Causal Markers Research Articles

Abstract 605: Association of blood lipid profile and lung cancer risk: Results from the Southern Community Cohort Study

Abstract Lung cancer is the second most common cancer and the leading cause of cancer death in the U.S. African Americans (AAs) have a higher incidence rate than any other racial group. Lipid metabolism and homeostasis play important roles in the growth of cancer cells and the regulation of membrane proteins. Some previous epidemiological studies have evaluated the association between blood lipid levels and lung cancer risk; however, the results were inconsistent, and few explored patterns among AAs. To investigate the association of blood lipid levels and lung cancer risk, particularly in a low socioeconomic population and AAs, we conducted a nested case-control study using resources from the Southern Community Cohort Study, a well-characterized prospective cohort study of approximately 86,000 adult men and women, two-thirds of whom are AAs. Blood lipid profiles, including total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TRIG), and lipoprotein-a (Lp-a), were measured in 372 lung cancer cases and 721 matched controls. AAs had lower median levels of TRIG, and higher levels of HDL and Lp-a than European Americans (EAs). Conditional logistic regression analysis revealed an inverse association between TC and lung cancer risk, with an adjusted OR for the highest vs. lowest tertiles of 0.67 (95% CI: 0.45-0.99). This association was observed in both AAs and EAs, but was only statistically significant in EAs. Further stratified analysis found that this association was only significant in cases that were diagnosed within 2 years of blood collection. No significant associations of other lipid markers with lung cancer risk were observed. The findings from our study suggest that the inverse associations between TC and lung cancer risk more likely resulted from cancerous occurrence and progression and associated lifestyle changes rather than being indicative of causal markers. Citation Format: Yan Sun, Jie Wu, Hyung-Suk Yoon, Wei Zheng, William J. Blot, Qiuyin Cai. Association of blood lipid profile and lung cancer risk: Results from the Southern Community Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 605.

Children, Literacy and Ethnicity: Reading Identities in the Primary School By LexieScherer. UK: Palgrave MacMillan, 2016 ISBN 978‐1‐137‐53736‐2, 189 pp, £89.99 (hb)

This book presents a challenging child-eye view of what it means to be a ‘poor reader’. It specifically provides the views of linguistically diverse and minority ethnic children such as Nicole from Angola, Rahim from Bangladesh, Zora from Morocco, Malik from Iraq, Arvitas from Kosovo and many other children. These pupils range from new arrivals in the UK to those in long-settled communities. For educators and policy-makers, the takeaway learning is that we should listen to the children whom we teach and consider classroom reading from their perspectives. Working in a participative research framework, Lexie Scherer interviewed young children in a super-diverse urban UK primary school. Data illustrate the understandings that the children apply to their school reading, in complex weavings of race, religion, culture, language and ethnicity. The research focus is on picture books and how children ‘read their own concerns into the page’ (p. 106) in terms of images and characters that they consider to be ‘good’ or ‘bad’, and why. It can be uncomfortable for the reader — and for the author/researcher — to hear some children articulate prejudices in response to multicultural picture books, and Scherer reflects honestly on whether some of the children's apparently racist comments mean that they are actually racist children. Beyond the texts, the children are acutely aware of classroom reading hierarchies and peers who are better skilled, ‘more intelligent’ readers. The study reveals how young children from a variety of minority ethnic and linguistic backgrounds respond to the demands put on them by school reading instruction and assessment. It explores how they make sense of what they are given to read in relation to their understanding of themselves and the wider world, and how they self-manage school evaluations of themselves as readers. The book aims to examine the ‘taken for granted’ processes of learning to read, and these processes mainly appear to be the assessment and benchmarking systems. In this sense, Scherer explicitly shows how learning to read in school is an unspoken social, cultural and political process that makes a significant impact on children. The author controversially critiques campaigns and organisations such as the National Literacy Trust and Get London Reading for discourses that ‘race and place’ children, positioning minority status as a causal deficit marker of literacy underachievement, rather than consulting children about their experiences of learning to read. Scherer proposes a ‘Super 7’ set of classroom reading routines which include long-held effective practices such as reading aloud, silent reading, oral storytelling and cultural reading (everything from environmental print to analysing TV programmes and advertising). But there are two standout items in the ‘Super 7’: faith literacy and bilingual reading. Both items receive insufficient attention in primary schools. Most classroom teachers have little or no training in effective support for bilingual children's literacy learning, or how to engage with faith beyond the statutory syllabus and the antiterrorism ‘Prevent’ agenda. The ‘how to’ of the Super 7 is not articulated. Readers must look to programmes such as CLPE's ‘The Power of Reading’, or the ‘Teachers as Readers/Building Communities of Readers’ projects, for ideas on how to improve literacy pedagogy and inclusion in multilingual, multi-ethnic classrooms. Scherer acknowledges ‘informal chats’ with teaching staff and school leaders, but she is committed to foregrounding the voices of children. Her focus makes the salient point that debates about reading are adult-led. The research illustrates, often glaringly, that children in schools cannot alter how reading is taught. They can only succeed or fail within the assessment regime. This study provides, above all, irrefutable evidence that the children of the world are the norm in UK primary schools today. It calls on educators and schools to listen carefully to these children.

Required properties for markers used to calculate unbiased estimates of the genetic correlation between populations

BackgroundGenerally, populations differ in terms of environmental and genetic factors, which can create differences in allele substitution effects between populations. Therefore, a single genotype may have different additive genetic values in different populations. The correlation between the two additive genetic values of a single genotype in two populations is known as the additive genetic correlation between populations and thus, can differ from 1. Our objective was to investigate whether differences in linkage disequilibrium (LD) and allele frequencies of markers and causal loci between populations affect the bias of the estimated genetic correlation. We simulated two populations that were separated by 50 generations and differed in LD pattern between markers and causal loci, as measured by the LD-statistic r. We used a high marker density to represent a high consistency of LD between populations, and lower marker densities to represent situations with a lower consistency of LD between populations. Markers and causal loci were selected to have either similar or different allele frequencies in the two populations.ResultsOur results show that genetic correlations were underestimated only slightly when the difference in allele frequencies between the two populations was similar for the markers and the causal loci. A lower marker density, representing a lower consistency of LD between populations, had only a minor effect on the underestimation of the genetic correlation. When the difference in allele frequencies between the two populations was not similar for markers and causal loci, genetic correlations were severely underestimated. This bias occurred because the markers did not predict accurately the relationships at causal loci.ConclusionsFor an unbiased estimation of the genetic correlation between populations, the markers should accurately predict the relationships at the causal loci. To achieve this, it is essential that the difference in allele frequencies between populations is similar for markers and causal loci. Our results show that differences in LD phase between causal loci and markers across populations have little effect on the estimated genetic correlation.

Plasma angiopoietin-2 as a potential causal marker in sepsis-associated ARDS development: evidence from Mendelian randomization and mediation analysis.

A causal biomarker for acute respiratory distress syndrome (ARDS) could fuel precision therapy options. Plasma angiopoietin-2 (ANG2), a vascular permeability marker, is a strong candidate on the basis of experimental and observational evidence. We used genetic causal inference methods-Mendelian randomization and mediation-to infer potential effects of plasma ANG2. We genotyped 703 septic subjects, measured ICU admission plasma ANG2, and performed a quantitative trait loci (QTL) analysis to determine variants in the ANGPT2 gene associated with plasma ANG2 (p < 0.005). We then used linear regression and post-estimation analysis to genetically predict plasma ANG2 and tested genetically predicted ANG2 for ARDS association using logistic regression. We estimated the proportion of the genetic effect explained by plasma ANG2 using mediation analysis. Plasma ANG2 was strongly associated with ARDS (OR 1.59 (95% CI 1.35, 1.88) per log). Five ANGPT2 variants were associated with ANG2 in European ancestry subjects (n = 404). Rs2442608C, the most extreme cis QTL (coefficient 0.22, 95% CI 0.09-0.36, p = 0.001), was associated with higher ARDS risk: adjusted OR 1.38 (95% CI 1.01, 1.87), p = 0.042. No significant QTL were identified in African ancestry subjects. Genetically predicted plasma ANG2 was associated with ARDS risk: adjusted OR 2.25 (95% CI 1.06-4.78), p = 0.035. Plasma ANG2 mediated 34% of the rs2442608C-related ARDS risk. In septic European ancestry subjects, the strongest ANG2-determining ANGPT2 genetic variant is associated with higher ARDS risk. Plasma ANG2 may be a causal factor in ARDS development. Strategies to reduce plasma ANG2 warrant testing to prevent or treat sepsis-associated ARDS.

Gene-methylation epistatic analyses via the W-test identifies enriched signals of neuronal genes in patients undergoing lipid-control treatment

An increasing number of studies are focused on the epigenetic regulation of DNA to affect gene expression without modifications to the DNA sequence. Methylation plays an important role in shaping disease traits; however, previous studies were mainly experiment, based, resulting in few reports that measured gene–methylation interaction effects via statistical means. In this study, we applied the data set adaptive W-test to measure gene–methylation interactions. Performance was evaluated by the ability to detect a given set of causal markers in the data set obtained from the GAW20. Results from simulation data analyses showed that the W-test was able to detect most markers. The method was also applied to chromosome 11 of the experimental data set and identified clusters of genes with neuronal and retinal functions, including MPPED2I, GUCY2E, NAV2, and ZBTB16. Genes from the TRIM family were also identified; these genes are potentially related to the regulation of triglyceride levels. Our results suggest that the W-test could be an efficient and effective method to detect gene–methylation interactions. Furthermore, the identified genes suggest an interesting relationship between lipid levels and the etiology of neurological disorders.

Meta-Analysis of NOS3 G894T Polymorphisms with Air Pollution on the Risk of Ischemic Heart Disease Worldwide.

The purpose of this updated meta-analysis was to investigate the effect of nitric oxide synthase-3 (NOS3) G894T polymorphisms, air pollution and their interaction on ischemic heart disease (IHD) risk across populations worldwide. Recursive partition trees, nonlinear association curve fit and geographic information system maps were incorporated to verify results of conventional pooled analyses for sources of heterogeneity. Results from 61 studies (16,219 cases, 12,222 controls) revealed a significant increased relative risk (RR) of IHD associated with NOS3 894 polymorphisms TT (RR = 1.44) and GT (RR = 1.37). Subgroup analysis revealed that the TT polymorphism genotype had significantly increased risk of IHD in Caucasian, East Asian, South Asian, and Middle Eastern populations (all p < 0.05). It is important to point out that many countries demonstrated an average risk of greater than two, which identifies the NOS3 894 TT polymorphism as a potential causal factor and biological marker of IHD, based on criteria for strong evidence used in international consensus panels. These 10 countries include Ukraine, the United Kingdom, Brazil, Chile, Japan, South Korea, India, Iran, Egypt and Morocco. For these countries with elevated risk (RR > 2) from the NOS3 894 TT polymorphism, meta-predictive analysis demonstrated an increasing trend in air pollution association with increased NOS3 894 polymorphisms. Further studies are needed to explore the complexity of the associations among NOS3 gene polymorphisms per population stratifications within countries, detailed air pollution data for added specificity for geographic location across time, and disease risk.

A Genetic Programming Model for Association Studies to Detect Epistasis in Low Heritability Data

The genome-wide associations studies (GWAS) aims to identify the most influential markers in relation to the phenotype values. One of the substantial challenges is to find a non-linear mapping between genotype and phenotype, also known as epistasis, that usually becomes the process of searching and identifying functional SNPs more complex. Some diseases such as cervical cancer, leukemia and type 2 diabetes have low heritability. The heritability of the sample is directly related to the explanation defined by the genotype, so the lower the heritability the greater the influence of the environmental factors and the less the genotypic explanation. In this work, an algorithm capable of identifying epistatic associations at different levels of heritability is proposed. The developing model is a aplication of genetic programming with a specialized initialization for the initial population consisting of a random forest strategy. The initialization process aims to rank the most important SNPs increasing the probability of their insertion in the initial population of the genetic programming model. The expected behavior of the presented model for the obtainment of the causal markers intends to be robust in relation to the heritability level. The simulated experiments are case-control type with heritability level of 0.4, 0.3, 0.2 and 0.1 considering scenarios with 100 and 1000 markers. Our approach was compared with the GPAS software and a genetic programming algorithm without the initialization step. The results show that the use of an efficient population initialization method based on ranking strategy is very promising compared to other models.

When Words and Graphs Move the Eyes: The Processing of Multimodal Causal Relations.

Research on causal relations in multisemiotic texts constituted by words and graphs has been scarce with only a few exceptions. In the current study, eye movement behavior was studied in seventy-six Chilean high school students, who read a set of twelve causally-related economics texts in Spanish in four experimental conditions. The objective is twofold. We aimed, on the one hand, to observe the main effects of the causal discourse marker (DM) por tanto and the statistical causal graph (G), as well as the interaction effect of both variables on different eye tracking measures. On the other, we seek to observe the effects of the DM on the same eye tracking measures for the graph system (GS) area of interest (AOI). The findings showed that the conjoint presence of the DM and the G did not positively influence the processing of selected AOIs. Analyses also reveal no significant effects on the GS AOI. Thus, the results indicate that the DM tend to decrease processing times, while the G increases them. Additional analyses conducted on the integrative transitions between the verbal system and the graph system reveal that more transitions were identified between the consequence segment and the graph system, thereby confirming that the consequence segment is crucial for the integration of both semiotic systems.

Genetic association of complement component 2 variants with chronic hepatitis B in a Korean population.

Numerous single nucleotide polymorphisms associated with an increased risk of liver diseases, chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma have been identified. In this study, we scrutinized the genetic effects of C2 variants, which were conflicting in previous results, on the risk of chronic hepatitis B in a Korean population. We genotyped 22 common C2 genetic variants of 977 chronic hepatitis B cases including 302 chronic hepatitis B-related hepatocellular carcinoma cases and 785 population controls. Statistical analysis was performed to examine the effects of genotype on the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma. Logistic regression analyses showed that six C2 single nucleotide polymorphisms had significant associations with the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma among the Korean subjects. Stepwise analysis revealed that causal markers (rs9267665 and rs10947223) were identified among the C2 variants (stepwise P=3.32×10-9 and 2.04×10-5 respectively). In further conditional analysis with previous chronic hepatitis B-associated loci, these two single nucleotide polymorphisms were independently associated with the risk of chronic hepatitis B. In addition, we investigated the ability of genetic risk scores combining 12 multi-chronic hepatitis B loci to predict the risk of chronic hepatitis B. Individuals with higher genetic risk scores showed increased risk for chronic hepatitis B. Our results suggested that the C2 gene might be a susceptibility locus for chronic hepatitis B in Korean populations. The cumulative genetic effects may contribute to future etiological explanations for chronic hepatitis B.

Model-based directional analysis of cardiovascular variability identifies patients developing atrial fibrillation after coronary artery bypass grafting

BackgroundPostoperative atrial fibrillation (AF) might be favored by cardiovascular control impairment. We hypothesize that cardiovascular regulation indexes derived from directional model-based analysis of the spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP) can identify subjects at risk to develop AF after coronary artery bypass graft (CABG) surgery. MethodsBeat-to-beat HP and SAP series were derived from electrocardiogram (ECG) and invasive arterial pressure recorded for 5 min just before CABG surgery in conscious condition. The group comprised subjects who did develop AF (AF, n = 37, 71 ± 8 years, 27 males) or did not (noAF, n = 92, 65 ± 10 years, 85 males). From HP and SAP variabilities we computed classical time-domain, spectral, cross-spectral and complexity indexes characterizing autonomic function and cardiac baroreflex control. Moreover, we performed model-based directional analysis assessing the gain and strength of the relations from SAP to HP along cardiac baroreflex feedback and from HP to SAP along the feedforward pathway while disambiguating the effect of respiration as estimated from respiratory-related ECG modulations. ResultsClassical HP and SAP variability indexes and baroreflex sensitivity could not separate AF from noAF individuals. Causality markers, and more specifically, the strength of the dynamical interactions from SAP to HP and vice versa, could distinguish the two groups: indeed, AFs have a lower degree of association from SAP to HP and vice versa. ConclusionsAn impairment of the feedforward and feedback arms of the HP-SAP closed loop relation predisposes subjects undergoing CABG surgery to develop postoperative AF. PerspectivesCompetency in medical knowledge: Atrial fibrillation (AF) is a frequent complication after coronary artery bypass graft (CABG) surgery lengthening hospitalization duration and increasing healthcare system costs.Translational outlook 1: CABG patients who developed AF had a less preserved cardiovascular interactions due to less active physiological control mechanisms as resulting from the lower degree of dependence of systolic arterial pressure on heart period and vice versa before CABG surgery.Translational outlook 2: Cardiovascular control markers improve stratification of the AF risk after CABG surgery above and beyond more traditional demographic and clinical indexes.

Cause and Effect Extraction from Biomedical Corpus

The objective of the present work is to automatically extract the cause and effect from discourse analyzed biomedical corpus. Cause-effect is defined as a relation established between two events, where first event acts as the cause of second event and the second event is the effect of first event. Any causative constructions need three components, a causal marker, cause and effect. In this study, we consider the automatic extraction of cause and effect realized by explicit discourse connective markers. We evaluated our system using BIONLP/NLPBA 2004 shared task test data and obtained encouraging results.

Genomic prediction accuracies in space and time for height and wood density of Douglas-fir using exome capture as the genotyping platform

BackgroundGenomic selection (GS) can offer unprecedented gains, in terms of cost efficiency and generation turnover, to forest tree selective breeding; especially for late expressing and low heritability traits. Here, we used: 1) exome capture as a genotyping platform for 1372 Douglas-fir trees representing 37 full-sib families growing on three sites in British Columbia, Canada and 2) height growth and wood density (EBVs), and deregressed estimated breeding values (DEBVs) as phenotypes. Representing models with (EBVs) and without (DEBVs) pedigree structure. Ridge regression best linear unbiased predictor (RR-BLUP) and generalized ridge regression (GRR) were used to assess their predictive accuracies over space (within site, cross-sites, multi-site, and multi-site to single site) and time (age-age/ trait-trait).ResultsThe RR-BLUP and GRR models produced similar predictive accuracies across the studied traits. Within-site GS prediction accuracies with models trained on EBVs were high (RR-BLUP: 0.79–0.91 and GRR: 0.80–0.91), and were generally similar to the multi-site (RR-BLUP: 0.83–0.91, GRR: 0.83–0.91) and multi-site to single-site predictive accuracies (RR-BLUP: 0.79–0.92, GRR: 0.79–0.92). Cross-site predictions were surprisingly high, with predictive accuracies within a similar range (RR-BLUP: 0.79–0.92, GRR: 0.78–0.91). Height at 12 years was deemed the earliest acceptable age at which accurate predictions can be made concerning future height (age-age) and wood density (trait-trait). Using DEBVs reduced the accuracies of all cross-validation procedures dramatically, indicating that the models were tracking pedigree (family means), rather than marker-QTL LD.ConclusionsWhile GS models’ prediction accuracies were high, the main driving force was the pedigree tracking rather than LD. It is likely that many more markers are needed to increase the chance of capturing the LD between causal genes and markers.

Agents and Patients in Physical Settings: Linguistic Cues Affect the Assignment of Causality in German and Tongan.

Linguistic cues may be considered a potent tool for focusing attention on causes or effects. In this paper, we explore how different cues affect causal assignments in German and Tongan. From a larger screening study, two parts are reported here: Part 1 dealt with syntactic variations, including word order (agent vs. patient in first/subject position) and case marking (e.g., as ergative vs. non-ergative in Tongan) depending on verb type (transitive vs. intransitive). For two physical settings (wood floating on water and a man breaking a glass), participants assigned causality to the two entities involved. In the floating setting, speakers of the two languages were sensitive to syntactic variations, but differed in the entity regarded as causative. In the breaking setting, the human agent was uniformly regarded as causative. Part 2 dealt with implicit verb causality. Participants assigned causality to subject or object of 16 verbs presented in minimal social scenarios. In German, all verbs showed a subject (agent) focus; in Tongan, the focus depended on the verb; and for nine verbs, the focus differed across languages. In conclusion, we discuss the question of domain-specificity of causal cognition, the role of the ergative as causal marker, and more general differences between languages.

Preoperative Tracheostomy Is Associated with Poor Disease-Free Survival in Recurrent Laryngeal Cancer.

Objectives It is unknown if preoperative tracheostomy for persistent/recurrent laryngeal squamous cell carcinoma (LSCC) plays a role in unrecognized local disease spread and disease recurrence after salvage laryngectomy. The goals of this study were to determine the effect of preoperative tracheostomy on disease-free survival (DFS) in patients with recurrent/persistent LSCC undergoing salvage laryngectomy. Study Design Retrospective case series derived from prospectively maintained database. Setting Tertiary care academic center. Subjects Patients with recurrent/persistent LSCC after radiation/chemoradiation (RT/CRT) who underwent salvage laryngectomy at the University of Michigan from 1997 to 2015. Methods Demographic, clinical, pathologic, and survival data were collected. Kaplan-Meier survival estimates were performed. Results DFS was worse for patients with tracheostomy prior to laryngectomy than patients without a tracheostomy (5 year: 39% vs 67%; P < .001). Patients with tracheostomy prior to RT/CRT compared to patients with tracheostomy after RT/CRT or patients without a tracheostomy had worse DFS (5-year: 25%, 49%, and 67%, respectively; P < .001). In bivariable analyses controlling for T classification, N classification, or overall stage, preoperative tracheostomy was associated with worse DFS. In multivariable analysis, presence of a preoperative tracheostomy had a worse DFS (hazard ratio, 1.63; 95% confidence interval, 1.00-2.67; P = .048). Conclusion Preoperative tracheostomy is associated with disease recurrence in patients with persistent/recurrent LSCC undergoing salvage laryngectomy, particularly in patients who had tracheostomy prior to completion of initial RT/CRT. Notably, preoperative tracheostomy as a causal factor vs marker for disease recurrence is difficult to ascertain. Nevertheless, clinicians should be aware of the increased risk of locoregional recurrence in patients with preoperative tracheostomy when counseling on surgical salvage and when considering the role of additional therapy.

Conceptual and Procedural Aspects of Causal Meaning: Corpus-Analytic Evidence from Modern Greek

Τheoretical-pragmatic research in the field of Modern Greek causality suggests the need for a differentiating treatment of the two prototypical, monolexemic and seemingly synonymous causal subordinators γiati and epiδi, especially in view of real-language data. In fact, recent relevance-theoretic investigations have supported this claim, applying the distinction between conceptual and procedural meaning to the analysis of these two markers. Thus, while epiδi is reserved for a conceptual characterization, γiati qualifies for either a conceptual or a procedural appraisal, depending on the context where it occurs. Despite their descriptive vigor, the arguments underlying this claim have often been challenged, especially on the grounds of lack of empirical support. The current project undertakes to respond to this long-standing request. To this effect, it conducts a corpus-analytic study of causal meaning. In doing so, it exploits corpora adduced in the Corpus of Greek Texts. On this type of analysis, we avail ourselves of the opportunity to examine the behavior of the two causal markers from a wide textual perspective: in conceptual versus procedural conjunctions within a range of contextual settings (or genres) in both written and spoken discourse. Ultimately, the results of the present corpus analysis come to confirm the claim that the two markers bear distinct types of meaning.

The image‐schematic basis of causation and concession in English and Spanish

AbstractCognitive linguistics holds that meaning in language is the mapping between linguistic expressions and cognitive structures that arise from our direct sensory experience and interactions with the world. Taking as a starting point the notions of image schema (Lakoff &amp; Johnson ) and force dynamics (Talmy ), in two experiments, we tested naïve subjects’ intuitions about the image‐schematic basis of causal and concessive discourse markers. In the first experiment, conducted in English and Spanish, subjects were confronted with a series of animation that depicted forceful interactions between two entities and were asked to make a force‐choice response indicating the sentences that best described the animations that they had watched. English and Spanish participants showed a general preference for descriptions with causal connectives when one of the entities involved in the interaction was overcome by the other. On the contrary, sentences with concessive connectors were favored when the attempts of one of the entities to control the other were unsuccessful. Similar results were obtained in a second experiment where subjects’ judgments were explicitly guided by the sentence connectors given that the linguistic descriptions that accompanied the animations included a nonce verb in their coda such that literal references to the notion of force were avoided. Altogether, these results support the hypothesis that there is consistency across‐ subjects in the imagistic basis of causal and concessive connectives, which seem to recruit our experiential knowledge about forces as part of their meaning.

Influence of Concessive and Causal Conjunctions on Pragmatic Processing: Online Measures from Eye Movements and Self-Paced Reading

ABSTRACTThis study investigates the influence of causal and concessive relations on discourse coherence in Chinese by means of eye movement and self-paced reading techniques. We use the sentential structure like “NPHUMAN moved from place A to place B, {because (因为 yinwei) /although (尽管 jinguan) /no conjunction} + pronoun (he/she) + verb (e.g., like) + there (nali)… + NP”. The eye-movement data (Experiment 1) recorded from regions of interest consistently showed that the processing of concessive meaning is much slower than the processing of causal meaning, irrespective of whether the causal relation is explicitly coded through a causal marker (i.e., yinwei [because]) or not. In particular, although sentences containing pragmatic anomalies were processed more slowly than sentences containing no pragmatic anomalies in causal structures, there was no such distinction in concessive structures, indicating that the processing of a concessive relation can override that of a pragmatic incongruence. Moreover, although the initial place was reread more in cases of concessive structures as compared with causal structures in region 1 (e.g., place A), there was no difference between them in region 2 (e.g., place B). The results from self-paced reading (Experiment 2) showed that the difficulties observed from processing concessive compared with causal relations were not caused by the difference in pronoun resolution. These findings suggest that processing concessive meaning is cognitively more demanding than processing causal meaning, a conclusion that is also supported by a fine-grained linguistic (i.e., conceptual and pragmatic) analysis of causal and concessive relations.

Abstract P1-04-07: Environmental influence on epigenetic markers in the development of breast cancer

Abstract Aberrant DNA methylation plays an important role in breast cancer initiation and progression. We hypothesize that environmental risk factors contribute to causal alterations in DNA methylation and that such causal changes have already occurred prospectively in normal breast tissue before tumor occurrence. In order to test this hypothesis, normal breast tissue from healthy women must be used. We therefore conducted an integrative molecular epidemiological study that combined the environmental regulation of DNA methylation in normal breast tissue and the differential DNA methylation profiling in tumor and normal breast tissue. We examined for the first time the environmental impact on DNA methylation in normal breast tissue from healthy women and determine the association of these epigenetic changes with breast cancer development. Potentially causal DNA methylation markers identified from our study has the potential to make a major scientific and clinical impact in understanding breast cancer etiology as well as developing novel, more effective prevention and treatment strategies. Citation Format: He C, Wu W, Gao H, Nephew K, Li L, Schneider B, Han J, Liu Y. Environmental influence on epigenetic markers in the development of breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-04-07.

ACID: Association Correction for Imbalanced Data in GWAS.

Genome-wide association study (GWAS) has been widely witnessed as a powerful tool for revealing suspicious loci from various diseases. However, real world GWAS tasks always suffer from the data imbalance problem of sufficient control samples and limited case samples. This imbalance issue can cause serious biases to the result and thus leads to losses of significance for true causal markers. To tackle this problem, we proposed a computational framework to perform association correction for imbalanced data (ACID) that could potentially improve the performance of GWAS under the imbalance condition. ACID is inspired by the imbalance learning theory but is particularly modified to address the task of association discovery from sequential genomic data. Simulation studies demonstrate ACID can dramatically improve the power of traditional GWAS method on the dataset with severe imbalances. We further applied ACID to two imbalanced datasets (gastric cancer and bladder cancer) to conduct genome wide association analysis. Experimental results indicate that our method has better abilities in identifying suspicious loci than the regression approach and shows consistencies with existing discoveries.

The Frequency of Rapid Pupil Dilations as a Measure of Linguistic Processing Difficulty.

While it has long been known that the pupil reacts to cognitive load, pupil size has received little attention in cognitive research because of its long latency and the difficulty of separating effects of cognitive load from the light reflex or effects due to eye movements. A novel measure, the Index of Cognitive Activity (ICA), relates cognitive effort to the frequency of small rapid dilations of the pupil. We report here on a total of seven experiments which test whether the ICA reliably indexes linguistically induced cognitive load: three experiments in reading (a manipulation of grammatical gender match / mismatch, an experiment of semantic fit, and an experiment comparing locally ambiguous subject versus object relative clauses, all in German), three dual-task experiments with simultaneous driving and spoken language comprehension (using the same manipulations as in the single-task reading experiments), and a visual world experiment comparing the processing of causal versus concessive discourse markers. These experiments are the first to investigate the effect and time course of the ICA in language processing. All of our experiments support the idea that the ICA indexes linguistic processing difficulty. The effects of our linguistic manipulations on the ICA are consistent for reading and auditory presentation. Furthermore, our experiments show that the ICA allows for usage within a multi-task paradigm. Its robustness with respect to eye movements means that it is a valid measure of processing difficulty for usage within the visual world paradigm, which will allow researchers to assess both visual attention and processing difficulty at the same time, using an eye-tracker. We argue that the ICA is indicative of activity in the locus caeruleus area of the brain stem, which has recently also been linked to P600 effects observed in psycholinguistic EEG experiments.