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In an effort to begin validating the large number of discovered candidate biomarkers, proteomics is beginning to shift from shotgun proteomic experiments towards targeted proteomic approaches that provide solutions to automation and economic concerns. Such approaches to validate biomarkers necessitate the mass spectrometric analysis of hundreds to thousands of human

In an effort to begin validating the large number of discovered candidate biomarkers, proteomics is beginning to shift from shotgun proteomic experiments towards targeted proteomic approaches that provide solutions to automation and economic concerns. Such approaches to validate biomarkers necessitate the mass spectrometric analysis of hundreds to thousands of human samples. As this takes place, a serendipitous opportunity has become evident. By the virtue that as one narrows the focus towards "single" protein targets (instead of entire proteomes) using pan-antibody-based enrichment techniques, a discovery science has emerged, so to speak. This is due to the largely unknown context in which "single" proteins exist in blood (i.e. polymorphisms, transcript variants, and posttranslational modifications) and hence, targeted proteomics has applications for established biomarkers. Furthermore, besides protein heterogeneity accounting for interferences with conventional immunometric platforms, it is becoming evident that this formerly hidden dimension of structural information also contains rich-pathobiological information. Consequently, targeted proteomics studies that aim to ascertain a protein's genuine presentation within disease- stratified populations and serve as a stepping-stone within a biomarker translational pipeline are of clinical interest. Roughly 128 million Americans are pre-diabetic, diabetic, and/or have kidney disease and public and private spending for treating these diseases is in the hundreds of billions of dollars. In an effort to create new solutions for the early detection and management of these conditions, described herein is the design, development, and translation of mass spectrometric immunoassays targeted towards diabetes and kidney disease. Population proteomics experiments were performed for the following clinically relevant proteins: insulin, C-peptide, RANTES, and parathyroid hormone. At least thirty-eight protein isoforms were detected. Besides the numerous disease correlations confronted within the disease-stratified cohorts, certain isoforms also appeared to be causally related to the underlying pathophysiology and/or have therapeutic implications. Technical advancements include multiplexed isoform quantification as well a "dual- extraction" methodology for eliminating non-specific proteins while simultaneously validating isoforms. Industrial efforts towards widespread clinical adoption are also described. Consequently, this work lays a foundation for the translation of mass spectrometric immunoassays into the clinical arena and simultaneously presents the most recent advancements concerning the mass spectrometric immunoassay approach.
ContributorsOran, Paul (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Ros, Alexandra (Committee member) / Williams, Peter (Committee member) / Arizona State University (Publisher)
Created2011
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Purpose: To examine: (1) whether Non-Hispanic Blacks (NHB) and Non-Hispanic Whites (NHW) with diagnosed arthritis differed in self-reported physical activity (PA) levels, (2) if NHB and NHW with arthritis differed on potential correlates of PA based on the Social Ecological Model (Mcleroy et al., 1988), and (3) if PA participation

Purpose: To examine: (1) whether Non-Hispanic Blacks (NHB) and Non-Hispanic Whites (NHW) with diagnosed arthritis differed in self-reported physical activity (PA) levels, (2) if NHB and NHW with arthritis differed on potential correlates of PA based on the Social Ecological Model (Mcleroy et al., 1988), and (3) if PA participation varied by race/ethnicity after controlling for age, gender, education, and BMI. Methods: This study was a secondary data analysis of data collected from 2006-2008 in Chicago, IL as part of the Midwest Roybal Center for Health Promotion. Bivariate analyses were used to assess potential differences between race in meeting either ACR or ACSM PA guidelines. Comparisons by race between potential socio-demographic correlates and meeting physical activity guidelines were assessed using Chi-squares. Potential differences by race in psychosocial, arthritis, and health-related and environmental correlates were assessed using T-tests. Finally, logistic regression analyses were used to examine if race was still associated with PA after controlling for socio-demographic characteristics. Results: A greater proportion of NHW (68.1% and 35.3%) than NHB (46.5% and 20.9%) met both the arthritis-specific and the American College of Sports Medicine (ACSM) recommendations for physical activity, respectively. NHB had significantly lower self-efficacy for exercise and reported greater impairments in physical function compared to NHW. Likewise, NHB reported more crime and less aesthetics within their neighborhood. NHW were 2.56 times more likely to meet arthritis-specific PA guidelines than NHB after controlling for age, gender, education, marital status, and BMI. In contrast, after controlling for sociodemographic characteristics, age and gender were the only significant predictors of meeting ACSM PA guidelines. Discussion: There were significant differences between NHB and NHW individuals with arthritis in meeting PA guidelines. After controlling for age, gender, education, and BMI non-Hispanic White individuals were still significantly more likely to meet PA guidelines. Interventions aimed at promoting higher levels of physical activity among individuals with arthritis need to consider neighborhood aesthetics and crime when designing programs. More arthritis-specific programs are needed in close proximity to neighborhoods in an effort to promote physical activity.
ContributorsChuran, Christopher (Author) / Der Ananian, Cheryl (Thesis advisor) / Adams, Marc (Committee member) / Campbell, Kathryn (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Signal processing techniques have been used extensively in many engineering problems and in recent years its application has extended to non-traditional research fields such as biological systems. Many of these applications require extraction of a signal or parameter of interest from degraded measurements. One such application is mass spectrometry immunoassay

Signal processing techniques have been used extensively in many engineering problems and in recent years its application has extended to non-traditional research fields such as biological systems. Many of these applications require extraction of a signal or parameter of interest from degraded measurements. One such application is mass spectrometry immunoassay (MSIA) which has been one of the primary methods of biomarker discovery techniques. MSIA analyzes protein molecules as potential biomarkers using time of flight mass spectrometry (TOF-MS). Peak detection in TOF-MS is important for biomarker analysis and many other MS related application. Though many peak detection algorithms exist, most of them are based on heuristics models. One of the ways of detecting signal peaks is by deploying stochastic models of the signal and noise observations. Likelihood ratio test (LRT) detector, based on the Neyman-Pearson (NP) lemma, is an uniformly most powerful test to decision making in the form of a hypothesis test. The primary goal of this dissertation is to develop signal and noise models for the electrospray ionization (ESI) TOF-MS data. A new method is proposed for developing the signal model by employing first principles calculations based on device physics and molecular properties. The noise model is developed by analyzing MS data from careful experiments in the ESI mass spectrometer. A non-flat baseline in MS data is common. The reasons behind the formation of this baseline has not been fully comprehended. A new signal model explaining the presence of baseline is proposed, though detailed experiments are needed to further substantiate the model assumptions. Signal detection schemes based on these signal and noise models are proposed. A maximum likelihood (ML) method is introduced for estimating the signal peak amplitudes. The performance of the detection methods and ML estimation are evaluated with Monte Carlo simulation which shows promising results. An application of these methods is proposed for fractional abundance calculation for biomarker analysis, which is mathematically robust and fundamentally different than the current algorithms. Biomarker panels for type 2 diabetes and cardiovascular disease are analyzed using existing MS analysis algorithms. Finally, a support vector machine based multi-classification algorithm is developed for evaluating the biomarkers' effectiveness in discriminating type 2 diabetes and cardiovascular diseases and is shown to perform better than a linear discriminant analysis based classifier.
ContributorsBuddi, Sai (Author) / Taylor, Thomas (Thesis advisor) / Cochran, Douglas (Thesis advisor) / Nelson, Randall (Committee member) / Duman, Tolga (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there

Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
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Objective: Increasing fruit/vegetable (FV) consumption and decreasing waste during the school lunch is a public health priority. Understanding how serving style of FV impacts FV consumption and waste may be an effective means to changing nutrition behaviors in schools. This study examined whether students were more likely to select, consume,

Objective: Increasing fruit/vegetable (FV) consumption and decreasing waste during the school lunch is a public health priority. Understanding how serving style of FV impacts FV consumption and waste may be an effective means to changing nutrition behaviors in schools. This study examined whether students were more likely to select, consume, and waste FV when FVs were cut vs. whole. Methods: Baseline data from the ASU School Lunch Study was used to explore associations between cut vs. whole FV serving style and objectively measured FV selection, consumption, and waste and grade level interactions among a random selection of students (n=6804; 47.8% female; 78.8% BIPOC) attending Arizona elementary, middle, and high schools (N=37). Negative binomial regression models evaluated serving style on FV weight (grams) selected, consumed, and wasted, adjusted for sociodemographics and school. Results: Students were more likely to select cut FVs (IRR=1.11; 95% CI: 1.04, 1.18) and waste cut FVs (IRR=1.20; 95% CI: 1.04, 1.39); however, no differences were observed in the overall consumption of cut vs. whole FVs. Grade-level interactions impacted students’ selection of FVs. Middle school students had a significantly higher effect modification for the selection of cut FVs (IRR=1.18; p=0.006) compared to high school and elementary students. Further, high school students had a significantly lower effect modification for the selection of cut FVs (IRR=0.83; p=0.010) compared to middle and elementary students. No other grade-level interactions were observed. Discussion: Serving style of FV may impact how much FV is selected and wasted, but further research is needed to determine causality between these variables.
ContributorsJames, Amber Chandarana (Author) / Bruening, Meredith (Thesis advisor) / Adams, Marc (Thesis advisor) / Koskan, Alexis (Committee member) / Arizona State University (Publisher)
Created2021
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Description
Background: Studies have examined student fruit/vegetable (FV) consumption, selection, and waste related to lunch duration and found that longer duration at lunch was associated with greater consumption, selection, and reduced waste. However, few studies have investigated the relationship between time to eat and FVs. The aim of this research is

Background: Studies have examined student fruit/vegetable (FV) consumption, selection, and waste related to lunch duration and found that longer duration at lunch was associated with greater consumption, selection, and reduced waste. However, few studies have investigated the relationship between time to eat and FVs. The aim of this research is to analyze the relationship between objective time to students took to eat (“time to eat”) as it relates to their fruit and vegetable consumption, selection, and plate waste.in elementary, middle, and high schools. Methods: A secondary analysis of cross-sectional study of 37 Arizona schools to discover the differences in the selection, consumption, and waste of FVs from students (Full N = 2226, Elementary N = 630, Middle School N = 699, High School N = 897) using objective time to eat measures. Zero-inflated negative binomial regressions examined differences in FV grams selected, consumed, and wasted adjusted for sociodemographics including race, ethnicity, eligibility for free or reduced lunch, academic year, and sex and clustering for students within schools. Results are presented across school level (elementary, middle, and high school). Results: The average time taken to eat ranged from 10-12 minutes for all students. The association of time to eat and lunch duration were not closely related (r=0.03, p = 0.172). In the count model for every additional minute spent, there was a 0.5% greater likelihood of selecting FVs for elementary kids among those who took any FVs. In the zero-inflated model, it was found that there was a statistically significant relationship between time spent eating and the selection of fruits and vegetables. For the total sample and high schoolers, a minute more of eating time was associated with a 4.3% and 8.8% greater odds of selecting FV. This means that longer eating time increased the likelihood of choosing fruits and vegetables. The results indicated that the longer students took to eat, the higher the likelihood of consuming more of FVs. Each 10 more minutes spent eating (i.e., time to eat) is associated with a 5% increase in grams of FV selected relative to mean (for those that chose FV) over 1 week this equates to 32 g increase of FV selected. However, for middle schoolers, the time to eat was not found to be significant in relation to the grams of fruits and vegetables consumed. There was some significance in the sociodemographic factors such as gender (all) and other (middle school). There was a relationship between time taken to eat and waste as a proportion for fruits and vegetables. For example, among those among the students who wasted something (as a proportion of selection), each additional 10 minutes of eating time was associated with a .6% decrease in waste relative to the mean (for those who chose fruits and vegetables) over a week, resulting in a decrease in waste percentage of 16.5%. Among high schoolers, males had a slightly higher odds of wasting a proportion of fruits and vegetables. Conclusions: This study aimed to examine the association between the time students take to eat during lunch and their fruit and vegetable (FV) consumption, selection, and plate waste. The findings revealed that the time to eat was related to FV consumption, depending on the school level. However, it was not significantly associated with FV selection or waste. The study emphasized the need for further research on time to eat, distinguishing it from the duration of lunch. Longer lunch periods and adequate time could influence better food choices, increased FV consumption, and reduced waste. The study highlighted the importance of interventions and school policies promoting healthier food choices and providing sufficient time for students to eat. Future research should validate these findings and explore the impact of socialization opportunities on promoting healthier eating habits. Understanding the relationship between lunch duration, time to eat, and students' dietary behaviors can contribute to improved health outcomes and inform effective strategies in school settings.
ContributorsDandridge, Christina Marie (Author) / Adams, Marc (Thesis advisor) / Whisner, Corrie (Committee member) / Bruening, Meg (Committee member) / Arizona State University (Publisher)
Created2023
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Description
Tools designed to help match people with behaviors they identify as likely to lead to a successful behavioral outcome remain under-researched. This study assessed the effect of a participant-driven behavior-matching intervention on 1) the adoption of a new behavior related to fruit and vegetable (F&V) consumption, 2) study attrition, and

Tools designed to help match people with behaviors they identify as likely to lead to a successful behavioral outcome remain under-researched. This study assessed the effect of a participant-driven behavior-matching intervention on 1) the adoption of a new behavior related to fruit and vegetable (F&V) consumption, 2) study attrition, and 3) changes in F&V consumption. In this two-arm randomized controlled trial, 64 adults who did not meet standard F&V recommendations were allocated to an intervention (n=33) or control group (n=31). Participants in the intervention group ranked 20 F&V-related behaviors according to their perceived likelihood of engagement in the behavior and their perception of the behavior’s efficacy in increasing F&V consumption. Participants in the intervention group were subsequently shown the list of 20 behaviors in order of their provided rankings, with the highest-ranked behaviors at the top, and were asked to choose a behavior they would like to perform daily for 4 weeks. The control group chose from a random-order list of the same 20 behaviors to adopt daily for 4 weeks. During the study period, text messages were sent to all participants 90 minutes before their reported bedtime to collect Yes/No data reflecting successful behavior engagement each day. The binary repeated-measures data collected from the text messages was analyzed using mixed-effects logistic regression, differences in attrition were assessed using log-rank analysis, and change scores in F&V consumption were compared between the two groups using the Man-Whitney U test. P<0.05 indicated significance. The rate of successful behavior adoption did not differ significantly between the two groups (b=0.09, 95%CI= -0.81, 0.98, p=0.85). The log rank test results indicated that there was no significant difference in attrition between the two groups (χ2=2.68, df=1, p=0.10). F&V consumption increased significantly over the 4 weeks in the total sample (Z=-5.86, p<0.001), but no differences in F&V change scores were identified between the control and intervention groups (Z=-0.21, p=0.84). The behavior-matching tool assessed in this study did not significantly improve behavior adoption, study attrition, or F&V intake over 4 weeks.
ContributorsCosgrove, Kelly Sarah (Author) / Wharton, Christopher (Thesis advisor) / Adams, Marc (Committee member) / DesRoches, Tyler (Committee member) / Grebitus, Carola (Committee member) / Johnston, Carol (Committee member) / Arizona State University (Publisher)
Created2023
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Objective: It’s not well understood how youth perceive existing fruit and vegetable (FV) marketing materials available in schools. This ancillary study sought to assess the acceptability of FV marketing materials freely available to schools among adolescents in grades 6-12.

Methods: Middle and high school adolescents (n=40; 50% female; 52.5% Hispanic) in

Objective: It’s not well understood how youth perceive existing fruit and vegetable (FV) marketing materials available in schools. This ancillary study sought to assess the acceptability of FV marketing materials freely available to schools among adolescents in grades 6-12.

Methods: Middle and high school adolescents (n=40; 50% female; 52.5% Hispanic) in the Phoenix, AZ area were asked to rank marketing materials (n=35) from favorite to least favorite in four categories: table tents, medium posters, large posters and announcements. Favorites were determined by showing participants two items at a time and having them choose which they preferred; items were displayed to each adolescent in a random order. Adolescents participated in a 20-30 minute interview on their favorite items in each category based on acceptance/attractiveness, comprehension, relevance, motivation and uniqueness of the materials. A content analysis was performed on top rated marketing materials. Top rated marketing materials were determined by the number of times the advertisement was ranked first in its category.

Results: An analysis of the design features of the items indicated that most participants (84%) preferred marketing materials with more than 4 color groups. Participant preference of advertisement length and word count was varied. A total of 5 themes and 20 subthemes emerged when participants discussed their favorite FV advertisements. Themes included: likes (e.g., colors, length, FV shown), dislikes (e.g., length, FV shown), health information (e.g., vitamin shown), comprehension (e.g., doesn’t recognize FV), and social aspects (e.g., peer opinion). Peer opinion often influenced participant opinion on marketing materials. Participants often said peers wouldn’t like the advertisements shown: “…kids my age think that vegetables are not good, and they like food more than vegetables.” Fruits and vegetable pictured as well as the information in the marketing materials also influenced adolescent preference.

Conclusion: Students preferred advertisements with more color and strong visual aspects. Word count had minimal influence on their opinions of the marketing materials, while information mentioned and peer opinion did have a positive effect. Further research needs to be done to determine if there is a link between adolescent preferences on FV marketing materials and FV consumption habits.
ContributorsPisano, Sydney Alexis (Author) / Bruening, Meg (Thesis advisor) / Adams, Marc (Committee member) / Grgich, Traci (Committee member) / Arizona State University (Publisher)
Created2019
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College students are a niche of young adults, characterized by abnormal sleeping habits and inactive lifestyles. Many students entering college are as young as 18 years old and graduate by 22 years old, a window of time in which their bones are still accruing mineral. The purpose of this cross-sectional

College students are a niche of young adults, characterized by abnormal sleeping habits and inactive lifestyles. Many students entering college are as young as 18 years old and graduate by 22 years old, a window of time in which their bones are still accruing mineral. The purpose of this cross-sectional study was to determine whether sleep patterns and physical activity observed in college students (N= 52) 18-25 years old at Arizona State University influenced bone biomarkers, osteocalcin (OC) and N-terminal telopeptide of type 1 collagen (NTX-1) concentrations. Students completed various dietary and health history questionnaires including the International Physical Activity Questionnaire short form. Students wore an actigraphy watch for 7 consecutive nights to record sleep events including total sleep time, sleep onset latency and wake after sleep onset. Total sleep time had a significant, negative correlation with OC (r = -0.298, p-value =0.036) while sleep onset latency had a significant, positive correlation with NTX-1 serum concentration (r = 0.293, p-value = 0.037). Despite correlational findings, only sleep percent was found to be significant (beta coefficient = 0.271 p-value = 0.788) among all the sleep components assessed, after adjusting for gender, race, BMI and calcium intake in multivariate regression models. Physical activity alone was not associated with either bone biomarker. Physical activity*sleep onset latency interactions were significantly correlated with osteocalcin (r = 0.308, p-value =0.006) and NTX-1 (r = 0.286, p-value = 0.042) serum concentrations. Sleep percent*physical activity interactions were significantly correlated with osteocalcin (r = 0.280, p-value = 0.049) but not with NTX-1 serum concentrations. Interaction effects were no longer significant after adjusting for covariates in the regression models. While sleep percent was a significant component in the regression model for NTX-1, it was not clinically significant. Overall, sleep patterns and physical activity did not explain OC and NTX-1 serum concentrations in college students 18-25 years old. Future studies may need to consider objective physical activity devices including accelerometers to measure activity levels. At this time, college students should review sleep and physical activity recommendations to ensure optimal healthy habits are practiced.
ContributorsMahmood, Tara Nabil (Author) / Whisner, Corrie (Thesis advisor) / Dickinson, Jared (Committee member) / Petrov, Megan (Committee member) / Adams, Marc (Committee member) / Arizona State University (Publisher)
Created2019
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Background In the United States (US), first-year university students typically live on campus and purchase a meal plan. In general, meal plans allow the student a set number of meals per week or semester, or unlimited meals. Understanding how students’ use their meal plan, and barriers and facilitators to meal

Background In the United States (US), first-year university students typically live on campus and purchase a meal plan. In general, meal plans allow the student a set number of meals per week or semester, or unlimited meals. Understanding how students’ use their meal plan, and barriers and facilitators to meal plan use, may help decrease nutrition-related issues.

Methods First-year students’ meal plan and residence information was provided by a large, public, southwestern university for the 2015-2016 academic year. A subset of students (n=619) self-reported their food security status. Logistic generalized estimating equations (GEEs) were used to determine if meal plan purchase and use were associated with food insecurity. Linear GEEs were used to examine several potential reasons for lower meal plan use. Logistic and Linear GEEs were used to determine similarities in meal plan purchase and use for a total of 599 roommate pairs (n=1186 students), and 557 floormates.

Results Students did not use all of the meals available to them; 7% of students did not use their meal plan for an entire month. After controlling for socioeconomic factors, compared to students on unlimited meal plans, students on the cheapest meal plan were more likely to report food insecurity (OR=2.2, 95% CI=1.2, 4.1). In Fall, 26% of students on unlimited meal plans reported food insecurity. Students on the 180 meals/semester meal plan who used fewer meals were more likely to report food insecurity (OR=0.9, 95% CI=0.8, 1.0); after gender stratification this was only evident for males. Students’ meal plan use was lower if the student worked a job (β=-1.3, 95% CI=-2.3, -0.3) and higher when their roommate used their meal plan frequently (β=0.09, 99% CI=0.04, 0.14). Roommates on the same meal plan (OR=1.56, 99% CI=1.28, 1.89) were more likely to use their meals together.

Discussion This study suggests that determining why students are not using their meal plan may be key to minimizing the prevalence of food insecurity on college campuses, and that strategic roommate assignments may result in students’ using their meal plan more frequently. Students’ meal plan information provides objective insights into students’ university transition.
Contributorsvan Woerden, Irene (Author) / Bruening, Meg (Thesis advisor) / Hruschka, Daniel (Committee member) / Schaefer, David (Committee member) / Vega-Lopez, Sonia (Committee member) / Adams, Marc (Committee member) / Arizona State University (Publisher)
Created2019