Levels Of Risk Factors Research Articles

Exploring Industry-Level Fairness of Auto Insurance Premiums by Statistical Modeling of Automobile Rate and Classification Data

The study of actuarial fairness in auto insurance has been an important issue in the decision making of rate regulation. Risk classification and estimating risk relativities through statistical modeling become essential to help achieve fairness in premium rates. However, because of minor adjustments to risk relativities allowed by regulation rules, the rates charged eventually may not align with the empirical risk relativities calculated from insurance loss data. Therefore, investigating the relationship between the premium rates and loss costs at different risk factor levels becomes important for studying insurance fairness, particularly from rate regulation perspectives. This work applies statistical models to rate and classification data from the automobile statistical plan to investigate the disparities between insurance premiums and loss costs. The focus is on major risk factors used in the rate regulation, as our goal is to address fairness at the industry level. Various statistical models have been constructed to validate the suitableness of the proposed methods that determine a fixed effect. The fixed effect caused by the disparity of loss cost and premium rates is estimated by those statistical models. Using Canadian data, we found that there are no significant excessive premiums charged at the industry level, but the disparity between loss cost and premiums is high for urban drivers at the industry level. This study will help better understand the extent of auto insurance fairness at the industry level across different insured groups characterized by risk factor levels. The proposed fixed-effect models can also reveal the overall average loss ratio, which can tell us the fairness at the industry level when compared to loss ratios by the regulation rules.

Elastic band resistance training increases adropin and ameliorates some cardiometabolic risk factors in elderly women: A quasi-experimental study

BackgroundThe decline in adropin over the aging process is associated with cardiometabolic risks, and resistance training may affect this decline. We hypothesized that elastic band resistance training (EBRT) would be an effective exercise for increasing adropin and improving the cardiometabolic profile in elderly women.MethodsWe randomly assigned 28 overweight elderly women (age = 74.04 ± 4.69 years) into one of two groups, EBRT (n = 14) or control (CON; n = 14), to participate in a 12-week (3d/wk) supervised EBRT program. The serum levels of adropin and cardiometabolic risk factors were evaluated at baseline and after the intervention. The exercise training protocol consisted of three supervised training sessions (55 min) per week for 12 weeks. Data were analyzed using two-way repeated-measures ANOVA and Pearson correlation coefficient.ResultsEBRT significantly increased serum adropin levels (p = 0.026), number of repetitions in the 30-second chair-stand test (p = 0.016), and number of repetitions in the 30-second arm curl test (p = 0.032). Moreover, EBRT significantly decreased serum levels of insulin (p = 0.035), TNF-α (p = 0.046), hsCRP (p = 0.037), and insulin resistance (p = 0.045) as well as body fat percentage (p = 0.023). There were no significant between-group differences (p > 0.05) in glucose, TC, TG, LDL-C, HDL-C, BMI, and WHR; however, glucose, TC, TG, and BMI significantly changed in the EBRT group (within-group). Furthermore, adropin correlated with body fat percentage (p = 0.020) and BMI (p = 0.014) at pretest and with body fat percentage at posttest (p = 0.016), however, delta values were not significantly related. No correlation was observed between adropin and other biomarkers at any stage of the study.ConclusionEBRT can increase serum adropin levels, which has been associated with improved insulin sensitivity, inflammation, body fat percentage, and physical function in overweight elderly women.

Barriers to adherence to iron chelation therapy among adolescent with transfusion dependent thalassemia.

Study backgroundThalassemia is the commonest genetic blood disorder in Malaysia which requires life-long blood transfusions. From a total of 7,984 thalassemia patients in Malaysia, adolescent age group account for the highest number of patients (2,680 patients, 33.57%). In developed countries, the average rate of adherence to long-term treatment among children and adolescents is only 58%. Sub-optimal adherence to iron chelation therapy may impact the outcome and quality of life in these patients. Thus, assessing adherence level and identification of risk factors for non-adherence is essential in optimizing management.ObjectivesTo determine the association between mean serum ferritin level with self-reported level of adherence to iron chelation therapy in transfusion dependent thalassemia (TDT) adolescents in Hospital Tengku Ampuan Afzan (HTAA), Kuantan and Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Cheras; to determine the association between socio-demographic factors and patients’ knowledge on thalassemia and iron chelation therapy with the level of adherence.Materials and methodsThis was a cross-sectional study conducted between 1st March 2019 and 31st March 2020. Data was collected through face-to-face interview by a single interviewer during the thalassemia clinic follow up, with content validated questionnaires. The questionnaires comprised four sections which included socio-demographic data, medication adherence questionnaire, knowledge of disease, and clinical characteristics of the participants.ResultsA total of 70 participants were recruited. Results showed that only 51.4% of participants had good adherence to iron chelation therapy. There was a significant association between monthly household incomes of the family with the level of adherence to iron chelation (p-value 0.006). There was also an association between the mean serum ferritin levels with total Adherence Starts with Knowledge (ASK-12) score (p-value 0.001). However, there was no association between knowledge on thalassemia with the level of adherence.ConclusionAdherence to iron chelation was generally unsatisfactory amongst adolescents with TDT as only 51.4% had good adherence. Low monthly household income of the family may affect adherence to iron chelation therapy in TDT patients. As adherence remains to be an issue amongst adolescent thalassemia patients, management should include regular and objective assessments to address this problem so as to optimize patient outcome.

Elevated platelet reactivity in patients with uncontrolled hypertension: the effect of CHA2DS2-VASc score

Abstract Background Hypertension is associated with vascular and endothelial dysfunction that may result in a greater propensity for reactive platelets to cause thrombosis. Purpose The aim of this study was to evaluate multiple platelet activation pathways in hypertensive patients with different level of blood pressure control and cardiovascular risk factors. Methods Thirty nine uncontrolled (office BP >140/90 mmHg and ambulatory daytime BP >135/85 mmHg, 27 males, aged 58±9 years) and 32 well controlled (office BP <140/80 mmHg and ambulatory daytime BP <135/85 mmHg, 21 males, aged 58±8 years) essential hypertensive patients were included in the study. Twenty four healthy individuals (12 males, aged 53±10 years) were served as control group. Blood samples were obtained before and 48 hours after the procedure and platelet aggregation was tested in platelet rich plasma after activation with arachidonic acid (AA), adenosine diphosphate ADP), collagen (Col), epinephrine (Epi) and ristocetin (Risto), by using AggRAM Platelet Aggregation Analyzer. Results Hypertensive patients showed elevated platelet reactivity in all platelet activation pathways compared to normotensive group (AA: 88.8±6.8% versus 79.5±7.3%, ADP: 86.8±9.1% versus 71.5±7.7%, Col: 86.5±5.7% versus 73.9±6.7%, Epi: 92.6±5.4% versus 80.5±5.7%, Risto: 93.8±6.8% versus 79.9±6.3%, p<0.05 for all). Col, Epi and Risto platelet activation pathway showed a statistically significant increase in patients with uncontrolled hypertension compared to the group with well controlled hypertension (AA: 88.8±6.1% versus 89.1±4.1%, ADP: 89.8±4.1% versus 87.5±4.7%, Col: 87.5±4.7% versus 81.9±6.7%, Epi: 93.6±4.4% versus 80.1±5.7%, Risto: 94.8±3.8% versus 80.9±4.3%,). Notably, strong correlations were found between the Col platelet pathway activation and Risto platelet pathway activation and CHA2DS2-VASc score (r=0.57, p<0.001 and r=0.61, p<0.001, respectively) in hypertensive patients. Conclusions Patients with uncontrolled hypertension showed elevated platelet reactivity. Patients with high CHA2DS2-VASc even without atrial fibrillation carry also a higher risk of thrombosis as indicated by the increased platelet aggregation under certain pathways of activation. Funding Acknowledgement Type of funding sources: None.

An Overview of Candidemia Patients in Tertiary Hospital, Surabaya, Indonesia

Candidaemia is a bloodstream infection (BSIs) caused by Candida spp. common in hospitalized patients. Candidemia has a high mortality and morbidity. This study aimed to give an idea about incidence, patient characteristics, species and patterns of candida susceptibility, and risk factors in candidaemia patients at Dr. Soetomo Hospital from January to December 2020. This is descriptive research using an observational research design. This study used a medical record instrument for candidemia patients in the inpatient ward of Dr. Soetomo and data in the form of records of blood culture results at the Clinical Microbiology Unit of RSUD Dr. Soetomo Surabaya for the period January-December 2020. The observed variables include incidence, sex, age, the origin of hospitalization, species distribution, frequency of antifungal sensitivity testing, and risk factors for candidemia. In 12 months, 53 candidemia patients were treated at Dr. Soetomo Hospital. The incidence of candidemia is 1.58 cases per 1000 person-years. Most of them are male (64.15%) and aged less than <1 year (28,30). Most of the medical units at the time of the diagnosis were intensive care units and pediatric wards (28.30%). Candida albicans was the most commonly found species (33.96%), then Candida tropicalis (26.41%) and Candida parapsilosis (24.53%). Two Candida glabrata isolates (40%) were susceptible to caspofungin, and all isolates (100%) of Candida albicans, Candida parapsilosis, Candida rugosa, Candida lusitaniae, Candida tropicalis, Candida dubliniensis, and were susceptible to the antifungals tested. Patients who use the Central Venous Catheter (CVC) have the highest level of risk factor, followed by patients with diabetes mellitus.

Ecological analysis in diplomacy, geopolitics and international cooperation: Driving accountability for social impact

It is not essentially the objective of this paper to elaborately (re)construct the salient spheres of diplomacy, geopolitics and international cooperation as they impact on civilization, rather it is a presentation regarding the essential disparities of inter alia scarce resources, military efforts, trade, and transboundary realizations of pollutants and irritants into the biosphere. Due to the multidimensional origin of environmental perturbations, although, with its ingrained complexity, it has become necessary to inculcate all pertinent concerns in decision making locally and globally. The levels of significant risk factors and social decision-making continue to undergo diverse alterations in several countries with their attendant geopolitics, gain-of-function research in biosecurity, environment, and health which necessitate international cooperation for peaceful coexistence within and across borders. A proper understanding of the cumulative impact of these changes in erstwhile, current and future trends is vital to harness and curb environmental disasters in vulnerable ecosystem cadastres, emerging and reemerging communicable and noncommunicable diseases or disorders.

Substance-Specific Risk Factors among Young Adults: Potential Prevention Targets across Cannabis-Permissive Environments

Purpose This study examined levels of substance-specific risk factors such as perception of harm from substance use among young adults in a range of cannabis-permissive environments. The main objective was to inform future preventive interventions aimed at reducing cannabis use in the context of increasingly permissive environments. Methods Data came from the Community Youth Development Study (CYDS) collected in 2016 when participants were about 23 years old (n = 1,722 participants residing in 46 U.S. states). Young adults self-reported their perceptions about the harms related to cannabis, alcohol, and cigarette use; attitudes about and ease of access to cannabis and other substances; and perceived wrongfulness and social acceptability of cannabis, alcohol, and cigarette use and of selling of cannabis and other illegal drugs. Results Young adults in more permissive cannabis contexts reported higher levels of all cannabis-specific risk factors (e.g., greater access to and more favorable attitudes about cannabis use), except for perception of harm from regular cannabis use. However, permissiveness of the cannabis environment was not associated with heightened levels of risk factors for other substance use (such as alcohol, cigarettes, and opioids). Conclusions Future preventive interventions for young adults living in more permissive cannabis contexts may need to focus on cannabis-specific risk factors in particular and go beyond considerations of harm from regular use. Future studies should replicate these findings with other samples.

Analysis of risk factors for quality management to blepharoplasty based on DEMATEL-ISM.

Blepharoplasty is a typical complex structural system, which involves many factors and the interaction among them. Therefore, it is the basis of controlling the occurrence of medical complications in blepharoplasty to clarify the hierarchical relationship of various risk factors and find out the key risk factors. On the basis of identifying the risk factors for quality management of blepharoplasty by means of literature research, questionnaire survey and expert interview, the risk factor model of blepharoplasty quality management were analyzed and constructed. The relationship between the risk factors and the degree of influence on the risk factors was studied using Decision-Making Trialand Evaluation Laboratory and Interpretative Structural Modeling Method, and the hierarchical structure model of the risk factors for blepharoplasty quality management was obtained. Six levels of risk factors in quality management of blepharoplasty were identified and classified, and the causal attributes among risk factors were determined. Six key risk factors in quality management of double eyelid surgery were determined according to centrality, and finally the above risk factors were divided into three categories: direct cause, excessive cause, and essential cause. This study realizes the comprehensive risk factor analysis of the complex system of quality management of blepharoplasty, which can provide reference for plastic surgeons to make safety decisions of blepharoplasty.

Global cirrhosis prevalence trends and attributable risk factors-an ecological study using data from 1990-2019.

Cirrhosis is a major public health issue worldwide with significant morbidity and mortality. We aimed to explore the time series associations between varying levels of risk factors and cirrhosis prevalence and predict the cirrhosis prevalence under alternative scenarios to consolidate evidence for further intervention plans. We collected data of cirrhosis and its risk factors from 1990 to 2019 across 178 countries and used a generalized linear mixed model to explore the time series associations between cirrhosis and risk factors. We simulated scenarios with varying levels of risk factors and investigated benefits gained from the control of risk factors compared with the status quo. The global cirrhosis prevalence varied geographically, with the highest observed in East and Southeast Asia, mainly due to high hepatitis prevalence. Our study revealed that each 1% increase in prevalence of hepatitis B and C, cirrhosis prevalence would correspondingly increase 0.028% and 0.288%. There would be approximately 392.15 million fewer cirrhosis patients if the goals of a 65% reduction in prevalence of hepatitis and a 10% reduction in alcohol consumption were achieved. Given that cirrhosis prevalence has different risk factors depending on geography, it is important to identify an appropriate set of interventions for cirrhosis that are adapted to the epidemiological situation in a specific country. Interventions targeting hepatitis may have a significant impact on global cirrhosis prevalence, therefore, the adoption of specific interventions for hepatitis in high-burden regions and high-risk groups is warranted to lower the global burden of cirrhosis.

Public and outpatients’ awareness of calling emergency medical services immediately by acute stroke in an upper middle-income country: a cross-sectional questionnaire study in greater Gaborone, Botswana

ObjectivesIn this cross-sectional study from Botswana, we investigated awareness of calling emergency medical services (EMS) and seeking immediate medical assistance by acute stroke among stroke risk outpatients and public.MethodClosed-ended questionnaires on awareness of calling EMS and seeking immediate medical assistance by acute stroke, were administered by research assistants to a representative selection of outpatients and public.ResultsThe response rate was 96.0% (93.0% for public (2013) and 96.6% for outpatients (795)). Public respondents had mean age of 36.1 ± 14.5 years (age range 18–90 years) and 54.5% were females, while outpatients had mean age of 37.4 ± 12.7 years (age range 18–80 years) and 58.1% were females.Awareness of calling EMS (78.3%), and of seeking immediate medical assistance (93.1%) by stroke attack was adequate. For calling EMS by acute stroke, outpatients had higher awareness than the public (p < 0.05) among those with unhealthy diet (90.9% vs 71.1%), family history of both stroke and heart diseases (90.7% vs 61.2%), no history of psychiatric diseases (93.2% vs 76.0%) and sedentary lifestyle (87.5% vs 74.8%).Predictors of low awareness of both calling EMS and seeking immediate medical assistance were no medical insurance, residing/working together, history of psychiatric diseases, and normal weight.Male gender, ≥50 years age, primary education, family history of both stroke and heart diseases, current smoking, no history of HIV/AIDS, and light physical activity were predictors of low awareness of need for calling EMS.ConclusionResults call for educational campaigns on awareness of calling EMS and seeking immediate medical assistance among those with high risk factor levels.

Association of diabetes and exposure to fine particulate matter (PM2.5) in the Southeastern United States

Fine particulate matter (PM2.5) exposure can cause premature death and harmful chronic disease such as diabetes. The U.S. Environmental Protection Agency (EPA) sets annual PM2.5 standards to reduce these negative health effects. Currently, annual average exposure over 12 µg/m3 is considered unhealthy. This study tests whether individuals living in locations exposed to elevated ambient levels of PM2.5 concentrations were more likely to self-report diabetes. We examined the association of long-term exposure to PM2.5 and diabetes at enrollment (2002–2009) in a cohort of 44,610 individuals residing in 12 states, recruited into the Southern Community Cohort Study (SCCS). Annual average PM2.5 was estimated using remotely sensed satellite data integrated with ground monitoring data at participants’ residence in urban and rural locations. We used multilevel mixed-effects logistic regression models to estimate the associations between self-reported diabetes and historical exposure to elevated ambient levels of PM2.5. We found a 10.1% increase in odds of reported diabetes with exposure to unhealthful levels of PM2.5 exposure (>12 µg/m3 at enrollment) compared to respondents living in areas with lower annual PM2.5 concentrations. Participants with medical histories of hypertension, hypercholesterolemia, and smoking had an overall 384% higher odds of reported diabetes than those without these clinical risk factors. Black participants were more likely to live in locations with higher ambient PM2.5 concentrations, report high levels of clinical risk factors, and had a 29.1% increase in odds of reported diabetes than Whites. In SCCS participants, exposures to high ambient levels of PM2.5 were associated with self-reported diabetes at enrollment. Reduction in PM2.5 standards for the U.S. are recommended.

Measurement of Risk Factors Associated With bereavement Severity and Deterioration by COVID-19: A Spanish Validation Study of the Pandemic Grief Risk Factors.

The present study translated and evaluated the psychometric evidence of the Pandemic Grief Risk Factors (PGRF) in a sample of 363 people from the general population of Peru who suffered the death of a loved one by COVID-19 (63-4% women and 36.6% men, where 78.5% were between 18 and 29years old). The findings indicated that the PGRF is a unidimensional and reliable measure. The PGRF items can differentiate between individuals with different levels of risk factors and thus cover a wide range of the latent construct. Also, a greater sense of distress for each of the risk factors for pandemic grief is necessary to answer the higher response categories. Risk factors significantly and positively predict COVID-19-associated dysfunctional grief. The results indicated that the PGRF in Spanish is a measure with adequate psychometric properties to measure risk factors for pandemic grief.

Achievements of primary prevention targets in individuals with high risk of cardiovascular disease: an 8-year follow-up of the Tromsø study.

AimsTo study change over 8 years in cardiovascular risk, achievement of national guideline-based treatment targets of lipids, blood pressure (BP) and smoking in primary prevention of cardiovascular disease (CVD), medication use, and characteristics associated with target achievement among individuals with high CVD risk in a general population.Methods and resultsWe followed 2524 women and men aged 40–79 years with high risk of CVD attending the population-based Tromsø study in 2007–08 (Tromsø6) to their participation in the next survey in 2015–16 (Tromsø7). We used descriptive statistics and regression models to study change in CVD risk and medication use, and characteristics associated with treatment target achievement. In total, 71.4% reported use of BP- and/or lipid-lowering medication at second screening. Overall, CVD risk decreased during follow-up, with a larger decrease among medication users compared with non-users. Treatment target achievement was 31.0% for total cholesterol <5 mmol/L, 27.3% for LDL cholesterol <3 mmol/L, 43.4% for BP <140/90 (<135/85 if diabetes) mmHg, and 85.4% for non-smoking. A total of 9.8% reached all treatment targets combined. Baseline risk factor levels and current medication use had the strongest associations with treatment target achievement.ConclusionWe found an overall improvement in CVD risk factors among high-risk individuals over 8 years. However, guideline-based treatment target achievement was relatively low for all risk factors except smoking. Medication use was the strongest characteristic associated with achieving treatment targets. This study has demonstrated that primary prevention of CVD continues to remain a major challenge.

Convergence in Diplomacy, Geopolitics and International Cooperation for Human Health and Environment

Global challenges require interactive global solutions. The disparities of inter alia scarce resources, military efforts, trade, and transboundary realizations of pollutants and irritants into the biosphere correlate to the multidimensional origin of health and environmental perturbations. Thus, taking into cognizance the inherent complexity of the world, it has become necessary to inculcate all pertinent concerns in decision making locally and globally. The levels of significant risk factors and social decision-making continue to undergo diverse alterations in several countries with their attendant geopolitics, gain-of-function research in biosecurity, environment, and health which necessitate international cooperation for peaceful coexistence within and across borders. A proper understanding of the cumulative impact of these changes in erstwhile, current and future trends is vital to harness and curb environmental health disasters in vulnerable ecosystem cadastres. Changes or trends in risk factor presentations or levels can be determined via disparate or collaborative spatiotemporal specific environmental cadastre and health surveys. International conflicts, hostilities, war, commodity crisis, inflation, trade imperfection, supply-chain disruption and labour shortages are being rebranded by multinationals and industrialized countries as health and environmentally virtuous policies.

Lifestyle factors as mediators of area-level socio-economic differentials in cardiovascular disease risk factors. The Tromsø Study

IntroductionCardiovascular disease (CVD) is a leading cause of death and disability and living in areas with low socio-economic status (SES) is associated with increased risk of CVD. Lifestyle factors such as smoking, physical inactivity, an unhealthy diet and harmful alcohol use are main risk factors that contribute to other modifiable risk factors, such as hypertension, raised blood cholesterol, obesity, and diabetes. The potential impact of area-level socio-economic status (ASES) on metabolic CVD risk factors via lifestyle behaviors independent of individual SES has not been investigated previously. AimsTo estimate associations of ASES with CVD risk factors and the mediating role of lifestyle behaviors independent of individual-level SES. MethodsIn this cross-sectional study, we included 19,415 participants (52% women) from the seventh survey of the Tromsø Study (2015–2016) (Tromsø7). The exposure variable ASES was created by aggregating individual-level SES variables (education, income, housing ownership) at the geographical subdivision level. Individual-level SES data and geographical subdivision of Tromsø municipality (36 areas) were obtained from Statistics Norway. Variables from questionnaires and clinical examinations obtained from Tromsø7 were used as mediators (smoking, snuff, alcohol, and physical activity), while the outcome variables were body mass index (BMI), total/high-density lipoprotein (HDL) cholesterol ratio, waist circumference, hypertension, diabetes. Mediation and mediated moderation analysis were performed with age as a moderator, stratified by sex. ResultsASES was significantly associated with all outcome variables. CVD risk factor level declined with an increase in ASES. These associations were mediated by differences in smoking habits, alcohol use and physical activity. The associations of ASES with total/HDL cholesterol ratio and waist circumference (women) were moderated by age, and the moderating effects were mediated by smoking and physical activity in both sexes. The largest mediated effects were seen in the associations of ASES with total/HDL cholesterol ratio, with the mediators accounting for 43% of the observed effects. ConclusionsLiving in lower SES areas is associated with increased CVD risk due to unhealthy lifestyle behaviors, such as smoking, alcohol use and physical inactivity. These associations were stronger in women and among older participants.

컨테이너 항만의 위험평가

This study is the second step in a series of research on risk management and evaluation of container ports in Korea and focuses on the development of the risk evaluation framework. And then, the framework was applied to Incheon port to evaluate the risk levels of the selected risk factors and the total risk level in the context of container operations. The port risk evaluation framework developed in this study is a hybrid model of the FER algorithm and Utility Techniques by incorporating AHP to evaluate the weights and risk level of each risk factor, leading to driving the weighted risk level of the individual risk factor as well as the total risk level of the alternative port. Consequently, the results obtained by the risk evaluation model are expected to be used by port risk managers as diagnostic tools to mitigate port risk or to improve risk management practices. In addition, the results will be used as basic data for the risk control options(RCOs) selection and the cost-benefit(C/B)analysis for further study.

Correlation of inflammatory cytokines and uric acid levels in coronary artery disease with and without type 2 diabetes mellitus.

Serum levels of inflammatory cytokines such as IL-6, high-sensitivity C-reactive protein as well as uric acids have been considered as predictors of severe outcomes in patients with coronary artery disease (CAD) associated with hypertension (HTN) and Type 2 Diabetes Mellitus (T2DM). Anthropometric parameters were recorded and measured the levels of major risk factors in 80 patients with hypertension, coronary artery disease with and without Type 2 diabetes mellitus and 40 healthy controls were included. Comparison were performed by classifying the study subjects into 3 groups namely- Group I: Controls (n=40); Group II: HTN, CAD without T2DM(n=40); and Group III: HTN,CAD with T2DM(n=40).The values of BMI, weight, SBP, DBP were greater in patients with T2DM CAD group when compared to without diabetes group. Data shows that there is a positive correlation between IL-6, hs-CRP and uric acid concentrations and are statistically significant. The evaluated high levels of inflammatory cytokines and uric acids in hypertensive CAD patients with diabetes might be helpful in the diagnosis of patients at greater risk.

IL-6/STAT3 axis dictates the PNPLA3-mediated susceptibility to non-alcoholic fatty liver disease

A number of genetic polymorphisms have been associated with susceptibility to or protection against non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms remain unknown. Here, we focused on the rs738409C>G single nucleotide polymorphism (SNP), which produces the I148M variant of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and is strongly associated with NAFLD. To enable mechanistic dissection, we developed a human pluripotent stem cell (hPSC)-derived multicellular liver culture by incorporating hPSC-derived hepatocytes, hepatic stellate cells, and macrophages. We first applied this liver culture to model NAFLD by utilising a lipotoxic milieu reflecting the circulating levels of disease risk factors in affected individuals. We then created an isogenic pair of liver cultures differing only at rs738049 and compared NAFLD phenotype development. Our hPSC-derived liver culture recapitulated many key characteristics of NAFLD development and progression including lipid accumulation and oxidative stress, inflammatory response, and stellate cell activation. Under the lipotoxic conditions, the I148M variant caused the enhanced development of NAFLD phenotypes. These differences were associated with elevated IL-6/signal transducer and activator of transcription 3 (STAT3) activity in liver cultures, consistent with transcriptomic data of liver biopsies from individuals carrying the rs738409 SNP. Dampening IL-6/STAT3 activity alleviated the I148M-mediated susceptibility to NAFLD, whereas boosting it in wild-type liver cultures enhanced NAFLD development. Finally, we attributed this elevated IL-6/STAT3 activity in liver cultures carrying the rs738409 SNP to increased NF-κB activity. Our study thus reveals a potential causal link between elevated IL-6/STAT3 activity and 148M-mediated susceptibility to NAFLD. An increasing number of genetic variants manifest in non-alcoholic fatty liver disease (NAFLD) development and progression; however, the underlying mechanisms remain elusive. To study these variants in human-relevant systems, we developed an induced pluripotent stem cell-derived multicellular liver culture and focused on a common genetic variant (i.e. rs738409 in PNPLA3). Our findings not only provide mechanistic insight, but also a potential therapeutic strategy for NAFLD driven by this genetic variant in PNPLA3. Our liver culture is therefore a useful platform for exploring genetic variants in NAFLD development.

O1-6 Objectively measured physical activity levels and association with BMI z-score among children and adolescents in Morocco

BackgroundPhysical activity is associated with improved psychological well-being and lower levels of cardio metabolic risk factors, diabetes, obesity among children and adolescent. The purpose of the study was 1- to examine gender, type of day, and age grade differences in objectively PA; 2- to examine the attainment of recommended physical activity guidelines; 3-to examine the association between PA levels and BMI z-score among children and adolescents in Morocco.Method172 Moroccan children/adolescents (mean age = 10.92 ± 1.55 years, mean BMI z-score = -0.16 ± 1.33; 19.2 % overweight) were recruited for this study and wore a tri-axial accelerometer (GT3X+) for 7 consecutive days. Two-way analysis of covariance was used to examine gender and age grade differences in physical activity level separately for weekdays and weekends, adjusted for body mass index for age (BMI z-score) and wear time. Logistic regression analyses were conducted to examine independent relationships between attainments of physical activity guidelines and gender. Pearson correlation was used to assess the association between physical activity levels and BMI z-score.ResultsIn both weekends and weekday, children spent more time in Light physical activity than adolescents (p > 0.001), boys were more engaged in moderate activity (p > 0.001) and vigorous (p > 0.001) activity and took more steps than girls. Boys were eight time more likely to meet the recommendation for at least 60 min of moderate to vigorous physical activity per day than girls (OR: 8.569; 95% [CI]: 4.23-17.32), p > 0.001. Among adolescent, moderate to vigorous PA were inversely correlated with BMI z-score (r = -0,213; p = 0.04).ConclusionThe findings can shed light on the need of urgent scaling up of implementation of known effective policies and programmes for adolescents and girls to increase their involvement in PA. Acknowledgements This study was performed with the support of the International Atomic Energy Agency (CRP E4.30.24; RAF 6042).

Is Gentrification a Carcinogen? Neighborhood Change and Cancerous Vehicle Emissions in Los Angeles County

Neighborhood disadvantage erodes residents’ mental and physical health. But whether rapid reductions in disadvantage spurred by gentrification attenuate or exacerbate these effects remains unknown due to mixed theoretical expectations and empirical results. To help clarify these dynamics, I propose a novel hypothesis that casts gentrification as a carcinogen. As neighborhoods receive inflows of affluent, White residents, influxes of private vehicles may come with them. In turn, stationary residents become exposed to higher vehicular emissions, and their risk of cancer—especially lung cancer—climbs. As an initial empirical test of these theoretical possibilities, I link Urban Displacement Project data identifying Los Angeles County neighborhoods that gentrified during the 2000s to tract-level data on vehicle ownership and cancer risk profiles—the latter from the Environmental Protection Agency’s National Air Toxics Assessment. Descriptive regressions that include a lagged dependent variable and municipal fixed effects suggest gentrifying tracts’ levels of cancer risk factors increased by ∼0.5 standard deviations more than those of disadvantaged neighborhoods that did not gentrify. Sobel tests of mediation indicate nearly half of this association may be explained by a pathway related to increasing vehicle density. The study thus motivates future research leveraging individual-level data and quasi-experimental methods to solidify whether gentrification is indeed a carcinogen.