Risk Of Elevated Levels Research Articles

Assessment of carcinogenic risk from exposure to chlororganic compounds of water of systems of centralized water supply

Introduction. The problem of providing the population with drinking water with guaranteed quality, safety, and physiological usefulness is highly relevant for many regions of Russia. The use of chlorination for disinfection of the water is a potential cause of the formation of excess concentrations of organochlorine compounds in it, including trihalogenomethanes, which leads to elevated levels of carcinogenic risk. The study’s object was: data on the content in water of centralized water supply systems of carcinogenic organochlorine compounds - chloroform, dichlorobromomethane and chlorodibromomethane. Material and methods. information on the incidence of the population of malignant neoplasms; the results of an experiment to evaluate the effectiveness of the preliminary ammonization method. The paper used methods of health risk assessment, variation statistics, and mathematical modeling. Results. The use of preliminary ammonization in Taganrog prevents the formation of trihalogenomethanes and ensures the maintenance of an individual multi-route carcinogenic risk at an acceptable level (9.933 · 10-6). Systematic unreasonable hyper chlorination of river water without prior ammoniation is the main reason for the excess content of chlororganic compounds and the high level of individual carcinogenic risk in the Primorsky rural settlement of the Neklinovsky District - up to 3.234 · 10-3 in 2015. Modeling on the basis of experimental chlorination of natural water indicates the high efficiency of preliminary ammonization in the disinfection mode, which ensures the content of free total active chlorine in tap water in the range from 0.8 to 1.2 mg/l. Conclusion. The high efficiency of the application of preliminary ammonization of natural water to prevent the formation of trihalogenomethanes and reduce carcinogenic risk has been confirmed. The priority factor for the formation of excess amounts of organochlorine compounds in drinking water is its hyper chlorination. Promising measures to reduce the carcinogenic risk of trihalogenomethanes in tap water include the systematic monitoring of their content, the use of preliminary ammonization, the exact dosage of chlorine, the deep purification of the source water before chlorination, the replacement of primary chlorination with ultraviolet disinfection, and others.

Cardiovascular outcome in patients with high risk cardiovascular events in Nakornping Hospital

Objectives Patients with atherosclerosis are at different levels of elevated risk of ischemic events depending on the specific manifestation of the disease and may have varying degrees of future risk for ischemic events. This study evaluated the incidence of composite cardiovascular outcomes of patients with high risk cardiovascular events in Nakornping Hospital. Methods This prospective observational non-interventional cohort study enrolled patients age 45 years or more who met the inclusion criteria of the Outpatient Department of Medicine, Nakornping Hospital, between January 2008 and December 2009. The follow-up period for each patient was 60 months. The composite cardiovascular outcome of cardiovascular deaths, non-fatal myocardial infarctions, non-fatal strokes and hospitalizations for heart failure was determined. Results Of the 387 patients in the Outpatient Department of Medicine of Nakornping Hospital, 103 were in the established atherosclerotic disease group and 284 were in the multiple risk factors group. The rate of overall composite cardiovascular events (cardiovascular death, non-fatal MI, non-fatal stroke, and hospitalization for heart failure) was 3.83%. The rate was higher in the established atherosclerotic disease group than in the multiple risk factors group 6.79% vs. 1.41% (HR = 14.28; 95% CI, 2.26-90.02, p = 0.005) which was driven by hospitalization for heart failure, but the established atherosclerotic disease group had a lower rate of medical treatment for diabetes than the multiple risk factors group. The rate of receipt of anti-diabetic drugs was statistically significantly lower in the established atherosclerotic disease group than in the multiple risk factors group. Conclusions Patients with established atherosclerotic disease have a higher rate of composite cardiovascular outcomes than patients with multiple risk factors, but they have a lower rate of medical treatment for diabetes.

Predator kairomones elicit bold, exploratory behaviours in juvenile bluegill, Lepomis macrochirus

Behavioural responses of animals are often placed conceptually along some axis characterized by the extremes, e.g. bold versus shy or timid. Ecological and evolutionary pressures can be associated with increased frequencies of different behavioural patterns that are also subject to intrinsic factors such as differing metabolic requirements or cognitive abilities. We exposed individual wild-caught juvenile bluegill, Lepomis macrochirus, to kairomones from predatory northern pike, Esox lucius, or to lake water controls during a Z-maze arena assay commonly used to assess relative levels of boldness and exploratory behaviours. Fish were subsequently lethally sampled for liver and brain mass to obtain estimates of relative body condition (hepato-somatic index, HSI) and cognitive capacity (brain-somatic index, BSI), as well as the state of the gallbladder, to test for relationships between these indices and observed boldness-related behaviours. Using principal components analysis (PCA) we identified a boldness–exploration syndrome in bluegill independent of chemical treatment and body metrics where bolder fish emerged from a start chamber in less time, travelled farther through the maze and crossed more lines than less bold fish. Bluegill exposed to kairomones were bolder on average than their counterparts in the control treatment independent of body metrics, suggesting that elevated risk levels indicated by predator kairomones can elicit behavioural responses consistent with boldness, exploration and risk taking. The role of relative cognitive ability in the expression of boldness and exploration is equivocal and may be resolved through repeated assays on individuals at different risk levels.

Identifying systemically important financial institutions in Turkey

This paper examines the systemic risk of financial firms in Turkey. Using Component Expected Shortfall, we provide estimates of systemic risk in Turkey using daily data from 2005 to 2018 and a comprehensive data set encompassing 54 financial firms. Empirical results show that the preponderance of systemic risk in the sample in Turkey is due to large commercial banks. Top ten systemically important financial institutions dominate systemic risk measures in Turkey and account for more than 90 % of total risk over the sample. Consequently, the risk in the Turkish financial system is concentrated in specific financial institutions and makes close monitoring of the top firms essential. Historical incidence of systemic risk in the sample shows elevated levels of systemic risk correspond to well-known external events. Finally, a bivariate VAR model shows that systemic risk is correlated with measures of global financial risks and has significant negative effects on the real economy particularly on industrial production. This is important from a financial stability point of view in that close monitoring of the systemic risk is important in maintaining a healthy financial system and a well- functioning market economy.

Executive Functioning in Adolescents with Chronic Musculoskeletal Pain.

Adolescents with chronic pain often suffer significant impairment in physical, emotional, and social domains. Surprisingly little is known about executive functioning (EF) in youth with chronic pain or how EF deficits may contribute to functional impairment. Study participants included 60 adolescents between the ages of 12 and 17 years (M = 14.57). Thirty participants with chronic musculoskeletal pain and 30 age- and gender-matched healthy controls were recruited from a large Midwestern children’s hospital in the United States. Participants completed the Behavior Rating Inventory of Executive Functioning (BRIEF-2) as well as multiple measures of functional impairment across key domains: school, social, emotional (anxiety, depression), and physical. Adolescents with chronic musculoskeletal pain reported significantly greater EF impairment compared to healthy age- and gender-matched peers. Clinically elevated risk levels of impairment were reported across all aspects of EF, with many adolescents in the chronic pain group scoring above the clinical risk cut off for working memory (52%), inhibition (45%), and cognitive flexibility (38%). EF was also significantly related to functional impairment across all domains. Findings suggest that EF may have an impact across several critical domains of functioning for youth with chronic pain.

Time series monitoring of impervious surfaces and runoff impacts in Metro Vancouver

Urban areas are increasing rapidly worldwide, leading to widespread changes in land surfaces over time. Urbanized land cover is heterogeneous, and is characterized by a large areal proportion of manufactured impervious surfaces which are linked to ecological degradation, habitat loss, and increase in precipitation runoff leading to pollution and safety risks. Data from the Landsat series of satellites present an opportunity to characterize urban land cover and impervious surfaces, over a large spatial and temporal scale. In this study, land cover changes from 1990 to 2015 are characterized in the large metropolitan area of Metro Vancouver, Western Canada. An ordinal regression is used to link Landsat spectral data with a detailed land classification containing classes of impervious surface used by municipal planners in the region (Spearman's Rho = 0.76). The regression is then used to classify a time series of imagery where static land classifications are not available, providing a 25-year time-series of change in impervious surface area. A trend in increasing impervious surface was detected across the municipalities in the region, with an overall areal increase of 31.96%. Precipitation events were then simulated at each time step, using precipitation rates adjusted for expected changes in climate by 2050. Both runoff depths and inundated area increased over time, with a 51% increase in area inundated by at least 5 cm. Runoff depths were evaluated for each municipality in the region, and compared to projected populations for 2050 to highlight communities that may face elevated levels of runoff risk. Results show a steady increase in impervious surfaces in the region. Impacts of future extreme precipitation events vary across the region, with flat and low-lying topographies appearing to be more severely affected, along with areas containing extensive impervious development.

Developing a framework for classifying water lead levels at private drinking water systems: A Bayesian Belief Network approach

The presence of lead in drinking water creates a public health crisis, as lead causes neurological damage at low levels of exposure. The objective of this research is to explore modeling approaches to predict the risk of lead at private drinking water systems. This research uses Bayesian Network approaches to explore interactions among household characteristics, geological parameters, observations of tap water, and laboratory tests of water quality parameters. A knowledge discovery framework is developed by integrating methods for data discretization, feature selection, and Bayes classifiers. Forward selection and backward selection are explored for feature selection. Discretization approaches, including domain-knowledge, statistical, and information-based approaches, are tested to discretize continuous features. Bayes classifiers that are tested include General Bayesian Network, Naive Bayes, and Tree-Augmented Naive Bayes, which are applied to identify Directed Acyclic Graphs (DAGs). Bayesian inference is used to fit conditional probability tables for each DAG. The Bayesian framework is applied to fit models for a dataset collected by the Virginia Household Water Quality Program (VAHWQP), which collected water samples and conducted household surveys at 2,146 households that use private water systems, including wells and springs, in Virginia during 2012 and 2013. Relationships among laboratory-tested water quality parameters, observations of tap water, and household characteristics, including plumbing type, source water, household location, and on-site water treatment are explored to develop features for predicting water lead levels. Results demonstrate that Naive Bayes classifiers perform best based on recall and precision, when compared with other classifiers. Copper is the most significant predictor of lead, and other important predictors include county, pH, and on-site water treatment. Feature selection methods have a marginal effect on performance, and discretization methods can greatly affect model performance when paired with classifiers. Owners of private wells remain disadvantaged and may be at an elevated level of risk, because utilities and governing agencies are not responsible for ensuring that lead levels meet the Lead and Copper Rule for private wells. Insight gained from models can be used to identify water quality parameters, plumbing characteristics, and household variables that increase the likelihood of high water lead levels to inform decisions about lead testing and treatment.

NT-proBNP: Can We Better Utilize Biomarkers in Patients With Diabetes?

B-type natriuretic peptide (BNP) is secreted from the atria of the heart as a response to myocardial stretch that occurs with increases in volume, afterload, and other hemodynamic changes that result in increased cardiovascular stress. The atria of the heart secrete BNP in its proform and it is subsequently cleaved into an inactive form (N-terminal [NT]-proBNP) and an active form (BNP) (1). Although there are some differences with regard to interpretation of the assays for these different metabolites, both NT-proBNP and BNP (referred to collectively as natriuretic peptides [NP]) can be measured and quantified and play an important role in the diagnosis and management of both acute and chronic heart failure. While the role of NP in the management of heart failure is well established, the role of NP outside of heart failure is less well defined. Prior studies consistently show a clear relationship between elevated levels of NP and subsequent risk of cardiovascular events, including atrial fibrillation (2), diastolic dysfunction (3), coronary heart disease, and stroke (4), and the development of diabetes (5). Given these associations, it is possible to use NP to assist in the risk stratification of patients into those who are at high and low risk of cardiovascular events in populations at risk for cardiovascular disease, with stable coronary artery disease, or following a myocardial infarction (6). Furthermore, it is possible that these biomarkers could also help to tailor therapy such that patients at high risk have intensification of …

Risk Assessment of Pesticide Mixtures in Australian Rivers Discharging to the Great Barrier Reef.

Rivers discharging to the Great Barrier Reef carry complex pesticide mixtures. Here we present a first comprehensive ecotoxicological risk assessment using species sensitivity distributions (SSDs), explore how risk changes with time and land use, and identify the drivers of mixture risks. The analyzed data set comprises 50 different pesticides and pesticide metabolites that were analyzed in 3741 samples from 18 river and creek catchments between 2011 and 2016. Pesticide mixtures were present in 82% of the samples, with a maximum of 23 pesticides and a median of five compounds per sample. Chemical-analytical techniques were insufficiently sensitive for at least seven pesticides (metsulfuron-methyl, terbutryn, imidacloprid, clothianidin, ametryn, prometryn, and thiamethoxam). The classical mixture concepts of concentration addition and independent action were applied to the pesticide SSDs, focusing on environmental threshold values protective for 95% of the species. Both concepts produced almost identical risk estimates. Mixture risk was therefore finally assessed using concentration addition, as the sum of the individual risk quotients. The sum of risk quotients ranges between 0.05 and 122 with a median of 0.66. An ecotoxicological risk (i.e., a sum of individual risk quotients exceeding 1) was indicated in 38.5% of the samples. Sixteen compounds accounted for 99% of the risk, with diuron, imidacloprid, atrazine, metolachlor, and hexazinone being the most important risk drivers. Analysis of land-use patterns in catchment areas showed an association between sugar cane farming and elevated risk levels, driven by the presence of diuron.

Reduced positive affect on days with stress exposure predicts depression, anxiety disorders, and low trait positive affect 7 years later.

Positive emotions serve important functions for mental health. Susceptibility to reduced positive emotions in the context of stress may increase risk for poor mental health outcomes, including anxiety and depressive disorders and low overall levels of positive emotion. In an 8-day daily diary study within a larger panel study (N = 1,517), we tested whether degree of reduction in time spent experiencing positive affect on days of stress exposure predicted lower levels of positive affect and elevated risk for major depressive and anxiety disorders (generalized anxiety disorder or panic disorder) 7 years later. Bayesian multilevel structural equation modeling controlling for overall levels of affect, stress exposure, leisure time, sex, age, and past year diagnoses of depression and anxiety disorders was conducted. Participants, on average, reported less time experiencing positive affect on days with stressors compared to days without stressors. In addition, participants varied in the extent to which their time spent experiencing positive affect differed across days with and without stressors. Those who reported an especially reduced proportion of the day experiencing positive affect on days with stressors also experienced lower positive affect and greater risk for major depressive disorder and anxiety disorders 7 years later. These prospective associations suggest that between-person differences in the within-person association between stress and positive emotions have implications for mental health years later. The efficacy of preventive interventions could be improved by fostering resilience of positive emotions during common stressful events. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Homozygous familial hypercholesterolemia in Italy: Clinical and molecular features

Background and aimsHomozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated plasma levels of low density lipoprotein cholesterol (LDL-C) and high risk of premature atherosclerotic cardiovascular disease (ASCVD). HoFH is caused by pathogenic variants in several genes, such as LDLR, APOB and PCSK9, responsible for autosomal dominant hypercholesterolemia (ADH), and LDLRAP1 responsible for autosomal recessive hypercholesterolemia (ARH). Aim of this study was the review of the clinical and molecular features of patients with HoFH identified in Italy from 1989 to 2019. MethodsData were collected from lipid clinics and laboratories, which had performed molecular diagnosis in suspected HoFH. Clinical data included baseline lipid levels and ASCVD events. ResultsA total of 125 subjects with ADH were identified, of whom 60 were true homozygotes, 58 compound heterozygotes and 7 double heterozygotes for LDLR (likely) pathogenic variants. Compared with compound heterozygotes, true homozygotes showed a more severe lipid phenotype and more ASCVD events. ADH carriers of LDLR negative variants (R-NEG) presented with a more aggressive phenotype, as compared to carriers of LDLR defective variants (R-DEF). Kaplan-Meier analysis showed that the median age of ASCVD event-free survival was 25 years of age in R-NEG as opposed to 50 years of age in R-DEF patients. A total of 66 patients with ARH were also identified, of whom 46 were homozygotes and 20 compound heterozygotes. The phenotypic features of ARH patients were similar to those of R-DEF/ADH patients. Overall, 45% ADH patients and 33% ARH patients did not meet the classic diagnostic criteria for HoFH. ConclusionsIn our cohort, the phenotypic variability of HoFH was dependent on the candidate gene involved and the functional impact of its variants on the LDL receptor pathway.

Outcome-based contracting from the customers' perspective: A means-end chain analytical exploration

Within the context of servitization, manufacturing firms increasingly offer outcome-based contracts (OBCs) which sell the outcome of a manufacturing process instead of the resources required for outcome creation. While extant studies have focused on the provider's viewpoint, this research explores industrial customers' requirements and goals when sourcing OBCs. We report the results of laddering interviews with purchasing and engineering managers from 32 actual and potential OBC customers. Based on a means-end chain analysis we find that, in addition to organizational goals, such as reducing costs or ensuring reliable supply, individual goals of the decision-makers also play a key role when purchasing OBCs. Specifically, the risk of being held accountable for problems that may occur in an OBC's implementation and operation emerges as an important concern of decision-makers. In contrast to extant research, that highlights how OBCs transfer operational risk from the customer to the supplier firm, our study indicates that customers also perceive elevated levels of individual and organizational risk when making OBC purchase decisions. Against this backdrop, OBC salespeople should address both individual and organizational goals of key decision-makers in the customer firm and focus on building trust in the supplier's ability to realize and operate an OBC.

Sleepiness on the flight deck: Reported rates of occurrence and predicted fatigue risk exposure associated with UK airline pilot work schedules

Survey and field studies conducted with commercial airline pilots suggest that in-flight sleepiness and related involuntary sleep phenomena are experienced by pilots during their duties. However, for methodological, practical and commercial reasons, there is a lack of publicly available research data of per-flight hour rates of sleepiness experienced by pilots or predicted fatigue risk rates associated with pilots’ hours of work. This empirical field study sought to address this gap by collecting self-reported sleepiness/alertness ratings from pilots from 18 different UK airlines via a mobile phone app over the period of August 2017. In tandem, predicted sleepiness levels and sleep opportunities associated with participants’ flown rosters were investigated using biomathematical fatigue modelling. Findings indicated that a quarter of all flying duty periods were predicted to be preceded by a main sleep opportunity shorter than six hours, whilst 10% of all flying hours were associated with elevated fatigue risk levels. Pilots reported 7.3 reports of involuntary sleep on the flight deck per 1000 flying hours, which represents a rate far greater than that previously reported to the regulator. By comparison, the rates of predicted and recorded fatigue-related incapacitations greatly exceeded the target rate of medical incapacitation permissible under the medical incapacitation safety standard for commercial aviation of less than one occurrence per 1,000,000 h.

Household Food Insecurity and the Association with Cumulative Biological Risk among Lower-Income Adults: Results from the National Health and Nutrition Examination Surveys 2007-2010.

Household food insecurity has been associated with adverse health outcomes; however, the mechanisms underlying these associations are not well-defined. Using data from 5005 adults from the 2007–2010 National Health and Nutrition Examination Surveys (NHANES), we examined associations between household food insecurity and cumulative biological risk, a measure of the body’s physiological response to chronic stress. Household food security was assessed using the 18-item Household Food Security Survey Module. Marginal food security refers to 1–2 positive responses, and food insecurity refers to ≥3 positive responses. The cumulative biological risk scores were calculated based on the distributions of ten biomarkers from the cardiovascular, metabolic, and immune systems. Elevated biological risk was defined as a risk score of ≥3. Multivariable regression models were used to examine associations between food security and cumulative biological risk scores, adjusting for sociodemographic characteristics. After multivariable adjustment, food insecurity was associated with a 0.14-unit higher cumulative biological risk score (95% CI 0.05–0.22, p-trend = 0.003) and higher odds of elevated biological risk (OR 1.20, 95% CI 1.05–1.37, p-trend = 0.003). These associations differed by gender. Among women, food insecurity was associated with 0.30-unit higher cumulative biological risk score (95% CI 0.14–0.45, p-trend = 0.0004) and higher odds of elevated biological risk (OR 1.61, 95% CI 1.29–2.00, p-trend < 0.0001). These associations were not observed in men. Women experiencing food insecurity demonstrated elevated levels of biological risk. These findings support the hypothesis that food insecurity may be associated with women’s chronic health outcomes through the pathway of chronic stress. Further research is needed to understand why these associations were not observed in men.

Prosthetically driven immediate implant placement at lower molar area; an anatomical study.

To examine the effectiveness and safety of immediate implant placement (IIP), we evaluated the risk of lingual plate perforation (LPP) and mandibular canal perforation (MCP) associated with posterior mandible anatomy using cone beam computed tomography (CBCT) images. A morphological study of the molar sockets of 135 patients (age: 18-84 y) was done and its relationship to the mandibular canal was investigated. The risk of LPP and MCP was recorded as yes or no. Mandibular cross-sectional morphology was defined as one of three types (U-P-C) using the criteria of Chan et al. The risk of LPP was significantly higher for second molars (p = 0.0001), and the risk increased with age (p = 0.039). There was a strong relationship between the risk of LPP and cross-section type U (p = 0.0001). The mean root to alveolar canal (RAC) distance (mm) of males was significantly higher than that of females. The mean RAC value was 5.02 mm for males and 3.49 mm for females. There was no statistically significant relationship between the risk of MCP and sex. There was a significant relationship between the risk of MCP and cross-section type U (p = 0.0001). Although the MCP risk was higher in second molars, there was no statistically meaningful relation between MCP and tooth type. The results suggest that IIP in the mandibular molar area carries a high risk of MCP and LPP. Based on the elevated level of risk, a delayed implant protocol should be considered.

Understanding trajectories of externalizing problems: Stability and emergence of risk factors from infancy to middle adolescence.

Despite considerable efforts to understand the processes that underlie the development of externalizing behavior problems, it is still unclear why externalizing problems remain chronically high for some children, emerge early and cease by late childhood for others, and arise in adolescence in some cases. The purpose of this study was to examine how a wide range of child and family risk factors are linked to trajectories of externalizing behavior and how these relationships vary from infancy to middle adolescence. We used data from the community-based Norwegian Tracking Opportunities and Problems (TOPP) study sample (n = 921). A Cholesky factorization model was specified to separate stable and emerging risk doses across four developmental periods (infancy, early and middle childhood, and middle adolescence). Children in the High Stable class were characterized by substantially elevated risk levels in multiple domains throughout the study period. Children in the High Childhood Limited class had very high levels of temperamental emotionality, internalizing symptoms, and maternal mental distress, suggesting a substantial intrinsic emotional basis for their externalizing problems. Intrinsic factors seemed less salient for the Adolescent Onset class. These findings emphasize the need for a dynamic perspective on risk factors and support the importance of prevention and intervention efforts across multiple domains from early childhood and throughout adolescence.

Risk Factors for Wound Complications After Periprosthetic Fractures.

The number of hip and knee arthroplasties performed annually continues to rise. Revision rates are projected to increase by 137% to 601%, with periprosthetic fractures to be among the leading cause of revision. Wound complications following surgical treatment of periprosthetic fractures are a major source of patient morbidity and health care costs. This study evaluated risk factors for wound healing complications in patients undergoing surgical management of periprosthetic fractures around the hip and knee. This was a retrospective analysis of 67 consecutive lower-extremity periprosthetic hip and knee fracture surgeries. Descriptive data, comorbidities, dressing type, and rates of wound complications treated nonoperatively and operatively were collected. Logistic regression analysis was performed to calculate odds ratios (ORs) of having a wound complication. There was an overall wound complication rate of 22%; the majority of these complications (16%) were treated operatively. On multivariate analysis, prior bariatric surgery (OR, 12.02; 95% confidence interval [CI], 1.24-116.71; P=.03), peripheral vascular disease (OR, 6.84; 95% CI, 1.32-35.39; P=.02), and pulmonary disease (OR, 11.23; 95% CI, 1.85-68.31; P=.01) were all associated with an increased risk of developing a wound complication. Closed-incision negative-pressure therapy was associated with a decreased risk of developing a wound complication (OR, 0.04; 95% CI, 0.00-0.49, P=.01). Surgery to treat hip and knee periprosthetic fractures is associated with a high rate of wound complications. History of bariatric surgery, peripheral vascular disease, and pulmonary disease are all associated with an increased risk of developing a wound complication. Future payment models should reflect this elevated level of complications and risk. [Orthopedics. 2020;43(4):e258-e262.].

Dietary fructose and dyslipidemia: new mechanisms involving apolipoprotein CIII.

Chronic consumption of fructose and fructose-containing sugars leads to dyslipidemia. Apolipoprotein (apo) CIII is strongly associated with elevated levels of triglycerides and cardiovascular disease risk. We reviewed the effects of fructose consumption on apoCIII levels and the role of apoCIII in fructose-induced dyslipidemia. Consumption of fructose increases circulating apoCIII levels compared with glucose. The more marked effects of fructose compared with glucose on apoCIII concentrations may involve the failure of fructose consumption to stimulate insulin secretion. The increase in apoCIII levels after fructose consumption correlates with increased postprandial serum triglyceride. Further, RNA interference of apoCIII prevents fructose-induced dyslipidemia in nonhuman primates. Increases in postprandial apoCIII after fructose, but not glucose consumption, are positively associated with elevated triglycerides in large triglyceride-rich lipoproteins and increased small dense LDL levels. ApoCIII might be causal in the lipid dysregulation observed after consumption of fructose and fructose-containing sugars. Decreased consumption of fructose and fructose-containing sugars could be an effective strategy for reducing circulating apoCIII and subsequently lowering triglyceride levels.

Corporate Risk: CEO Overconfidence and Incentive Compensation

Purpose – The purpose of this study is to investigate the association between corporate risk and the interaction between CEO incentive compensation and CEO overconfidence. Design/methodology/approach – This empirical study performs random and fixed effects regression analysis. It uses option-implied measures of CEO overconfidence. Findings – The authors contribute to the existing literature by showing 1) that the positive association between high CEO incentive compensation and corporate risk only exists in the sphere of overconfident CEOs and 2) that the positive association between overconfident CEOs and corporate risk only exists in the sphere of high CEO incentive compensation. The authors show that the combination of high CEO incentive compensation and CEO overconfidence is associated with an increase in corporate risk of approximately 6% while the individual effects are for all practical purposes negligible. The results imply that only the combination of high CEO incentive compensation and CEO overconfidence is associated with a significantly elevated level of corporate risk. Research limitations/implications – The findings are based on S&P 1500 non-financial firms in the period 2007-2016. Practical implications - The findings have important implications in terms of CEO selection and compensation. Originality – This study provides empirical evidence on the importance of the dual presence of high CEO incentive compensation and CEO overconfidence for corporate risk. Previous literature has primarily investigated these phenomena in isolation.

S01.07 The U19 Plans for Integration of Biomarkers Into Future Lung Cancer Screening

The goal of the U19 Integrative analysis of Lung Cancer Etiology and Risk (INTEGRAL) consortium is to develop biomarkers that characterize individual risk for development and progression from lung cancer. We are using a comprehensive strategy, depicted below in Figure 1, for this analysis and we are drawing on world-wide resources and expertise. There are three projects focusing on i) genetics of smoking behavior and lung cancer risk, ii) biomarker discovery and validation for identifying individuals at highest risk for developing lung cancer and iii) evaluation of these biomarkers in screening cohorts along with radiographic analaysis to evaluate risk for lung cancer development and nodule behavior. There are also administrative and biostatistics cores. We will discuss strategies and novel findings from these projects. For Project 1, to assist in genetic analysis, we have reimputed all the available data from lung cancer cases and controls using the haplotype reference consortium to bring together a data lake comprising data from over 100,000 individuals. The consortium provides data to its members and to collaborators who would like to evaluate hypotheses related to lung cancer by providing access for analyses and we currently are supporting 107 projects evaluating lung cancer risk. Additionally, consortium members from the University of Laval have performed transcriptomic analysis of normal lung tissue from over 500 participants undergoing surgery for lung cancer treatment. We are also studying the role that genetic factors have in influencing smoking behavior by collaborating with other large consortia and by studying multiethnic variation using Hawaiian multiethnic populations. Analyses of the genetic data and further extension to the UK Biobank have identified novel genetic loci that contribute to risk. Interaction analysis of the CHRNA3/A5/B4 cluster with all other genomic regions identifies interactions with the 15q25.1 nicotinic receptors that influence lung cancer risk. Results identified genes in the neuroactive ligand receptor interaction pathway as playing a key role in increasing lung cancer risk. A cross-ethnicity analysis identified genetic factors in the major histocompatibility complex (MHC) that affect risk for lung cancer. We imputed sequence variation for 26,044 cases and 20,836 controls in classical HLA genes, fine-mapped MHC associations for lung cancer risk with major histologies and compared results among ethnicities. Independent and novel associations within HLA genes were identified in Europeans primarily affecting risk for squamous cell histology including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets affecting adenocarcinoma risk primarily that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter was better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility. A rare variant analysis yielded a mutation of the ATM gene that is rare in all populations except individuals of Jewish descent that primarily increase risk for adenocarcinoma and has highest risk in nonsmoking women. Analyses of smoking and genetic data have identified gene-smoking interactions that contribute to lung cancer risk, and particularly several genes that protect at-risk smokers from lung cancer development. Mendelian randomization and mediation analyses are underway to evaluate novel biomarkers that can be further studied in project 2. This effort found a surprising result that elevated levels of vitamin B12 increase risk for lung cancer development. Project 2 has been bringing together an approach to analyzing biomarkers using data from existing cohort consortia, which have collected samples prior to the clinical presentation of lung cancers. Results of an initial study showed that analysis of 4 circulating proteins (CEA125, CEA, CYFRA 21-1 and pro-SFTB) yielded an area under the receiver operator curve accuracy of 83%. This level of accuracy is sufficient to consider the panel for recruitment of individuals for screening studies, but we anticipate that adding additional biomarkers will further improve the accuracy of risk prediction. Biomarkers that are being further considered include additional protein markers along with micoRNA species, the inclusion of polygenic risk scores and additional serum-derived biomarkers like vitamins B-6 and B-12 that have been shown in mendelian randomization studies to help in identifying high risk subjects. Project 3 is focused on the establishment and validation of the models in the LDCT screening programs. In collaboration with National Lung Screening Trial, Canadian LDCT screening programs, NELSON and United Kingdom Lung Study (UKLS), we have begun the data harmonization across LDCT studies, including clinic-epidemiological data as well as nodule characteristics. We have established a pipeline of feature extractions for the radiomics analysis and compared the inter-reader variability. The intraclass correlation coefficients are >0.75 for the majority of the radiomics features extracted. We will conduct cross-study validation for the model building to ensure the maximum generalizability of the model. We will start the work on biomarkers and assess their added values in these models. biomarkers, early detection, genetics