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The risk estimates of pneumoconiosis and its relevant complications: a systematic review and meta-analysis

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The risk estimates of pneumoconiosis and its relevant complications: a systematic review and meta-analysis

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The Risk Estimates of Pneumoconiosis and its Relevant Complications:
A Systematic Review and Meta-analysis
by
Baiyi Chen

A Dissertation Presented to the
FACULTY OF THE USC KECK SCHOOL OF MEDICINE
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF APPLIED BIOSTATISTICS AND EPIDEMIOLOGY

May 2023

Copyright 2023 Baiyi Chen

ii
Table of Contents
List of Tables .................................................................................................................................. iii
List of Figures ................................................................................................................................ iii
Abstract ........................................................................................................................................... v
Introduction ..................................................................................................................................... 1
Chapter 1: Methods ......................................................................................................................... 3
Chapter 2: Results ........................................................................................................................... 8
Chapter 3: Discussion ................................................................................................................... 13
Bibliography ................................................................................................................................. 15

iii
List of Tables
Table 1: Rob-SPEO risk of bias scores for eligible studies ............................................................ 9
Table 2: NOS study quality scores and AHRQ standards study quality ....................................... 10
Table 3: Synthesized effect measures of the main complications of Pneumoconiosis ................. 10
Table 4: Synthesized effect measures of other complications of Pneumoconiosis ....................... 10

iv
List of Figures
Figure 1: Flow diagram of study inclusion and exclusion .............................................................. 8
Figure 2: Forest Plot from random-effects model of meta-analysis for overall ORs of PF .......... 12

v
Abstract
Background: Pneumoconiosis and its associated complications are prevalent and significant
occupational diseases among miners. Previous research has concentrated on determining the
incidence and risk factors of pneumoconiosis and its various complications but has lacked a
comprehensive summary. To address the paucity of data, e compared different meta-analysis
techniques to identify the most appropriate approach for our study, considering the features of
the data extracted from the relevant studies.
Methods: Our study included articles published within the past five years on PubMed and
Web of Science that reported the prevalence or risk estimates of Pneumoconiosis-related
complications using multivariable analysis. We excluded articles that did not meet our analysis
requirements in terms of research type, research object, or outcome index, as well as those with
relatively small sample sizes, lack of authoritativeness, or unavailable full text. The Rob-SPEO
Risk of Bias Tool was used to assess the risk of bias based on the study type. We converted the
effect measure from each study into odds ratio (OR) scales and synthesize them to do the meta-
analysis and interpretation. We performed a meta-analysis using a random-effects model to
investigate the risk associated with Pulmonary Fibrosis (PF), which is a major complication of
Pneumoconiosis. Additionally, we reviewed the risk estimates of other complications of
Pneumoconiosis, such as Tuberculosis (TB), Chronic Obstructive Pulmonary (COP), Asthma,
Pneumonia, Lung cancer, and Acquired Immune Deficiency Syndrome (AIDS).
vi
Results: Out of nine eligible studies, five were considered for the meta-analysis, and there is
a statistically significant association that the odds of getting PF among people with
Pneumoconiosis was 4.07 times (95% CI =1.81, 6.34) compared to the odds of getting PF among
people without Pneumoconiosis (p = 0.0004). The Odds of getting TB, COP, Asthma,
Pneumonia, and Lung cancer among people with Pneumoconiosis were higher than the odds of
getting TB, COP, Asthma, Pneumonia, and Lung cancer among people without Pneumoconiosis.
There was a higher risk of getting AIDS among people with Pneumoconiosis than among people
without Pneumoconiosis.
Discussion: Our meta-analysis is suggestive of the higher risk of getting PF among
Pneumoconiosis patients than among people without Pneumoconiosis. The meta-analysis
included a limited number of eligible articles that had the potential of selection bias, which
provided estimates with very large confidence intervals that can potentially limit its
comprehensiveness and ability to fully capture the true impact of Pneumoconiosis on the risk of
Pulmonary Fibrosis.

1
Introduction
Pneumoconiosis is a systemic condition that is primarily defined by the widespread scarring
of lung tissue resulting from the prolonged inhalation of dust particles containing minerals or
metals encountered during occupational exposure. Despite preventive measures to reduce the
incidence, the disease remained prevalent with a case fatality rate of over 20%, making it one of
the most serious occupational diseases worldwide [1]. Treatment for pneumoconiosis patients
required avoiding exposure to occupational dust [2], but many patients were reluctant to give up
their jobs upon diagnosis [3], leading to underreporting and potentially higher case numbers.
Pneumoconiosis has numerous complications, including pulmonary fibrosis, tuberculosis,
bronchitis, pneumonia, emphysema, pulmonary heart disease, spontaneous pneumothorax,
bronchiectasis, and lung abscess [4, 5, 6]. These complications significantly impacted patient
treatment, progression, and prognosis, and might even lead to death [2, 6]. A comprehensive
summary of pneumoconiosis and its epidemiological status would be beneficial for patients and
clinicians to prevent, diagnose, and treat these complications. However, there is currently a lack
of a relatively complete summary of the epidemiological status of pneumoconiosis and its
complications for patients or clinicians to refer to and self-diagnose or diagnose promptly. We
hypothesized that pneumoconiosis could have an impact on the risk of the development of its
complications. Therefore, we conducted a systematic review and meta-analysis to examine the
epidemiological status of pneumoconiosis and its complications in the last five years. We
evaluated the fixed and random-effects models and selected the random-effects model based on
2
the suitability of our study data. The objective of our meta-analysis is to provide a foundation for
the prevention, diagnosis, and management of pneumoconiosis and its associated complications.

3
Chapter 1: Methods
For this study, we screened articles from the recent 5 years from the common databases
PubMed and Web of Science. Studies were screened by title using relevant keywords, such as
risk, prevalence, pneumoconiosis, the specifically related complications of pneumoconiosis, and
the combinations of those keywords, and then screened by abstract respectively. Studies were
considered eligible if they estimated the prevalence or risk of pneumoconiosis-relevant
complications in multivariable analysis in the general population, including all genders and
races. We excluded those articles whose research type, research object, and outcome index could
not meet the analysis requirements and those articles whose full text was unavailable, with a lack
of authority, for example, published on unofficial and non-academic websites, and with
relatively small sample size, for example, the single case studies. To ensure the quality of the
systematic review and meta-analysis, we conducted rigorous quality evaluations using the
validated tools Newcastle-Ottawa Scale (NOS) [7, 8] and the Rob-SPEO Risk of Bias Tool on
the articles that satisfied the criteria [9]. These tools assessed various aspects of study quality,
including randomization, allocation concealment, and handling of missing data. We extracted the
first author’s name, year of publication, study type, number of participants, country, ethnicity or
race, and variable analytic methods with results, including prevalence, odds ratios (ORs), risk
ratios (RRs), population attributable fraction (PAF) or hazard ratios (HRs) for pneumoconiosis
relevant complications.
4
We extracted the effect estimates such as ORs, PAF, RRs, and prevalence of
pneumoconiosis-relevant complications from eligible studies. The main complication of
pneumoconiosis is Pulmonary Fibrosis (PF). We synthesized the effect estimates outcomes for
the main complication of pneumoconiosis and conduct a meta-analysis [1, 10, 11, 12, 13]. In
addition, we found little data on other pneumoconiosis-relevant complications such as TB [8,
10], COP [9, 10], Asthma [10, 11], Chronic Bronchitis [10], Pneumonia [10], Lung Cancer [14],
and AIDS [15]. Therefore, we synthesize the effect estimates outcomes for each of the other
complications of pneumoconiosis and conduct a summary and interpretation.
We chose the Rob-SPEO Risk of Bias Tool to assess the risk of bias in the included studies
based on the study type. We assessed the risk of bias in eight domains: selection (S), blinding
(B), exposure misclassification (E), incomplete exposure data (I), selective reporting of
exposures (SR), conflict of interests (C), differences in the numerator and denominator (D), and
other bias (O). For each domain, the study was rated as having scores ranging from 1 to 5, 1 =
low risk of bias, 2 = probability low risk of bias, 3 = probability high risk of bias, 4 = high risk of
bias, 5 = no information. The overall risk of bias was determined by considering the ratings in all
domains and following the guidance provided by The Rob-SPEO Handbook on how to make
these assessments, including criteria for each domain. Besides, we carefully read the study
design, methods, and results, and consider the potential sources of bias in each of the domains to
assess the risk of bias in the included studies using the Rob-SPEO Risk of Bias tool. To assess
the publication bias for small study effects among the eligible studies for the effect estimates of
5
meta-analysis, we performed a visually inspecting funnel plot. Additionally, A regression-based
Egger test was conducted to assess the publication bias of eligible studies in the meta-analysis
using a random-effects model with ORs as the moderator. We considered all results from the
Rob-SPEO Risk of Bias Tool, the funnel plot, and the regression-based Egger test to assess the
stability of the effect estimates from eligible articles.
To assess the quality of eligible studies, we conducted the National Quality Assessment
(NQA) service using the NOS. In the Agency for Healthcare Research and Quality (AHRQ),
NOS scores ranged from zero to nine, which were assigned to each study based on the NOS
criteria. The higher scores indicate a higher quality of the study [7, 8]. The NOS scores contain
three parts, which are: the “Selection of study groups” that up to four points can be assigned
based on the selection of the study groups, such as the method used to identify the study groups
and the comparability of the groups), the “Comparison of groups” that up to two points can be
assigned based on the comparison of the groups, such as the adjustment for confounders and the
method used to assess the outcome and the “Assessment of outcome” that up to three points can
be assigned based on the measurement of outcome. We converted NOS scores according to the
AHRQ standards to determine the study quality: at least three points in the “Selection of study
groups” and at least one point in the “Comparison of groups” with at least two points in the
“Assessment of outcome” means good quality (+), two points in the “Selection of study groups”
and at least one point in the “Comparison of groups” with at least two points in the “Assessment
of outcome” means fair quality (=), zero or one point in the “Selection of study groups” or zero
6
point in the “Comparison of groups” or zero or one point in the “Assessment of outcome” means
poor quality (-).
We extracted effect measures from each eligible study showing as follows. For the main
complication of Pneumoconiosis - PF, Blanc reported a PAF = 26% [10], Go reported a
Prevalence = 26.7% [11], Lu reported a Prevalence = 30% [1], Reynolds reported a PAF = 26%
[12], and Rivera-Ortega reported a Prevalence = 23% [13]. For the other complications of
Pneumoconiosis - TB, Blanc reported an OR = 2.3 [10], and Ehrlich reported an OR = 2.09 [8].
For COP, Blanc reported a PAF = 14% [10], and Kurth reported a Prevalence = 16.4% [9]. For
Asthma, Blanc reported a PAF = 16% [10], and Go reported a Prevalence = 37.5% [11]. For
Chronic Bronchitis, Blanc reported a PAF = 13% [10]. For Pneumonia, Blanc reported a PAF =
10% [10]. For Lung Cancer, Miron reported an OR = 2.0 [14]. For AIDS, Raanan reported a RR
= 2.87 [15]. To do a meta-analysis of the main complication of pneumoconiosis, we converted
the effect measure from each study into OR scales. To synthesize the effect measures of each
eligible study, we converted PAF to ORs that PAF = Pc (OR - 1) / OR, in which Pc is the
proportion of exposed cases [10], and we converted Prevalence to ORs that OR = Prevalence in
Exposed / Prevalence in Unexposed, in which Exposed is the population with pneumoconiosis.
To better summarize and interpret the effect measures of the other complications of
Pneumoconiosis, we converted most of the effect measures into OR scales.
7
We conducted a heterogeneity analysis using the Chi-square (I
2
) test and assessed the
sensitivity via the influence of individual studies on the weighted estimates by repeating the
meta-analysis by omitting one study at a time [1, 16]. Before conducting the meta-analysis using
the data from eligible studies, we compared the different meta-analysis models, including the
fixed-effects model and the random-effects model. It is critical to choose an appropriate meta-
analysis model because it could ensure and improve the accuracy of various statistics
estimations, providing a basis for the purpose as well as the interpretation of the statistical
analysis [17]. The random-effects model assumes that the true effect sizes may vary among
studies, which is likely to be the case for the eligible statistics in the meta-analysis that have
different true effect sizes among the selected studies [1, 18, 19]. A forest plot from the random-
effects model for the overall effect size of PF was used for the graphical presentation of the
result of the meta-analysis [1, 12, 20]. All statistical analysis tests were performed with Stata
software (Version 17.0; Stata Corp LP, College Station, TX). All P values below 0.05 were
considered statistically significant.

8
Chapter 2: Results
A total of 236 abstracts and titles were initially identified through database searching and
other sources as shown in a flow diagram (Fig 1). After the removal of duplicates, there are
eighty-nine articles remained. Then, we excluded seventy-one articles after the title screening
and exclude five articles after the abstract screening. There were two articles excluded because
of non-full text. We assessed eleven full-text articles, in which two articles were excluded for
reasons that their study population does not satisfy this study [21, 22]. Then, nine studies were
included for the qualitative synthesis and five of them were quantitative syntheses in the meta-
analysis.

Figure 1: Flow diagram of study inclusion and exclusion
9
For 9 eligible studies, we assessed the risk of bias in each domain from the Rob-SPEO Risk
of Bias Tool (Table 1), in which almost all studies were assessed to have a high risk of bias. The
results from Rob-SPEO risk of bias scores showed that most of the studies were at high risk of
selection bias and blinding in the process of the study designs, screening articles, and data
collection. The results from the Rob-SPEO Risk of Bias Tool of the nine eligible studies showed
that those eligible studies have a relatively low representative and a low degree of confidence in
the validity and accuracy [12]. The result of the funnel plot which assessed the publication bias
for small study effects showed that there was no obvious asymmetry, and the result of the
regression-based Egger test indicated there was no statistically significant publication bias for all
eligible studies (p < 0.05).
Author, Year S B E I SR C D O
Blanc et al, 2019 3 4 2 2 2 1 1 1
Ehrlich et al, 2021 4 4 2 2 2 1 1 1
Go et al, 2020 4 4 2 2 3 1 1 1
Kurth et al, 2020 4 4 2 2 2 1 1 1
Lu et al, 2021 3 4 2 2 2 1 1 1
Miron et al, 2020 4 4 2 2 2 1 1 1
Raanan et al, 2022 4 4 2 2 3 1 1 1
Reynolds et al, 2020 3 4 2 2 3 1 1 1
Rivera-Ortega et al, 2019 4 4 2 2 2 1 1 1
Table 1: Rob-SPEO risk of bias scores for eligible studies
The results from the NOS study quality scores and the results converted to AHRQ standards
showed that all nine studies were of good study quality. Five studies containing the effect
measures of the main complications of Pneumoconiosis determined as good quality were
included in the meta-analysis. Other studies were of good quality to interpret the effect measures
10
of other complications of Pneumoconiosis containing TB, COP, Asthma, Pneumonia, Lung
Cancer, and AIDS. We used a table to visualize the synthesized effect measures (ORs) for TB,
COP, Asthma, Pneumonia, Lung Cancer, and RR for AIDS from eligible studies, then
interpreted the effect measures from the study results.
Author, Year
Selection of
Study Groups
Comparability of
Groups
Assessment of
Outcome
Convert to AHRQ
Standards
Blanc et al, 2019 3 2 3 +
Ehrlich et al, 2021 3 1 3 +
Go et al, 2020 3 1 3 +
Kurth et al, 2020 3 2 3 +
Lu et al, 2021 3 1 2 +
Miron et al, 2020 3 1 3 +
Raanan et al, 2022 3 1 2 +
Reynolds et al, 2020 3 1 3 +
Rivera-Ortega et al, 2019 3 1 3 +
Table 2: NOS study quality scores and AHRQ standards study quality
Studies of Main Complications of
Pneumoconiosis (PF)
Synthesized Effect
Measures (ORs)
95% Confidence Interval N
Blanc et al, 2019 7.50 5.05 9.95 1229
Kurth et al, 2020 6.34 3.61 9.06 5316
Lu et al, 2021 2.31 0.036 4.58 3674
Reynolds et al, 2020 2.71 0.476 4.94 1229
Rivera-Ortega et al, 2019 1.77 -0.692 4.14 2425
Table 3: Synthesized effect measures of the main complications of Pneumoconiosis
Other Complications of Pneumoconiosis Synthesized Effect Measures (ORs)
TB 2.3 (Blanc et al, 2019) 2.09 (Ehrlich et al, 2021)
COP 1.88 (Blanc et al, 2019) 1.62 (Kurth et al, 2020)
Asthma 2.14 (Blanc et al, 2019) 4.93 (Go et al, 2020)
Pneumonia 1.5 (Blanc et al, 2019)
2.0 (Miron et al, 2020)
RR = 2.87 (Raanan et al, 2022)
Lung Cancer
AIDS
Table 4: Synthesized effect measures of other complications of Pneumoconiosis
11
The results from the table of synthesized effect measures of other complications of
Pneumoconiosis indicated that the Odds of getting TB, COP, Asthma, Pneumonia, and Lung
cancer among people with Pneumoconiosis are higher than the odds of getting TB, COP,
Asthma, Pneumonia, and Lung cancer among people without Pneumoconiosis. For AIDS, there
was a higher risk of getting AIDS among people with Pneumoconiosis than among people
without Pneumoconiosis.
Based on the characteristics among the selected studies that had different true effect sizes to
do the meta-analysis, the random-effects meta-analysis model was applied to synthesize the
effect measures of Pulmonary Fibrosis (PF) given anticipated statistical heterogeneity [1, 18, 19]
The result of the heterogeneity analysis showed that there is a relatively high degree of
heterogeneity (I
2
= 77.57%) among the eligible studies which indicates that we should use a
random-effects model to do the meta-analysis [1, 18]. In addition, Cochran’s Q test analysis was
performed which also indicates that there is significant heterogeneity among the studies (Q =
17.44, P = 0.0016) [23]. The sensitivity analysis result indicated that the estimates were not
sensitive to individual studies.
12

Figure 2: Forest Plot from random-effects model of meta-analysis for overall ORs of PF
The result of the forest plot from the random-effects model of the meta-analysis shows that
the overall OR of FP is 4.07, with a 95% CI from 1.81 to 6.34 (p = 0.0004), which indicated that
the odds of getting PF among people with Pneumoconiosis is 4.07 times (95% CI =1.81, 6.34)
compared to the odds of getting PF among people without Pneumoconiosis and is of statistical
significance (p = 0.0004).
Blanc2019
Kurth2020
Lu2021
Reynolds2020
RiveraOrtega2019
Overall
Heterogeneity: τ
2
= 5.18, I
2
= 77.57%, H
2
= 4.46
Test of θ
i
= θ
j
: Q(4) = 17.44, p = 0.00
Test of θ = 0: z = 3.52, p = 0.00
Study
0 5 10
with 95% CI
OR
7.50 [
6.34 [
2.31 [
2.71 [
1.77 [
4.07 [
5.05,
3.62,
0.04,
0.48,
-0.60,
1.81,
9.95]
9.06]
4.58]
4.94]
4.14]
6.34]
19.85
18.82
20.51
20.66
20.15
(%)
Weight
Random-effects REML model
13
Chapter 3: Discussion
As a substantial public health concern affecting specific populations, such as coal workers,
the detrimental impact of Pneumoconiosis and its complications cannot be overstated. In this
study, we thoroughly analyzed the risk of bias and study quality after screening the articles based
on pre-determined inclusion and exclusion criteria. Subsequently, we identified five eligible
articles for inclusion in our meta-analysis. Our findings showed that the random-effects meta-
analysis model was more appropriate than the fixed-effects model, as it allowed for variation in
true effect sizes among all studies, leading to a more balanced weighting of each study and
providing a wider confidence interval for the statistical results. The synthesized data from five
eligible articles were extracted to do the random-effects meta-analysis of the main
Pneumoconiosis complication PF. The results of the meta-analysis indicated a statistically
significant relationship: the odds of getting PF among people with Pneumoconiosis is 4.07 times
(95% CI =1.81, 6.34) compared to the odds of getting PF among people without Pneumoconiosis
(p = 0.0004). In addition, there was evidence that getting Pneumoconiosis may increase the risk
of getting TB, COP, Asthma, Pneumonia, Lung cancer, and AIDS, which means pneumoconiosis
patients and the target population should be aware of the relevant high-risk of complications and
to prevent, be diagnosed or treat in advance if possible.
However, this study had some limitations that need to be acknowledged. First, the high risk
of bias in the eligible studies included in the meta-analysis may affect the confidence in the
results. The Rob-SPEO Risk of Bias Tool revealed a relatively high risk of bias in all eligible
14
studies due to selection bias and lack of blinding, which affected confidence in the results of the
meta-analysis and could lead to false-positive results. Second, the small number of eligible
articles included in the meta-analysis might not fully represent the true effects of
Pneumoconiosis on FP, which could limit the comprehensiveness and representativeness of the
meta-analysis. Furthermore, the random-effects model used in the meta-analysis required
sufficient studies to obtain good precision. With the limited number of studies included, accurate
estimation of the between-studies and within-study variance might not be achieved.
This study performed a meta-analysis of the main complication of pneumoconiosis PF and a
review of the epidemiological status of pneumoconiosis and its complications, including TB,
COP, Asthma, Pneumonia, Lung cancer, and AIDS based on the data from eligible articles
reported in the last five years to provide a basis for the prevention, diagnosis, and treatment of
pneumoconiosis and its related complications. Future research should retrieve more eligible
articles in statistical analysis and include articles with a relatively low risk of bias to ensure the
quality of the study and the reliability of the results. In addition, there were other complications
not included in this study such as pulmonary heart disease, etc. because of a lack of eligible
articles and results. Therefore, future research should include more eligible articles to conduct a
more complete analysis including the complications of Pneumoconiosis as many as possible.

15
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Abstract (if available)

Abstract Background: Pneumoconiosis and its associated complications are prevalent and significant occupational diseases among miners. Previous research pointed to risk factors of pneumoconiosis but lacked a comprehensive summary. We compared different meta-analysis techniques to identify the most appropriate approach for our study.
Methods: Our study included articles published within the past five years on PubMed and Web of Science that reported the prevalence or risk estimates of Pneumoconiosis-related complications. The Rob-SPEO Risk of Bias Tool was used to assess the risk of bias based on the study type. We converted the effect measure into OR scales and synthesize them. We performed a meta-analysis using a random-effects model to investigate the risk associated with Pulmonary Fibrosis and reviewed the risk estimates of other complications.
Results: 5 of 9 studies were considered for the meta-analysis, and there is a statistically significant association that the odds of getting Pulmonary Fibrosis among people with Pneumoconiosis was 4.07 times (95% CI =1.81, 6.34) compared to the odds among people without Pneumoconiosis (p = 0.0004). The Odds of getting other complications among people with Pneumoconiosis were higher than the odds among people without Pneumoconiosis.
Discussion: Due to selection bias and lack of blinding, a relatively high risk of bias could affect confidence in the results of the meta-analysis and could lead to false-positive results. The meta-analysis included a limited number of eligible articles, which could potentially limit its comprehensiveness and ability to fully capture the true impact of Pneumoconiosis on the risk of Pulmonary Fibrosis.

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Asset Metadata

Creator Chen, Baiyi (author)

Core Title The risk estimates of pneumoconiosis and its relevant complications: a systematic review and meta-analysis

School Keck School of Medicine

Degree Master of Science

Degree Program Applied Biostatistics and Epidemiology

Degree Conferral Date 2023-05

Publication Date 04/11/2023

Defense Date 04/11/2023

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag meta-analysis,OAI-PMH Harvest,pneumoconiosis,risk estimate,systematic review

Format theses (aat)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Li, Ming (committee chair), Choudhury, Farzana (committee member), Piao, Jin (committee member)

Creator Email baiyic@usc.edu,baiyichen1998@126.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-oUC113010389

Unique identifier UC113010389

Identifier etd-ChenBaiyi-11607.pdf (filename)

Legacy Identifier etd-ChenBaiyi-11607

Document Type Thesis

Format theses (aat)

Rights Chen, Baiyi

Internet Media Type application/pdf

Type texts

Source 20230412-usctheses-batch-1020 (batch), University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

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