are means ± SDs for continuous variables and percentages for categorical variables as specified in row titles.
2
P values based on t test for means and chi-square for frequencies.
3
Defined as trade certificate or higher qualification.

never smokers), the presence of hypertension (defined as either systolic
blood pressure ≥160 mm Hg, diastolic blood pressure ≥100 mm Hg
or self-reported hypertension or use of antihypertensive medications),
diabetes (defined as fasting blood glucose ≥7.0 mmol/L, self-reported
diabetes or use of diabetic medication), myopia (spherical equivalent of
less than −1.0 diopter), and self-reported use of inhaled or oral steroids.
Baseline characteristics were compared between those who were
followed-up and those who were lost to follow-up (Table 1).
Characteristics of participants attending the follow-up visits were
compared across quartiles of baseline total diet score (Table 2).
Differences in baseline characteristics were tested using independent
t test for continuous variables (means ± SDs) and Pearson’s chi-
square test for categorical variables (frequencies in percentages). Cox’s
discrete logistic regression models for time-to-event data (18, 19)
were used to assess associations between baseline total diet score
and incidence of each cataract type. The discrete logistic regression
model is similar to the Cox regression model in that it is a survival
analysis model incorporating time-to-event information. However, the
time information used in this model was treated as being discrete in
truth instead of a continuous time spectrum (e.g., number of days or
months to the incidence). This logistic regression model is appropriate
for our data as incident cataract cases were detected at discrete time-
points (the 5-y and/or 10-y follow-up visits) in our study. The discrete
time hazard is related to the covariates by a logistic regression equation
(18, 19). In SAS, this was executed through PROC PHREG, where a
partial likelihood estimation method was used. OR with 95% CI are
presented. P value for trend was calculated using median trend methods.
As a previous report from the BMES population found a protective
association between total diet score and visual impairment among
those aged ≥65 y (6), interaction between total diet score and age
was evaluated. Considering the relation between diet and body weight
status, interaction between total diet score and BMI was also evaluated.
Cross-product terms were added to the regression models, 1 at a
time, to test for multiplicative interactions between total diet score
and age (TDS∗Age), or between total diet score and BMI (TDS∗BMI),
to exclude the possibility of modifying effect of age or BMI on
the association between total diet score and cataract incidence. For
significant interactions, further analyses were conducted in subgroups
stratified by the effect modifier.
Results
Of the 3654 participants at baseline, 2897 (79.2%) had usable
data from baseline FFQ and therefore had total diet scores
estimated, and 2564 (70.2%) had returned to 1 or both follow-
up visits after 5 y and/or 10 y. As a result, 2173 (84.7% of the
2564) participants had both total diet scores and lens status
assessed at 1 or both follow-up examinations.
Nonparticipants were more likely to be older, male, current
smokers, less likely to have higher education and more likely to
have hypertension, diabetes, myopia, low mean BMI, and low
mean total diet score than participants who were followed-up
(Table 1).
Baseline total diet score ranged from 3.2 to 15.4 out of a total
score of 20 (median 9.3, IQR 3.1) among those who attended

TABLE 2 Baseline characteristics of participants who attended the 5-y and/or 10-y follow-up examination of the Blue Mountains Eye
Study by quartiles of baseline total diet score1

Total diet score

Quartile 1 Quartile 2 Quartile 3 Quartile 4
Baseline characteristics n = 540 n = 550 n = 540 n = 543 P2
Total diet score, mean (range) 6.6 (3.2–7.8) 8.6 (7.8–9.3) 10.1 (9.3–10.9) 12.2 (10.9–15.4)
Age, y 63.1 ± 8.6 64.5 ± 8.5 63.4 ± 8.6 64.8 ± 7.9 0.001
Female, % 41.5 56.9 60.0 69.8 <0.0001
Current smoker, % 21.2 13.9 10.5 5.7 <0.0001
Diabetes, % 5.0 6.2 6.3 7.4 0.46
Hypertension, % 42.4 42.5 40.3 44.3 0.62
Education, %3 59.1 61.2 62.8 63.5 0.47
Myopia, % 17.8 14.3 14.8 14.2 0.35
BMI, kg/m2 26.3 ± 4.4 26.6 ± 4.5 26.4 ± 4.2 25.9 ± 4.3 0.056
1
Values are means ± SDs for continuous variables and percentages for categorical variables as specified in row titles.
2
P values based on t test for means and chi-square for frequencies.
3
Defined as trade certificate or higher qualification.

Total diet score, BMI, and incident cataract 3

TABLE 3 Association between total diet score and cumulative 5-y and 10-y incident cataracts in the Blue Mountains Eye Study1

Cortical cataract PSC cataract Nuclear cataract

2 2
Total diet score n/N OR (95% CI) P n/N OR (95% CI) P n/N OR (95% CI) P2
All participants
Quartile 1 83/394 1.00 (ref.) 0.18 30/437 1.00 (ref.) 0.60 78/280 1.00 (ref.) 0.35
Quartile 2 75/373 0.91 (0.63, 1.32) 21/423 0.65 (0.36, 1.20) 93/266 1.30 (0.88, 1.92)
Quartile 3 77/378 1.03 (0.72, 1.48) 28/427 0.87 (0.50, 1.54) 81/276 0.99 (0.66, 1.48)
Quartile 4 99/390 1.23 (0.86, 1.75) 38/437 1.05 (0.60, 1.82) 85/272 0.90 (0.60, 1.36)
Per unit increase in total diet 334/1535 1.04 (0.98, 1.10) 0.23 117/1724 1.03 (0.93, 1.13) 0.59 337/1094 0.95 (0.87, 1.01) 0.08

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score
1
Models adjusted for baseline age, sex, smoking status, hypertension, diabetes, education, use of inhaled or oral steroids, and myopia. n/N, number of cases/number at risk;
PSC, posterior subcapsular.
2
P values are P-trend across quartiles.

follow-up examinations. Participants in the lowest quartile of
total diet score were more likely to be younger, male, and current
smokers at baseline compared to those in the highest quartile
(Table 2).
Cumulative 10-y incidence rates of cortical, nuclear, and
PSC cataracts in this cohort were 21.8% (334/1535), 30.8%
(337/1094), and 6.8% (117/1724), respectively. Increasing
quartiles of total diet score were not associated with any type
of incident cataract (Table 3, findings from all participants).
After adjusting for age, sex, education level, smoking status, the
presence of hypertension, diabetes, or myopia, and the use of
inhaled or oral steroids, there was a marginally nonsignificant,
decreased risk of incident nuclear cataract associated with each
unit increase in total diet score (OR: 0.95; 95% CI: 0.87,
1.01; P = 0.08) (Table 3). No association was evident between
increased total diet score and incident cortical (per unit total
diet score increase, adjusted OR: 1.04; 95% CI: 0.98, 1.10;
P = 0.23) or incident PSC cataract (adjusted OR: 1.03; 95%
CI: 0.93, 1.13; P = 0.59) (Table 3).
We detected a significant interaction between BMI
and total diet score for nuclear cataract development (P-
interaction = 0.04). Analyses stratified by 2 BMI categories
(<25, ≥25 kg/m2 ) showed a 10% decreased risk of incident
nuclear cataract associated with each unit increase in total
diet score among participants with BMI <25, after adjusting
for the same set of co-variables (OR: 0.90; 95% CI: 0.81,
0.99; P = 0.02) (Table 4). In this BMI subgroup, there was a
nonsignificant trend (P-trend = 0.08) of decreasing incident
nuclear cataract with increasing quartiles of total diet score:
OR 1.07, 0.74, and 0.64 for the second, third, and fourth
quartiles of baseline total diet score, respectively, referencing
to the first quartile. No similar associations were observed
among participants with BMI ≥25 (Table 4). There was no
interaction observed between total diet score and age for any
type of cataract (P-interaction >0.05 for all types of cataract).
Discussion
In this population-based cohort of older Australians, we did
not observe any significant associations between healthy diet,
indicated by high adherence to dietary guidelines, and the
incidence of age-related cataract. However, BMI appeared to
modify the association between total diet score and incidence
of nuclear cataract. After stratification by BMI: in persons
with baseline BMI <25, increasing baseline total diet score
was associated with a decreased risk of nuclear cataract
development in 5–10 y.
Although previous studies have reported protective associa-
tions between diet quality and prevalent nuclear cataract (7–9),
and we previously reported increasing baseline total diet score
associated with low risk of visual impairment development in
the BMES population (6), there has been no study investigating
whether adherence to dietary guidelines is associated with
cataract development in a population-based cohort. In this
current study, we found largely negative findings between

TABLE 4 Association between total diet score and nuclear cataract stratified by BMI categories1

Nuclear cataract
Total diet score n/N OR (95% CI) P2
Participants with BMI <25
Quartile 1 41/117 1.00 (ref.) 0.08
Quartile 2 34/96 1.07 (0.58, 1.97)
Quartile 3 31/104 0.74 (0.40, 1.38)
Quartile 4 38/134 0.64 (0.35, 1.15)
Per unit increase in total diet score 144/451 0.90 (0.81, 0.99) 0.02
Participants with BMI ≥25
Quartile 1 35/160 1.00 (ref.) 0.61
Quartile 2 56/167 1.55 (0.90, 2.65)
Quartile 3 50/170 1.37 (0.79, 2.38)
Quartile 4 46/136 1.25 (0.71, 2.22)
Per unit increase in total diet score 187/633 1.00 (0.92, 1.10) 0.95
1
Models adjusted for baseline age, sex, smoking status, hypertension, diabetes, education, use of inhaled or oral steroids, and
myopia. n/N, number of cases/number at risk.
2
P values are P-trend across quartiles.

4 Tan et al.
adherence to dietary guidelines and incident cortical and PSC
cataract over 10 y, except for the protective association between
increasing baseline total diet score and decreasing incidence of
nuclear cataract among participants with BMI <25.
The reported associations between BMI and nuclear cataract
have not been consistent, and no overall longitudinal as-
sociation was found in the BMES (20), although there is
evidence from a meta-analysis of increasing BMI associated
with increased risk of cataract (21). It may be possible that a
combination of healthy diet and healthy BMI is needed to have
beneficial effect on cataract development or on aging. As nuclear
cataract may be considered an aging marker (22), our finding
could suggest that adherence to a healthy diet and maintaining
a healthy body weight may be beneficial to biological aging.
Biological aging is a gradual process of accumulation
of molecular and cellular damages, resulting in declining
physiological functioning and capacity (23). The rate of damage
accumulation can be influenced by a variety of different factors
from the environment and the individual (23, 24). One of the
main drivers, common to both biological aging and nuclear
cataract formation, is oxidative stress from increased reactive
oxygen species (ROS) (22, 23). ROS increase during aging as a
result of a decrease in activity and concentration of antioxidants
that scavenge ROS (23). Similar processes have been described
for nuclear cataract development (22, 25). Higher amounts of
antioxidants were reported to be associated with decreased risk
of nuclear cataract (26–28).
Both healthy diets and healthy BMI were documented
beneficial to mortality risk and overall healthy aging (29, 30).
Moreover, adherence to multiple healthy habits in combination
was associated with greater likelihood of successful aging (29,
31), and maintaining healthy diet and healthy weight are key
recommendations for both healthy aging (32, 33) and eye health
(34). Our findings are in keeping with the current knowledge of
nuclear cataract and aging.
Limitations of this study include potential survival bias,
as participants who were lost to follow-up or had died were
more likely to have cataract risk factors at baseline, such as
smoking and diabetes, and had lower mean total diet score than
those who were followed-up. Such differential survival could
have biased our study findings towards the null. The use of
FFQs in our study to estimate dietary intake could potentially
overestimate intakes of fruits, vegetables, and dairy products.
This potential overestimation has been reported in several
studies using FFQs (13, 35–38) and is inherent to FFQs when the
item list for fruits and vegetables is long (39). Accordingly, we
have made adjustment to minimize overestimation by increasing
the cut-points for high daily intake of fruits and vegetables to be
≥3 servings and ≥ 5servings, respectively. As participants were
unaware of the study questions at baseline, the likelihood of
differential recalling (recall bias) is minimal.
The total diet scores of this study population suggest
relatively low compliance to the dietary guidelines overall
among older Australians, with the highest score (15.4 out of
20) reaching about 77% compliance and the median total diet
scores (9.3/20) is at 46.5% compliance only. The relatively
low compliance observed in our study sample is consistent
with the findings of the 1995 Australian National Nutrition
Survey from an Australian population aged ≥19 y (40). This
low compliance may explain the lack of association observed
for the other cataract types. We cannot exclude the possibility
of residual confounding from unmeasured or unknown factors.
The findings from this largely homogenous population may
only be generalizable to other older populations with similar
demographic and socioeconomic characteristics.
Strengths of our study include the large population-based
sample with reasonably good follow-up (∼75% of survivors),
detailed data collection procedures for risk factor information,
and the use of the same standardized cataract grading proce-
dures to determine cataract status across the 3 examinations.
The longitudinal study design provides a clear temporal relation
between diet at baseline and subsequent cataract development.
In summary, healthy diet, indicated by high adherence to
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dietary guidelines, does not have an appreciable influence
overall on cataract formation over the long term in this
older Australian population. However, adherence to a healthy
diet and maintaining healthy BMI appear beneficial to the
development of nuclear cataract, a marker for biological
aging. Further investigation of the link between healthy diet
and biological aging in different population-based samples is
warranted.
Acknowledgments
The authors’ responsibilities were as follows—AGT, JJW, RGC,
and PM: designed the research; AGT, JJW, RGC, PM, JR, and
VMF: conducted research; AGT, AK, and GB: analyzed data
or performed statistical analyses; AGT, VMF, and JJW: wrote
the manuscript; AGT and JJW: had primary responsibility for
final content; and all authors: read and approved the final
manuscript.
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