Inverse Causality Research Articles

460P - Mendelian randomization study showed no causality between metformin use and lung cancer risk

BackgroundReduced lung cancer incidence was observed after the use of metformin. However, previous reports from observational study can be biased by confounders, inverse causality and so on, keeping the causality between observed decreased lung cancer risk and metformin use uncertain. Mendelian randomization (MR) analysis is a novel approach for the estimation of causality, eliminating the effect of confounders by using single-nucleotide polymorphisms (SNPs) as instrument variables. Growth Differentiation Factor 15 (GDF 15) is a robust biomarker of metformin use. To verify the potential preventive effect of metformin on lung cancer, we aimed to assess the causality, using SNPs of GDP 15. MethodsWe utilized the genome-wide association study (GWAS) summary data of GDF 15 and lung cancer. Two-sample MR was used to investigate the causality. In detail, Inverse-Variance Weighted, MR-Egger and Weighted Median methods were conducted. Single SNP analysis and leave-one-out analysis were performed to assess whether the result was driven by a single SNP. We also conducted the MR-Egger regression to evaluate the pleiotropy. ResultsThe result of this study did not support a causality between metformin use and lung cancer incidence (OR = 0.988, 95% CI = 0.914-1.069, P-value = 0.768), which was not driven by single SNP. (Table) Directional horizontal pleiotropy did not seem to exist in the MR-Egger regression (intercept β = −0.02, P = 0.69).Table460P Mendelian randomization estimates of the causality between metformin utilization and lung CaExpoTableExposureOutcomeInverse variance weightedMR EggerWeighted medianOR# (95%CI*)P-valueOR# (95%CI*)P-valueOR# (95%CI*)P-valueMetformin UtilizationLung Cancer0.988 (0.914-1.069)0.7681.049 (0.797-1.381)0.7540.982 (0.894-1.079)0.705#Odds ratio.*Confidence interval. ConclusionsThis study indicated no causality between metformin and lung cancer. The potential use of metformin in lung cancer prevention need further verification in randomized controlled trials. Further studies are warranted to investigate the shared and modifiable risk factors of metformin use and lung cancer contributing to the observed reverse association, which will be beneficial to the control of lung cancer incidence. Legal entity responsible for the studyThe authors. FundingNational Key R&D Program of China (2016YFC0905500, 2016YFC0905503); Science and Technology Program of Guangdong (2017B020227001); Science and Technology Program of Guangzhou (201704020072). DisclosureAll authors have declared no conflicts of interest.

Epidemiology, environmental risk factors and genetics of Parkinson's disease

Parkinson's disease (PD) is a frequent neurodegenerative disease with a premotor phase that lasts several years. Risk factors that have been linked to PD are tobacco, caffeine, black tea, pesticides and calcium channel blockers. Some risk factors may be due to inverse causality (e.g. changes in personality during the premotor phase). The genetics of PD are complex with a contribution of Mendelian (e.g. SNCA, LRRK2, Parkin, Pink1,…) and non-Mendelian factors (e.g. single nucleotide polymorphisms). Glucocerebrosidase gene mutations (Gaucher disease) are currently the strongest genetic risk factor for PD. Studying risk factors will help to better understand the pathogenesis of PD.

Academic Failure and Child-to-Parent Violence: Family Protective Factors.

A reduction in academic achievement over the course of adolescence has been observed. School failure is characterized by difficulties to teaching school goals. A variety of other behavioral problems are often associated with school failure. Child-to-parent violence has been associated with different school problems. The main objective of current study was to examine the contribution of family variables (parental education level, family cohesion, and positive family discipline) on academic failure and child-to-parent violence of adolescents from a community sample. Moreover, a goal was to explore if academic failure was a valid predictor of child-to-parent violence. To this end, it has been developed a comprehensive statistical model through Structural Equation Modeling (SEM). Participants were 584 children from eight secondary schools in the Basque Country (Spain) and aged between 12 and 18. Among other scales Conflict Tactics Scale and Family Environment Scale were administrated for measuring child-to-parent violence and family cohesion environment, respectively. The structural model revealed that parental education level is a relevant protective factor against academic failure. Positive family discipline (inductive discipline, supervision, and penalty) show a significant association with child-to-parent violence and academic failure. Disciplinary practices could be more efficient to prevent child-to-parent violence or school failure if children perceive a positive environment in their home. However, these findings could be explained by inverse causality, because some parents respond to child-to-parent violence or academic failure with disciplinary strategies. School failure had indirect effects on child-to-parent violence through family cohesion. For all that, education policies should focus on parental education courses for disadvantaged families in order to generate appropriate learning environments at home and to foster improvement of parent-child relationships.

Inequality in the Face of Death: The Socioeconomic Gradient in Mortality of the Spanish Working-Age Population

The purpose of this paper is to evaluate the association between income and mortality over a three year period for working-age Spaniards. Method Data on 693,994 individuals was taken from a social security sampling using a logit model to estimate the probabilities of death for each income decile and the mortality rate ratios (MRR) in three different models: 1) using only income, controlled by age and sex,2) adding socio-economic and geographic variables and, 3) adding level of education. Results: A gradient appears in the mortality rate over income deciles with a maximum MRR of 3.41 in men and 1.68 in women. The shape of the adjustment is clearly non-linear and levels out as income increases. The gradient attenuates for both sexes when variables are introduced that try to capture the inverse causality (2.4 and 1.3). Controlling by level of education reduces the gradient for men (2.2) and intensifies it for women (1.5). Conclusion: The association of the relationship between income and mortality is verified, as well as its non-linear nature, the greater intensity for men than for women, and its persistence when controlling for variables that try to capture causality.

Nordic MS Epidemiology. Introduction.

Nordic MS Epidemiology. Introduction.

Military Expenditures and Unemployment Nexus for Selected South Asian Countries

The objective of the study is to examine the relationship between military expenditures and unemployment rate in the panel of selected SAARC countries namely India, Nepal, Pakistan and Sri Lanka over the period ranging from 1990 to 2013. In particular, the study used multivariate framework to examine the long-run relationship between military expenditures and unemployment rate by taking into account the effect of macroeconomic variables namely energy consumption, GDP per capita, Foreign Direct Investment (FDI) net inflows and population growth rate. The empirical results show that all the variables exhibit non-stationary behavior and have long-run relationships between them. The results of panel DOLS show that military expenditures favor the employment rate in the SAARC region, as the estimated coefficient of military expenditure has a negative and more elastic relationship with the unemployment rate. Other factors i.e., energy consumption, GDP per capita and incoming FDI significantly decreases the unemployment rate in the SAARC region. However, population growth rate does not exhibit significant association with the unemployment rate during the period under the study. In a second regression apparatus, energy consumption, and GDP per capita significantly decrease the military spending, however, population growth rate significantly increases the military expenditures in the region. The results of causality indicate that there is an inverse causality between energy consumption, GDP per capita and population growth rate with the unemployment rate, while there is no significant causation between military spending and the rest of the variables in the short-run. In the long-run, there is a significant causation between the variables with the exception of population growth rate in SAARC region. These results are valuable both for policy makers and government officials to formulate their strategic polices for SAARC countries.

Evolution of Subway Network Systems, Subway Accessibility, and Change of Urban Landscape

The subway is one of the major passenger transport systems in Seoul, Korea. Over the last 30 years, the subway system has interacted with urban land use. This study aims to describe the subway system evolution and reveal the causal relations with land rent and population distributions in conjunction with the evolution of the subway system. Extensive and rapid expansion of subway networks have increased subway accessibility in all regional areas over time and have simultaneously strengthened the status of Central Business Districts (CBDs). These facts indirectly imply a possible strong association amongst land rent, population, and subway accessibility. To reveal these relationships, the Granger-causality test in vector auto-regression form is employed. The results confirm the hypothesis of a causal relationship, the influence of the subway accessibility to the land rent in nearby CBD areas. However, inverse causality also exists between these two variables, implying a more complex relationship. In contrast, population variables have a comparably weak causal relationship with subway accessibility in the spatial context of the subway system in Seoul.

“Couch-potatoeism” and childhood obesity: The inverse causality hypothesis

The bulk of cross-sectional studies suggests that lower levels of physical activity are associated with childhood obesity. Although this has led to the general understanding that “couch-potatoes” are fat on account of their inactive lifestyles, cross-sectional studies do not imply causality. On the contrary, the contribution of physical activity to obesity during childhood is currently unclear, and lately, studies have suggested that “couch-potatoeism” could be the result of obesity rather than its cause. Coupled with evidence suggesting that interventions have had little effect on children's physical activity levels as well as on obesity, this inverse causality challenges the role of physical activity in childhood obesity prevention strategies.

Targeting Epstein-Barr virus infection as an intervention against multiple sclerosis.

We here review contemporary data on genetic and environmental risk factors, particularly Epstein-Barr virus infection, for multiple sclerosis. There is an important immunogenetic etiological factor for multiple sclerosis. However, a general assumption is that immune defense genes are activated by the environment, basically by infections. We contend that the relationship between infectious mononucleosis and multiple sclerosis cannot be completely explained by genetics and inverse causality. Epstein-Barr infection as indicated by positive serology is an obligatory precondition for multiple sclerosis, which is a stronger attribute than a risk factor only. Data on events in the early pathogenesis of multiple sclerosis are cumulating from bio-banks with presymptomatic specimens, but there is only little information from the critical age when Epstein-Barr infection including infectious mononucleosis is acquired, nor on the detailed immunological consequences of this infection in individuals with and without multiple sclerosis. We discuss how focused bio-banking may elaborate a rationale for the development of treatment or vaccination against Epstein-Barr virus infection. A cohort in which intervention against Epstein-Barr infections was performed should be the object of neurological follow-up.

Does R&D Matter for Economic Growth or Vice-Versa? An Application to Portugal and Other European Countries

Significant research has studied the impact of Research and Development (R&D) on Gross Domestic Product (GDP) at the country level. However, few studies consider the possibility that a country’s GDP can also be a driver for R&D. This paper investigates the causal relationship linking R&D and growth in a sample of European Union (EU) countries, with an emphasis on Portugal. A causal relationship from growth to R&D can only be proven for France and Spain, whereas the inverse causality only seems to exist for The Netherlands. The co-integration results question the existence of a long-run relationship between R&D and GDP. Keywords: R&D, Economic growth, Co-integration, Granger causality, European countries, Portugal.

Functional ability loss in sensory impaired and sensory unimpaired very old adults: analyzing causal relations with positive affect across four years

This paper focuses on the relationship between functional ability (FA) and positive affect (PA), a major component of well-being, in sensory impaired very old adults (SI) compared with sensory unimpaired individuals (UI). Previous research mostly suggests a robust causal impact of FA on PA. However, some research, drawing from Fredrickson's broaden-and-build theory, also points to the possibility of an inverse causality between FA and PA. We examine in this paper both of these causal directions in SI as well as UI individuals across a 4year observation period. Additionally, we checked for the role of negative affect (NA). The T1–T2 sample comprised 81 out of 237 SI individuals (visually or hearing impaired) assessed at T1, with a mean age at T1 of 81.8years, and 87 UI individuals out of 150 assessed at T1, with a mean age at T1 of 81.5years. Established scales were used to assess FA, PA, and NA. Using cross-lagged panel analysis to examine the direction of causality, our findings indicate that FA has significant impact on PA in both the SI and the UI group, whereas the alternative causal pathway was not confirmed. Both cross-lagged relationships between FA and NA were non-significant. No group differences in path strengths between SI and UI were present. Our study provides evidence that FA is a key competence for successful emotional aging in vulnerable groups of very old adults such as SI as well as in UI adults in advanced old age.

Patterns of exposure to infectious diseases and social contacts in early life and risk of brain tumours in children and adolescents: an International Case–Control Study (CEFALO)

Background:Infectious diseases and social contacts in early life have been proposed to modulate brain tumour risk during late childhood and adolescence.Methods:CEFALO is an interview-based case–control study in Denmark, Norway, Sweden and Switzerland, including children and adolescents aged 7–19 years with primary intracranial brain tumours diagnosed between 2004 and 2008 and matched population controls.Results:The study included 352 cases (participation rate: 83%) and 646 controls (71%). There was no association with various measures of social contacts: daycare attendance, number of childhours at daycare, attending baby groups, birth order or living with other children.Cases of glioma and embryonal tumours had more frequent sick days with infections in the first 6 years of life compared with controls. In 7–19 year olds with 4+ monthly sick day, the respective odds ratios were 2.93 (95% confidence interval: 1.57–5.50) and 4.21 (95% confidence interval: 1.24–14.30).Interpretation:There was little support for the hypothesis that social contacts influence childhood and adolescent brain tumour risk. The association between reported sick days due to infections and risk of glioma and embryonal tumour may reflect involvement of immune functions, recall bias or inverse causality and deserve further attention.

Family Economic Well-Being, and (Class) Relative Wealth: An Empirical Analysis of Life Satisfaction of Secondary School Students in Three Italian Cities

The aim of the study is to shed light on an under-investigated topic—the determinants of life satisfaction of the young—by means of an econometric analysis which focuses specifically on the relationship between household wealth and life satisfaction of secondary school students living in three Italian cities: Rome, Milan and Genoa. We find that family home ownership, mortgages and (class) relative wealth significantly affect the life satisfaction of students. Other significant controls are geographical residence (those living in Milan are significantly less satisfied with life), the mother’s occupation, and trust in family and friendships. The characteristics of our household wealth variables make it hard to conceive any inverse causality (and endogeneity highly unlikely), thus suggesting a direct causality nexus for these factors. We explain why our research provides important insights that should be taken into account when developing policies to promote the subjective well-being of the young.

Kvalita lidského kapitálu a ekonomický růst

The topic of the relationship between human capital and economic growth has been intensively examined in empirical studies since the 1980s. Although the positive impact of education and human capital on growth has been repeatedly confirmed, there are still doubts about the strength and probable inverse causality of the relationship. The quality of human capital is frequently mentioned in the empirical literature as an important factor which can help to understand and properly determine the link. The quality of human capital is a key focus of this paper. It tests and confi rms the hypothesis that the quality is an important factor which significantly influences the intensity of the relationship. The main hypothesis has been tested using the dynamic panel data technique (GMM estimation) on panel data covering 65 countries in 1960-2005. It has been confirmed that the years of schooling have a higher positive impact on economic growth in countries with a higher quality of education.

Contrary to time conditionals in Talmudic logic

We consider conditionals of the form A ⇒ B where A depends on the future and B on the present and past. We examine models for such conditional arising in Talmudic legal cases. We call such conditionals contrary to time conditionals.Three main aspects will be investigated: 1. Inverse causality from future to past, where a future condition can influence a legal event in the past (this is a man made causality). 2. Comparison with similar features in modern law. 3. New types of temporal logics arising from modelling the Talmudic examples. We shall see that we need a new temporal logic,which we call Talmudic temporal logic with linear open advancing future and parallel changing past, based on two parameters for time.

Family Money, Relational Life and (Class) Relative Wealth: An Empirical Analysis on Life Satisfaction of Secondary School Students

We investigate factors affecting happiness on a sample of Italian secondary school students. We find that money matters since family’s house ownership, mortgages and (class) relative wealth significantly affect life satisfaction. Other crucial factors are geographical residence (those living in Milan are significantly less happy), mother’s occupation, trust on family and friendships. Even though we cannot rule out inverse causality and other forms of endogeneity, the characteristics of many of the significant regressors such as family wealth, parental job and geographical residence (not under the decisional power of the student) suggest a direct causality nexus for these factors.

On the origin of shared beliefs (and corporate culture)

This article shows how corporate culture, in the sense of shared beliefs and values, originates (often unintentionally) through screening, self-sorting, and manager-directed joint learning. It shows that such culture will be stronger among more important employees and in older and more successful firms where employees make important decisions and the manager has strong beliefs. It further shows how a manager's beliefs influence culture, how culture persists despite turnover, and why the suggested link between culture and performance may be a case of inverse causality. It finally shows that, from an outsider's perspective, organizations may tend to overinvest in corporate culture.

Leisure-time physical activity, cardiovascular risk factors and mortality during a 34-year follow-up in men

The inverse relationship between physical activity and mortality may be confounded by socioeconomic factors, cardiovascular risk factors and inverse causality. We investigated long-term association between self-reported regular physical activity and mortality in a socioeconomically homogeneous, initially healthy middle-aged (mean age 47) male cohort (the Helsinki Businessmen Study). In 1974, the men were assessed with questionnaires, clinical and laboratory examinations. Cardiovascular disease (CVD) risk factors (including body mass index [BMI], age, cholesterol, glucose, systolic blood pressure and smoking) and details of physical activity of 782 men were available. Leisure time physical activity was collapsed into 3 categories: low (n = 148), moderate (n = 398) and high activity (n = 236). Physical activity was also briefly assessed in questionnaire surveys in 1985-1986 and in 2000. Total mortality up to 2007 was retrieved from the Central Population Register. Altogether 295 men (37.7%) died during the 34-year follow-up, and leisure-time physical activity was significantly related to mortality in a step-wise manner: 45.9% (n = 68), 37.7% (n = 150), and 32.6% (n = 77) died in the low, moderate, and high activity groups, respectively (P < 0.001). With high activity group as referent and adjusted for midlife CVD risk, perceived health and fitness at baseline, hazard ratio for total mortality was 1.21 (95% confidence interval: 0.90, 1.62), and 1.61 (95% confidence interval: 1.13, 2.30) in the moderate and low activity groups, respectively. During the 34-year follow-up, leisure-time physical activity in initially healthy middle-aged men had a graded association with reduced mortality that was independent of CVD risk, glucose and BMI.

Risk analysis of early childhood eczema

The increasing prevalence of eczema suggests the role of environmental factors triggering a genetic predisposition. To analyze the effect of environmental exposures in early life and genetic predisposition on the development of eczema before age 3 years. The Copenhagen Study on Asthma in Childhood is a prospective clinical study of a birth cohort of 411 children born of mothers with asthma. Eczema was diagnosed, treated, and monitored at the clinical research unit, and complete follow-up for the first 3 years of life was available for 356 children. Risk assessments included filaggrin loss-of-function mutation; parent's atopic disease; sex; social status; previous deliveries; third trimester complications and exposures; anthropometrics at birth; month of birth; duration solely breast-fed; introduction of egg, cow's milk, and fish; time spent in day care; cat and dog at home; feather pillow; nicotine in infant's hair; and temperature and humidity in bedroom. Eczema developed in 43.5% of the infants. Filaggrin mutation (odds ratio [OR], 3.20; 95% CI, 1.46-7.02; P = .004), mother's eczema (OR, 2.80; 95% CI, 1.70-4.63; P < .0001), and father's allergic rhinitis (OR, 1.91; 95% CI, 1.09-3.33; P = .02) were directly associated with risk of eczema. Risk of eczema was significantly reduced by birth length (OR per cm increase, 0.87; 95% CI, 0.78-0.97; P = .02), increased bedroom temperature (probably inverse causality; OR, 0.80; 95% CI, 0.66-0.97; P = .02), and dog living in the home (OR, 0.44; 95% CI, 0.23-0.87; P = .02). Dog exposure reduced the risk of eczema, whereas short length at birth, filaggrin mutation, and parental atopy increased the risk of eczema by age 3 years.

615 力学的エネルギーを直接扱う力学の改革

Innovation of dynamics is presented directly based on the principle of energy conservation, in order to make it possible to construct the virtual product used on design and development process in various mechanical makers. First, in addition to the conventional causality, that is force causes motion, the inverse causality, that is motion causes force, is introduced into the new dynamics for explaining closed causality of physical phenomena Second, static and dynamic functions of mass and compliance are defined, and it is made evident that mass and compliance are in counter pair each other. Third, the three new laws are proposed, which are in counter pairs of Newton's three laws. Forth, new definition of work is presented which is done by action of velocity to compliance. Two phenomena of collision and connection are compared each other as an example of symmetrical relation of physical laws.