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1.
Microorganisms ; 12(3)2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38543560

ABSTRACT

BACKGROUND: Understanding the immune response to evolving viral strains is crucial for evidence-informed public health strategies. The main objective of this study is to assess the influence of vaccination on the neutralizing activity of SARS-CoV-2 delta and omicron infection against various SARS-CoV-2 variants. METHODS: A total of 97 laboratory-confirmed COVID-19 cases were included. To assess the influence of vaccination on neutralizing activity, we measured the neutralizing activity of SARS-CoV-2 delta or omicron (BA.1 or BA.2) infection against wild-type (WT), delta, BA.1, and BA.2, with the results stratified based on vaccination status. RESULTS: The neutralizing activity against the WT, delta, and omicron variants (BA.1 and BA.2) was significantly higher in the vaccinated patients than those in the unvaccinated patients. In the unvaccinated individuals infected with the delta variant, the decrease in binding to BA.1 and BA.2 was statistically significant (3.9- and 2.7-fold, respectively) compared to the binding to delta. In contrast, vaccination followed by delta breakthrough infection improved the cross-neutralizing activity against omicron variants, with only 1.3- and 1.2-fold decreases in BA.1 and BA.2, respectively. Vaccination followed by infection improved cross-neutralizing activity against WT, delta, and BA.2 variants in patients infected with the BA.1 variant, compared to that in unvaccinated patients. CONCLUSIONS: Vaccination followed by delta or BA.1 infection is associated with improved cross-neutralizing activity against different SARS-CoV-2 variants. The enhanced protection provided by breakthrough infections could have practical implications for optimizing vaccination strategies.

2.
J Interpers Violence ; 38(11-12): 7728-7753, 2023 06.
Article in English | MEDLINE | ID: mdl-36748671

ABSTRACT

This study examines the effects of social networks on the disclosure of stigmatizing and traumatic sexual assault experiences. We analyzed publicly archived oral histories of Korean "comfort women" from World War II, employing an innovative method combining word embedding analysis, word frequency comparison, and grounded theory. By extracting their significant social relationships from narrated survivor stories, we parsed two distinctive disclosure patterns according to timing of disclosure: early disclosers and late disclosers. The latter were more socially embedded than the former, indicating the constraining aspect of social networks, in which the size of social networks was positively associated with delayed disclosure. Qualitative findings further elaborated that social networks have double-edged effects. Survivors' familial networks functioned as both social constraints and social support for public disclosure. Yet, the late disclosers tend to exploit it more as constraints for the fear of transgenerational transmission of social scorn and stigma. The findings contribute to enhancing a culturally relevant understanding of trauma and the repercussions of human trafficking.


Subject(s)
Disclosure , Sex Offenses , Humans , Female , Interpersonal Relations , Social Networking , Republic of Korea
3.
Sci Rep ; 13(1): 1726, 2023 01 31.
Article in English | MEDLINE | ID: mdl-36721061

ABSTRACT

In this study, we reveal the distinctive communication network structures and contents of online breast cancer community posts in accordance with different cancer stages. Using data collected from community.breastcancer.org, a major online breast cancer community (28,139 original posts and 663,748 replies), we traced the communication network structures and contents of replies associated with its severity. By combining network and quantitative content analyses, we deciphered the functions and utilities of health-related online communication. We found an inverse relationship between offline epidemiological prevalence and online communication activation. Despite the relatively small percentage of breast cancer patients, it was found that the more severe the condition of breast cancer, the more active online communication was. We further found that as pathological severity advances, communication networks move from informational exchange to emotional support. The capture of online social networks based on the cancer stage can help unpack the distinctive communication patterns found across different cancer severities. Our results provide insights into a possible online communication intervention design tailored to symptom severity.


Subject(s)
Breast Neoplasms , Health Communication , Internet-Based Intervention , Humans , Female , Breast Neoplasms/epidemiology , Social Networking
4.
Sci Rep ; 12(1): 4327, 2022 03 14.
Article in English | MEDLINE | ID: mdl-35289331

ABSTRACT

The stroke incidence has increased rapidly in South Korea, calling for a national-wide system for long-term stroke management. We investigated the effects of socioeconomic status (SES) and geographic factors on chronic phase survival after stroke. We retrospectively enrolled 6994 patients who experienced a stroke event in 2009 from the Korean National Health Insurance database. We followed them up from 24 to 120 months after stroke onset. The endpoint was all-cause mortality. We defined SES using a medical-aid group and four groups divided by health insurance premium quartiles. Geographic factors were defined using Model 1 (capital, metropolitan, city, and county) and Model 2 (with or without university hospitals). The higher the insurance premium, the higher the survival rate tended to be (P < 0.001). The patient survival rate was highest in the capital city and lowest at the county level (P < 0.001). Regions with a university hospital(s) showed a higher survival rate (P = 0.006). Cox regression revealed that the medical-aid group was identified as an independent risk factor for chronic phase mortality. Further, NHIP level had a more significant effect than geographic factors on chronic stroke mortality. From these results, long-term nationwide efforts to reduce inter-regional as well as SES discrepancies affecting stroke management are needed.


Subject(s)
Stroke , Geography , Humans , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Social Class , Socioeconomic Factors , Stroke/epidemiology
5.
Front Oncol ; 12: 759272, 2022.
Article in English | MEDLINE | ID: mdl-35211396

ABSTRACT

BACKGROUND: Breast cancer is one of the most commonly diagnosed cancers among women in the United States and pain is the most common side effect of breast cancer and its treatment. Yet, the relationships between social determinants of pain and pain experience/intensity remain under-investigated. We examined the associations between social determinants of pain both at the individual level and the neighborhood level to understand how social conditions are associated with pain perception among early stage breast cancer patients. METHODS: We conducted integrated statistical analysis of 1,191 women with early stage breast cancer treated at a large cancer center in Memphis, Tennessee. Combining electronic health records, patient-reported data and census data regarding residential address at the time of first diagnosis, we evaluated the relationships between social determinants and pain perception. Pain responses were self-reported by a patient as a numerical rating scale score at the patient's initial diagnosis and follow-up clinical visits. We implemented two sets of statistical analyses of the zero-inflated Poisson model and estimated the associations between neighborhood poverty prevalence and breast cancer pain intensity. After adjustment for demographic characteristics, cancer stage, and chemotherapy, pain perception was significantly associated with poverty and blight level of the neighborhood. RESULTS: Among women living in the highest-poverty areas, the odds of reporting pain were 2.48 times higher than those in the lowest-poverty area. Women living in the highest-blight area had 5.43 times higher odds of reporting pain than those in the lowest-blight area. Neighborhood-level social determinants were significantly associated with pain intensity among women diagnosed with early-stage breast cancer. CONCLUSIONS: Distressed neighborhood conditions are significantly associated with higher pain perception. Breast cancer patients living in socio-economically disadvantaged neighborhoods and in poor environmental conditions reported higher pain severity compared to patients from less distressed neighborhoods. Therefore, post-diagnosis pain treatment design needs to be tailored to the social determinants of the breast cancer patients.

6.
Stud Health Technol Inform ; 281: 1036-1040, 2021 May 27.
Article in English | MEDLINE | ID: mdl-34042836

ABSTRACT

This study merges multiple COVID-19 data sources from news articles and social media to propose an integrated infodemic surveillance system (IISS) that implements infodemiology for a well-tailored epidemic management policy. IISS is an à-la-carte infodemic surveillance solution that enables users to gauge the epidemic related consensus, which compiles epidemic-related data from multiple sources and equipped with various methodological toolkits - topic modeling, Word2Vec, and social network analysis. IISS can provide reliable empirical evidence for proper policymaking. We demonstrate the heuristic utilities of IISS using empirical data from the first wave of COVID-19 in South Korea. Measuring discourse congruence allows us to gauge the distance between the discourse corpus from different sources, which can highlight consensus and conflicts in epidemic discourse. Furthermore, IISS detects discrepancies between social concerns and main actors.


Subject(s)
COVID-19 , Epidemics , Social Media , Humans , Republic of Korea/epidemiology , SARS-CoV-2
7.
Epidemiol Health ; 43: e2021035, 2021.
Article in English | MEDLINE | ID: mdl-33971700

ABSTRACT

OBJECTIVES: We aimed to examine how comorbidities were associated with outcomes (illness severity or death) among hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: Data were provided by the National Medical Center of the Korea Disease Control and Prevention Agency. These data included the clinical and epidemiological information of all patients hospitalized with COVID-19 who were discharged on or before April 30, 2020 in Korea. We conducted comorbidity network and multinomial logistic regression analyses to identify risk factors associated with COVID-19 disease severity and mortality. The outcome variable was the clinical severity score (CSS), categorized as mild (oxygen treatment not needed), severe (oxygen treatment needed), or death. RESULTS: In total, 5,771 patients were included. In the fully adjusted model, chronic kidney disease (CKD) (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.19 to 5.61) and chronic obstructive pulmonary disease (COPD) (OR, 3.19; 95% CI, 1.35 to 7.52) were significantly associated with disease severity. CKD (OR, 5.35; 95% CI, 2.00 to 14.31), heart failure (HF) (OR, 3.15; 95% CI, 1.22 to 8.15), malignancy (OR, 3.38; 95% CI, 1.59 to 7.17), dementia (OR, 2.62; 95% CI, 1.45 to 4.72), and diabetes mellitus (OR, 2.26; 95% CI, 1.46 to 3.49) were associated with an increased risk of death. Asthma and hypertension showed statistically insignificant associations with an increased risk of death. CONCLUSIONS: Underlying diseases contribute differently to the severity of COVID-19. To efficiently allocate limited medical resources, underlying comorbidities should be closely monitored, particularly CKD, COPD, and HF.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Adult , Aged , Aged, 80 and over , Comorbidity , Diabetes Mellitus/epidemiology , Female , Heart Failure/epidemiology , Humans , Hypertension/epidemiology , Logistic Models , Male , Middle Aged , Oxygen Inhalation Therapy/statistics & numerical data , Prevalence , Pulmonary Disease, Chronic Obstructive/epidemiology , Renal Insufficiency, Chronic/epidemiology , Republic of Korea/epidemiology , Risk Factors , SARS-CoV-2 , Severity of Illness Index
8.
Front Pediatr ; 9: 620848, 2021.
Article in English | MEDLINE | ID: mdl-33777865

ABSTRACT

Background: Scientific evidence confirm that significant racial disparities exist in healthcare, including surgery outcomes. However, the causal pathway underlying disparities at preoperative physical condition of children is not well-understood. Objectives: This research aims to uncover the role of socioeconomic and environmental factors in racial disparities at the preoperative physical condition of children through multidimensional integration of several data sources at the patient and population level. Methods: After the data integration process an unsupervised k-means algorithm on neighborhood quality metrics was developed to split 29 zip-codes from Memphis, TN into good and poor-quality neighborhoods. Results: An unadjusted comparison of African Americans and white children showed that the prevalence of poor preoperative condition is significantly higher among African Americans compared to whites. No statistically significant difference in surgery outcome was present when adjusted by surgical severity and neighborhood quality. Conclusions: The socioenvironmental factors affect the preoperative clinical condition of children and their surgical outcomes.

9.
Stud Health Technol Inform ; 272: 17-20, 2020 Jun 26.
Article in English | MEDLINE | ID: mdl-32604589

ABSTRACT

The increased prevalence and frequency of infectious diseases are alarming with respect to the disproportionate fatalities across different regions, socio-economic conditions, and demographic groups. Combining pathological data, socio-environmental data, and extracted knowledge from white papers, we proposed a Globally Localized Epidemic Knowledge base (GLEK) that can be utilized for efficient and optimal epidemic surveillance. GLEK merges social, environmental, pathological, and governmental intervention data to provide efficient advice for epidemic control and intervention. Heuristically utilizing multi-locus data sources, GLEK can identify the best tailored intervention.


Subject(s)
Communicable Diseases , Epidemics , Humans , Intelligence , Knowledge Bases
10.
Stud Health Technol Inform ; 262: 332-335, 2019 Jul 04.
Article in English | MEDLINE | ID: mdl-31349335

ABSTRACT

Adverse Childhood Experiences (ACEs) are negative events or states that affect children, with lasting impacts throughout their adulthood. ACES are considered one of the major risk factors for several adverse health outcomes and are associated with low quality of life and many detrimental social and economic consequences. In order to enact better surveillance of ACEs and their associated conditions, it is instrumental to provide tools to detect, monitor and respond effectively. In this paper, we present a recommender system tasked with simplifying data collection, access, and reasoning related to ACEs. The recommender system uses both semantic and statistical methods to enable content and context-based filtering.


Subject(s)
Adverse Childhood Experiences , Data Analysis , Quality of Life , Adult , Child , Humans , Risk Factors
11.
Stud Health Technol Inform ; 262: 336-339, 2019 Jul 04.
Article in English | MEDLINE | ID: mdl-31349336

ABSTRACT

Chronic diseases and conditions are the leading cause of death and disability in the United States. The number of people living with two or more chronic conditions has increased in the last decades and is expected to continue to rise over the upcoming years. Yet, traditional chronic disease surveillance practices have been specialized for a specific symptom or a single health condition. To better understand the complication and complexity of multimorbidity in chronic diseases, this paper suggests the use of network science for multimorbidity network surveillance (MNS). We discuss why the relational perspective in surveillance is critical and how network science can help and be integrated into surveillance and public health practice.


Subject(s)
Disabled Persons , Information Services , Multimorbidity , Population Surveillance , Chronic Disease , Humans , Research , United States
12.
JMIR Ment Health ; 6(5): e13498, 2019 May 21.
Article in English | MEDLINE | ID: mdl-31115344

ABSTRACT

BACKGROUND: Adverse Childhood Experiences (ACEs), a set of negative events and processes that a person might encounter during childhood and adolescence, have been proven to be linked to increased risks of a multitude of negative health outcomes and conditions when children reach adulthood and beyond. OBJECTIVE: To better understand the relationship between ACEs and their relevant risk factors with associated health outcomes and to eventually design and implement preventive interventions, access to an integrated coherent dataset is needed. Therefore, we implemented a formal ontology as a resource to allow the mental health community to facilitate data integration and knowledge modeling and to improve ACEs' surveillance and research. METHODS: We use advanced knowledge representation and semantic Web tools and techniques to implement the ontology. The current implementation of the ontology is expressed in the description logic ALCRIQ(D), a sublogic of Web Ontology Language (OWL 2). RESULTS: The ACEs Ontology has been implemented and made available to the mental health community and the public via the BioPortal repository. Moreover, multiple use-case scenarios have been introduced to showcase and evaluate the usability of the ontology in action. The ontology was created to be used by major actors in the ACEs community with different applications, from the diagnosis of individuals and predicting potential negative outcomes that they might encounter to the prevention of ACEs in a population and designing interventions and policies. CONCLUSIONS: The ACEs Ontology provides a uniform and reusable semantic network and an integrated knowledge structure for mental health practitioners and researchers to improve ACEs' surveillance and evaluation.

13.
Stud Health Technol Inform ; 258: 31-35, 2019.
Article in English | MEDLINE | ID: mdl-30942708

ABSTRACT

Adverse Childhood Experiences (ACEs) have been proven to be linked to increased risks of a multitude of negative health outcomes and conditions when children reach adulthood and beyond. To better understand the relationship between ACEs and the associated health outcomes and eventually to pan and implement preventive interventions, access to an integrated coherent actionable data set is crucial. In this paper, we introduce a formal reusable ontological framework to capture the knowledge in the domain of Adverse Childhood Experiences to improve ACEs surveillance and response.


Subject(s)
Adverse Childhood Experiences , Population Surveillance , Adult , Biological Ontologies , Child , Data Mining , Humans
14.
JAMA Netw Open ; 2(1): e186963, 2019 01 04.
Article in English | MEDLINE | ID: mdl-30646208

ABSTRACT

Importance: This study examines how different types of social network structures are associated with early cognitive development in children. Objectives: To assess how social relationships and structures are associated with early cognitive development and to elucidate whether variations in the mother's social networks alter a child's early cognitive development patterns. Design, Setting, and Participants: This cohort study used data from 1082 mother-child pairs in the University of Tennessee Health Science Center-Conditions Affecting Neurocognitive Development and Learning and Early Childhood project to examine the association between networks of different levels of complexity (triad, family, and neighborhood) and child cognitive performance after adjustment for the mother's IQ, birth weight, and age, and the father's educational level. The final model was adjusted for the household poverty level. Data were collected from December 2006 through January 2014 and analyzed from October through November 2018. Exposures: The child-mother relationship, child-mother-father triad, family setting, child's dwelling network, mother's social support network, and neighborhood networks. Main Outcomes and Measures: Measure of cognitive development of the child using Bayley Scales of Infant Development (BSID) at 2 years of age. Results: Of 1082 participants, 544 (50.3%) were males and 703 (65.1%) were African American; the mean (SD) age was 2.08 (0.12) years. Large family size had a negative association with early cognitive development, with a mean 2.21-point decrease in BSID coefficient score (95% CI, 0.40 to 4.02; P = .01). Mother's social support network size was positively associated early cognitive development, with a mean 0.40-point increase in BSID coefficient score (95% CI, 0.001 to 0.80; P = .05). Knowing many neighbors was not statistically significantly associated with early cognitive development, with a mean 1.39-point increase in BSID coefficient score (95% CI, -0.04 to 2.83; P = .06). Conclusions and Relevance: The findings suggest that maternal social relationships are associated with cognitive development in children and that social relationships beyond the mother-child-father triad are significantly associated with children's cognitive development. This study investigates the environmental influences on child health outcomes and, specifically, how early cognitive development is associated with social networks for the primary caregiver.


Subject(s)
Child Development , Cognition , Family Relations/psychology , Father-Child Relations , Mother-Child Relations , Social Environment , Adult , Child, Preschool , Cohort Studies , Female , Humans , Interpersonal Relations , Male , Social Networking , Tennessee
15.
JAMIA Open ; 2(3): 317-322, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31984364

ABSTRACT

OBJECTIVE: Our objective was to develop and test a new concept (affinity) analogous to multimorbidity of chronic conditions for individuals at census tract level in Memphis, TN. The use of affinity will improve the surveillance of multiple chronic conditions and facilitate the design of effective interventions. METHODS: We used publicly available chronic condition data (Center for Disease Control and Prevention 500 Cities project), socio-demographic data (US Census Bureau), and demographics data (Environmental Systems Research Institute). We examined the geographic pattern of the affinity of chronic conditions using global Moran's I and Getis-Ord Gi* statistics and its association with socio-economic disadvantage (poverty, unemployment, and crime) using robust regression models. We also used the most common behavioral factor, smoking, and other demographic factors (percent of the male population, percent of the population 67 years, and over and total population size) as control variables in the model. RESULTS: A geo-distinctive pattern of clustered chronic affinity associated with socio-economic deprivation was observed. Statistical results confirmed that neighborhoods with higher rates of crime, poverty, and unemployment were associated with an increased likelihood of having a higher affinity among major chronic conditions. With the inclusion of smoking in the model, however, only the crime prevalence was statistically significantly associated with the chronic affinity. CONCLUSION: Chronic affinity disadvantages were disproportionately accumulated in socially disadvantaged areas. We showed links between commonly co-observed chronic diseases at the population level and systematically explored the complexity of affinity and socio-economic disparities. Our affinity score, based on publicly available datasets, served as a surrogate for multimorbidity at the population level, which may assist policymakers and public health planners to identify urgent hot spots for chronic disease and allocate clinical, medical and healthcare resources efficiently.

16.
Stud Health Technol Inform ; 255: 80-84, 2018.
Article in English | MEDLINE | ID: mdl-30306911

ABSTRACT

African American children are more than twice as likely as white American children to die after surgery, and have increased risk for longer hospital stays, post-surgical complications, and higher hospital costs. Prior research into disparities in pediatric surgery outcomes has not considered interactions between patient-level Clinical Risk Factors (CRFs) and population-level Social, Economic, and Environmental Factors (SEEFs) primarily due to the lack of integrated data sets. In this study, we analyze correlations between SEEFs and CRFs and correlations between CRFs and surgery outcomes. We used a dataset from a cohort of 460 surgical cases who underwent surgery at a children's hospital in Memphis, Tennessee in the United States. The analysis was conducted on 23 CRFs, 9 surgery outcomes, and 10 SEEFs and demographic variables. Our results show that population-level SEEFs are significantly associated with both patient-level CRFs and surgery outcomes. These findings may be important in the improved understanding of health disparities in pediatric surgery outcomes.


Subject(s)
Black or African American , Healthcare Disparities , Socioeconomic Factors , Child , Data Analysis , Humans , Risk Factors , Tennessee/epidemiology , United States , White People
17.
Stud Health Technol Inform ; 247: 436-440, 2018.
Article in English | MEDLINE | ID: mdl-29677998

ABSTRACT

Most pediatric asthma cases occur in complex interdependencies, exhibiting complex manifestation of multiple symptoms. Studying asthma comorbidities can help to better understand the etiology pathway of the disease. Albeit such relations of co-expressed symptoms and their interactions have been highlighted recently, empirical investigation has not been rigorously applied to pediatric asthma cases. In this study, we use computational network modeling and analysis to reveal the links and associations between commonly co-observed diseases/conditions with asthma among children in Memphis, Tennessee. We present a novel method for geo-parsed comorbidity network analysis to show the distinctive patterns of comorbidity networks in urban and suburban areas in Memphis.


Subject(s)
Asthma/complications , Child , Comorbidity , Humans , Tennessee
18.
NPJ Digit Med ; 1: 50, 2018.
Article in English | MEDLINE | ID: mdl-31304329

ABSTRACT

The importance of social components of health has been emphasized both in epidemiology and public health. This paper highlights the significant impact of social components on health outcomes in a novel way. Introducing the concept of sociomarkers, which are measurable indicators of social conditions in which a patient is embedded, we employed a machine learning approach that uses both biomarkers and sociomarkers to identify asthma patients at risk of a hospital revisit after an initial visit with an accuracy of 66%. The analysis has been performed over an integrated dataset consisting of individual-level patient information such as gender, race, insurance type, and age, along with ZIP code-level sociomarkers such as poverty level, blight prevalence, and housing quality. Using this uniquely integrated database, we then compare the traditional biomarker-based risk model and the sociomarker-based risk model. A biomarker-based predictive model yields an accuracy of 65% and the sociomarker-based model predicts with an accuracy of 61%. Without knowing specific symptom-related features, the sociomarker-based model can correctly predict two out of three patients at risk. We systematically show that sociomarkers play an important role in predicting health outcomes at the individual level in pediatric asthma cases. Additionally, by merging multiple data sources with detailed neighborhood-level data, we directly measure the importance of residential conditions for predicting individual health outcomes.

19.
Stud Health Technol Inform ; 235: 481-485, 2017.
Article in English | MEDLINE | ID: mdl-28423839

ABSTRACT

Most chronic diseases are a result of a complex web of causative and correlated factors. As a result, effective public health or clinical interventions that intend to generate a sustainable change in these diseases most often use a combination of strategies or programs. To optimize comparative effectiveness evaluations and select the most efficient intervention(s), stakeholders (i.e. public health institutions, policy-makers and advocacy groups, practitioners, insurers, clinicians, and researchers) need access to reliable assessment methods. Building on the theory of Evidence-Based Public Health (EBPH) we introduce a knowledge-based framework for evaluating the consistency and effectiveness of public health programs, interventions, and policies. We use a semantic inference model that assists decision-makers in finding inconsistencies, identifying selection and information biases, and with identifying confounding and hidden dependencies in different public health programs and interventions. The use of formal ontologies for automatic evaluation and assessment of public health programs improves program transparency to stakeholders and decision makers, which in turn increases buy-in and acceptance of methods, connects multiple evaluation activities, and strengthens cost analysis.


Subject(s)
Population Health , Semantics , Costs and Cost Analysis , Decision Making , Evidence-Based Practice , Humans
20.
Stud Health Technol Inform ; 245: 1335, 2017.
Article in English | MEDLINE | ID: mdl-29295416

ABSTRACT

The major goal of our study is to provide an automatic evaluation framework that aligns the results generated through semantic reasoning with the best available evidence regarding effective interventions to support the logical evaluation of public health policies. To this end, we have designed the POLicy EVAlUation & Logical Testing (POLE.VAULT) Framework to assist different stakeholders and decision-makers in making informed decisions about different health-related interventions, programs and ultimately policies, based on the contextual knowledge and the best available evidence at both individual and aggregate levels.


Subject(s)
Decision Making , Health Policy , Semantics , Humans , Knowledge , Policy Making
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